Single Center Outcomes from Parenchymal-sparing Resections and Microwave Ablations for Neuroendocrine Tumor Liver Metastases

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Lee, Jelani Williams, Rachel Nordgren, Jason L. Schwarz, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2649826/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : Surgical debulking of neuroendocrine tumor (NET) is used as a therapeutic approach for metastatic NETs in selected centers. Reported outcomes after parenchymal-sparing liver resections (PSR) in NET patients with high numbers of liver metastases are sparse. Methods : NET patients that underwent surgical debulking from 2019 to 2021 were reviewed. Trends in perioperative liver function was examined, as well as symptom response, complications, and progression free survival. Results : 1069 liver lesions (median=17) were debulked from 53 patients with a combination of PSR (45%) and ultrasound-guided microwave ablations (MWA) (55%). Post-operative transaminitis was proportional to the number of lesions debulked: Median POD1 AST was 681 IU/L for 1-15 lesions vs. 1396 IU/L for >15 lesions, p =0.01 (R 2 =0.271, p <0.001) and ALT was 596 IU/L vs 1149 IU/L, respectively, p =0.01 (R 2 =0.221, p 15 lesions, p =0.04; R 2 =0.163, p =0.003). Synthetic liver function measured by postoperative INR (median POD1 INR 1.3 vs 1.4, p =0.21) and total bilirubin (median POD 2 TB 1.35 vs 0.95 mg/dL; p =0.67) did not differ according to number of lesions debulked. 13% of patients sustained a Clavien-Dindo grade 3/4 complication which was not associated with the number of lesions targeted. All patients with preoperative symptoms had improvement after surgery. Median time to recurrence was 10.9 months. Conclusions : PSR with MWA for large numbers of NET liver metastases is safe and effective for symptom control and does not affect synthetic liver function. Transaminitis and thrombocytopenia are proportionate to the amount of liver lesions debulked. neuroendocrine tumor hepatic debulking liver metastases parenchymal-sparing resection microwave ablation Figures Figure 1 Figure 2 Figure 3 Introduction While generally considered rare, neuroendocrine tumors (NETs) have a rising incidence in the United States, affecting over 12,000 patients each year ( 1 ). Although described as indolent, these neoplasms exhibit significant metastatic potential most commonly to the liver ( 2 ). Neuroendocrine tumor liver metastases (NETLM) affect up to two-thirds of patients at initial diagnosis and progression of disease is common ( 3 ). Increasing hepatic tumor burden can lead to liver failure and death ( 4 ). Thus, control of liver disease is an important prognostic marker for these patients ( 5 ). Available treatment options for NETLMs include systemic radiolabeled-, targeted- and cytotoxic chemotherapy, non-surgical liver directed therapy (LDT), and surgical resection. Although rarely curative, surgical debulking reduces tumor load in the liver, palliates symptoms and can dramatically improve overall survival with up to 90% 5-year survival reported ( 6 – 8 ). Moreover, debulking thresholds are typically set above 70% in patients with operable disease to achieve maximal benefits ( 7 , 9 ). Surgical approaches to hepatic tumor debulking for NETLMs range from formal anatomic resections to parenchymal-sparing resections (PSR) which include enucleations, wedge resections and partial lobectomies ( 10 , 11 ). As debulking is applied to larger patient groups with increasing number of NETLMs, concerns about associated complications emerge. Reported perioperative outcomes of surgical debulking in NETLM patients have been lacking with respect to impact on liver function and morbidity proportionality to tumor burden. In this study, we report our single institutional experience in surgical debulking of NETLM patients using PSR and microwave ablative (MWA) techniques. Our objectives were to assess 1) feasibility of 90% tumor debulking in patients with large numbers of lesions, 2) safety of advanced debulking by comparing the incidence and degree of complications among patients with various numbers of lesions, and 3) the impact of debulking on postoperative liver function, symptom control and progression-free survival (PFS). Methods In accordance with an IRB-approved protocol, a retrospective review of NETLM patients that underwent surgical debulking at our institution from January 2019 to December 2021 was performed. All patients were under the care of our multidisciplinary NET program and were operated on by the same primary surgeon. Preoperatively, hepatic tumor burden and extrahepatic disease were assessed by abdominopelvic MRI with hepatobiliary contrast (EOVIST) and DOTATE-PET/CT ( 68 Ga and 64 Cu) imaging. A debulking goal of at least 90% was attempted when possible, and all patients had ≤ 25% liver tumor involvement, as defined by semi-quantitative measurements ( 12 ). Operations included first time surgical debulking with or without primary tumor resection, and re-operative debulking in patients with recurrent liver metastases after initial primary resection or prior debulking. Operations were performed using PSR, as described previously, combined with intraoperative ultrasound-guided 3-dimensional navigation MWA (Medtronic). The number of lesions targeted were delineated in operative reports. Wedge resections and enucleations were classified as the same technique for practicality. Percent of tumor debulked was estimated by the surgical team as the number of lesions targeted intraoperatively divided by the total number of lesions identified on pre-operative MRI. All patients underwent serial postoperative imaging every 3 months with MRI with EOVIST. Various clinicopathologic data were reviewed. Since most patients had either a pancreatic NET (PNET) or small bowel NET (SBNET), comparative analyses were performed between these two groups. Specifically, trends between laboratory values for platelets, hepatic enzymes, phosphorus, and coagulation factors in the preoperative and immediate post-operative periods were analyzed. Serum and urine tumor markers for chromogranin A and serotonin were also compared pre- and post- operatively to assess for a biochemical response to surgery which was defined as > 50% decrease from a baseline elevated level. Post-operative symptomatic response was a secondary endpoint defined upon review of standardized clinical documentation during follow up visits. Somatostatin analogues (SSA) were continued post-operatively for patients who remained symptomatic, had limited debulking, or G2 PNETs. Patients with progressive disease after surgery were offered subsequent therapies in the form of chemotherapy (capecitabine-temozolomide; CAPTEM), peptide receptor radionuclide therapy (PRRT), and LDT. Recurrence or progression of disease after debulking was defined as new or evolving lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 standards on serial surveillance MRI (Fig. 1 ) ( 13 ). PFS was assessed using the Kaplan-Meier method. A univariate analysis for clinicopathologic variables was performed using Cox’s proportional hazards regression. Patient characteristics, complication rates and perioperative laboratory values between patient groups were compared using linear regression, Fisher’s exact, Kruskal-Wallis, and Wilcoxon Signed Rank tests. All statistical analyses were performed in R (v 4.1.1, Vienna, Austria). Perioperative morbidity and mortality were assessed using the Clavien-Dindo classification. Results Preoperative clinicopathologic characteristics of 53 NETLM patients who underwent debulking are displayed in Table 1 . The majority had a well differentiated, metastatic SBNET ( n = 34) or a PNET ( n = 15) with grade 1 or 2 disease. One patient had a well-differentiated grade 3 NET and was one of two patients with unknown etiology of primary tumor. The remaining two patients had either a gastric or lung NET. The median age at time of operation was 57 years. 43% of the patient cohort had symptomatic disease, of which 40% had carcinoid syndrome. Over 95% of patients had bilobar liver metastases, and 23% of patients had extrahepatic disease (EHD), with common sites including the peritoneum (diaphragm, omentum and pelvis) or bone. Preoperative systemic therapy with SSA, CAPTEM and/or PRRT had been given in 79%, 11%, and 7.5% of patients, respectively. Table 1 . “Comparison of NET patients preoperative clinicopathologic characteristics” All SBNET PNET p Median age (yrs; range) 57 (49-60) 57 (49.5-62.3) 57 (48-60) 0.68 Sex Male 29/53 19/34 7/15 0.76 Female 24/53 15/34 8/15 Race/Ethnicity White Black Hispanic 38/48 8/48 2/48 23/32 8/32 1/32 12/13 0/13 1/13 0.13 Primary tumor location Unknown Stomach Lung Head of pancreas Tail/body of pancreas SB 2 1 1 3 12 34 -- -- -- -- -- 34 -- -- -- 3 12 -- Symptomatic disease 25/53 21/34 3/15 0.01 Carcinoid syndrome 21/52 19/34 1/14 0.03 Tumor grade G1 G2 G3 29/52 22/52 1/52 25/33 8/33 0/33 4/15 11/15 0/15 0.003 Chromogranin (CgA) 200.5 (93.5-771) 225.5 (125-621) 68 (51-113) 0.01 Elevated CgA 31/42 24/25 4/11 0.006 Serotonin 894 (185-1818) 1140 (566-1955) 176 and 256 0.16 Elevated serotonin or 5-HIAA 23/26 21/23 2/3 -- AST 23 (19-27.8) 22 (19-27) 23 (20-25.5) 0.42 ALT 22 (16.8-33) 19 (15-31) 23 (18.5-32.5) 0.26 Total Bilirubin 0.5 (0.3-0.8) 0.5 (0.3-0.9) 0.5 (0.4 – 0.8) 0.88 INR 1 (1-1) 1 (1-1.1) 1 (1-1) 0.48 Bilateral liver mets 51/53 32/34 15/15 1.00 Lymphadenopathy 35/53 24/34 8/15 0.33 Extrahepatic disease 12/53 8/34 4/15 1.00 Preop systemic therapy Somatostatin analogue Chemo (CAPTEM) PRRT 43/53 42/53 6/53 4/53 28/34 28/34 0/34 2/34 14/15 13/15 6/15 2/15 0.41 1.00 0.004 0.58 Intraoperative characteristics are reported in Table 2 . A total of 1069 hepatic lesions were debulked collectively with PSR (45%) and MWA (55%). Stratified by number of lesions, 21% ( n = 11) had up to 5 lesions, 23% ( n = 12) had 6–15, 28% ( n = 15) had 16–25, and 28% ( n = 15) had > 25 lesions debulked. The highest number of lesions debulked in one patient was fifty-six. The median number of lesions targeted was 17 overall. All patients, except for two, had > 90% tumor debulking at the time of operation. Over 70% of patients had synchronous resection of the primary tumor as their first operation, which they had on average 6.5 months after initial diagnosis. The average estimated blood loss (EBL) was 300 ml for all cases, 13% of which required at least 1 intraoperative transfusion of packed red blood cells. Table 2 . “Operative characteristics for NETLM patients by tumor type” All SBNET PNET p Time to 1 st surgery (months) 6.5 (3.0-13.9) ( n=38 ) 5.1 (2.8-13.5) ( n=26 ) 11.9 (9.9-16.3) ( n=10 ) 0.07 Primary tumor resection 38/52 28/34 9/15 0.15 Type of liver debulking Partial lobectomy Wedge/enucleation MWA Superficial ablation Formal resection 60 total in 38/53 417 total in 48/53 438 total in 47/53 152 total in 6/53 2 total in 3/53 36 total in 23/34 294 total in 32/34 244 total in 29/34 52 total in 2/34 2 total in 2/34 26 total in 14/15 90 total in 13/15 175 total in 14/15 100 total in 4/15 0/15 0.03 0.51 0.03 0.05 0.36 Median # of lesions debulked Total # of lesions debulked 17.5 (7-29) 1069 16.5 (6-25.8) 632 22 (15-38.5) 402 0.10 Sites of extrahepatic mets Intraperitoneal (diaphragm, pelvis, omentum) Bone 10/12 2/12 7/8 1/8 3/4 1/4 1.00 1.00 EBL 300 ( n=52 ) (150-500) 225 (100-388) 500 (250-825) 0.007 Intraoperative Transfusion 7/53 2/34 5/15 0.02 With respect to liver function, a surge in liver enzymes measured on post-operative day (POD) 1 was proportional to the numbers of debulked lesions (Fig. 2 A, B, C). For patients with 1–15 lesions targeted, the median POD 1 AST and ALT values were 681 and 596 IU/L, respectively, compared to 1396 and 1149 IU/L, respectively, for patients with greater than 15 lesions (Fig. 2 A; p = 0.01, p = 0.01). The degree of transaminitis linearly correlated with increasing numbers of hepatic lesions debulked (Fig. 2 C; p < 0.0001, p < 0.0001) but this effect typically resolved by POD 5. Synthetic liver function, assessed by changes in post-operative INR, did not differ significantly among patients and did not have a linear correlation with increasing number of lesions (Fig. 2 C; p = 0.151). Hypophosphatemia, a common post-operative finding after liver resection, was noted to be most prominent on POD 2, but the degree did not differ among the various numbers of lesions debulked (Fig. 2 C). The median length of inpatient stay after debulking was 7 days (Table 3 ). Thrombocytopenia (platelets < 150 x 10 9 /L) was the most common complication occurring in over 75% of patients and most cases were transient. Two patients developed heparin-induced thrombocytopenia (HIT) and were excluded from further analyses. The severity of thrombocytopenia was proportionate to the number of lesions debulked (Fig. 2 C; p = 0.003) with median POD2 platelet values 157 x 10 9 /L for 1–15 lesions vs. 109 x 10 9 /L for > 15 lesions (Fig. 2 A; p = 0.04). However, the incidence of thrombocytopenia did not significantly differ between groups. Table 3 . “Morbidity and Mortality for patients per NET type and number of lesions debulked”. LOS = length of stay; EBL = intraoperative estimated blood loss ALL NET Type No. of lesions debulked SBNET PNET p 1-5 6-15 16-25 >25 p Total complications Any GI Readmission Bile leak PVT HIT Thrombocytopenia Hemorrhage or Anemia Infection Need for re-exploration 1 (1-2) 45/53 4/53 4/53 4/53 1/53 2/53 41/53 19/53 8/53 2/53 1 (1-2) 27/34 2/34 0/34 2/34 0/34 1/34 25/34 9/34 1/34 2/34 2 (1-3) 10/14 2/15 2/15 1/15 0/15 0/15 12/15 9/15 6/15 0/15 0.006 0.41 0.58 0.08 1.00 1.00 1.00 0.73 0.05 0.002 1.00 1 (0.5-1.5) 8/11 1/11 1/11 1/11 0/11 0/11 7/11 2/11 0/11 0/11 1 (1-3) 11/12 2/12 1/12 2/12 1/12 1/12 9/12 5/12 3/12 1/12 1 (0.5-2) 11/15 0/15 0/15 1/15 0/15 0/15 11/15 6/15 1/15 0/15 2 (1-2) 15/15 1/15 2/15 0/15 0/15 1/15 14/15 6/15 4/15 1/15 0.30 0.08 0.43 0.60 0.43 0.43 0.84 0.30 0.60 0.16 0.84 Clavien-Dindo class None I II III IV 7/53 25/53 14/53 6/53 1/53 7/34 18/34 7/34 1/34 1/34 0/15 5/15 7/15 3/15 0/15 0.06 3/11 6/11 1/11 1/11 0/11 1/12 5/12 4/12 1/12 1/12 3/15 6/15 3/15 3/15 0/15 0/15 8/15 6/15 1/15 0/15 0.69 Intraop transfusion 7/53 2/34 5/15 0.02 1/11 3/12 0/15 3/15 0.16 Post op transfusion 17/53 9/34 8/15 0.10 1/11 5/12 5/15 6/15 0.32 30-day mortality 0/50 0/34 0/11 0/10 0/12 0/14 0/14 1 year mortality 1/31 0/22 1/8 0.27 0/5 0/9 0/11 1/6 0.35 LOS (days) 7 (6-8) (n=52) 6.5 (6-7) 7 (6-8) (n=14) 0.58 6 (5-6) 6.5 (6-8) 7 (5-8) 7 (6-7) 0.18 EBL (mL) 300 (n=47) (150-500) 225 (100-388) 500 (250-825) 0.007 250 (100-400) 250 (100-675) 300 (150-550) 350 (200-500) 0.71 Post-operative blood loss anemia requiring transfusion was the second most common complication, affecting 36% of patients. Active post-operative hemorrhage occurred in 4 patients as UGI bleeding ( n = 2) or intraabdominal bleeding ( n = 2) requiring re-exploration. Bile leaks occurred in four patients with a leak-to-resected lesion ratio of 0.9%. Two cases resolved spontaneously without added intervention, one case resulted in a biloma requiring percutaneous drainage, and one case occurred after re-exploration for delayed intra-abdominal bleeding and required biliary stenting. GI complications including persistent ileus ( n = 2), delayed gastric emptying ( n = 1) or post-operative bowel obstruction ( n = 1) occurred in 4 patients. Of these, the obstructed patient required re-exploration to rule out bowel ischemia. There was one case of portal vein thrombosis that occurred in the setting of HIT and required anticoagulation. Infectious complications including urinary tract infection ( n = 2), pancreatic fistula ( n = 3), or intra-abdominal abscess ( n = 3) requiring intervention occurred in 8 patients. Overall, 13% of patients had a Clavien-Dindo grade 3 or 4 complication. While there was no 30-day mortality in our patient group, one patient died on POD 38 from NSAID-induced UGI bleeding that was managed outside of our institution. Post-operatively, median long-term follow-up was 12.1 months (Table 4 ). All symptomatic patients reported symptom improvement or relief after surgery. Over 80% of patients had a biochemical response with a > 50% decrease in serotonin levels after surgery. 50% of patients did not require subsequent systemic therapy at their most-recent follow-up and either had no evidence of disease ( n = 17) or stable disease without progression ( n = 9). The median time to recurrence after debulking was 10.9 months for all patients. There was no significant difference in PFS between PNET and SBNET patients (Fig. 3 A 11.9 vs. 22.3 months; p = 0.095) or between patients with higher vs. lower number of lesions debulked (Fig. 3 B 1–15 lesions: 22.8 months vs. >15 lesions: 16 months; p = 0.38). In cases of disease progression, five patients required the addition of PRRT: 40% had decrease in hepatic lesion size while 60% halted in disease progression. One PNET patient required CAPTEM as subsequent systemic therapy followed by pembrolizumab for tumor de-differentiation. Seven patients underwent post-operative LDT for disease recurrence with either bland embolization or percutaneous ablation. Hazard regression univariate analysis (Table 5 ) indicated that among our cohort, primary tumor size, higher numbers of hepatic lesions, EHD, and other pathologic variables did not correlate with disease progression. Table 4 . “Postoperative characteristics after tumor debulking by NET type”. All SBNET PNET p Symptomatic response Biochemical response Chromogranin Serotonin 24/24 12/19 -- 21/21 11/17 5/6 3/3 1/2 -- 1.00 1.00 Final Pathology Ki-67 10% Lymphovascular invasion Perineural invasion Mesenteric deposits 25/35 5/35 4/35 1/35 35/36 33/37 20/53 21/26 2/26 2/26 1/26 25/26 24/27 20/34 4/9 3/9 2/9 0/9 10/10 9/10 0/15 0.08 1.00 1.00 <0.001 Adjuvant systemic therapy None 1 agent 2 agents 3 or more agents 26/51 17/51 4/51 4/51 17/34 12/34 2/34 3/34 6/14 5/14 2/14 1/14 0.41 Liver-directed perc ablation 8/43 3/29 5/11 0.01 Median time to (months): Most recent follow-up Recurrence 1 st adjuvant therapy 2 nd adjuvant therapy 3 rd adjuvant therapy Liver-directed therapy 12.1 (3.9-21.0) ( n=52 ) 10.9 (6.7-18.7) ( n=24 ) 1.6 (0.9-8.3) ( n=23 ) 12.0 (10.3-21.2) ( n=7 ) 14.0, 16.3, & 21.9 ( n=3 ) 14.5 (9.0-20.5) ( n=8 ) 15.0 (4.8-22.7) ( n=34 ) 13.6 (7.4-19.4) ( n=16 ) 4.9 (1.5-14.6) ( n=15 ) 16 (10.7-22.6) ( n=4 ) 16.3 and 21.9 ( n=2 ) 10.2, 16.8, & 20.0 ( n=3 ) 6.7 (2.4-18.5) ( n=15 ) 9.6 (5.8-15.6) ( n=7 ) 0.8 (0.6-1.0) ( n=8 ) 10.1, 10.4 & 22.4 ( n=3 ) 14.0 ( n=1 ) 12.1 (5.7-21.9) ( n=5 ) 0.13 0.41 0.004 0.86 0.67 1.00 Table 5. “Univariate analysis of clinicopathologic variables associated with progression free survival.” Hazard Ratio p -value Age >= 65 0.69 0.55 Gender: Male vs. Female 1.13 0.77 Race/Ethnicity White vs. Black Hispanic vs. Black 1.79 2.33 0.67 SBNET vs. PNET 0.46 0.12 Synchronous vs. Metachronous 1.07 0.88 Symptomatic disease 1.11 0.80 Tumor grade (2 vs. 1) 1.75 0.18 Bilateral liver metastases 2.39 0.36 Extrahepatic disease 2.52 0.08 # of liver lesions debulked 1.01 0.53 Number of lesions 6-15 vs. 1-5 16-25 vs. 1-5 >25 vs. 1-5 2.80 2.91 2.27 0.33 Primary tumor >= 2cm 1.01 0.99 Largest met >= 5cm 0.64 0.32 Lymphovascular invasion 0.89 0.92 Perineural invasion 0.62 0.65 Mesenteric deposits 0.54 0.17 Ki-67* 3-5% vs. <3% 6-10% vs. <3% 1.42 1.08 0.91 Any preop systemic therapy Somatostatin analogue Chemo (CAPTEM) PRRT 7.12 3.58 0.64 1.32 0.01 0.04 0.65 0.72 Adjuvant (post op) systemic therapy 1 agent vs. 0 agents 2 or more agents vs. 0 agents SSA Chemo PRRT Ablation (MWA, RFA) Embolization Any LDT 0.79 4.07 1.40 3.35 3.24 3.28 3.86 3.83 0.66 0.01 0.44 0.33 0.04 0.03 0.07 0.01 Preop LAD on imaging 1.04 0.92 Discussion Surgical debulking has been shown to palliate symptoms and prolong survival in NETLM patients ( 8 , 14 – 16 ). Nonetheless, recurrence after debulking is universal, and both the preservation of normal liver parenchyma and minimization of complications should be prioritized for this reason. Herein, we show that PSR and MWA allows for effective debulking of hepatic disease in patients with high numbers of lesions without compromising synthetic liver function, and that such procedures can be with low morbidity in experienced centers. Maxwell et al reported on 108 PNET and SBNET patients with NETLM who underwent 70% tumor debulking with a median number of 6 lesions in their cohort. In their series they correlated 10 hepatic lesions with roughly a 10–19% hepatic replacement and concluded that patients with 10) of liver lesions using PSR and ablative techniques ( 17 ). While this study reported survival outcomes and postoperative complications across a wide range of debulking thresholds (mean 79%) with varying degrees of liver tumor involvement (5–70%) and numbers of lesions (median number 10), little is known about the effects on liver function and outcomes associated with higher degrees of surgical debulking. To address this, we analyzed our institutional data among patients with high volume of operable liver metastases who underwent 90% debulking. While the overall liver tumor involvement was less than 25%, more than half of our cohort had 16 lesions or greater. On assessing the impact of tumor debulking on liver function, we noted that while the degree of post-operative transaminitis, indicating hepatocellular injury, correlates with the extent of debulking, synthetic liver function was not affected by higher numbers of targeted lesions. Thrombocytopenia and anemia were the most common complications after surgical debulking. Thrombocytopenia, a post-operative phenomenon that can occur after liver resection, is thought to be due to a consumptive process in liver regeneration ( 18 – 20 ). In our series, we noted thrombocytopenia occurred commonly, but the severity was proportional to the numbers of lesions debulked. Overall, thrombocytopenia was generally transient with nadirs reached by POD 2, and a quicker recovery was noted than what has been reported after formal anatomic liver resections ( 21 ). Post-operative anemia requiring blood transfusion occurred in over a third of patients, although active hemorrhage was rare. Major complications defined as Clavien-Dindo grade 3 or 4 occurred in 13% of patients, but there were no differences in type or incidence based on the number of lesions debulked. Given our short study interval with median follow-up of 12 months, we assessed PFS rather than overall survival (OS). Although SBNETs seemed to have a longer PFS than PNETs, a trend that other studies have reported ( 1 , 10 , 22 , 23 ), our results did not reach statistical significance and may be due to multiple reasons, including smaller sample size, earlier detection of PFS due to better imaging, and perhaps even the difference in routine usage of SSA postoperatively. The median time to recurrence overall was 10.9 months, and while this is lower than what has been previously reported ( 10 , 24 ), we defined time to recurrence according to RECIST 1.1 criteria and had comparable results with a study who also applied this model ( 9 ). For surveillance, we used MRI abdomen with EOVIST, the most sensitive method for detection of new liver lesions or progression ( 25 ) which could impact our time to recurrence. Moreover, we only initiated SSA therapy immediately postoperatively in 20% of patients. Although data remains sparse, patients on SSA after debulking surgery may perhaps benefit with extended PFS. Various studies have reported poorer survival outcomes in NETLM patients with EHD and have questioned whether surgical debulking is beneficial ( 26 , 27 ). Interestingly, the presence of EHD in our patient cohort did not correlate with disease progression. In fact, we noted that of our twelve patients with EHD, only one patient with bone metastases had significant disease progression after surgical debulking that required several additional therapies. Contrastingly, nine patients that had EHD limited to the abdomen and pelvis either had no recurrence or stable disease without significant progression at most recent follow-up. Whether or not the location and extent of EHD (i.e, bone vs intraperitoneal) impacts survival differently requires further investigation. Among patients who had symptoms prior to debulking, all reported either improvement or relief of symptoms. At most recent follow-up after debulking, nearly half of patients did not have any disease progression. While SSA was eventually initiated in most patients postoperatively, only a few required additional treatments such as PRRT or chemo for disease progression. Our study is limited by its retrospective nature, small cohort and short term follow up interval. Furthermore, due to the highly-specialized, multi-disciplinary and standardized care that we provide for NET patients as one of few high-volume NET programs nationwide, our outcomes may not be entirely generalizable. Conclusions Tumor debulking in NETLM patients with larger numbers of lesions is feasible and safe with the use of PSR and MWA. Perioperative outcomes such as complications, mortality, and synthetic liver function are not affected by higher numbers of lesions and most patients have symptom relief after debulking. Thus, this therapy should be considered for NETLM patients with larger number of hepatic lesions as it may offer symptom and disease control. Abbreviations NET neuroendocrine tumor PSR parenchymal-sparing liver resections Abbreviations NET – neuroendocrine tumor PSR – parenchymal-sparing liver resections MWA - microwave ablations NETLM - neuroendocrine tumor liver metastases POD - postoperative day AST - aspartate aminotransferase ALT - alanine aminotransferase INR - international normalized ratio TB - total bilirubin LDT - liver directed therapy PNET - pancreatic neuroendocrine tumor SBNET - small bowel neuroendocrine tumor SSA - somatostatin analogues CAPTEM - capecitabine-temozolomide PRRT - peptide receptor radionuclide therapy RECIST - response evaluation criteria in solid tumors PFS - progression free survival EBL - estimated blood loss EHD - extrahepatic disease Declarations Ethics approval and consent to participate: Due to the retrospective nature of this study and deidentification of all data used for purposes of this study informed consent was waived and approved by our institutional review board. Consent for publication: not applicable. Availability of data and materials: All data and materials are maintained on a secure, encrypted drive and are available for review upon request. Competing interest: The authors declare that they have no conflicts nor competing interests. Funding: This study was conducted without any funding sources. Authors’ contributions: FT designed the study and performed data acquisition and manuscript preparation, JW assisted with data acquisition, RN performed data analysis and interpretation. JS, KR, BP, GR, CL and MM contributed meaningful revisions in the manuscript. XK conceived and helped to design the study and substantively revised it. Acknowledgements: We would like to acknowledge all the ancillary staff of our Neuroendocrine Tumor Program who assisted in the care NET patients and associated documentation. References Dasari A, Shen C, Halperin D, Zhao B, Zhou S, Xu Y, et al. Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States. JAMA Oncol. 2017;3(10):1335–42. Riihimäki M, Hemminki A, Sundquist K, Sundquist J, Hemminki K. The epidemiology of metastases in neuroendocrine tumors. Int J Cancer. 2016;139(12):2679–86. Garcia-Carbonero R, Sorbye H, Baudin E, Raymond E, Wiedenmann B, Niederle B, et al. ENETS Consensus Guidelines for High-Grade Gastroenteropancreatic Neuroendocrine Tumors and Neuroendocrine Carcinomas. Neuroendocrinology. 2016;103(2):186–94. Howe JR, Cardona K, Fraker DL, Kebebew E, Untch BR, Wang YZ, et al. The Surgical Management of Small Bowel Neuroendocrine Tumors: Consensus Guidelines of the North American Neuroendocrine Tumor Society. Pancreas. 2017;46(6):715–31. Keutgen XM, Schadde E, Pommier RF, Halfdanarson TR, Howe JR, Kebebew E. Metastatic neuroendocrine tumors of the gastrointestinal tract and pancreas: A surgeon's plea to centering attention on the liver. Semin Oncol. 2018;45(4):232–5. Glazer ES, Tseng JF, Al-Refaie W, Solorzano CC, Liu P, Willborn KA, et al. Long-term survival after surgical management of neuroendocrine hepatic metastases. HPB (Oxford). 2010;12(6):427–33. Graff-Baker AN, Sauer DA, Pommier SJ, Pommier RF. Expanded criteria for carcinoid liver debulking: Maintaining survival and increasing the number of eligible patients. Surgery. 2014;156(6):1369–76; discussion 76 – 7. Norton JA, Warren RS, Kelly MG, Zuraek MB, Jensen RT. Aggressive surgery for metastatic liver neuroendocrine tumors. Surgery. 2003;134(6):1057–63; discussion 63 – 5. Morgan RE, Pommier SJ, Pommier RF. Expanded criteria for debulking of liver metastasis also apply to pancreatic neuroendocrine tumors. Surgery. 2018;163(1):218–25. Maxwell JE, Sherman SK, O'Dorisio TM, Bellizzi AM, Howe JR. Liver-directed surgery of neuroendocrine metastases: What is the optimal strategy? Surgery. 2016;159(1):320–33. Tran CG, Sherman SK, Chandrasekharan C, Howe JR. Surgical Management of Neuroendocrine Tumor Liver Metastases. Surg Oncol Clin N Am. 2021;30(1):39–55. Luo Y, Ameli S, Pandey A, Khoshpouri P, Ghasabeh MA, Pandey P, et al. Semi-quantitative visual assessment of hepatic tumor burden can reliably predict survival in neuroendocrine liver metastases treated with transarterial chemoembolization. Eur Radiol. 2019;29(11):5804–12. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47. Givi B, Pommier SJ, Thompson AK, Diggs BS, Pommier RF. Operative resection of primary carcinoid neoplasms in patients with liver metastases yields significantly better survival. Surgery. 2006;140(6):891-7; discussion 7–8. Sarmiento JM, Heywood G, Rubin J, Ilstrup DM, Nagorney DM, Que FG. Surgical treatment of neuroendocrine metastases to the liver: a plea for resection to increase survival. J Am Coll Surg. 2003;197(1):29–37. Mayo SC, de Jong MC, Pulitano C, Clary BM, Reddy SK, Gamblin TC, et al. Surgical management of hepatic neuroendocrine tumor metastasis: results from an international multi-institutional analysis. Ann Surg Oncol. 2010;17(12):3129–36. Scott AT, Breheny PJ, Keck KJ, Bellizzi AM, Dillon JS, O'Dorisio TM, et al. Effective cytoreduction can be achieved in patients with numerous neuroendocrine tumor liver metastases (NETLMs). Surgery. 2019;165(1):166–75. McCaughan GW, Herkes R, Powers B, Rickard K, Gallagher ND, Thompson JF, et al. Thrombocytopenia post liver transplantation. Correlations with pre-operative platelet count, blood transfusion requirements, allograft function and outcome. J Hepatol. 1992;16(1–2):16–22. Alkozai EM, Nijsten MW, de Jong KP, de Boer MT, Peeters PM, Slooff MJ, et al. Immediate postoperative low platelet count is associated with delayed liver function recovery after partial liver resection. Ann Surg. 2010;251(2):300–6. Lesurtel M, Graf R, Aleil B, Walther DJ, Tian Y, Jochum W, et al. Platelet-derived serotonin mediates liver regeneration. Science. 2006;312(5770):104–7. Siu J, McCall J, Connor S. Systematic review of pathophysiological changes following hepatic resection. HPB (Oxford). 2014;16(5):407–21. Spolverato G, Bagante F, Tsilimigras DI, Pawlik TM. Liver transplantation in patients with liver metastases from neuroendocrine tumors. Minerva Chir. 2019;74(5):399–406. Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, et al. One hundred years after "carcinoid": epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26(18):3063–72. Keck KJ, Choi A, Maxwell JE, Li G, O'Dorisio TM, Breheny P, et al. Increased Grade in Neuroendocrine Tumor Metastases Negatively Impacts Survival. Ann Surg Oncol. 2017;24(8):2206–12. Morse B, Jeong D, Thomas K, Diallo D, Strosberg JR. Magnetic Resonance Imaging of Neuroendocrine Tumor Hepatic Metastases: Does Hepatobiliary Phase Imaging Improve Lesion Conspicuity and Interobserver Agreement of Lesion Measurements? Pancreas. 2017;46(9):1219–24. Ejaz A, Reames BN, Maithel S, Poultsides GA, Bauer TW, Fields RC, et al. The impact of extrahepatic disease among patients undergoing liver-directed therapy for neuroendocrine liver metastasis. J Surg Oncol. 2017;116(7):841–7. Spolverato G, Bagante F, Aldrighetti L, Poultsides GA, Bauer TW, Fields RC, et al. Management and outcomes of patients with recurrent neuroendocrine liver metastasis after curative surgery: An international multi-institutional analysis. J Surg Oncol. 2017;116(3):298–306. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2649826","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":180970870,"identity":"f226b7dd-4ea4-4b65-8d5e-08e9c3f63de9","order_by":0,"name":"Frances T. Lee","email":"","orcid":"","institution":"Southern Illinois University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Frances","middleName":"T.","lastName":"Lee","suffix":""},{"id":180970871,"identity":"e60323a1-b2a2-471b-b453-a6d50edee517","order_by":1,"name":"Jelani Williams","email":"","orcid":"","institution":"University of Chicago","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jelani","middleName":"","lastName":"Williams","suffix":""},{"id":180970872,"identity":"389e1a6c-a2d0-4a96-905f-6774eee39992","order_by":2,"name":"Rachel Nordgren","email":"","orcid":"","institution":"University of Chicago","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Rachel","middleName":"","lastName":"Nordgren","suffix":""},{"id":180970873,"identity":"abd287b2-c58b-4b82-a412-a8339cf71213","order_by":3,"name":"Jason L. Schwarz","email":"","orcid":"","institution":"University of Chicago","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jason","middleName":"L.","lastName":"Schwarz","suffix":""},{"id":180970874,"identity":"9d369f94-89e4-48fd-865e-561cf815b7a4","order_by":4,"name":"Namrata Setia","email":"","orcid":"","institution":"University of Chicago","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Namrata","middleName":"","lastName":"Setia","suffix":""},{"id":180970875,"identity":"c87b0504-3d96-46f4-9aa3-d02734ac4eef","order_by":5,"name":"Kevin Roggin","email":"","orcid":"","institution":"University of Chicago","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Kevin","middleName":"","lastName":"Roggin","suffix":""},{"id":180970876,"identity":"dea95b51-d090-4aa5-8689-ad51aff4d888","order_by":6,"name":"Blase Polite","email":"","orcid":"","institution":"University of Chicago","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Blase","middleName":"","lastName":"Polite","suffix":""},{"id":180970877,"identity":"a32e6b4e-2314-47ec-b8d0-c2d169a5b86c","order_by":7,"name":"Govind Rangrass","email":"","orcid":"","institution":"University of Chicago","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Govind","middleName":"","lastName":"Rangrass","suffix":""},{"id":180970878,"identity":"cd0d011c-ad07-4071-a931-ec5efa6ae101","order_by":8,"name":"Chih-Yi Liao","email":"","orcid":"","institution":"University of Chicago","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Chih-Yi","middleName":"","lastName":"Liao","suffix":""},{"id":180970879,"identity":"2e236da5-e4d7-47fe-bfcb-45f7dd213251","order_by":9,"name":"J. Michael Millis","email":"","orcid":"","institution":"University of Chicago","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"J.","middleName":"Michael","lastName":"Millis","suffix":""},{"id":180970880,"identity":"3c65ad67-957e-4244-be7f-8caca2cc4e19","order_by":10,"name":"Xavier M. Keutgen","email":"data:image/png;base64,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","orcid":"","institution":"University of Chicago","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Xavier","middleName":"M.","lastName":"Keutgen","suffix":""}],"badges":[],"createdAt":"2023-03-03 05:14:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2649826/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2649826/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":34042376,"identity":"cfc35981-531d-4105-b404-9dd7d18cfb35","added_by":"auto","created_at":"2023-03-10 00:08:32","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":339973,"visible":true,"origin":"","legend":"\u003cp\u003eMRI abdomen with EOVIST for NET patients demonstrating enhancing metastatic liver lesions (white arrowhead) prior to surgical debulking and ablation in (a) SBNET and (d) PNET patient. Representative surveillance images for SBNET patient after primary tumor resection, one partial lobectomy, nine enucleations and nine microwave ablations at 3 months (b) and 36 months (c) after debulking showing hypodense post-ablation zones (yellow arrow) without disease progression. Representative images for a PNET patient after distal pancreatectomy of primary tumor, one partial lobectomy, and eight microwave ablations at 3 months (e) and 15 months (f) without disease progression.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2649826/v1/8a34986817ff5c03ec00bf87.jpg"},{"id":34042375,"identity":"1c1900a6-8fd1-49ae-9130-8c0c863fdc94","added_by":"auto","created_at":"2023-03-10 00:08:32","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":342646,"visible":true,"origin":"","legend":"\u003cp\u003e“Perioperative laboratory trends of liver function tests in NET patients stratified by number of lesions debulked”. Daily median laboratory values for alanine aminotransferase (ALT; IU/L), aspartate aminotransferase (AST; IU/L), prothrombin time international normalized ratio (INR), inorganic phosphate (phos; mg/dL), platelets (PLT; 10\u003csup\u003e9\u003c/sup\u003e/L) and total bilirubin (TB; mg/dL) represented over the first 5 days of surgical debulking in NETLM patients. (a) Stratification by patients with 1-15 or greater than 15 lesions, respectively: POD 1 ALT (596 vs 1149 IU/L; \u003cem\u003ep\u003c/em\u003e = 0.01). POD 1 AST (681 vs 1396 IU/L; \u003cem\u003ep\u003c/em\u003e = 0.01). POD 1 INR (1.3 vs 1.4; \u003cem\u003ep\u003c/em\u003e=0.21). POD 2 phos (2.05 vs 1.8; \u003cem\u003ep\u003c/em\u003e= 0.74). POD 2 PLT (157 x 10\u003csup\u003e9\u003c/sup\u003e vs 109 x10\u003csup\u003e9\u003c/sup\u003e/L; \u003cem\u003ep\u003c/em\u003e=0.04). POD 2 TB (1.35 vs 0.95 mg/dL; \u003cem\u003ep\u003c/em\u003e = 0.67). (b) Stratification by patients with 0-5 lesions, 6-15 lesions, 16-25 lesions, and greater than 25 lesions.\u003c/p\u003e","description":"","filename":"2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-2649826/v1/7ff753a74caf2227bf56112d.jpeg"},{"id":34043405,"identity":"0b2d567a-d21f-4bab-8ce8-eab0eca1def9","added_by":"auto","created_at":"2023-03-10 00:16:32","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":116093,"visible":true,"origin":"","legend":"\u003cp\u003e“Progression-free survival in NETLM patients post debulking with PSR and MWA”. Progression free survival (PFS) stratified by NET tumor type (a) and number of lesions (b).\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2649826/v1/d06f43f1bb25a99175136c24.jpg"},{"id":36476714,"identity":"9f811e89-ac2f-460a-b66a-41eda0bf429c","added_by":"auto","created_at":"2023-04-30 15:14:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":926023,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2649826/v1/52e9f973-ab4f-4644-8763-2c0bc7038959.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Single Center Outcomes from Parenchymal-sparing Resections and Microwave Ablations for Neuroendocrine Tumor Liver Metastases","fulltext":[{"header":"Introduction","content":"\u003cp\u003eWhile generally considered rare, neuroendocrine tumors (NETs) have a rising incidence in the United States, affecting over 12,000 patients each year (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Although described as indolent, these neoplasms exhibit significant metastatic potential most commonly to the liver (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Neuroendocrine tumor liver metastases (NETLM) affect up to two-thirds of patients at initial diagnosis and progression of disease is common (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Increasing hepatic tumor burden can lead to liver failure and death (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Thus, control of liver disease is an important prognostic marker for these patients (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAvailable treatment options for NETLMs include systemic radiolabeled-, targeted- and cytotoxic chemotherapy, non-surgical liver directed therapy (LDT), and surgical resection. Although rarely curative, surgical debulking reduces tumor load in the liver, palliates symptoms and can dramatically improve overall survival with up to 90% 5-year survival reported (\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Moreover, debulking thresholds are typically set above 70% in patients with operable disease to achieve maximal benefits (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSurgical approaches to hepatic tumor debulking for NETLMs range from \u003cem\u003eformal\u003c/em\u003e anatomic resections to \u003cem\u003eparenchymal-sparing\u003c/em\u003e resections (PSR) which include enucleations, wedge resections and partial lobectomies (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). As debulking is applied to larger patient groups with increasing number of NETLMs, concerns about associated complications emerge. Reported perioperative outcomes of surgical debulking in NETLM patients have been lacking with respect to impact on liver function and morbidity proportionality to tumor burden. In this study, we report our single institutional experience in surgical debulking of NETLM patients using PSR and microwave ablative (MWA) techniques. Our objectives were to assess 1) feasibility of 90% tumor debulking in patients with large numbers of lesions, 2) safety of advanced debulking by comparing the incidence and degree of complications among patients with various numbers of lesions, and 3) the impact of debulking on postoperative liver function, symptom control and progression-free survival (PFS).\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e In accordance with an IRB-approved protocol, a retrospective review of NETLM patients that underwent surgical debulking at our institution from January 2019 to December 2021 was performed. All patients were under the care of our multidisciplinary NET program and were operated on by the same primary surgeon. Preoperatively, hepatic tumor burden and extrahepatic disease were assessed by abdominopelvic MRI with hepatobiliary contrast (EOVIST) and DOTATE-PET/CT (\u003csup\u003e68\u003c/sup\u003eGa and \u003csup\u003e64\u003c/sup\u003eCu) imaging. A debulking goal of at least 90% was attempted when possible, and all patients had \u0026le; 25% liver tumor involvement, as defined by semi-quantitative measurements (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Operations included first time surgical debulking with or without primary tumor resection, and re-operative debulking in patients with recurrent liver metastases after initial primary resection or prior debulking. Operations were performed using PSR, as described previously, combined with intraoperative ultrasound-guided 3-dimensional navigation MWA (Medtronic). The number of lesions targeted were delineated in operative reports. Wedge resections and enucleations were classified as the same technique for practicality. Percent of tumor debulked was estimated by the surgical team as the number of lesions targeted intraoperatively divided by the total number of lesions identified on pre-operative MRI. All patients underwent serial postoperative imaging every 3 months with MRI with EOVIST.\u003c/p\u003e \u003cp\u003eVarious clinicopathologic data were reviewed. Since most patients had either a pancreatic NET (PNET) or small bowel NET (SBNET), comparative analyses were performed between these two groups. Specifically, trends between laboratory values for platelets, hepatic enzymes, phosphorus, and coagulation factors in the preoperative and immediate post-operative periods were analyzed. Serum and urine tumor markers for chromogranin A and serotonin were also compared pre- and post- operatively to assess for a biochemical response to surgery which was defined as \u0026gt;\u0026thinsp;50% decrease from a baseline elevated level. Post-operative symptomatic response was a secondary endpoint defined upon review of standardized clinical documentation during follow up visits. Somatostatin analogues (SSA) were continued post-operatively for patients who remained symptomatic, had limited debulking, or G2 PNETs. Patients with progressive disease after surgery were offered subsequent therapies in the form of chemotherapy (capecitabine-temozolomide; CAPTEM), peptide receptor radionuclide therapy (PRRT), and LDT. Recurrence or progression of disease after debulking was defined as new or evolving lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 standards on serial surveillance MRI (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). PFS was assessed using the Kaplan-Meier method. A univariate analysis for clinicopathologic variables was performed using Cox\u0026rsquo;s proportional hazards regression. Patient characteristics, complication rates and perioperative laboratory values between patient groups were compared using linear regression, Fisher\u0026rsquo;s exact, Kruskal-Wallis, and Wilcoxon Signed Rank tests. All statistical analyses were performed in R (v 4.1.1, Vienna, Austria). Perioperative morbidity and mortality were assessed using the Clavien-Dindo classification.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003ePreoperative clinicopathologic characteristics of 53 NETLM patients who underwent debulking are displayed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The majority had a well differentiated, metastatic SBNET (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;34) or a PNET (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;15) with grade 1 or 2 disease. One patient had a well-differentiated grade 3 NET and was one of two patients with unknown etiology of primary tumor. The remaining two patients had either a gastric or lung NET. The median age at time of operation was 57 years. 43% of the patient cohort had symptomatic disease, of which 40% had carcinoid syndrome. Over 95% of patients had bilobar liver metastases, and 23% of patients had extrahepatic disease (EHD), with common sites including the peritoneum (diaphragm, omentum and pelvis) or bone. Preoperative systemic therapy with SSA, CAPTEM and/or PRRT had been given in 79%, 11%, and 7.5% of patients, respectively.\u003c/p\u003e \u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e. \u0026ldquo;Comparison of NET patients preoperative clinicopathologic characteristics\u0026rdquo;\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAll\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSBNET\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePNET\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian age (yrs; range)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e57 (49-60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e57 (49.5-62.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e57 (48-60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e29/53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e19/34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e7/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e24/53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e15/34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRace/Ethnicity\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eWhite\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Black\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Hispanic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e38/48\u003c/p\u003e\n \u003cp\u003e8/48\u003c/p\u003e\n \u003cp\u003e2/48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e23/32\u003c/p\u003e\n \u003cp\u003e8/32\u003c/p\u003e\n \u003cp\u003e1/32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12/13\u003c/p\u003e\n \u003cp\u003e0/13\u003c/p\u003e\n \u003cp\u003e1/13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrimary tumor location\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eUnknown\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Stomach\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Lung\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Head of pancreas\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Tail/body of pancreas\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;SB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSymptomatic disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e25/53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e21/34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCarcinoid syndrome\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e21/52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e19/34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1/14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTumor grade\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eG1\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;G2\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;G3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e29/52\u003c/p\u003e\n \u003cp\u003e22/52\u003c/p\u003e\n \u003cp\u003e1/52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e25/33\u003c/p\u003e\n \u003cp\u003e8/33\u003c/p\u003e\n \u003cp\u003e0/33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4/15\u003c/p\u003e\n \u003cp\u003e11/15\u003c/p\u003e\n \u003cp\u003e0/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eChromogranin (CgA)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e200.5 (93.5-771)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e225.5 (125-621)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e68 (51-113)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eElevated CgA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e31/42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e24/25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4/11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSerotonin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e894 (185-1818)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1140 (566-1955)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e176 and 256 \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eElevated serotonin or 5-HIAA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e23/26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e21/23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2/3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAST\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e23 (19-27.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e22 (19-27)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e23 (20-25.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.42\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eALT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e22 (16.8-33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e19 (15-31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e23 (18.5-32.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal Bilirubin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.5 (0.3-0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.5 (0.3-0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.5 (0.4 \u0026ndash; 0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eINR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1 (1-1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1 (1-1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1 (1-1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBilateral liver mets\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e51/53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e32/34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e15/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eLymphadenopathy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e35/53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e24/34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eExtrahepatic disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e12/53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8/34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePreop systemic therapy\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eSomatostatin analogue\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Chemo\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;(CAPTEM)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;PRRT\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e43/53\u003c/p\u003e\n \u003cp\u003e42/53\u003c/p\u003e\n \u003cp\u003e6/53\u003c/p\u003e\n \u003cp\u003e4/53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e28/34\u003c/p\u003e\n \u003cp\u003e28/34\u003c/p\u003e\n \u003cp\u003e0/34\u003c/p\u003e\n \u003cp\u003e2/34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e14/15\u003c/p\u003e\n \u003cp\u003e13/15\u003c/p\u003e\n \u003cp\u003e6/15\u003c/p\u003e\n \u003cp\u003e2/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\u003cbr\u003e \u003cp\u003eIntraoperative characteristics are reported in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. A total of 1069 hepatic lesions were debulked collectively with PSR (45%) and MWA (55%). Stratified by number of lesions, 21% (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;11) had up to 5 lesions, 23% (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;12) had 6\u0026ndash;15, 28% (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;15) had 16\u0026ndash;25, and 28% (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;15) had\u0026thinsp;\u0026gt;\u0026thinsp;25 lesions debulked. The highest number of lesions debulked in one patient was fifty-six. The median number of lesions targeted was 17 overall. All patients, except for two, had\u0026thinsp;\u0026gt;\u0026thinsp;90% tumor debulking at the time of operation. Over 70% of patients had synchronous resection of the primary tumor as their first operation, which they had on average 6.5 months after initial diagnosis. The average estimated blood loss (EBL) was 300 ml for all cases, 13% of which required at least 1 intraoperative transfusion of packed red blood cells.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e. \u0026ldquo;Operative characteristics for NETLM patients by tumor type\u0026rdquo;\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"32.37179487179487%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.512820512820515%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAll\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.871794871794872%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSBNET\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.55128205128205%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePNET\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"32.37179487179487%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime to 1\u003csup\u003est\u003c/sup\u003e surgery (months)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.512820512820515%\"\u003e\n \u003cp\u003e6.5 (3.0-13.9) (\u003cem\u003en=38\u003c/em\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.871794871794872%\"\u003e\n \u003cp\u003e5.1 (2.8-13.5) (\u003cem\u003en=26\u003c/em\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.55128205128205%\"\u003e\n \u003cp\u003e11.9 (9.9-16.3) (\u003cem\u003en=10\u003c/em\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"32.37179487179487%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrimary tumor resection\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.512820512820515%\"\u003e\n \u003cp\u003e38/52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.871794871794872%\"\u003e\n \u003cp\u003e28/34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.55128205128205%\"\u003e\n \u003cp\u003e9/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"32.37179487179487%\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of liver debulking\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Partial lobectomy\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Wedge/enucleation\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;MWA\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Superficial ablation\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Formal resection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.512820512820515%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;60 total in 38/53\u003c/p\u003e\n \u003cp\u003e417 total in 48/53\u003c/p\u003e\n \u003cp\u003e438 total in 47/53\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;152 total in 6/53\u003c/p\u003e\n \u003cp\u003e2 total in 3/53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.871794871794872%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e36 total in 23/34\u003c/p\u003e\n \u003cp\u003e294 total in 32/34\u003c/p\u003e\n \u003cp\u003e244 total in 29/34\u003c/p\u003e\n \u003cp\u003e52 total in 2/34\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;2 total in 2/34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.55128205128205%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e26 total in 14/15\u003c/p\u003e\n \u003cp\u003e90 total in 13/15\u003c/p\u003e\n \u003cp\u003e175 total in 14/15\u003c/p\u003e\n \u003cp\u003e100 total in 4/15\u003c/p\u003e\n \u003cp\u003e0/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003cp\u003e0.51\u003c/p\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"32.37179487179487%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian # of lesions debulked\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTotal # of lesions debulked\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.512820512820515%\"\u003e\n \u003cp\u003e17.5 (7-29)\u003c/p\u003e\n \u003cp\u003e1069\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.871794871794872%\"\u003e\n \u003cp\u003e16.5 (6-25.8)\u003c/p\u003e\n \u003cp\u003e632\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.55128205128205%\"\u003e\n \u003cp\u003e22 (15-38.5)\u003c/p\u003e\n \u003cp\u003e402\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e0.10\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"32.37179487179487%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSites of extrahepatic mets\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003e Intraperitoneal (diaphragm,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003epelvis, omentum)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Bone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.512820512820515%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e10/12\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2/12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.871794871794872%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7/8\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1/8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.55128205128205%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3/4\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1/4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"32.37179487179487%\"\u003e\n \u003cp\u003e\u003cstrong\u003eEBL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.512820512820515%\"\u003e\n \u003cp\u003e300 (\u003cem\u003en=52\u003c/em\u003e)\u003c/p\u003e\n \u003cp\u003e(150-500)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.871794871794872%\"\u003e\n \u003cp\u003e225\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(100-388)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.55128205128205%\"\u003e\n \u003cp\u003e500\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(250-825)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"32.37179487179487%\"\u003e\n \u003cp\u003e\u003cstrong\u003eIntraoperative Transfusion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.512820512820515%\"\u003e\n \u003cp\u003e7/53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.871794871794872%\"\u003e\n \u003cp\u003e2/34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.55128205128205%\"\u003e\n \u003cp\u003e5/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.6923076923076925%\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eWith respect to liver function, a surge in liver enzymes measured on post-operative day (POD) 1 was proportional to the numbers of debulked lesions (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA, B, C). For patients with 1\u0026ndash;15 lesions targeted, the median POD 1 AST and ALT values were 681 and 596 IU/L, respectively, compared to 1396 and 1149 IU/L, respectively, for patients with greater than 15 lesions (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01). The degree of transaminitis linearly correlated with increasing numbers of hepatic lesions debulked (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) but this effect typically resolved by POD 5. \u003cem\u003eSynthetic\u003c/em\u003e liver function, assessed by changes in post-operative INR, did not differ significantly among patients and did not have a linear correlation with increasing number of lesions (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.151). Hypophosphatemia, a common post-operative finding after liver resection, was noted to be most prominent on POD 2, but the degree did not differ among the various numbers of lesions debulked (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe median length of inpatient stay after debulking was 7 days (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Thrombocytopenia (platelets\u0026thinsp;\u0026lt;\u0026thinsp;150 x 10\u003csup\u003e9\u003c/sup\u003e/L) was the most common complication occurring in over 75% of patients and most cases were transient. Two patients developed heparin-induced thrombocytopenia (HIT) and were excluded from further analyses. The severity of thrombocytopenia was proportionate to the number of lesions debulked (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003) with median POD2 platelet values 157 x 10\u003csup\u003e9\u003c/sup\u003e/L for 1\u0026ndash;15 lesions vs. 109 x 10\u003csup\u003e9\u003c/sup\u003e/L for \u0026gt;\u0026thinsp;15 lesions (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.04). However, the incidence of thrombocytopenia did not significantly differ between groups.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e. \u0026ldquo;Morbidity and Mortality for patients per NET type and number of lesions debulked\u0026rdquo;. LOS = length of stay; EBL = intraoperative estimated blood loss\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"750\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"20.8%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"10.4%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eALL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" width=\"25.6%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNET Type\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"top\" width=\"43.2%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo. of lesions debulked\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"13.953488372093023%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSBNET\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.953488372093023%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePNET\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.30232558139535%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.953488372093023%\"\u003e\n \u003cp\u003e\u003cstrong\u003e1-5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.953488372093023%\"\u003e\n \u003cp\u003e\u003cstrong\u003e6-15\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.790697674418604%\"\u003e\n \u003cp\u003e\u003cstrong\u003e16-25\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.953488372093023%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026gt;25\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.13953488372093%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20.8%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal complications\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eAny\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eGI\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eReadmission\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eBile leak\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePVT\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHIT\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eThrombocytopenia\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHemorrhage or Anemia\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eInfection\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNeed for re-exploration\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.4%\"\u003e\n \u003cp\u003e1 (1-2)\u003c/p\u003e\n \u003cp\u003e45/53\u003c/p\u003e\n \u003cp\u003e4/53\u003c/p\u003e\n \u003cp\u003e4/53\u003c/p\u003e\n \u003cp\u003e4/53\u003c/p\u003e\n \u003cp\u003e1/53\u003c/p\u003e\n \u003cp\u003e2/53\u003c/p\u003e\n \u003cp\u003e41/53\u003c/p\u003e\n \u003cp\u003e19/53\u003c/p\u003e\n \u003cp\u003e8/53\u003c/p\u003e\n \u003cp\u003e2/53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e1 (1-2)\u003c/p\u003e\n \u003cp\u003e27/34\u003c/p\u003e\n \u003cp\u003e2/34\u003c/p\u003e\n \u003cp\u003e0/34\u003c/p\u003e\n \u003cp\u003e2/34\u003c/p\u003e\n \u003cp\u003e0/34\u003c/p\u003e\n \u003cp\u003e1/34\u003c/p\u003e\n \u003cp\u003e25/34\u003c/p\u003e\n \u003cp\u003e9/34\u003c/p\u003e\n \u003cp\u003e1/34\u003c/p\u003e\n \u003cp\u003e2/34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e2 (1-3)\u003c/p\u003e\n \u003cp\u003e10/14\u003c/p\u003e\n \u003cp\u003e2/15\u003c/p\u003e\n \u003cp\u003e2/15\u003c/p\u003e\n \u003cp\u003e1/15\u003c/p\u003e\n \u003cp\u003e0/15\u003c/p\u003e\n \u003cp\u003e0/15\u003c/p\u003e\n \u003cp\u003e12/15\u003c/p\u003e\n \u003cp\u003e9/15\u003c/p\u003e\n \u003cp\u003e6/15\u003c/p\u003e\n \u003cp\u003e0/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.4%\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003cp\u003e0.73\u003c/p\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e1 (0.5-1.5)\u003c/p\u003e\n \u003cp\u003e8/11\u003c/p\u003e\n \u003cp\u003e1/11\u003c/p\u003e\n \u003cp\u003e1/11\u003c/p\u003e\n \u003cp\u003e1/11\u003c/p\u003e\n \u003cp\u003e0/11\u003c/p\u003e\n \u003cp\u003e0/11\u003c/p\u003e\n \u003cp\u003e7/11\u003c/p\u003e\n \u003cp\u003e2/11\u003c/p\u003e\n \u003cp\u003e0/11\u003c/p\u003e\n \u003cp\u003e0/11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e1 (1-3)\u003c/p\u003e\n \u003cp\u003e11/12\u003c/p\u003e\n \u003cp\u003e2/12\u003c/p\u003e\n \u003cp\u003e1/12\u003c/p\u003e\n \u003cp\u003e2/12\u003c/p\u003e\n \u003cp\u003e1/12\u003c/p\u003e\n \u003cp\u003e1/12\u003c/p\u003e\n \u003cp\u003e9/12\u003c/p\u003e\n \u003cp\u003e5/12\u003c/p\u003e\n \u003cp\u003e3/12\u003c/p\u003e\n \u003cp\u003e1/12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.8%\"\u003e\n \u003cp\u003e1 (0.5-2)\u003c/p\u003e\n \u003cp\u003e11/15\u003c/p\u003e\n \u003cp\u003e0/15\u003c/p\u003e\n \u003cp\u003e0/15\u003c/p\u003e\n \u003cp\u003e1/15\u003c/p\u003e\n \u003cp\u003e0/15\u003c/p\u003e\n \u003cp\u003e0/15\u003c/p\u003e\n \u003cp\u003e11/15\u003c/p\u003e\n \u003cp\u003e6/15\u003c/p\u003e\n \u003cp\u003e1/15\u003c/p\u003e\n \u003cp\u003e0/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e2 (1-2)\u003c/p\u003e\n \u003cp\u003e15/15\u003c/p\u003e\n \u003cp\u003e1/15\u003c/p\u003e\n \u003cp\u003e2/15\u003c/p\u003e\n \u003cp\u003e0/15\u003c/p\u003e\n \u003cp\u003e0/15\u003c/p\u003e\n \u003cp\u003e1/15\u003c/p\u003e\n \u003cp\u003e14/15\u003c/p\u003e\n \u003cp\u003e6/15\u003c/p\u003e\n \u003cp\u003e4/15\u003c/p\u003e\n \u003cp\u003e1/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.6%\"\u003e\n \u003cp\u003e0.30\u003c/p\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003cp\u003e0.60\u003c/p\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003cp\u003e0.84\u003c/p\u003e\n \u003cp\u003e0.30\u003c/p\u003e\n \u003cp\u003e0.60\u003c/p\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003cp\u003e0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20.8%\"\u003e\n \u003cp\u003e\u003cstrong\u003eClavien-Dindo class\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;None\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;I\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;II\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;III\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;IV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.4%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7/53\u003c/p\u003e\n \u003cp\u003e25/53\u003c/p\u003e\n \u003cp\u003e14/53\u003c/p\u003e\n \u003cp\u003e6/53\u003c/p\u003e\n \u003cp\u003e1/53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7/34\u003c/p\u003e\n \u003cp\u003e18/34\u003c/p\u003e\n \u003cp\u003e7/34\u003c/p\u003e\n \u003cp\u003e1/34\u003c/p\u003e\n \u003cp\u003e1/34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0/15\u003c/p\u003e\n \u003cp\u003e5/15\u003c/p\u003e\n \u003cp\u003e7/15\u003c/p\u003e\n \u003cp\u003e3/15\u003c/p\u003e\n \u003cp\u003e0/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.4%\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3/11\u003c/p\u003e\n \u003cp\u003e6/11\u003c/p\u003e\n \u003cp\u003e1/11\u003c/p\u003e\n \u003cp\u003e1/11\u003c/p\u003e\n \u003cp\u003e0/11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1/12\u003c/p\u003e\n \u003cp\u003e5/12\u003c/p\u003e\n \u003cp\u003e4/12\u003c/p\u003e\n \u003cp\u003e1/12\u003c/p\u003e\n \u003cp\u003e1/12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.8%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3/15\u003c/p\u003e\n \u003cp\u003e6/15\u003c/p\u003e\n \u003cp\u003e3/15\u003c/p\u003e\n \u003cp\u003e3/15\u003c/p\u003e\n \u003cp\u003e0/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0/15\u003c/p\u003e\n \u003cp\u003e8/15\u003c/p\u003e\n \u003cp\u003e6/15\u003c/p\u003e\n \u003cp\u003e1/15\u003c/p\u003e\n \u003cp\u003e0/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.6%\"\u003e\n \u003cp\u003e0.69\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20.8%\"\u003e\n \u003cp\u003e\u003cstrong\u003eIntraop transfusion\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.4%\"\u003e\n \u003cp\u003e7/53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e2/34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e5/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.4%\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e1/11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e3/12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.8%\"\u003e\n \u003cp\u003e0/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e3/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.6%\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20.8%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePost op transfusion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.4%\"\u003e\n \u003cp\u003e17/53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e9/34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e8/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.4%\"\u003e\n \u003cp\u003e0.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e1/11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e5/12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.8%\"\u003e\n \u003cp\u003e5/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e6/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.6%\"\u003e\n \u003cp\u003e0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20.8%\"\u003e\n \u003cp\u003e\u003cstrong\u003e30-day mortality\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.4%\"\u003e\n \u003cp\u003e0/50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e0/34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e0/11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.4%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e0/10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e0/12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.8%\"\u003e\n \u003cp\u003e0/14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e0/14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.6%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20.8%\"\u003e\n \u003cp\u003e\u003cstrong\u003e1 year mortality\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.4%\"\u003e\n \u003cp\u003e1/31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e0/22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e1/8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.4%\"\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e0/5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e0/9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.8%\"\u003e\n \u003cp\u003e0/11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e1/6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.6%\"\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20.8%\"\u003e\n \u003cp\u003e\u003cstrong\u003eLOS (days)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.4%\"\u003e\n \u003cp\u003e7 (6-8)\u0026nbsp;(n=52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e6.5 (6-7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e7 (6-8)\u0026nbsp;(n=14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.4%\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e6 (5-6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e6.5 (6-8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.8%\"\u003e\n \u003cp\u003e7 (5-8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e7 (6-7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.6%\"\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20.8%\"\u003e\n \u003cp\u003e\u003cstrong\u003eEBL (mL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.4%\"\u003e\n \u003cp\u003e300 (n=47)\u003c/p\u003e\n \u003cp\u003e(150-500)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e225\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(100-388)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e500\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(250-825)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.4%\"\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e250\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(100-400)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e250\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(100-675)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.8%\"\u003e\n \u003cp\u003e300\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(150-550)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.6%\"\u003e\n \u003cp\u003e350\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(200-500)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.6%\"\u003e\n \u003cp\u003e0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\u003c/p\u003e \u003cp\u003ePost-operative blood loss anemia requiring transfusion was the second most common complication, affecting 36% of patients. Active post-operative hemorrhage occurred in 4 patients as UGI bleeding (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2) or intraabdominal bleeding (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2) requiring re-exploration. Bile leaks occurred in four patients with a leak-to-resected lesion ratio of 0.9%. Two cases resolved spontaneously without added intervention, one case resulted in a biloma requiring percutaneous drainage, and one case occurred after re-exploration for delayed intra-abdominal bleeding and required biliary stenting. GI complications including persistent ileus (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2), delayed gastric emptying (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1) or post-operative bowel obstruction (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1) occurred in 4 patients. Of these, the obstructed patient required re-exploration to rule out bowel ischemia. There was one case of portal vein thrombosis that occurred in the setting of HIT and required anticoagulation. Infectious complications including urinary tract infection (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2), pancreatic fistula (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;3), or intra-abdominal abscess (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;3) requiring intervention occurred in 8 patients. Overall, 13% of patients had a Clavien-Dindo grade 3 or 4 complication. While there was no 30-day mortality in our patient group, one patient died on POD 38 from NSAID-induced UGI bleeding that was managed outside of our institution.\u003c/p\u003e \u003cp\u003ePost-operatively, median long-term follow-up was 12.1 months (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). All symptomatic patients reported symptom improvement or relief after surgery. Over 80% of patients had a biochemical response with a\u0026thinsp;\u0026gt;\u0026thinsp;50% decrease in serotonin levels after surgery. 50% of patients did not require subsequent systemic therapy at their most-recent follow-up and either had no evidence of disease (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;17) or stable disease without progression (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;9). The median time to recurrence after debulking was 10.9 months for all patients. There was no significant difference in PFS between PNET and SBNET patients (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA 11.9 vs. 22.3 months; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.095) or between patients with higher vs. lower number of lesions debulked (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB 1\u0026ndash;15 lesions: 22.8 months vs. \u0026gt;15 lesions: 16 months; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.38). In cases of disease progression, five patients required the addition of PRRT: 40% had decrease in hepatic lesion size while 60% halted in disease progression. One PNET patient required CAPTEM as subsequent systemic therapy followed by pembrolizumab for tumor de-differentiation. Seven patients underwent post-operative LDT for disease recurrence with either bland embolization or percutaneous ablation. Hazard regression univariate analysis (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e indicated that among our cohort, primary tumor size, higher numbers of hepatic lesions, EHD, and other pathologic variables did not correlate with disease progression.\u003c/p\u003e \u003cp\u003e\u003cstrong\u003eTable 4\u003c/strong\u003e. \u0026ldquo;Postoperative characteristics after tumor debulking by NET type\u0026rdquo;.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"629\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"31.904761904761905%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.841269841269842%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAll\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.682539682539684%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSBNET\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.365079365079364%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePNET\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.206349206349206%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"31.904761904761905%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSymptomatic response\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eBiochemical response\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Chromogranin\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Serotonin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.841269841269842%\"\u003e\n \u003cp\u003e24/24\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12/19\u003c/p\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.682539682539684%\"\u003e\n \u003cp\u003e21/21\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e11/17\u003c/p\u003e\n \u003cp\u003e5/6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.365079365079364%\"\u003e\n \u003cp\u003e3/3\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1/2\u003c/p\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.206349206349206%\"\u003e\n \u003cp\u003e\u0026nbsp; 1.00\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"31.904761904761905%\"\u003e\n \u003cp\u003e\u003cstrong\u003eFinal Pathology\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Ki-67\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026lt; 3%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 3-5%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 5-10%\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026gt;10%\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Lymphovascular invasion\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Perineural invasion\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Mesenteric deposits\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.841269841269842%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e25/35\u003c/p\u003e\n \u003cp\u003e5/35\u003c/p\u003e\n \u003cp\u003e4/35\u003c/p\u003e\n \u003cp\u003e1/35\u003c/p\u003e\n \u003cp\u003e35/36\u003c/p\u003e\n \u003cp\u003e33/37\u003c/p\u003e\n \u003cp\u003e20/53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.682539682539684%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e21/26\u003c/p\u003e\n \u003cp\u003e2/26\u003c/p\u003e\n \u003cp\u003e2/26\u003c/p\u003e\n \u003cp\u003e1/26\u003c/p\u003e\n \u003cp\u003e25/26\u003c/p\u003e\n \u003cp\u003e24/27\u003c/p\u003e\n \u003cp\u003e20/34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.365079365079364%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4/9\u003c/p\u003e\n \u003cp\u003e3/9\u003c/p\u003e\n \u003cp\u003e2/9\u003c/p\u003e\n \u003cp\u003e0/9\u003c/p\u003e\n \u003cp\u003e10/10\u003c/p\u003e\n \u003cp\u003e9/10\u003c/p\u003e\n \u003cp\u003e0/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.206349206349206%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"31.904761904761905%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjuvant systemic therapy\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;None\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;1 agent\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;2 agents\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;3 or more agents\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.841269841269842%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e26/51\u003c/p\u003e\n \u003cp\u003e17/51\u003c/p\u003e\n \u003cp\u003e4/51\u003c/p\u003e\n \u003cp\u003e4/51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.682539682539684%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e17/34\u003c/p\u003e\n \u003cp\u003e12/34\u003c/p\u003e\n \u003cp\u003e2/34\u003c/p\u003e\n \u003cp\u003e3/34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.365079365079364%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6/14\u003c/p\u003e\n \u003cp\u003e5/14\u003c/p\u003e\n \u003cp\u003e2/14\u003c/p\u003e\n \u003cp\u003e1/14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.206349206349206%\"\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"31.904761904761905%\"\u003e\n \u003cp\u003e\u003cstrong\u003eLiver-directed perc ablation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.841269841269842%\"\u003e\n \u003cp\u003e8/43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.682539682539684%\"\u003e\n \u003cp\u003e3/29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.365079365079364%\"\u003e\n \u003cp\u003e5/11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.206349206349206%\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"31.904761904761905%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian time to (months):\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Most recent follow-up\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Recurrence\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;1\u003csup\u003est\u003c/sup\u003e adjuvant therapy\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;2\u003csup\u003end\u003c/sup\u003e adjuvant therapy\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;3\u003csup\u003erd\u003c/sup\u003e adjuvant therapy\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Liver-directed therapy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.841269841269842%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12.1 (3.9-21.0) (\u003cem\u003en=52\u003c/em\u003e)\u003c/p\u003e\n \u003cp\u003e10.9 (6.7-18.7) (\u003cem\u003en=24\u003c/em\u003e)\u003c/p\u003e\n \u003cp\u003e1.6 (0.9-8.3) (\u003cem\u003en=23\u003c/em\u003e)\u003c/p\u003e\n \u003cp\u003e12.0 (10.3-21.2) (\u003cem\u003en=7\u003c/em\u003e)\u003c/p\u003e\n \u003cp\u003e14.0, 16.3, \u0026amp; 21.9 (\u003cem\u003en=3\u003c/em\u003e)\u003c/p\u003e\n \u003cp\u003e14.5 (9.0-20.5) (\u003cem\u003en=8\u003c/em\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.682539682539684%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15.0 (4.8-22.7) (\u003cem\u003en=34\u003c/em\u003e)\u003c/p\u003e\n \u003cp\u003e13.6 (7.4-19.4) (\u003cem\u003en=16\u003c/em\u003e)\u003c/p\u003e\n \u003cp\u003e4.9 (1.5-14.6) (\u003cem\u003en=15\u003c/em\u003e)\u003c/p\u003e\n \u003cp\u003e16 (10.7-22.6) (\u003cem\u003en=4\u003c/em\u003e)\u003c/p\u003e\n \u003cp\u003e16.3 and 21.9\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(\u003cem\u003en=2\u003c/em\u003e)\u003c/p\u003e\n \u003cp\u003e10.2, 16.8, \u0026amp; 20.0\u003c/p\u003e\n \u003cp\u003e(\u003cem\u003en=3\u003c/em\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.365079365079364%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6.7 (2.4-18.5) (\u003cem\u003en=15\u003c/em\u003e)\u003c/p\u003e\n \u003cp\u003e9.6 (5.8-15.6) (\u003cem\u003en=7\u003c/em\u003e)\u003c/p\u003e\n \u003cp\u003e0.8 (0.6-1.0) (\u003cem\u003en=8\u003c/em\u003e)\u003c/p\u003e\n \u003cp\u003e10.1, 10.4 \u0026amp; 22.4 (\u003cem\u003en=3\u003c/em\u003e)\u003c/p\u003e\n \u003cp\u003e14.0\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(\u003cem\u003en=1\u003c/em\u003e)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; 12.1 (5.7-21.9) (\u003cem\u003en=5\u003c/em\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.206349206349206%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.86\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5.\u003c/strong\u003e \u0026ldquo;Univariate analysis of clinicopathologic variables associated with progression free survival.\u0026rdquo;\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHazard Ratio\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge \u0026gt;= 65\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender: Male vs. Female\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.77\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRace/Ethnicity\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp;White vs. Black\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp;Hispanic vs. Black\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.79\u003c/p\u003e\n \u003cp\u003e2.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSBNET vs. PNET\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSynchronous vs. Metachronous\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSymptomatic disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.80\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTumor grade (2 vs. 1)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBilateral liver metastases\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eExtrahepatic disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e# of liver lesions debulked\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of lesions\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; 6-15 vs. 1-5\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp;16-25 vs. 1-5\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp;\u0026gt;25 vs. 1-5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2.80\u003c/p\u003e\n \u003cp\u003e2.91\u003c/p\u003e\n \u003cp\u003e2.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrimary tumor \u0026gt;= 2cm\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eLargest met \u0026gt;= 5cm\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eLymphovascular invasion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.92\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePerineural invasion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMesenteric deposits\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eKi-67*\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e3-5% vs. \u0026lt;3%\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e6-10% vs. \u0026lt;3%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.42\u003c/p\u003e\n \u003cp\u003e1.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.91\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAny preop systemic therapy\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; Somatostatin analogue\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; Chemo\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;(CAPTEM)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; PRRT\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e7.12\u003c/p\u003e\n \u003cp\u003e3.58\u003c/p\u003e\n \u003cp\u003e0.64\u003c/p\u003e\n \u003cp\u003e1.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003cp\u003e0.65\u003c/p\u003e\n \u003cp\u003e0.72\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjuvant (post op) systemic therapy\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; 1 agent vs. 0 agents\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; 2 or more agents vs. \u0026nbsp;0 agents\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; SSA\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; Chemo\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; PRRT\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; Ablation (MWA, RFA)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; Embolization\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; Any LDT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.79\u003c/p\u003e\n \u003cp\u003e4.07\u003c/p\u003e\n \u003cp\u003e1.40\u003c/p\u003e\n \u003cp\u003e3.35\u003c/p\u003e\n \u003cp\u003e3.24\u003c/p\u003e\n \u003cp\u003e3.28\u003c/p\u003e\n \u003cp\u003e3.86\u003c/p\u003e\n \u003cp\u003e3.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.66\u003c/p\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003cp\u003e0.44\u003c/p\u003e\n \u003cp\u003e0.33\u003c/p\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePreop LAD on imaging\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.92\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003eSurgical debulking has been shown to palliate symptoms and prolong survival in NETLM patients (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Nonetheless, recurrence after debulking is universal, and both the preservation of normal liver parenchyma and minimization of complications should be prioritized for this reason. Herein, we show that PSR and MWA allows for effective debulking of hepatic disease in patients with high numbers of lesions without compromising synthetic liver function, and that such procedures can be with low morbidity in experienced centers.\u003c/p\u003e \u003cp\u003eMaxwell \u003cem\u003eet al\u003c/em\u003e reported on 108 PNET and SBNET patients with NETLM who underwent 70% tumor debulking with a median number of 6 lesions in their cohort. In their series they correlated 10 hepatic lesions with roughly a 10\u0026ndash;19% hepatic replacement and concluded that patients with \u0026lt;\u0026thinsp;25% liver tumor involvement had better outcomes than those with greater tumor burden (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Subsequently, Scott \u003cem\u003eet. al\u003c/em\u003e demonstrated the efficacy and safety of debulking large numbers (\u0026gt;\u0026thinsp;10) of liver lesions using PSR and ablative techniques (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). While this study reported survival outcomes and postoperative complications across a wide range of debulking thresholds (mean 79%) with varying degrees of liver tumor involvement (5\u0026ndash;70%) and numbers of lesions (median number 10), little is known about the effects on liver function and outcomes associated with higher degrees of surgical debulking. To address this, we analyzed our institutional data among patients with high volume of operable liver metastases who underwent 90% debulking. While the overall liver tumor involvement was less than 25%, more than half of our cohort had 16 lesions or greater.\u003c/p\u003e \u003cp\u003eOn assessing the impact of tumor debulking on liver function, we noted that while the degree of post-operative transaminitis, indicating hepatocellular injury, correlates with the extent of debulking, synthetic liver function was not affected by higher numbers of targeted lesions. Thrombocytopenia and anemia were the most common complications after surgical debulking. Thrombocytopenia, a post-operative phenomenon that can occur after liver resection, is thought to be due to a consumptive process in liver regeneration (\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). In our series, we noted thrombocytopenia occurred commonly, but the severity was proportional to the numbers of lesions debulked. Overall, thrombocytopenia was generally transient with nadirs reached by POD 2, and a quicker recovery was noted than what has been reported after formal anatomic liver resections (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Post-operative anemia requiring blood transfusion occurred in over a third of patients, although active hemorrhage was rare. Major complications defined as Clavien-Dindo grade 3 or 4 occurred in 13% of patients, but there were no differences in type or incidence based on the number of lesions debulked.\u003c/p\u003e \u003cp\u003eGiven our short study interval with median follow-up of 12 months, we assessed PFS rather than overall survival (OS). Although SBNETs seemed to have a longer PFS than PNETs, a trend that other studies have reported (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e), our results did not reach statistical significance and may be due to multiple reasons, including smaller sample size, earlier detection of PFS due to better imaging, and perhaps even the difference in routine usage of SSA postoperatively. The median time to recurrence overall was 10.9 months, and while this is lower than what has been previously reported (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e), we defined time to recurrence according to RECIST 1.1 criteria and had comparable results with a study who also applied this model (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). For surveillance, we used MRI abdomen with EOVIST, the most sensitive method for detection of new liver lesions or progression (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) which could impact our time to recurrence. Moreover, we only initiated SSA therapy immediately postoperatively in 20% of patients. Although data remains sparse, patients on SSA after debulking surgery may perhaps benefit with extended PFS.\u003c/p\u003e \u003cp\u003eVarious studies have reported poorer survival outcomes in NETLM patients with EHD and have questioned whether surgical debulking is beneficial (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Interestingly, the presence of EHD in our patient cohort did not correlate with disease progression. In fact, we noted that of our twelve patients with EHD, only one patient with bone metastases had significant disease progression after surgical debulking that required several additional therapies. Contrastingly, nine patients that had EHD limited to the abdomen and pelvis either had no recurrence or stable disease without significant progression at most recent follow-up. Whether or not the location and extent of EHD (i.e, bone vs intraperitoneal) impacts survival differently requires further investigation.\u003c/p\u003e \u003cp\u003eAmong patients who had symptoms prior to debulking, all reported either improvement or relief of symptoms. At most recent follow-up after debulking, nearly half of patients did not have any disease progression. While SSA was eventually initiated in most patients postoperatively, only a few required additional treatments such as PRRT or chemo for disease progression.\u003c/p\u003e \u003cp\u003eOur study is limited by its retrospective nature, small cohort and short term follow up interval. Furthermore, due to the highly-specialized, multi-disciplinary and standardized care that we provide for NET patients as one of few high-volume NET programs nationwide, our outcomes may not be entirely generalizable.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eTumor debulking in NETLM patients with larger numbers of lesions is feasible and safe with the use of PSR and MWA. Perioperative outcomes such as complications, mortality, and synthetic liver function are not affected by higher numbers of lesions and most patients have symptom relief after debulking. Thus, this therapy should be considered for NETLM patients with larger number of hepatic lesions as it may offer symptom and disease control.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNET\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eneuroendocrine tumor\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePSR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eparenchymal-sparing liver resections\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eNET \u0026ndash; neuroendocrine tumor\u003c/p\u003e\n\u003cp\u003ePSR \u0026ndash; parenchymal-sparing liver resections\u003c/p\u003e\n\u003cp\u003eMWA - microwave ablations\u003c/p\u003e\n\u003cp\u003eNETLM - neuroendocrine tumor liver metastases\u003c/p\u003e\n\u003cp\u003ePOD - postoperative day\u003c/p\u003e\n\u003cp\u003eAST - aspartate aminotransferase\u003c/p\u003e\n\u003cp\u003eALT - alanine aminotransferase\u003c/p\u003e\n\u003cp\u003eINR - international normalized ratio\u003c/p\u003e\n\u003cp\u003eTB - total bilirubin\u003c/p\u003e\n\u003cp\u003eLDT - liver directed therapy\u003c/p\u003e\n\u003cp\u003ePNET - pancreatic neuroendocrine tumor\u003c/p\u003e\n\u003cp\u003eSBNET - small bowel neuroendocrine tumor\u003c/p\u003e\n\u003cp\u003eSSA - somatostatin analogues\u003c/p\u003e\n\u003cp\u003eCAPTEM - capecitabine-temozolomide\u003c/p\u003e\n\u003cp\u003ePRRT - peptide receptor radionuclide therapy\u003c/p\u003e\n\u003cp\u003eRECIST - response evaluation criteria in solid tumors\u003c/p\u003e\n\u003cp\u003ePFS - progression free survival\u003c/p\u003e\n\u003cp\u003eEBL - estimated blood loss\u003c/p\u003e\n\u003cp\u003eEHD - extrahepatic disease\u003c/p\u003e"},{"header":"Declarations","content":"\u003col\u003e\n \u003cli\u003eEthics approval and consent to participate: Due to the retrospective nature of this study and deidentification of all data used for purposes of this study informed consent was waived\u0026nbsp; and approved by our institutional review board.\u003c/li\u003e\n \u003cli\u003eConsent for publication: not applicable.\u003c/li\u003e\n \u003cli\u003eAvailability of data and materials: All data and materials are maintained on a secure, encrypted drive and are available for review upon request.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eCompeting interest: The authors declare that they have no conflicts nor competing\u0026nbsp;interests.\u003c/li\u003e\n \u003cli\u003eFunding: This study was conducted without any funding sources.\u003c/li\u003e\n \u003cli\u003eAuthors\u0026rsquo; contributions: FT designed the study and performed data acquisition and manuscript preparation, JW assisted with data acquisition, RN performed data analysis and interpretation. JS, KR, BP, GR, CL and MM contributed meaningful revisions in the manuscript. XK conceived and helped to design the study and substantively revised it.\u003c/li\u003e\n \u003cli\u003eAcknowledgements: We would like to acknowledge all the ancillary staff of our Neuroendocrine Tumor Program who assisted in the care NET patients and associated documentation.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDasari A, Shen C, Halperin D, Zhao B, Zhou S, Xu Y, et al. Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States. JAMA Oncol. 2017;3(10):1335\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRiihim\u0026auml;ki M, Hemminki A, Sundquist K, Sundquist J, Hemminki K. The epidemiology of metastases in neuroendocrine tumors. Int J Cancer. 2016;139(12):2679\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGarcia-Carbonero R, Sorbye H, Baudin E, Raymond E, Wiedenmann B, Niederle B, et al. ENETS Consensus Guidelines for High-Grade Gastroenteropancreatic Neuroendocrine Tumors and Neuroendocrine Carcinomas. Neuroendocrinology. 2016;103(2):186\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHowe JR, Cardona K, Fraker DL, Kebebew E, Untch BR, Wang YZ, et al. The Surgical Management of Small Bowel Neuroendocrine Tumors: Consensus Guidelines of the North American Neuroendocrine Tumor Society. Pancreas. 2017;46(6):715\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKeutgen XM, Schadde E, Pommier RF, Halfdanarson TR, Howe JR, Kebebew E. Metastatic neuroendocrine tumors of the gastrointestinal tract and pancreas: A surgeon's plea to centering attention on the liver. Semin Oncol. 2018;45(4):232\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGlazer ES, Tseng JF, Al-Refaie W, Solorzano CC, Liu P, Willborn KA, et al. Long-term survival after surgical management of neuroendocrine hepatic metastases. HPB (Oxford). 2010;12(6):427\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGraff-Baker AN, Sauer DA, Pommier SJ, Pommier RF. Expanded criteria for carcinoid liver debulking: Maintaining survival and increasing the number of eligible patients. Surgery. 2014;156(6):1369\u0026ndash;76; discussion 76 \u0026ndash; 7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNorton JA, Warren RS, Kelly MG, Zuraek MB, Jensen RT. Aggressive surgery for metastatic liver neuroendocrine tumors. Surgery. 2003;134(6):1057\u0026ndash;63; discussion 63 \u0026ndash; 5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMorgan RE, Pommier SJ, Pommier RF. Expanded criteria for debulking of liver metastasis also apply to pancreatic neuroendocrine tumors. Surgery. 2018;163(1):218\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaxwell JE, Sherman SK, O'Dorisio TM, Bellizzi AM, Howe JR. Liver-directed surgery of neuroendocrine metastases: What is the optimal strategy? Surgery. 2016;159(1):320\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTran CG, Sherman SK, Chandrasekharan C, Howe JR. Surgical Management of Neuroendocrine Tumor Liver Metastases. Surg Oncol Clin N Am. 2021;30(1):39\u0026ndash;55.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLuo Y, Ameli S, Pandey A, Khoshpouri P, Ghasabeh MA, Pandey P, et al. Semi-quantitative visual assessment of hepatic tumor burden can reliably predict survival in neuroendocrine liver metastases treated with transarterial chemoembolization. Eur Radiol. 2019;29(11):5804\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228\u0026ndash;47.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGivi B, Pommier SJ, Thompson AK, Diggs BS, Pommier RF. Operative resection of primary carcinoid neoplasms in patients with liver metastases yields significantly better survival. Surgery. 2006;140(6):891-7; discussion 7\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSarmiento JM, Heywood G, Rubin J, Ilstrup DM, Nagorney DM, Que FG. Surgical treatment of neuroendocrine metastases to the liver: a plea for resection to increase survival. J Am Coll Surg. 2003;197(1):29\u0026ndash;37.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMayo SC, de Jong MC, Pulitano C, Clary BM, Reddy SK, Gamblin TC, et al. Surgical management of hepatic neuroendocrine tumor metastasis: results from an international multi-institutional analysis. Ann Surg Oncol. 2010;17(12):3129\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eScott AT, Breheny PJ, Keck KJ, Bellizzi AM, Dillon JS, O'Dorisio TM, et al. Effective cytoreduction can be achieved in patients with numerous neuroendocrine tumor liver metastases (NETLMs). Surgery. 2019;165(1):166\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcCaughan GW, Herkes R, Powers B, Rickard K, Gallagher ND, Thompson JF, et al. Thrombocytopenia post liver transplantation. Correlations with pre-operative platelet count, blood transfusion requirements, allograft function and outcome. J Hepatol. 1992;16(1\u0026ndash;2):16\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlkozai EM, Nijsten MW, de Jong KP, de Boer MT, Peeters PM, Slooff MJ, et al. Immediate postoperative low platelet count is associated with delayed liver function recovery after partial liver resection. Ann Surg. 2010;251(2):300\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLesurtel M, Graf R, Aleil B, Walther DJ, Tian Y, Jochum W, et al. Platelet-derived serotonin mediates liver regeneration. Science. 2006;312(5770):104\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSiu J, McCall J, Connor S. Systematic review of pathophysiological changes following hepatic resection. HPB (Oxford). 2014;16(5):407\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSpolverato G, Bagante F, Tsilimigras DI, Pawlik TM. Liver transplantation in patients with liver metastases from neuroendocrine tumors. Minerva Chir. 2019;74(5):399\u0026ndash;406.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, et al. One hundred years after \"carcinoid\": epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26(18):3063\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKeck KJ, Choi A, Maxwell JE, Li G, O'Dorisio TM, Breheny P, et al. Increased Grade in Neuroendocrine Tumor Metastases Negatively Impacts Survival. Ann Surg Oncol. 2017;24(8):2206\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMorse B, Jeong D, Thomas K, Diallo D, Strosberg JR. Magnetic Resonance Imaging of Neuroendocrine Tumor Hepatic Metastases: Does Hepatobiliary Phase Imaging Improve Lesion Conspicuity and Interobserver Agreement of Lesion Measurements? Pancreas. 2017;46(9):1219\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEjaz A, Reames BN, Maithel S, Poultsides GA, Bauer TW, Fields RC, et al. The impact of extrahepatic disease among patients undergoing liver-directed therapy for neuroendocrine liver metastasis. J Surg Oncol. 2017;116(7):841\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSpolverato G, Bagante F, Aldrighetti L, Poultsides GA, Bauer TW, Fields RC, et al. Management and outcomes of patients with recurrent neuroendocrine liver metastasis after curative surgery: An international multi-institutional analysis. J Surg Oncol. 2017;116(3):298\u0026ndash;306.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"neuroendocrine tumor, hepatic debulking, liver metastases, parenchymal-sparing resection, microwave ablation","lastPublishedDoi":"10.21203/rs.3.rs-2649826/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2649826/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Surgical debulking of neuroendocrine tumor (NET) is used as a therapeutic approach for metastatic NETs in selected centers. Reported outcomes after parenchymal-sparing liver resections (PSR) in NET patients with high numbers of liver metastases are sparse.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: NET patients that underwent surgical debulking from 2019 to 2021 were reviewed. Trends in perioperative liver function was examined, as well as symptom response, complications, and progression free survival.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: 1069 liver lesions (median=17) were debulked from 53 patients with a combination of PSR (45%) and ultrasound-guided microwave ablations (MWA) (55%).\u0026nbsp; Post-operative transaminitis was proportional to the number of lesions debulked: Median POD1 AST was 681 IU/L for 1-15 lesions vs. 1396 IU/L for \u0026gt;15 lesions, \u003cem\u003ep\u003c/em\u003e=0.01 (R\u003csup\u003e2\u003c/sup\u003e=0.271, \u003cem\u003ep\u003c/em\u003e\u0026lt;0.001) and ALT was 596 IU/L vs 1149 IU/L, respectively, \u003cem\u003ep\u003c/em\u003e=0.01 (R\u003csup\u003e2\u003c/sup\u003e=0.221, \u003cem\u003ep\u003c/em\u003e\u0026lt;0.001). Thrombocytopenia occurred in 75% of patients and severity correlated with increasing number of lesions (median POD2 platelets 157 x 10\u003csup\u003e9\u003c/sup\u003e/L for 1-15 lesions vs. 109 x 10\u003csup\u003e9\u003c/sup\u003e/L\u0026nbsp; for \u0026gt;15 lesions, \u003cem\u003ep\u003c/em\u003e=0.04; R\u003csup\u003e2\u003c/sup\u003e=0.163, \u003cem\u003ep\u003c/em\u003e=0.003). Synthetic liver function measured by postoperative INR (median POD1 INR 1.3 vs 1.4, \u003cem\u003ep\u003c/em\u003e=0.21) and total bilirubin (median POD 2 TB 1.35 vs 0.95 mg/dL; \u003cem\u003ep\u003c/em\u003e=0.67) did not differ according to number of lesions debulked. 13% of patients sustained a Clavien-Dindo grade 3/4 complication which was not associated with the number of lesions targeted. All patients with preoperative symptoms had improvement after surgery. Median time to recurrence was 10.9 months.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: PSR with MWA for large numbers of NET liver metastases is safe and effective for symptom control and does not affect synthetic liver function. Transaminitis and thrombocytopenia are proportionate to the amount of liver lesions debulked.\u003c/p\u003e","manuscriptTitle":"Single Center Outcomes from Parenchymal-sparing Resections and Microwave Ablations for Neuroendocrine Tumor Liver Metastases","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-03-10 00:08:27","doi":"10.21203/rs.3.rs-2649826/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b96993be-dc79-433a-a5df-d5b82b946efd","owner":[],"postedDate":"March 10th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-04-30T15:14:22+00:00","versionOfRecord":[],"versionCreatedAt":"2023-03-10 00:08:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2649826","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2649826","identity":"rs-2649826","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}