Is pancreaticoduodenectomy justified for metastatic melanoma to the ampulla of Vater?

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Chieh-Ning Hsi, Shin-E Wang, Bor-Shiuan Shyr, Shih-Chin Chen, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3857389/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 Metastatic melanoma to the ampulla of Vater is rare. The purpose of this study is to summarize the characteristics and outcomes of metastatic melanoma to the ampulla of Vater, and to highlight the impact of surgery on the prognosis of patients with metastatic melanoma. Methods The pooled data from a case encountered at our institution and all the sporadic cases published on PubMed and MEDLINE from 1996 to 2023 were included for analysis. Results A total of 14 cases of metastatic melanoma to the ampulla of Vater were recruited. Seventy-three percent of the primary melanomas were cutaneous type, and 27% mucosal type. The most common symptom was jaundice (86%). The size of metastatic melanoma to ampulla ranged from 1.5 cm to 8 cm, with a median of 2.75 cm. Concomitant metastasis to other organs occurred in 82% at the diagnosis of this tumor, most commonly to the brain, lungs, and liver (36% each, respectively). Among all the reported cases, pancreaticoduodenectomy was performed in five patients. The overall 1-year survival rate was 27.3%, with a median of 4 months. Wide excision of the primary lesion and chemotherapy significantly improve the survival rate ( p = 0.048). There is a trend toward improved survival in those undergoing pancreaticoduodenectomy followed by chemotherapy. Conclusions Given the availability of effective systemic therapy, metastatic melanoma to the ampulla of Vater is not necessarily to preclude a major surgery. metastatic melanoma ampulla of Vater pancreaticoduodenectomy adjuvant systemic therapy Figures Figure 1 Figure 2 Figure 3 Background Melanoma, the leading cause of skin cancer-related deaths, encompasses a diverse spectrum of malignant melanocytic proliferations.[ 1 ] Melanoma with distant metastasis in the abdominal cavity most commonly affects the liver and the gastrointestinal tract,[ 2 ] while metastasis to the ampulla of Vater is uncommon with a dismal prognosis.[ 3 ] As various therapeutic agents advance, the effective treatment of patients with distant melanoma metastasis has become a reality, significantly enhancing their quality of life.[ 4 ] However, the optimal therapeutic approach for metastatic melanoma to the ampulla of Vater remains uncertain, given the rarity of such metastatic lesions. The appropriateness of aggressive surgical strategy, such as pancreaticoduodenectomy, remains a topic of uncertainty in this context. We hereby presented a rare case of malignant melanoma with multiple metastases to the ampulla of Vater and right kidney of a 64-year-old man, aiming to share our experience for clinicians to guide further management plan in patients with advanced stage of melanoma. We have also collected all cases of metastatic melanoma to the ampulla of Vater that were published on PubMed and MEDLINE until 2023 for the pooled data of analysis. Additionally, we reviewed studies that highlight the impact of surgery on the prognosis of patients with metastatic melanoma. Methods Brief descriptions were made for the case of a metastatic melanoma to the ampulla of Vater encountered at our institution. The study has been approved by the Institutional Review Board of Taipei Veterans General Hospital (IRB-TPEVGH No.: 2023-11-006CC). Data and materials described in this manuscript, including all relevant raw data, will be freely available to any scientist willing to use them for non-commercial purposes, without breaching participant confidentiality. To clarify the characteristics and outcomes of metastatic melanoma to the ampulla of Vater, individualized data of cases published in the English literature were extracted and added to our database to expand the sample size for a more complete analysis. Two methods were utilized in searching for relevant cases. First, to identify the articles dealing with metastatic melanoma to the ampulla of Vater in the literature, a computerized search was performed on the PubMed and MEDLINE electronic database, covering data from 1996 to 2023. The following keywords were used for the search: metastatic melanoma, ampulla of Vater metastasis, pancreaticoduodenectomy, metastasectomy, and adjuvant systemic therapies. Second, the reference lists of PubMed-selected metastatic melanoma to the ampulla of Vater articles were screened systematically for additional studies of interests.[ 1 , 4 – 18 ] The data pooled from the literature cases and our case were analyzed to determine the characteristics of metastatic melanoma to ampulla of Vater including demographics, primary tumor sites and thickness, clinical presentations, concomitant metastasis to other site, tumor size, lymph nodes status, treatment, and survival outcomes. Statistical analyses were conducted using Statistical Product and Service Solutions (SPSS) version 23.0 software (SPSS Inc., IBM, Armonk, NY, USA). All continuous data were calculated using median (range) and mean ± standard deviation (SD), and case number (%) were presented when appropriate to the type of data. Actuarial survival was estimated using the Kaplan–Meier method, and a log rank test was used to determine differences in the subgroups. For all analyses, a p value less than 0.050 was considered statistically significant. Results A total of 14 cases of metastatic melanoma to the ampulla of Vater were recruited for this study, including 13 cases from the published literature [ 3 , 19 – 29 ] and 1 from our institution (Table 1 ). Table 1 Case reports of metastatic melanoma to the ampulla of Vater Author Year Age /Sex Primary site Surgical treatment Systemic therapy Follow-up (Month) Outcome Sans [ 19 ] 1996 51/M NA ES None 3 Dead Meyers [ 20 ] 1998 56/M Skin PD None 3 Dead Caballero [ 21 ] 1999 48/M Skin ES CT 4 Dead Medina [ 22 ] 1999 60/M NA PPPD None 6 Dead Le Borgne [ 23 ] 2000 62/F Skin PD CT 12 Survived Le Borgne [ 23 ] 2000 33/F Skin PD None 2 Survived Bokhoven [ 24 ] 2006 66/F Skin ES None NA NA Uiterwaal [ 25 ] 2010 41/F Skin None CCRT 8 Dead Berger [ 3 ] 2010 66/F Skin ES CT 15 Dead Nakayama [ 26 ] 2011 81/F Vagina None None 1 Dead Bendic [ 27 ] 2013 52/M Ampulla PD None 4 Dead Yamakawa [ 28 ] 2017 83/M Bucca BD None NA NA Armany [ 29 ] 2023 75/M Skin ES None NA NA M male, F female, NA not available, PD pancreaticoduodenectomy, PPPD pylorus-preserving pancreaticoduodenectomy, ES endoscopic sphincterotomy, BD biliary drainage, CT chemotherapy, CCRT concurrent chemoradiotherapy Our case was a 64-year-old man who presented with a 3-week-history of jaundice. Biochemical analysis demonstrated an obstructive liver function test pattern with a total bilirubin of 8.09 mg/dL, direct bilirubin of 6.67 mg/dL, alkaline phosphate of 780 U/L, gamma-glutamyl transferase of 1056 U/L, amylase of 231 U/L and lipase of 271 U/L along with elevated carbohydrate antigen 19 − 9 (CA-199) of 64.1 U/ml. Abdominal computed tomography (CT) scanning revealed a tumor at periampullary area, measured 3cm in size, causing dilatation of common bile duct and intrahepatic ducts (Fig. 1 a). Meanwhile, another 5.5cm mass was noted at the upper pole of the right kidney (Fig. 1 b). On physical examination, there was one pigmented, hard, and ill-defined skin lesion at the right lateral chest wall, which the patient claimed to have been noted for more than 10 years. He underwent robotic pancreaticoduodenectomy (Fig. 2 a), peri-renal tumor resection (Fig. 2 b), and wide excision of the skin tumor. Histopathologic examination revealed the tumor cells with pleomorphic nuclei, prominent nucleoli, and intracytoplasmic melanin pigments deposition (Fig. 3 a-b). They were immunoreactive to SRY-related HMG-BOX gene 10 (SOX10) (Fig. 3 c), human melanoma black-45 (HMB45) (Fig. 3 d) markers, focally positive for cluster of differentiation 117 (CD117) marker, and negative for discovered on gastrointestinal stromal tumors protein 1 (DOG1), cluster of differentiation 34 (CD34) markers, and B-Raf proto-oncogene (BRAF) (Fig. 3 e). BAP1 (BReast CAncer gene 1 associated protein 1) stains showed aberrant loss of expression (Fig. 3 f). Sections of the right chest wall skin tumor and the right perirenal space tumor demonstrated similar morphology as the periampullary tumor. The tumor was analyzed for mutations in 52 genes and guanine nucleotide-binding protein subunit alpha-11 (GNA11) mutation was detected. Based on the patient’s clinical presentation, molecular and immunohistochemistry findings of the tumor, a diagnosis of blue nevus-like melanoma with BAP1 loss was established. Our patient underwent adjuvant chemotherapy using dacarbazine and received immunotherapy with pembrolizumab and is reported to be alive 18 months after operation. The demographics and clinical presentations of the 14 cases of metastatic melanoma to the ampulla of Vater are listed in Table 2 . The median age at the diagnosis of was 60 years old, ranging from 33 to 83 years old for overall patients, and this tumor occurred more frequently in Western countries (71%) than in Asia (29%). Most melanomas originate from the skin (73%), with only 27% of the cases being of the mucosal type. Thickness of primary melanoma ranged from 1.2 mm to 30 mm with a median of 2.75 mm, and the median interval between diagnoses of primary and metastatic melanoma to ampulla was 36 months, with the longest duration up to 120 months. The most common symptom was jaundice (86%), followed by abdominal pain (36%). Table 2 Demographics and clinical presentations of metastatic melanoma to the ampulla of Vater Demographics n (%) Sex (n = 14) Male 8 (57%) Female 6 (43%) Age (y/o, n = 14) Median (range) 60 (33–83) Mean ± SD 58.57 ± 14.46 Area (n = 14) Western 10 (71%) Asia 4 (29%) Primary site of tumor (n = 11) Cutaneous 8 (73%) Mucosal 3 (27%) Primary tumor thickness (mm, n = 8) Median (range) 2.75 (1.2–30) Mean ± SD 6.66 ± 9.95 Interval of metastasis (month, n = 9) Median (range) 36 (10–120) Mean ± SD 46 ± 37.5 Symptoms (n = 14) Jaundice 12 (86%) Abdominal pain 5 (36%) Nausea/vomit 3 (21%) Body weight loss 2 (14%) Anorexia 2 (14%) Symptoms duration (month, n = 10) Median (range) 0.85 (0.06-11) Mean ± SD 2.38 ± 3.31 Diagnosis method (n = 14) Endoscopy (ERCP) 11 (78%) CT scan 6 (43%) Sonography 1 (7%) SD standard deviation, CT computed tomography, ERCP endoscopic retrograde cholangiopancreatography Table 3 described the characteristics and treatment of metastatic melanoma to the ampulla of Vater. The size of metastatic melanoma to ampulla of Vater ranged from 1.5 cm to 8 cm, with a median of 2.75 cm. Concomitant metastasis to other organs occurred in 82% of the cases at the diagnosis of this tumor, most commonly in the brain, lungs, and liver (36% each, respectively). Wide excision of the primary lesion improved the outcome significantly ( p = 0.048, Table 4 ). Forty-three percent of patients underwent pancreaticoduodenectomy; however, more than half (57%) of them did not receive chemotherapy. Patients who received chemotherapy experienced a significantly higher overall 1-year survival rate of 50% compared to those who did not (0%, p = 0.048). While there was a trend toward improved survival in patients undergoing pancreaticoduodenectomy, it was worth noting that this difference did not achieve statistical significance (33.3% V.S 20%, p = 0.301). Lymph node metastasis, number of the metastatic site, metastatic tumor size or interval between primary and metastasis seemed to have no survival impact. Table 3 Characteristics and treatment of metastatic melanoma to the ampulla of Vater Characteristics n (%) Metastatic tumor size (cm, n = 8) Median (range) 2.75 (1.5-8) Mean ± SD 3.49 ± 2.1 Metastasis to other distant organs (n = 11) Brain 4 (36%) Chest (lungs, mediastinum) 4 (36%) Liver 4 (36%) Pelvis 3 (27%) Spleen 2 (18%) Pancreas 1 (9%) Intestines 1 (9%) None 2 (18%) Surgical treatment (n = 14) Pancreaticoduodenectomy 6 (43%) Internal stents 5 (36%) Biliary drainage 1 (7%) No treatment 2 (14%) Positive lymph node status (n = 9) Yes 7 (78%) No 2 (22%) Chemotherapy (n = 14) Yes 6 (43%) No 8 (57%) SD standard deviation Table 4 Survival outcomes of metastatic melanoma to the ampulla of Vater Case Number Median (range), month Mean ± SD, month 1-year survival p value Total 11 4 (1–15) 7.09 ± 4.23 27.3% Ampullary metastasis 0.223 Solitary 2 7 (2–12) 7 50% Combined with other sites metastasis 9 4 (1–15) 7.67 ± 4.89 22.2% Metastatic tumor size (cm) 0.59 ≤ 2 cm 4 3.5 (2–12) 5.25 ± 3.9 25% > 2 cm 4 10.5 (3–15) 9.75 ± 5.33 50% Interval between primary and metastasis (months) 0.351 ≤ 1 year 1 8 8 0% > 1 year 4 13.5 (3–15) 11.3 ± 4.97 75% Thickness of the primary lesion 0.853 ≤ 2 mm 1 8 8 0% 2.01-4 mm 1 15 15 100% > 4 mm 2 8 (1–15) 8 50% Site of the primary lesion 0.081 Cutaneous type 6 10 (3–18) 10 ± 5.5 50% Mucosal type 2 2.5 (1–4) 2.5 0% Wide excision of the primary lesion 0.048 Yes 6 10 (3–15) 9.5 ± 4.51 50% No 5 3 (1–6) 3.2 ± 1.47 0% Pancreaticoduodenectomy 0.301 Yes 6 5 (2–15) 7 ± 4.83 33.3% No 5 4 (1–15) 6.2 ± 4.96 20% Chemotherapy 0.048 Yes 6 10 (3–15) 9.5 ± 4.86 50% No 5 3 (1–6) 3.2 ± 1.72 0% positive lymph nodes status 0.118 yes 6 3.5 (1–12) 4.67 ± 3.66 16.6% no 2 15 15 100% Discussion Malignant melanomas are aggressive cancers, accounting for 90% of skin cancer-related deaths.[ 1 ] Metastasis within the abdominal cavity typically affects the liver and gastrointestinal tract,[ 2 ] while metastasis to the ampulla of Vater is extremely rare.[ 3 ] To date, there have only been 13 reported cases of metastatic melanoma to the ampulla of Vater and of those, only five patients underwent surgical pancreaticoduodenectomy. The median follow-up time was 4 months, two patients were reported to be alive at 2 and 12 months after surgery, reported by Le Borgne et al.,[ 23 ] while the remaining cases either died or were not documented. Similar to Le Borgne's report, our patient also underwent pancreaticoduodenectomy followed by chemotherapy, and both individuals survived for over one year after the surgery. In our study, we noticed there was a trend toward favorable outcome among those who underwent pancreaticoduodenectomy. However, it's important to acknowledge that this trend did not attain statistical significance, primarily due to the limitation imposed by the small sample size in this study. On the other hand, primary site tumor excision markedly enhanced the survival rate (50% vs. 0%, p = 0.048), underscoring the crucial role of surgery in the management of melanoma. Blue nevus-associated melanoma comprises a heterogenous and relative uncommon group of melanomas, which demonstrate a similar histopathological and mutational pattern with uveal melanoma, including guanine nucleotide-binding protein subunit alpha-11 (GNA11) or guanine nucleotide-binding protein subunit alpha Q (GNAQ) mutations.[ 30 , 31 ] Additional BAP1 loss is associated with younger diagnostic age, larger average lesion thickness and a higher risk of metastasis.[ 32 ] In the presenting case, our patient was diagnosed with blue nevus-like melanoma with GNA11 mutation and BAP1 loss, which has been reported to have a higher metastatic rate in published literature. Historically, patients who develop distant metastasis in melanoma have had a poor prognosis, with a median survival of 6 to 7.5 months and 5-year survival rate of less than 10% [ 16 , 33 , 34 ]. Our study reveals an overall 1-year survival rate of 27.3% and a median survival of 4 months, highlighting a particularly unfavorable outcome in the cases of metastatic melanoma to the ampulla of Vater in literature. Although traditional chemotherapy, like dacarbazine, has been associated with a reported low response rate (approximately 15–20%) in literature,[ 12 ] our study revealed a notable enhancement in survival outcomes among patients who underwent chemotherapy (50% vs. 0%, p = 0.048). Since the introduction of the eighth edition American Joint Committee on Cancer staging system in 2018,[ 35 ] the landscape of treatment options for advanced stage melanoma has rapidly evolved. Ipilimumab, a monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4 markedly improved the overall survival of patients with metastatic melanoma.[ 10 , 18 ] Targeted BRAF/MEK inhibitors also revolutionized the therapeutic landscape, which significantly prolonged the overall survival in patients with BRAF mutant melanoma.[ 8 ] Therefore, since 2013, a significant improvement in metastatic melanoma mortality rates was observed, largely attributed to the advent of effective systemic therapies.[ 6 ] With the availability of these novel therapies, the patterns of surgical intervention and the indications for surgery evolved in parallel. A retrospective cohort study including 138 patients with stage IV melanoma showed a significant increase in potentially curative operations among patients managed in the modern treatment era.[ 13 ] Recently, a systemic review and meta-analysis was conducted to access the role of surgery for patients with metastatic melanoma.[ 14 ] This review included 40 studies and 31,282 patients, and it showed that patients who underwent curative metastasectomy had a significantly lower rate of death than those who did not (HR 0.42; 95% confidence interval 0.38–0.47; p < 0.00001). The phase III trial of Malignant Melanoma Active Immunotherapy (MMAIT) has reported that long-term survival can be achieved through metastasectomy.[ 9 ] Some studies pointed out that the prognosis was independent of immunotherapy, the stage at initial operation and the anatomic site of metastasis, while number of metastases did not affect the overall survival rate after complete resection.[ 11 , 15 ] Our study also revealed that neither the number of metastatic sites nor the size of metastatic tumors had a detrimental impact on survival outcomes. Conclusions To the best of our knowledge, this study reports the longest follow-up period for a patient with metastatic melanoma to the ampulla of Vater who underwent pancreaticoduodenectomy followed by adjuvant chemotherapy and immunotherapy, and is currently alive 18 months after operation. With the continued development of effective therapeutic agents, surgery in metastatic melanoma has evolved from a palliative approach to a more aggressive role aimed at eradicating the disease. This study also demonstrated that adopting an aggressive surgical approach can yield favorable outcomes, even when combined solely with traditional chemotherapy rather than relying on novel therapeutic agents. Nevertheless, it's important to acknowledge that the findings of this study are constrained by a limited sample size, attributable to the rarity of metastatic melanoma to the ampulla of Vater. In conclusion, resection of metastatic lesions followed by systemic therapy may offer benefits to patients with metastatic melanoma, regardless of the number, location, or tumor size of the metastasis. Given the availability of various effective systemic therapy options, metastatic melanoma to the ampulla of Vater is not necessarily to preclude a major surgery. Pancreaticoduodenectomy should be considered when feasible to improve overall survival outcomes. Abbreviations CA 19-9: Carbohydrate antigen 19-9 CT: Computed tomography SOX10: SRY-related HMG-BOX gene 10 HMB45: Human melanoma black-45 CD: Cluster of differentiation DOG1: Gastrointestinal stromal tumors protein 1 BRAF: B-Raf proto-oncogene BAP1: BReast CAncer gene 1 associated protein 1 GNA11: Guanine nucleotide-binding protein subunit alpha-11 GNAQ: Guanine nucleotide-binding protein subunit alpha Q AJCC: American Joint Committee on Cancer MMAIT: Malignant Melanoma Active Immunotherapy PD: pancreaticoduodenectomy PPPD: pylorus-preserving pancreaticoduodenectomy ES: endoscopic sphincterotomy BD: biliary drainage CCRT: concurrent chemoradiotherapy Declarations Ethics approval and consent to participate The study has been approved by the Institutional Review Board of Taipei Veterans General Hospital (IRB-TPEVGH No.: 2023-11-006CC). Appropriate written informed consent to participate was obtained from the patient. Consent for publication Not applicable. Availability of data and materials Data and materials described in this manuscript, including all relevant raw data, will be freely available to any scientist willing to use them for non-commercial purposes, without breaching participant confidentiality. Competing interests The authors declare that they have no competing interests. Funding declaration This work was financially supported by grants from the Taipei Veterans General Hospital (V112C-009, V112C-188, and V112B-001), the Ministry of Science and Technology (NSTC 112-2314-B-075-016 -), and the Ministry of Health and Welfare (MOHW111-TDU-B-221-014015). Authors’ contributions H.C.N. and S.B.S. equally contributed to this paper. H.C.N., W.S.E., S.B.U. and S.Y.M. made substantial contributions to conception and design, acquisition of data, and analysis and interpretation of data. H.C.N. was a major contributor in writing the manuscript. S.B.S. was involved in drafting the manuscript or revising it critically for important intellectual content. W.S.E. was involved in drafting the manuscript or revising it critically for important intellectual content and agreed to be accountable for all aspects of the imaging studies in ensuring that questions related to the accuracy. H.C.N., S.B.U. and S.Y.M. made substantial contributions to conception and design, acquisition of data, and analysis and interpretation of data and gave final approval of the version to be published. All authors read and approved the final manuscript. Acknowledgements The authors would like to acknowledge the support of the Biobank of Taipei Veterans General Hospital, Common Well Foundation and statistical team of Taipei Veterans General Hospital. References Garbe C, Amaral T, Peris K, Hauschild A, Arenberger P, Basset-Seguin N, Bastholt L, Bataille V, Del Marmol V, Dréno B et al: European consensus-based interdisciplinary guideline for melanoma. Part 1: Diagnostics: Update 2022 . Eur J Cancer 2022, 170 :236-255. Ionescu S, Nicolescu AC, Madge OL, Simion L, Marincas M, Ceausu M: Intra-Abdominal Malignant Melanoma: Challenging Aspects of Epidemiology, Clinical and Paraclinical Diagnosis and Optimal Treatment-A Literature Review . Diagnostics (Basel) 2022, 12(9) :2054. Marks JA, Rao AS, Loren D, Witkiewicz A, Mastrangelo MJ, Berger AC: Malignant Melanoma Presenting as Obstructive Jaundice Secondary to Metastasis to the Ampulla of Vater . JOP. 2010 Mar 5; 11(2) :173-175. Jenkins RW, Fisher DE: Treatment of Advanced Melanoma in 2020 and Beyond . J Invest Dermatol 2021, 1 41(1) :23-31. Allen AC SS: Malignant melanoma: a clinicopathological analysis of the criteria for diagnosis and prognosis . Cancer 1953 , 6 :1-45. Berk-Krauss J, Stein JA, Weber J, Polsky D, Geller AC: New Systematic Therapies and Trends in Cutaneous Melanoma Deaths Among US Whites, 1986-2016 . Am J Public Health 2020, 110(5) :731-733. Deutsch GB, Flaherty DC, Kirchoff DD, Bailey M, Vitug S, Foshag LJ, Faries MB, Bilchik AJ: Association of Surgical Treatment, Systemic Therapy, and Survival in Patients With Abdominal Visceral Melanoma Metastases, 1965-2014: Relevance of Surgical Cure in the Era of Modern Systemic Therapy . JAMA Surg 2017, 152(7) :672-678. Dobry AS, Zogg CK, Hodi FS, Smith TR, Ott PA, Iorgulescu JB: Management of metastatic melanoma: improved survival in a national cohort following the approvals of checkpoint blockade immunotherapies and targeted therapies . Cancer Immunol Immunother 2018, 67(12) :1833-1844. Faries MB, Mozzillo N, Kashani-Sabet M, Thompson JF, Kelley MC, DeConti RC, Lee JE, Huth JF, Wagner J, Dalgleish A et al: Long-Term Survival after Complete Surgical Resection and Adjuvant Immunotherapy for Distant Melanoma Metastases . Ann Surg Oncol 2017, 24(13) :3991-4000. Hersh EM, O'Day SJ, Powderly J, Khan KD, Pavlick AC, Cranmer LD, Samlowski WE, Nichol GM, Yellin MJ, Weber JS: A phase II multicenter study of ipilimumab with or without dacarbazine in chemotherapy-naïve patients with advanced melanoma . Invest New Drugs 2011, 29(3) :489-498. Howard JH, Thompson JF, Mozzillo N, Nieweg OE, Hoekstra HJ, Roses DF, Sondak VK, Reintgen DS, Kashani-Sabet M, Karakousis CP et al: Metastasectomy for distant metastatic melanoma: analysis of data from the first Multicenter Selective Lymphadenectomy Trial (MSLT-I) . Ann Surg Oncol 2012 , 19(8) :2547-2555. Middleton MR, Grob JJ, Aaronson N, Fierlbeck G, Tilgen W, Seiter S, Gore M, Aamdal S, Cebon J, Coates A et al: Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma . J Clin Oncol 2000 , 18(1) :158-166. Smith MJF, Smith HG, Joshi K, Gore M, Strauss DC, Hayes AJ, Larkin J: The impact of effective systemic therapies on surgery for stage IV melanoma . Eur J Cancer 2018, 103 :24-31. Wankhede D, Grover S: Outcomes After Curative Metastasectomy for Patients with Malignant Melanoma: A Systematic Review and Meta-analysis . Ann Surg Oncol 2022, 29(6) :3709-3723. Wood TF, DiFronzo LA, Rose DM, Haigh PI, Stern SL, Wanek L, Essner R, Morton DL: Does complete resection of melanoma metastatic to solid intra-abdominal organs improve survival? Ann Surg Oncol 2001, 8(8) :658-662. Manola J AM, Ibrahim J, et al: Prognostic factors in metastatic melanoma: a pooled analysis of Eastern Cooperative Oncology Group trials . J Clin Oncol 2000, 18(22) :3782-3793. Prabhakaran S, Fulp WJ, Gonzalez RJ, Sondak VK, Kudchadkar RR, Gibney GT, Weber JS, Zager JS: Resection of Gastrointestinal Metastases in Stage IV Melanoma: Correlation with Outcomes. Am Surg 2016, 82(11) :1109-1116. Robert C, Thomas L, Bondarenko I, O'Day S, Weber J, Garbe C, Lebbe C, Baurain JF, Testori A, Grob JJ et al: Ipilimumab plus dacarbazine for previously untreated metastatic melanoma . N Engl J Med 2011, 364(26) :2517-2526. M Sans JL, J M Bordas, V Andreu, A Campo, A Castells, E Mondelo, J Terés, J Rodés: Metastatic malignant melanoma of the papilla of Vater- an unusual case of obstructive cholestasis treated with biliary prostheses . Endoscopy 1996, 28 :791-792. M O Meyers DJF, E A Levine: Pancreaticoduodenectomy for melanoma metastatic to the duodenum- a case report and review of the literature . Am Surgeon 1998, 64(12) :1174-1176. Caballero-Mendoza E, Gallo-Reynoso S, Arista-Nasr J, Angeles-Angeles A: Obstructive Jaundice as the First Clinical Manifestation of a Metastatic Malignant Melanoma in the Ampulla of Vater . J Clin Gastroenterol 1999, 29(2) :188-189. H Medina-Franco NBH, J S Aldrete: Pancreaticoduodenectomy for Metastatic Tumors to the Periampullary Region . J Gastrointest Surg 1999, 3 :119-122. Le Borgne CP, P Glemain, B Dupas, B de Kerviller: Pancreaticoduodenectomy for metastatic ampullary and pancreatic tumors . Hepatogastroenterology 2000, 47 :540-544. van Bokhoven MM, Aarntzen EH, Tan AC: Metastatic melanoma of the common bile duct and ampulla of Vater. Gastrointest Endosc 2006, 63(6) :873-874. Uiterwaal MT, Mooi WJ, Van Weyenberg SJ: Metastatic melanoma of the ampulla of Vater. Dig Liver Dis 2011, 43(4) :e8. Nakayama H, Miyazaki S, Kikuchi H, Saito N, Shimada H, Sakai S, Suzuki M, Kimura K: Malignant vaginal melanoma with metastases to the papilla of Vater in a dialysis patient: a case report . Intern Med 2011, 50(4) :345-349. Bendic A, Glavina Durdov M, Stipic R, Karaman I: Melanoma in the ampulla of Vater. Hepatobiliary Pancreat Dis Int 2013, 12(1) :106-108. Yamakawa K, Kurita A, Azuma S, Kudo Y, Yazumi S: Metastatic melanoma in the ampulla of Vater . Gastrointest Endosc 2018, 87(4) :1156-1158. Armany D, Gosal P, Adams S: The ampulla of Vater: A potential target for metastatic melanoma? J Surg Case Rep 2023, 2023(1) :rjac621. Van Raamsdonk CD BV, Green G et al.: Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi . Nature 2009, 457 :599-602. Borgenvik TL, Karlsvik TM, Ray S, Fawzy M, James N: Blue nevus-like and blue nevus-associated melanoma: a comprehensive review of the literature . ANZ J Surg 2017, 87(5) :345-349. Li-Wei Chang VK, Rashek Kazi, Diwakar Davar, Robert L Ferris, Jonhan Ho, Arivarasan Karunamurthy, Jaroslaw J Jedrych, Yuri L Bunimovich: Melanoma Ex Blue Nevus With GNA11 Mutation and BAP1 Loss: Case Report and Review of the Literature . Am J Dermatopathol 2020, 42(11) :854-857. Barth A WL, Morton DL: Prognostic factors in 1,521 melanoma patients with distant metastases. J Am Coll Surg 1995, 181(3) :193-201. Unger JM FL, Liu PY, et al: Gender and other survival predictors in patients with metastatic melanoma on Southwest Oncology Group trials . Cancer 2001, 91(6) :1148-1155. Keung EZ, Gershenwald JE: The eighth edition American Joint Committee on Cancer (AJCC) melanoma staging system: implications for melanoma treatment and care . 2018, 18(8) :775-784. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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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-3857389","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":267509378,"identity":"56cfeea5-a1d1-40ea-8e95-b6ed052bf459","order_by":0,"name":"Chieh-Ning Hsi","email":"","orcid":"","institution":"Taipei Veterans General Hospital; National Yang Ming Chiao Tung University, Taipei","correspondingAuthor":false,"prefix":"","firstName":"Chieh-Ning","middleName":"","lastName":"Hsi","suffix":""},{"id":267509379,"identity":"c881a5e4-0749-4fff-ada6-8114740fc6a9","order_by":1,"name":"Shin-E Wang","email":"","orcid":"","institution":"Taipei Veterans General Hospital; National Yang Ming Chiao Tung University, Taipei","correspondingAuthor":false,"prefix":"","firstName":"Shin-E","middleName":"","lastName":"Wang","suffix":""},{"id":267509380,"identity":"2f9477a1-196a-4f70-9d68-1871bedc8f0d","order_by":2,"name":"Bor-Shiuan Shyr","email":"","orcid":"","institution":"Taipei Veterans General Hospital; National Yang Ming Chiao Tung University, Taipei","correspondingAuthor":false,"prefix":"","firstName":"Bor-Shiuan","middleName":"","lastName":"Shyr","suffix":""},{"id":267509381,"identity":"0980aed2-9fc7-4aaa-b313-63edb64a970d","order_by":3,"name":"Shih-Chin Chen","email":"","orcid":"","institution":"Taipei Veterans General Hospital; National Yang Ming Chiao Tung University, Taipei","correspondingAuthor":false,"prefix":"","firstName":"Shih-Chin","middleName":"","lastName":"Chen","suffix":""},{"id":267509382,"identity":"467fa9e9-f5eb-4929-a123-4a36a34272dc","order_by":4,"name":"Yi-Ming Shyr","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Yi-Ming","middleName":"","lastName":"Shyr","suffix":""},{"id":267509383,"identity":"0b11dfd6-086d-4bad-b051-fe38fc7e16c3","order_by":5,"name":"Bor-Uei Shyr","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA00lEQVRIiWNgGAWjYHACZoYENhs7NvYGINvAgmgtacn8PAdAWiSI1MLAdphx5owEEIcILeYSuYcNHpSlMRvcfH51w48CCQb+9u4EvFosZ+QlJyScs+EzuJ1TdrMH6DCJM2c34NVicCPH+EBiG9CW2zlpN3iAWgwkconScphxw80zaTf/EKslAaRl5gz2Y7eJssWy542xQcI5UCDnsN2WMZDgIegXc/YcY8kfZaCoPP7s5ps/NnL87b0EHIZg8oDZPHiVo2lhf0BQ9SgYBaNgFIxMAABYgUgOARwc/QAAAABJRU5ErkJggg==","orcid":"","institution":"Taipei Veterans General Hospital; National Yang Ming Chiao Tung University, Taipei","correspondingAuthor":true,"prefix":"","firstName":"Bor-Uei","middleName":"","lastName":"Shyr","suffix":""}],"badges":[],"createdAt":"2024-01-12 15:16:50","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3857389/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3857389/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49827163,"identity":"1ad747ab-ae80-45d3-b514-70105991aef9","added_by":"auto","created_at":"2024-01-18 15:56:30","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":2632806,"visible":true,"origin":"","legend":"\u003cp\u003eA 3 cm hypodense mass at ampulla of Vater (\u003cem\u003ered arrow\u003c/em\u003e), causing dilatation of common bile duct and intrahepatic ducts (a), and a 5.5 cm mass (\u003cem\u003eyellow arrow\u003c/em\u003e) at perirenal space in upper pole of right kidney (b).\u003c/p\u003e","description":"","filename":"Figure1CTscan.png","url":"https://assets-eu.researchsquare.com/files/rs-3857389/v1/1bc87bcc24d9229daf534725.png"},{"id":49827161,"identity":"7e064ec4-5de0-4253-a3f6-46bc62f1e1ea","added_by":"auto","created_at":"2024-01-18 15:56:29","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":5539716,"visible":true,"origin":"","legend":"\u003cp\u003eA 3.7 x 3.3 x 3.0 cm tan to black tumor noted at ampulla of Vater with necrotic center (a), and a 6.6 x 5.2 x 3.2 cm tumor noted at right peri-renal space (b).\u003c/p\u003e","description":"","filename":"Figure2Gross.png","url":"https://assets-eu.researchsquare.com/files/rs-3857389/v1/4b391cb9452d3f1bcf76f6bf.png"},{"id":49827153,"identity":"8e889217-e133-49fa-b8b3-b17816b4ed79","added_by":"auto","created_at":"2024-01-18 15:56:28","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":15736050,"visible":true,"origin":"","legend":"\u003cp\u003eThe tumor was composed of spindle to epithelioid atypical melanocytes (a, b) with pleomorphic nuclei, prominent nucleoli, and brisk mitotic activity (\u003cem\u003ered arrows\u003c/em\u003e), forming nests (\u003cem\u003eyellow circles\u003c/em\u003e). The tumor cells were immunoreactive to SOX10 (c), HMB45 (d) and negative for BRAF (e) stains. BAP1 stains (f) shows aberrant loss of expression.\u003c/p\u003e","description":"","filename":"Figure3Histopathology.png","url":"https://assets-eu.researchsquare.com/files/rs-3857389/v1/1c654b77835e44f7f83268f2.png"},{"id":51259605,"identity":"4ae47588-9246-4df4-bfe2-9f3cc04d1f1b","added_by":"auto","created_at":"2024-02-17 08:07:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5804591,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3857389/v1/fcc0a8ba-716a-4866-a9f6-a6fff0d829f4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Is pancreaticoduodenectomy justified for metastatic melanoma to the ampulla of Vater?","fulltext":[{"header":"Background","content":"\u003cp\u003eMelanoma, the leading cause of skin cancer-related deaths, encompasses a diverse spectrum of malignant melanocytic proliferations.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] Melanoma with distant metastasis in the abdominal cavity most commonly affects the liver and the gastrointestinal tract,[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] while metastasis to the ampulla of Vater is uncommon with a dismal prognosis.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] As various therapeutic agents advance, the effective treatment of patients with distant melanoma metastasis has become a reality, significantly enhancing their quality of life.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] However, the optimal therapeutic approach for metastatic melanoma to the ampulla of Vater remains uncertain, given the rarity of such metastatic lesions. The appropriateness of aggressive surgical strategy, such as pancreaticoduodenectomy, remains a topic of uncertainty in this context.\u003c/p\u003e \u003cp\u003eWe hereby presented a rare case of malignant melanoma with multiple metastases to the ampulla of Vater and right kidney of a 64-year-old man, aiming to share our experience for clinicians to guide further management plan in patients with advanced stage of melanoma. We have also collected all cases of metastatic melanoma to the ampulla of Vater that were published on PubMed and MEDLINE until 2023 for the pooled data of analysis. Additionally, we reviewed studies that highlight the impact of surgery on the prognosis of patients with metastatic melanoma.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eBrief descriptions were made for the case of a metastatic melanoma to the ampulla of Vater encountered at our institution. The study has been approved by the Institutional Review Board of Taipei Veterans General Hospital (IRB-TPEVGH No.: 2023-11-006CC). Data and materials described in this manuscript, including all relevant raw data, will be freely available to any scientist willing to use them for non-commercial purposes, without breaching participant confidentiality. To clarify the characteristics and outcomes of metastatic melanoma to the ampulla of Vater, individualized data of cases published in the English literature were extracted and added to our database to expand the sample size for a more complete analysis. Two methods were utilized in searching for relevant cases. First, to identify the articles dealing with metastatic melanoma to the ampulla of Vater in the literature, a computerized search was performed on the PubMed and MEDLINE electronic database, covering data from 1996 to 2023. The following keywords were used for the search: metastatic melanoma, ampulla of Vater metastasis, pancreaticoduodenectomy, metastasectomy, and adjuvant systemic therapies. Second, the reference lists of PubMed-selected metastatic melanoma to the ampulla of Vater articles were screened systematically for additional studies of interests.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] The data pooled from the literature cases and our case were analyzed to determine the characteristics of metastatic melanoma to ampulla of Vater including demographics, primary tumor sites and thickness, clinical presentations, concomitant metastasis to other site, tumor size, lymph nodes status, treatment, and survival outcomes.\u003c/p\u003e \u003cp\u003eStatistical analyses were conducted using Statistical Product and Service Solutions (SPSS) version 23.0 software (SPSS Inc., IBM, Armonk, NY, USA). All continuous data were calculated using median (range) and mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD), and case number (%) were presented when appropriate to the type of data. Actuarial survival was estimated using the Kaplan\u0026ndash;Meier method, and a log rank test was used to determine differences in the subgroups. For all analyses, a \u003cem\u003ep\u003c/em\u003e value less than 0.050 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 14 cases of metastatic melanoma to the ampulla of Vater were recruited for this study, including 13 cases from the published literature [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan additionalcitationids=\"CR20 CR21 CR22 CR23 CR24 CR25 CR26 CR27 CR28\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] and 1 from our institution (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCase reports of metastatic melanoma to the ampulla of Vater\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAuthor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYear\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003cp\u003e/Sex\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePrimary site\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSurgical treatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSystemic therapy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFollow-up (Month)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSans [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1996\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eES\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eDead\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMeyers [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e 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\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSkin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eES\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eDead\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedina [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1999\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePPPD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eDead\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLe Borgne [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62/F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSkin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSurvived\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLe Borgne [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33/F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSkin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSurvived\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBokhoven [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66/F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSkin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eES\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUiterwaal [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41/F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSkin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCCRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eDead\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBerger [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66/F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSkin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eES\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eDead\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNakayama [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81/F\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eVagina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eDead\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBendic [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAmpulla\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eDead\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYamakawa [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBucca\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eBD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArmany [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSkin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eES\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003e\u003cem\u003eM\u003c/em\u003e male, \u003cem\u003eF\u003c/em\u003e female, \u003cem\u003eNA\u003c/em\u003e not available, \u003cem\u003ePD\u003c/em\u003e pancreaticoduodenectomy, \u003cem\u003ePPPD\u003c/em\u003e pylorus-preserving pancreaticoduodenectomy, \u003cem\u003eES\u003c/em\u003e endoscopic sphincterotomy, \u003cem\u003eBD\u003c/em\u003e biliary drainage, \u003cem\u003eCT\u003c/em\u003e chemotherapy, \u003cem\u003eCCRT\u003c/em\u003e concurrent chemoradiotherapy\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eOur case was a 64-year-old man who presented with a 3-week-history of jaundice. Biochemical analysis demonstrated an obstructive liver function test pattern with a total bilirubin of 8.09 mg/dL, direct bilirubin of 6.67 mg/dL, alkaline phosphate of 780 U/L, gamma-glutamyl transferase of 1056 U/L, amylase of 231 U/L and lipase of 271 U/L along with elevated carbohydrate antigen 19\u0026thinsp;\u0026minus;\u0026thinsp;9 (CA-199) of 64.1 U/ml. Abdominal computed tomography (CT) scanning revealed a tumor at periampullary area, measured 3cm in size, causing dilatation of common bile duct and intrahepatic ducts (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea). Meanwhile, another 5.5cm mass was noted at the upper pole of the right kidney (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb). On physical examination, there was one pigmented, hard, and ill-defined skin lesion at the right lateral chest wall, which the patient claimed to have been noted for more than 10 years. He underwent robotic pancreaticoduodenectomy (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea), peri-renal tumor resection (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb), and wide excision of the skin tumor. Histopathologic examination revealed the tumor cells with pleomorphic nuclei, prominent nucleoli, and intracytoplasmic melanin pigments deposition (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea-b). They were immunoreactive to SRY-related HMG-BOX gene 10 (SOX10) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec), human melanoma black-45 (HMB45) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ed) markers, focally positive for cluster of differentiation 117 (CD117) marker, and negative for discovered on gastrointestinal stromal tumors protein 1 (DOG1), cluster of differentiation 34 (CD34) markers, and B-Raf proto-oncogene (BRAF) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ee). BAP1 (BReast CAncer gene 1 associated protein 1) stains showed aberrant loss of expression (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ef). Sections of the right chest wall skin tumor and the right perirenal space tumor demonstrated similar morphology as the periampullary tumor. The tumor was analyzed for mutations in 52 genes and guanine nucleotide-binding protein subunit alpha-11 (GNA11) mutation was detected. Based on the patient\u0026rsquo;s clinical presentation, molecular and immunohistochemistry findings of the tumor, a diagnosis of blue nevus-like melanoma with BAP1 loss was established. Our patient underwent adjuvant chemotherapy using dacarbazine and received immunotherapy with pembrolizumab and is reported to be alive 18 months after operation.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe demographics and clinical presentations of the 14 cases of metastatic melanoma to the ampulla of Vater are listed in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The median age at the diagnosis of was 60 years old, ranging from 33 to 83 years old for overall patients, and this tumor occurred more frequently in Western countries (71%) than in Asia (29%). Most melanomas originate from the skin (73%), with only 27% of the cases being of the mucosal type. Thickness of primary melanoma ranged from 1.2 mm to 30 mm with a median of 2.75 mm, and the median interval between diagnoses of primary and metastatic melanoma to ampulla was 36 months, with the longest duration up to 120 months. The most common symptom was jaundice (86%), followed by abdominal pain (36%).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographics and clinical presentations of metastatic melanoma to the ampulla of Vater\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDemographics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (57%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (43%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAge (y/o, n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60 (33\u0026ndash;83)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58.57\u0026thinsp;\u0026plusmn;\u0026thinsp;14.46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eArea (n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWestern\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (71%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (29%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePrimary site of tumor (n\u0026thinsp;=\u0026thinsp;11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCutaneous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (73%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMucosal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (27%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePrimary tumor thickness (mm, n\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.75 (1.2\u0026ndash;30)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.66\u0026thinsp;\u0026plusmn;\u0026thinsp;9.95\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eInterval of metastasis (month, n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (10\u0026ndash;120)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46\u0026thinsp;\u0026plusmn;\u0026thinsp;37.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSymptoms (n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJaundice\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (86%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbdominal pain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (36%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNausea/vomit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (21%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody weight loss\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (14%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnorexia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (14%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSymptoms duration (month, n\u0026thinsp;=\u0026thinsp;10)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.85 (0.06-11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.38\u0026thinsp;\u0026plusmn;\u0026thinsp;3.31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDiagnosis method (n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndoscopy (ERCP)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (78%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCT scan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (43%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSonography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e\u003cem\u003eSD\u003c/em\u003e standard deviation, \u003cem\u003eCT\u003c/em\u003e computed tomography, \u003cem\u003eERCP\u003c/em\u003e endoscopic retrograde cholangiopancreatography\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e described the characteristics and treatment of metastatic melanoma to the ampulla of Vater. The size of metastatic melanoma to ampulla of Vater ranged from 1.5 cm to 8 cm, with a median of 2.75 cm. Concomitant metastasis to other organs occurred in 82% of the cases at the diagnosis of this tumor, most commonly in the brain, lungs, and liver (36% each, respectively). Wide excision of the primary lesion improved the outcome significantly (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.048, Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Forty-three percent of patients underwent pancreaticoduodenectomy; however, more than half (57%) of them did not receive chemotherapy. Patients who received chemotherapy experienced a significantly higher overall 1-year survival rate of 50% compared to those who did not (0%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.048). While there was a trend toward improved survival in patients undergoing pancreaticoduodenectomy, it was worth noting that this difference did not achieve statistical significance (33.3% V.S 20%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.301). Lymph node metastasis, number of the metastatic site, metastatic tumor size or interval between primary and metastasis seemed to have no survival impact.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics and treatment of metastatic melanoma to the ampulla of Vater\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCharacteristics n (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMetastatic tumor size (cm, n\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.75 (1.5-8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.49\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMetastasis to other distant organs (n\u0026thinsp;=\u0026thinsp;11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBrain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (36%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChest (lungs, mediastinum)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (36%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLiver\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (36%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePelvis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (27%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpleen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (18%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePancreas\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntestines\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (18%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSurgical treatment (n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePancreaticoduodenectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (43%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInternal stents\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (36%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBiliary drainage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (14%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePositive lymph node status (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (78%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (22%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eChemotherapy (n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (43%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (57%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e\u003cem\u003eSD\u003c/em\u003e standard deviation\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSurvival outcomes of metastatic melanoma to the ampulla of Vater\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase Number\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMedian (range), month\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, month\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1-year survival\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003cp\u003evalue\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (1\u0026ndash;15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.09\u0026thinsp;\u0026plusmn;\u0026thinsp;4.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e27.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eAmpullary metastasis 0.223\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSolitary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (2\u0026ndash;12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCombined with other sites metastasis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (1\u0026ndash;15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.67\u0026thinsp;\u0026plusmn;\u0026thinsp;4.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e22.2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eMetastatic tumor size (cm) 0.59\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;2 cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.5 (2\u0026ndash;12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.25\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;2 cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.5 (3\u0026ndash;15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.75\u0026thinsp;\u0026plusmn;\u0026thinsp;5.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eInterval between primary and metastasis (months) 0.351\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;1 year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;1 year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.5 (3\u0026ndash;15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e75%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eThickness of the primary lesion 0.853\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;2 mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2.01-4 mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;4 mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (1\u0026ndash;15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eSite of the primary lesion 0.081\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCutaneous type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (3\u0026ndash;18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMucosal type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.5 (1\u0026ndash;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eWide excision of the primary lesion 0.048\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (3\u0026ndash;15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (1\u0026ndash;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003ePancreaticoduodenectomy 0.301\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (2\u0026ndash;15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e33.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (1\u0026ndash;15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.2\u0026thinsp;\u0026plusmn;\u0026thinsp;4.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eChemotherapy 0.048\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (3\u0026ndash;15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (1\u0026ndash;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003epositive lymph nodes status 0.118\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.5 (1\u0026ndash;12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.67\u0026thinsp;\u0026plusmn;\u0026thinsp;3.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eMalignant melanomas are aggressive cancers, accounting for 90% of skin cancer-related deaths.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] Metastasis within the abdominal cavity typically affects the liver and gastrointestinal tract,[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] while metastasis to the ampulla of Vater is extremely rare.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] To date, there have only been 13 reported cases of metastatic melanoma to the ampulla of Vater and of those, only five patients underwent surgical pancreaticoduodenectomy. The median follow-up time was 4 months, two patients were reported to be alive at 2 and 12 months after surgery, reported by Le Borgne et al.,[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] while the remaining cases either died or were not documented. Similar to Le Borgne's report, our patient also underwent pancreaticoduodenectomy followed by chemotherapy, and both individuals survived for over one year after the surgery. In our study, we noticed there was a trend toward favorable outcome among those who underwent pancreaticoduodenectomy. However, it's important to acknowledge that this trend did not attain statistical significance, primarily due to the limitation imposed by the small sample size in this study. On the other hand, primary site tumor excision markedly enhanced the survival rate (50% vs. 0%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.048), underscoring the crucial role of surgery in the management of melanoma.\u003c/p\u003e \u003cp\u003eBlue nevus-associated melanoma comprises a heterogenous and relative uncommon group of melanomas, which demonstrate a similar histopathological and mutational pattern with uveal melanoma, including guanine nucleotide-binding protein subunit alpha-11 (GNA11) or guanine nucleotide-binding protein subunit alpha Q (GNAQ) mutations.[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] Additional BAP1 loss is associated with younger diagnostic age, larger average lesion thickness and a higher risk of metastasis.[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] In the presenting case, our patient was diagnosed with blue nevus-like melanoma with GNA11 mutation and BAP1 loss, which has been reported to have a higher metastatic rate in published literature. Historically, patients who develop distant metastasis in melanoma have had a poor prognosis, with a median survival of 6 to 7.5 months and 5-year survival rate of less than 10% [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Our study reveals an overall 1-year survival rate of 27.3% and a median survival of 4 months, highlighting a particularly unfavorable outcome in the cases of metastatic melanoma to the ampulla of Vater in literature.\u003c/p\u003e \u003cp\u003eAlthough traditional chemotherapy, like dacarbazine, has been associated with a reported low response rate (approximately 15\u0026ndash;20%) in literature,[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] our study revealed a notable enhancement in survival outcomes among patients who underwent chemotherapy (50% vs. 0%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.048). Since the introduction of the eighth edition American Joint Committee on Cancer staging system in 2018,[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] the landscape of treatment options for advanced stage melanoma has rapidly evolved. Ipilimumab, a monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4 markedly improved the overall survival of patients with metastatic melanoma.[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] Targeted BRAF/MEK inhibitors also revolutionized the therapeutic landscape, which significantly prolonged the overall survival in patients with BRAF mutant melanoma.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] Therefore, since 2013, a significant improvement in metastatic melanoma mortality rates was observed, largely attributed to the advent of effective systemic therapies.[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] With the availability of these novel therapies, the patterns of surgical intervention and the indications for surgery evolved in parallel. A retrospective cohort study including 138 patients with stage IV melanoma showed a significant increase in potentially curative operations among patients managed in the modern treatment era.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] Recently, a systemic review and meta-analysis was conducted to access the role of surgery for patients with metastatic melanoma.[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] This review included 40 studies and 31,282 patients, and it showed that patients who underwent curative metastasectomy had a significantly lower rate of death than those who did not (HR 0.42; 95% confidence interval 0.38\u0026ndash;0.47; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.00001). The phase III trial of Malignant Melanoma Active Immunotherapy (MMAIT) has reported that long-term survival can be achieved through metastasectomy.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] Some studies pointed out that the prognosis was independent of immunotherapy, the stage at initial operation and the anatomic site of metastasis, while number of metastases did not affect the overall survival rate after complete resection.[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] Our study also revealed that neither the number of metastatic sites nor the size of metastatic tumors had a detrimental impact on survival outcomes.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eTo the best of our knowledge, this study reports the longest follow-up period for a patient with metastatic melanoma to the ampulla of Vater who underwent pancreaticoduodenectomy followed by adjuvant chemotherapy and immunotherapy, and is currently alive 18 months after operation. With the continued development of effective therapeutic agents, surgery in metastatic melanoma has evolved from a palliative approach to a more aggressive role aimed at eradicating the disease. This study also demonstrated that adopting an aggressive surgical approach can yield favorable outcomes, even when combined solely with traditional chemotherapy rather than relying on novel therapeutic agents. Nevertheless, it's important to acknowledge that the findings of this study are constrained by a limited sample size, attributable to the rarity of metastatic melanoma to the ampulla of Vater.\u003c/p\u003e \u003cp\u003eIn conclusion, resection of metastatic lesions followed by systemic therapy may offer benefits to patients with metastatic melanoma, regardless of the number, location, or tumor size of the metastasis. Given the availability of various effective systemic therapy options, metastatic melanoma to the ampulla of Vater is not necessarily to preclude a major surgery. Pancreaticoduodenectomy should be considered when feasible to improve overall survival outcomes.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCA 19-9: Carbohydrate antigen 19-9\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCT: Computed tomography\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSOX10: SRY-related HMG-BOX gene 10\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHMB45: Human melanoma black-45\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCD: Cluster of differentiation\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDOG1: Gastrointestinal stromal tumors protein 1\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBRAF: B-Raf proto-oncogene\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBAP1: BReast CAncer gene 1\u0026nbsp;associated protein 1\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGNA11: Guanine nucleotide-binding protein subunit alpha-11\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGNAQ: Guanine nucleotide-binding protein subunit alpha Q\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAJCC: American Joint Committee on Cancer\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMMAIT:\u0026nbsp;Malignant Melanoma Active Immunotherapy\u003c/p\u003e\n\u003cp\u003ePD: pancreaticoduodenectomy\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePPPD: pylorus-preserving pancreaticoduodenectomy\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eES: endoscopic sphincterotomy\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBD: biliary drainage\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCCRT: concurrent chemoradiotherapy\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study has been approved by the Institutional Review Board of Taipei Veterans General Hospital (IRB-TPEVGH No.: 2023-11-006CC). Appropriate written informed consent to participate was obtained from the patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData and materials described in this manuscript, including all relevant raw data, will be freely available to any scientist willing to use them for non-commercial purposes, without breaching participant confidentiality.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was financially supported by grants from the Taipei Veterans General Hospital (V112C-009, V112C-188,\u0026nbsp;and\u0026nbsp;V112B-001), the Ministry of Science and Technology (NSTC 112-2314-B-075-016 -), and the Ministry of Health and Welfare (MOHW111-TDU-B-221-014015).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eH.C.N. and S.B.S. equally contributed to this paper. H.C.N., W.S.E., S.B.U. and S.Y.M. made substantial contributions to conception and design, acquisition of data, and analysis and interpretation of data. H.C.N. was a major contributor in writing the manuscript. S.B.S. was involved in drafting the manuscript or revising it critically for important intellectual content. W.S.E. was involved in drafting the manuscript or revising it critically for important intellectual content and agreed to be accountable for all aspects of the imaging studies in ensuring that questions related to the accuracy. H.C.N., S.B.U. and S.Y.M. made substantial contributions to conception and design, acquisition of data, and analysis and interpretation of data and gave final approval of the version to be published. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to acknowledge the support of the Biobank of Taipei Veterans General Hospital,\u0026nbsp;Common Well Foundation and\u0026nbsp;statistical team of\u0026nbsp;Taipei Veterans General Hospital.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGarbe C, Amaral T, Peris K, Hauschild A, Arenberger P, Basset-Seguin N, Bastholt L, Bataille V, Del Marmol V, Dr\u0026eacute;no B et al: \u003cstrong\u003eEuropean consensus-based interdisciplinary guideline for melanoma. Part 1: Diagnostics: Update 2022\u003c/strong\u003e. \u003cem\u003eEur J Cancer\u003c/em\u003e 2022, \u003cstrong\u003e170\u003c/strong\u003e:236-255.\u003c/li\u003e\n\u003cli\u003eIonescu S, Nicolescu AC, Madge OL, Simion L, Marincas M, Ceausu M: \u003cstrong\u003eIntra-Abdominal Malignant Melanoma: Challenging Aspects of Epidemiology, Clinical and Paraclinical Diagnosis and Optimal Treatment-A Literature Review\u003c/strong\u003e. \u003cem\u003eDiagnostics (Basel)\u003c/em\u003e 2022, \u003cstrong\u003e12(9)\u003c/strong\u003e:2054.\u003c/li\u003e\n\u003cli\u003eMarks JA, Rao AS, Loren D, Witkiewicz A, Mastrangelo MJ, Berger AC: \u003cstrong\u003eMalignant Melanoma Presenting as Obstructive Jaundice Secondary to Metastasis to the Ampulla of Vater\u003c/strong\u003e. JOP. 2010 Mar 5;\u003cstrong\u003e11(2)\u003c/strong\u003e:173-175. \u003c/li\u003e\n\u003cli\u003eJenkins RW, Fisher DE: \u003cstrong\u003eTreatment of Advanced Melanoma in 2020 and Beyond\u003c/strong\u003e. \u003cem\u003eJ Invest Dermatol\u003c/em\u003e 2021, 1\u003cstrong\u003e41(1)\u003c/strong\u003e:23-31.\u003c/li\u003e\n\u003cli\u003eAllen AC SS: \u003cstrong\u003eMalignant melanoma: a clinicopathological analysis of the criteria for diagnosis and prognosis\u003c/strong\u003e. \u003cem\u003eCancer 1953\u003c/em\u003e, \u003cstrong\u003e6\u003c/strong\u003e:1-45.\u003c/li\u003e\n\u003cli\u003eBerk-Krauss J, Stein JA, Weber J, Polsky D, Geller AC: \u003cstrong\u003eNew Systematic Therapies and Trends in Cutaneous Melanoma Deaths Among US Whites, 1986-2016\u003c/strong\u003e. \u003cem\u003eAm J Public Health \u003c/em\u003e2020, \u003cstrong\u003e110(5)\u003c/strong\u003e:731-733.\u003c/li\u003e\n\u003cli\u003eDeutsch GB, Flaherty DC, Kirchoff DD, Bailey M, Vitug S, Foshag LJ, Faries MB, Bilchik AJ: \u003cstrong\u003eAssociation of Surgical Treatment, Systemic Therapy, and Survival in Patients With Abdominal Visceral Melanoma Metastases, 1965-2014: Relevance of Surgical Cure in the Era of Modern Systemic Therapy\u003c/strong\u003e. \u003cem\u003eJAMA Surg \u003c/em\u003e2017, \u003cstrong\u003e152(7)\u003c/strong\u003e:672-678.\u003c/li\u003e\n\u003cli\u003eDobry AS, Zogg CK, Hodi FS, Smith TR, Ott PA, Iorgulescu JB: \u003cstrong\u003eManagement of metastatic melanoma: improved survival in a national cohort following the approvals of checkpoint blockade immunotherapies and targeted therapies\u003c/strong\u003e. \u003cem\u003eCancer Immunol Immunother \u003c/em\u003e2018, \u003cstrong\u003e67(12)\u003c/strong\u003e:1833-1844.\u003c/li\u003e\n\u003cli\u003eFaries MB, Mozzillo N, Kashani-Sabet M, Thompson JF, Kelley MC, DeConti RC, Lee JE, Huth JF, Wagner J, Dalgleish A et al: \u003cstrong\u003eLong-Term Survival after Complete Surgical Resection and Adjuvant Immunotherapy for Distant Melanoma Metastases\u003c/strong\u003e. \u003cem\u003eAnn Surg Oncol \u003c/em\u003e2017, \u003cstrong\u003e24(13)\u003c/strong\u003e:3991-4000.\u003c/li\u003e\n\u003cli\u003eHersh EM, O\u0026apos;Day SJ, Powderly J, Khan KD, Pavlick AC, Cranmer LD, Samlowski WE, Nichol GM, Yellin MJ, Weber JS: \u003cstrong\u003eA phase II multicenter study of ipilimumab with or without dacarbazine in chemotherapy-na\u0026iuml;ve patients with advanced melanoma\u003c/strong\u003e. \u003cem\u003eInvest New Drugs\u003c/em\u003e 2011, \u003cstrong\u003e29(3)\u003c/strong\u003e:489-498.\u003c/li\u003e\n\u003cli\u003eHoward JH, Thompson JF, Mozzillo N, Nieweg OE, Hoekstra HJ, Roses DF, Sondak VK, Reintgen DS, Kashani-Sabet M, Karakousis CP et al: \u003cstrong\u003eMetastasectomy for distant metastatic melanoma: analysis of data from the first Multicenter Selective Lymphadenectomy Trial (MSLT-I)\u003c/strong\u003e. \u003cem\u003eAnn Surg Oncol 2012\u003c/em\u003e, \u003cstrong\u003e19(8)\u003c/strong\u003e:2547-2555.\u003c/li\u003e\n\u003cli\u003eMiddleton MR, Grob JJ, Aaronson N, Fierlbeck G, Tilgen W, Seiter S, Gore M, Aamdal S, Cebon J, Coates A et al: \u003cstrong\u003eRandomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma\u003c/strong\u003e. \u003cem\u003eJ Clin Oncol 2000\u003c/em\u003e, \u003cstrong\u003e18(1)\u003c/strong\u003e:158-166.\u003c/li\u003e\n\u003cli\u003eSmith MJF, Smith HG, Joshi K, Gore M, Strauss DC, Hayes AJ, Larkin J: \u003cstrong\u003eThe impact of effective systemic therapies on surgery for stage IV melanoma\u003c/strong\u003e. \u003cem\u003eEur J Cancer \u003c/em\u003e2018, \u003cstrong\u003e103\u003c/strong\u003e:24-31.\u003c/li\u003e\n\u003cli\u003eWankhede D, Grover S: \u003cstrong\u003eOutcomes After Curative Metastasectomy for Patients with Malignant Melanoma: A Systematic Review and Meta-analysis\u003c/strong\u003e. \u003cem\u003eAnn Surg Oncol\u003c/em\u003e 2022, \u003cstrong\u003e29(6)\u003c/strong\u003e:3709-3723.\u003c/li\u003e\n\u003cli\u003eWood TF, DiFronzo LA, Rose DM, Haigh PI, Stern SL, Wanek L, Essner R, Morton DL: \u003cstrong\u003eDoes complete resection of melanoma metastatic to solid intra-abdominal organs improve survival? \u003c/strong\u003e\u003cem\u003eAnn Surg Oncol \u003c/em\u003e2001,\u003cstrong\u003e 8(8)\u003c/strong\u003e:658-662.\u003c/li\u003e\n\u003cli\u003eManola J AM, Ibrahim J, et al: \u003cstrong\u003ePrognostic factors in metastatic melanoma: a pooled analysis of Eastern Cooperative Oncology Group trials\u003c/strong\u003e. \u003cem\u003eJ Clin Oncol \u003c/em\u003e2000, \u003cstrong\u003e18(22)\u003c/strong\u003e:3782-3793.\u003c/li\u003e\n\u003cli\u003ePrabhakaran S, Fulp WJ, Gonzalez RJ, Sondak VK, Kudchadkar RR, Gibney GT, Weber JS, Zager JS: \u003cstrong\u003eResection of Gastrointestinal Metastases in Stage IV Melanoma: Correlation with Outcomes.\u003c/strong\u003e\u003cem\u003eAm Surg\u003c/em\u003e 2016, \u003cstrong\u003e82(11)\u003c/strong\u003e:1109-1116.\u003c/li\u003e\n\u003cli\u003eRobert C, Thomas L, Bondarenko I, O\u0026apos;Day S, Weber J, Garbe C, Lebbe C, Baurain JF, Testori A, Grob JJ et al: \u003cstrong\u003eIpilimumab plus dacarbazine for previously untreated metastatic melanoma\u003c/strong\u003e. \u003cem\u003eN Engl J Med \u003c/em\u003e2011, \u003cstrong\u003e364(26)\u003c/strong\u003e:2517-2526.\u003c/li\u003e\n\u003cli\u003eM Sans JL, J M Bordas, V Andreu, A Campo, A Castells, E Mondelo, J Ter\u0026eacute;s, J Rod\u0026eacute;s: \u003cstrong\u003eMetastatic malignant melanoma of the papilla of Vater- an unusual case of obstructive cholestasis treated with biliary prostheses\u003c/strong\u003e. \u003cem\u003eEndoscopy\u003c/em\u003e 1996, \u003cstrong\u003e28\u003c/strong\u003e:791-792.\u003c/li\u003e\n\u003cli\u003eM O Meyers DJF, E A Levine: \u003cstrong\u003ePancreaticoduodenectomy for melanoma metastatic to the duodenum- a case report and review of the literature\u003c/strong\u003e. \u003cem\u003eAm Surgeon\u003c/em\u003e 1998, \u003cstrong\u003e64(12)\u003c/strong\u003e:1174-1176.\u003c/li\u003e\n\u003cli\u003eCaballero-Mendoza E, Gallo-Reynoso S, Arista-Nasr J, Angeles-Angeles A: \u003cstrong\u003eObstructive Jaundice as the First Clinical Manifestation of a Metastatic Malignant Melanoma in the Ampulla of Vater\u003c/strong\u003e. \u003cem\u003eJ\u003c/em\u003e\u003cem\u003e Clin Gastroenterol\u003c/em\u003e 1999, \u003cstrong\u003e29(2)\u003c/strong\u003e:188-189.\u003c/li\u003e\n\u003cli\u003eH Medina-Franco NBH, J S Aldrete: \u003cstrong\u003ePancreaticoduodenectomy for Metastatic Tumors to the Periampullary Region\u003c/strong\u003e. \u003cem\u003eJ Gastrointest Surg\u003c/em\u003e 1999, \u003cstrong\u003e3\u003c/strong\u003e:119-122.\u003c/li\u003e\n\u003cli\u003eLe Borgne CP, P Glemain, B Dupas, B de Kerviller: \u003cstrong\u003ePancreaticoduodenectomy for metastatic ampullary and pancreatic tumors\u003c/strong\u003e. \u003cem\u003eHepatogastroenterology \u003c/em\u003e2000, \u003cstrong\u003e47\u003c/strong\u003e:540-544.\u003c/li\u003e\n\u003cli\u003evan Bokhoven MM, Aarntzen EH, Tan AC: \u003cstrong\u003eMetastatic melanoma of the common bile duct and ampulla of Vater.\u003c/strong\u003e\u003cem\u003eGastrointest Endosc\u003c/em\u003e 2006, \u003cstrong\u003e63(6)\u003c/strong\u003e:873-874.\u003c/li\u003e\n\u003cli\u003eUiterwaal MT, Mooi WJ, Van Weyenberg SJ: \u003cstrong\u003eMetastatic melanoma of the ampulla of Vater.\u003c/strong\u003e\u003cem\u003eDig Liver Dis\u003c/em\u003e 2011, \u003cstrong\u003e43(4)\u003c/strong\u003e:e8.\u003c/li\u003e\n\u003cli\u003eNakayama H, Miyazaki S, Kikuchi H, Saito N, Shimada H, Sakai S, Suzuki M, Kimura K: \u003cstrong\u003eMalignant vaginal melanoma with metastases to the papilla of Vater in a dialysis patient: a case report\u003c/strong\u003e.\u003cem\u003e Intern Med\u003c/em\u003e 2011, \u003cstrong\u003e50(4)\u003c/strong\u003e:345-349.\u003c/li\u003e\n\u003cli\u003eBendic A, Glavina Durdov M, Stipic R, Karaman I: \u003cstrong\u003eMelanoma in the ampulla of Vater.\u003c/strong\u003e\u003cem\u003eHepatobiliary Pancreat Dis Int\u003c/em\u003e 2013, \u003cstrong\u003e12(1)\u003c/strong\u003e:106-108.\u003c/li\u003e\n\u003cli\u003eYamakawa K, Kurita A, Azuma S, Kudo Y, Yazumi S: \u003cstrong\u003eMetastatic melanoma in the ampulla of Vater\u003c/strong\u003e. \u003cem\u003eGastrointest Endosc\u003c/em\u003e 2018, \u003cstrong\u003e87(4)\u003c/strong\u003e:1156-1158.\u003c/li\u003e\n\u003cli\u003eArmany D, Gosal P, Adams S: \u003cstrong\u003eThe ampulla of Vater: A potential target for metastatic melanoma?\u003c/strong\u003e\u003cem\u003eJ Surg Case Rep\u003c/em\u003e 2023, \u003cstrong\u003e2023(1)\u003c/strong\u003e:rjac621.\u003c/li\u003e\n\u003cli\u003eVan Raamsdonk CD BV, Green G et al.: \u003cstrong\u003eFrequent somatic mutations of GNAQ in uveal melanoma and blue naevi\u003c/strong\u003e. \u003cem\u003eNature\u003c/em\u003e 2009, \u003cstrong\u003e457\u003c/strong\u003e:599-602.\u003c/li\u003e\n\u003cli\u003eBorgenvik TL, Karlsvik TM, Ray S, Fawzy M, James N:\u003cstrong\u003e Blue nevus-like and blue nevus-associated melanoma: a comprehensive review of the literature\u003c/strong\u003e. \u003cem\u003eANZ J Surg \u003c/em\u003e2017, \u003cstrong\u003e87(5)\u003c/strong\u003e:345-349.\u003c/li\u003e\n\u003cli\u003eLi-Wei Chang VK, Rashek Kazi, Diwakar Davar, Robert L Ferris, Jonhan Ho, Arivarasan Karunamurthy, Jaroslaw J Jedrych, Yuri L Bunimovich: \u003cstrong\u003eMelanoma Ex Blue Nevus With GNA11 Mutation and BAP1 Loss: Case Report and Review of the Literature\u003c/strong\u003e. \u003cem\u003eAm J Dermatopathol \u003c/em\u003e2020, \u003cstrong\u003e42(11)\u003c/strong\u003e:854-857.\u003c/li\u003e\n\u003cli\u003eBarth A WL, Morton DL: \u003cstrong\u003ePrognostic factors in 1,521 melanoma patients with distant metastases.\u003c/strong\u003e\u003cem\u003eJ Am Coll Surg\u003c/em\u003e 1995, \u003cstrong\u003e181(3)\u003c/strong\u003e:193-201.\u003c/li\u003e\n\u003cli\u003eUnger JM FL, Liu PY, et al: \u003cstrong\u003eGender and other survival predictors in patients with metastatic melanoma on Southwest Oncology Group trials\u003c/strong\u003e. \u003cem\u003eCancer\u003c/em\u003e 2001, \u003cstrong\u003e91(6)\u003c/strong\u003e:1148-1155.\u003c/li\u003e\n\u003cli\u003eKeung EZ, Gershenwald JE: \u003cstrong\u003eThe eighth edition American Joint Committee on Cancer (AJCC) melanoma staging system: implications for melanoma treatment and care\u003c/strong\u003e. 2018, \u003cstrong\u003e18(8)\u003c/strong\u003e:775-784.\u003c/li\u003e\n\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":"metastatic melanoma, ampulla of Vater, pancreaticoduodenectomy, adjuvant systemic therapy","lastPublishedDoi":"10.21203/rs.3.rs-3857389/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3857389/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eMetastatic melanoma to the ampulla of Vater is rare. The purpose of this study is to summarize the characteristics and outcomes of metastatic melanoma to the ampulla of Vater, and to highlight the impact of surgery on the prognosis of patients with metastatic melanoma.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThe pooled data from a case encountered at our institution and all the sporadic cases published on PubMed and MEDLINE from 1996 to 2023 were included for analysis.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 14 cases of metastatic melanoma to the ampulla of Vater were recruited. Seventy-three percent of the primary melanomas were cutaneous type, and 27% mucosal type. The most common symptom was jaundice (86%). The size of metastatic melanoma to ampulla ranged from 1.5 cm to 8 cm, with a median of 2.75 cm. Concomitant metastasis to other organs occurred in 82% at the diagnosis of this tumor, most commonly to the brain, lungs, and liver (36% each, respectively). Among all the reported cases, pancreaticoduodenectomy was performed in five patients. The overall 1-year survival rate was 27.3%, with a median of 4 months. Wide excision of the primary lesion and chemotherapy significantly improve the survival rate (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.048). There is a trend toward improved survival in those undergoing pancreaticoduodenectomy followed by chemotherapy.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eGiven the availability of effective systemic therapy, metastatic melanoma to the ampulla of Vater is not necessarily to preclude a major surgery.\u003c/p\u003e","manuscriptTitle":"Is pancreaticoduodenectomy justified for metastatic melanoma to the ampulla of Vater?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-18 15:56:19","doi":"10.21203/rs.3.rs-3857389/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":"c200c805-7a65-4627-ba3d-955111ca878c","owner":[],"postedDate":"January 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-02-17T07:59:15+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-18 15:56:19","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3857389","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3857389","identity":"rs-3857389","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}