Two cases of primary leiomyosarcoma of sigmoid colon treated with laparoscopic surgery: a case report and a review of literature

Two cases of primary leiomyosarcoma of sigmoid colon treated with laparoscopic surgery: a case report and a review of literature | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Two cases of primary leiomyosarcoma of sigmoid colon treated with laparoscopic surgery: a case report and a review of literature Ali-Mohammad Bananzadeh, Maral Mokhtari, Maryam Sohooli, Ramin Shekouhi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-214702/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 30 Sep, 2021 Read the published version in International Journal of Surgery Case Reports → Version 1 posted You are reading this latest preprint version Abstract Background Leiomyosarcoma (LMS) of the colon is an unbelievably rare and highly invasive tumor arising from the muscularis propria of the gastrointestinal tract. After the introduction of the oncogenic role of KIT by immunohistochemistry (IHC), the reported cases of gastrointestinal leiomyosarcoma were limited. True LMS of the colon is such a rare disorder that there isn’t enough description of its nature. The classical colon LMS presents with a vast majority of non-specific symptoms including mild abdominal pain, fresh/obscure rectal bleeding, and weight loss. Case presentation: we experienced two extremely rare cases of colonic LMS. First patient was a 48-year-old man referred to our surgical outpatient clinic with mild intermittent abdominal pain and occasional rectal bleeding. After the initial investigation patient underwent colonoscopy that was suggestive of a large polypoid mass in 15 centimeters from the anal verge. Histopathology and Subsequent immunohistochemistry were in favor of LMS of sigmoid colon, and he underwent Laparoscopic anterior resection. The second patient was a 49-year-old man with 3-month history of fatigue, melena, and unintentional weight loss. Colonoscopy revealed a large circumferential mass in sigmoid colon 40 cm from the anal verge with the diagnosis of LMS. He underwent Laparoscopic left hemicolectomy. Conclusion: Herein, we reported two rare cases of primary leiomyosarcoma of sigmoid colon treated with laparoscopic surgery. The tumors were surgically removed via laparoscopic approach. Overall, colonic LMS is a highly invasive neoplasm with poor oncologic outcome. Gastrointestinal Surgery Cancer Biology colon cancer leiomyosarcoma sigmoid colon Figures Figure 1 Background: Leiomyosarcoma (LMS) of the colon is an unbelievably rare and highly invasive tumor arising from the muscularis propria of the gastrointestinal tract.[ 1 ] Before 1998, every neoplasm raised from mesenchymal cells was mistakenly classified as LMS; However, after the introduction of the oncogenic role of KIT by immunohistochemistry(IHC), only a very small number of true gastrointestinal leiomyosarcomas was reported[ 2 ]. Immunohistochemically, true LMS expresses actin(SMA) and desmin without the expression of GIST markers(CD117, CD34, and DOG1.1) and KIT mutations, which allows distinguishing LMS from other GI mesenchymal neoplasms[ 1 , 3 ]. We herein describe two rare cases of Leiomyosarcoma of sigmoid colon that were treated with laparoscopic resection. Case Presentation: Case 1: We reported a case of a 48-year-old man referred to our surgical outpatient clinic in December 2019. He presented with mild intermittent abdominal pain and occasional rectal bleeding for eight months without any history of weight loss, fatigue or night sweating. Furthermore, He had a blank family history of malignant neoplasia. General examination and vital signs were normal. Abdominal examinations revealed an ill-defined round mass at the left lower quadrant. Digital rectal examination was normal. Routine lab data were unremarkable, except mild microcytic anemia that was due to his thalassemia trait (Mentzer index=13.46). Carcinoembryonic antigen (CEA) test was normal. After the initial investigation patient underwent colonoscopy that was suggestive of a large polypoid mass with hard texture in 15 centimeters from the anal verge; rest of the colon were unremarkable. Histopathology revealed a neoplasm consists of spindle cells with hyperchromatic nuclei and mild pleomorphism. Subsequent immunohistochemistry showed immunoreactivity for smooth muscle actin and desmin but the tumor cells were negative for S100, CD34, C-KIT and DOG-1. The Ki-67 index was 15-20%. KIT mutation study also showed no mutation in exon 9, 11, 13 and 17. Therefore, the diagnosis of leiomyosarcoma was made. Treatment: Before the operation, patient was scheduled for a routine metastatic workup with Contrast-enhanced computed tomography (CT) of thoracic and abdomen and pelvis, and liver function test (LFT). The abdominal CT showed diffuse wall thickening of the sigmoid colon and distal part of the left colon associated with enhancing soft tissue mass measuring about 72mm × 40mm in sigmoid colon that was suggestive of a malignant process. Also, evidence of multiple regional lymph nodes was seen adjacent to the sigmoid colon. Chest CT and Liver function test (LFT) were unremarkable. The surgery was conducted under general anesthesia with the purpose of complete resection of the tumor and involved lymph nodes. Laparoscopic anterior resection was performed with resection of sigmoid colon and upper part of rectum. Colorectal anastomosis was performed with no diverting ileostomy. Tumor dimensions were 8×6×4.5 cm with a smooth surface and the cross-section showed homogenous white appearance. The specimen was sent for IHC profiling and histologic evaluation. Outcome and Follow-up: The post-operative course was uneventful without any signs of short-term complications. The patient discharged four days after surgery. The patient was scheduled for Contrast-enhanced computed tomography (CT) of thoracic and abdomino-pelvic every 6 months, and colonoscopy every 12 months. Patient has no signs of local recurrence or distant metastasis Up-to-date. We will follow the patient for at least 5 years of close surveillance. Case2: On April 29 th 2020, a 49-year-old man came to Shiraz Colorectal Clinic with 3-month history of fatigue, melena, and unintentional weight loss. Family history was negative for any previous disease. General examination showed temporal wasting and cachexia. Vital signs and abdominal examinations were unremarkable. Digital rectal examination showed grade-II internal hemorrhoids. Lab data was in favor of microcytic-hypochromic anemia (HB=11.7). Carcinoembryonic antigen (CEA) test was normal. Colonoscopy revealed a large 3*4*3.5 cm circumferential mass with deep central ulceration in sigmoid colon 40 cm from anal verge. Prior to surgery, Abdomino-perineal CT showed circumferential wall thickening of distal descending colon in Lt. lower quadrant with maximum wall thickness of 24mm and length of involvement about 43mm. Also, thickening of adjacent peritoneum was demonstrated. Pre-op chest CT was normal. Treatment: Laparoscopic left hemicolectomy was conducted under general anesthesia with the purpose of complete resection of the tumor and involved lymph nodes. The specimen was extracted via a mid-midline incision and extra-corporal anastomosis was done. The specimen was sent for IHC profiling and histologic evaluation. Outcome and Follow-up: Surgery was successfully performed without any short-time complications and patient was discharged 4 days after surgery. Histology of tumor was suggestive of spindle cells with hyperchromatic nuclei with moderate pleomorphism (mitotic activity> 5 / 50 HPF). IHC results were positive for desmin and SMA. Ki-67 was positive in 15-20% of neoplastic cells. C-KIT, CD34, DOG1, and S100 were negative. Furthermore, histologic evaluations revealed peritoneal and abdominal wall involvement by high grade sarcoma. He was referred to an oncologist for chemotherapy initiation with Adriamycin, and Ifosfamide. The patient was scheduled for Contrast-enhanced computed tomography (CT) of Thoracic and Abdomino-pelvis every 6 months, and colonoscopy every 12 months. Follow-up CT scan revealed multiple small nodules in both lungs with the largest being 4-mm in lateral segment of right lower lobe in favor of metastatic lesions. Abdominal CT showed multiple malignant-looking lesion in peritoneal cavity with the largest being 38*39mm. Patient is alive and is under close follow up by an oncologist. Discussion: GISTs are the most common mesenchymal GI malignancies with the incidence of 1–3 % of all GI malignancies. Moreover, LMS is an extremely rare cancer representing 3–6% of all GI mesenchymal tumors. They arise from muscularis mucosae or propria occurring mostly in middle-aged males[ 3 , 4 ]. In the pre-KIT area, most of the GI mesenchymal malignancies were wrongfully diagnosed as leiomyoma, LMS, or leiomyoblastomas. However, their incidence declined after the diagnosis of KIT mutations and the immunohistochemical differences between LMS and other GI mesenchymal tumors, particularly GISTs[ 5 ]. In 1998, Hirota et al identified the presence of activating KIT-mutations in 94% of GISTs[ 6 ]. Kit gene, a tyrosine kinase receptor proto-oncogene, causes increased cellular proliferation. Subsequently, this mutation can lead to cellular atypia and neoplasia. Later studies confirmed that 95% of GISTs expressed CD34, CD137, and DOG1.1 [ 7 ]. On the contrary, the LMS is negative for kit-mutations and mostly positive for desmin, SMA, h-caldesmon, and vimentin[ 8 ]. Differentiation between LMS and GISTs is paramount importance since they have very similar clinical presentations but require radically different courses of treatment. The cellular origin of GISTs, the interstitial cells of Cajal, was first introduced in mid-1990s. however, LMS originates from muscle fibers of the muscularis mucosae and muscularis propria [ 9 ]. Most of the colon LMS are polypoid, while esophageal LMS is mainly intramural[ 10 ]. The most common location of GI involvement in GISTS is in the stomach (55%), small intestine (29%), colon (2.9%), and rectum (2.7%) [ 11 ]. Furthermore, GI LMS mainly involves stomach followed by small intestines, rarely colon and rectum[ 12 ]. True LMS of the colon is such a rare disorder that there isn’t enough description of its nature. The classical colon LMS presents with a vast majority of non-specific symptoms including mild abdominal pain, fresh/obscure rectal bleeding, intra-abdominal hemorrhage, weight loss, changes in bowel habits, bowel obstruction, and tenesmus. [ 13 ] Diagnosis is based on colonoscopy and histologic evaluation and IHC profiling. Based on our survey, there are only thirty-four previous cases of published colonic LMS after the pre-kit era that was confirmed with immunohistochemistry (Table 1 ). The most common location for colonic LMS is the sigmoid colon, followed by the ascending colon. The prognostic factors for the disease outcome have not been established properly. The most important prognostic factor for survival and recurrence seemed to be age, tumor grade, disseminated disease and tumor size[ 14 ]. Yamamoto et al, concluded that the only negative predictive factor for survival is tumor size of more than 5 centimeters[ 15 ]. However, based on previous case studies local and distal recurrence occurred even with favorable tumor features[ 13 ]. Compared with adults, infantile LMS has a better prognosis even with poor histologic features[ 16 ]. Table 1 All cases of published colonic LMS after the pre-kit era. Case Year Age Sex site Size (CM) Local recurrence Metastasis survival c-kit α-SMA Desmin CD-34 1 [ 23 ] 2000 54 M D 3.2 U U Dead Neg Pos+ Pos+ Neg 2 [ 23 ] 2000 61 M A 4.2 None None Alive Neg Pos+ U Neg 3 [ 23 ] 2000 75 M A 6.5 U U Dead Neg Pos+ U Neg 4 [ 23 ] 2000 76 F C 7.8 U U Dead Neg Pos+ U Neg 5 [ 23 ] 2000 36 F S 6.5 None Lung Dead Neg Pos+ Pos+ Neg 6 [ 23 ] 2000 66 M A U None Liver Dead Neg Pos+ U Neg 7 [ 23 ] 2000 41 M C 7.5 None Humerus Alive Neg Pos+ Pos+ Neg 8 [ 24 ] 2004 65 M D 10 None Positive(U) Dead Neg Pos+ Pos+ Neg 9 [ 25 ] 2004 67 F T 5.7 None None Alive Neg Pos+ U Neg 10 [ 10 ] 2007 77 F S U Positive None U Neg Pos+ Pos+ Neg 11 [ 10 ] 2007 52 M S U None Liver U Neg Pos+ Pos+ Neg 12 [ 26 ] 2009 74 F A 6 None Lung Dead Neg Pos+ U U 13 [ 27 ] 2011 70 F S 3.7 None None Dead Neg Pos+ Pos+ Neg 14 [ 27 ] 2011 56 M C U None Liver Alive Neg Pos+ Pos+ Neg 15 [ 28 ] 2012 66 F S 3 None Liver Dead Neg Pos+ Pos+ Neg 16 [ 15 ] 2013 94 F D 25 None Liver Dead Neg Pos+ U Neg 17 [ 15 ] 2013 56 M S 1 None LN Alive Neg Pos+ U Neg 18 [ 15 ] 2013 78 F S 8.5 None Lung Dead Neg Pos+ U Neg 19 [ 15 ] 2013 87 M T 11 None None Dead Neg Pos+ U Neg 20 [ 29 ] 2013 65 M S U None None Alive Neg Pos+ U U 21 [ 30 ] 2014 66 F T 4 None None Alive Neg Pos+ U Neg 22 [ 29 ] 2014 65 M S U None None Alive Neg Pos+ U U 23 [ 5 ] 2015 46 M T 11.8 Positive None Alive Neg Pos+ U Neg 24 [ 31 ] 2015 89 F A 4.5 None Liver U Neg Pos+ U U 25 [ 4 ] 2015 54 M A 13 Positive None Alive Neg Pos+ Pos+ Neg 26 [ 32 ] 2015 59 M A 10 None None Alive Neg Pos+ Pos+ Neg 27 [ 33 ] 2016 89 M C 2.2 None None Alive Neg Pos+ Pos+ U 28 [ 34 ] 2016 51 F D 4 None None Alive Neg Pos+ Pos+ Neg 29 [ 35 ] 2016 44 M SF 8.5 None None Alive Neg Pos+ Pos+ Neg 30 [ 8 ] 2017 55 F A 8 None None Alive Neg Pos+ Pos+ Neg 31 [ 13 ] 2018 57 F S U U U Alive Neg Pos+ U Neg 32 [ 13 ] 2018 88 M A 6.5 None Liver Dead Neg Pos+ U U 33 [ 36 ] 2019 53 M S 3.5 None None Alive Neg Pos+ Pos+ Neg 34 [ 3 ] 2019 46 M S 4.2 None None Alive Neg Pos+ Pos+ Neg 35 (case1) 2019 48 M S 7.2 None None Alive Neg Pos+ Pos+ Neg 36 (case2) 2020 49 M S 4 None Peritoneum Lungs Alive Neg Pos+ Pos+ Neg According to the recent survey by Faraj et al., lymph node involvement is very unlikely and distant metastasis is mostly by hematogenous spread[ 17 ]. Liver is the most common site of secondary tumor metastasis followed by lungs and peritoneum.[ 17 ] Due to the paucity of data, there is not enough evidence to establish reliable mortality estimates. However, based on a study by Aggarwal et al. in 2012 only 2 of 11 cases of colon LMS survived in 5-year surveillance[ 1 ]. The main cause of death was spreading of the primary tumor and multiple organ failure[ 1 ]. Medical therapy is the main course of treatment in mesenchymal GI malignancies, particularly GISTs. However, Due to absence of KIT-mutations in LMS, tyrosine kinase inhibitors (TKI) are not effective in tumor treatment. Therefore, Surgery is considered as the gold standard treatment for LMS[ 18 ]. Since, there are only a few numbers of true LMS cases reported, no standard therapeutic strategy has been established. Radical excision is the most reasonable option since even with low-grade tumors recurrences occurred[ 19 ]. According to YTNM Lee et al., all cases of smooth muscle sarcomas, should undergo wide excisional surgery with 4 cm tumor margin involving mesentery[ 20 ]. Although lymph node involvement is very uncommon in LMS, lymph node dissection is recommended due to its highly invasive nature[ 3 , 15 ]. Anthracyclines, first-line conventional chemotherapy regimen for soft tissue sarcomas, have minimal to no effect on LMS. A multi-drug regimen of Doxorubicin plus dacarbazine may have some clinical response in treatment. In conclusion, Adjuvant chemotherapy is unnecessary when tumors are completely resected. [ 18 ]. However, neoadjuvant chemotherapy may decrease the risk of local recurrence in some cases of rectal sarcomas[ 21 ]. Furthermore, radiotherapy is completely unbeneficial since LMS is highly radio-resistant[ 22 ]. Conclusion: Herein, we described two rare cases of colon LMS which was confirmed with IHC. The tumors were surgically removed via laparoscopic approach, with wide, tumor-free margins. Due to the rarity of disease, there is not enough information about tumor characteristics. Overall, colonic LMS is a highly invasive neoplasm with poor oncologic outcome. Declarations Availability of data and materials : All data generated or analyzed during this study are included in this published article. Acknowledgements: Not applicable. Funding: No funding was obtained for this study. Compliance with ethical standards: Conflict of interest: The authors declare that they have no competing interests. Ethics Approval and consent to participate : The purpose of this research was completely explained to the patient, and was assured that their information will be kept confidential by the researchers. The present study was approved by the medical ethics committee of the academy. Consent for publication : Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Authors' contributions: AB – drafted the manuscript and provided images. MS- helped with the draft and reviewed the literature. MM- provided histologic evaluations. RS- Supervisor, provided initial feedback and reviewed the final manuscript (corresponding author). The authors read and approved the final manuscript. References Aggarwal G, et al. Primary leiomyosarcomas of the gastrointestinal tract in the post–gastrointestinal stromal tumor era. Annals of diagnostic pathology. 2012;16(6):532–40. Katz SC, DeMatteo RP. Gastrointestinal stromal tumors and leiomyosarcomas. Journal of surgical oncology. 2008;97(4):350–9. Yahagi M, et al. Laparoscopic surgery to treat leiomyosarcomas of the sigmoid colon: a case report and literature review. Surgical Case Reports. 2019;5(1):20. Kiran P, et al. Diagnosis of leiomyosarcoma of colon. J Cancer Res Ther. 2015;11(4):1035. Kono M, et al. Primary leiomyosarcoma of the colon. Clinical journal of gastroenterology. 2015;8(4):217–22. Hirota S, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998;279(5350):577–80. Liegl B, et al. Monoclonal antibody DOG1. 1 shows higher sensitivity than KIT in the diagnosis of gastrointestinal stromal tumors, including unusual subtypes. Am J Surg Pathol. 2009;33(3):437–46. Yang J. Primary leiomyosarcoma in the colon: A case report . Medicine, 2018. 97(7). Miettinen M, Lasota J. Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis, and differential diagnosis. Arch Pathol Lab Med. 2006;130(10):1466–78. Agaimy A, Wünsch PH. True smooth muscle neoplasms of the gastrointestinal tract: morphological spectrum and classification in a series of 85 cases from a single institute. Langenbeck's archives of surgery. 2007;392(1):75–81. Ma GL, et al. Epidemiology of gastrointestinal stromal tumors in the era of histology codes: results of a population-based study. Cancer Epidemiology Prevention Biomarkers. 2015;24(1):298–302. Singh P, et al. Rectal leiomyosarcoma in association with ulcerative colitis: a rare condition with an unusual presentation. Int J Colorectal Dis. 2014;29(7):887–8. Crystal JS, et al., Primary leiomyosarcoma of the colon: a report of two cases, review of the literature, and association with immunosuppression for IBD and rheumatoid arthritis. Case reports in surgery, 2018. 2018 . Gladdy RA, et al. Predictors of survival and recurrence in primary leiomyosarcoma. Ann Surg Oncol. 2013;20(6):1851–7. Yamamoto H, et al. Clinicopathological features of primary leiomyosarcoma of the gastrointestinal tract following recognition of gastrointestinal stromal tumours. Histopathology. 2013;63(2):194–207. Yamamoto H, et al. Infantile intestinal leiomyosarcoma is prognostically favorable despite histologic aggressiveness: case report and literature review. Journal of pediatric surgery. 2004;39(8):1257–60. Faraj W, et al. Liver resection for metastatic colorectal leiomyosarcoma: a single center experience. Journal of gastrointestinal oncology. 2015;6(5):E70. Group EESNW. Soft tissue and visceral sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(suppl_3):iii102–12. Ng E. N, Pollock RE, Munsell MF, Atkinson EN, Romsdahl MM. 1992 Prognostic factors influencing survival in gastrointestinal leiomyosarcomas: implications for surgical management and staging . Ann Surg. 215: p. 68–77. Lee Y-TNM. Leiomyosarcoma of the gastro-intestinal tract: general pattern of metastasis and recurrence. Cancer treatment reviews. 1983;10(2):91–101. Luna-Pérez P, et al. Colorectal sarcoma: analysis of failure patterns. Journal of surgical oncology. 1998;69(1):36–40. Koczkowska M, et al. Primary leiomyosarcoma of the mesentery in two sisters: clinical and molecular characteristics. Pol J Pathol. 2013;64(1):59–63. Miettinen M, et al. Gastrointestinal stromal tumors and leiomyosarcomas in the colon: a clinicopathologic, immunohistochemical, and molecular genetic study of 44 cases. Am J Surg Pathol. 2000;24(10):1339–52. Insabato L, et al. Malignant gastrointestinal leiomyosarcoma and gastrointestinal stromal tumor with prominent osteoclast-like giant cells. Arch Pathol Lab Med. 2004;128(4):440–3. Michalopoulos A, et al. Colorectal gastrointestinal mesenchymal tumours. Report of a stromal case of the rectum (GIST) and a leiomyosarcoma of the transverse colon. Tech Coloproctol. 2004;8(1):s155–7. Alvite CM, et al., Leiomyosarcoma of the colon with lung metastases as the first manifestation. Revista espanola de enfermedades digestivas: organo oficial de la Sociedad Espanola de Patologia Digestiva, 2009. 101(2): p. 145. Resch T, et al. Leiomyosarcoma of the colon: unresolved issues of a rare but highly aggressive malignancy. Am Surg. 2011;77(4):E62. Hamai Y, et al. Leiomyosarcoma of the sigmoid colon with multiple liver metastases and gastric cancer: a case report. BMC Gastroenterol. 2012;12(1):98. Samie AA, et al. Leiomyosarcoma of the sigmoid colon: a rare cause of intestinal intussusception. Journal of gastrointestinal cancer. 2014;45(1):6–9. Yaren A, et al. Primary mesenchymal tumors of the colon: a report of three cases. Turk J Gastroenterol. 2014;25(3):314–8. Granero-Peiró L, et al. Leiomyosarcoma of the ascending colon: a rare tumor with poor prognosis. Revista Española de Enfermedades Digestivas. 2015;107(9):580–1. Janevski V, et al. Leiomyosarcoma of the colon. Medicinski Pregled. 2015;68(11–12):413–7. Kim VM, Goicochea L, Fang SH. Case report: collision tumour of colon leiomyosarcoma and adenocarcinoma. Journal of clinical diagnostic research: JCDR. 2016;10(6):PD03. Akutsu D, et al. A rare case of colonic leiomyosarcoma in association with ulcerative colitis. Intern Med. 2016;55(19):2799–803. Jideh B, Yang T, Turner IB. Rectal bleeding due to leiomyosarcoma . Clinical Gastroenterology and Hepatology, 2017: p. e1-e2. Devriendt S, Leman G, Vanrykel F. Primary leiomyosarcoma of the colon: a case report and review of the literature . Acta Chirurgica Belgica, 2019: p. 1–4. Supplementary Files CAREchecklist.pdf Cite Share Download PDF Status: Published Journal Publication published 30 Sep, 2021 Read the published version in International Journal of Surgery Case Reports → 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies 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-214702","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":11306959,"identity":"3b3676c0-e4ff-4180-abb9-163e1bc40f03","order_by":0,"name":"Ali-Mohammad Bananzadeh","email":"","orcid":"","institution":"Shiraz University of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ali-Mohammad","middleName":"","lastName":"Bananzadeh","suffix":""},{"id":11306960,"identity":"8a4e25bb-b774-41cf-9f32-cd021a62ab1f","order_by":1,"name":"Maral Mokhtari","email":"","orcid":"","institution":"Shiraz University of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Maral","middleName":"","lastName":"Mokhtari","suffix":""},{"id":11306961,"identity":"dbf208a1-35c6-49f2-95ef-5089777c5191","order_by":2,"name":"Maryam Sohooli","email":"","orcid":"","institution":"Shiraz University of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Maryam","middleName":"","lastName":"Sohooli","suffix":""},{"id":11306962,"identity":"ae666fdd-2605-4cba-bd94-998742b72a85","order_by":3,"name":"Ramin Shekouhi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA90lEQVRIiWNgGAWjYDACCQZmIHmAB8xJYLABkoyNB0jRkgbS0kCUFhj3MJjEq0V+dvNhg49td2QYpA8/3fBwx3m7te2HgbbU2ETj0mJw51hy4sy2ZzwMfGlmNxLP3E7ediYRqOVYWm4DLi0SOcaHedsO8zDwMAC1tN1ONjsA1MLYcBinFvkZ+Z+hWti/AbWcSzY7/xC/FoYbOczJEC08IFsO2AFJ/FoMbqQZG844d5iHjYenDKglOcHsBtCWBDx+kZ+R/FjiQ9lhe34e9m03f7bZ2ZudT3/44EONDW6HwQAblE4Eq0wgpBwZ2JOieBSMglEwCkYGAADaimOzEafPCAAAAABJRU5ErkJggg==","orcid":"","institution":"Shiraz Medical School: Shiraz University of Medical Sciences","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Ramin","middleName":"","lastName":"Shekouhi","suffix":""}],"badges":[],"createdAt":"2021-02-06 07:22:32","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-214702/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-214702/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1016/j.ijscr.2021.106420","type":"published","date":"2021-10-01T00:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":5981522,"identity":"5bd661d0-c0fd-477d-adfc-b09d4ca83ac9","added_by":"auto","created_at":"2021-02-15 17:42:58","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":446550,"visible":true,"origin":"","legend":"Spindle cell neoplasm with nuclear hyperchromasia and mild pleomorphism, H\u0026E, X200(a), Desmin immunoreactivity. Note the negative colonic crypts and positive tumoral cells for desmin, X400(b), Smooth muscle actin, Negative colonic crypts and positive tumoral cells for C-KIT, X400(d)","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-214702/v1/290c33820f07411acf3e9270.png"},{"id":14907047,"identity":"939e5102-eadb-4273-bf53-b673528d32d6","added_by":"auto","created_at":"2021-10-26 14:17:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":798872,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-214702/v1/a464d1c3-c3cd-42f0-a3f4-8b780c118d97.pdf"},{"id":5981521,"identity":"df929407-c78b-4fe7-97c7-0a4ec71af259","added_by":"auto","created_at":"2021-02-15 17:42:58","extension":"pdf","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":672816,"visible":true,"origin":"","legend":"","description":"","filename":"CAREchecklist.pdf","url":"https://assets-eu.researchsquare.com/files/rs-214702/v1/a8b965d2f6afff1607e28bd1.pdf"}],"financialInterests":"","formattedTitle":"Two cases of primary leiomyosarcoma of sigmoid colon treated with laparoscopic surgery: a case report and a review of literature","fulltext":[{"header":"Background:","content":" \u003cp\u003eLeiomyosarcoma (LMS) of the colon is an unbelievably rare and highly invasive tumor arising from the muscularis propria of the gastrointestinal tract.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] Before 1998, every neoplasm raised from mesenchymal cells was mistakenly classified as LMS; However, after the introduction of the oncogenic role of KIT by immunohistochemistry(IHC), only a very small number of true gastrointestinal leiomyosarcomas was reported[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Immunohistochemically, true LMS expresses actin(SMA) and desmin without the expression of GIST markers(CD117, CD34, and DOG1.1) and KIT mutations, which allows distinguishing LMS from other GI mesenchymal neoplasms[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. We herein describe two rare cases of Leiomyosarcoma of sigmoid colon that were treated with laparoscopic resection.\u003c/p\u003e "},{"header":"Case Presentation:","content":"\u003cp\u003e\u003cstrong\u003eCase 1:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe reported a case of a 48-year-old man referred to our surgical outpatient clinic in December 2019. He presented with mild intermittent abdominal pain and occasional rectal bleeding for eight months without any history of weight loss, fatigue or night sweating. Furthermore, He had a blank family history of malignant neoplasia. General examination and vital signs were normal. Abdominal examinations revealed an ill-defined round mass at the left lower quadrant. Digital rectal examination was normal. Routine lab data were unremarkable, except mild microcytic anemia that was due to his thalassemia trait (Mentzer index=13.46).\u0026nbsp;Carcinoembryonic antigen (CEA) test was normal.\u0026nbsp;After the initial investigation patient underwent colonoscopy that was suggestive of a large polypoid mass with hard texture in 15 centimeters from the anal verge; rest of the colon were unremarkable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHistopathology revealed a neoplasm consists of spindle cells with hyperchromatic nuclei and mild pleomorphism. Subsequent immunohistochemistry showed immunoreactivity for smooth muscle actin and desmin but the tumor cells were negative for S100, CD34, C-KIT and DOG-1. The Ki-67 index was 15-20%. KIT mutation study also showed no mutation in exon 9, 11, 13 and 17. Therefore, the diagnosis of leiomyosarcoma was made.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTreatment:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBefore the operation, patient was scheduled for a routine metastatic workup with\u0026nbsp;Contrast-enhanced computed tomography\u0026nbsp;(CT)\u0026nbsp;of thoracic and abdomen and pelvis, and\u0026nbsp;liver function test (LFT). The abdominal CT showed diffuse wall thickening of the sigmoid colon and distal part of the left colon associated with enhancing soft tissue mass measuring about 72mm\u003cspan dir=\"RTL\"\u003e\u0026times;\u003c/span\u003e40mm in sigmoid colon that was suggestive of a malignant process. Also, evidence of multiple regional lymph nodes was seen adjacent to the sigmoid colon. Chest CT and Liver function test (LFT) were unremarkable. The surgery was conducted under general anesthesia with the purpose of complete resection of the tumor and involved lymph nodes. Laparoscopic anterior resection was performed with resection of sigmoid colon and upper part of rectum. Colorectal anastomosis was performed with no diverting ileostomy. Tumor dimensions were 8\u0026times;6\u0026times;4.5 cm with a smooth surface and the cross-section showed homogenous white appearance. \u0026nbsp;The specimen was sent for IHC profiling and histologic evaluation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcome and Follow-up:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe post-operative course was uneventful without any signs of short-term complications. The patient discharged four days after surgery. The patient was scheduled for\u0026nbsp;Contrast-enhanced computed tomography\u0026nbsp;(CT)\u0026nbsp;of thoracic and abdomino-pelvic every 6 months, and colonoscopy every 12 months. Patient has no signs of local recurrence or distant metastasis Up-to-date. We will follow the patient for at least 5 years of close surveillance.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase2:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOn April 29\u003csup\u003eth\u003c/sup\u003e 2020, a 49-year-old man came to Shiraz Colorectal Clinic with 3-month history of fatigue, melena, and unintentional weight loss. Family history was negative for any previous disease.\u0026nbsp;General examination showed temporal wasting and cachexia. Vital signs and abdominal examinations were unremarkable. Digital rectal examination showed grade-II\u0026nbsp;internal hemorrhoids. Lab data was in favor of microcytic-hypochromic anemia (HB=11.7).\u0026nbsp;Carcinoembryonic antigen (CEA) test was normal. Colonoscopy revealed a large 3*4*3.5 cm circumferential mass with deep central ulceration in sigmoid colon 40 cm from anal verge.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePrior to surgery, Abdomino-perineal\u0026nbsp;CT showed circumferential wall thickening of distal descending colon in Lt. lower quadrant with maximum wall thickness of 24mm and length of involvement about 43mm. Also, thickening of adjacent peritoneum was demonstrated. Pre-op chest CT was normal. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTreatment:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLaparoscopic left hemicolectomy\u0026nbsp;was conducted under general anesthesia with the purpose of complete resection of the tumor and involved lymph nodes. The specimen was extracted via a mid-midline incision and extra-corporal anastomosis was done.\u0026nbsp;The specimen was sent for IHC profiling and histologic evaluation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcome and Follow-up:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSurgery was successfully performed without any short-time complications and patient was discharged 4 days after surgery.\u0026nbsp;Histology of tumor was suggestive of spindle\u0026nbsp;cells with hyperchromatic nuclei with moderate pleomorphism (mitotic activity\u0026gt; 5 / 50 HPF). IHC results were positive for desmin and SMA. Ki-67 was positive in 15-20% of neoplastic cells. C-KIT, CD34, DOG1, and S100 were negative. Furthermore,\u0026nbsp;histologic evaluations revealed peritoneal and abdominal wall involvement by high grade sarcoma. He was referred to an oncologist for chemotherapy initiation with\u0026nbsp;Adriamycin, and\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eIfosfamide. The patient was scheduled for Contrast-enhanced computed tomography (CT) of Thoracic and Abdomino-pelvis every 6 months, and colonoscopy every 12 months. Follow-up CT scan revealed multiple small nodules in both lungs with the largest being 4-mm in lateral segment of right lower lobe in favor of metastatic lesions. Abdominal CT showed multiple malignant-looking lesion in peritoneal cavity with the largest being 38*39mm. Patient is alive and is under close follow up by an oncologist.\u003c/p\u003e"},{"header":"Discussion:","content":"\u003cp\u003eGISTs are the most common mesenchymal GI malignancies with the incidence of 1\u0026ndash;3 % of all GI malignancies. Moreover, LMS is an extremely rare cancer representing 3\u0026ndash;6% of all GI mesenchymal tumors. They arise from muscularis mucosae or propria occurring mostly in middle-aged males[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In the pre-KIT area, most of the GI mesenchymal malignancies were wrongfully diagnosed as leiomyoma, LMS, or leiomyoblastomas. However, their incidence declined after the diagnosis of KIT mutations and the immunohistochemical differences between LMS and other GI mesenchymal tumors, particularly GISTs[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn 1998, Hirota et al identified the presence of activating KIT-mutations in 94% of GISTs[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Kit gene, a tyrosine kinase receptor proto-oncogene, causes increased cellular proliferation. Subsequently, this mutation can lead to cellular atypia and neoplasia. Later studies confirmed that 95% of GISTs expressed CD34, CD137, and DOG1.1 [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. On the contrary, the LMS is negative for kit-mutations and mostly positive for desmin, SMA, h-caldesmon, and vimentin[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eDifferentiation between LMS and GISTs is paramount importance since they have very similar clinical presentations but require radically different courses of treatment. The cellular origin of GISTs, the interstitial cells of Cajal, was first introduced in mid-1990s. however, LMS originates from muscle fibers of the muscularis mucosae and muscularis propria [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Most of the colon LMS are polypoid, while esophageal LMS is mainly intramural[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe most common location of GI involvement in GISTS is in the stomach (55%), small intestine (29%), colon (2.9%), and rectum (2.7%) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Furthermore, GI LMS mainly involves stomach followed by small intestines, rarely colon and rectum[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. True LMS of the colon is such a rare disorder that there isn\u0026rsquo;t enough description of its nature. The classical colon LMS presents with a vast majority of non-specific symptoms including mild abdominal pain, fresh/obscure rectal bleeding, intra-abdominal hemorrhage, weight loss, changes in bowel habits, bowel obstruction, and tenesmus. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] Diagnosis is based on colonoscopy and histologic evaluation and IHC profiling.\u003c/p\u003e\u003cp\u003eBased on our survey, there are only thirty-four previous cases of published colonic LMS after the pre-kit era that was confirmed with immunohistochemistry (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The most common location for colonic LMS is the sigmoid colon, followed by the ascending colon. The prognostic factors for the disease outcome have not been established properly. The most important prognostic factor for survival and recurrence seemed to be age, tumor grade, disseminated disease and tumor size[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Yamamoto et al, concluded that the only negative predictive factor for survival is tumor size of more than 5 centimeters[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. However, based on previous case studies local and distal recurrence occurred even with favorable tumor features[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Compared with adults, infantile LMS has a better prognosis even with poor histologic features[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\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\u003eAll cases of published colonic LMS after the pre-kit era.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"13\"\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCase\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\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSex\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003esite\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eSize\u003c/p\u003e\u003cp\u003e(CM)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eLocal recurrence\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eMetastasis\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003esurvival\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003ec-kit\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003eα-SMA\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c12\"\u003e\u003cp\u003eDesmin\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c13\"\u003e\u003cp\u003eCD-34\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e1\u003c/b\u003e[\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=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e54\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eDead\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e2\u003c/b\u003e[\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=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eAlive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e3\u003c/b\u003e[\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=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eDead\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e4\u003c/b\u003e[\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=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e7.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eDead\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e5\u003c/b\u003e[\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=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eLung\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eDead\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e6\u003c/b\u003e[\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=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eLiver\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eDead\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e7\u003c/b\u003e[\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=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e7.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eHumerus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eAlive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e8\u003c/b\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2004\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePositive(U)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eDead\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e9\u003c/b\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2004\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eAlive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e10\u003c/b\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2007\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e77\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003ePositive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e11\u003c/b\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2007\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eLiver\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e12\u003c/b\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2009\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eLung\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eDead\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e13\u003c/b\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\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=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eDead\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e14\u003c/b\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\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=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eLiver\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eAlive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e15\u003c/b\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2012\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eLiver\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eDead\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e16\u003c/b\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\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=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e94\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eLiver\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eDead\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e17\u003c/b\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\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=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eLN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eAlive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e18\u003c/b\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\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=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e8.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eLung\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eDead\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e19\u003c/b\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\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=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e87\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eDead\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e20\u003c/b\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\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=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eAlive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e21\u003c/b\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2014\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eAlive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e22\u003c/b\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2014\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eAlive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e23\u003c/b\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2015\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e11.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003ePositive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eAlive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e24\u003c/b\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2015\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e89\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eLiver\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e25\u003c/b\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2015\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e54\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003ePositive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eAlive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e26\u003c/b\u003e[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2015\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e59\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eAlive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e27\u003c/b\u003e[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2016\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e89\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eAlive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e28\u003c/b\u003e[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2016\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eAlive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e29\u003c/b\u003e[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2016\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e8.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eAlive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e30\u003c/b\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\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=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e55\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eAlive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e31\u003c/b\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2018\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eAlive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e32\u003c/b\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2018\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e88\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eLiver\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eDead\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eU\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e33\u003c/b\u003e[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2019\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eAlive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e34\u003c/b\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2019\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eAlive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e35\u003c/b\u003e(case1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2019\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e7.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eAlive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e36\u003c/b\u003e(case2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2020\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePeritoneum\u003c/p\u003e\u003cp\u003eLungs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eAlive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003ePos+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eNeg\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAccording to the recent survey by Faraj et al., lymph node involvement is very unlikely and distant metastasis is mostly by hematogenous spread[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Liver is the most common site of secondary tumor metastasis followed by lungs and peritoneum.[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] Due to the paucity of data, there is not enough evidence to establish reliable mortality estimates. However, based on a study by Aggarwal et al. in 2012 only 2 of 11 cases of colon LMS survived in 5-year surveillance[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The main cause of death was spreading of the primary tumor and multiple organ failure[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eMedical therapy is the main course of treatment in mesenchymal GI malignancies, particularly GISTs. However, Due to absence of KIT-mutations in LMS, tyrosine kinase inhibitors (TKI) are not effective in tumor treatment. Therefore, Surgery is considered as the gold standard treatment for LMS[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Since, there are only a few numbers of true LMS cases reported, no standard therapeutic strategy has been established. Radical excision is the most reasonable option since even with low-grade tumors recurrences occurred[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. According to YTNM Lee et al., all cases of smooth muscle sarcomas, should undergo wide excisional surgery with 4 cm tumor margin involving mesentery[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAlthough lymph node involvement is very uncommon in LMS, lymph node dissection is recommended due to its highly invasive nature[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Anthracyclines, first-line conventional chemotherapy regimen for soft tissue sarcomas, have minimal to no effect on LMS. A multi-drug regimen of Doxorubicin plus dacarbazine may have some clinical response in treatment. In conclusion, Adjuvant chemotherapy is unnecessary when tumors are completely resected. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. However, neoadjuvant chemotherapy may decrease the risk of local recurrence in some cases of rectal sarcomas[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Furthermore, radiotherapy is completely unbeneficial since LMS is highly radio-resistant[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e"},{"header":"Conclusion:","content":" \u003cp\u003eHerein, we described two rare cases of colon LMS which was confirmed with IHC. The tumors were surgically removed via laparoscopic approach, with wide, tumor-free margins. Due to the rarity of disease, there is not enough information about tumor characteristics. Overall, colonic LMS is a highly invasive neoplasm with poor oncologic outcome.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e:\u003cbr\u003e\u0026nbsp;All data generated or analyzed during this study are included in this published article.\u003cbr\u003e\u0026nbsp;\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;\u003c/strong\u003eNot applicable.\u003cbr\u003e\u0026nbsp;\u003cstrong\u003eFunding:\u003c/strong\u003e\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;\u003c/strong\u003eNo funding was obtained for this study.\u003cbr\u003e\u0026nbsp;\u003cstrong\u003eCompliance with ethical standards:\u003c/strong\u003e\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eConflict of interest:\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval and consent to participate\u003c/strong\u003e: The purpose of this research was completely explained to the patient, and was assured that their information will be kept confidential by the researchers. The present study was approved by the medical ethics committee of the academy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u003cbr\u003e\u0026nbsp;\u003c/strong\u003eAB \u0026ndash; drafted the manuscript and provided images. MS- helped with the draft and reviewed the literature. MM- provided histologic evaluations. RS- Supervisor, provided initial\u003cbr\u003e\u0026nbsp;feedback and reviewed the final manuscript (corresponding author). The authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAggarwal G, et al. Primary leiomyosarcomas of the gastrointestinal tract in the post\u0026ndash;gastrointestinal stromal tumor era. Annals of diagnostic pathology. 2012;16(6):532\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKatz SC, DeMatteo RP. Gastrointestinal stromal tumors and leiomyosarcomas. Journal of surgical oncology. 2008;97(4):350\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYahagi M, et al. Laparoscopic surgery to treat leiomyosarcomas of the sigmoid colon: a case report and literature review. Surgical Case Reports. 2019;5(1):20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKiran P, et al. Diagnosis of leiomyosarcoma of colon. J Cancer Res Ther. 2015;11(4):1035.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKono M, et al. Primary leiomyosarcoma of the colon. Clinical journal of gastroenterology. 2015;8(4):217\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHirota S, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998;279(5350):577\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiegl B, et al. Monoclonal antibody DOG1. 1 shows higher sensitivity than KIT in the diagnosis of gastrointestinal stromal tumors, including unusual subtypes. Am J Surg Pathol. 2009;33(3):437\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang J. \u003cem\u003ePrimary leiomyosarcoma in the colon: A case report\u003c/em\u003e. Medicine, 2018. 97(7).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMiettinen M, Lasota J. Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis, and differential diagnosis. Arch Pathol Lab Med. 2006;130(10):1466\u0026ndash;78.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAgaimy A, W\u0026uuml;nsch PH. True smooth muscle neoplasms of the gastrointestinal tract: morphological spectrum and classification in a series of 85 cases from a single institute. Langenbeck's archives of surgery. 2007;392(1):75\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMa GL, et al. Epidemiology of gastrointestinal stromal tumors in the era of histology codes: results of a population-based study. Cancer Epidemiology Prevention Biomarkers. 2015;24(1):298\u0026ndash;302.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSingh P, et al. Rectal leiomyosarcoma in association with ulcerative colitis: a rare condition with an unusual presentation. Int J Colorectal Dis. 2014;29(7):887\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCrystal JS, et al., \u003cem\u003ePrimary leiomyosarcoma of the colon: a report of two cases, review of the literature, and association with immunosuppression for IBD and rheumatoid arthritis.\u003c/em\u003e Case reports in surgery, 2018. \u003cb\u003e2018\u003c/b\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGladdy RA, et al. Predictors of survival and recurrence in primary leiomyosarcoma. Ann Surg Oncol. 2013;20(6):1851\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYamamoto H, et al. Clinicopathological features of primary leiomyosarcoma of the gastrointestinal tract following recognition of gastrointestinal stromal tumours. Histopathology. 2013;63(2):194\u0026ndash;207.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYamamoto H, et al. Infantile intestinal leiomyosarcoma is prognostically favorable despite histologic aggressiveness: case report and literature review. Journal of pediatric surgery. 2004;39(8):1257\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFaraj W, et al. Liver resection for metastatic colorectal leiomyosarcoma: a single center experience. Journal of gastrointestinal oncology. 2015;6(5):E70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGroup EESNW. Soft tissue and visceral sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(suppl_3):iii102\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNg E. N, Pollock RE, Munsell MF, Atkinson EN, Romsdahl \u003cem\u003eMM. 1992 Prognostic factors influencing survival in gastrointestinal leiomyosarcomas: implications for surgical management and staging\u003c/em\u003e. Ann Surg. 215: p.\u0026nbsp;68\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee Y-TNM. Leiomyosarcoma of the gastro-intestinal tract: general pattern of metastasis and recurrence. Cancer treatment reviews. 1983;10(2):91\u0026ndash;101.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLuna-P\u0026eacute;rez P, et al. Colorectal sarcoma: analysis of failure patterns. Journal of surgical oncology. 1998;69(1):36\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKoczkowska M, et al. Primary leiomyosarcoma of the mesentery in two sisters: clinical and molecular characteristics. Pol J Pathol. 2013;64(1):59\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMiettinen M, et al. Gastrointestinal stromal tumors and leiomyosarcomas in the colon: a clinicopathologic, immunohistochemical, and molecular genetic study of 44 cases. Am J Surg Pathol. 2000;24(10):1339\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eInsabato L, et al. Malignant gastrointestinal leiomyosarcoma and gastrointestinal stromal tumor with prominent osteoclast-like giant cells. Arch Pathol Lab Med. 2004;128(4):440\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMichalopoulos A, et al. Colorectal gastrointestinal mesenchymal tumours. Report of a stromal case of the rectum (GIST) and a leiomyosarcoma of the transverse colon. Tech Coloproctol. 2004;8(1):s155\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlvite CM, et al., \u003cem\u003eLeiomyosarcoma of the colon with lung metastases as the first manifestation.\u003c/em\u003e Revista espanola de enfermedades digestivas: organo oficial de la Sociedad Espanola de Patologia Digestiva, 2009. 101(2): p.\u0026nbsp;145.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eResch T, et al. Leiomyosarcoma of the colon: unresolved issues of a rare but highly aggressive malignancy. Am Surg. 2011;77(4):E62.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHamai Y, et al. Leiomyosarcoma of the sigmoid colon with multiple liver metastases and gastric cancer: a case report. BMC Gastroenterol. 2012;12(1):98.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSamie AA, et al. Leiomyosarcoma of the sigmoid colon: a rare cause of intestinal intussusception. Journal of gastrointestinal cancer. 2014;45(1):6\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYaren A, et al. Primary mesenchymal tumors of the colon: a report of three cases. Turk J Gastroenterol. 2014;25(3):314\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGranero-Peir\u0026oacute; L, et al. Leiomyosarcoma of the ascending colon: a rare tumor with poor prognosis. Revista Espa\u0026ntilde;ola de Enfermedades Digestivas. 2015;107(9):580\u0026ndash;1.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJanevski V, et al. Leiomyosarcoma of the colon. Medicinski Pregled. 2015;68(11\u0026ndash;12):413\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim VM, Goicochea L, Fang SH. Case report: collision tumour of colon leiomyosarcoma and adenocarcinoma. Journal of clinical diagnostic research: JCDR. 2016;10(6):PD03.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAkutsu D, et al. A rare case of colonic leiomyosarcoma in association with ulcerative colitis. Intern Med. 2016;55(19):2799\u0026ndash;803.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJideh B, Yang T, Turner IB. \u003cem\u003eRectal bleeding due to leiomyosarcoma\u003c/em\u003e. Clinical Gastroenterology and Hepatology, 2017: p.\u0026nbsp;e1-e2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDevriendt S, Leman G, Vanrykel F. \u003cem\u003ePrimary leiomyosarcoma of the colon: a case report and review of the literature\u003c/em\u003e. Acta Chirurgica Belgica, 2019: p.\u0026nbsp;1\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":true,"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":"colon cancer, leiomyosarcoma, sigmoid colon","lastPublishedDoi":"10.21203/rs.3.rs-214702/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-214702/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eLeiomyosarcoma (LMS) of the colon is an unbelievably rare and highly invasive tumor arising from the muscularis propria of the gastrointestinal tract. After the introduction of the oncogenic role of KIT by immunohistochemistry (IHC), the reported cases of gastrointestinal leiomyosarcoma were limited. True LMS of the colon is such a rare disorder that there isn\u0026rsquo;t enough description of its nature. The classical colon LMS presents with a vast majority of non-specific symptoms including mild abdominal pain, fresh/obscure rectal bleeding, and weight loss. Case presentation: we experienced two extremely rare cases of colonic LMS. First patient was a 48-year-old man referred to our surgical outpatient clinic with mild intermittent abdominal pain and occasional rectal bleeding. After the initial investigation patient underwent colonoscopy that was suggestive of a large polypoid mass in 15 centimeters from the anal verge. Histopathology and Subsequent immunohistochemistry were in favor of LMS of sigmoid colon, and he underwent Laparoscopic anterior resection. The second patient was a 49-year-old man with 3-month history of fatigue, melena, and unintentional weight loss. Colonoscopy revealed a large circumferential mass in sigmoid colon 40 cm from the anal verge with the diagnosis of LMS. He underwent Laparoscopic left hemicolectomy. Conclusion: Herein, we reported two rare cases of primary leiomyosarcoma of sigmoid colon treated with laparoscopic surgery. The tumors were surgically removed via laparoscopic approach. Overall, colonic LMS is a highly invasive neoplasm with poor oncologic outcome.\u003c/p\u003e","manuscriptTitle":"Two cases of primary leiomyosarcoma of sigmoid colon treated with laparoscopic surgery: a case report and a review of literature","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-02-15 17:42:56","doi":"10.21203/rs.3.rs-214702/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":"1b5a6e39-1c6b-48f1-adf5-abae8ca18491","owner":[],"postedDate":"February 15th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":2420901,"name":"Gastrointestinal Surgery"},{"id":2420902,"name":"Cancer Biology"}],"tags":[],"updatedAt":"2021-10-26T14:17:10+00:00","versionOfRecord":{"articleIdentity":"rs-214702","link":"https://doi.org/10.1016/j.ijscr.2021.106420","journal":{"identity":"international-journal-of-surgery-case-reports","isVorOnly":true,"title":"International Journal of Surgery Case Reports"},"publishedOn":"2021-10-01 00:00:00","publishedOnDateReadable":"October 1st, 2021"},"versionCreatedAt":"2021-02-15 17:42:56","video":"","vorDoi":"10.1016/j.ijscr.2021.106420","vorDoiUrl":"https://doi.org/10.1016/j.ijscr.2021.106420","workflowStages":[]},"version":"v1","identity":"rs-214702","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-214702","identity":"rs-214702","version":["v1"]},"buildId":"369fNeqWncA4NS6XSWjrt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}