Udagawa et al. surg case rep (2020) 6:252 https://doi.org/10.1186/s40792-020-01025-2

CASE REPORT Open Access Surgery for colloid carcinoma of the with portal vein tumor thrombus: a case report Daisuke Udagawa1, Motohide Shimazu1* , Tadayuki Sakuragawa1, Shotaro Maruyama1, Yusuke Uchi1, Eisuke Miura2, Yohei Masugi2 and Michiie Sakamoto2

Abstract Background: The portal vein is occasionally invaded by advanced malignant tumors in the pancreatic head region. However, pancreatic rarely has portal vein tumor thrombi. We report a case of with a mas- sive portal vein tumor thrombus undergoing pancreatoduodenectomy with combined resection of the portal vein. Case presentation: A 71-year-old man visited a clinic with complaints of abdominal discomfort and vomiting. Gastroscopy showed a massive tumor in the . He was referred to our hospital for further examinations and treatment. The CT showed a low-density tumor with a maximum diameter of 10 cm located on the pancreas head. A tumor widely invaded the duodenum and had a 6-cm portal vein tumor thrombus. MRCP did not show obvious stenosis of the pancreatic duct due to tumor invasion. There were no fndings suggesting distant metastases. Biopsy of the duodenum revealed . He was diagnosed with primary pancreatic cancer or duodenal cancer with portal vein tumor thrombus and underwent pancreatoduodectomy with resection and reconstruction of the portal vein. He sufered no postoperative complications and was discharged 2 months after surgery. The fnal histo- pathological diagnosis was pancreatic colloid carcinoma. He received adjuvant , but died 16 months after surgery. Conclusions: Colloid carcinoma of the pancreas is rare, and pancreatic carcinoma seldom forms a portal vein tumor thrombus. We experienced a very rare case of pancreatic colloid carcinoma with portal vein tumor thrombus and performed radical resection of the pancreas and portal vein. Keywords: Portal vein tumor thrombus, Pancreatic colloid carcinoma, Pancreatoduodenectomy, Resection of the portal vein

Background Case presentation Te portal vein occasionally becomes invaded by Te patient is a 71-year-old man who presented with advanced malignant tumors in the pancreatic head abdominal discomfort and vomiting after a meal. region. However, pancreatic cancer rarely has a portal Upper gastrointestinal endoscopy revealed a tumor in vein tumor thrombus [1]. We report a case of pancreatic the duodenal bulb, and he was referred to our hospi- colloid carcinoma with a portal vein tumor thrombus tal for further examination and treatment. Laboratory with some relevant literature review. tests revealed anemia, elevation of CEA (87.0 ng/ml) and CA19-9 (136 ng/ml), and a normal total bilirubin value (0.7 mg/dl). He underwent upper gastrointesti- *Correspondence: [email protected] 1 Department of Surgery, Tama Kyuryo Hospital, 1491 Shimooyamadacho, nal endoscopy again, which revealed an irregular tumor Machida‑shi, Tokyo 194‑0297, Japan occupying the lumen of the duodenal bulb, and the 2nd Full list of author information is available at the end of the article portion could not be observed. Te biopsy result was

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adenocarcinoma (Fig. 1a, b). CT scan revealed a 10-cm with cardiopulmonary function and no evidence of dis- tumor with poor contrast efect in the pancreatic head tant metastasis. He was diagnosed with primary pancre- region, and a 6-cm tumor thrombus was observed from atic cancer or primary duodenal cancer with portal vein the superior mesenteric vein to the junction of the por- tumor thrombus. We planned to perform pancreatoduo- tal and splenic vein (Fig. 2a, b). Invasion into the gas- denectomy combined with portal vein resection to cure troduodenal artery was suspected, but no invasion into and relieve the symptoms. the celiac or superior mesenteric arteries was revealed. At operation, a large tumor was found in the head of MRCP showed no signifcant dilation of the common the pancreas and the descending duodenum (Fig. 5). duct or main pancreatic duct (Fig. 3). In abdominal GDA was not involved. Tere were no obvious fndings ultrasonography, the lesion invading the superior mesen- of peritoneal dissemination or liver metastasis, so we teric vein was considered to be a tumor thrombus with performed , with combined an echogenic region in the vascular lumen (Fig. 4). After resection of the portal vein replaced by the right exter- admission, frequent blood transfusions were required nal iliac vein graft (Fig. 6). Te caudal limit of the tumor due to bleeding from the tumor. Tere were no problems thrombus was just above the frst branch of the SMV,

Fig. 1 Upper gastrointestinal endoscopy. a Pylorus observed from the side. b Duodenal bulb lumen. An irregular tumor occupying the lumen of the duodenal bulb was revealed. The biopsy result was adenocarcinoma

Fig. 2 Abdominal enhanced CT. Approximately 10 cm tumor with poor contrast efect was observed in the pancreatic head area (*). A tumor thrombus (arrowhead) of about 6 cm was observed from the superior mesenteric vein (up arrow) to the junction of the portal splenic vein (down arrow) Udagawa et al. surg case rep (2020) 6:252 Page 3 of 6

Fig. 3 Abdominal MRCP. A large tumor was observed in the head of the pancreas, but no signifcant dilation of the common and the main pancreatic duct was observed Fig. 5 Operation fndings. 1. A huge tumor was found in the pancreatic head

Fig. 4 Abdominal ultrasonography. There was an echogenic region Fig. 6 Operation fndings 2. After specimen removal, portal vein in the lumen of the blood vessel at a section less than 6 cm from the reconstruction was performed using a right external iliac vein graft upper end of the superior mesenteric vein, which was considered a (arrow) tumor thrombus (arrow)

pancreas and invading the duodenal lumen (Fig. 7). Te and the SMV was cut at one orifce. Te cranial side of tumor showed a gelatinous appearance on cross section the portal vein was cut in the hepatoduodenal ligament, and was mainly located in the pancreas head. Te tumor and the splenic vein was ligated. Te portal vein was size was 105 × 70 × 100 mm in three dimensions. Histo- reconstructed by the interposition of the right external pathological fndings showed colloid carcinoma of the iliac vein graft. Te portal vein fow was gradually inter- pancreas, as adenocarcinoma cells foating in the mucus rupted by thrombosis formation so that collateral vessels lake were observed (Fig. 8a, b). No adenomatous lesions developed. SMV fow was completely blocked, and the were observed in the adjacent duodenum mucosa. Tere fow seemed to run through collateral vessels. Tis made was a tumor thrombus in the portal vein. Tumor thrombi surgery difcult due to hemorrhage. On the other hand, were also observed in small vessels within and around the temporary bypass was not necessary because collateral tumor bed (Fig. 8c). Because we did not observe any dis- vessels were well developed. Te operation time was tinct evidence of direct cancer involvement into the por- 615 min, and blood loss was 2405 g. Te resected speci- tal vein (Fig. 8d), we considered that this tumor thrombus men showed a large tumor occupying the head of the in the portal vein was formed by intravascular extension Udagawa et al. surg case rep (2020) 6:252 Page 4 of 6

and CDX-2+, which were consistent with colloid carci- noma of the pancreas. Te postoperative course was uneventful, and there were no complications, including pancreatic fstula. He was discharged from the hospital approximately 2 months after the operation after moving to the reha- bilitation ward. He moved to the rehabilitation ward not only for medical reasons, but also for social rea- sons. After 6 weeks of surgery, S-1 was administered as adjuvant chemotherapy, which was discontinued and switched to gemcitabine monotherapy as he had severe diarrhea. Liver metastases appeared 12 months postop- eratively, so gemcitabine was used in combination with Fig. 7 Section of lesion. A tumor occupying the head of the pancreas and invading the duodenal lumen. a Mucosa of duodenum, b portal nab-paclitaxel for 2 months. However, his physical status vein, c common bile duct, d tumor worsened, and chemotherapy was discontinued. He died at home 16 months after the operation.

Discussion through venous vessels. According to the general rules Since the portal vein and superior mesenteric artery run of the AICC/UICC 8th edition TNM staging system, the close to the head of the pancreas, malignant tumors aris- tumor was described as pT3N0M0. Te resection mar- ing in this area occasionally invade these important blood gin was positive for the tumor thrombus at the proximal vessels. Primary pancreatic cancer rarely has portal vein stump of the portal vein. Immunohistochemistry studies tumor thrombus. A search for “pancreatic carcinoma” showed that it was CK7+, CK20−, CA19-9+, CK19+, and “portal vein tumor thrombus” in the Central Medical

Fig. 8 Pathological fndings. a Medium magnifcation image: abundant mucus and cell mass foating in the mucus lake are recognized. b High-magnifcation image: cells with densely stained and swollen irregular nuclei form clumps and foat with some connectivity. This is a fnding of colloid cancer. c Portal vein: the portal vein (white arrowheads) was full of tumor, and the small vessel around the tumor (black arrowheads) was also full of tumor. d The high-magnifcation image of c (rectangle). There was no distinct evidence of the tumor directly involving into the portal vein Udagawa et al. surg case rep (2020) 6:252 Page 5 of 6

Journal and PubMed was conducted, and 16 cases of pan- According to Adsay et al. 9 cases of 17 colloid carci- creatic cancer with a portal vein tumor thrombus were nomas were derived from IPMN [19], indicating that reported, of which only three cases were primary pancre- there are many IPMN-derived pancreatic mucinous atic ductal carcinomas [1, 2], all of which were resected. carcinomas. In this case, no IPMN component was Tis is the 4th case of pancreatic ductal carcinoma with a observed in either the invasive or noninvasive parts of portal vein tumor thrombus. the tumor, and it can be diagnosed as de novo colloid Table 1 summarizes the cases of pancreatic ductal carcinoma in the invasive ductal carcinoma portion. carcinoma with portal vein tumor thrombus, including On the other hand, the biological and clinical features the current case. Compared with the other three cases, of IPMN-derived colloid carcinoma and de novo colloid this case had a larger tumor diameter and longer tumor carcinoma have not been clarifed. Nakahashi [20] et al. thrombus length. In all cases, resection combined with summarized 23 cases of de novo colloid carcinoma portal vein was performed, but vein graft interposition of the pancreas. Tey showed that tumors were often was performed only in this case. Te likelihood of recur- located on the pancreas head, and the average tumor rence pattern, timing of recurrence of pancreatic cancer size was 51.1 mm. According to Sakoda [16], metastasis with portal vein tumor thrombosis has not been reported. often occurs in the liver; however, they also reported a Tere is no general guideline for resection for portal vein case of lung metastasis. Adsay [19] et al. reported that tumor thrombus. However, there are some reports that the 5-year survival rate of colloid carcinoma was 57%, if it can be resected according to pancreatic cancer with which is better than that of invasive ductal carcinoma. portal vein invasion, surgery can be performed without However, their data may include cases of IPMN-derived any problem [1, 2]. In this case, gastrointestinal bleeding colloid carcinoma. Te accumulation of cases of colloid was caused by the tumor so that resection was also nec- carcinoma as pancreatic ductal carcinoma is still lim- essary as an oncologic emergency. ited, and the relationship between portal vein tumor Tere have been more reports on pancreatic tumors thrombus and pancreatic colloid cancer is unclear. To other than ductal carcinoma. According to Yamato et al. our knowledge, there has been no report of a case of [2] 5 cases of endocrine carcinoma [2–6], 3 cases of aci- pancreatic colloid carcinoma complicated with portal nar cell carcinoma [7–9], 2 cases of solid pseudopapillary vein tumor thrombus. tumor [10, 11], 2 cases of IPMC [12], 1 case of pancrea- Hepatic metastasis seems to easily occur via hematoge- toblastoma [13] and 1 case melanoma [14] have been nous transfer in pancreatic cancer with portal vein tumor reported. In the case of melanoma and endocrine carci- thrombus. Te incidence of liver metastasis has not been noma, the survival period was 25 months on average, but reported in cases with portal vein tumor thrombosis, in the other cases, no case showed long-term survival, of so it is not clear whether liver metastases after surgery which the longest survival was only 20 months. occur more frequently in cases with portal thrombus Te present case was a pancreatic colloid carcinoma, than in cases with portal invasion. In this case, chemo- which is rare among pancreatic ductal carcinomas [15, therapy administration was started with S-1 according 16]. Te frequency of pancreatic colloid carcinoma was to the recommended postoperative chemotherapy for reported as 0.6% of all pancreatic cancer and 1.4% of pancreatic cancer in the guidelines of the Japan Pancreas invasive pancreatic ductal carcinoma [17]. In a pathologi- Society. However, in the early postoperative period, liver cal study of 24 cases of colloid carcinoma of the pancreas, metastases were noted. If the general condition allows, it Seidel et al. reported that all cases were derived from may be necessary to start with stronger chemotherapy, IPMN [18]. such as FOLFIRINOX, even though efective therapy

Table 1 Cases of pancreatic ductal carcinoma with portal vein tumor thrombus Author Year Tumor size (cm) Thrombus Operation Pathology Prognosis Recurrent site Adjuvant chemo size (mm)

1 Yamato 2009 3.5 3.5 15 DP PVR Por 4 months dead Local None × + 2 Yamato 2009 2.9 1.9 35 SSPPD PVR Tub2 19 months arrive Liver GEM S-1 × + → 3 Murase 2015 2.7 1.6 22 SSPPD PVR Tub1 27 months dead Local S-1 × + Lung 4 Udagawa 2020 10.5 7.0 60 PD PVR Muc (colloid) 16 months dead Liver S-1 × + GEM→ GEM → nabPTX+ Udagawa et al. surg case rep (2020) 6:252 Page 6 of 6

after surgery for pancreatic cancer with portal vein tumor 2. Yamato H, Kawakami H, Kuwatani M, et al. Pancreatic carcinoma associ- ated with portal vein tumor thrombus : three cases reports. Intern Med. thrombosis has not been reported. 2009;48:142–50. 3. Obuz F, Bora S, Sarioglu S. Malignant islet cell tumor of the pancreas Conclusions associated with portal venous thrombus. Eur Radiol. 2001;11:1642–4. 4. Bedirli A, Patiroglu TE, Sakrak O, Artias Y. Portal vein resection for a portal We report a very rare case of pancreatic colloid carci- vein thrombus caused by nonfunctioning islet cell carcinoma: report of a noma with a portal vein tumor thrombus. To our knowl- case. Surg Today. 2004;34:802–4. edge, there is no report of such a case. 5. Nguyen BD. Pancreatic neuroendocrine tumor with portal vein tumor thrombus: PET demonstration. Clin Nucl Med. 2005;30:628–9. 6. Kawakami H, Kuwatani M, Hirano S, et al. Pancreatic endocrine tumors with intraductal growth into the main pancreatic duct and tumor throm- Abbreviations bus in the portal vein: A case report and review of the literature. Intern CEA: Carcinoembryonic antigen; CA19-9: Carbohydrate antigen 19-9; PM: Med. 2007;46:273–7. Proximal margin; DM: Distal margin; RM: Radial margin; MRCP: Magnetic 7. Yamauchi N, Ozeki Y, Sumi Y, et al. A case of alpha-fetoprotein producing resonance cholangiopancreatography; IMPC: Intraductal papillary mucinous acinar cell carcinoma of the pancreas with portal vein obstruction. Tan to carcinoma; IPMN: Intraductal papillary mucinous ; DP: Distal pan- sui (J Pancreas). 2001;22:1011–6 (in Japanese). createctomy; PVR: Portal vein resection; SSPPD: Subtotal stomach-preserving 8. Ouchi A, Isogai M, Harada T, et al. A case of resected acinar cell carcinoma pancreaticoduodectomy; PD: Pancreaticoduodectomy; S-1: Tegafur/gimeracil/ of the pancreas body with tumor thrombus extending into the portal oteracil; GEM: Gemcitabine; nabPTX: Nab-paclitaxel. vein. J Jpn Surg Assoc. 2012;45:1052–8 (in Japanese). 9. Machimoto T, Aisu Y, Honda K, et al. A case of resection for a huge pancre- Acknowledgements atic acinar cell carcinoma with tumor thrombus in the portal vein. Jpn We would like to thank American Journal Experts (https​://www.aje.com) for Cancer Chemother. 2014;41:2196–8 (in Japanese). English language editing. 10. Saiura A, Umekita N, Matsui Y, et al. Successful surgical resection of solid cystic tumor of the pancreas with multiple liver metastases and a tumor Authors’ contributions thrombus in the portal vein. Hepatogastroenterology. 2000;47:887–9. DU designed the study and wrote the initial draft of the manuscript. EM and 11. Usatof V, Wittkop B, Devalia K, Guest P, Buckels J. Solid papillary-cystic YM diagnosed pathological examinations. MS contributed to the analysis and carcinoma of the pancreas with portal vein tumor thrombus. ANZ J Surg. interpretation of the data and assisted in the preparation of the manuscript. 2004;74:291–3. All other authors have contributed to the data collection and interpreta- 12. Tomimaru Y, Ishikawa O, Ohigashi H, et al. Intraductal papillary- mucinous tion and critically reviewed the manuscript. All authors approved the fnal carcinoma of the pancreas with tumor thrombus in the portal vein: a manuscript. report of two cases. Hepatogastroenterology. 2007;54:1585–8. 13. Yonekura T, Kosumi T, Hokim M, et al. Aggressive surgical and chemo- Funding therapeutic treatment of advanced associated with This research received no specifc grant from any funding agency in the pub- tumor thrombus in portal vein. J Pediatr Surg. 2006;41:596–8. lic, commercial, or not-for-proft sectors. 14. Mizushima T, Tanioka H, Emori Y, et al. Metastatic pancreatic malignant melanoma: tumor thrombus formed in portal venous system 15 years Ethics approval and consent to participate after initial surgery. Pancreas. 2003;27:201–3. Not applicable. 15. Saezusa H, Nakata S, Watanabe M. Mucinous carcinoma of the pancreas: A case report and literature review. Suizo (J Jpn Panc Soc). 2014;29:749– Consent for publication 55 (in Japanese). When obtaining informed consent for surgical procedures, general consent 16. Sakoda T, Murakami Y, Uemura K, et al. Two cases of mucinous(non-cystic) for publication and presentation was obtained from the patient. carcinoma of the pancreas without intraductal papillary mucinous neo- plasm. Suizo (J Jpn Panc Soc). 2015;30:600–6 (in Japanese). Competing interests 17. Takao K, Ishii H, Araki Y, et al. A case of pancreatic mucinous carcinoma The authors declare that they have no competing interests. with tumor thrombosis in the pancreatic duct. J Jpn Surg Assoc. 2018;79:2355–9 (in Japanese). Author details 18. Seidel G, Zahurak M, Iacobuzio-Donahue C, et al. Almost all infltrat- 1 Department of Surgery, Tama Kyuryo Hospital, 1491 Shimooyamadacho, ing colloid carcinomas of the pancreas and periampullary region arise Machida‑shi, Tokyo 194‑0297, Japan. 2 Department of Pathology, Keio Uni- from in situ papillary : a study of 39 cases. Am J Surg Pathol. versity School of Medicine, 35 Shinamomachi, Shinjuku‑ku, Tokyo 160‑8582, 2002;26:56–63. Japan. 19. Adsay NV, Pierson C, Sarkar E, et al. Colloid mucinous noncystic carcinoma of the pancreas. Am J Surg Pathol. 2001;25:26–422. Received: 26 July 2020 Accepted: 21 September 2020 20. Nakahashi G, Yamaguchi R, Watanabe S, et al. A case of rapid growing mucinous carcinoma of the pancreas without intraductal papillary muci- nous neoplasm. J Biliary Tract Pancreas. 2017;38:885–90 (in Japanese).

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