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Case of the Month

The comments and content shown here is for educational purposes, and intended for improving the overall quality of patient care. No comments, questions, or information shown here should be interpreted as or considered to be medical advice.

Case 1

Resectable pancreatic neuroendocrine tumor with liver metastases
Sonia T. Orcutt MD1, Alexandra Gangi MD1, Pamela Hodul MD1, Daniel A. Anaya MD1
Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL

CASE PRESENTATION

The patient is a 61 year old female who initially presented at a community hospital with symptoms of vague abdominal pain and reflux. On imaging workup she was found to have evidence of cholecystitis as well as several liver lesions. She was taken to the operating room and underwent a laparoscopic cholecystectomy and liver biopsy. The biopsy demonstrated a well differentiated neuroendocrine tumor. She was asymptomatic, with no flushing or diarrhea, and her urinary 5-HIAA was normal. She underwent additional tests in an attempt to identify the location of the primary tumor, including esophagogastroduodenoscopy, colonoscopy, and capsule endoscopy, none of which identified a primary site.

She was then referred to our institution for additional work-up. Octreotide scan demonstrated three avid lesions in segments 3, 6, and 7 of the liver, as well as avid upper abdominal lymph nodes, without a clear site of primary malignancy (see Figure 1). She was started on octreotide long-acting release depot for its antiproliferative effect and for its demonstrated improvement in progression free survival1 while continuing her work-up. Based on the octreotide avidity close to the pancreas, and to differentiate a primary tumor from a second site of mesenteric lymph node metastasis that could originate from a small bowel carcinoid, she underwent repeat esophagogastroduodenoscopy and endoscopic ultrasound at our institution. This identified a 9 x 15 mm subepithelial lesion in the second portion of the duodenum, which appeared to originate from within the muscularis propria of the duodenum in close association with the pancreatic head, and confirmed enlarged lymph nodes (largest 2.2 cm) in the periduodenal/peripancreatic area at the root of the mesentery (see Figure 2). Her case was discussed and all work-up reviewed at the hepatopancreatobiliary multidisciplinary tumor board, and the findings were interpreted as a resectable duodenal/pancreatic head well-differentiated neuroendocrine tumor with mesenteric lymph nodes and liver metastasis.

The patient was taken to the operating room with plans for removing all three sites of disease – the primary in the duodenum/pancreatic head, the liver metastases, and the lymph nodes at the root of the mesentery. In the operating room, the primary tumor was identified in the second portion of the duodenum and inseparable from the pancreatic head. A pancreaticoduodenectomy was performed to resect the primary tumor. Of note, the associated lymph nodes at the root of the mesentery required careful dissection from the superior mesenteric artery to achieve complete removal. Subsequently, intraoperative liver ultrasound was used to identify the three previously noted lesions, and all of these were resected with wide negative margins (all > 1 cm). A small subcentimeter lesion was noted in segment 4A, but due to proximity to the middle hepatic vein and lack of activity on preoperative imaging, the decision was made for close follow-up and monitoring of this lesion. At the conclusion of the case, the patient had undergone complete resection of her disease.

She recovered well from the operation. Her final pathology demonstrated a 1.9 cm well-differentiated pancreatic neuroendocrine tumor in the head of the pancreas invading the duodenal wall with 2 of 13 lymph nodes positive for malignancy. All margins were negative. The partial liver resections demonstrated metastatic well-differentiated neuroendocrine tumor with negative resection margins.

DISCUSSION

This case discusses surgical management of a pancreatic neuroendocrine tumor with synchronous liver metastases. Liver metastases from gastrointestinal or pancreatic neuroendocrine tumors are common, with over half of patients presenting with liver metastases at diagnosis. While liver masses can often be easily identified on standard imaging, as evidenced by this case report, small pancreatic tumors are often difficult to identify. Endoscopic ultrasound has been demonstrated to aid in the diagnosis of pancreatic neuroendocrine tumors, with a recent meta-analysis reporting sensitivity of detection at 87% and specificity of 98%.2

Well-differentiated neuroendocrine tumors are slow-growing, and patients can have long survival if adequate control of their disease can be obtained. For the primary tumor, this involves resection of the primary with associated lymph nodes, potentially en-bloc with adjacent organs. There are a variety of treatment options for neuroendocrine liver metastases, including systemic therapy, intra-arterial therapy, ablation, and surgical resection,3-5 and there is still controversy of which approach to take for each individual patient. However, it is clear that surgical resection of liver metastases provides the best long-term results, and has been shown to be effective when microscopically negative margins can be obtained. Even if negative margins cannot be obtained, major debulking (when over 80-90% of the tumor burden can be resected) can aid in symptomatic control, with improved survival even if the primary tumor is left in situ.6 Patients with untreated gastrointestinal or pancreatic neuroendocrine liver metastases have 5-year survival rates of about 30%, which compares poorly to 60-80% after margin-negative resection. However, it should be noted that over 90% of patients will experience recurrence within 5 years of resection,6-8 making the decision of when to resect or when to use other liver-directed therapy critical in the treatment of this disease. For neuroendocrine tumors, poor differentiation has been shown to be the most important negative prognostic indicator of oncologic outcomes; and aggressive surgical approaches of well-differentiated tumors have been shown to improve survival.9 Other predictors of poor long-term survival in patients with neuroendocrine liver metastases include synchronous disease, nonfunctional tumors, and concomitant extrahepatic disease.6

Additional considerations for this patient’s surgical treatment included the timing of pancreaticoduodenectomy in relation to hepatectomy. As the patient was relatively young with an excellent performance status, she was considered to be a good candidate for a combined approach. In addition, despite a theoretically higher risk of post-hepatectomy infection with combined resection due to exposure of bowel contents through the biliary tract after pancreaticoduodenectomy, recent reports of combined pancreaticoduodenectomy and hepatectomy have demonstrated safety with this combined surgical strategy.10 Thus, the decision was made to perform a combined pancreas and liver resection rather than to use a staged approach. With this strategy, the patient was successfully able to be rendered free of disease with expected improved overall survival. In addition, she has no need for continued medical therapy with octreotide which due to costs and side-effects profile, is an important advantage from a patient-centered perspective. This case report demonstrates the importance of a multidisciplinary approach to patients with neuroendocrine tumors, and highlights the value of thoughtful planning, particularly for patients presenting with a primary site and liver metastasis.

Figure 1. (A), (B), and (C) depict the avid lesions in the liver on octreotide scan. (C) depicts avidity in the periduodenal area, which corresponded to the primary duodenal lesion seen on endoscopic ultrasound. (D) depicts the avid lymph nodes at the root of the mesentery.

avid lesions in the liver on octreotide scan

Figure 2. (A). Endoscopic ultrasound images of the mass and its location adjacent to the uncinate process of the pancreas without clear involvement. (B). Endoscopic ultrasound images of enlarged retroperitoneal lymph nodes.

Endoscopic ultrasound images of the mass and its location adjacent to the uncinate process of the pancreas without clear involvement.

REFERENCES

  1. Rinke A, Muller HH, Schade-Brittinger C, et al: Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol 27:4656-63, 2009
  2. Puli SR, Kalva N, Bechtold ML, et al: Diagnostic accuracy of endoscopic ultrasound in pancreatic neuroendocrine tumors: a systematic review and meta analysis. World J Gastroenterol 19:3678-84, 2013
  3. Siperstein AE, Berber E: Cryoablation, percutaneous alcohol injection, and radiofrequency ablation for treatment of neuroendocrine liver metastases. World J Surg 25:693-6, 2001
  4. Soreide JA: Treatment of liver metastases from neuroendocrine tumours in relation to the extent of hepatic disease (Br J Surg 2009; 96: 175-184). Br J Surg 96:823; author reply 823-4, 2009
  5. Maxwell JE, Sherman SK, O'Dorisio TM, et al: Liver-directed surgery of neuroendocrine metastases: What is the optimal strategy? Surgery 159:320-33, 2016
  6. Mayo SC, de Jong MC, Pulitano C, et al: Surgical management of hepatic neuroendocrine tumor metastasis: results from an international multi-institutional analysis. Ann Surg Oncol 17:3129-36, 2010
  7. Grandhi MS, Lafaro KJ, Pawlik TM: Role of Locoregional and Systemic Approaches for the Treatment of Patients with Metastatic Neuroendocrine Tumors. J Gastrointest Surg 19:2273-82, 2015
  8. Sarmiento JM, Que FG, Grant CS, et al: Concurrent resections of pancreatic islet cell cancers with synchronous hepatic metastases: outcomes of an aggressive approach. Surgery 132:976-82; discussion 982-3, 2002
  9. Birnbaum DJ, Turrini O, Vigano L, et al: Surgical management of advanced pancreatic neuroendocrine tumors: short-term and long-term results from an international multi-institutional study. Ann Surg Oncol 22:1000-7, 2015
  10. Ebata T, Yokoyama Y, Igami T, et al: Review of hepatopancreatoduodenectomy for biliary cancer: an extended radical approach of Japanese origin. J Hepatobiliary Pancreat Sci 21:550-5, 2014

Case 2

Celiac axis resection for distal pancreatic cancer
Sarah Markham, MD, George Kazantsev, MD, CK Chang, MD
Kaiser Oakland, CA

63-year old male presented with a 5-cm mass in the body of the pancreas with involvement of the hepatic artery. Endoscopic ultrasound showed the mass to be adenocarcinoma involving the body and tail of the pancreas, causing main duct dilation and involving the hepatic artery. CA 19-9 was initially elevated to 2973. The patient underwent neoadjuvant treatment with 4 cycles of FOLFIRINOX with partial radiologic response, followed by 5 weeks of Xeloda and radiation. His CA 19-9 decreased to 25. The patient underwent a distal subtotal pancreatectomy with splenectomy, celiac axis resection, and cholecystectomy (modified Appleby’s procedure). His pathology revealed a 4-cm pancreatic adenocarcinoma with negative nodes (pT2 N0). Approximately two weeks after his surgery, the patient presented to clinic with weakness and emesis. Endoscopy revealed wide, shallow ulcers diagnostic of ischemic gastropathy. The patient was treated with bowel rest, proton-pump inhibitor administration, and total parenteral nutrition for 1 month. Repeat endoscopy showed complete resolution of the ischemic gastropathy and the patient returned to a normal diet. The patient subsequently completed 6 cycles of adjuvant chemotherapy with Gemzar, but has recently had increasing CA 19-9 values likely signifying occult recurrence or metastasis.

DISCUSSION

This case highlights an uncommon procedure and a rare complication not often discussed in the literature—distal pancreatectomy with celiac axis resection (DP-CAR) and ischemic gastropathy. Dr. Lyon Appleby first described his eponymous procedure in 1953 [1]. The Appleby procedure referred to a distal pancreatectomy with splenectomy, omentectomy, total gastrectomy, and celiac artery resection, which he posited as a superior treatment for gastric cancer [1]. Appleby observed that the celiac axis could be removed with preservation of hepatobiliary circulation via the preserved pancreaticoduodenal arcade [1]. The procedure facilitated removal of all nearby lymph nodes, something he considered a basic principle for cancer surgery. In his words, “surgery of any cancer must be radical enough to leave no residue and must in the final results be measured by the amount of worthwhile living it restores” [1].

Over time, Appleby’s procedure was modified to preserve the stomach to improve postoperative quality of life [2]. Gastric-preserving DP-CAR is contingent on several principles [2]. The arterial arcade of the pancreas must be preserved [2]. The blood supply to the stomach depends on the right gastric artery and right gastroepiploic arteries receiving collateral flow via the gastroduodenal artery from the pancreaticoduodenal arteries off the superior mesenteric artery [3]. This blood supply is critical for both the liver and the stomach [2]. The stomach should be preserved if the organ itself is involved or if the perigastric lymph nodes harbor disease [2]. The benefits of the modified Appleby procedure include increased likelihood of resection, better prognosis, and improved pain control secondary to dissection of the celiac axis ganglia [2, 4]. However, when compared to a traditional distal pancreatectomy, this comes at the expense of increased likelihood of kidney dysfunction postoperatively, longer operative times, and a clinically significant postoperative mortality increase from 1 to 10% [4]. There is also a trend towards increased need for blood transfusions with the modified Appleby procedure [4].

Ischemic gastropathy is a rare complication of the modified Appleby procedure. As in the patient described, it manifests with atypical gastric ulcerations, which respond to acid-reducing medication with complete resolution [3]. This postoperative complication can be obviated by preserving the right gastric artery and the right gastroepiploic arteries; compromise of either one may make one more prone to ischemic gastropathy [3]. Some surgeons try to prevent this complication via preoperative coil embolization of the hepatic artery to induce the formation of robust collateral vessels from the SMA to the GDA [3]. Another strategy described in the literature to lessen the risk of ischemic gastropathy is to create a bypass from the middle colic artery to the right gastroepiploic artery [3]. It is unclear given the paucity of literature available on the subject, whether either of these maneuvers should be routinely performed to decrease the likelihood of postoperative ischemic gastropathy after DP-CAR.

Pre and Post neoadjuvant chemotherapy and radiation.

REFERENCES

  1. Appleby LH. The coeliac axis in the expansion of the operation for gastric carcinoma. Cancer 1953;6:704-7
  2. Mayumi T, Nimura Y, Kamiya J et al. Distal pancreactectomy with en bloc resection of the celiac artery for carcinoma of the body and tail of the pancreas. Int J Pancreatol 1997;22:15-21
  3. Kondo S, Katoh H, Hirano S et al. Ischemic Gastropathy After Distal Pancreatectomy with Celiac Axis Resection. Surg Today (2004) 34:337–340
  4. Beane JD, House MG, Pitt SC, et al. Distal pancreatectomy with celiac axis resection: what are the added risks? HPB 2015, 17, 777-784

Case 3

57 year old male with perforated colon mass and metastatic liver disease

A 57-year-old patient reported a one-year history of constipation, abdominal pain, foul smelling stool, change in caliber of stool, decreasing appetite and a weight loss of 20 pounds. He underwent a CT of the abdomen as well as a lower endoscopy at an outside hospital. This demonstrated a large distal colon mass and a large liver lesion suspicious for metastatic disease.

He was referred to our clinic after a colonoscopy demonstrated biopsy proven moderately differentiated invasive adenocarcinoma. Completion staging CT scans were ordered and demonstrated a descending colon mass, 7.7 cm x 6.0 cm x 10.6 cm soft tissue mass with inflammatory change and a 2.6 cm x 1.5 cm soft tissue structure with locules of air and fluid component were noted (Figure 1a and 1b). In addition, incompletely characterized large heterogeneous mass with irregular margins primarily in hepatic segments 6 and 7 that measured 6.7 cm (AP) by 7.9 cm (TV) by 7.3 cm (CC)(Figure 2). Initial multidiscipilinary discussion was planned to initiate systemic chemotherapy immediately based on outside films. However, with the demonstration of a perforation the patient was urgently taken to the OR.

The patient underwent a formal left hemicolectomy with primary anastomosis and ultrasound of the liver. The mass was isolated to the right lobe abutting the right branch of the portal vein and extending to the right hepatic vein. Synchronous resection was decided against due to the need for a formal lobectomy in the same setting of resection of a large perforated distal transverse colon mass.

The patient recovered well from surgery and was started on systemic chemotherapy for three months of a modified FOLFOX 6 regimen (Oxaliplatin, Leucovorin, 5-FU). While on chemotherapy the patient underwent subsequent imaging to evaluate tumor response. CT of liver masss demonstrated tumor response and no evidence of disease progression (Figure 3). The patient underwent a formal right hepatectomy and tolerated the procedure well. Postoperatively the patient was restarted on systemic chemotherapy.

Figure 1a. Completion CT demonstrating incidental finding of perforation of colon mass

Figure 1a.  Completion CT demonstrating incidental finding of perforation of colon mass

Figure 1b. CT of abdomen and pelvis demonstrating contained perforation of colon mass

Figure 1b. CT of abdomen and pelvis demonstrating contained perforation of colon mass

Figure 2a. CT of abdomen and pelvis demonstrating metastatic liver mass

Figure 2a.  CT of abdomen and pelvis demonstrating metastatic liver mass

Figure 2b. CT of abdomen and pelvis demonstrating metastatic liver mass

Figure 2b.  CT of abdomen and pelvis demonstrating metastatic liver mass

Figure 3. Restaging CT demonstrating 5.5 x 4.0 cm Liver mass

Figure 3.  Restaging CT demonstrating 5.5 x 4.0 cm Liver mass

The comments and content shown here is for educational purposes, and intended for improving the overall quality of patient care. No comments, questions, or information shown here should be interpreted as or considered to be medical advice.

 


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