Surgical approach to tumor recurrence and metastatic lesions of the liver in a patient with malignant endocrine tumors of the pancreas: case report

We describe herein a 72-year-old woman with tumor recurrence in the residual pancreas and metastasis to the liver following a pylorus-preserving pancreatoduodenectomy for multiple endocrine tumors in the head of the pancreas. Abdominal ultrasonography performed 7 years after the initial surgery detected new lesions in the residual pancreas and liver. After recurrence of endocrine tumors of the pancreas and metastasis to the liver were diagnosed, the lesions were successfully resected by total pancreatectomy with distal gastrectomy and both lateral segmentectomy and partial resection of segment 8. Genetic analysis using a blood specimen showed that this patient carried the multiple endocrine neoplasia type 1 (MEN1) gene mutation. One year after the second resection, the patient remains in good health using insulin and has not shown any sign of recurrence. This case report describes successful surgical resection for recurrence and metastasis of malignant endocrine tumors in a patient with the MEN1 gene mutation.     

EUS-guided FNA diagnosis of pancreatic endocrine tumors: new trends identified

BACKGROUND: Pancreatic endocrine tumors (PETs) are rare (1 per 100,000 population) and are thought to be functioning in up to 85% of cases and are generally less than 2 cm in size. By previous reports, 15% to 50% of PETs are nonfunctioning and are discovered either incidentally or by symptom evaluation from a mass effect. EUS-guided FNA (EUS-FNA) has been shown to accurately diagnose PETs and to localize tumors for surgical resection. OBJECTIVE: To describe a single-center experience of EUS-FNA diagnosis of PETs and its impact on surgical management. DESIGN: Retrospective cohort study. SETTING: University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. PATIENTS: Patients with PETs diagnosed via EUS-FNA over a 4-year period were identified through the authors' EUS database. Clinical history, laboratory values, diagnostic studies, EUS findings, cytology, pathology, operative records, and surgical pathology records were reviewed. MAIN OUTCOME MEASUREMENT: Impact of definitive preoperative diagnosis of PET on surgical management. RESULTS: Forty-one patients were diagnosed by EUS-FNA with PET. Thirty-five PETs were nonfunctioning PET; 6 were functioning PET. The mean tumor sizes of functioning and nonfunctioning PETs were 19 mm and 28 mm, respectively. The majority of tumors were located in the pancreatic head. Surgery was performed in 78% of patients; of these, 34% were resected laparoscopipcally. LIMITATIONS: Retrospective design and selection bias. CONCLUSIONS: In this study, nonfunctioning PETs were more commonly diagnosed compared with functioning PETs. In addition, the PETs were smaller than previously reported, likely because of increasing detection of incidental lesions through widespread use of abdominal imaging.     

Solid-pseudopapillary tumor of the pancreatic head causing marked distal atrophy: a tumor originated posterior to the main pancreatic duct

Summary We report the case of a solid-pseudopapillary tumor (SPT) of the head of the pancreas causing occlusion of the main pancreatic duct (MPD) and marked pancreatic atrophy distal to the tumor disproportionate to the tumor size. A 15-yr-old girl was diagnosed with 5-cm solid-pseudopapillary tumor of the pancreatic head with marked distal pancreatic atrophy. Endoscopic retrograde cholangiopancreatography demonstrated obstruction of the MPD in the pancreatic head. We performed a duodenum-preserving pancreatic head resection to avoid postoperative exocrine and endocrine insufficiency. The surgical specimen showed the typical gross appearance of a SPT, with only a thin rim of pancreas anterior to the tumor. We believe that this presentation results when a tumor originates posterior to the MPD. Thus, whether or not pancreatic atrophy occurs depends strongly on the anterior/posterior relationship between the enlarging tumor and the MPD. The risk of SPT causing severe pancreatic atrophy should be kept in mind to avoid irreversible pancreatic insufficiency in young females.     

Operative tumour yield obviates preoperative pancreatic tumour localization in multiple endocrine neoplasia type 1

Abstract. The efficiency of pancreatic tumour localization was prospectively evaluated in 12 consecutive patients with multiple endocrine neoplasia type 1 (MEN1), who were subjected to extirpation of 56 islet cell neoplasms of 0.2–4 cm in diameter (mean 0.8 cm) during pancreatic resection and enucleation. Computed tomography, angiography of the coeliac trunc and superior mesenteric artery, and percutaneous ultrasound correctly localized 7–12% of the tumours and 21–37% of the 19 lesions measuring at least one centimetre in diameter. Transhepatic portal vein sampling correctly located tumour sites in the proximal or distal portions of the pancreas in four out of six patients, but demonstrated unsatisfactory specificity. Intra-operative ultrasound and bidigital palpation of the pancreas had overall sensitivities of 86 and 45%, respectively, and eight lesions below 0.3 cm in diameter remained undetected with intraoperative ultrasound. It is concluded that diagnosis of endocrine pancreatic neoplasms is biochemical in MEN1 and that broad screening of tumour markers efficiently reveals pancreatic involvement decades before the development of a clinically overt disease. Intra-operative ultrasound is a requisite for pancreatic endocrine surgery in MEN1, and it obviates the need for conventional pancreatic imaging unless a pre-operative search for metastatic disease and anatomical aberrations is considered important.     

Huge endocrine tumor of the pancreas

We report a case of a huge endocrine tumor of the pancreas. A 76-year-old woman was admitted for a left upper abdominal mass. She showed neither hormonal symptoms nor abnormal serum hormone levels. Ultrasound imaging showed that a heterogeneously solid and partly calcified tumor was located in the retroperitoneal space. Computed tomography showed a hypervascular tumor with central degeneration. Open laparotomy revealed that the tumor originated from the pancreas; it was removed in a mass including the spleen and the pancreatic body and tail. The resected specimen demonstrated that the 580-g tumor was multi-lobulated, encapsulated, and 14 × 14 × 7?cm in size. Microscopically, the tumor consisted of cuboidal cells with round nuclei; the cells formed palisade and trabecular structures. Immunohistologically, chromogranin A, neuronspecific enolase, and glucagon were positive only for the tumor cells. Final diagnosis was endocrine tumor of the pancreas immunohistochemically producing glucagon. No tumor recurrence has been found 3 years after the surgery. We conclude that huge tumors in the retroperitoneal space must be differentiated from nonfunctioning endocrine tumors of the pancreas because the clinical course is markedly different.     

Solid-pseudopapillary tumor of the pancreatic tail

We report a case of the rare solid-pseudopapillary tumor of the pancreas. In contrast to other pancreatic tumors, the solid-pseudopapillary tumor has a favorable prognosis. The 60-year-old female patient we report on here was treated by left pancreatic resection combined with splenectomy for a non-metastasizing tumor of the pancreas. A solid-pseudopapillary tumor was found on histology. The patient had no signs of metastases at present. Since a microscopically invasive tumor growth is assumed, oncologically curative resection should be preferred vs the less radical enucleation. The rare solid-pseudopapillary tumor of the pancreas has a good prognosis after successful oncological resection.     

Identification of a lobe in the adult human pancreas rich in pancreatic polypeptide

Summary Systematic sampling of human necropsy pancreases has revealed that pancreatic polypeptide (PP) cells are not distributed equally in the gland. PP-cells are the most abundant cell type in the posterior part of the pancreatic head while they are scarce or absent in the remainder of the gland. The PP-rich part of the head can be separated by blunt dissection from the pancreas as a discrete lobe. This lobe probably originates from the ventral pancreatic bud during embryogenesis. A quantitative study of the immunofluorescent endocrine cell types (insulin, glucagon, somatostatin and pancreatic polypeptide cells) in PP-rich and PP-poor regions of pancreases in 8 subjects with ages ranging from 33 fetal weeks to 80 years, showed that the proportions of the cell types were different in youngs and adults.     

胰腺转移癌10例诊断及治疗

目的 探讨胰腺转移癌的诊断及治疗方法.方法 对1997年7月至2007年7月中国医科大学附属第一医院收治的10例胰腺转移癌进行回顾性分析.结果 原发肿瘤为肺癌3例、结肠癌2例、胃癌2例、肾癌2例、鼻咽癌1例.胰腺转移距发现原发肿瘤时间间隔平均40个月(0-192个月).10例转移灶均位于胰腺头颈部,单发9例,多发1例,肿瘤最大径平均3.03cm.主要临床表现为腹痛、腹胀、厌食、黄疸等.行胰十二指肠切除术2例.胰动脉灌注化疗1例,经皮经肝胆管内支架置入术1例,全身化疗2例.放疗1例,3例未行进一步治疗.7例获得随访,生存时间2-44个月,平均10.6个月.结论 胰腺转移癌临床少见,表现无特异性,应根据具体情况选择合理的治疗措施,对可切除者应积极手术治疗.     

Immunocytochemical staining for islet amyloid polypeptide in pancreatic endocrine tumors

Aims/hypothesis: Islet amyloid polypeptide is originally identified as the chief constituent of amyloid in insulinomas and type 2 diabetic islets. This study aimed to identify islet amyloid polypeptide by immunocytochemical staining in pancreatic endocrine tumors including 30 cases of insulinomas and non-β-cell pancreatic endocrine tumors. Results: In normal islets, 62% of islet cells and 52% of insulin cells were granularly positive for insulin and IAPP, respectively, with more insulin positive cells than IAPP positive cells and some densely positive staining for insulin and IAPP in irregularly shaped a nuclear, degenerating islet β-cells. In pancreatic endocrine tumors, all 10 insulinomas were positive for islet amyloid polypeptide but 2 glucogonomas, 1 somatostatinoma, 6 of 7 pancreatic polypeptidomas, all 7 gastrinomas and all 3 non-functioning pancreatic endocrine tumors were negative for islet amyloid polypeptide whereas one pancreatic polypeptidoma was positive for islet amyloid polypeptide. Methods: Using commercially available rabbit anti-islet amyloid polypeptide antibody, immunocytochemical staining was performed on 30 cases of pancreatic endocrine tumors, consisting of 10 insulinomas, 2 glucagonomas, 1 somatostatinoma, 7 pancreatic polypeptidomas, 7 gastrinomas and 3 non-functioning pancreatic endocrine tumors. Pancreatic tissues containing pancreatic endocrine tumors were systematically immunostained for insulin, glucagon, somatostatin, pancreatic polypeptide, gastrin and chromogranin A, in addition to islet amyloid polypeptide. When normal pancreatic tissues adjacent to pancreatic endocrine tumors were present, insulin, glucagon, somatostatin and islet amyloid polypeptide positive cells were counted for a total of 20 islets, which were divided into large islets and medium islets for each case. Conclusions/Interpretations: All 10 insulinomas and 1 pancreatic polypeptidoma were granularly positive for islet amyloid polypeptide, suggesting all 10 insulinomas contained enough insulin granules for IAPP whereas only one non-β-cell pancreatic endocrine tumor was co-localized with islet amyloid polypeptide in their secretary granules.     

Immunocytochemical staining for islet amyloid polypeptide in pancreatic endocrine tumors

Aims/hypothesis: Islet amyloid polypeptide is originally identified as the chief constituent of amyloid in insulinomas and type 2 diabetic islets. This study aimed to identify islet amyloid polypeptide by immunocytochemical staining in pancreatic endocrine tumors including 30 cases of insulinomas and non-β-cell pancreatic endocrine tumors.

Results: In normal islets, 62% of islet cells and 52% of insulin cells were granularly positive for insulin and IAPP, respectively, with more insulin positive cells than IAPP positive cells and some densely positive staining for insulin and IAPP in irregularly shaped a nuclear, degenerating islet β-cells. In pancreatic endocrine tumors, all 10 insulinomas were positive for islet amyloid polypeptide but 2 glucogonomas, 1 somatostatinoma, 6 of 7 pancreatic polypeptidomas, all 7 gastrinomas and all 3 non-functioning pancreatic endocrine tumors were negative for islet amyloid polypeptide whereas one pancreatic polypeptidoma was positive for islet amyloid polypeptide.

Methods: Using commercially available rabbit anti-islet amyloid polypeptide antibody, immunocytochemical staining was performed on 30 cases of pancreatic endocrine tumors, consisting of 10 insulinomas, 2 glucagonomas, 1 somatostatinoma, 7 pancreatic polypeptidomas, 7 gastrinomas and 3 non-functioning pancreatic endocrine tumors. Pancreatic tissues containing pancreatic endocrine tumors were systematically immunostained for insulin, glucagon, somatostatin, pancreatic polypeptide, gastrin and chromogranin A, in addition to islet amyloid polypeptide. When normal pancreatic tissues adjacent to pancreatic endocrine tumors were present, insulin, glucagon, somatostatin and islet amyloid polypeptide positive cells were counted for a total of 20 islets, which were divided into large islets and medium islets for each case.

Conclusions/Interpretations: All 10 insulinomas and 1 pancreatic polypeptidoma were granularly positive for islet amyloid polypeptide, suggesting all 10 insulinomas contained enough insulin granules for IAPP whereas only one non-β-cell pancreatic endocrine tumor was co-localized with islet amyloid polypeptide in their secretary granules.     

Experience with multiple endocrine neoplasia type 1 screening

Abstract. Screening for multiple endocrine neoplasia type 1 (MEN1) may be conducted for a variety of reasons. The principal aims may be more or less scientific, such as early identification of the trait. Other reasons for screening comprise attempts to avoid endocrine morbidity and possibly forthcoming problems from malignant transformation, as well as attempts to identify and treat gene carriers with a clinically overt disease. Several reports have substantiated the diagnostic yield from screening efforts among MEN1 kindreds. Such increases in detection of the disease ideally should be accompanied by enhanced rates of survival in order to fully justify an unlimited search for the trait. However, studies are lacking a clearly verifying reduction of mortality from the detection of presymptomatic MEN1 individuals. While waiting for the results of survival studies in progress, the generally prevailing opinion favours widespread screening because of the evidently decreased morbidity resulting from early diagnosis of the MEN1 trait, which apparently persists even during decades of follow-up. This paper presents the clinical features of the disease and experience derived from a prospective screening programme for MEN1 detection.     

A calcitonin and vasoactive intestinal peptide-producing pancreatic endocrine tumor associated with the WDHA syndrome

Background. Although pancreatic endocrine tumor can produce a variety of hormones, few pancreatic tumors produce a high systemic calcitonin concentration. Furthermore, calcitonin-producing pancreatic tumors rarely produce elevations of VIP in addition. Methods. We evaluated and treated a 50-yr-old woman with the WDHA syndrome. Abdominal computed tomography (CT) detected a tumor in the tail of the pancreas. Peripheral plasma calcitonin and VIP concentrations were markedly increased to 2000 pg/mL (normal, <74 pg/mL) and 7200 pg/mL (normal, <100 pg/mL), respectively. We diagnosed a calcitonin- and VIP-producing pancreatic endocrine tumor, which was removed by distal pancreatectomy including splenectomy. Results. Plasma calcitonin and VIP were determined in blood from the vein draining the tumor and splenic vein, sampled at operation. These secreted concentrations were extremely high: 4640 and 3610 pg/mL for calcitonin; 24700 and 13500 pg/mL for VIP. Calcitonin and VIP were also highly elevated in the resected tumor. Plasma calcitonin and VIP rapidly decreased after tumor resection. The patient has been well without recurrence for over 20 yr. Conclusion. An unusual pancreatic tumor secreting vasoactive intestinal peptide (VIP) caused WDHA syndrome (watery diarrhea, hypokalemia, and achlorhydria/hypochlorhydria) and also hypercalcemia. The latter was only partially offset by a large excess of calcitonin also secreted by the tumor.     

Cystic tumors of the pancreas: Opportunities and risks

Pancreatic cystic neoplasms(PCNs) are a high prevalence disease. It is estimated that about 20% of the general population is affected by PCNs. Some of those lesions can progress till cancer, while others behave in a benign fashion. In particular intraductal papillary mucinousneoplasms of the pancreas can be considered as the pancreatic analogon to colonic polyps. Treatment of these precursor lesions at an early stage can potentially reduce pancreas cancer mortality and introduce a new era of preemptive pancreatic surgery. However, only few of those lesions have an aggressive behavior. The accuracy of preoperative diagnosis, i.e., the distinction between the various PCNs is around 60%, and the ability to predict the future outcome is also less accurate. For this reason, a significant number of patients are currently over-treated with an unnecessary, high-risk surgery. Furthermore, the majority of patients with PCN are on life-long follow-up with imaging modality, which has huge cost implications for the Health Care System for limited benefits considering that a significant proportion of PCNs are or behave like benign lesions. The current guidelines for the diagnosis and management of PCNs are more based on expert opinion than on evidence. For all those reasons, the management of cystic tumors of the pancreas remains a controversial area of pancreatology. On one hand, the detection of PCNs and the surgical treatment of pre-cancerous neoplasms can be considered a big opportunity to reduce pancreatic cancer related mortality. On the other hand, PCNs are associated with a considerable risk of under- or over- treatment of patients and incur high costs for the Health Care System.     

A gastrointestinal stromal tumor of the duodenum masquerading as a pancreatic head tumor

Gastrointestinal stromal tumor （GIST） represents the most common kind of mesenchymal tumor that arises from the alimentary tract. GIST is currently defined as a gastrointestinal tract mesenchymal tumor showing CD117 （c-kit protein） positivity at immunohistochemistry. Throughout the whole length of the gastrointestinal tract, GIST arises most commonly from the stomach followed by the small intestine, the colorectum, and the esophagus. Only 3%-5% of GISTs occur in the duodenum, and especially, if GIST arises from the C loop of the duodenum, it can be difficult to differentiate from the pancreas head mass because of its anatomical proximity. Here, we report a case of duodenal GIST, which was assessed as a pancreatic head tumor preoperatively.     

Multidisciplinary management of nonfunctional neuroendocrine tumor of the pancreas

Pancreatic neuroendocrine tumors(PNETs) are a rare and diverse group of tumors; nonfunctional(NF) PNETs account for the majority of cases. Most patients with NF-PNETs have metastatic disease at the time of presentation. A variety of treatment modalities exist, including medical, liver directed, and surgical treatments. Aggressive surgical management is associated with prolonged survival, however available data are limited by selection bias and the frequent combination of PNETs with carcinoid tumors. Although few patients with metastatic disease will be cured, application of currently available therapies in a multidisciplinary setting can lead to excellent outcomes with prolonged patient survival.     

Macrocystic serous cystadenoma of the pancreas

Summary Background. Serous cystic neoplasms of the pancreas are uncommon tumors classified as microcystic adenomas. In this article, the authors report clinico-pathologic features of seven cases of macrocystic variant of the serous cystadenoma. Methods. Seven patients (5 females and 2 males) with a diagnosis of cystic lesion of the pancreas were observed after 1995. Clinical, radiological, and pathologic features, including immunohistochemistry, were reported. Enzymes and tumor markers CEA, CA 19-9, CA 125, CA 15-3, CA 72-4, and mucin-like carcinoma-associated antigen (MCA) were investigated in the serum and cyst fluid of the patients. Cytology was also performed. Results. Six patients were symptomatic complaining abdominal pain. All cases had radiologic evidence of unilocular cyst of the pancreas. The suspected diagnosis was consistent with mucinous cystic neoplasm. Serum tumor markers were all in the normal range. After surgery, pathology showed in all cases a cyst lined with cuboidal, periodic acid-Schiff (PAS)-positive epithelium, without mucin content or atypia. Minute microcysts were found surrounding the main cavity. Immunohistochemical stains were positive for cytokeratin, CA19-9, CA15-3, CA 72-4, and MCA. CEA was unexpressed. CA 125 in the cyst fluid were found elevated in three cases and CA 19-9 in three cases. Cytology was negative in all cases. Conclusion. When a unilocular pancreatic cyst is found, without history of pancreatitis and gallstones, having low serum tumor markers levels and negativity of CA 72-4 and MCA in the cyst fluid, the diagnosis of the macrocystic variant of the serous cystadenoma may be suggested. At present, the diagnosis is still based on pathological examination after cyst removal.     

Obstruction of the pancreatic duct by a granular cell tumor

Summary A 31-year-old woman presented with constant epigastric pain. Obstruction of the pancreatic duct was observed by ultrasonography and CT scan and was further defined by ERCP. Surgical exploration of the pancreas revealed a tumor in the pancreatic head. Histologic and immunocytochemical examination revealed a benign granular cell tumor, a neoplasm not previously described as causing obstruction in the pancreas.