VIPoma with expression of both VIP and VPAC1 receptors in a patient with WDHA syndrome

We report a case of VIPoma in a 72-year-old female patient who presented with excessive diarrhea, severe hypokalemia, and acidemia. She had been referred to our hospital three times because of severe diarrhea. No primary tumor site was found by conventional techniques, including contrast-enhanced CT and MRI, angiography, endoscopy, and positron emission tomography (PET), but a tumor was subsequently found in the head of the pancreas by octreotide scanning. Her diarrhea diminished dramatically after octreotide treatment, while her diarrhea has ceased without the therapy of octreotide at the first admission in the course of 2 years of her disease. Immunohistochemial analysis of the excised tumor tissue revealed the expression of both vasoactive intestinal peptide (VIP) and VIP and pituitary adenylate cyclase-activating peptide 1 (VPAC1) receptors. This is the first case report of a VIPoma that immunostains for VIP and VPAC1 receptors and indicates that abundant VIP produced by VIPoma might inhibit its growth and reduce VIP secretion via the VPAC1 receptor in vivo.     

Vipoma of the Pancreas Complicating Ulcerative Colitis

We report a case of vipoma of the pancreas in conjunction with ulcerative colitis in a 20-yr-old woman. Twenty months after the onset of ulcerative colitis, the patient complained of watery diarrhea and was found to have an electrolyte disorder. A pancreatic tumor was detected by ultrasonography and computed tomography, along with an elevation of serum vasoactive intestinal polypeptide (VIP). The secretory diarrhea diminished dramatically, and the serum VIP level decreased into the normal range immediately after resection of the pancreatic tumor. Immunohistochemical staining revealed a pancreatic vipoma. Despite removal of the vipoma, she underwent restorative proctocolectomy and ileal J-pouch anal anastomosis 2 yr later due to progression of the ulcerative colitis. Postoperative course was uneventful, with excellent functional results. Knowledge of this rare condition accompanying ulcerative colitis may help in the management of the patient with an atypical clinical course.     

Role of intra-arterial steroid administration in the management of steroid-refractory acute gastrointestinal graft-versus-host disease

We report here a case of severe steroid-refractory gastrointestinal graft-versus-host disease treated with intra-arterial administration of corticosteroids. A 53-year-old female with non-Hodgkin's lymphoma received peripheral blood hematopoietic stem cell transplant from her HLA-matched sibling. She developed grade II skin and grade IV gastrointestinal graft-versus-host disease with no hepatic involvement. Therapy with oral prednisone easily controlled her skin rash but she had profuse diarrhea that did not respond to high dose intravenous corticosteroids and denileukin diftitox. Infusion of methyl-prednisolone into superior and inferior mesenteric arteries produced dramatic improvement of diarrhea, with complete resolution of gastrointestinal graft-versus-host disease.     

Octreotide-sensitive ectopic ACTH production by islet cell carcinoma with multiple liver metastases

We report a 21-year-old woman with ectopic ACTH syndrome due to islet cell carcinoma with multiple liver metastases. On admission, she showed Cushingoid appearance (moon face, central obesity etc.) and had acute respiratory distress syndrome due to pneumocystis carinii pneumonia. Laboratory examination revealed marked elevations of plasma ACTH (735 pg/ml) and cortisol (145 microg/dl) with a profound hypokalemia (2.0 mEq/l). She was found to have multiple masses in the liver and a solid mass in the tail of pancreas by abdominal computerized tomography scanning. Treatment with octreotide successfully reduced elevated plasma ACTH and cortisol levels, and she received frequent transhepatic arterial embolization and chemotherapy. The primary pancreatic tumor was surgically removed, revealing islet cell carcinoma which contained high content of ACTH (100 microg/g wet weight) and abundantly expressed proopiomelanocortin and somatostatin receptor subtype-2 mRNAs as determined by Northern blot analysis. Postoperatively, she was free from symptoms for almost one year. However, progressive enlargement of multiple liver metastases refractory to chemotherapy led her to decide on total hepatectomy and liver transplantation from her father. After liver transplantation, she remained almost free from symptoms for almost one year. However, metastases developed to the mediastinal and paraaortic lymph nodes as detected by 111[In] pentetreotide scintigraphy. Eleven months after liver transplantation, she was again treated with octreotide and, 16 months after, with metyrapone, both of which were effective in reducing ACTH and cortisol levels, respectively, until she died of acute respiratory failure. This case of a young female patient with ectopic ACTH-producing islet cell carcinoma of the pancreas was quite unique in that she survived for 5 years despite the acute onset and rapid progression of the multiple liver metastases at least in part due to the long-lasting favorable response to octreotide and living-related liver transplantation.     

Multimodality treatment for gastric carcinoid tumor with liver metastases

Carcinoid tumors are the most common neuroendocrine tumors in the gastrointestinal tract, and between 10% and 30% of these tumors are gastric in origin. Three types of gastric carcinoid tumors are recognized: type I, associated with chronic atrophic gastritis type A; type II, associated with multiple endocrine neoplasia; and type III, sporadic and the most malignant. We present a patient with an aggressive, sporadic-type gastric carcinoid that metastasized to the liver. Her symptomatic treatment included the somatostatin analog octreotide. Octreotide scintigraphy demonstrated that this tumor avidly bound the peptide. The patient's gastric carcinoid (assessed by endoscopy and endoscopic ultrasound) regressed and she underwent hepatic artery embolization for her liver metastases. After initial partial CT resolution the tumor grew, compressing the inferior vena cava. The patient underwent orthotopic liver transplant with excellent recovery, although she was subsequently found to have two small lung metastases. She has responded well to adjuvant Indium-111 octreotide receptor targeted therapy. This case highlights the therapeutic options for metastatic neuroendocrine tumors, including liver transplantation and adjuvant receptor targeted therapy.     

Streptozotocin treatment in pancreatic cholera (Verner-Morrison) syndrome

A case of pancreatic cholera (Verner-Morrison syndrome) associated with a pancreatic endocrine tumor and hepatic metastases is presented. VIP and HPP plasma levels, initially elevated, were accurately followed in various conditions: during corticosteroid therapy, after pancreatic tumor excision, during and after streptozotocin therapy (1.5 g/m2) by repeated intraarterial route). Only streptozotocin therapy resulted in a reduction of the stool volume with concomitant decrease in VIP plasma levels. However, the size of the hepatic metastases was unchanged and HPP plasma levels remained elevated. It is suggested that VIP represents the tumoral secretion and HPP a marker of the residual malignant tissue.     

Plasma vasoactive intestinal polypeptide concentration determination in patients with diarrhea

Determination of plasma levels of vasoactive intestinal polypeptide (VIP) has been used for screening patients with chronic diarrhea to identify potential neuroendocrine tumors. This 6-year blinded study from 1981 to 1986 examines the causes of elevated VIP levels in patients. In healthy volunteers ( n = 144), VIP concentrations ranged from 14 to 76 pg/mL (mean +/- SE, 28 +/- 12), whereas in chronic renal failure, 4 of 34 patients or 12% [serum creatinine 4.5 - 9.0 mg/dL (397-795 mumols/L)] had an elevation to greater than 100 pg/mL. No patient with idiopathic hepatic cirrhosis (n = 12) had elevation of serum concentration of this peptide. Among 588 consecutive unselected patients undergoing evaluation for chronic diarrhea (n = 362; 62%) or possible neuroendocrine tumor (n = 214; 36%), 23 patients (3.9%) had concentrations greater than 76 pg/mL. In this group, 5 patients had functioning (VIP, 160-5975 pg/mL) and 5 had nonfunctioning (VIP, 80-120 pg/mL) pancreatic islet cell carcinomas: all 10 patients had hepatic metastases. Other known cases of elevated levels of VIP, ranging from 80 to 340 pg/mL, included other neurogenic tumors (n = 3), small- bowel resection (n = 2), inflammatory bowel disease (n = 2), chronic renal failure (n = 1), and prolonged fasting (n = 1). Patients with diarrhea in which VIP-secreting tumors were identified had plasma vasoactive intestinal peptide concentrations greater than 140 pg/mL. In patients with chronic diarrhea, determination of plasma vasoactive intestinal peptide levels did identify tumors secreting this peptide, but the results from this referral institution did not show identification of these tumors early in their clinical course.     

Treatment of metastatic glucagonoma to the liver: case report and literature review

Glucagonoma, a rare neuroendocrine pancreatic tumour, is frequently malignant and often accompanied by hepatic metastases. Our aim was to consider the different treatments of metastatic glucagonoma to the liver and their results. A case of glucagonoma with metachronous, small, multiple and bilobar liver metastases is reported. Combined treatment with octreotide and hepatic arterial chemoembolization was applied with good results in terms of symptom relief, plasma glucagon levels and regression of hepatic metastases. Survival rates were also improved. Based on our experience, glucagonoma with metachronous, multiple, diffuse and bilobar hepatic metastases should be treated with octreotide plus hepatic arterial chemoembolization with improved outcome and prognosis.     

Hypercalcitonemia revealing a somatostatinoma

Somatostatinoma are rare well-differentiated endocrine tumors with malignant behavior arising from the pancreas and duodenum. They are defined by somatostatin positive immunostaining of the majority of tumor cells. The main clinical features are diabetes, diarrhea and biliary lithiasis related to somatostatin production. Somatostatinoma secreting both calcitonin and somatostatin may be unrecognized as a small number of such observations have been published. We report the case of a 57- year-old woman referred for weight loss, diarrhea and worsening diabetes. Computer tomography scan revealed multiple hypervascular liver lesions suggestive of metastases. High plasma calcitonin level was evidenced, with normal chromogranin-A value, and high plasma somatostatin results lately communicated. Calcitonin secretion of extra-thyroidal origin was suspected leading to the identification of a pancreatic mass by further multiphase CT. The patient underwent left pancreatectomy with surgical hepatic resection. Histological and immunostaining studies confirmed definitive diagnosis of somatostatinoma secreting both somatostatin and calcitonin. Plasma calcitonin should be measured in the assessment of duodeno-pancreatic endocrine neoplasm. Calcitonin determination is available, more reproducible than other specific pancreatic endocrine markers and could be effective for diagnosis and follow-up of such foregut-derived endocrine neoplasia.     

Symptomatic pancreatic polypeptide-secreting tumor of the distal pancreas (PPoma)

Our report describes a 46-yr-old woman who presented with watery diarrhea in the presence of multiple endocrine neoplasia type I (MEN I) syndrome. Of various potential pancreatic endocrine hormones, only serum levels of pancreatic polypeptide were elevated. Radiologic imaging failed to identify a pancreatic tumor; her diarrhea was therefore managed with subcutaneous administration of somatostatin. Three years later she developed gallstone pancreatitis with the subsequent development of a pancreatic pseudocyst. At exploration for drainage of the pseudocyst, intraoperative ultrasound identified a 6-mm tumor in the distal pancreas that was resected. Final pathology documented a pancreatic endocrine tumor with immunohistochemical staining demonstrating the presence of pancreatic polypeptide. The present case illustrates the symptomatology that may be associated with pancreatic polypeptide-secreting endocrine tumors of the pancreas.     

Metastatic pancreatic neuroendocrine tumor presenting as a pituitary space occupying lesion: a case report

Neuroendocrine tumor metastases to the pituitary gland are very rare. There are few case reports of carcinoid tumor metastases to the pituitary, but no cases of pancreatic neuroendocrine pituitary metastases have been reported. In this report we present a 55-year-old female with a sellar mass, ophthalmoplegia and headaches initially thought to represent an invasive null cell pituitary adenoma. However a histological (trans-sphenoidal and liver biopsies) and systemic investigation proved it to be a metastasis of an undiagnosed pancreatic neuroendocrine tumor. Our patient was unique in respect to the location of the metastasis and the uncharacteristically high proliferative index of her tumor. She received conventional therapy consisting of Sandostatin, chemotherapy and radiotherapy as well as labeled somatostatin following an avid uptake on octreotide scanning. Despite a radiological improvement the patient suffered progressive clinical deterioration and died.     

Vipoma in an adolescent: treatment with a delayed-action somatostatin analog, octreotide or SMS 201-995, and surgical removal

We report the case of a VIPoma diagnosed in a 15-year-old teenager who experienced profuse secretory diarrhea associated with hypokalemia, metabolic acidosis and high plasma levels of vasoactive intestinal peptide (VIP) and pancreatic polypeptide (PP). Angiography showed an abnormal mass in the head of the pancreas. Before surgery, subcutaneous injections (100 micrograms every 8 hours) of the long-acting somatostatin analogue octreotide or SMS 201-995, were administered in order to stabilize the clinical status of the patient and to reduce the intravenous administration of fluid and electrolytes. This treatment resulted in prompt relief of the symptoms and in a partial decrease of the plasma levels of VIP and PP. At subsequent laparotomy, there was a tumour localized in the head of the pancreas, which was completely removed by Whipple resection. The immunohistochemical staining revealed the presence of VIP and PP inside the tumour cells. Two years after surgical resection, the patient is healthy without clinical or laboratory evidence of recurrence.     

Four year treatment with a long acting somatostatin analogue in a patient with Verner-Morrison syndrome.

The case is described of a woman with a Verner-Morrison syndrome of extreme severity, caused by an occult VIPoma. Administration of SMS 201-995 (Sandoz) (SMS) at the dose of 150 and subsequently of 250 micrograms daily, decreased plasma levels of vasoactive intestinal polypeptide (VIP) from about 500 to 100 pg/ml (highest normal limit 60 pg/ml). This was associated with complete regression of the diarrhea and normalization of serum potassium levels and hence with the return of the patient to a fully normal life. After 36 months of clinical remission, watery diarrhea recurred together with elevation of VIP plasma levels and appearance of liver metastases. Laparotomic exploration led to the removal of a pancreatic VIPoma and its liver secondarisms, which was followed by a second remission. Reappearance of the symptoms and development of new liver metastases 8 months later required reinstitution of SMS therapy, which allowed once again to control the clinical picture. Anterior pituitary function, assessed by dynamic testing, was unaffected by chronic SMS administration with the exception of the stimulated growth hormone secretion that was inhibited. Glucose tolerance and insulin secretion remained normal during treatment. Glucose intolerance ensued after pancreatectomy and was not worsened by reintroduction of SMS. Treatment with SMS may allow long-lasting remission of Verner-Morrison syndrome associated to VIPoma, though it does not arrest the progression of the tumor.     

Pancreatic VIPomas from China: Case reports and literature review

Vasoactive intestinal polypeptide-secreting tumors (VIPomas) are rare neuroendocrine tumors that often present as watery diarrhea, hypokalemia, and achlorhydria or hypochlorhydria. In this study, we present our institutional experience of diagnosis and treatment of VIPomas, along with a review of the Chinese literature since 1980. Patient #1, diagnosed in 1984 and with intact clinical records, shows the natural history of this disease. Patient #2, diagnosed in 2015, shows the results of evaluation by nuclear medicine techniques and the outcomes of standardized treatment. Comprehensive review of 41 cases allows evaluation of clinical characteristics, treatments and outcomes of pancreatic VIPoma patients. All patients presented with watery diarrhea. The average stool volume reached 3247?mL per day. Average serum VIP level was 839.3?ng/L. Twelve of the 41 cases were reported to have metastases at diagnosis. Somatostatin receptor scintigraphy and ¹⁸FDG PET-CT are efficient methods for detection of VIPoma. Surgical excision can promptly alleviate hormonal symptoms.     

Protein-losing enteropathy exacerbated with the appearance of symptoms of systemic lupus erythematosus

A 38-year-old woman visited our hospital with edema on her face and conjunctivae. The underlying disease was not clarified, and she did not visit the hospital afterwards. She suffered from diarrhea, polyarthralgia, Raynaud's phenomenon, malar rash and hair loss in the subsequent two years, and was hospitalized because of hypoproteinemia. Her urine, liver and heart test results did not account for her hypoproteinemia. She was diagnosed as having protein-losing enteropathy (PLE) associated with SLE based on the 99mtechnetium-labeled human serum albumin scintigraphy findings, clinical findings and laboratory results of antinuclear and anti-Sm antibodies. This case report demonstrates a strong association between PLE and SLE because PLE was aggravated along with the appearance of SLE symptoms and PLE subsided with prednisolone treatment along with improvement of SLE.     

Carcinoid crisis and reversible right ventricular dysfunction after embolization in untreated carcinoid syndrome.

A 59-year-old white male with carcinoid tumor and hepatic metastases underwent hepatic artery embolization. The patient developed carcinoid crisis and a subsequent transthoracic echocardiogram showed classic findings of carcinoid heart disease along with a dilated hypertrophied right ventricle and severely depressed right ventricular ejection fraction. After treatment with octreotide the patient's clinical condition improved and a repeat transthoracic echocardiogram showed a significant improvement and normalization of right ventricular systolic function. Serotonin levels showed a progressive decline that correlated well with the patient's improved clinical condition. These findings suggest that the acute right ventricular dysfunction was secondary to acute carcinoid crisis and resolution resulted in a significant improvement of both right ventricular systolic function and clinical condition.     

Results of long-term continuous subcutaneous octreotide administration in 14 patients with medullary thyroid carcinoma

OBJECTIVE: Treatment by octreotide has been suggested in medullary thyroid carcinoma patients with post-surgery metastases. The purpose of this study was to evaluate if the tumoral regression could be improved by a high dose and by prolonged octreotide treatment. DESIGN: Fourteen thyroidectomized patients were studied. All patients had persistently elevated plasma calcitonin levels with normal or elevated carcino-embryonic antigen levels. Five hundred micrograms/day of octreotide were administered by continuous subcutaneous infusion for 90 days. MEASUREMENTS: Plasma calcitonin and carcino-embryonic antigen levels were determined at days -30, -20, -2, -1, 0, +30, +60, +90, +120; morphological extension was evaluated every month. RESULTS: Continuous infusion of octreotide did not induce any significant decrease of calcitonin levels, or any morphological improvement, and had no major undesirable effect. However, in 4/14 patients calcitonin levels fell during treatment (-43, -50, -15, -20%), and in 9 patients calcitonin increased (+22 to +130%) after cessation of therapy. CONCLUSION: Biological or morphological parameters of medullary thyroid carcinoma are not significantly improved in a large series of patients treated by octreotide.     

Hypercalcitoninemia in a patient with a recurrent goitre and insulinoma: a case report.

Serum calcitonin has become a very sensitive and specific marker for medullary thyroid carcinoma that should be determined in patients with nodular thyroid disease. However, a few earlier reports indicated that tumors other than medullary thyroid carcinoma including insulinomas arising from pancreatic islet cells may also produce calcitonin. Of the few cases of calcitonin-producing insulinomas previously reported, most had incomplete data or lack of documentation of the association between raised serum calcitonin concentration and immunohistochemical detection of calcitonin in pancreatic islet cell tumors. In this paper we are reporting a 54-year-old woman with a history of partial thyroidectomy for multinodular goitre at the age of 50 yrs, she was evaluated for a 2-months history of fasting hypoglycemia (plasma glucose 1.9 mmol/L during a supervised fast), raised serum insulin (at the time of hypoglycemia 88.8 microU/ml; normal, 5 - 35 microU/ml) and C-peptide levels (at the time of hypoglycemia 6.1 ng/ml; normal, 1.37 - 3.51 ng/ml), markedly increased serum calcitonin concentration (481 pg/ml; normal, < 9.9 pg/ml), and an enlarged residual thyroid gland. Aspiration biopsy of the thyroid was negative for parafollicular C-cell hyperplasia or medullary thyroid carcinoma. Abdominal ultrasound and CT scan revealed a tumor in the head of the pancreas, which was surgically removed. Histopathological evaluation of the pancreatic tumor showed typical features of a neuroendocrine neoplasm with strong immunostaining for both insulin and calcitonin. After removal of the pancreatic tumor, clinical symptoms resolved and biochemical markers normalized (serum insulin, 14.9 microU/ml; C-peptide, 3.0 ng/ml; calcitonin, 2.9 pg/ml) confirming the causal relationship between insulinoma and markedly increased serum calcitonin levels.     

Reversible sclerosing cholangitis secondary to cryptosporidiosis in a renal transplant patient

Cryptosporidium parvum is a well-known cause of chronic diarrhea. In human immunodeficiency virus (HIV)-infected patients as well as in other immunocompromised patients it has also been shown to cause sclerosing cholangitis. We report a case of reversible C. parvum-induced sclerosing cholangitis in a renal transplant patient. This 40-year-old female received a renal transplant 9 years prior to presentation. She had no history of liver disease and was doing well on tacrolimus, prednisone, and azathioprine. She developed diarrhea and was found to have C. parvum present in the stool. Shortly after, she developed clinical, biochemical, radiologic, and histologic features of SC. After accidental reduction in her immunesuppression secondary to starting her on rifampin to treat her itching, she cleared C. parvum from her stool and had a marked improvement in her diarrhea, jaundice, and general health. Her liver enzymes normalized and magnetic resonance cholangiography showed complete resolution of biliary abnormalities. To our knowledge, this is the first case of C. parvum-induced sclerosing cholangitis in a renal transplant patient and one of a few in non-HIV patients. It is also the first to document resolution of sclerosing cholangitis after eradication of C. parvum in a non-HIV patient.