[A Case of WDHA Water Diarrhea Hypokalemia Achlorhydria Syndrome that Developed after Multimodal Therapy for Retroperitoneal Paraganglioma].

A 45-year-old woman visited a local clinic with left-flank abdominal pain. Abdominal computed tomography (CT) revealed a tumor 20 cm in diameter in the left adrenal gland. She was referred to our hospital for further treatment. No endocrinological abnormality was detected on either serum or urine examination. CT and haematology findings led to a preoperative diagnosis of primary adrenal carcinoma, and we performed a left adrenalectomy. Histopathological examination revealed a paraganglioma with intact adrenal gland. Therefore we diagnosed this case as primary retroperitoneal paraganglioma. Six months after the surgery, she developed peritoneal dissemination including bilateral ovarian metastases. After cytoreductive metastasectomy, she received 131I-meta-iodobenzylguanidine (MIBG) radiotherapy. During the following five-year follow-up, MIBG radiotherapy in conjunction with cytoreductive metastasectomy (3 surgeries and 6 sessions of 131I-MIBG radiotherapy) was performed, aiming at disease control. Five years after the initial surgery, liver, lung, and intra-peritoneal dissemination progressed. Thereafter, she developed severe diarrhea, hypokalemia, and metabolic acidosis with an elevated level of vasoactive intestional peptide, which was consistent with water diarrhea, hypokalemia, achlorhydria (WDHA) syndrome. Despite intensive treatments such as with a somatostatin analogue, she died two months after the onset of this syndrome.

Prevalence of Vibrio cholerae O1 serogroup in Assam, India: A hospital-based study.

BACKGROUND & OBJECTIVES: Although cholera remains to be an important public health problem, studies on reliable population-based estimates of laboratory confirmed cholera in endemic areas are limited worldwide. The aim of this hospital-based study was to evaluate the prevalence of Vibrio cholerae serogroup in Assam, India, during 2003-2013. METHODS: Stool samples/rectal swabs were collected from acute watery diarrhoea (AWD) cases during 2003-2013 and processed by standard microbiological procedures. Antibiotic sensitivity test was done following the Clinical and Laboratory Standards Institute guidelines. Year-wise epidemiological trend of cholera was analyzed. RESULTS: Cholera contributed to 3.93 per cent of AWD cases. In Assam, cholera was found to be more prevalent in the rural areas (6.7%) followed by the tea gardens (5.06%), urban slum (1.9%) and urban areas (1.4%). Highest proportion of cholera (13.7%) was observed in 0-10 yr age group. Of them, 11.5 per cent belonged to 0-5 yr age group. V. cholerae O1 El Tor serotype Ogawa was the predominant isolate. Multiple drug-resistant isolates of V. cholerae O1 Ogawa were reported in the study. INTERPRETATION & CONCLUSIONS: Emergence of resistance amongst V. cholerae towards many antibiotics is a matter of concern. Hence, continuous surveillance for diarrhoeal disorders is necessary to control the future outbreaks of cholera in this region.

Ventricular fibrillation resulting from electrolyte imbalance reveals vipoma in MEN1 syndrome.

Sporadic VIPoma is an exceedingly rare tumor with an annual incidence of 1:10 million people worldwide, yet it is described in approximately 5 % of MEN1 patients. The majority of VIPomas are malignant and radical surgery is the best therapeutic option. A 58-year-old man presented with cardiocirculatory arrest due to ventricular fibrillation. The patient had a 3-month history of epigastric pain with diarrhea. After reanimation, laboratory data revealed severe hypokalemia and hypercalcemia. Further investigations showed hyperparathyroidism, left adrenal adenoma and pituitary microprolactinoma and genetic diagnosis of MEN1 syndrome was made. Abdominal computed tomography revealed a 45 × 30 mm mass of the pancreatic head and two hepatic lesions, which proved to be neuroendocrine after 68 Ga PET and needle biopsy. Vasoactive intestinal peptide (VIP) serum level had increased. Subsequently the patient underwent pylorus-preserving pancreaticoduodenectomy and hepatic resection. Intraoperative VIP returned to normal values. Histopathology confirmed a pancreatic VIPoma metastatic to the liver. The postoperative course was unremarkable and the patient is well with no evidence of disease at a 48 months follow-up. Even in case of anusual presentation, when two or more main clinical findings of MEN1 related tumors are present, unrespectively to the presence of MEN1 mutation, MEN1 syndrome should be suspected. Surgery in MEN1 pancreatic neuroendocrine tumors is indicated both to treat symptoms and to avoid oncological progression even in advanced cases.

Intractable and dramatic diarrhea in liver transplantation recipient with vasoactive intestinal peptide-producing tumor after split liver transplantation: a case report.

Diarrhea after liver transplantation is a common complication. Vasoactive intestinal peptide-producing tumor (VIPoma) is a rare cause of watery diarrhea; 80% of such tumors occur in the pancreas, but it is rare in liver. Hypersecretion of vasoactive intestinal polypeptide can stimulate intestinal water and electrolyte secretion, and patients with VIPoma present with watery diarrhea, hypokalemia, and dehydration. Here we report on a 50-year-old man who presented with a 7-month history of watery diarrhea. He had undergone an orthotopic split-liver transplantation for hepatocellular carcinoma in November 2011. Two months after the liver transplantation, he presented with watery diarrhea, dehydration, and hypokalemia. Antibiotics, immunosuppressive drugs modification, antidiarrheal agents, antispasmodics, adsorbents, and fasting were alternately used to control the diarrhea, but his symptoms remained unchanged. A chromogranin examination, a marker of pancreatic neuroendocrine neoplasm, was positive in the third month of the diarrhea history and VIPoma was considered. Treatment with somatostatin immediately controlled the diarrhea, but the primary lesion could not be identified even after corresponding examinations were completed. In the ninth month of diarrhea, a 1 × 1-cm lesion was detected in the right liver by ultrasonography. Radiofrequency ablation was performed, and the diarrhea stopped. Seventeen months later, the chromogranin level decreased to normal and the patient was asymptomatic. Neither the recipient sharing the other liver portion nor the donor presented with any symptoms, so we wondered how the tumor occurred. It is possible that a small VIPoma lesion existed in the liver donor before the transplantation, and that the immunosuppressive drugs induced tumor development.

MSH2 and CXCR4 involvement in malignant VIPoma.

BACKGROUND: Vasoactive intestinal polypeptide secreting tumors(VIPomas) are rare endocrine tumors of the pancreas with an estimated incidence of 0.1 per million per year. The molecular mechanisms that mediate development of VIPomas are poorly investigated and require definition. METHODS: A genome- and gene expression analysis of specimens of a primary pancreatic VIPoma with hepatic metastases was performed. The primary tumor, the metastases, the corresponding healthy tissue of the liver, and the pancreas were compared with each other using oligonucleotide microarrays and loss of heterozygosity (LOH). RESULTS: The results revealed multiple LOH events and several differentially expressed genes. Our finding of LOH and downregulation was conspicuous in the microarray analysis for the mismatch repair gene MSH2 in the primary pancreatic VIPoma tumor, the hepatic metastasis but not in the corresponding healthy tissue. Further a strong overexpression of the chemokine CXCR4 was detected in the hepatic metastases compared to its pancreatic primary. With a review of the literature we describe the molecular insights of metastatic development in VIPoma. CONCLUSION: In VIPoma, defects in the mismatch repair system especially in MSH2 may contribute to carcinogenesis, and increased CXCR4 may be associated with liver metastasis.

Calcitonin-secreting pancreatic endocrine tumors: systematic analysis of a rare tumor entity.

OBJECTIVE: Pancreatic endocrine tumors (PETs) are characterized by the presence of hormone syndromes. Reports focusing on calcitonin-secreting PET (CTsPETs) are very rare. This study aimed to define a CTsPET-associated syndrome in regard to chemical, anatomical, and developmental aspects. METHODS: A computerized MEDLINE search was conducted under the search items: "pancreatic endocrine tumor," "calcitonin," "neuroendocrine pancreatic tumor," and "pancreas." Results of clinical, histopathological, immunohistochemical, and biochemical assessments of all patients identified with CTsPET were registered and statistically analyzed. RESULTS: Thirty-seven patients with CTsPET were identified. Mean serum calcitonin was elevated to the 89.2-fold of the upper reference value. Main symptoms were watery diarrhea (51.4%) and abdominal pain (35.1%). Most patients (59.5%) presented with metastatic spread at the time of diagnosis. Of all patients, 66.7% were alive after a mean follow-up of 28.9 months. Survival was higher in patients who underwent more aggressive surgical therapies independent from tumor sizes and in those with no metastases at the time of diagnosis. CONCLUSIONS: High calcitonin levels should always raise suspicion of medullary thyroid carcinomas. However, when thyroid examination remains without pathological findings, a CTsPET should be excluded. An aggressive surgical approach even in cases with large primary tumor sizes may lead to a longer survival.

Rapidly growing collagenomas in multiple endocrine neoplasia type I.

Patients with multiple endocrine neoplasia type I (MEN-I) frequently develop skin lesions including collagenomas, angiofibromas, and lipomas. We report a patient with MEN-I who exhibited rapid growth of multiple collagenomas after pancreatic enucleation of a vasoactive intestinal peptide-secreting tumor (VIPoma) and excision of multiple pancreatic masses. Five of the collagenomas were protuberant, with the bulk of the lesion protruding above the skin. Histologic analysis of the collagenomas revealed broad collagen bundles in a haphazard arrangement and decreased elastic fibers. Rapid growth of protuberant collagenomas appears to be unusual in MEN-I, but we suggest that MEN-I be considered in patients with apparent eruptive collagenoma.

Large cell carcinoma with calcitonin and vasoactive intestinal polypeptide-associated Verner-Morrison syndrome.

Verner-Morrison syndrome, characterized by diarrhea, hypokalemia, and hypochlorhydria, is caused most commonly by vasoactive intestinal polypeptide-secreting islet cell tumors of the pancreas. Verner-Morrison syndrome has not been described as a paraneoplastic syndrome in non-small cell lung cancer. We describe a 38-year-old man with metastatic non-small cell lung cancer of large cell carcinoma with neuroendocrine differentiation who presented with bone metastasis and intractable secretory diarrhea that was unresponsive to pharmacological treatment, including octreotide. Laboratory evaluation indicated elevated serum calcitonin and vasoactive intestinal polypeptide levels. Chemotherapy resulted in a transient response in the patient's diarrhea and neuroendocrine markers. The patient did not respond to further therapy and died 5 months after onset of back pain. To our knowledge, this is the first published case of large cell carcinoma with neuroendocrine differentiation associated with treatment-responsive paraneoplastic Verner-Morrison syndrome.

[Heavy diarrhea by low malignant B cell lymphoma]. / Schwere Durchfälle bei niedrig malignem B-Zell-Lymphom.

A 52-year old female presented with a low, malignant centroblastic-centrocytic lymphoma. After splenectomy and under steroid therapy it came to the eruption of a latent Strongyloides stercoralis infection, which the patient had presumably been suffering from for several years. Due to the immunodeficient condition and under continued steroid therapy even three courses of high dose anthelmintic therapy could not eradicate the parasites. The patient died of fulminant sepsis.

[Acrocyanosis: crucial symptom in a case of chronic diarrhea and weight loss]. / Akrozyanose. Wegweisender Befund bei chronischer Diarrhö und Gewichtsverlust.

The patient reported here was admitted because of severe dehydration caused by watery diarrhea. As underlying disease we found bacterial overgrowth of the small bowel due to myopathic dysmotility of the small bowel as a manifestation of CREST syndrome. An important clue to the diagnosis was the result of a ward round: the patient showed Raynaud's phenomenon when exposed to the cold at an open window airing the room. A leading tool for diagnosis and therapy proved to be small bowel manometry which is further discussed in this case report.

Alcalosis metabólica hipocaliémica con pérdida salina secundaria a hipertensión arterial vasculorenal en una niña afecta de síndrome nefrótico / No disponible

Presentamos el estudio de una niña afectada de estenosis unilateral de la arteria renal. Se trata de una niña de cuatro años que presenta cuadro clínico caracterizado por vómitos de doce horas de evolución, acompañado de deshidratación, poliuria con alcalosis metabólica hipokaliémica e hiponatrémica, convulsiones y coma por encefalopatía hipertensiva. Entre los antecedentes personales, la paciente está diagnosticada de síndrome nefrótico corticosensible e hipertensión arterial, precisando tratamiento farmacológico con captopril y nifedipina para el control. Once meses antes del episodio actual se realiza angioplastia transluminal percutánea por estenosis de la arteria renal izquierda con buen resultado. En el momento del cuadro recibe tratamiento con prednisona a dosis de 40 mg/m2/48h. Se realiza nueva arteriografía renal observándose reestonosis de la arteria renal izquierda, sin resultados con angioplastia transluminal percutánea. A la vista de estudios de imagen, se realiza una nefrectomía izquierda. Buena evolución tras ocho años de seguimiento. No precisa medicación para control de su tensión arterial y no ha presentado nuevas recaídas de su síndrome nefrótico (AU)

We present the study of a girl suffering from unilateral stenosis of the renal artery. This is a four year old girl who presents a clinical picture characterized by 12 hour long vomiting, accompanied by dehydration, polyuria with hypokaliemic and hyponatremic metabolic alkalosis, seizures and coma due to hypertensive encephalopathy. Among her personal background, the patient has been diagnosed of corticosensentive nephrotic syndrome and arterial hypertension, that required drug treatment with captropril and niphdipine for the control. Eleven months before the present event, a percutaneous transluminal angioplasty was performed due to stenosis of the left renal artery with good result. At the time of the picture, she was receiving treatment with prednisone, at a dose of 40mg/m2/48h. A new renal arteriography was performed, observing restenosis of the left renal artery, without results with percutaneous transluminal angioplasty. Based on the imaging studies, a left nephrectomy was performed. Good evolution after eight years of follow up. She does not require medication to control her blood pressure and has not presented new relapses of her nephrotic syndrome (AU)

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.

[Colchicine poisoning by accidental ingestion of the bulbs of Sandersonia aurantiaca: report of a case].

We report a case of colchicine poisoning in an 82-year-old woman. She had suffered from senile dementia and in her confused state ingested two bulbs of Sandersonia aurantiaca (Christmas-bells, Chinese lantern lily). She was admitted complaining of gastrointestinal symptoms, mainly severe watery diarrhea. The duration of her diarrhea was approximately 40 hours. On the 3rd day after ingestion, leukopenia and thrombocytopenia occurred. Although 50 micrograms of granulocyte-colony stimulating factor was administered from the 5th day to the 8th day, her white blood cell count did not increase and revealed nadir (100/microliter) on the 7th day. Her platelet count also revealed nadir on the 7th day. She died of respiratory failure in the early morning of the 9th day. The bulb of Sandersonia was found to contain colchicine at a concentration of 4.7 mg/g, and her serum level of colchicine was 6.3 ng/ml on the 6th day. Colchicine is an alkaroid extractable from the plants like Colchicum autumnale (meadow saffron, autumn crocus), and Gloriosa supra tuber. These plants belong to the lily family. Sandersonia aurantiaca also belongs to the lily family and we found that its bulb contained colchicine. To our knowledge, this is the first report of colchicine poisoning by Sandersonia aurantiaca.

Paraneoplastic manifestations in children.

Paraneoplastic manifestations are signs and symptoms observed in patients with cancer, distant from the tumour or its metastases and not caused by invasion, obstruction or bulk mass. In children with cancer, paraneoplastic manifestations are rare and distinct from those observed in adults. Knowledge about paraneoplastic manifestations can be of great clinical importance because they may be the presenting sign of a tumour or its recurrence and hence facilitate early diagnosis. In contrast, they sometimes mask the symptoms of a tumour and cause diagnostic delay. In this review, paraneoplastic manifestations in children are described, including hypercalcaemia, Cushing syndrome, precocious puberty, opsoclonus/myoclonus, acquired von Willebrand disease, watery diarrhoea syndrome, and hypertension. The mechanisms causing these manifestations are also discussed.

Vasoactive intestinal polypeptide-secreting ganglioneuromatosis affecting the entire colon and rectum.

This report describes a 7-year-old boy presenting with watery diarrhea, hypokalemia, and hypochlohydria associated with vasoactive intestinal polypeptide (VIP)-secreting ganglioneuromatosis involving the entire colon and rectum. The child's symptoms resolved following proctocolectomy, and the VIP levels returned to normal. Although 55 previous children have been reported with VIP-secreting tumors, this case is the first involving the entire colon and rectum.