Chronic Secretory Diarrhea Research Articles

Vasoactive Intestinal Peptide-Producing Neuroblastic Tumors: A Rare Cause of Refractory Diarrhea.

Neuroblastic tumors are the most common malignant extracranial solid tumors of childhood. A small subgroup presents chronic incoercible diarrhea due to the tumor's production of vasoactive intestinal peptide (VIP). The hypothesis of an occult tumor is not always considered, which delays and impairs treatment. We aim to identify these patients' characteristics and help alert health professionals to the hypothesis of a neuroblastic tumor in children with chronic diarrhea refractory to the usual approach. We carried out an epidemiological study on all retrievable reports of neuroblastic tumors between 1975 and 2021 described in the Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), and Latin American & Caribbean Health Sciences Literature (LILACS) databases. Patient information was divided into categories, and we performed a descriptive analysis. We analyzed 96 cases; 83 (86.5%) cases had diarrhea prior to the diagnosis of the neoplasm, 49 (51%) were ganglioneuroblastomas, 69 (71.8%) were abdominal, and 59 of the 60 patients (98%) with reported acid-base disorders had hypokalemia. When serum VIP was reported, the majority of values varied between one and 20 times the upper reference limit. Seventy-two (75%) patients underwent complete tumor resection, and the overall survival rate was 70%. Serum VIP production by neuroblastic tumors is related to cell differentiation and better prognosis. Such children often require intensive hospital support to reverse the malnutrition and acid-base disorders related to this paraneoplastic syndrome. Its early diagnosis and treatment significantly change the prognosis and quality of life. We, therefore, suggest screening for neuroblastic tumors when health professionals encounter unmanageable chronic secretory diarrhea in children with no defined etiology in the usual investigations.

Prikaz slučaja 30-godišnjeg muškarca sa megacistis-mikrokolon-intestinalnim hipoperistaltičkim sindromom sa de novo mutacijom gena ACTG2

Introduction: Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a very rare genetic disorder of visceral motility of the gastrointestinal and genitourinary system. According to our knowledge, so far there has been no description of a patient with megacystis-microcolon-intestinal hypoperistalsis syndrome and chronic secretory diarrhea. Case report: We have presented a case report of a 30-year-old male with a genetically verified novel (de novo) mutation p.R257H in the smooth muscle actin (ACTG2) gene. At 8 months of age he was diagnosed with suspected Hirschsprung's disease, partial resection of the colon was performed. During the first year of his life, subtotal colectomy with cecorectal anastomosis was performed and, simultaneously, deteriorated emptying of the urinary bladder was confirmed. The patient was subjected to several unsuccessful abdominal and urological operations. At age of 18, the differential diagnosis was narrowed to micro-villus inclusion disease and congenital chloride diarrhea. The patient was tolerant to oral feeding all the time, where intermittent parenteral nutrition started only in adolescence. At the age of 26, due to urethral stenosis, perineal urethrostomy was performed. Since the age of 29, due to complications of the underlying disease the patient was administered chronic dialysis treatment, and a year later, genetic testing provided the definitive diagnosis of MMIHS. Therefore, combined kidney and intestinal transplantation was proposed. The patient continued the treatment with daily fluid and electrolyte compensation along with adequate parenteral nutrition through a triple-lumen central catheter. Conclusion: Timely genetic testing leads to avoiding repeated surgical interventions and numerous complications. Multivisceral transplantation represents a significant improvement in the treatment of patients with this syndrome.

McKittrick-Wheelock Syndrome: A Neoplastic Cause of Electrolyte Imbalance.

The authors present the case of a 79-year-old woman who presented with chronic secretory diarrhoea and severe electrolyte imbalance. A large rectal tubulovillous adenoma was discovered, leading to surgical resection of the tumour with complete resolution of the diarrhoea and electrolyte imbalance. The diagnosis of McKittrick-Wheelock syndrome was made.We hope this case report will contribute to a greater awareness among health professionals about this clinical condition. A multidisciplinary approach is essential for the best outcome.LEARNING POINTSMcKittrick-Wheelock syndrome is an important differential diagnosis in patients presenting with electrolyte abnormalities and secretory diarrhoea.A multidisciplinary approach from the beginning is important for a timely diagnosis and better outcome.Surgical removal of the hypersecretory villous adenoma is the definitive treatment for McKittrick–Wheelock syndrome and can be life-saving.

VIPoma: a rare cause of diarrhea. A case report

Introduction: Vasoactive intestinal peptide-secreting tumor (VIPoma) is a rare functional pancreatic neuroendocrine tumor (F-PNET) characterized by secretory diarrhea, hypokalemia, and hypochlorhydria. Its low incidence and high risk of malignancy pose a clinical challenge that requires a high degree of clinical suspicion. Case presentation: A 61-year-old woman visited the emergency department of a tertiary care hospital in Medellín, Colombia, due to chronic diarrhea (7 months) that led to dehydration, renal failure, metabolic acidosis, and hypokalemia. As a result, a treatment based on loperamide, intravenous fluids and broad-spectrum antibiotics was started. In addition, chromogranin A levels of 477 ug/L (<100) were reported, while an abdominal MRI showed a 33x30mm mass in the head and uncinate process of the pancreas, so outpatient surgical management was decided. However, three days after discharge, and due to the persistence of clinical signs, the patient was admitted to another hospital (also a tertiary care hospital), where, given the high suspicion of VIPoma, and once the diarrhea was solved, the mass was removed (Whipple procedure) without any complication. Finally, the diagnosis was confirmed based on serum vasoactive intestinal peptide levels (930 pg/mL (RV<75)) and the pathology report (PNET tumor grade 2). Two years after the surgery, the patient was asymptomatic, and no residual lesions or metastases were evident in a control MRI. Conclusion: Late diagnosis of VIPoma is associated with worsened quality of life, severe complications, and high prevalence of metastasis. Therefore, it should be suspected in patients with chronic secretory diarrhea that is not caused by an infection, since early diagnosis and timely treatment can contribute to achieving better survival rates in these patients.

Pancreatic VIPoma as a Differential Diagnosis in Chronic Pediatric Diarrhea: A Case Report and Review of the Literature

Chronic diarrhea is a common chief complaint in the pediatric population with a wide range of diagnostic differentials; as such, whilst suspecting common causes, less prevalent conditions tend to be overlooked, such as neuroendocrine tumor pathologies. VIPomas are characterized by hypersecretion of the vasoactive intestinal peptide (VIP), causing watery diarrhea, hypokalemia, and achlorhydria. Nonetheless, its low incidence rate in children makes it an easily unnoticed pathology. Herein, we report a case of a 14-year-old female patient and a review of relevant literature. The patient complained of 7-month history of watery diarrhea, multiple emetic episodes, and relevant past medical history of multiple hospitalizations. Chronic diarrheal disease work-up studies, including a high VIP scintigram, showed a lesion suggestive of a VIPoma-type neuroendocrine pancreatic tumor. A distal pancreatectomy was performed with a complete resolution of the symptoms. When faced with a pediatric patient presenting with chronic secretory diarrhea and whose work-up studies rule out the most common pathologies, the possible presence of a neuroendocrine tumor as VIPoma should be considered. J Med Cases. 2021;12(5):195-201 doi: https://doi.org/10.14740/jmc3535

1517 No Microscope Needed: A Macroscopic Presentation of Collagenous Colitis

INTRODUCTION: Microscopic colitis (MC) is a common cause of chronic secretory diarrhea. Diagnosis has been considered to be histopathologic with otherwise normal-appearing colonic mucosa. However, accumulating evidence suggests distinct endoscopic features may be associated with MC. We present a rare case of MC that illuminates the importance of recognizing these macroscopic findings as they not only aid in diagnosis but also have significant management implications. CASE DESCRIPTION/METHODS: A 61-year-old female with rheumatoid arthritis presented with one month of watery, non-bloody diarrhea. She reported lower quadrant, crampy abdominal pain and a 20 lb weight loss. Her medications included pantoprazole 20 mg, escitalopram 20 mg, and ibuprofen three times weekly. Physical exam demonstrated diffuse abdominal tenderness and laboratory assessment revealed acute renal insufficiency and ESR of 28 (normal range: 0-15). Infectious stool studies were negative. A CT abdomen/pelvis revealed diffuse colonic wall thickening and mild mucosal hyperenhancement consistent with pancolitis. Colonoscopy revealed diffuse erythematous mucosa and multiple shallow, linear mucosal rents were created with minimal insufflation of CO2 during scope insertion. Targeted biopsies were taken and pathology demonstrated significant subepithlial collagen deposition consistent with a diagnosis of severe collagenous colitis (CC). DISCUSSION: While endoscopic findings may occur in up to 16.5% of patients with MC, only 1.1% of cases detail isolated linear ulcerations. Association with transmural inflammation is even more rare and to our knowledge this is the first report of CC with both radiographic evidence of pancolitis and discrete mucosal ulcerations. It has been hypothesized that collagen deposition reduces colonic compliance predisposing to mucosal tears that may herald colonic perforation. Although some studies suggest similar diagnostic yields between right versus left-sided biopsies (98.7% v. 98.9%), there are no descriptions of targeted biopsies in this condition. While our patient did not have any noted procedural complications, a flexible sigmoidoscopy may have been sufficient for a diagnosis. This case highlights an atypical presentation of CC with pancolitis and discrete endoscopic lesions that should prompt endoscopists to alter management. Flexible sigmoidoscopy with CO2 insufflation or water emersion should be considered in patients with macroscopic findings of MC, but the case should be aborted if deep mucosal tears occur.

Hypersecretion of Fluids and Electrolytes? Think Inside The Gut

Most adenomatous polyps cause no symptoms, but in rare cases these may produce unexpected clinical consequences. The McKittirck-Wheelock syndrome (MKWS) is a rare and life-threatening disease usually caused by a villous adenoma leading to a classic triad of chronic secretory diarrhea, electrolyte disturbances and renal failure. If promptly diagnosed and treated, it is a reversible illness. This is the case of a 73-year-old man with medical history of prostate cancer and chronic kidney disease stage 3, who presented with a 3 weeks history of worsening diarrhea. He reported a 2-year history of intermittent involuntary passage of a gelatinous material with small amount of brown soft stools and occasional rectal bleeding. These symptoms persisted when on fasting and woke him up during the night. He denied fever, abdominal pain, weight loss, recent travel and prior use of antibiotics. His oral mucosa was dry and the abdominal exam was normal. Digital rectal exam revealed a large palpable mass and abundant gelatinous fluid. Initial labs showed hypochromic microcytic anemia, severe hypokalemia (2.1 mEq/L), hyponatremia (129 mEq/L), hypochloremia (82 mEq/L), hypomagnesemia (1.5 mg/dL), acute over chronic kidney injury (Cr 5.1 mg/dL, BUN 137 mg/dL) and high anion gap metabolic acidosis. Stool workup was negative. After aggressive intravenous fluids and electrolytes replacement, the patient underwent a diagnostic colonoscopy in which a large polypoid mass obstructing the lumen was seen (Figure 1). Non-contrast abdominopelvic CT showed a 4.7 x 6.2 cm lobulated and heterogeneous intraluminal mass at the rectum (Figure 2). Histological exam revealed a fragmented tubulovillous adenoma with foci of high grade dysplasia. The MKWS is a rare condition, first described in 1954, caused by fluid and electrolyte secretion by a colonic neoplasm. Distal villous adenomas are the most common culprits. Diarrhea may be present for years and is initially compensated by renal adaptation and increased oral intake. The syndrome is more severe with increasing size of the lesion and by distal location of the tumor. Overexpression of prostaglandin E2 causes abnormal secretory activity leading to hypokalemia and hyponatremia and in severe cases, such as in our case, to severe hypochloremic metabolic acidosis and acute renal failure. Definitive treatment is surgical resection, which results in normalization of electrolytes and reduces the risk of invasive cancer.Figure: Large polypoid mass obstructing the lumen.Figure: Non-contrast abdominopelvic CT showing a lobulated and heterogeneous intraluminal mass at the rectum.

電解質喪失症候群（EDS）を呈した直腸絨毛腫瘍の1症例

An 82-year-old woman with disturbance of consciousness was admitted to our hospital. Blood examination results showed renal failure, hyponatremia, and hypokalemia. Endocrine function was normal. Abdominal computed tomography images revealed a 53-mm tumor and intussusception in the recto-sigmoid. Contrast enema results revealed a concave pressure defect. Endoscopic examination revealed a continuous circumferential villous tumor located at 5 cm from the lower rectum, which could have intussuscepted due to peristalsis. We diagnosed EDS due to villous tumor of rectum and performed a Hartmann procedure ; the resected specimen showed a 140 × 110 mm circumferential villous tumor, and pathological investigation revealed adenocarcinoma with an adenoma component. EDS is a rare disorder characterized by a villous tumor leading to chronic secretory diarrhea which in turn leads hypokalemia, hyponatremia, and renal failure. Intussusception in adults is rare in comparison with children.

An uncommon cause of unexplained nonbloody diarrhea: When mind knows eyes may see

AbstractCollagenous colitis (CC) is characterized by chronic secretory diarrhea with the apparently normal gross appearance of the colonic mucosa. A biopsy is usually diagnostic. The symptoms of CC appear most commonly in the elderly. In CC, the major microscopic characteristic is a thickened collagen layer beneath the colonic mucosa. The reported case represents unexplained nonbloody diarrhea of a systemic lupus erythematosus patient, on extensive evaluation found to have CC. This case highlights the importance of considering a rare possibility of CC as a differential in a patient of unexplained nonbloody diarrhea.

Case Report: Mediastinal Ganglioneuroma Presented as Chronic Diarrhea in a Young Saudi Girl

Ganglioneuromas (GN) are rare, benign neurogenic tumors that arise from sympathetic ganglia. They are often asymptomatic. However, in rare cases, they may secrete catecholamines, vasoactive intestinal polypeptides (VIP), or androgenic hormones and manifest with flushing, symptoms of catecholamine excess or chronic diarrhea. We report a young Saudi girl with chronic secretory diarrhea, severe hypokalemia and abdominal distension. After an extensive work up, a well-defined hypodense heterogeneous mediastinal mass was noted in radio imaging. A complete recovery was seen after surgical removal of that mediastinal mass which turned to be a ganglioneuroma.

Crofelemer for the treatment of chronic diarrhea in patients living with HIV/AIDS

Diarrhea is a common comorbidity present in patients with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) who are treated with highly active antiretroviral therapy. With a multifactorial etiology, this diarrhea often becomes difficult to manage. In addition, some antiretrovirals are associated with chronic diarrhea, which potentially creates an adherence barrier to antiretrovirals and may ultimately affect treatment outcomes and future therapeutic options for HIV. A predominant type of diarrhea that develops in HIV patients has secretory characteristics, including increased secretion of chloride ions and water into the intestinal lumen. One proposed mechanism that may lead to this type of secretory diarrhea is explained by the activation of the cystic fibrosis transmembrane conductance regulator and calcium-activated chloride channels. Crofelemer is a novel antidiarrheal agent that works by inhibiting both of these channels. The efficacy and safety of crofelemer has been evaluated in clinical trials for various types of secretory diarrhea, including cholera-related and acute infectious diarrhea. More recently, crofelemer was approved by the US Food and Drug Administration for the symptomatic relief of noninfectious diarrhea in adult patients with HIV/AIDS on antiretroviral therapy. Results from the ADVENT trial showed that crofelemer reduced symptoms of secretory diarrhea in HIV/AIDS patients. Because crofelemer is not systemically absorbed, this agent is well tolerated by patients, and in clinical trials it has been associated with minimal adverse events. Crofelemer has a unique mechanism of action, which may offer a more reliable treatment option for HIV patients who experience chronic secretory diarrhea from antiretroviral therapy.

PTU-139 Colonic histological abnormalities are non-specific and non-significant in bile acid malabsorption

IntroductionBile acid malabsorption (BAM) is a common cause of chronic secretory diarrhoea via poorly characterised mechanisms. The aim of this study was to determine if histological abnormalities in colonic mucosa...

Chronic Diarrhea in Children

Chronic Diarrhea in Children

Follow‐up of a child with congenital chloride diarrhoea caused by a novel mutation

Congenital chloride diarrhoea (CLD) is a rare autosomal recessive disease with chronic secretory diarrhoea and a need for lifelong salt replacement therapy. We describe a male newborn of consanguineous parents with CLD. Postnatally, frequent watery diarrhoea and electrolyte disturbances were noted from the day 8 of his life. At molecular level, a homozygous mutation was detected in the solute carrier family 26 member A3 gene (SLC26A3), confirming the clinical diagnosis of CLD. The relatively late onset of persistent clinical and laboratory signs may demonstrate a new clinical course of CLD. These findings support the need of a tight follow-up and monitoring if such a diagnosis is considered.

Chronic diarrhea

Chronic diarrhea

Treatment of pediatric autoimmune enteropathy with tacrolimus (FK506)

Autoimmune enteropathy is characterized by chronic secretory diarrhea, villous atrophy, associated autoantibodies, and a partial response to immunosuppression. Currently available therapy (including steroids and cyclosporine) has resulted in remission only in a subset of patients. We evaluated the effects of tacrolimus (FK506) in patients with autoimmune enteropathy refractory to steroids and cyclosporine. Three patients with diagnosed autoimmune enteropathy who continued to have intractable diarrhea despite treatment with steroids and/or cyclosporine were treated with oral tacrolimus. Despite documented histological villous atrophy and poor absorption of oral cyclosporine, therapeutic tacrolimus levels were easily achieved in all 3 patients. All patients showed clinical improvement as documented by decreased stool output and ability to be weaned off parenteral nutrition; response time ranged from 1 to 4 months after tacrolimus was begun. Histological improvement was noted in all patients, and the small bowel biopsy specimens of 2 of the 3 patients showed a return to normal. All patients have been followed up for at least 6 months and are in clinical remission; 1 has received a bone marrow transplant for underlying immunodeficiency. Tacrolimus is a useful drug in the treatment of autoimmune enteropathy, even in patients who have not responded to steroids or cyclosporine. No long-term follow-up of patients with autoimmune enteropathy treated with tacrolimus is currently available. (Gastroenterology 1996 Jul;111(1):237-43)

Safety Hazard With Intravenous Pumps

Sir .—The following patient reports document a safety hazard associated with the IMED (model 960) volumetric infusion pump (IMED Corp, San Diego, Calif). Patient Reports .—Patient1.—A 3-year-old black girl presented with chronic secretory diarrhea. She had been receiving total parental nutrition since the first year of life. During recent hospitalization for suspected central line sepsis, the patient played with the settings on the IMED volumetric infusion pump (model 960), changing the rate to 632 mL/h, thereby self-administering a 120-mL bolus of the 25% dextrose, with 2.5 g of protein per deciliter of the total parenteral nutrition solution. The patient was discovered in an obtunded state, with blood pressure elevated to 146/94 mm/Hg. Findings of an initial laboratory examination were consistent with a hyperosmolar, hyperglycemic, nonketotic state: glucose, 65.5 mmol/L; serum osmolarity, 375 mOsm/L; calcium, 2.74 mmol/L; magnesium, 1.15 mmol/L; phosphorus, 2.29 mmol/L; potassium, 5.7 mmol/L; and serum

Treatment of chronic secretory diarrhea of unknown origin by lithium carbonate

A 49-yr-old patient developed severe chronic secretory diarrhea associated with hypokalemia and gastric hypochlorhydria. Small bowel perfusion study revealed active proximal intestinal secretion. Despite thorough investigation, the cause of her secretory diarrhea was not elucidated. Her diarrhea was refractory to indomethacin, prednisone, and trifluoperazine therapy. The life-threatening profuse watery diarrhea responded, however, to oral lithium carbonate, an agent reported to inhibit cyclic adenosine monophosphate synthesis. Diarrhea stopped within 4 days of initiation of lithium chloride therapy. Discontinuation of lithium 2 wk later resulted in return of watery diarrhea. Lithium therapy was reinstituted and her diarrheal symptoms resolved completely. Three months later, lithium carbonate was discontinued. The patient continued to be well and remained asymptomatic 15 mo after discontinuation of therapy. Therefore, in patients with chronic secretory diarrhea in whom exhaustive tests fail to reveal an etiology, a trial of oral lithium therapy may be beneficial in ameliorating the disabling symptoms and could be life-saving.

Normal Jejunal Cyclic Nucleotide Content in a Patient With Secretory Diarrhea

A case of chronic secretory diarrhea with elevated plasma vasoactive intestinal peptide (VIP) and serum gastrin levels is described. Plasma secretin, glucagon, insulin, and cyclic adenosine and guanine monophosphate (cAMP and (CGMP) concentrations were normal. Administration of a prostaglandin synthetase inhibitor failed to decrease the volume of diarrhea. There was no evidence of laxative abuse, antral cell hyperplasia, gastric hypersecretion, or pancreatic hypersecretion. The pancreatic histology was interpreted as islet cell hyperplasia. Jejunal tissue cAMP and cGMP concentrations were in the same range as those obtained from three control subjects. This report suggests that cyclic nucleotides may not mediate intestinal secretion in hormone-induced diarrhea.