Endoscopic management of post-liver transplant biliary complications.

Biliary complications are being increasingly encountered in post liver transplant patients because of increased volume of transplants and longer survival of these recipients. Overall management of these complications may be challenging, but with advances in endoscopic techniques, majority of such patients are being dealt with by endoscopists rather than the surgeons. Our review article discusses the recent advances in endoscopic tools and techniques that have proved endoscopic retrograde cholangiography with various interventions, like sphincterotomy, bile duct dilatation, and stent placement, to be the mainstay for management of most of these complications. We also discuss the management dilemmas in patients with surgically altered anatomy, where accessing the bile duct is challenging, and the recent strides towards making this prospect a reality.

Colonic perforation following polypectomy of a gastrointestinal follicular lymphoma masquerading as a colon polyp.

INTRODUCTION: The gastrointestinal (GI) tract is the predominant site for primary extranodal non-Hodgkin lymphomas (NHL), accounting for 5-10% of all extranodal disease. CASE: A 74-year-old man underwent colonoscopy for a positive fecal occult blood test. Colonoscopy revealed a 3.5-cm polyp in the descending colon and was removed by snare cautery polypectomy. Post-polypectomy site showed a 0.3-0.5-cm mucosal defect. Five endoclips were applied to close the mucosal defect. The patient remained stable during subsequent intensive monitoring and never required surgical intervention. Pathology of the polyp revealed follicular lymphoma (FL) involving the lamina propria of the mucosa with extension into the submucosa. The patient had no systemic symptoms, and staging for NHL with contrast computerized tomography of the chest, abdomen, and pelvis revealed no evidence suggestive of lymphoma. DISCUSSION: Approximately 6-20% of all primary GI-NHL are in the colon. The frequency of GI-FL accounts for 1-3.6% of all GI-NHL. After a search of the current literature, there have been no cases of a follicular lymphoma presenting solely as an isolated colon polyp. Likewise, bowel perforation due to polypectomy of such polyps has never been cited. Retrospectively, the diagnosis and extent of the polyp could have been established using endoscopic end-to-end forceps biopsy and/or endoscopic ultrasound with a radial scanning catheter probe and fine-needle aspiration of the lesion. Such a diagnosis could have changed the strategy for endoscopic removal of the polyp. Our case is interesting because it is the first report of a follicular lymphoma presenting as a single isolated colon polyp involving all layers of the colonic mucosa.

Rare case of dysphagia.

Wound botulism is exceedingly rare and occurs almost exclusively among injection drug users. In 2008 there was a case of wound botulism in a noninjecting drug user reported to the Centers for Disease Control and Prevention (CDC). We report a case of a Caucasian male developing dysphagia due to wound botulism after having a motorcycle accident that left him with open fractures. The CDC was contacted and the patient was transferred to medical intensive care unit to be emergently started on hepatavalent Clostridium botulinum antitoxin. Early suspicion of wound botulism is essential for effective therapy with antitoxin in this life-threatening disease. If not suspected, this patient would likely have died. Nevertheless, the delay in diagnosis and treatment resulted in the patient's suffering dysphagia and neurological deficits. The patient required a percutaneous endoscopic gastrostomy tube and months of dysphagia therapy, supportive care, and rehabilitation. Our aim is to increase the awareness for wound botulism when a patient presents with dysphagia and diplopia after suffering open wounds. If suspected early, the morbidity and mortality from this disease can be prevented.

Promotion of melanoma growth by the metabolic hormone leptin.

We have previously shown that melanoma cells proliferate in response to the metabolic hormones TRH and TSH. The objective of the present study was to test the hypothesis that a third metabolic hormone, leptin, serves as a growth factor for melanoma. Using western blotting, indirect immunofluorescence, and RT-PCR, leptin receptors were found to be expressed by human melanoma cells. In contrast, cultured melanocytes expressed message for the receptor without detectable protein. Melanoma cells responded to treatment with leptin by activating the MAPK pathway and proliferating. Melanoma cells but not melanocytes, also expressed leptin protein, creating a potential autocrine loop. Examination of human melanoma tumors by immunohistochemistry revealed that melanomas and nevi expressed leptin at a high frequency. Melanomas also strongly expressed the leptin receptor, whereas nevi expressed this receptor to a much lesser degree. We conclude that leptin is a melanoma growth factor and that a leptin autocrine-loop may contribute to the uncontrolled proliferation of these cells.

Lack of maturation with anti-leptin receptor antibody in melanoma but not in nevi.

We have previously shown thryotropin-releasing hormone expression in nevi and melanoma. Thryotropin-releasing hormone regulation by leptin has been shown in the hypothalamus. The present study was therefore undertaken to evaluate leptin and leptin receptor in nevi and melanoma. Leptin receptor expression as assessed using an anti-leptin receptor antibody showed uniform expression throughout the lesion in 14 of 17 melanomas; 3 melanomas lacked leptin receptor immunoreactivity. In contrast, out of 15 nevi, 10 showed weak to moderate leptin receptor immunoreactivity, with positivity present only in the superficial dermal component. Thus, maturation was present in nevi but not in melanoma with the anti-leptin receptor antibody (P<0.0001). Anti-leptin antibody, in contrast, did not show a significant difference in maturation between nevi and melanoma. We also compared leptin receptor in Spitz nevi and melanoma, as the two can sometimes be difficult to distinguish. Spitz nevi showed moderate to strong immunopositivity. Of 19 Spitz nevi, 7 showed lack of maturation, a finding statistically significant from both melanoma and nevi. Our results suggest a role for leptin receptor in melanoma, and we show for the first time that melanomas show more intense immunoreactivity as compared to nevi (but not Spitz nevi) and that maturation with anti-leptin receptor antibody may be a diagnostically useful tool in distinguishing melanomas, especially nevoid ones, from nevi in difficult cases.

Human melanoma cells express functional receptors for thyroid-stimulating hormone.

We have reported a high prevalence of hypothyroidism in the cutaneous melanoma population, suggesting that the pathologic hormonal environment of hypothyroidism promotes melanoma growth. The objective of this study was to test the hypothesis that TSH, which circulates at elevated levels in hypothyroid individuals, stimulates the growth of melanoma cells. Our results show that TSH receptors (TSHR) are expressed by virtually all cutaneous melanocytic lesions, including benign nevi, dysplastic nevi, and melanomas, with higher expression found in malignant and pre-malignant lesions. The finding of TSHR expression by human tumors is confirmed in cultured melanoma cells and melanocytes, in which TSHR expression is demonstrated by immunofluorescent staining, western blotting, and reverse transcriptase-PCR. Melanoma TSHR are functional, as evidenced by the ability of TSH to induce the formation of cAMP and to activate the mitogen-activated protein kinase (MAPK) pathway. Cultured melanoma cells, but not melanocytes, are induced to proliferate at a physiologically relevant concentration of TSH. Taken together, these data support the hypothesis that TSH is a growth factor for human melanoma. Our findings have broad clinical implications for the prevention of melanoma and the management of established disease.