Methotrexate-associated lymphoproliferative disorder in the stomach and duodenum: a case report.

BACKGROUND: Methotrexate-associated lymphoproliferative disorder (MTX-LPD) can present as a benign lymphoid proliferation or a malignant lymphoma in patients taking MTX. Almost 50% of MTX-LPD cases show spontaneous remission after withdrawal of MTX treatment. Studies have suggested that the hyper-immune state of rheumatoid arthritis, the immunosuppressive state associated with MTX, and the carcinogenicity of the Epstein-Barr virus might contribute to MTX-LPD development. Although most cases of MTX-LPD occur at extranodal sites, few cases of MTX-LPD affecting the stomach and duodenum have been reported. To our knowledge, no other study has reported on the endoscopic observations of dramatic withdrawal and appearance of multiple digestive tract lesions in a short period of time. Herein, we report the clinical course and imaging findings of our case, which may be useful for understanding the pathological condition of MTX-LPD. CASE PRESENTATION: We describe the case of a 70-year-old woman with MTX-LPD of the stomach and duodenum. Disease regression was temporarily achieved after cessation of MTX treatment; however, it subsequently recurred, and complete response was only achieved after six cycles of rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisolone (R-CHOP) chemotherapy. CONCLUSIONS: The first-choice therapy for patients taking MTX who develop suspected MTX-LPD should be the withdrawal of MTX treatment. Even after remission is achieved, patients should be kept under careful observation, and if the disease recurs, chemotherapy should be commenced promptly.

De Novo Development of Hamartomatous Duodenal Polyps in a Patient With Short Bowel Syndrome During Teduglutide Therapy: A Case Report.

Teduglutide (TG) is approved for the treatment of parenteral nutrition (PN)-dependent adult patients with short bowel syndrome (SBS). Its well-known adverse effect is expedited growth of colon polyps and potential formation of new polyps. Apart from animal studies, de novo development of duodenal polyps in a patient during TG therapy has not been reported in the literature. We report a case of a 71-year-old man with SBS on TG who developed multiple new duodenal polyps that were found incidentally during a diagnostic endoscopy. Furthermore, an accelerated growth of duodenal polyps was noted while on TG therapy, suggesting a potential trophic effect of TG on these polyps. There are no current recommendations for the surveillance of intestinal polyps in patients on TG therapy, but we recommend exercising caution and possible need for surveillance based on this case report.

Aortoduodenal fistula in a patient on intravitreal bevacizumab injections: a case report.

An 88-year-old woman on long-term intravitreal bevacizumab presented with acute gastrointestinal hemorrhage. She was stabilized and underwent nonrevealing upper endoscopy. She continued to require intermittent blood transfusions, and resulting computed tomography of the abdomen revealed an aortoduodenal fistula. The patient was undergoing treatment for her macular degeneration with intravitreal bevacizumab, an angiogenesis inhibitor frequently used to treat solid organ malignancies. Systemic administration has been associated with serious adverse events, including gastrointestinal hemorrhage, perforation, and fistula formation. Intravitreal bevacizumab has been used off-label to treat macular degeneration, but data on the safety of this therapy are limited. Given her lack of other risk factors, the authors postulate a potential association between intravitreal bevacizumab and aortoduodenal fistula formation in this patient.

Duodenal ischemia and upper GI bleeding are dose-limiting toxicities of 24-h continuous intra-arterial pancreatic perfusion of gemcitabine following vascular isolation of the pancreatic head: early results from the Regional Chemotherapy in Locally Advanced Pancreatic Cancer (RECLAP) study.

BACKGROUND: Regional chemotherapy is used successfully in the treatment of both primary and secondary malignancies, in particular of the peritoneal surface and the liver, and is currently explored as an attractive approach for patients with locally advanced pancreatic ductal adenocarcinoma. To establish the feasibility and toxicity of regional intra-arterial gemcitabine delivered as a 24-h continuous infusion to the pancreas as a novel treatment option for patients with locally advanced PDAC a phase I clinical trial was conducted. METHODS: Between April 2011 and September 2013 six patients with biopsy confirmed, borderline or unresectable pancreatic adenocarcinoma, and having received at least one line of systemic chemotherapy, underwent vascular redistribution of the inflow to the head of the pancreas by arterial coil embolization followed by perfusion catheter placement within the splenic artery. Patients were treated with increasing doses of gemcitabine administered by continuous splenic arterial infusion over 24 h with inter-patient and intra-patient dose escalation scheme. The primary endpoint was toxicity of the intra-arterial gemcitabine regimen and to establish the maximum tolerated dose. RESULTS: Catheter placement and gemcitabine infusion was successful in all patients enrolled to date (n = 6). Four out of six patients experienced catheter tip migration requiring replacement or revision. Patients received a median of four doses of 24-h gemcitabine infusion. Two patients developed grade 3 and 4 duodenal ischemia and upper gastrointestinal bleeding. Median overall survival was 15.3 months and median time to progression was 3 months. Three patients (50 %, n = 3/6) progressed systemically. Two patients had stable disease >4 months following treatment and underwent pancreaticoduodenectomy. CONCLUSIONS: While technically feasible to treat locally advanced pancreatic ductal adenocarcinoma, prolonged regional pancreatic perfusion with gemcitabine following pancreatic arterial redistribution carries a high risk for gastrointestinal toxicity. Shorter infusion schedules with frequent on treatment evaluations should be considered for future clinical trials.

Brunner's gland lesions in rats induced by a vascular endothelial growth factor receptor inhibitor.

Vascular endothelial growth factor (VEGF) receptor tyrosine kinase (RTK) inhibitors are reported to cause reversible mucosal hyperplasia (adenosis) in the duodenum of rats; however, the pathogenesis is not fully elucidated. Using lenvatinib, a VEGF RTK inhibitor, we characterized the histologic time course of this duodenal change in rats. At 4 weeks, there was degeneration and necrosis of Brunner's gland epithelium accompanied by neutrophil infiltration around the affected glands. At 13 weeks, the inflammation was more extensive, and Brunner's gland epithelium was attenuated and flattened and was accompanied by reactive hyperplasia of duodenal epithelium. At 26 weeks, the changes became more severe and chronic and characterized by marked cystic dilation, which extended to the external muscular layer. These dilated glands exhibited morphological characteristics of duodenal crypt epithelium, suggestive of replacement of disappeared Brunner's glands by regenerative duodenal crypt epithelial cells. Similar changes were not present in similar time course studies in dog and monkey studies, suggesting that this is a rodent- or species-specific change. Based on the temporal progression of Brunner's gland lesion, we identify degeneration and necrosis of the Brunner's glands as the primary change leading to inflammation, cystic dilatation, and regeneration with cells that are morphologically suggestive of duodenal crypt epithelium.

Spontaneous intramural small-bowel hematoma secondary to anticoagulant therapy: a case series.

Spontaneous small-bowel hematomas most commonly involve the jejunum, followed by the ileum and duodenum, and occur in patients who receive excessive anticoagulation with phenprocoumon/warfarin or who have additional risk factors for bleeding. We report three cases of intramural small-bowel hematoma, all complications of treatment with phenprocoumon, which nowadays is used extensively for therapeutic and prophylactic purposes. Diagnosis can be readily attained by sonography and confirmed using computed tomography. Early diagnosis is crucial because most patients can be treated successfully without surgery. Based on this experience and data from the literature, conservative treatment is recommended for intramural intestinal hematomas, when other complications needing laparotomy have been excluded.

Mortality and end-stage renal disease incidence among dry cleaning workers.

OBJECTIVE: Perchloroethylene (PCE) is a known animal carcinogen and probable human carcinogen. Dry cleaning exposures, particularly PCE, are also associated with renal toxicity. The objective was to follow-up a cohort of dry cleaners to evaluate mortality and assess end-stage renal disease (ESRD) morbidity. METHODS: This study adds 8 years of mortality follow-up for 1704 dry cleaning workers in four cities. Employees eligible for inclusion worked for ≥1 year before 1960 in a shop using PCE as the primary solvent. Life table analyses for mortality and ESRD morbidity were conducted. Only employees alive on 1 January 1977 were included in ESRD analyses. RESULTS: Overall cancer deaths were in significant excess in this cohort (standardised mortality ratio (SMR) 1.22, 95% CI 1.09 to 1.36). Oesophageal, lung and tongue cancers had significant excesses of deaths. Oesophageal cancer risk was highest among those employed in a PCE-using shop for ≥5 years with ≥20 years' latency since first such employment. Deaths from non-malignant underlying diseases of the stomach and duodenum were in significant excess. Hypertensive ESRD morbidity was significantly elevated in the entire cohort (standardised incidence ratio (SIR) 1.98, 95% CI 1.11 to 3.27), and among workers employed only in PCE-using dry cleaning shops for ≥5 years. CONCLUSION: Employment in the dry cleaning industry and occupational exposure to PCE are associated with an increased risk for ESRD and for cancer at several sites. The employment duration findings for oesophageal cancer and hypertensive ESRD further support an association with PCE exposure instead of lifestyle or socioeconomic factors.

Rescue strategies against non-steroidal anti-inflammatory drug-induced gastroduodenal damage.

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed drugs worldwide, which attests to their efficacy as analgesic, antipyretic and anti-inflammatory agents as well as anticancer drugs. However, NSAID use also carries a risk of major gastroduodenal events, including symptomatic ulcers and their serious complications that can lead to fatal outcomes. The development of "coxibs" (selective cyclooxygenase-2 [COX-2] inhibitors) offered similar efficacy with reduced toxicity, but this promise of gastroduodenal safety has only partially been fulfilled, and is now dented with associated risks of cardiovascular or intestinal complications. Recent advances in basic science and biotechnology have given insights into molecular mechanisms of NSAID-induced gastroduodenal damage beyond COX-2 inhibition. The emergence of newer kinds of NSAIDs should alleviate gastroduodenal toxicity without compromising innate drug efficacy. In this review, novel strategies for avoiding NSAID-associated gastroduodenal damage will be described.

Correlation between erosive oesophageal and gastro-duodenal diseases. the influence of aspirin, simple analgesics, and Helicobacter pylori.

OBJECTIVE: Previous erosive oesophagitis studies have excluded patients with peptic ulcers or taking aspirin, and conflicting results have been reported concerning the influence of. We aimed to study the possible correlation between erosive oesophageal and gastro-duodenal diseases in patients with or without erosive oesophagitis who are taking low-dose aspirin, or simple analgesics, or those infected with. METHODS: Endoscopic oesophageal and gastro-duodenal lesions were graded in 287 patients with reflux oesophagitis, median age 57 years, including 168 with oesophageal erosions, 131 infected with, 45 patients taking aspirin 75 mg daily, and 65 patients taking simple analgesics containing paracetamol/codeine. RESULTS: The grades of oesophageal erosions correlated positively with the duodenal scores (r = 0.15; P = 0.01) in the study group as a whole (n = 287), and in patients (n = 131) with (r = 0.169; P = 0.05). Eighty of 168 patients with erosive oesophagitis had (48%), compared with 51 of 119 patients (43%) with non-erosive oesophageal disease (P = 0.47). Oesophageal scores were highest in the aspirin group (P = 0.04; Kruskal-Wallis test), with grades > or =3 being found in 36% of patients on aspirin, 22% on simple analgesics, and in 18% of other patients. CONCLUSIONS: The degree of oesophageal damage correlates positively with that in the duodenal mucosa, although the overall prevalence of erosive oesophagitis is not influenced by. Also, patients taking aspirin have a greater degree of oesophageal damage. These indicate the presence of a common process mediating both oesophageal and duodenal diseases in at least some patients with these disorders.