Gastrointestinal (GI) complications including graft-versus-host disease (GVHD) are a major cause of morbidity and mortality in allogenic stem transplant recipients. Although several studies have previously looked into the acute GI complications, fewer smaller studies have reported late complications. In this large study we focus on the late (100 days post-transplant) GI complications in allogenic stem transplant recipients. In this single-center, retrospective study of all adult allogenic stem cell transplant recipients who had their transplant at Duke University over a 6-year period, 479 patients underwent allogenic stem cell transplant, of whom 392 recipients survived for at least 100 days post-transplant. Late GI symptoms were noted in 71 patients, prompting endoscopic evaluation. The primary endpoint of our study was the diagnosis of GI-GVHD based on endoscopic findings, whereas overall survival and nonrelapse mortality were the secondary endpoints. Of the 71 patients who underwent endoscopy, 45 (63%) had GI-GVHD. Of these 45 patients, 39 (87%) had late acute GVHD, 1 (2%) had chronic GVHD, and 5 patients (11%) had overlap disease. Of the patients who did not have GVHD, the symptoms were mostly related to infectious and inflammatory causes. Less common causes included drug toxicity, food intolerance, disease relapse, and motility issues. In a multivariate analysis the factors most indicative of GI-GVHD were histologic findings of apoptosis on the tissue specimen (odds ratio, 2.35; 95% confidence interval, 1.18 to 4.70; P = .015) and clinical findings of diarrhea (odds ratio, 5.43; 95% confidence interval, 1.25 to 23.54; P = .024). The median survival time from the first endoscopy was 8.5 months. The incidence of nonrelapse mortality at 6 months was 31% in patients with GI-GVHD and 19% in patients without GI-GVHD (P = .42). All patients with GI-GVHD were on steroid therapy, and 31% of them received total parenteral nutrition. In our population close to one-fifth of allogenic transplant recipients experienced late GI complications, warranting endoscopic evaluation. Most of these patients were found to have GI-GVHD that had a high incidence of nonrelapse mortality at 6 months and close to one-third of these patients needed total parenteral nutrition.

Background Graft-versus-host disease (GVHD) complicates half of hematopoietic stem cell transplants (HCT), and the gastrointestinal tract is commonly affected. Endoscopic biopsies have a key role in the diagnosis. The optimal procedure(s) to perform and site(s) to biopsy remain unclear. Methods We retrospectively analyzed the charts of all adult patients who underwent allogeneic HCT at Duke University Medical Center between 1/1/05 and 1/1/11 and extracted data from those who underwent endoscopic biopsy for suspected GVHD. All histology was re-evaluated by blinded pathologists using 2006 NIH diagnostic criteria and then compared to the original clinical diagnosis of GVHD. Results A total of 169 adult patients underwent 250 endoscopic procedures to evaluate GVHD. The sensitivity of biopsies for clinical GVHD was 76 and 72 % for upper and lower tract sites, respectively. In the presence of nausea, upper tract biopsies were positive for GVHD in 65 %, 70 % while lower tract biopsies were positive in 61–70 %. In the presence of diarrhea, lower tract biopsies were positive in 65 %, while upper tract sites were positive in 64–69 %. Twenty six (40 %) of the sixty-five endoscopies that simultaneously sampled upper and lower tract sites had discordant results. All were histologically positive for GVHD, yet 15 % of upper tract biopsies and 25 % of lower tract biopsies were negative. Conclusions In this large review, the overall sensitivity of biopsies taken during EGD and Flex-Sig was 76 and 72 %, respectively. A symptom-driven biopsy approach was not clearly supported as upper tract and lower tract biopsies were similarly diagnostic for GVHD regardless of symptoms.

Brincidofovir (CMX001) is an oral agent with activity against double-strand DNA viruses undergoing clinical trials in immunocompromised patients. We report a patient clinically diagnosed with brincidofovir-related gastrointestinal (GI) toxicity and his histologic findings. A 2-year-old boy with medulloblastoma undergoing autologous hematopoietic cell transplantation developed adenovirus viremia 9 days posttransplant. After initial treatment with intravenous cidofovir he was started on oral brincidofovir as part of a clinical trial. He developed hematochezia, anorexia, and emesis 11 weeks later. Sigmoid colon biopsy showed marked crypt drop out, moderate epithelial apoptosis, and lamina propria edema. The pathologic diagnosis was drug-related injury versus infection. Brincidofovir toxicity was diagnosed clinically and the drug was discontinued. His GI symptoms improved in 2 weeks with supportive care and octreotide. Brincidofovir causes GI toxicity and histologically demonstrates epithelial apoptosis and crypt injury, similar to graft versus host disease and mycophenolate mofetil toxicity.

Background. Perineural invasion (PNI) is an adverse prognostic histologic finding and increases the risk of local recurrence and metastasis. Objective. We aimed to determine if dual immunohistochemical (IHC) staining with S-100 and AE1/3 would increase the detection of PNI on nonmelanoma skin cancers (NMSCs). Methods. We collected 45 specimens of NMSCs in which there was clinical suspicion for PNI. Two dermatopathologists independently reviewed the tumors for the unequivocal presence of PNI. Results. Unequivocal PNI was present on 10 of the 45 tumors by H&E staining and on 15 of the 45 tumors by IHC staining. Large nerves (>0.1 mm) were involved in 3 of 10 H&E-stained cases and 3 of 15 IHC-stained cases, with 2 of the 4 cases demonstrating large nerve involvement with both staining methods. Of the 8 cases of PNI detected only on IHC, 7 were small nerves (≤0.1 mm). Limitations. All cases were selected because they were clinically suspicious for PNI, and this may be considered selection bias. Conclusions. PNI detection may be increased using dual S-100 and AE1/3 staining, but the majority of additional cases detected were small nerves. The clinical significance, given the small size of the involved nerves, is unclear.

- Use of the NIH histology consensus guidelines results in a high sensitivity and specificity, thereby decreasing false-negatives. Additionally, use of the NIH guidelines aids in creating uniformity and diagnostic clarity. Correlation with clinical and laboratory findings is critical in evaluating the differential diagnosis and to avoid false-positives. As expected, increased apoptosis with decreased inflammation was associated with a pathologic diagnosis of graft-versus-host disease and supports the NIH guidelines.

Familial adenomatous polyposis (FAP) is a rare inherited syndrome that is characterised by innumerable adenomas of the colon and rectum, a high risk of colorectal cancer and a variety of extracolonic manifestations. FAP presents as hundreds to thousands of colonic adenomas beginning in adolescence. The syndrome is associated with less than 1% of all colorectal cancer cases, but there is a nearly 100% lifetime risk of colorectal cancer in individuals with FAP. This case demonstrates a 60-year-old man with FAP who developed high-grade neuroendocrine carcinoma with glandular and squamous differentiation, and regional lymph node and liver metastases. Early diagnosis of FAP is of the utmost importance to start screening colonoscopies to assess disease burden, perform polypectomies and to make management decisions. Neuroendocrine carcinomas rarely occur in patients with FAP, and awareness of this association among general medical physicians and pathologists is essential for the diagnosis and care of these patients.

A case of suicidal death due to intravenous self-administration of vecuronium and etomidate by a registered nurse is being reported. Toxicologic blood analysis showed a vecuronium concentration of 0.023 mg/L, an etomidate concentration of 0.041 μg/mL, and an ethanol concentration of 113 mg/dL. The autopsy, toxicologic analysis, and crime scene investigation findings indicated that this was suicidal death caused by respiratory failure secondary to vecuronium administration exacerbated by sedation secondary to etomidate and ethanol use. Review of the medical literature and popular press media has identified several instances in which vecuronium has been used in homicidal deaths, but it has identified few cases in which vecuronium or etomidate, alone or in conjunction with another drug, have been used to commit suicide.

mg/kg/day on days-3 and-2) and TBI (2 Gy on day-1). GVHD prophylaxis consisted of Cy (50 mg/kg/day on days 3 and 4), tacrolimus (days 5 to 180), and mycophenolate mofetil (days 5 to 60). Our primary endpoint was the incidence of nonrelapse mortality (NRM) at day 100. Secondary endpoints included overall survival (OS), disease-free survival (DFS), the incidence of engraftment, acute GVHD, and relapse. Results: Median age was 48 (range 21-65) with 22 male and 9 female. Diagnosis of the patients included AML (n¼17), ALL/LBL (n¼8), MDS/MPN (n¼4), and lymphoma (n¼2). The majority (61.3%) of patients were not in remission and 13 patients (41.9%) had a history of prior allogeneic stem cell transplantation (allo-SCT). Twenty-seven patients (87.1%) engrafted with median neutrophil engraftment on 19 days (range 15-27). The cumulative incidence of grades II-IV and III-IV acute GVHD at day 100 was 22.6% (95% CI, 9.8-38.6%) and 3.2% (95% CI, 0.2-14.4%), respectively. NRM at day 100 was 19.4% (95% CI, 7.7-34.9%). Cumulative incidence of relapse at day 100 was 19.4% (95% CI, 7.7-35.0%). With a median follow-up of 171 days, OS and DFS was 74.2% (95% CI, 55.0-86.2%) and 61.3% (95% CI, 42.0-75.8%), respectively, at day 100. Subgroup analysis showed that patients who had a history of prior allo-SCT had higher NRM (30.8% vs. 11.1%, p¼0.07) and less lower OS (53.8% vs. 83.9%, p¼0.03) than those in patients without a history of prior allo-SCT. Conclusions: Our results suggest that posttransplant Cy based HLA-haploidentical PBSCT after busulfan containing reduced-intensity conditioning achieves stable donor engraftment and low incidence of GVHD. NRM was acceptable in the setting of the first allo-SCT. Given the promising results of GVHD and NRM, phase II study in much larger scale are now under investigation.