Diagnosis and evaluation of intestinal graft-versus-host disease after allogeneic hematopoietic stem cell transplantation following reduced-intensity and myeloablative conditioning regimens

Colonoscopic evaluation of mucosal tissues after allogeneic hematopoietic stem cell transplantation (HSCT) is very useful in evaluating pathogenesis and diagnosis of intestinal graft-versus-host disease (GVHD). However, information on the timing and sites of biopsies and the immunohistological evaluation of mucosal tissues for diagnosing intestinal GVHD, especially following reduced-intensity (RIC) regimens, remains very limited. A total of 33 patients with histologically proven GVHD after allogeneic HSCT with RIC (n = 23) and myeloablative conditioning (MAC, n = 10) regimens were enrolled in the present study. Colonoscopy was performed due to gastrointestinal symptoms, especially diarrhea and anorexia. Sites of biopsies with the worst histopathological grading were the terminal ileum in 67 % of patients. In the RIC group, the onset of diarrhea prior to colonoscopy examination was later (median: RIC, 57 vs. MAC, 27 days) and the number of patients who developed abdominal pain tended to be higher (RIC, 70 % vs. MAC, 30 %). A lower number of CD4+ cells and a higher ratio of Foxp3+ cells to CD4+ cells were detected in the involved lesions of intestinal GVHD following RIC. These differences in the RIC and MAC groups suggest that regimen-specific therapeutic strategies are required for diagnosing intestinal GVHD.     

Upregulation of P53 protein in rat heart subjected to a transient occlusion of the coronary artery followed by reperfusion

The accumulation of p53 protein in cardiomyocyte nuclei was immunohistochemically demonstrated by the pronounced staining of p53 antibody in 4 h-reperfused ventricular tissue after a 45-min coronary occlusion. The occurrence of apoptosis in the reperfused ventricular tissue was evidenced by positive TUNEL staining and DNA laddering on agarose gels.     

Preoperative retrolisthesis as a predictive risk factor of reoperation due to delayed-onset symptomatic foraminal stenosis after central decompression for lumbar canal stenosis without fusion

Background Context

For patients diagnosed with lumbar central canal stenosis with asymptomatic foraminal stenosis (FS), surgeons occasionally only decompress central stenosis and preserve asymptomatic FS. These surgeries have the potential risk of converting preoperative asymptomatic FS into symptomatic FS postoperatively by accelerating spinal degeneration, which requires reoperation. However, little is known about delayed-onset symptomatic FS postoperatively.

A Propensity Score-Based Analysis of Laparoscopic Liver Resection for Liver Malignancies in Elderly Patients

Purpose: Laparoscopic liver resection is safe, feasible and associated with less blood loss, shorter hospital stays and fewer postoperative complications in the working age patients with malignant liver tumors. However, it is still unclear if the elderly patients with malignant liver tumors would also benefit from that approach as the younger patients. So, the aim of the study was to compare the clinical outcomes of laparoscopic versus open liver resection for malignant liver tumors in elderly patients. Materials and Methods: Between March 2009 and July 2016, all elderly patients (≥70 years old) who underwent laparoscopic (n = 40) and open (n = 202) liver resection for malignant liver tumors were included. A one to one propensity score matching analysis was performed, based on 6 covariates, to decrease the selection bias. Results: There was no significant difference between the laparoscopic and open liver resection groups regarding the patient characteristics and tumor features. The operative time was comparable between both groups (Laparoscopic group 259 min vs Open group 308 min, p = .86), while patients who underwent laparoscopic liver resection had lower intraoperative blood loss (30 ml vs 517 ml, p < .0001), shorter hospital stays (10 days vs 23 days, p < .0001), and less overall morbidity (15% vs 38%, p = .04). The one-, three-, and five-year survival for patients with hepatocellular carcinoma was comparable between both groups (Laparoscopic group 96%, 74%, 47%, vs Open group 94%, 71%, 48%, p = .82), whereas The one-, three-, and five-year recurrence-free survival for patients with hepatocellular carcinoma was significantly higher in the laparoscopic group (88%, 60%, 60% vs 54%, 25%, 19%, p = .019). Conclusions: Laparoscopic approach for minor liver resection in elderly patients is safe and feasible with less blood loss, a shorter hospital stay, less postoperative complications and a better oncological outcome.     

Impact of total body irradiation on successful neutrophil engraftment in unrelated bone marrow or cord blood transplantation

Total body irradiation (TBI) has been thought to promote donor cell engraftment in allogeneic hematopoietic cell transplantation (HCT) from alternative donors. However, recent progress in HCT strategies may affect the clinical significance of TBI on neutrophil engraftment. With the use of a Japanese transplant registry database, we analyzed 3933 adult recipients (>15 y.o.) who underwent HCT between 2006 and 2013 from an 8/8 HLA‐matched unrelated bone marrow donor (MUD, n = 1367), an HLA‐mismatched unrelated bone marrow donor (MMUD, n = 1102), or unrelated cord blood (CBT, n = 1464). Conditioning regimens were divided into five groups: High‐TBI‐(>8Gy), Low‐TBI‐ (≤8Gy), and no‐TBI‐myeloablative conditioning (MAC), and Low‐TBI‐ and no‐TBI‐reduced‐intensity conditioning (RIC). In both MUD and MMUD, neutrophil engraftment rate was >90% in each of the five conditioning groups, and TBI was not associated with prompt neutrophil engraftment in multivariate analyses. Conversely, in CBT, TBI regimens had a higher rate of day‐30 neutrophil engraftment than no‐TBI‐regimens: 78% in High‐TBI‐MAC, 83% in Low‐TBI‐MAC, and 76% in Low‐TBI‐RIC versus 65% in No‐TBI‐MAC, and 68% in No‐TBI‐RIC (P < .001). Multivariate analyses in CBT demonstrated that TBI‐regimens were significantly associated with a higher rate of neutrophil engraftment. Subsequently focusing on CBT patients alone, TBI‐regimens were significantly associated with a higher rate of neutrophil engraftment in patients who received CBT with a 4/6 or less HLA allele‐match, or who had anti‐HLA antibodies. In summary, TBI‐regimens had no impact on neutrophil engraftment in the current practice of unrelated bone marrow transplantation. However, in CBT, TBI is still necessary to enhance engraftment.     

Expression and activity of transglutaminase II in spontaneous tumours of dogs and cats

Tissue transglutaminase II (TGase II) is a dual function protein with both transamidating and guanidine triphosphate (GTP)-binding capabilities. Previous studies have implicated TGase as a pro-apoptotic molecule; however, our recent findings indicate that TGase II may act as a survival factor in various cell types. The purpose of this study was to survey TGase II expression in normal tissue and spontaneous tumours of dogs and cats, by Western blotting and immunohistochemistry. Bladder, liver and adrenal gland exhibited prominent expression of TGase II while other tissues, including mammary gland, displayed limited expression and activity. TGase II GTP-binding in normal tissues was proportional to the level of expression in all tissues examined. Normal mammary tissue and that showing benign hyperplasia did not express TGase II. However, 11/25 (44%) of canine mammary carcinomas and 10/12 (83%) of feline mammary carcinomas strongly expressed TGase II in either a stromal, cellular or combined pattern. The pattern of expression was not related to the classification of mammary carcinoma (solid, tubulopapillary, complex or anaplastic), except that two anaplastic canine mammary carcinomas showed prominent TGase II expression. Two canine mammary carcinoma cell lines showed prominent TGase expression, and when the TGase activity was inhibited, the cells became more sensitive to doxorubicin-induced cell death. Thus, TGase II was significantly expressed in mammary cancers from dogs and cats and immunoreactivity of TGase II was similar to that reported in humans beings. The pro-survival effect of TGase II in canine mammary carcinoma cell lines was similar to that previously reported in humans patients.     

Improved QOL in a case of remnant gastric cancer with common bile duct obstruction treated with weekly paclitaxel therapy and cholecystojejunostomy

We report a patient with unresectable remnant gastric cancer with common bile duct stricture, whose quality of life(QOL) was improved by switching to cholecystojejunostomy from percutaneous transhepatic gallbladder drainage(PTGBD). He was a 69-year-old man who underwent distal gastrectomy(Billroth I reconstruction)3 years previously, and he vomited many times due to cancer at the anastomosis. It could not be resected because of its involvement with the hepatoduodenal ligament, and therefore, gastrojejunostomy was performed. Four days later, abdominal pain occurred and gallbladder swelling was observed, resulting from common bile duct obstruction. PTGBD relieved the pain, and four courses of S-1/cisplatin (CDDP)treatment were performed. The bile duct stenosis was still so severe that the chemotherapy regimen was changed to weekly paclitaxel(PTX). The bile amount of PTGBD decreased after its four courses and the tube, which was a great burden for the patient, was removed. Because abdominal pain recurred in 2 weeks, the tube needed to be reinserted. An endoscopic stent was not inserted successfully. We performed cholecystojejunostomy and he was finally free from the PTGBD tube. The spread of cancer to the cystic duct was controlled by continuing the PTX for more than 20 courses. Thus, this case highlights PTX's contribution toward improving the patient's QOL.     

Long‐term follow‐up after proton beam therapy for pediatric tumors: a Japanese national survey

Proton beam therapy (PBT) is a potential new alternative to treatment with photon radiotherapy that may reduce the risk of late toxicity and secondary cancer, especially for pediatric tumors. The goal of this study was to evaluate the long‐term benefits of PBT in cancer survivors. A retrospective observational study of pediatric patients who received PBT was performed at four institutions in Japan. Of 343 patients, 62 were followed up for 5 or more years. These patients included 40 males and 22 females, and had a median age of 10 years (range: 0–19 years) at the time of treatment. The irradiation dose ranged from 10.8 to 81.2 GyE (median: 50.4 GyE). The median follow‐up period was 8.1 years (5.0–31.2 years). The 5‐, 10‐ and 20‐year rates for grade 2 or higher late toxicities were 18%, 35% and 45%, respectively, and those for grade 3 or higher late toxicities were 6%, 17% and 17% respectively. Univariate analysis showed that the irradiated site (head and neck, brain) was significantly associated with late toxicities. No malignant secondary tumors occurred within the irradiated field. The 10‐ and 20‐year cumulative rates for all secondary tumors, malignant secondary tumors, and malignant nonhematologic secondary tumors were 8% and 16%, 5% and 13%, and 3% and 11%, respectively. Our data indicate that PBT has the potential to reduce the risk of late mortality and secondary malignancy. Longer follow‐up is needed to confirm the benefits of PBT for pediatric tumors.