Cyclin D2 is overexpressed in proliferation centers of chronic lymphocytic leukemia/small lymphocytic lymphoma

The D cyclins are important cell cycle regulatory proteins involved in the pathogenesis of some lymphomas. Cyclin D1 overexpression is a hallmark of mantle cell lymphoma, whereas cyclins D2 and D3 have not been shown to be closely associated with any particular subtype of lymphoma. In the present study, we found that cyclin D2 was specifically overexpressed in the proliferation centers (PC) of all cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) examined (19/19). To examine the molecular mechanisms underlying this overexpression, we immunohistochemically examined the expression of nuclear factor (NF)-κB, p15, p16, p18, and p27 in the PC of six patients. Five cases showed upregulation of NF-κB expression, which is known to directly induce cyclin D2 by binding to the promoter region of CCND2. All six PC examined demonstrated downregulation of p27 expression. In contrast, upregulation of p15 expression was detected in five of six PC examined. This discrepancy suggests that unknown cell cycle regulatory mechanisms involving NF-κB-related pathways are also involved, because NF-κB upregulates cyclin D2 not only directly, but also indirectly through c-Myc, which is believed to downregulate both p27 and p15. In conclusion, cyclin D2 is overexpressed in the PC of CLL/SLL and this overexpression is due, in part, to the upregulation of NF-κB-related pathways.     

Case of sarcomatoid carcinoma of the urinary bladder

A 57-year-old man was referred to our hospital for bladder tumor. The computed tomographic scan demonstrated an 8 cm solid mass in the posterior wall of the bladder. Cystoscopy revealed a non-papillary large bulky tumor and a necrotic tumor surface. The tumor was transurethrally resected and its histology showed sarcomatoid carcinoma composed of a urothelial cell carcinoma. Total cystectomy was performed and an ileal neobladder was constructed. He now shows no evidence of disease 43 months after the operation.     

A simple controlled-rate freezing method without a rate-controlled programmed freezer provides optimal conditions for both large-scale and small-scale cryopreservation of umbilical cord blood cells

BACKGROUND: Umbilical cord blood (CB) is being used as a source of alternative HPCs for transplantation with increasing frequency. The goal of CB banks for unrelated transplantation is to provide good quality-controlled CB units that can be transplanted for HPCs into the largest possible number of patients. STUDY DESIGN AND METHODS: Large CB samples in freezing bags wrapped with insulators and small samples in cryotubes placed into double styrene-foam boxes were cryopreserved at -85 degrees C without a rate-controlled freezing machine, followed by storage in the liquid phase of nitrogen. After thawing these cells, the viability and recovery of cells, as well as the recovery rate of HPCs such as CD34+ cells, CFU-GM, and total CFU were evaluated. RESULTS: Measurement of the freezing rate in CB bags and cryotubes demonstrated that this simple method for cryopreservation of CB cells provided optimal conditions for both large-scale and small-scale cryopreservation. Recovery of CB progenitor cells after cryopreservation was also shown to be potentially acceptable when evaluated with CD34+ cells, CFU-GM, and total CFU. These results were comparable to the method using a rate-controlled programmed freezer. CONCLUSIONS: A simple method for cryopreservation of CB cells without a rate-controlled programmed freezer could provide a sufficient-enough potential for the transplantability of HPCs after thawing.     

Schwannoma mimicking pancreatic carcinoma: A case report

BACKGROUNDSchwannoma of the pancreas is extremely rare. We report a case of pancreatic schwannoma that was difficult to distinguish from pancreatic carcinoma before surgery.CASE SUMMARYA 66-year-old male underwent a right-lobe hepatectomy for hepatocellular carcinoma. Post-surgical computed tomography showed a 10 mm long solid mass with ischemia, with no expansion into the main pancreatic duct. Upon magnetic resonance cholangiopancreatography, the tumor had high signal intensity in diffusion weighted images, consistent with pancreatic carcinoma. Endoscopic ultrasound (EUS) was performed to obtain more information about the tumor, and showed a 14 mm solid and hypoechoic mass in the pancreatic body. Contrast enhanced EUS revealed that the tumor showed a hyperechoic mass in the early phase, and the contrasting effect continuation was very short; findings also consistent with pancreatic carcinoma. Thus, we preoperatively diagnosed his condition as a pancreatic carcinoma and performed distal pancreatectomy with splenectomy. Microscopic examination showed that the tumor was in fact a benign schwannoma. Histology showed a proliferation of spindle-shaped cell in a vague fascicular and haphazard pattern, with palisading arrangement.CONCLUSIONSchwannoma of the pancreas is very rare, however, clinicians should consider schwannoma as the differential diagnosis for pancreatic tumors.     

Comparing outcomes of nonoperative treatment for adhesive small bowel obstruction with and without antibiotics

IntroductionSome clinicians administer antibiotics in adhesive SBO treatment to prevent bacterial translocation without evidence confirming reduced sepsis and mortality. We aimed to evaluate the effectiveness of preventive antibiotic administration in nonoperative treatment of adhesive small bowel obstruction (SBO) in a retrospective study.MethodsUsing a Japanese national inpatient database, we identified 114,786 eligible patients with adhesive SBO and divided patients into a group who did not receive intravenous antibiotics in the initial 2 consecutive days after admission (control group, n = 71,666) and a group who received intravenous antibiotics ≥2 days after admission (antibiotic group, n = 43,120). To compare the in-hospital mortality, occurrence of sepsis, septic shock, Clostridioides difficile colitis, length of stay, and total costs between the two groups, we performed instrumental variable analyses to adjust for measured and unmeasured confounding factors.ResultsOverall, in-hospital mortality was 2.2%, and the occurrence of sepsis was 0.8%. In the instrumental variable analyses, no significant differences were found for in-hospital mortality, occurrence of sepsis, septic shock, Clostridioides difficile colitis, or total hospitalization costs. The antibiotic group showed a longer length of stay than the control group (coefficient, 1.9 days; 95% confidence interval, 0.6–3.2).ConclusionsIn this large nationwide cohort of patients with adhesive SBO, we found no benefit regarding preventive antibiotic administration in nonoperative treatment; however, antibiotic administration was associated with a longer hospital stay. These results did not support routine administration of antibiotics at admission to prevent bacterial translocation.     

Automated imaging and quantitation of tumor cells and CFU-GM colonies in microcapillary cultures: toward therapeutic index-based drug screening

Human colony forming units (CPUs) from both malignant and hematopoietic tissues can be assayedin vitro in microcapillary cultures, an alternative cloning system to the Petri dish methodology. For technical reasons, microcapillary culture may be ideally suited for new drug screening by therapeutic index. To achieve the high output required by screening programs, automated quantitation of CFUs is required. Toward this end, this paper reports the development of a prototype CapScan^TM, an image analysis system that uses a novel axial laser illumination system to detect tumor cell colonies and, with technical modifications, CFU-granulocyte-macrophage (CFU-GM) colonies in microcapillary cultures. As currently configured, the CapScan can quantify colonies grown in a rack of 18 microcapillary cultures in 30 minutes or less. The sensitivity and detection specificity of tumor cell colonies is >90% with a coefficient of variance of 5–40%, dependent upon colony number. Over a range of colony numbers, CapScan and manual colony counts showed a linear correlation >–0.9, and yielded identical results in assays of doxorubicin inhibition of clonogenic P388 cells. As an additional advantage, the growth kinetics of individual colonies can also be monitored with the CapScan, making distinctions between cytotoxic and cytostatic drugs possible; colonies of freshly isolated human tumor cells can also be quantified. Thus, a microcapillary-based human tumor cloning assay that tests for resistance and/or sensitivity to chemotherapeutic agents may be useful in drug development programs and may also facilitate the development of chemotherapy for individual patient tumors, especially when tumor availability is limited.