[A Case of Surgically Treated Primary Anorectal Malignant Melanoma Detected by Colorectal Cancer Screening].

Anorectal malignant melanoma(AMM)is a relatively rare disease with an extremely poor prognosis. We experienced a case of this disease detected by colorectal cancer screening and report it here with a literature review. Our 67-year-old female patient was referred to the Department of Gastroenterology at our hospital for a thorough examination of the gastrointestinal tract after an abnormal fecal occult blood count(+/+ on 2 occasions)was noted during a colorectal cancer screening. Lower gastrointestinal endoscopy revealed a small easily bleeding lesion near the anal verge for which endoscopic mucosal resection was performed. A histopathological examination revealed a primary malignant melanoma of the rectum, and the patient underwent abdominoperineal rectal amputation. According to the rules for the treatment of T1b (1,200 µm), N0, P0, H0, M(-), StageⅠ, Cur A colorectal cancer. A histopathological examination of the resected specimen showed no remnant tumor cells. About 2 years have passed since the surgery, and the patient is still alive without recurrence. Considering its characteristics, patients with AMM will require further careful follow-up. Here we summarize our experience diagnosing and treating a case of early-stage AMM.

Unusual case of tacrolimus vascular toxicity after deceased donor renal transplantation.

We report a case of tacrolimus vascular toxicity found on a protocol biopsy shortly after a deceased donor renal transplantation. The patient was immunologically high-risk and acute antibody-mediated rejection during post-transplant dialysis phase was suspected on the protocol biopsy. Although the patient was stable after treatment of rejection, a further examination showed a very rare but specific side-effect of tacrolimus. It is sometimes difficult to make a differential diagnosis during postoperative dialysis period among AMR, primary non-functioning, drug toxicity, infection or just prolonged recovery from the damage of a long agonal phase on the non-heart beating donor. Although the possibilities of coexistence of rejection or other causes such as infection have not been completely excluded, it is important to be aware of this unusual side effect of tacrolimus.

Biopsy findings on a stable recipient after secondary donor specific antibody (DSA) positive and ABO incompatible kidney transplantation.

Using desensitization protocol, we performed a secondary donor specific antibody (DSA) positive and ABO incompatible kidney transplantation. One-hour biopsy showed no C4d deposition. The protocol biopsy after 2 weeks showed diffuse C4d deposition with peritubulitis. After 12 weeks, however, the protocol biopsy showed disappearance of tubulitis in spite of remaining C4d deposition. The recipient was in stable condition with excellent graft function despite high titer of the DSA. Monitoring of protocol biopsy is critical while antibody titer and the interpretation of the histological findings correlating with clinical markers must be considered.

Pancreas transplantation: a single-institution experience in Japan.

PURPOSE: We herein report our experience with pancreas transplantation in 26 patients at a single institution in Japan between August 2001 and December 2011. METHODS: We reviewed the medical records of 26 pancreas transplantations performed in our institute. RESULTS: The early complications (within 2 weeks) included one graft venous thrombosis, one arterial thrombosis, and two reoperations for bleeding. Of the 26 pancreas transplant recipients, five lost pancreas graft function. Of 24 simultaneous pancreas-kidney recipients, three lost kidney graft function due to noncompliance. The patient, pancreas, and kidney survival rates were 100, 96 and 93 % at 1 year; 100, 80 and 93 % at 5 years; and 100, 67 and 68 % at 10 years, respectively. Of all these complications, venous thrombosis after pancreas transplantation was the most critical. CONCLUSIONS: As the largest series of pancreas transplantations in a single institution in Japan, our series yielded better results than the worldwide data recorded by the International Pancreas Transplant Registry. Routine postoperative anticoagulation therapy is not necessary for the prevention of graft thrombosis if sufficient fluid infusion is strictly controlled and the graft blood flow is frequently monitored. When graft thrombosis occurs, both early detection and appropriate intervention are extremely important if the pancreas graft is to survive.

Bisphenol A stabilizes Nrf2 via Ca2+ influx by direct activation of the IP3 receptor.

Bisphenol A (BPA) is an endocrine-disrupting chemical used in polycarbonate and epoxy resins. Previously, we found that BPA stabilized the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) by inducing Ca2+ efflux into the cytosol, followed by nitric oxide synthase activation, resulting in the enhanced nitrosylation of Keap1, which is a negative regulator of Nrf2. However, the mechanisms behind the stimulation of Ca2+ efflux by BPA remain unknown. In the present study, we found that BPA stimulated Ca2+ efflux into the cytosol from the ER, but not from outside of cells through the plasma membrane in Hep3B cells. Ca2+ efflux and Nrf2 stabilization by BPA were inhibited by an inhibitor of the inositol 1,4,5-trisphosphate (IP3) receptor, 2-aminoethoxydiphenylborane, in the endoplasmic reticulum. IP3 is produced by activation of phospholipase C (PLC) from a membrane lipid, phosphatidylinositol 4,5-bisphosphate (PIP2). The induction of Nrf2 by BPA was not inhibited by a PLC inhibitor, U-73122, suggesting that BPA does not induce the production of IP3 via PLC activation. We found that BPA bound directly to the IP3 binding core domain of the IP3 receptor, and BPA competed with IP3 on this site. In addition, overexpression of this domain of the IP3 receptor in Hep3B cells inhibited the stabilization of Nrf2 by BPA. These results clarified that the IP3 receptor is a new target of BPA, and that BPA induces Ca2+ efflux from the endoplasmic reticulum via activation of the IP3 receptor.

Preoperative white blood cell count predicts anastomotic leakage in patients with left-sided colorectal cancer.

To determine whether preoperative white blood cell (WBC) counts reflect risk of anastomotic leak (AL) for patients with colorectal cancer (CRC), we retrospectively examined data from records of 208 consecutive patients who had undergone resections for left-sided CRC, including their clinicopathological parameters and preoperative laboratory data. The diagnostic value of WBC count for AL was evaluated and compared with those of neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, lymphocyte-monocyte ratio and platelet count × C-reactive protein level multiplier (P-CRP) value; optimal cut-off values were derived from receiver operating characteristic curves. AL was observed in 11 of the 208 patients (5.3%). Compared with the no-AL group, the AL group had a significantly higher mean WBC count and smoking rate. In multivariate analysis, WBC count and smoking were independent risk factors for AL. Compared with the other tested inflammatory indicators, the cut-off value for WBC (6,200/µL) had the highest sensitivity (81.8%) and negative predictive value (98.4%), as well as the lowest likelihood ratio (0.289). Preoperative WBC count could therefore be a convenient predictor of AL in patients with left-sided CRC.

Evaluation of Blood Supply with Indocyanine Green Fluorescence in Resection for Concurrent Gastric and Pancreatic Cancer: A Case Report.

We present a rare case of concurrent resection of pancreatic and gastric cancer in which indocyanine green (ICG) fluorescence was used to evaluate the remnant stomach. An 80-year-old man was referred with a tumor in the distal pancreas. Computed tomography showed a 25-mm mass in the pancreatic tail; endoscopic ultrasound-guided fine-needle aspiration revealed adenocarcinoma. Upper gastrointestinal endoscopy and subsequent upper gastrointestinal series revealed advanced gastric cancer in the mid-stomach. Concurrent resection of the pancreatic and gastric tumors was performed. After distal pancreatectomy and distal gastrectomy, ICG evaluation of the stomach showed fluorescence extending only 3 cm distal from the cardia. To avoid ischemic change at the remnant stomach, total gastrectomy was performed. Since remnant gastric necrosis and anastomotic leak following ischemia can lead to fatal outcomes, the use of ICG to evaluate blood supply at anastomotic sites can help determine the extent of safe resection in such cases.

Risk analysis of feline immunodeficiency virus infection in Tsushima leopard cats (Prionailurus bengalensis euptilurus) and domestic cats using a geographic information system.

In this study, based on the data from FIV screening surveys of captive cats conducted by the Kyushu Veterinary Union and collaborators as part of the infection control program for Tsushima leopard cats (Prionailurus bengalensis euptilurus), we elucidated the spatial distribution of FIV-positive individuals among leopard cats and domestic cats using a geographic information system. Data from FIV screening surveys carried out among 86 leopard cats (1996-2006) and 713 captive domestic cats (2001-2006) were used for analysis. The analysis results were then spatially layered with the population density of leopard cats and that of captive domestic cats estimated from the number of households and used for assessment of FIV infection risk in each area. The prevalence rates of FIV were 3% (3/86) in leopard cats in Kami-shima, 13.6% (38/280) in domestic cats in Kami-shima and 10.6% (46/433) in domestic cats in Shimo-shima. The distribution of FIV on Tsushima Island was not uniform; on Kami-shima Island, FIV-positive domestic cats were concentrated in particular areas. We also performed risk analysis based on the population density of leopard cats, the prevalence rate of FIV among domestic cats in each area and the estimated population density of captive domestic cats and identified high FIV infection risk areas. All FIV-positive leopard cats were found in the identified high FIV infection risk areas.

[Current situation of pancreas transplantation in Japan].

Pancreas transplantation has been recognized as the best treatment for advanced type 1 diabetic patients. In Japan, we have performed 64 SPK, PAK or PTA from 62 brain-dead donors and two non-heart beating donors since the enforcement of Organ Transplant Act in 1997. In addition, 18 cases have been performed from living related donors. The patient survival, pancreas graft survival and kidney graft survival rate of the cadaveric transplantation at five years are 97.5%, 73.9% and 71.0%, respectively. The QOL of the recipients in both mental and physical aspects has been wonderfully improved leading to the happy second life. In front of the revised low in this year, the number of the donor and the transplantation are expected to increase.

Treatment of arteriovenous shunts after renal transplantation.

PURPOSE: Immunosuppressive drugs have improved the results of renal transplantation dramatically in recent years; however, there is still no consensus on the treatment of arteriovenous (A-V) shunts after successful transplantation. We evaluated the treatment of A-V shunts after transplantation. METHODS: We reviewed all patients who underwent shunt closure at our hospital between 2005 and 2007 assessing surgical methods, operative time, blood loss, and complications. RESULTS: Fifty-two patients underwent shunt closure, as a simple transection in 5 patients, resection of the anastomotic site in 16, resection and reconstruction of the artery in 26, and graftectomy in 5. Graftectomy was associated with copious blood loss and a long operative time. The most frequent complication was phlebitis, but there were no nerve complications. CONCLUSIONS: An A-V shunt after renal transplantation may result in an aneurysm, severe venous dilatation, pain, bloating of the arm, infection, and cardiac problems. Thus, after successful transplantation, shunt closure should be performed to prevent these complications and to improve quality of life.

A novel fully human anti-CD40 monoclonal antibody, 4D11, for kidney transplantation in cynomolgus monkeys.

BACKGROUND: CD40-CD154 pathway blockade by anti-CD154 monoclonal antibodies (mAbs) significantly prolongs allograft survival in nonhuman primates. However, thromboembolic complications have prevented clinical application. Thus, blockade of the counter molecule by a novel fully human anti-CD40 mAb, 4D11, is an attractive alternative. METHODS: Kidney transplantations were performed between outbred cynomolgus monkeys (stimulation index >3 in a mixed lymphocyte reaction). The animals were divided into five groups: nontreatment control (Group 1, n=3), 10-week treatment with either 10 mg/kg (Group 2, n=3), 20 mg/kg (Group 3, n=3), or 40 mg/kg (Group 4, n=1), and 4-week treatment (Group 5, n=1 each) with 10 mg/kg, 20 mg/kg, or 40 mg/kg followed by monthly administration. Graft survival, biochemistry, complete blood counts, lymphocyte phenotypes, blood drug levels, antidonor and antidrug antibodies, and renal histology were examined. RESULTS: Survival (days) was as follows: Group 1 (5, 6, 7), Group 2 (150, 108, 108), Group 3 (84, 108, 379), Group 4 (147), and Group 5 (147, 102, 112). Two animals in Group 3 with normal graft function were killed upon development of hydronephrosis and cerebral infarction. B lymphocytes fell to one-third of the preoperative value at 4 weeks after transplantation in all animals. Antidonor antibodies developed in most of the animals after stopping drug treatment or at the time of death. No animals except for one formed anti-4D11 antibody. CONCLUSION: 4D11 appears to be a promising agent for antirejection treatment in clinical organ transplantation.

Metastatic melanoma of the gallbladder.

We report the findings of a magnetic resonance (MR) imaging analysis of metastatic melanoma of the gallbladder in a 36-year-old woman. MR imaging revealed that the gallbladder wall was diffusely thickened, and the tumor showed slightly high-intensity on T1-weighted images. The apparent diffusion coefficient value of the tumor was 0.69 x 10(-3)mm(2)/s, indicating high cellularity. Surgical specimens revealed that the tumor was a metastatic melanoma showing medullary growth with intratumoral hemorrhaging. These MR findings are helpful for preoperative diagnosis.

Effect of synthetic protease inhibitor gabexate mesilate on the attenuation of ischemia/reperfusion injury in canine kidney autotransplantation.

BACKGROUND: Kidneys from non-heart-beating donors are associated with delayed graft function and a high rejection rate due to the long period of warm ischemia. Gabexate mesilate (GM), a synthetic serine protease inhibitor, has been shown to improve organ function by suppressing cytokine activity and neutrophil function after ischemia/reperfusion. In this study, we evaluated the effect of GM on renal function after warm ischemia in a canine kidney autotransplantation model. METHODS: After 60 minutes of warm ischemia, the left kidney was transplanted into the iliac fossa, and the right kidney was removed. The control group (n = 7) and GM group (n = 7) were evaluated for serum creatinine and blood urea nitrogen (BUN) concentrations, renal tissue blood flow, resistive index, pulsatility index, interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha mRNA expression levels in peripheral blood mononuclear cells, apoptotic index, CD10 immunolabeling as an indicator of brush border injury, and standard histopathology. RESULTS: Compared with controls, administration of GM resulted in lower serum creatinine concentrations (11.3 +/- 2.4 vs 5.2 +/- 3.3 mg/dL at 72 hours; P = .04) and BUN concentrations (188 +/- 26 mg/dL vs 98 +/- 41 mg/dL at 72 hours; P = .04), as well as better tissue blood flow, improvement of brush border injury and apoptotic index (each P < .05). The expression of IL-1beta and TNF-alpha mRNA did not change after administration of GM. CONCLUSIONS: The present study shows that GM protected renal function after warm ischemia/reperfusion by inhibition of serine proteases, maintenance of tissue blood flow, and amelioration of tubular apoptosis.

[Current status of pancreas transplantation in Japan].

The pancreas transplantation is widely performed for the patients with type 1 diabetes. To date in Japan we had 20 SPK or PAK transplants under the new brain death law launched in 1997. Despite severe shortage of organ donors and marginal donors such as old age, unstable homodynamic situation at agonal phase and atherosclerosis, all patients enjoy a post-operative life except two patients who had grafts removed due because of thrombosis and perforation. There are some reports recently presented at the meeting with respect to simultaneous pancreas kidney transplantations from living donors. It will be expected to have more donors and transplantation with satisfactory results in Japan as well.

Biliary sphincter motility after neural isolation of the pancreatoduodenal region in conscious dogs.

BACKGROUND: Several neural and hormonal factors are known to affect the motility of the sphincter of Oddi. However, the precise mechanisms of the control of sphincter motility have not been completely explored. We investigated the relationship of canine biliary sphincter motility when it is extrinsically denervated by neural isolation of the pancreatoduodenal region. METHODS: Interdigestive and postprandial sphincter motility in a denervated pancreatoduodenal segment and effects of cholecystokinin-octapeptide were studied in 7 conscious dogs. Data were compared with those of 7 neurally intact control dogs. RESULTS: After extrinsic denervation of the pancreatoduodenal region, sphincter motility exerted a cyclic change in concert with the duodenal myoelectric cycles; this change involved short cyclic bursts of motor activity, which gradually increased in intensity. The increase in the cyclic bursts of motor activity was also cyclic and associated with an increase in the plasma motilin concentration. Neural isolation of the pancreatoduodenal region increased sphincter basal pressure and motility index (integral per minute). In the denervated biliary sphincter, the feeding pattern and temporary inhibitory effect of feeding, as seen in controls, were absent, which suggests the role of extrinsic nerves in delivering bile into the duodenum after feeding. In the denervated dogs, cholecystokinin-octapeptide caused excitation of the sphincter activity, instead of relaxation observed in controls. CONCLUSIONS: Extrinsic innervation to the pancreatoduodenal region has an inhibitory effect on biliary sphincter motility. Abnormalities in extrinsic innervation to the biliary sphincter might increase the resistance of the sphincter to the bile flow and induce bile stagnation.

Attenuation of renal ischemia-reperfusion injury by FR167653 in dogs.

BACKGROUND: Inflammatory cytokines are known to contribute to ischemia-reperfusion injury. We investigated the effect of FR167653 (FR), a suppressor of interleukin-1beta and tumor necrosis factor-alpha, on ischemia-reperfusion injury of the kidney in dogs. METHODS: The left kidney was subjected to ischemia for 60 minutes followed by removal of the right kidney. A control group (n = 10) and an FR group (n = 8) were evaluated for tissue blood flow; resistive index, pulsatility index, arterial oxygen pressure, serum creatinine, blood urea nitrogen, aspartate transaminase, and alanine transaminase levels; interleukin-1beta messenger RNA expression in the peripheral blood; apoptotic index; and histopathology. RESULTS: The FR group showed lower creatinine, serum urea nitrogen, aspartate transaminase, and alanine transaminase levels (P <.038 each) and lower interleukin-1beta mRNA expression and apoptotic index (P <.041 each) than did the control group. Arterial oxygen pressure during the 120 minutes after reperfusion in the FR group decreased but recovered quickly (P =.024). Renal tissue damage in the FR group was less than that in the control group (P =.036). CONCLUSIONS: FR ameliorates ischemia-reperfusion injury of the kidney potentially by reduced production of inflammatory cytokines that may contribute to damage to the ischemic kidney and the distant organs.

Autoimmune pancreatitis starting as a localized form.

Autoimmune pancreatitis is a rare type of pancreatitis that is characterized by diffuse swelling of the pancreas and irregular stenosis of the pancreatic ductal system ("sclerosing" pantreatitis), caused by autoimmune processes. Previous reports have shown the complete form of the disease, but very few have presented follow-up imagings from the beginning to the complete form. We, herein, report a case of autoimmune pancreatitis starting as a localized form. A-56-year-old Japanese man developed obstructive jaundice. Ultrasonography showed a hypoechoic mass in the head of the pancreas, and endoscopic retrograde pancreatography (ERP) showed localized stenosis of the pancreatic duct in the head of the pancreas. Computed tomography (CT) showed enlargement, with a capsule-like rim, in the head of the pancreas. Internal biliary tube drainage was performed to relieve the obstructive jaundice. The patient was followed-up under the tentative diagnosis of localized "mass-forming" pancreatitis. Four months after the drainage, CT showed diffuse swelling of the pancreas, with a capsule-like rim, and ERP demonstrated diffuse irregular narrowing of the pancreatic duct. Glucose intolerance was noted for the first time. Steroid was given as a diagnostic treatment for autoimmune pancreatitis. Two months after initiation of the steroid treatment, the ERP findings were normal, and CT showed a normal pancreas. The biliary tube was removed, and the glucose intolerance was subsequently alleviated. To summarize, we report a case of autoimmune pancreatitis starting as localized "mass-forming" pancreatitis with a peripheral rim on imagings. It is very important to be well aware of the presence of the localized form of autoimmune pancreatitis.

Factors affecting surgical outcome for gallbladder carcinoma.

BACKGROUND/AIMS: The outcome of advanced gallbladder carcinoma is dismal despite aggressive surgery. The aim of this study was to evaluate the surgical outcome and prognostic factors for patients with gallbladder carcinoma and to identify patients who may benefit from radical surgery. METHODOLOGY: Fifty-six patients who underwent surgical resection of gallbladder carcinoma were retrospectively reviewed. Their tumor markers, operative management, pathological factors and survival were analyzed. RESULTS: The serum carcinoembryonic antigen level was elevated in 9 of 51 patients (18%) with data available as was the serum carbohydrate antigen 19-9 level in 14 of 47 patients (30%). Univariate analysis showed that jaundice, serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels, the number, size, macroscopic type, and histological grade of the tumor, the depth of tumor invasion (pT), pathological stage, lymph node metastasis (pN), lymphatic invasion, vascular invasion, perineural infiltration, curability of lymph node dissection and surgical margins have prognostic significance for survival. Multivariate analysis revealed jaundice, high histological grade, pT3 or pT4, and surgical margins were independent prognostic factors for survival. CONCLUSIONS: Preoperative serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels are potential predictors and informative for survival. There are still difficulties to treat gallbladder carcinoma infiltrating beyond subserosa or revealing jaundice.