[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.

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.

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.

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.

Introducing hand-assisted retroperitoneoscopic live donor nephrectomy: learning curves and development based on 413 consecutive cases in four centers.

BACKGROUND: Hand-assisted and retroperitoneoscopic techniques reduce the risk of bleeding and intraabdominal complications in living donor nephrectomy (LDN). This study reports on our four-center experience, development, and learning curves from the first 413 LDNs using a hand-assisted retroperitoneoscopic (HARS) technique. METHODS: The first 413 consecutive donors operated on using HARS were included in the study. Donor demographics, perioperative and postoperative data, complications, and recipient outcomes have been compiled. The data were analyzed as a whole and separately for each center, looking at center differences and learning curves over time. RESULTS: Significant differences were found in donor demographics between centers for the variables: age, body mass index, number of arteries, and side of operation. Mean operating time was 170.2 min, with significant differences between centers. Operating time was also significantly influenced by learning curves, sex/body mass index, and side of operation. Warm ischemia time differed significantly between centers and was influenced by center-wise learning and number of arteries. Overall conversion rate was 2.4% and differed significantly between centers. There was no mortality and no intraabdominal complications. Apart from the conversions and one pulmonary embolism, there were no major intraoperative or postoperative complications. Overall 3-month graft survival was 99%, with 96% immediate onset of function and 1% ureteral complications. CONCLUSIONS: The HARS technique reduces the risk of intraabdominal complications. It can be implemented with excellent donor and recipient outcomes despite different population demographics and center/surgeon-related tradition and experience. On the basis of our experience, we recommend the technique to increase the safety margin of LDN.

[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.

Serum tissue inhibitor of metalloproteinases 1 (TIMP-1) predicts organ recovery from delayed graft function after kidney transplantation from donors after cardiac death.

Donors after cardiac death (DCD) have recently become an important source of renal transplants to alleviate the shortage of renal grafts in kidney transplantation (KTx), although DCD kidneys often have complications associated with a delayed graft function (DGF). A microarray-based approach using renal biopsy samples obtained at 1 h after KTx from DCD identified the tissue inhibitor of metalloproteinases 1 (TIMP-1) gene as a potential predictive marker for DGF. The current study measured serum TIMP-1 in patients undergoing KTx and analyzed the time course after KTx. The average serum TIMP-1 level before KTx was 240 ± 10 ng/ml (n = 34). In patients undergoing KTx from a living donor (n = 23), the serum TIMP-1 levels showed no increase after KTx (POD1: 226 ± 12, POD2: 211 ± 12, and POD3: 195 ± 10 ng/ml), but in one case, the only patient who required post-KTx HD due to DGF, the level on POD1 was the highest among subjects (361 ng/ml). In contrast, patients undergoing KTx from DCDs (n = 11), the serum TIMP-1 levels increased rapidly after a KTx (POD1: 418 ± 32, POD2: 385 ± 42, and POD3: 278 ± 25 ng/ml). However, two patients who avoided post-KTx HD due to the immediate function of the graft did not show increased levels (<370 ng/ml) on either POD1 or POD2. The peak serum TIMP-1 values appeared to correlate to the post-KTx dialysis period. Furthermore, the increment of serum TIMP-1 on the early POD was found to be predictive of immediate or delayed function of the grafts. These data suggest that monitoring of serum TIMP-1 levels allow the prediction of graft recovery and the need for HD after a KTx from a DCD.

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.

Rhabdomyolysis developing after transcatheter arterial chemoembolization for hepatocellular carcinoma.

A 25-year-old man with hepatocellular carcinoma developed severe muscular weakness and pain 15 days after transcatheter arterial chemoembolization (TACE). The diagnosis of rhabdomyolysis was made based on myalgia localized in the bilateral upper extremities (bilateral trapezius, deltoid, biceps brachii, and teres major muscles) on magnetic resonance imaging and increased levels of muscle-derived serum enzymes. In this case, some drugs administered during the clinical course of TACE (diclofenac, famotidine, and cefotiam dihydrochloride) were suspected to be involved in the rhabdomyolysis, but the exact cause of rhabdomyolysis was not identified. The symptoms were completely improved by right trisegmentectomy of the liver following conservative treatment.

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.

Revival of effective and safe high-dose mizoribine for the kidney transplantation.

We investigated whether high-dose Mizoribine (MIZ: a water-soluble anti-metabolite), 4-6 mg/kg/d was as effective and safe as mycophenolate mofetil (MMF) for patients after kidney transplantation. Between January 2001 and December 2005, 36 recipients at a stable phase more than one month passed after transplantation underwent conversion from MMF to MIZ, two from Azathioprine to MIZ, and two cases on MIZ from the beginning. There were 24-male and 16-female patients whose average age was 43.3 yr old and average weight was 54.0 kg. The types of transplantations were living donor renal transplantation 25, cadaveric renal transplantation 11, and simultaneous pancreas-kidney transplantation four examples. Of these, 33 patients were on Tacrolimus-based triple regimen and seven patients on Cyclosporine A base. The drugs used together with MIZ were basically the same as those before conversion. The reasons for conversion to MIZ were infection in 18 cases (45.0%), bone marrow suppression in nine cases (22.5%) and diarrhea in eight cases (20.0%), and post-transplant lymphoproliferative disorder in one case (2.5%). We initiated 4-6 mg/kg/d of MIZ divided twice a day depending on the serum creatinine (sCr) value of each patient. There was no big difference in the sCr value before and after MIZ administration in each individual patient, 1.79 +/- 1.37 and 1.65 +/- 1.30 mg/dL, respectively. A 12 h pharmaco-kinetic study of MIZ revealed that a peak value reached 2.87 microg/mL on average at three h (C3) followed by a slow decrease afterward. Acute rejection occurred in two cases and adverse effects were seen in five cases. The results of analysis of 349 points divided into three groups by renal function were as follows; poor renal function Group A revealed a trough level of 2.21 +/- 0.99 microg/mL and dosage 2.20 +/- 1.06 mg/kg, good renal function Group B had a trough level of 1.06 +/- 0.82 microg/mL and dosage 4.40 +/- 1.72 mg/kg, and excellent function Group C had a trough level of 0.92 +/- 0.55 microg/mL and dosage of 4.36 +/- 1.08 mg/kg. High-dose MIZ 4-6 mg/kg/d is an anti-metabolite having an equivalent immunosuppressive effect, fewer serious adverse events and good cost-effectiveness as MMF even for patients with prolonged hemodialysis period and declined digestive function in Japan.

[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.