[A Case of Colon Cancer with DPD Deficiency That Showed Severe Myelosuppression by CapeOX Adjuvant Chemotherapy after Colon Resection].

A 57-year-old female patient received ileocecal colon resection because of colon cancer. Pathological findings showed pSSN2M0(pStage III b). After surgery, CapeOX was administered as an adjuvant chemotherapy. On day 13 of CapeOX treatment, severe oral mucositis and Grade 4 myelosuppression appeared, and the CapeOX treatment was immediately stopped. However, these adverse effects continued for 19 days, and she gradually recovered. The severe myelosuppression was caused bydeficiencyof DPD, which is a keyenzy me that metabolizes 5-FU. While DPD deficiencyis veryrare, we need to consider that 5-FU causes severe adverse events in patients with DPD deficiency.

[Long-Term Successful Management of Recurrent Rectal Cancer in the Predialysis State with FOLFIRI Chemotherapy].

A 71-year-old man with predialysis terminal renal insufficiency experienced peritoneal dissemination 1.5 years after low anterior resection for advanced rectal cancer. He received FOLFIRI therapy (70% dose); he achieved partial response (PR) under computed tomography and stable disease (SD) was maintained over a long term. Although Grade 3 myelosuppression was occasionally noted, he was treated with FOLFIRI for 2 years without other severe complications and without requiring the initiation of hemodialysis. After the initiation of hemodialysis, FOLFIRI treatment was continued for 1 year until progressive disease (PD). He received mFOLFOX6 as second-line therapy for 6 months, followed by LV-5-FU and a molecular targeting agent. These treatments prolonged his survival for 1 year and 8 months. FOLFIRI can be administered as an effective first-line therapy even for patients with predialysis terminal renal impairment without major renal damage. FOLFOX and molecular targeting agents should be made available and prolonged survival can be expected for advanced colorectal cancer patients with terminal renal disease after the initiation of hemodialysis.

[Successful management using laparoscopic splenectomy for splenomegaly and thrombocytopenia caused by oxaliplatin-based chemotherapy for advanced rectal cancer].

We report a case of advanced rectal cancer treated with chemotherapy, for which laparoscopic splenectomy had been effective for thrombocytopenia. A 56-year-old man suffered from advanced rectal cancer with multiple lung metastases. He underwent Hartmann's procedure and received chemotherapy with FOLFOX and FOLFIRI with bevacizumab. After 3 years and 2 months, he also suffered from splenomegaly and thrombocytopenia. Laparoscopic splenectomy produced and increased the thrombocyte count, allowing for a restart of chemotherapy. Oxaliplatin-based chemotherapy might produce hepatic sinusoid injury and induce splenomegaly owing to portal hypertension. Laparoscopic splenectomy seemed to be useful for treating thrombocytopenia, and allowed the continuation of chemotherapy.

Extrahepatic control of the middle hepatic vein with inflow control by pedicle clamping in major liver surgery.

Surgical techniques commonly used for controlling bleeding during major liver surgery are hepatic inflow occlusion (Pringle maneuver) or total hepatic vascular exclusion (THVE), which are effective procedures of diminishing intraoperative blood loss. However, it is difficult to control retrograde bleeding from the hepatic veins using Pringle maneuver and some patients do not tolerate hemodynamic changes caused by THVE. We isolated the left and middle hepatic veins separately using Arantius' ligament approach to these hepatic veins, and extrahepatic control of the relevant to the liver segment to be resected hepatic veins with inflow control by Glissonian pedicle clamping was successfully performed.

Ventral pancreatectomy associated with segmental duodenectomy including the major papilla.

During embryonic development, the head of the pancreas comprises ventral and dorsal primordia. The embryological fusion plane between the ventral and dorsal primordia reportedly separates the adult pancreas into the ventral and dorsal pancreas. The duct of Wirsung drains the ventral pancreas and terminates in the major papilla, while the duct of Santorini drains the dorsal pancreas and terminates in the minor papilla. However, complete resection of the ventral pancreas is difficult and impractical because the lower bile duct is buried in ventral pancreatic parenchyma and resection may lead to postoperative ischemic necrosis of the duodenum, particularly around the major papilla. We have therefore performed ventral pancreatectomy associated with segmental duodenectomy including the major papilla in 3 cases with intraductal papillary mucinous neoplasm that involved only the duct of Wirsung.

Two-staged hepato-pancreatoduodenectomy and interventional pancreaticojejunostomy.

Two-staged pancreatoduodenectomy, including exteriorization of the pancreatic juice and second-look pancreaticojejunostomy, has been recommended for high-risk patients to avoid pancreatic leakage, which often causes intra-abdominal hemorrhage. We present a new technique of interventional pancreaticojejunostomy under both fluoroscopy and endoscopy without second-look laparotomy. A 77-year-old woman with local recurrence and liver metastasis from colon cancer underwent hepato-pancreatoduodenectomy with the external drainage of pancreatic juice via the pancreatic duct tube without pancreaticojejunostomy. Two months later, the jejunum was punctured with the insertion of a 5-F needle-knife into the pancreatic fistula during endoscopic observation of jejunal lumen, followed by the insertion of two 0.35-inch guidewires into the jejunum and the pancreatic fistula. Finally, a 10-Fr stenting tube was placed between the jejunum and the pancreatic fistula. No complications developed.

Prediction of chronic renal allograft dysfunction from evaluations of TGFBeta1 and the renin-angiotensin system.

BACKGROUND: Growth factors, cytokines, and the renin-angiotensin system (RAS) are involved in chronic allograft dysfunction. However, it is unclear whether clinical evaluations of TGFBeta1 and the RAS in longterm stable transplant patients can predict the development of chronic allograft dysfunction. METHODS: Urinary TGFBeta1 excretion and the response of plasma renin activity (PRA) to angiotensin I converting-enzyme inhibition (ACE-I) were prospectively examined in transplant patients who had had stable graft function (n = 16) for at least 1 year after renal transplantation. Four-year follow-up studies were undertaken to evaluate the impact of these parameters on the development of chronic allograft dysfunction. RESULTS: Urinary TGFBeta1 excretion and PRA response to ACE-I in renal transplant patients who developed chronic allograft nephropathy 4 years after the evaluations (n = 7) were significantly higher and greater, respectively, than these values in those who did not ( n = 9; P < 0.01). If the cutoff level for urinary TGFBeta1 excretion was 250 pg/min, the 4-year positive predictive value (PPV) with respect to the development of chronic allograft nephropathy was 83% and the negative predictive value (NPV) was 78% (sensitivity [sen.], 71%; specificity [sp.], 88%). If the cutoff level for PRA at 60 min after ACE-I was 4.0 ng/ml per h, the 4-year PPV was 71% and NPV was 75% (sen., 70%; sp., 75%). The stable transplant patients with high TGFBeta1 excretion and exaggerated PRA response showed significantly higher rates of chronic allograft dysfunction than those with low TGFBeta1 excretion and weak PRA response. CONCLUSIONS: This study demonstrates that some transplant patients with longterm stable graft function show increases in the activities of the TGFBeta system and the RAS. Evaluations of urinary TGFBeta1 excretion and PRA response to ACE-I present a possibility for predicting the development of chronic allograft dysfunction, with significant 4-year predictive values.

Acutely exaggerated hepatitis B induced by the withdrawal of immunosuppressants in a seroconverted renal transplant recipient: report of a case.

The long-term reciprocal impact of renal transplantation on infection by hepatitis B virus (HBV) is still a matter of intense debate, and the topic remains controversial. We herein report the case of a 50-year-old male asymptomatic HBV carrier who had seroconverted to positive anti-HBe antibody (Ab) and received a kidney transplantation from a cadaver donor (HB surface(s) antigen (Ag)-negative). Nine months later, his kidney function deteriorated due to chronic rejection, and hemodialysis was temporarily required. Triple drug therapy (cyclosporine, prednisolone, azathioprine) for immunosuppression was changed to two-drug therapy (cyclosporine and prednisolone) at a reduced dosage because of this episode. After that episode, severe hepatitis with HBV antigenemia developed without any change in the serological state. The levels of DNA polymerase in a potential recipient from a cadaveric donor should be checked before transplantation to predict the occurrence of hepatitis when the recipient is an asymptomatic carrier of HBV, especially in cases of serologically HBeAg-negative, and anti-HBeAb-positive carriers.

Prevention of primary nonfunction of canine islet autografts by treatment with pravastatin.

BACKGROUND: Nonspecific inflammation is the primary cause of early islet graft loss. We have shown in mice that pravastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, prevents primary nonfunction of islet isografts by reducing inflammatory reactions at the graft site. This study was designed to test the effectiveness of this agent in a large animal model, dogs, by transplanting autologous islets. METHODS: After total pancreatectomy, islets were isolated by using a two-step digestion method, followed by discontinuous gradient centrifugation on EuroFicoll. A known number of freshly isolated islets were immediately transplanted back into the same dog via the portal vein. RESULTS: First, we determined the minimal islet number required to reverse diabetes by transplanting 3,000-10,000 IEQ/kg with no additional treatment. The number was found to be 4,000 IEQ/kg, and islets less than 4,000 IEQ/kg consistently failed. To test the effect of pravastatin, 3,000 IEQ/kg were transplanted into dogs that either received no further treatment or were treated daily with 20 mg/kg of pravastatin from days -2 to 14. Without pravastatin, this number of islets lowered blood glucose only transiently, and all four of these dogs became hyperglycemic within 1 week. In contrast, four of the five dogs treated with pravastatin became normoglycemic (<150 mg/dL) and maintained this level during the observation period of 12 weeks (P<0.05). Postprandial plasma glucose and insulin levels returned to normal, and K values of intravenous glucose tolerance tests were significantly higher in pravastatin-treated dogs than in controls (P<0.04 at week 2 and P<0.01 at week 4). CONCLUSION: Peritransplant pravastatin treatment reduced the number of autologous islets required to reverse diabetes in totally pancreatectomized dogs. These results suggest that pravastatin may also facilitate better islet graft survival and function in clinical transplantation.