Successful Resection of Ampullary Carcinoma in a Father and Adenoma in a Daughter with Familial Adenomatous Polyposis Following Detection by Surveillance: Report of Two Cases

This report describes the successful resection of ampullary carcinoma in a 58-year-old man and an adenoma in his 28-year-old daughter after they had undergone proctocolectomy for familial adenomatous polyposis (FAP). Both patients had been monitored by surveillance endoscopy once a year since their proctocolectomy. The father was found to have an ampullary adenoma 26 years after proctocolectomy, and ampullary carcinoma was detected 2 years later, for which pancreatoduodenectomy was performed. Histological examination of the specimen revealed an ampullary carcinoma, 2.5 × 1.7 cm, that had invaded the submucosal layer, but no lymph node metastasis was found. The patient's daughter underwent endoscopy, which showed an ampullary polyp 6 years after total colectomy. Endoscopic mucosal resection of the peri-ampullary lesion was performed, and histological examination revealed a dysplastic tubular adenoma 0.6 × 0.4 cm in diameter. This report reinforces the importance of long-term periodic surveillance of patients with FAP by gastroduodenal endoscopy. Received: January 9, 2001 / Accepted: July 17, 2001     

Persistent subclinical rejection associated with nodular B-cell infiltrates in a renal transplant recipient

Abstract:  Recently, B-cell infiltrates in acute rejection grafts have attracted interest as an indicator of refractory rejection. Here, we report a case of deceased donor renal transplantation in a Japanese recipient operated overseas in which the recipient suffered from persistent tubulointerstitial rejection episodes associated with B-cell infiltrates. A 59-yr-old man with end-stage renal disease caused by immunoglobulin A nephropathy underwent deceased donor renal transplantation overseas in December 2005. The initial post-operative course was uneventful. The patient was referred to our hospital one month after transplantation. He maintained stable renal function throughout the follow-up period. The maintenance immunosuppressive regimen consisted of tacrolimus, mycophenolate mofetil and methylprednisolone. His serum creatinine concentration remained around 1.0 mg/dL, with no evidence of proteinuria. However, a discrepancy was detected between the renal function and the pathological findings. The pathology showed subclinical tubulointerstitial rejection with nodular B-cell infiltrates refractory to aggressive antirejection therapy. A steroid pulse and 15-deoxyspergualin were ineffective and the patient developed interstitial fibrosis and tubular atrophy by one yr after the transplantation, with persistent tubulitis and B-cell infiltrates. We treated the refractory rejection with B-cell infiltrates with a single 200 mg/body dose of rituximab and obtained an improvement. The pathological findings after administering rituximab consisted of mild tubulitis classified as Banff borderline, and elimination of the nodular B-cell infiltrates. At present, 20 months after renal transplantation, the patient continues to maintain stable renal function, with a good serum creatinine concentration (0.87 mg/dL).     

Carotid artery stenting via a transbrachial artery: techniques and problems

Recently, carotid artery stenting (CAS) has been reported to be an alternative of carotid endarterectomy (CEA) for internal carotid artery (ICA) stenosis due to the improvement of protection devices. In general, the transfemoral approach has been chosen for CAS because of the sizes of the devices. However, the transfemoral route seems to be unavailable or at high risk, in cases of severe atherosclerotic changes or aneurysm of the femoral, iliac artery or aorta, or after bypass graft placement. In this report, we presented 5 patients who underwent CAS using the transbrachial approach. The mean stenotic rate of 84% before treatment was reduced to 14% after the procedures. The 30-day morbidity and mortality were both 0%. Major local complications at the puncture site were not encountered. There has been no stroke nor death during a mean follow-up period of 6 months. We suggest that CAS via transbrachial route is an effective and safe treatment for ICA stenosis, by use of low-profile devices and bi-plane DSA equipment, especially in patients who are not eligible for the transfemoral access.     

The sinusoidal pressure during ischemia-reperfusion injury in perfused mouse liver pretreated with or without L-NAME

BACKGROUND: Hepatic ischemia-reperfusion (I/R) is accompanied by liver weight gain and ascites formation possibly caused by an increase in the sinusoidal pressure, a determinant of hepatic transvascular fluid movement. However, changes in the sinusoidal pressure during hepatic I/R in mice are not known. It is also controversial whether nitric oxide (NO) exerts a beneficial or detrimental effect on hepatic I/R injury. We determined the changes in hepatic sinusoidal pressure and liver weight, and the effect of a NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) on I/R injury of isolated mouse liver. MATERIALS AND METHODS: Isolated liver from 20 male outbred ddY mice was perfused portally with diluted blood (Hct 3%). After pretreatment with L-NAME (100 microm) or D-NAME (100 microm), ischemia was induced at room temperature by occlusion of the inflow line of the portal vein for 1 h followed by 1-h reperfusion in a recirculating manner. The sinusoidal pressure was assessed by the double vascular occlusion pressure (Pdo), and pre- and postsinusoidal resistance was determined. Liver injury was assessed by blood levels of alanine aminotransferase (ALT). RESULTS: In the d-NAME group (n=7), immediately after reperfusion, the portal pressure increased by 2.8 +/- 0.1 (SE) mmHg, which was accompanied by an increase in Pdo of 1.5 +/- 0.1 mmHg, indicating increases in pre- and postsinusoidal resistance to a similar degree. Then, presinusoidal, but not postsinusoidal, resistance sustained increased until 60 min after reperfusion. Liver weight increased to 0.14 +/- 0.04 g/g liver after reperfusion, followed by a gradual return to baseline. Blood ALT levels increased at 60 min after reperfusion. There were no significant differences in changes in the variables between the D- and L-NAME (n=7) groups. In the time-matched non- I/R control group (n=6), no changes in variables were observed for 2 h. CONCLUSIONS: Mouse hepatic I/R causes marginal liver weight gain associated with a small and transient increase in the sinusoidal pressure, and nitric oxide does not play any significant roles in this injury.     

Two cases of primary female urethral cancer

Herein, we report two cases of female urethral cancer. Case 1 presented with acute urinary retention and case 2 presented with a painful perineal mass. Magnetic resonance imaging (MRI) revealed a urethral tumor in both cases. Histopathological examination of transperineal biopsy specimens from both patients suggested clear cell adenocarcinoma in case 1 and squamous cell carcinoma in case 2. Both cases underwent total urethrectomy with partial resection of the vaginal wall and cystostomy urinary diversion. With reference to case 1, obturator lymph node metastases were observed during surgery, and treatment comprised combined radiotherapy to 60 Gy and chemotherapy with 5-fluorouracil and cisplatin following surgery. However, metastases appeared in the lung 6 months after initial treatment and she died 20 months after surgery. For case 2, tumor marker failure was observed 5 months after surgery. The same combined treatment was performed and a complete response was obtained. At 19 months after surgery, the patient showed no evidence of recurrence.     

Laparoscopic Nephrectomy,Ex Vivo Repair,and Autotransplantation for a Renal Artery Aneurysm: Report of a Case

A 57-year-old woman was hospitalized with a left renal artery aneurysm (RAA). The aneurysm measured 35 mm in diameter and was located at the renal artery bifurcation. We performed a laparoscopic nephrectomy using a retroperitoneal approach and performed an ex vivo repair of the renal artery. The reconstructed kidney was then autotransplanted at the left iliac fossa. The patient's postoperative course was uneventful. A laparoscopic nephrectomy and ex vivo repair are both considered to be effective for treating complex RAA.     

Preoperative proximal splenic artery embolization: a safe and efficacious portal decompression technique that improves the outcome of live donor liver transplantation

Terminal liver cirrhosis is associated with marked severe portal hypertension, which increases the risk of intraoperative hemorrhage and graft hyper-perfusion, especially, in small-for-size graft. In cases with developed collateral vessels, we often face difficulties in perihepatic dissection with blood stanching against bleeding during recipient hepatectomy. For aseptic preoperative portal decompression, we established the proximal splenic artery embolization (PSAE) technique. Sixty adult living donor liver transplantation recipients with viral/alcoholic hepatic failure were divided into two groups; PSAE group (n = 30) and non-PSAE (n = 30). In the PSAE group, the splenic artery was embolized proximal to the splenic hilum 12-18 h before surgery. PSAE enabled shortening of operating time, reduced blood loss, led to less need for transfusion, and significantly reduced the post-transplant portal venous velocity and ascites. PSAE was not associated with complications, e.g., splenic infarction, abscess, or portal thrombosis. Six of the non-PSAE patients required additional surgical intervention to resolve postoperative hemorrhage and three patients required secondary PSAE for arterial-steal-syndrome. The hospital mortality rate of PSAE patients (3.3%) was significantly better than that of the PSAE group (13.3%, P < 0.05). Preoperative noninvasive PSAE makes more efficient use of portal decompression; thus, it can potentially contribute to improvement of outcome.     

Optic radiation tractography integrated into simulated treatment planning for Gamma Knife surgery

OBJECT: No definitive method of preventing visual field deficits after stereotactic radiosurgery for lesions near the optic radiation (OR) has been available so far. The authors report the results of integrating OR tractography based on diffusion tensor (DT) magnetic resonance imaging into simulated treatment planning for Gamma Knife surgery (GKS). METHODS: Data from imaging studies performed in 10 patients who underwent GKS for treatment of arteriovenous malformations (AVMs) located adjacent to the OR were used for the simulated treatment planning. Diffusion tensor images performed without the patient's head being secured by a stereotactic frame were used for DT tractography, and the OR was visualized by means of software developed by the authors. Data from stereotactic 3D imaging studies performed after frame fixation were coregistered with the data from DT tractography. The combined images were transferred to a GKS treatment-planning workstation. Delivered doses and distances between the treated lesions and the OR were analyzed and correlated with posttreatment neurological changes. RESULTS: In patients presenting with migraine with visual aura or occipital lobe epilepsy, the OR was located within 11 mm from AVMs. In a patient who developed new quadrantanopia after GKS, the OR had received 32 Gy. A maximum dose to the OR of less than 12 Gy did not cause new visual field deficits. A maximum dose to the OR of 8 Gy or more was significantly related to neurological change (p < 0.05), including visual field deficits and development or improvement of migraine. CONCLUSIONS: Integration of OR tractography into GKS represents a promising tool for preventing GKS-induced visual disturbances and headaches. Single-session irradiation at a dose of 8 Gy or more was associated with neurological change.     

Effect of the XIAP inhibitor Embelin on TRAIL-induced apoptosis of pancreatic cancer cells

BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent inducer of apoptosis in a wide variety of tumor cells, while it has no toxicity for the majority of normal cells.Therefore, TRAIL may be a suitable agent for anticancer therapy. We previously reported that a number of pancreatic cancer cell lines show resistance to TRAIL-induced apoptosis via overexpression of XIAP and FLIP. The present study was conducted to further examine TRAIL-based therapeutic strategies by aiming to restore functional apoptotic pathways in resistant pancreatic cancer cells. METHODS: In various pancreatic cancer cell lines, TRAIL-induced apoptosis was evaluated in the presence or absence of an XIAP-inhibitor (Smac peptide). Second, TRAIL-induced apoptosis was evaluated in TRAIL-resistant AsPC-1 cells with or without FLIP antisense. Third, the combined effect of Smac peptide and FLIP antisense was tested, and the activation of apoptosis-related caspases and poly (ADP-ribose) polymerase was evaluated. Finally, TRAIL-induced apoptosis was evaluated in the presence or absence of FLIP antisense and an XIAP inhibitor (embelin). RESULTS: Smac peptide enhanced TRAIL-induced apoptosis in a dose-dependent manner for several pancreatic cancer cell lines, but showed no effect on TRAIL-resistant AsPC-1 cells. Smac peptide alone had no influence on cell viability. TRAIL-induced apoptosis was restored in TRAIL-resistant AsPC-1 cells by exposure to FLIP antisense, which suppressed the expression of FLIP. The effect of TRAIL was augmented by the combination of FLIP antisense and Smac peptide. Similarly, TRAIL-induced apoptosis was restored by the combination of FLIP antisense and embelin. Activation of apoptotic caspases and cleavage of poly (ADP-ribose) polymerase was observed after sensitization of TRAIL-resistant pancreatic cancer cells. CONCLUSIONS: Pancreatic cancer cells gain resistance to TRAIL-induced apoptosis via expression of the antiapoptotic proteins XIAP and FLIP. Smac peptide and FLIP antisense could restore the apoptotic effect of TRAIL. An XIAP inhibitor, embelin, enhanced the effect of TRAIL in the presence of FLIP antisense. These findings may provide useful information for the development of TRAIL-based therapeutic strategies by restoring functional apoptotic pathways in resistant pancreatic cancer cells. In addition, a low molecular weight XIAP inhibitor like embelin could be a lead compound for the development of effective XIAP inhibitors.     

Tacrolimus as prophylaxis for acute graft-versus-host disease in reduced intensity cord blood transplantation for adult patients with advanced hematologic diseases

BACKGROUND: Myeloablative cord blood transplantation (CBT) for adult patients offers a 90% chance of engraftment with a 50% rate of transplant-related mortality, mostly attributable to infection. We have demonstrated the feasibility of reduced-intensity CBT (RI-CBT) for adult patients, in which cyclosporine was used for acute graft-versus-host disease (GVHD) prophylaxis. Transplantation-related mortality (TRM) was 27% within 100 days. Therefore our objective was to evaluate the feasibility of RI-CBT with tacrolimus as GVHD prophylaxis for adult patients with hematologic malignancies. METHODS: Thirty-four patients with a median age of 56.5 years (range; 22-68) with hematologic diseases underwent RI-CBT at Toranomon Hospital between November 2003 and September 2004. Preparative regimen comprised fludarabine 25 mg/m2 on days -7 to -3, melphalan 80 mg/m2 on day -2, and 4 Gy total body irradiation on day -1. GVHD prophylaxis was continuous intravenous infusion of tacrolimus 0.03 mg/kg, starting on day -1. RESULTS: Thirty-one patients achieved neutrophil engraftment at a median of day 20. Median infused total cell dose was 2.4 x 10E7/kg (range; 1.6-4.8). Thirty-two patients achieved complete donor chimerism at day 60. Grade II-IV acute GVHD occurred in 45% of patients, with a median onset of day 26. Primary disease recurred in five patients, and TRM within 100 days was 12%. Estimated 1-year overall survival was 70%. CONCLUSION: This study demonstrated the possible improvement in transplant-related mortality by tacrolimus as GVHD prophylaxis in adult RI-CBT recipients.