Contralateral occurrence after laparoscopic total extraperitoneal hernia repair for unilateral inguinal hernia.

PURPOSE: Although laparoscopic total extraperitoneal repair (TEP) has been reported to have a low recurrence rate and relatively little postoperative pain, there have been few studies reported regarding contralateral occurrence after TEP. Although a high incidence of occult contralateral hernias has been reported in the literature, it is unknown whether occult hernias have any significance in clinical settings. The aim of this study was to evaluate the incidence of contralateral occurrence after TEP for unilateral inguinal hernia. METHODS: We retrospectively reviewed the medical charts of 157 TEPs between April 2003 and May 2009. No patients had undergone contralateral exploration during TEP for unilateral inguinal hernias. RESULTS: Five (3.2%) of 157 unilateral TEPs developed a hernia on the contralateral side. In three patients, the initial hernia was on the right side, and in two it was on the left side. In four patients the initial hernia was indirect, and in one it was direct. The mean duration to contralateral occurrence was 12.2 months. Three patients had contralateral occurrence within 6 months after the primary TEP, while in two over a year passed before contralateral occurrence. All five patients had undergone TEP for contralateral occurrence. The mean operation time was 87.2 min, and there was little intraoperative blood loss. There were no complications during and after the second TEP. CONCLUSIONS: The incidence of contralateral occurrence after TEP was found to be low. TEP is a valuable procedure with a low contralateral occurrence rate, and repeated TEP for contralateral occurrence can be performed easily.

Feasibility of reduced intensity hematopoietic stem cell transplantation from an HLA-matched unrelated donor.

To evaluate the feasibility of reduced intensity stem cell transplantation (RIST) with bone marrow from a matched unrelated donor (MUD), we retrospectively investigated 20 patients with hematological disorders who received RIST in the Tokyo SCT consortium from January 2000 to October 2002. The preparative regimens were fludarabine-based (150-180 mg/m(2), n=18) or cladribine-based (0.77 mg/kg, n=2). To enhance engraftment, antithymocyte globulin (ATG) and 4 or 8 Gy total body irradiation (TBI) were added to these regimens in nine and 11 patients, respectively. GVHD prophylaxis was cyclosporine with or without methotrexate. In all, 19 achieved primary engraftment. Three developed graft failure (one primary, two secondary), and five died of treatment-related mortality within 100 days of transplant. Seven of the 19 patients who achieved initial engraftment developed grade II-IV acute GVHD, and seven of 13 patients who survived >100 days developed chronic GVHD. At a median follow-up of 5.5 months, estimated 1-year overall survival was 35%. Compared with a TBI-containing regimen, an ATG-containing regimen was associated with a high risk of graft failure (30 vs 0%, P=0.0737). This study supports the feasibility of RIST from MUD; however, procedure-related toxicities remain significant in its application to patients.

High complete response rate after allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning regimens in advanced malignant lymphoma.

The possible advantage of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a graft-versus-lymphoma effect. We explored the feasibility and efficacy of allo-HSCT with reduced-intensity (RI) regimens in advanced malignant lymphoma (ML). A total of 20 patients with indolent (n=9) or aggressive lymphoma (n=11) received allo-HSCT with an RI regimen (RIST). The preparative regimen consisted of a combination of purine analog and alkylating agent with or without antithymocyte globulin. A total of 11 patients had chemorefractory disease, seven had chemosensitive relapsed disease and two had residual disease. All of the patients received G-CSF-mobilized blood stem cells from HLA-matched siblings. Of the 20 patients, 19 achieved engraftment with acceptable regimen-related toxicities. Seven patients developed grade II-IV acute GVHD and 15 developed chronic GVHD. Of the 15 patients with evaluable disease, 12 achieved a complete response. One died of invasive fusariosis, four subsequently died of GVHD complicated with fungal infection and one died of progressive disease. With a median follow-up of 358 days, the Kaplan-Meier estimates for 1-year overall and progression-free survival were both 70%. The high response rate with low relapse observed in this study suggests that RIST may be an effective alternative curative treatment for patients with advanced ML.

Crystal structure of human AUH protein, a single-stranded RNA binding homolog of enoyl-CoA hydratase.

BACKGROUND: The AU binding homolog of enoyl-CoA hydratase (AUH) is a bifunctional protein that has two distinct activities: AUH binds to RNA and weakly catalyzes the hydration of 2-trans-enoyl-coenzyme A (enoyl-CoA). AUH has no sequence similarity with other known RNA binding proteins, but it has considerable sequence similarity with enoyl-CoA hydratase. A segment of AUH, named the R peptide, binds to RNA. However, the mechanism of the RNA binding activity of AUH remains to be elucidated. RESULTS: We determined the crystal structure of human AUH at 2.2 A resolution. AUH adopts the typical fold of the enoyl-CoA hydratase/isomerase superfamily and forms a hexamer as a dimer of trimers. Interestingly, the surface of the AUH hexamer is positively charged, in striking contrast to the negatively charged surfaces of the other members of the superfamily. Furthermore, wide clefts are uniquely formed between the two trimers of AUH and are highly positively charged with the Lys residues in alpha helix H1, which is located on the edge of the cleft and contains the majority of the R peptide. A mutational analysis showed that the lysine residues in alpha helix H1 are essential to the RNA binding activity of AUH. CONCLUSIONS: Alpha helix H1 exposes a row of Lys residues on the solvent-accessible surface. These characteristic Lys residues are named the "lysine comb." The distances between these Lys residues are similar to those between the RNA phosphate groups, suggesting that the lysine comb may continuously bind to a single-stranded RNA. The clefts between the trimers may provide spaces sufficient to accommodate the RNA bases.

Absorption and urinary excretion of (-)-epicatechin after administration of different levels of cocoa powder or (-)-epicatechin in rats.

(-)-Epicatechin is a major polyphenol component of cocoa powder. The absorption and urinary excretion of (-)-epicatechin following administration of different levels of either cocoa powder (150, 750, and 1500 mg/kg) or (-)-epicatechin (1, 5, and 10 mg/kg) were evaluated in rats. Both the sum of plasma (-)-epicatechin metabolites at 1 h postadministration and peak plasma concentrations increased in a dose-dependent fashion. The sum of (-)-epicatechin metabolites in urine, excreted within 18 h postadministration, also increased with dose. Moreover, the sum of (-)-epicatechin metabolites excreted in urine reached the same level in both (-)-epicatechin and cocoa powder administration groups for equivalent amounts of (-)-epicatechin. These results suggest that, in the dose range examined in this study, bioavailability of (-)-epicatechin following administration of either (-)-epicatechin or cocoa powder shows dose dependence and that the various compounds present in cocoa powder have little effect on the bioavailability of (-)-epicatechin in cocoa powder.

Successful bone marrow transplantation for adult T-cell leukemia from a donor with oligoclonal proliferation of T-cells infected with human T-cell lymphotropic virus.

We describe a patient who underwent successful BMT from her sibling for the treatment of adult T-cell leukemia/lymphoma. Pre-transplant examination of the donor revealed oligoclonal integration of HTLV-I proviruses within the germ line, and our concern was that clinical sequelae of HLTV-I infection might become evident in the setting of post-transplant immunosuppression. However, the patient has been in complete remission for 14 months after transplantation, and no clonality of HTLV-I provirus was detected in the peripheral blood cells using southern blotting analysis. Our experience supports the possibility of transplantation from HTLV-I positive donors.

The potential risk for upper extremity thromboembolism in patients with occluded axillofemoral bypass grafts: two case reports.

Axillofemoral bypass grafts (AxFG) are widely used in the management of poor-risk patients with aortoiliac occlusive disease. On the other hand, AxFGs are associated with a variety complications to the upper extremity (UE). UE thromboembolism represents a significant and specific complication of occluded AxFGs in our series (2.6% of patients, 33.3% of occluded grafts). This article describes two cases of late axillary artery thrombosis caused by the occlusion of externally-supported AxFGs. The two patients were treated by graft disconnection, a distal embolectomy, and patch angioplasty of the axillary artery. Their postoperative courses were uneventful. Based on the authors' experience and a review of the literature, they suggest that an occluded AxFG represents a high risk for use of a donor artery and that such patients must therefore be very carefully followed. To prevent late UE thromboembolism in patients with occluded grafts, the authors strongly advise that such patients undergo a surgical operation with careful follow-up after surgery.

Fundic adenomyomatosis bulged with the subserosal excessive fat of the gallbladder mimicking polypoid carcinoma: a case report with unusual imaging and morphological features.

This report describes a 41-year-old female who presented with adenomyomatosis of the gallbladder mimicking polypoid carcinoma, on the diagnostic imaging findings and revealing unusual histologic features for such a localized adenomyomatosis. The mass was located on the gallbladder liver-side wall at the fundus and papillary hyperechoic growth showed no clear ultrasonographic features of adenomyomatosis. The patient underwent a laparoscopic cholecystectomy with a tentative diagnosis of superficial polypoid carcinoma. Histologically, the tumor bulged due to subserosal excessive fat tissue.

Predictive factors for long-term survival in patients with intrahepatic cholangiocarcinoma.

BACKGROUND: In order to elucidate the predictive factors for long-term survival in patients with intrahepatic cholangiocarcinoma (ICC), we evaluated 7 patients who survived for more than 5 years (5-year survivors). METHODS: We examined the clinicopathologic and biologic factors of the 5-year survivors, and these findings were then compared with those in 20 patients who died within 5 years after surgery (control group). RESULTS: In the 5-year survivors, the gross appearance of the tumors included a mass-forming (MF) type in 5 cases, an intraductal growth (IG) type in 1, and another type (microcarcinoma with hepatolithiasis) in 1. No case demonstrated a periductal infiltrating (PI) type. Except for 1 case with an IG type tumor, no lymph node metastasis was seen in any patients. All of the 5-year survivors were classified from stage I to III, and all also underwent a curative resection. The clinicopathologic factors demonstrating significant differences between the 5-year survivors and the control group included the gross type of the tumor, lymph node involvement, the surgical margin, curability, and pTNM stage. CONCLUSION: The predictive factors for long-term survival in patients with ICC are thus suggested to include not only tumor staging and curability, but also lymph node metastasis and the gross type of the tumors.

Systemic fusariosis after a preparative regimen including thiotepa, VP-16 and busulfan used for blood stem cell transplantation in Hodgkin's disease.

Fusarium infection is rare but important infection after bone marrow transplantation (BMT). A 27-year-old man developed systemic fusarial infection following severe skin damage probably caused by high-dose thiotepa administration. Systemic fusariosis rapidly progressed to a variety of organs despite antifungal treatment, and he finally died of this infection on day 75. Considering that this organism usually invades via damaged skin and that the penile lesion was the first manifestation of systemic fusariosis in this patient, careful examination of the skin might be helpful for early diagnosis of fusarial infection. His clinical course provided us with an important clue for diagnosis of fusarial infection.

Long-term results of hepaticojejunostomy for hepatolithiasis.

The results of a hepaticojejunostomy as a biliary-enteric bypass for benign disease are usually excellent. On the other hand, hepatolithiasis features a high rate of residual and recurrent stones with cholangitis after surgery. This study aims to evaluate the long-term results of a hepaticojejunostomy for hepatolithiasis regarding both the degree of the occurrence of postoperative cholangitis and the outcome. The clinical records of 159 patients with hepatolithiasis who underwent surgical treatment over a 23-year period were also retrospectively reviewed. Ninety-four of 159 patients underwent a hepatecetomy and 65 patients were subjected to liver-preserving surgery by means of intra- and postoperative endoscopic lithotripsy. In addition 72 patients underwent a hepaticojejunostomy. The rate of residual or recurrent stones was 31.4 per cent after complete stone removal. Twenty-two (30.6%) of the 72 patients developed some kind of cholangitis. This rate was significantly higher than that (three of 87 patients) of the non-biliary-enteric anastomosis group regarding the occurrence of biliary complications. We conclude that the use of a hepaticojejunostomy for patients with possible residual stones or intrahepatic bile duct lesions remains controversial.

Pneumocystis carinii pneumonia with an atypical granulomatous response in a patient with chronic lymphocytic leukemia.

We have recently seen a patient who developed Pneumocystis carinii pneumonia (PCP) in the course of treatment for chronic lymphocytic leukemia (CLL). This case showed uncommon pathological findings with extensive formation of granulomatous lesions. Despite advanced CLL associated with poor B-cell function, she responded well to anti-PCP treatment. In contrast to B-cell function, the T-cell functions were well preserved in vitro, and the numbers of peripheral CD4- and CD8-positive cells were normal, and T-cell functions were normal. These findings suggest that the production of granulomatous lesions to PCP may have been associated with the patients' immune status, and that it may constitute a good indicator in PCP infection in patients with underlying hematological malignancy.

Congenital absence of the portal vein associated with focal nodular hyperplasia of the liver and congenital choledochal cyst: a case report.

A congenital absence of the portal vein (CAPV) is a rare malformation, which almost is always associated with other anomalies such as hepatic tumors and cardiac malformations. This case report describes a 3-year-old girl with a congenital absence of the portal vein, focal nodular hyperplasia (FNH) of the liver, and a congenital choledochal cyst (CCC). Angiography findings showed the mesenteric vein and splenic vein to be joined together to form a common trunk that entered the inferior vena cava directly above the liver. This is the first known reported case of CAPV with concurrent CCC. J Pediatr Surg 36:622-625.

N-Terminally extended human ubiquitin-conjugating enzymes (E2s) mediate the ubiquitination of RING-finger proteins, ARA54 and RNF8.

We have previously cloned cDNAs encoding the N-terminally extended class III human ubiquitin-conjugating enzymes (E2s), UBE2E2 and UBE2E3, the biological functions of which are not known. In this study, we performed yeast two-hybrid screening for protein(s) interacting with UBE2E2, and two RING-finger proteins, ARA54 and RNF8, were identified. Both ARA54, a ligand-dependent androgen receptor coactivator, and RNF8 interacted with class III E2s (UBE2E2, UbcH6, and UBE2E3), but not with other E2s (UbcH5, UbcH7, UbcH10, hCdc34, and hBendless) in the yeast two-hybrid assay. The use of various deletion mutants of UBE2E2 and RING-finger proteins and two RING point mutants, ARA54 C(220)S and RNF8 C(403)S, in which the RING structure is disrupted, showed that the UBC domain of UBE2E2 and the RING domain of these RING-finger proteins were involved in this association. Wild-type ARA54 and RNF8, expressed in insect Sf9 cells, catalyzed E2-dependent autoubiquitination in vitro, whereas the point mutated proteins showed markedly reduced activity. Ubiquitination of wild-type ARA54 and RNF8, expressed in COS-7 cells, was also observed, and a proteasome inhibitor, MG132, prevented the degradation of these wild-type proteins, but was much less effective in protecting the RING mutants. Transfection of COS-7 cells with a green fluorescent protein chimera showed that RNF8 was localized in the nucleus, and ARA54 in both the cytoplasm and nucleus. Our results suggest that ARA54 and RNF8 possibly act as Ub-ligases (E3) in the ubiquitination of certain nuclear protein(s).

Clinical relevance of the concentrations of both pyrimidine nucleoside phosphorylase (PyNPase) and dihydropyrimidine dehydrogenase (DPD) in colorectal cancer.

BACKGROUND: Pyrimidine nucleoside phosphorylase (PyNPase) converts 5'-deoxy-5-fluorouridine (5'-DFUR) to 5'-fluorouracil (5-FU), which exerts an anti-cancer effect before being catabolized by dihydropyrimidine dehydrogenase (DPD). We examined the possible correlation of the tissue concentrations of both PyNPase and DPD with the clinicopathological features of colorectal cancer. METHODS: In 36 cases of colorectal cancer, the concentrations of both PyNPase and DPD in fresh-frozen samples from either tumor or normal tissue were quantified using ELISA. RESULTS: The concentration of PyNPase was found to be significantly higher in the tumor than in the normal tissue (p = 0.001), whereas DPD showed no difference. The tumor/normal tissue ratio of PyNPase was higher in advanced stage cases, and also in the presence of liver metastasis, lymph node metastasis and vessel invasion (each p < 0.05). On the other hand, the tumor/normal tissue ratio of DPD was also higher in advanced stage cases and also in the presence of vessel invasion (each p < 0.05), thus indicating a poor response to 5-FU. The PyNPase/DPD ratio, which is known to be correlated with the tissue concentration of 5'-DFUR, was higher in the tumor than in the normal tissue (p = 0.001). CONCLUSIONS: The tumor/normal tissue ratios of both PyNPase and DPD might be useful candidates for predicting the prognosis of colorectal cancer. The PyNPase/DPD ratio was higher in the tumor tissue than in the normal tissue; however, further investigations are needed to clarify the effectiveness of fluoropyrimidine therapy.

A proposed mechanism for the potentiation of cAMP-mediated acid secretion by carbachol.

Acid secretion in isolated rabbit gastric glands was monitored by the accumulation of [(14)C]aminopyrine. Stimulation of the glands with carbachol synergistically augmented the response to dibutyryl cAMP. The augmentation persisted even after carbachol was washed out and was resistant to chelated extracellular Ca(2+) and to inhibitors of either protein kinase C or calmodulin kinase II. Cytochalasin D at 10 microM preferentially blocked the secretory effect of carbachol and its synergism with cAMP, whereas it had no effect on histamine- or cAMP-stimulated acid secretion within 15 min. Cytochalasin D inhibited the carbachol-stimulated intracellular Ca(2+) concentration ([Ca(2+)](i)) increase due to release from the Ca(2+) store. Treatment of the glands with cytochalasin D redistributed type 3 inositol 1,4,5-trisphosphate receptor (the major subtype in the parietal cell) from the fraction containing membranes of large size to the microsomal fraction, suggesting a dissociation of the store from the plasma membrane. These findings suggest that intracellular Ca(2+) release by cholinergic stimulation is critical for determining synergism with cAMP in parietal cell activation and that functional coupling between the Ca(2+) store and the receptor is maintained by actin microfilaments.