Species-differences in the in vitro biotransformation of trifluoroethene (HFO-1123).

1,1,2-Trifluoroethene (HFO-1123) is anticipated for use as a refrigerant with low global warming potential. Inhalation studies on HFO-1123 in rats indicated a low potential for toxicity (NOAELs ≥ 20,000 ppm). In contrast, single inhalation exposure of Goettingen® minipigs (≥ 500 ppm) and New Zealand white rabbits (≥ 1250 ppm) resulted in severe toxicity. It has been suggested that these pronounced species-differences in toxicity may be attributable to species-differences in biotransformation of HFO-1123 via the mercapturic acid pathway. Therefore, the overall objective of this study was to evaluate species-differences in glutathione (GSH) dependent in vitro metabolism of HFO-1123 in susceptible versus less susceptible species and humans as a basis for human risk assessment. Biotransformation of HFO-1123 to S-(1,1,2-trifluoroethyl)-L-glutathione (1123-GSH) and subsequent cysteine S-conjugate ß-lyase-mediated cleavage of the corresponding cysteine conjugate (1123-CYS) was monitored in hepatic and renal subcellular fractions of mice, rats, minipigs, rabbits, and humans. While 1123-GSH formation occurred at higher rates in rat and rabbit liver S9 compared to minipig and human S9, increased ß-lyase cleavage of 1123-CYS was observed in minipig kidney cytosol as compared to cytosolic fractions of other species. Increased ß-lyase activity in minipig cytosol was accompanied by time-dependent formation of monofluoroacetic acid (MFA), a highly toxic compound that interferes with cellular energy production via inhibition of aconitase. Consistent with the significantly lower ß-lyase activity in human cytosols, the intensity of the MFA signal in human cytosols was only a fraction of the signal obtained in minipig subcellular fractions. Even though the inconsistencies between GSH and ß-lyase-dependent metabolism do not allow to draw a firm conclusion on the overall contribution of the mercapturic acid pathway to HFO-1123 biotransformation and toxicity in vivo, the ß-lyase data suggest that humans may be less susceptible to HFO-1123 toxicity compared to minipigs.

A case of pubic abscess after prostate cancer surgery and radiotherapy treated with rectus femoris muscle flap.

We report the case of a 95-year-old man with soft tissue deficiency associated with a pubic abscess that occurred 30 years after prostate cancer surgery and radiation therapy. A fistula with purulent discharge without any obvious cause appeared in the midline of the lower abdomen and progressed to a soft tissue defect in which several calcium phosphate stones of 5-8 mm in diameter were found. Computed tomography showed calcium deposits on the surface of the pubis and irregular zonal calcifications extending from the pubis to the medial region of both thighs. Conservative treatment did not improve the patient's condition; thus, surgical treatment was performed. The pedicled rectus femoris muscle flap was elevated from the left thigh and transferred to fill the tissue defect, then a split thickness skin graft was applied on it. The tissue defect was successfully repaired, and the patient was able to regain ambulation ability. In the present case, it was presumed that urine exudation around the bladder due to radiation cystitis was involved in the formation of ectopic calculi and subsequent infection. In reconstructing a complex defect associated with infection, using muscle flaps to fill the dead space with well vascularized tissue is considered to be appropriate. In our case, we chose a rectus femoris muscle flap, which has advantages in volume and versatility of transposition owing to long vascular pedicle and requires no microsurgical vascular anastomosis. As a result, the preoperative activity was maintained, the infection was treated, and a good course was obtained.

Successful treatment with hydroxychloroquine for systemic lupus erythematosus with cutaneous involvement accompanied by a xanthomatous reaction.

Antimalarials are usually recommended for the first-line systemic treatment of cutaneous lupus erythematosus. Alopecia in patients with discoid lupus erythematosus (DLE) is sometimes a refractory condition in spite of topical therapies. We herein described a case of DLE on the scalp with a pathological change of a xanthomatous reaction, which was successfully treated with hydroxychloroquine (HCQ). A 34-year-old woman presented with hair loss to the parietal region. She had been diagnosed with systemic lupus erythematosus (SLE) four years previously. Treatment with 30 mg/day of prednisolone (PSL) had been initiated, and the dose was gradually reduced. At 10 mg/day of PSL, she had noticed her hair loss. Physical examination revealed some small erythematous lesions to the parietal region with accompanying hair loss. Pathological findings of the erythematous lesion on her head revealed thickening of the basement membrane zone, the interface dermatitis with vacuolar degeneration, and both superficial perivascular and perifollicular infiltration of inflammatory cells in the dermis. In addition, there was an infiltrate of xanthomatous cells detected in the papillary dermis, which were positive for CD68 and CD163. The patient started treatment with HCQ at a dose of 200 mg/day. The skin lesions completely resolved within five months after initiation of HCQ without increase in the dose of PSL. Xanthomatous reactions are rarely recognized in lupus erythematosus. The chronic epithelial injury in DLE could be implicated in triggering the secondary reactive process of a xanthomatous reaction. We believe that the reaction seen in our patient was a secondary change to pathological alteration due to SLE. However, as yet unrecognized factors may play a role in the development of a xanthomatous reaction in DLE.

Autoantibody to transcriptional intermediary factor-1ß as a myositis-specific antibody: clinical correlation with clinically amyopathic dermatomyositis or dermatomyositis with mild myopathy.

BACKGROUND: Myositis-specific autoantibodies (MSAs) are associated with unique clinical subsets in polymyositis/dermatomyositis (PM/DM). Autoantibodies against transcriptional intermediary factor (TIF)-1γ and TIF-1α are known to be MSAs. Previously, we reported that TIF-1ß is also targeted in patients with DM with or without concomitant anti-TIF-1α/γ antibodies. OBJECTIVES: To evaluate the clinical features of seven cases with anti-TIF-1ß antibodies alone. METHODS: Serum autoantibody profiles were determined, and protein and RNA immunoprecipitation studies were conducted. Western blotting was performed to confirm autoantibody reactivity against TIF-1ß. RESULTS: Anti-TIF-1ß antibody was identified by immunoprecipitation assay in 24 cases. Among them, seven patients were positive for anti-TIF-1ß antibody alone. Six of the seven patients were classified as having DM. Among the six cases of DM, two patients had no muscle weakness and normal creatine kinase (CK) levels, and were classified as having clinically amyopathic DM. Four patients had muscle weakness, but three of them had normal serum CK levels that responded well to systemic steroids. Characteristic features of DM included skin rashes, such as Gottron sign, periungual erythema, punctate haemorrhage on the perionychium and facial erythema including heliotrope, which were observed in 86%, 57%, 86% and 71% of our cases, respectively. One of the seven patients had appendiceal cancer. None of the patients had interstitial lung disease. CONCLUSIONS: Seven patients were confirmed to have anti-TIF-1ß antibody without any other MSAs, including TIF-1α/γ antibodies, and six of them were diagnosed with DM. We suggest that anti-TIF-1ß antibody is an MSA, and that it is associated with clinically amyopathic DM or DM with mild myopathy.

Palisaded neutrophilic and granulomatous dermatitis associated with systemic lupus erythematosus: possible involvement of CD163+ M2 macrophages in two cases, and a review of published works.

BACKGROUND: Palisaded neutrophilic and granulomatous dermatitis (PNGD) is a commonly occurring condition related to systemic autoimmune disease. It is characterized histopathologically by a distinct pattern of granulomatous inflammation in the presence or absence of leukocytoclastic vasculitis. The properties of granulomatous cells in PNGD are still uncertain. OBJECTIVE: We sought further investigation on the phenotype of the infiltrated cells in PNGD from two patients with systemic lupus erythematosus (SLE) and reviewed the previous published reports in order to provide a comprehensive summary on the clinical features of PNGD in SLE. METHODS: The immunohistochemical features of granulomatous cells in PNGD associated with SLE were analyzed. Immunohistochemical studies were performed on sections from our two cases using antibodies against CD68, CD163, CD15, Factor XIIIa, myeloperoxidase and neutrophil elastase. The clinical characteristics of the SLE patients who developed PNGD were also evaluated. We included all cases retrieved through a PubMed search with the key words PNGD and SLE. RESULTS: Cutaneous lesions consisted of erythematous plaques distributed on the face and upper limbs in both cases. The infiltrated cells were mainly positive for CD68 and CD163, a phenotype suggestive of M2 macrophages. Some mature neutrophils and lymphocytes were also present. A review of the literature of PNGD associated with SLE revealed a predominance in females, high prevalence of lupus nephritis and a good response to systemic steroids, with frequent skin lesions relapses during tapering of the treatment. LIMITATIONS: This study examined only two cases; the pathogenesis of the disease remains to be clarified. CONCLUSION: PNGD lesions were abundantly infiltrated by M2 macrophages, suggesting that they may have a role in this condition. SLE accompanied by PNGD might be associated with lupus nephritis and frequent relapses of skin lesions.

Residual carcinoma cells after chemoradiotherapy for esophageal squamous cell carcinoma patients: striving toward appropriate judgment of biopsy.

In esophageal squamous cell carcinoma (ESCC) patients who are treated with chemoradiotherapy (CRT), identification of the presence or absence of residual or recurrent carcinoma is usually pivotal in their clinical management. In addition, the extent of carcinoma invasion into the esophageal wall could determine the clinical outcome of these patients following CRT. Therefore, in this study, we evaluated the response to CRT both macroscopically and histologically in a consecutive series of 42 ESCC patients receiving neoadjuvant chemoradiotherapy following curative esophageal resection at Tohoku University Hospital between August 2011 and December 2012. The histological grading of tumor regression was as follows: grade 3, markedly effective (no viable residual tumor cells); grade 2, moderately effective (residual tumor cells in less than one-third of the tumor); grade 1, slightly effective (1b, residual tumor cells in one-third to two-thirds of the tumor; 1a, residual tumor cells in more than two-thirds of the tumor); and grade 0, ineffective. In this study, we selected grade 2 and 1b cases because they might show a complete response with definitive CRT. We evaluated the presence of any residual in situ lesions and tumor depth in detail. The grading of tumor regression in primary sites was as follows: grade 3 (7 cases), grade 2 (16 cases), grade 1b (13 cases), and grade 1a (6 cases). The concordance rate between macroscopic and histopathological evaluation on the depth of the tumor was 40% (17/42). Among 29 cases (grade 2 and grade 1b), intraepithelial lesions were not detected in 17 cases, and tumor nests were not detected in the lamina propria mucosae in 9 cases. The results of this study highlight the difficulties of detecting residual carcinoma cells using conventional endoscopic biopsy in patients who have received CRT. Therefore, when residual cancer is clinically suspected in patients who have received CRT, the biopsy specimen should be obtained from the deep layer of the esophagus whenever possible. Additionally, close follow-up is required using positron emission tomography/computed tomography, endoscopy, and other radiological evaluations.

Current assessment of choledochoduodenostomy: 130 consecutive series.

Introduction Cholelithiasis usually can be managed successfully by endoscopic sphincterotomy. Choledochoduodenostomy (CDD) is one of the surgical treatment options but its acceptance remains debated because of the risk of reflux cholangitis and sump syndrome. The aim of this study was to assess the current features and outcomes of patient undergoing CDD. Patients and methods We retrospectively analysed the surgical results of consecutive 130 patients treated by CDD between 1991 and 2013 and excluded five cases with a malignant disorder. Indications for surgery included endoscopic management where stones were difficult or failed to pass and primary common bile duct stones with choledochal dilatation. Incidences of reflux cholangitis, stone recurrence, pancreatitis or sump syndrome were investigated and the data between end-to-side and side-to-side CDD were compared. Results Reflux cholangitis and stone recurrence was 1.6% (2/125) and 0% (0/125) of cases by CDD. There is no therapeutic-related pancreatitis in CDD. Sump syndrome was not also observed in side-to-side CDD. Conclusions This study is a first comparative study between end-to-side and side-to-side CDD. The surgical outcomes for CDD treatment of choledocholithiasis were acceptable. The incidence of reflux cholangitis, stone recurrence, pancreatitis and sump syndrome was very low.

A randomized, open-label, phase III trial comparing amrubicin versus docetaxel in patients with previously treated non-small-cell lung cancer.

Background: Amrubicin is approved for treating non-small-cell lung cancer (NSCLC) and small-cell lung cancer. However, no direct comparisons between amrubicin and docetaxel, a standard treatment for NSCLC, have been reported. Patients and methods: We conducted a randomized phase III trial of Japanese NSCLC patients after one or two chemotherapy regimens. Patients were randomized to amrubicin (35 mg/m2 on days 1-3 every 3 weeks) or docetaxel (60 mg/m2 on day 1 every 3 weeks). Outcomes included progression-free survival, overall survival, tumor responses, and safety. Results: Between October 2010 and June 2012, 202 patients were enrolled across 32 institutions. Median progression-free survival (3.6 versus 3.0 months; P = 0.54) and overall survival (14.6 versus 13.5 months; P = 0.86) were comparable in the amrubicin and docetaxel groups, respectively. The overall response rate was 14.4% (14/97) and 19.6% (19/97) in the amrubicin and docetaxel groups, respectively (P = 0.45). The disease control rate was 55.7% in both groups. Adverse events occurred in all patients, and included grade ≥3 neutropenia occurred in 82.7% and 78.8% of patients in the amrubicin and docetaxel groups, respectively, grade ≥3 leukopenia occurred in 63.3% and 70.7%, and grade ≥3 febrile neutropenia occurred in 13.3% and 18.2% of patients in the amrubicin and docetaxel groups, respectively. Of eight cardiac-related events in the amrubicin group, three were considered related to amrubicin and resolved without treatment discontinuation. Conclusions: This was the first phase III study to compare amrubicin and docetaxel in patients with pretreated NSCLC. Amrubicin did not significantly improve the primary endpoint of PFS compared with docetaxel. Clinical trial registration: NCT01207011 (ClinicalTrials.gov).

IL-6, IL-8, IP-10, MCP-1 and G-CSF are significantly increased in cerebrospinal fluid but not in sera of patients with central neuropsychiatric lupus erythematosus.

OBJECTIVE: To determine whether the intrathecal concentrations of cytokines/chemokines are associated with, or influenced by, serum concentrations in patients with central neuropsychiatric systemic lupus erythematosus (NPSLE), and to ascertain whether the increased production of cytokines/chemokines intrathecally relative to serum levels is associated with the presence of central NPSLE. METHODS: 52 SLE patients (30 with central NPSLE and 22 with non-NPSLE), for whom the CSF and serum samples were obtained at the same time, were enrolled. 27 kinds of cytokine/chemokine concentrations other than IFN-α in the cerebrospinal fluid (CSF) and serum samples were measured by Bio-Plex Pro Assays. IFN-α concentration and anti-ribosomal P protein antibody (anti-P) titres in CSF and serum samples were measured by ELISA. RESULTS: The mean concentrations of IL-6, IL-8, IP-10, MCP-1, G-CSF and GM-CSF were higher in the CSF than in the sera, respectively, while the mean concentrations of other 22 cytokines/chemokines, including RANTES and IFN-α, in the CSF were much lower than those in the sera, respectively. Furthermore, the concentrations of IL-6, IL-8, IP-10, MCP-1 and G-CSF in the CSF of the 30 patients with NPSLE were significantly higher than in the 22 patients with non-NPSLE (p = 6.82 × 10(-5), p = 0.00037, p = 0.0028, p = 0.00065, and p = 0.0001, respectively), while the concentration of GM-CSF in the CSF of the 30 patients with NPSLE was not significantly higher than in the 22 patients with non-NPSLE. Most importantly, the largest difference occurred in CSF IL-6 concentrations. A significant positive correlation between CSF anti-P titres and serum anti-P titres in 52 patients with SLE (r = 0.6316, p = 6.44 × 10(-6)) was found, while no significant positive correlation was observed between CSF levels and serum levels of each cytokine/chemokine in the 52 SLE patients. CONCLUSION: In central NPSLE the production of IL-6, IL-8, IP-10, MCP-1 and G-CSF might take place in the central nervous system (CNS). These increased CSF cytokines/chemokines along with anti-P might have a prerequisite role in the pathogenesis of central NPSLE.

A randomized phase III trial of oral S-1 plus cisplatin versus docetaxel plus cisplatin in Japanese patients with advanced non-small-cell lung cancer: TCOG0701 CATS trial.

BACKGROUND: Platinum-based two-drug combination chemotherapy has been standard of care for patients with advanced nonsmall-cell lung cancer (NSCLC). The primary aim was to compare overall survival (OS) of patients with advanced NSCLC between the two chemotherapy regimens. Secondary end points included progression-free survival (PFS), response, safety, and quality of life (QoL). PATIENTS AND METHODS: Patients with previously untreated stage IIIB or IV NSCLC, an Eastern Cooperative Oncology Group performance status of 0-1 and adequate organ function were randomized to receive either oral S-1 80 mg/m(2)/day on days 1-21 plus cisplatin 60 mg/m(2) on day 8 every 4-5 weeks, or docetaxel 60 mg/m(2) on day 1 plus cisplatin 80 mg/m(2) on day 1 every 3-4 weeks, both up to six cycles. RESULTS: A total of 608 patients from 66 sites in Japan were randomized to S-1 plus cisplatin (n = 303) or docetaxel plus cisplatin (n = 305). OS for oral S-1 plus cisplatin was noninferior to docetaxel plus cisplatin [median survival, 16.1 versus 17.1 months, respectively; hazard ratio = 1.013; 96.4% confidence interval (CI) 0.837-1.227]. Significantly higher febrile neutropenia (7.4% versus 1.0%), grade 3/4 neutropenia (73.4% versus 22.9%), grade 3/4 infection (14.5% versus 5.3%), and grade 1/2 alopecia (59.3% versus 12.3%) were observed in the docetaxel plus cisplatin than in the S-1 plus cisplatin. There were no differences found in PFS or response between the two arms. QoL data investigated by EORTC QLQ-C30 and LC-13 favored the S-1 plus cisplatin. CONCLUSION: Oral S-1 plus cisplatin is not inferior to docetaxel plus cisplatin and is better tolerated in Japanese patients with advanced NSCLC. CLINICAL TRIAL NUMBER: UMIN000000608.

Prognosis of arterial aneurysm after surgery in patients with Behçet's disease.

AIM: Despite improvements in therapeutic modalities, the treatment of arterial aneurysms complicating Behçet's disease (BD) is still challenging. This study examined the long-term prognosis after surgery for arterial aneurysms in BD. METHODS: This study included 9 patients with BD (8 men and 1 woman) who underwent surgery for arterial aneurysms between 1989 and 2008. The outcomes after the surgical intervention were assessed, including procedure-related complications and survival. RESULTS: The initial surgical procedures were performed for aortic or iliac aneurysms in 5 patients and for lower-extremity aneurysms in 4 patients. There was no operative mortality. The mean follow-up period was 135±69 months, ranging from 53 to 259 months. Patients with aortic or iliac aneurysms underwent graft interposition with Dacron prostheses. Their postoperative courses were uneventful, and all patients were alive during the follow-up with no procedure-related complications. Those treated for lower-extremity aneurysms tended to show perioperative and postoperative complications, including aneurysmal degeneration of the autogenous vein graft in 2 patients. One patient who initially underwent surgery for a popliteal artery aneurysm died due to the rupture of a dissecting aortic aneurysm after serial surgical interventions for multiple aneurysms. Concomitant aortic or iliac aneurysms in 2 patients were followed up without any change in size under medical treatment using colchicine and corticosteroids. CONCLUSION: Although we cannot draw a firm conclusion because of the small number of cases in the present series, graft interposition can lead to a favorable prognosis in BD patients with aortic or iliac aneurysms, whereas surgical treatment of BD-related lower-extremity aneurysms is frequently associated with short- and long-term postoperative complications. Immunosuppressive therapy might possibly improve treatment outcomes.

Identification of chemoresistant factors by protein expression analysis with iTRAQ for head and neck carcinoma.

BACKGROUND: Cisplatin and other anticancer drugs are important in the treatment of head and neck squamous cell carcinoma; however, some tumours develop drug resistance. If chemoresistance could be determined before treatment, unnecessary drug administration would be avoided. Here, we investigated chemoresistance factors by comprehensive analyses at the protein level. METHODS: Four human carcinoma cell lines were used: cisplatin-sensitive UM-SCC-23, UM-SCC-23-CDDPR with acquired cisplatin resistance, naturally cisplatin-resistant UM-SCC-81B, and UM-SCC-23/WR with acquired 5-fluorouracil resistance. Extracted proteins were labelled with iTRAQ and analysed by tandem mass spectrometry to identify resistance. Protein expression was confirmed by western blotting and functional analysis was carried out using siRNA. RESULTS: Thirteen multiple-drug resistance proteins were identified, as well as seven proteins with specific resistance to cisplatin, including α-enolase. Differential expression of these proteins in cisplatin-resistant and -sensitive cell lines was confirmed by western blotting. Functional analysis for α-enolase by siRNA showed that cisplatin sensitivity significantly was increased in UM-SCC-81B and slightly in UM-SCC-23-CDDPR but not in UM-SCC-23/WR cells. CONCLUSIONS: We identified proteins thought to mediate anticancer drug resistance using recent proteome technology and identified α-enolase as a true cisplatin chemoresistance factor. Such proteins could be used as biomarkers for anticancer agent resistance and as targets of cancer therapy.

Efficacy of revascularization for critical limb ischemia in patients with end-stage renal disease.

OBJECTIVE: To evaluate the outcomes of surgical revascularization for critical limb ischemia in patients with end-stage renal disease (ESRD). PATIENTS AND METHODS: From 2004 to 2010, 184 patients with 213 critically ischaemic limbs caused by arteriosclerosis were admitted to The University of Tokyo Hospital. The outcomes of primarily surgical revascularization-based treatments were retrospectively compared in patients with ESRD (ESRD group: 79 patients, 101 limbs) and without ESRD (non-ESRD group: 105 patients, 112 limbs) during the same period. RESULTS: Arterial reconstruction was performed on 56 limbs in 46 patients in the ESRD group and 78 limbs in 73 patients in the non-ESRD group (55% vs. 70%; p = .03). Major amputation was performed in 6 of 48 limbs with patent grafts in the ESRD group because of uncontrolled infection or progression of necrosis. The limb salvage rate after arterial reconstruction was significantly lower in the ESRD group than in the non-ESRD group (p = .0019). The postoperative survival rate was lower in the ESRD group than in the non-ESRD group, although this difference was not significant (p = .052). Associated cardiovascular disease and systemic infection were the most frequent causes of death in the ESRD group. There was no significant difference in graft patency between the two groups after distal bypass surgery; however, the limb salvage rate was significantly lower in the ESRD group than in the non-ESRD group (p = .03). CONCLUSIONS: Critical limb ischemia associated with ESRD has a poor prognosis. Infection control is particularly important for achievement of good treatment outcomes.

Palmar dislocation of the thumb metacarpophalangeal joint: report of four cases and a review of the literature.

We report four cases of palmar dislocation of the thumb metacarpophalangeal joint and review of an additional 22 cases in the literature. Our four cases were associated with ligamentous injuries that prevented stable closed reduction. The patients were treated with open reduction and ligament repair and ultimately had a decreased range of motion. Our four cases and the 22 cases from literature fall into three types: Type A - stable joint (the metacarpophalangeal joint is stable, without severe ligament injury); Type B - tendon block (palmar displaced extensor tendons within the metacarpophalangeal joint prevents reduction); and Type C - joint instability (the metacarpophalangeal joint is unstable because of severe collateral ligament disruption). Type B is the most commonly reported type of palmar dislocation of the thumb metacarpophalangeal joint, with distinct features of the involvement of the collateral ligaments and failure of attempted manual reduction. The patients without severe collateral ligament disruption were managed with conservative treatment. The patients with interposition of extensor tendons and the patients with instability resulting from severe ligamentous injuries require surgical treatment.

Fate of the asymptomatic contralateral limb after initial intervention for ipsilateral critical limb ischemia.

AIM: In Trans-Atlantic Inter-Society Concensus (TASC) II, patients at risk for critical limb ischemia (CLI) without symptoms are termed "chronic subclinical ische mia," but research are still lacking. The objective was to find out whether clinically asymptomatic contralateral limbs at the time of treatment for ipsilateral CLI could be regarded as "chronic subclinical ischemia". METHODS: Ninety-six patients with CLI who had no symptoms in the contralateral limb were retrospectively reviewed. The symptoms of the contralateral limb after initial intervention for the ipsilateral limb were surveyed. Risk factors for developing CLI and tissue loss were then analyzed. RESULTS: Five patients (5.2%) became claudicants, 37 patients (38.5%) had symptoms of CLI, and 14 (14.6%) experienced tissue loss during the follow-up period. The overall CLI-free rates at 12, 36, and 60 months were 79.2%, 55.2%, and 45.8%, respectively, while the tissue loss-free rates at 12, 36, and 60 months were 91.3%, 78.8%, and 78.8%, respectively. Risk factor for developing CLI on the contralateral limb was having skin perfusion pressure (SPP) <40 mmHg at the surgery for ipsilateral limb. The presence of SPP <40 mmHg and end stage renal failure with hemodialysis resulted in a significantly high probability of tissue loss. CONCLUSION: Patients with CLI with an asymptomatic contralateral limb with an SPP value <40 mmHg are at a high risk of developing CLI and tissue loss during the follow-up period. Information on the contralateral limb at initial surgery may help to speculate the fate of the asymptomatic contralateral limb.

Feasibility trial for adjuvant chemotherapy with docetaxel plus cisplatin followed by single agent long-term administration of S-1 chemotherapy in patients with completely resected non-small cell lung cancer: Thoracic Oncology Research Group Study 0809.

BACKGROUND: We conducted a multicentre feasibility study for single agent long-term S-1 chemotherapy following docetaxel plus cisplatin in patients with curatively resected stage II-IIIA non-small cell lung cancer. METHODS: Patients received three cycles of docetaxel (60 mg m(-2)) plus cisplatin (80 mg m(-2)) and then received S-1 (40 mg m(-2) twice daily) for 14 consecutive days with a 1-week rest for >6 months (maximum, 1 year). The primary end point was feasibility, which was defined as the proportion of patients who completed eight or more cycles of S-1 chemotherapy. If the lower 95% confidence interval (CI) of this proportion was 50% or more, then the treatment was considered as feasible. The sample size was set at 125 patients. RESULTS: One hundred and thirty-one patients were enrolled, of whom 129 patients were eligible and assessable. In all, 109 patients (84.5%) completed 3 cycles of docetaxel plus cisplatin and 66 patients (51.2%, 95% CI: 42.5-59.8) completed 8 or more cycles of S-1 treatment. Grade 3/4 toxicities during the S-1 chemotherapy included anaemia (7.3%), neutropaenia (3.7%), and anorexia (3.7%). CONCLUSION: The toxicity level was acceptable, although the results did not meet our criterion for feasibility. Modification of the treatment schedule for S-1 chemotherapy might improve the treatment compliance.

Clinical outcomes of laparoscopic adhesiolysis for mechanical small bowel obstruction.

INTRODUCTION: Laparoscopy for small bowel obstruction (SBO) has increasingly been performed for the advantages minimally invasive surgery provides. However, its benefit remains unclear. METHODS: From January 2004 to July 2011, we enrolled 28 consecutive patients who underwent a laparoscopic operation for SBO, secondary to postoperative adhesions. We compared the results of SBO patients treated laparoscopically with those of 25 patients who underwent conventional open laparotomy in a retrospective matched-pair analysis. RESULTS: Laparoscopic treatment was completed in 25 patients (89%), including 17 laparoscopic-assisted cases. The mean procedural time was 112 minutes in the laparoscopic group and 79 minutes in the open group (P < 0.05). Patients resumed oral intake after a mean of 3 days in the laparoscopic group compared with a mean of 6.5 days in the open group (P < 0.05). The length of hospital stay was 11 and 22 days (P < 0.05), respectively, in the laparoscopic and open groups. Postoperative complications occurred in two patients in the laparoscopy group and 14 patients in the open group (P < 0.05). CONCLUSION: The laparoscopic approach was effective for the management of mechanical SBO in selected patients. Furthermore, minimally invasive laparoscopic adhesiolysis is also feasible and brings the benefit of cosmetic results.

Induction chemotherapy followed by gefitinib and concurrent thoracic radiotherapy for unresectable locally advanced adenocarcinoma of the lung: a multicenter feasibility study (JCOG 0402).

BACKGROUND: We conducted a feasibility study of induction chemotherapy followed by gefitinib and thoracic radiotherapy (TRT) for unresectable locally advanced adenocarcinoma of the lung. PATIENTS AND METHODS: Patients received induction chemotherapy with cisplatin (80 mg/m(2), days 1 and 22) and vinorelbine (25 mg/m(2), days 1, 8, 22, and 29) followed by gefitinib (250 mg daily, beginning on day 43, for 1 year) and TRT (60 Gy/30 fractions, days 57-98). The primary end point was feasibility, which was defined as the proportion of patients who completed 60 Gy of TRT and received >75% of the planned dose of gefitinib without developing grade 2 or worse pneumonitis. RESULTS: Of the 38 enrolled patients, 23 patients [60.5% ; 80% confidence interval (CI) 48.8-71.3] completed treatment without experiencing grade 2 or worse pneumonitis. During the chemoradiation phase, grade 3-4 alanine aminotransferase elevations were observed in 37.1% of the patients. The overall response rate was 73.0% . The median survival time was 28.5 months (95% CI 22.5-38.2), and the 2-year survival rate was 65.4% . CONCLUSIONS: Although the results did not meet our criterion for feasibility, the toxicity was acceptable. This treatment warrants further evaluation among patients with locally advanced non-small-cell lung cancer harboring epidermal growth factor receptor mutations.

Outcomes after open surgery and endovascular aneurysm repair for abdominal aortic aneurysm in patients with massive neck atheroma.

OBJECTIVE: We retrospectively analysed surgically treated abdominal aortic aneurysm (AAA) in patients with massive atheroma in the aneurysmal neck and compared the outcomes of endovascular aneurysm repair (EVAR) and open surgery (OS) to determine an appropriate strategy for massive neck atheroma cases. METHODS: A retrospective study was performed in 326 consecutive patients who underwent EVAR and in 247 patients who underwent OS. We defined massive neck atheromas if the following characteristics were observed: (1) thickness ≥ 5 mm; (2) the circumference of the infrarenal aorta ≥ 75%; and (3) length ≥ 5 mm. Twenty-eight patients (8.5%) in the EVAR group and 22 (8.9%) in the OS group met these criteria. We modified the previously published reporting standards on the basis of the selection of systemic and embolisation-related complications. RESULTS: Patients in the EVAR group had less intra-operative blood loss, shorter operation time, and shorter hospital stays after the operation (P < 0.01). No perioperative deaths were observed in either group. Major complications were categorised as early (in-hospital) or late (outpatient, within 6 months). Five and three patients in the OS and EVAR groups had early complications, but the difference was not statistically significant. In contrast, 7 patients in the EVAR group had late complications, compared to no patients in the OS group (P = 0.01). Kaplan-Meier analysis revealed a significantly higher survival rate in the OS group (P = 0.011). Two of the 4 patients with suprarenal clamping developed major complications. Mild eosinophilia was observed in 10 patients in the EVAR group. Proteinuria occurred or worsened in 5 EVAR patients and 1 OS patient. CONCLUSION: Compared to OS patients, EVAR patients with massive neck atheroma tend to develop late-phase complications possibly related to cholesterol crystal embolisation. The clinical features of massive neck atheroma patients receiving EVAR should be carefully monitored even after hospital discharge.

Comparative risk of common peroneal nerve injury in far anteromedial portal drilling and transtibial drilling in anatomical double-bundle ACL reconstruction.

PURPOSE: The purpose of this study was to investigate the risk of common peroneal nerve injury in FM drilling as compared to transtibial drilling in anatomical double-bundle ACL reconstruction. METHODS: Ten cadaveric knees without ligament injury or significant arthritis were used for this study. Knees were secured at 90° and 120° of flexion. In transtibial drilling groups, a guide pin was drilled through either the anteromedial bundle (AMB) or posterolateral bundle (PLB) tibial insertion site to either the AMB or PLB femoral insertion site (tibial insertion site-femoral insertion site: AM-AM, PL-PL, PL-AM and AM-PL). In FM drilling groups (FM-AM and FM-PL),the pin was drilled at the AMB or PLB femoral insertion site through the FM. We measured the shortest distance between the point at which the pin ran through the lateral cortex of the femur and the ipsilateral common peroneal nerve at a knee flexion of 90° and 120°. RESULTS: At a knee flexion of 90°, the shortest mean distance to the common peroneal nerve was 15.3 mm in the FM-PL group, 13.4 mm in the FM-AM group, 27.9 mm in the PL-PL group, 30.8 mm in the AM-AM group, 37.8 mm in the PL-AM group and 29.5 mm in the AM-PL group. At a knee of flexion 120°, the mean distance was 17.3 mm in the FM-PL group, 18.1 mm in the FM-AM group, 32.2 mm in the PL-PL group, 36.6 mm in the AM-AM group, 38.0 mm in the PL-AM group and 35.2 mm in the AM-PL group. Significant differences were observed between 90° and 120° of knee flexion in the FM-AM, PL-PL, AM-AM and AM-PL groups (P < 0.05). Significant differences were observed at flex 90° between the FM-AM group and AM-AM group, and between the FM-AM group and PL-AM group. Significant differences were observed at flex 120° between the FM-AM group and AM-AM group, between the FM-AM group and PL-AM group and between the FM-PL group and AM-PL group. CONCLUSION: The distance to the peroneal nerve in FM drilling was significantly longer at 120° than at 90° of knee flexion. Therefore, the risk of peroneal injury using FM drilling should decrease at a higher angle of knee flexion.