Incidence of and risk factors for incisional hernia after abdominal surgery.

BACKGROUND: Few larger studies have estimated the incidence of incisional hernia (IH) after abdominal surgery. METHODS: Patients who had abdominal surgery between November 2009 and February 2011 were included in the study. The incidence rate and risk factors for IH were monitored for at least 180 days. RESULTS: A total of 4305 consecutive patients were registered. Of these, 378 were excluded because of failure to complete follow-up and 3927 patients were analysed. IH was diagnosed in 318 patients. The estimated incidence rates for IH were 5·2 per cent at 12 months and 10·3 per cent at 24 months. In multivariable analysis, wound classification III and IV (hazard ratio (HR) 2·26, 95 per cent confidence interval 1·52 to 3·35), body mass index of 25 kg/m(2) or higher (HR 1·76, 1·35 to 2·30), midline incision (HR 1·74, 1·28 to 2·38), incisional surgical-site infection (I-SSI) (HR 1·68, 1·24 to 2·28), preoperative chemotherapy (HR 1·61, 1·08 to 2·37), blood transfusion (HR 1·46, 1·04 to 2·05), increasing age by 10-year interval (HR 1·30, 1·16 to 1·45), female sex (HR 1·26, 1·01 to 1·59) and thickness of subcutaneous tissue for every 1-cm increase (HR 1·18, 1·03 to 1·35) were identified as independent risk factors. Compared with superficial I-SSI, deep I-SSI was more strongly associated with the development of IH. CONCLUSION: Although there are several risk factors for IH, reducing I-SSI is an important step in the prevention of IH. REGISTRATION NUMBER: UMIN000004723 (University Hospital Medical Information Network, http://www.umin.ac.jp/ctr/index.htm).

Early results of multicenter phase II trial of perioperative oxaliplatin and capecitabine without radiotherapy for high-risk rectal cancer: CORONA I study.

BACKGROUNDS: Perioperative introduction of developed chemotherapy into the treatment strategy for locally advanced rectal cancer (LARC) may be a promising option. However, the most prevalent treatment for high-risk LARC remains preoperative chemoradiotherapy (CRT) in Western countries. PATIENTS AND METHODS: A phase II trial was undertaken to evaluate safety and efficacy of perioperative XELOX without radiotherapy (RT) for patients with high-risk LARC. Patients received 4 cycles of XELOX before and after surgery, respectively. Primary endpoint was disease-free survival. RESULTS: We enrolled 41 patients between June 2012 and April 2014. The completion rate of the preoperative XELOX was 90.3%. Twenty-nine patients (70.7%) could start postoperative XELOX, 15 of these patients (51.7%) completed 4 cycles. Allergic reaction to oxaliplatin was experienced by 5 patients (17.2%) during postoperative XELOX. One patient received additional RT after preoperative XELOX. Consequently, the remaining 40 patients underwent primary resection. Major complications occurred in 6 of 40 patients (15.0%). Pathological complete response (pCR) rate was 12.2%, and good tumor regression was exhibited in 31.7%. N down-staging (cN+ to ypN0) and T down-staging were detected in 56.7% and 52.5%, respectively. Clinical T4 tumor was a predictor of poor pathological response (p < 0.001). CONCLUSIONS: We could show the favorable pCR rate after preoperative XELOX alone. However, the T and N down-staging rate was likely to be insufficient. When tumor regression is essential for curative resection, the use of preoperative CRT is likely to be recommended. For patients with massive LN metastasis, the additional Bev to NAC might be a promising option.

A variation of the vascular pedicle of the latissimus dorsi muscle.

A case of a rare variation of the vascular pedicle of the latissimus dorsi musculocutaneous flap is described. Its main vascular pedicle was the circumflex scapular vessel.

Examination of local anti-inflammatory activities of new steroids, hemisuccinyl methyl glycolates.

To overcome the side effects of steroids, novel steroid-17-yl methyl glycolates with succinyl group at C-20, derived from prednisolone and dexamethasone were prepared based on a concept of the antedrug. Their topical anti-inflammatory activity and systemic effects were evaluated through croton oil-induced ear edema and paper disk granuloma bioassay. Among them, (20S)-succinyl dexamethasone derivatives (7 and 11) indicated more potent anti-inflammatory activity than the parent dexamethasone and did not show corticosteroidal side effects of thymic, adrenal involution or body weight loss. Both 7 and 11 were immediately metabolized into active compound 3 and this metabolite was eliminated with mean half-lives of 0.786 to 0.866 h in rat serum. Our findings suggest that these two compounds might be candidates as the novel steroids, and that that introduction of the succinyl group into the methyl glycolates at C-20 is useful to avoid suppression of organs due to the side effects of corticosteroids.

Examination on biological activities and fates of new steroids, steroid-17-yl methyl glycolate derivatives.

A variety of acyl derivatives based on the "antedrug" concept were synthesized to evaluate their biological activities, in vitro fate in human serum and examine pharmacokinetics in rats. Among the prepared compounds, acetyl and pivaloyl derivatives (8 and 9) showed strong to vasoconstrictive activity in human, exceeding that of dexamethasone. In rats, topical administration of the compound 8 significantly reduced oxazolone-induced ear edema compared to that of control. These activities were almost equal to that of prednisolone, however 9 did not show any suppression of the oxazolone-induced edema. The in vitro half-lives of 8 and 9 in human serum were 18.2 and 43.8 hours, respectively. Prednisolone and dexamethasone were extremely stable under the used conditions. When compound 8 was intravenously administrated to rats, its metabolites, 20(R)-methyl dexamethasonate (4) and carboxylic acid (18), were found in the systemic blood. The total body clearance of 8 was 1734 ml x hr(-1) x kg(-1), which was about 12 times larger than that of dexamethasone. On the other hand, 9 was found to be metabolized instantaneously to methyl prednisolonate (1) in systemic serum. Acetyl derivative 8 derived from dexamethasone may thus be useful as a topical steroid which offers the advantage of a low potential for systemic and local side effects.

NAK is an IkappaB kinase-activating kinase.

Phosphorylation of IkappaB by the IkappaB kinase (IKK) complex is a critical step leading to IkappaB degradation and activation of transcription factor NF-kappaB. The IKK complex contains two catalytic subunits, IKKalpha and IKKbeta, the latter being indispensable for NF-kappaB activation by pro-inflammatory cytokines. Although IKK is activated by phosphorylation of the IKKbeta activation loop, the physiological IKK kinases that mediate responses to extracellular stimuli remain obscure. Here we describe an IKK-related kinase, named NAK (NF-kappaB-activating kinase), that can activate IKK through direct phosphorylation. NAK induces IkappaB degradation and NF-kappaB activity through IKKbeta. Endogenous NAK is activated by phorbol ester tumour promoters and growth factors, whereas catalytically inactive NAK specifically inhibits activation of NF-kappaB by protein kinase C-epsilon (PKCepsilon). Thus, NAK is an IKK kinase that may mediate IKK and NF-kappaB activation in response to growth factors that stimulate PKCepsilon activity.