Alteration of gut microbiota by a Westernized lifestyle and its correlation with insulin resistance in non-diabetic Japanese men.

AIMS/INTRODUCTION: The severity of insulin resistance is higher in Japanese-American people with American lifestyles than in native Japanese people with Japanese lifestyles. Recently, the role of gut microbiota in the control of host metabolic homeostasis and organ physiology has been recognized. In addition, gut microbiota alterations have been suggested to contribute to pathogenesis of insulin resistance. The principle aim of the present study was to evaluate the impact of a Westernized lifestyle on the gut microbiota of Japanese-Americans versus native Japanese, and its correlation with insulin resistance. MATERIALS AND METHODS: A total of 14 native Japanese men living in Hiroshima, Japan, and 14 Japanese-American men living in Los Angeles, USA, were included. A 75-g oral glucose tolerance test was carried out for all participants to assess their glucose tolerance, and normal glucose tolerance was observed. We compared the insulin response with oral glucose load, the Matsuda Index, and the composition of the gut microbiota between the native Japanese and Japanese-American men. RESULTS: Japanese-American men showed higher area under the curve values for serum insulin concentrations during the oral glucose tolerance test and lower Matsuda Index than native Japanese men. Gut microbiota composition of the Japanese-American men was different; in particular, they showed a relatively lower abundance of Odoribacter than native Japanese men. The ratio between relative abundance of Odoribacter and Matsuda Index was positively correlated between the two groups. CONCLUSIONS: Our findings suggest that Westernized lifestyles alter gut microbiota, and its alteration might induce insulin resistance in non-diabetic Japanese men.

Measurement of midnight ACTH levels is useful for the evaluation of midnight cortisol levels.

OBJECTIVE: Elevated midnight cortisol levels induced by non-suppressed ACTH levels may lead to false-positive results for hypercortisolism in patients with adrenal incidentaloma. We investigated whether plasma ACTH-associated high midnight serum cortisol levels are correlated with other endocrinological findings with respect to hypothalamic-pituitaryadrenal function or hypercortisolism status. METHODS: Two-hundred-forty-six patients with adrenocortical adenoma were evaluated via measurements of midnight ACTH and cortisol levels, a 1-mg dexamethasone suppression test (DST), and a cosyntropin-releasing hormone (CRH) stimulation test. Patients were divided into four groups according to their midnight plasma ACTH levels. RESULTS: The groups with higher midnight ACTH levels had significantly higher basal ACTH levels. A positive relationship was observed between midnight serum cortisol and serum cortisol in the 1-mg DST for all groups; stronger associations were observed in the group with lower midnight ACTH. In the CRH test, peak, delta, and sigma ACTH had significant inverse relationships with midnight cortisol levels in the lowest and second lowest midnight ACTH groups. Patients with midnight cortisol levels >3.5 µg/dL were further divided into two groups according to whether their midnight plasma ACTH levels were below or above 10.0 pg/mL. There were significantly fewer patients with hypercortisolism in the higher ACTH group; midnight serum cortisol levels were associated with hypercortisolism only in the lower ACTH group. CONCLUSION: We demonstrated that midnight ACTH-associated cortisol values were not correlated with other endocrinological findings or hypercortisolism state. Measurement of midnight ACTH levels is important, and careful evaluation is needed for patients with higher midnight ACTH levels.

Roles of Gut-Derived Secretory Factors in the Pathogenesis of Non-Alcoholic Fatty Liver Disease and Their Possible Clinical Applications.

The rising prevalence of non-alcoholic fatty liver disease (NAFLD) parallels the global increase in the number of people diagnosed with obesity and metabolic syndrome. The gut-liver axis (GLA) plays an important role in the pathogenesis of NAFLD/non-alcoholic steatohepatitis (NASH). In this review, we discuss the clinical significance and underlying mechanisms of action of gut-derived secretory factors in NAFLD/NASH, focusing on recent human studies. Several studies have identified potential causal associations between gut-derived secretory factors and NAFLD/NASH, as well as the underlying mechanisms. The effects of gut-derived hormone-associated drugs, such as glucagon-like peptide-1 analog and recombinant variant of fibroblast growth factor 19, and other new treatment strategies for NAFLD/NASH have also been reported. A growing body of evidence highlights the role of GLA in the pathogenesis of NAFLD/NASH. Larger and longitudinal studies as well as translational research are expected to provide additional insights into the role of gut-derived secretory factors in the pathogenesis of NAFLD/NASH, possibly providing novel markers and therapeutic targets in patients with NAFLD/NASH.

High-dose rate intracavitary brachytherapy pretreatment dwell position verification using a transparent applicator.

PURPOSE: The major errors in HDR brachytherapy are related to treatment distance, almost all of which are caused by incorrect applicator information. The aim of this study is to propose a quick pretreatment verification method to evaluate channel length and dwell position with a transparent applicator, which, in addition, is suitable as an education tool to assist in the understanding of the applicator structure. METHODS: A transparent applicator model was fabricated using a three-dimensional printer and transparent resin. Its aim is to be a replica of a real gynecological applicator. The pretreatment verification is performed by observing the planned dwell positions of a check cable inside a transparent applicator. A digital camera acquired images and the dwell positions of the radioactive source and check cable were evaluated by comparing them with respect to the theoretical dwell positions marked by the proper x-ray marker. The potential effectiveness of verification using a transparent applicator was also evaluated using brachytherapy events reported in the literature. RESULTS: The transparent applicator closely resembles the real applicator in shape and had an error of less than 0.2 mm. The average dwell position displacement between the radioactive source and check cable was 0.4 mm. The analysis of brachytherapy events showed that channel-length, dwell-position, and step-size errors made up 50% of all events, but affected 64% of all patients. CONCLUSIONS: The transparent applicator model enables a noninvasive, repeatable verification of the channel length and dwell positions to be performed before treatment. This verification has the potential to help prevent common errors in treatment delivery. In addition, the transparent applicator model can be used as a teaching tool to help clinicians understand the operation of the applicator, lowering the risk of events.

Capsular bag irrigation using 0.025% povidone-iodine in balanced salt solution PLUS for the treatment of postoperative endophthalmitis.

We examined the effectiveness and adverse events of using balanced salt solution (BSS) PLUS containing 0.025% povidone-iodine, a non-oculotoxic concentration, for capsular bag irrigation in a case of endophthalmitis mainly involving the anterior chamber. A 57-year-old female underwent cataract surgery and developed hypopyon on day 3 after surgery, with mainly anterior chamber inflammation. The capsular bag was irrigated with BSS PLUS containing 0.025% povidone-iodine. Gram-negative rods were detected from the anterior chamber fluid. Post-procedural visual acuity was 24/20. In a case, endophthalmitis was resolved and there were no adverse events. With the recent increase in multidrug-resistant bacteria, use of 0.025% povidone-iodine in BSS PLUS for anterior chamber irrigation is expected to be useful.

Gut Microbiota as a Therapeutic Target for Metabolic Disorders.

BACKGROUND: Gut microbiota play a vital role not only in the digestion and absorption of nutrients, but also in homeostatic maintenance of host immunity, metabolism and the gut barrier. Recent evidence suggests that gut microbiota alterations contribute to the pathogenesis of metabolic disorders. OBJECTIVE AND METHOD: In this review, we discuss the association between the gut microbiota and metabolic disorders, such as obesity, type 2 diabetes mellitus and non-alcoholic fatty liver disease, and the contribution of relevant modulating interventions, focusing on recent human studies. RESULTS: Several studies have identified potential causal associations between gut microbiota and metabolic disorders, as well as the underlying mechanisms. The effects of modulating interventions, such as prebiotics, probiotics, fecal microbiota transplantation, and other new treatment possibilities on these metabolic disorders have also been reported. CONCLUSION: A growing body of evidence highlights the role of gut microbiota in the development of dysbiosis, which in turn influences host metabolism and disease phenotypes. Further studies are required to elucidate the precise mechanisms by which gut microbiota-derived mediators induce metabolic disorders and modulating interventions exert their beneficial effects in humans. The gut microbiota represents a novel potential therapeutic target for a range of metabolic disorders.

Effect of miglitol on the suppression of nonalcoholic steatohepatitis development and improvement of the gut environment in a rodent model.

BACKGROUND: The gut environment has been considered to play a role in the development of nonalcoholic steatohepatitis (NASH). α-glucosidase inhibitors (α-GIs) delay carbohydrate absorption and may change the gut environment. We considered that the protective effect of α-GIs against NASH development is related to changes in the gut environment and thus investigated the effects of miglitol, an α-GI, on NASH development and the gut environment. METHODS: Mice were divided into three groups and fed a normal chow diet (NCD), a high-fat high-sucrose diet (HFHSD), or HFHSD plus 0.04% miglitol (HFHSD plus M) for 12 weeks. RESULTS: Insulin resistance developed more in the HFHSD group than in the NCD group, whereas it was suppressed in the HFHSD plus M group. NASH was evaluated histologically, biochemically, and on the basis of messenger RNA expression levels. Miglitol treatment suppressed HFHSD-induced NASH development with the suppression of hepatic Toll-like receptor 4 expression, increased glucagon-like peptide 1 (GLP-1) concentration, and reduced lipopolysaccharide concentration in portal plasma. Regarding the gut environment, the intestinal transit time was shortened and colon inflammation was suppressed in the HFHSD plus M group compared with the HFHSD group. Regarding the gut microbiota, the abundances of Erysipelotrichaceae and Coriobacteriaceae were increased in the HFHSD group compared with the NCD group, whereas the increase was suppressed in the HFHSD plus M group. CONCLUSIONS: We demonstrated that miglitol has a protective effect against HFHSD-induced NASH development. The increased GLP-1 secretion and the suppression of endotoxemia, associated with the changes in the gut environment, including the gut microbiota, could contribute to the underlying mechanisms.

A robust measurement point for dose verification in delivery quality assurance for a robotic radiosurgery system.

In this CyberKnife® dose verification study, we investigated the effectiveness of the novel potential error (PE) concept when applied to the determination of a robust measurement point for targeting errors. PE was calculated by dividing the differences between the maximum increases and decreases in dose distributions by the original distribution after obtaining the former by shifting the source-to-axis and off-axis distances of each beam by ±1.0 mm. Thus, PE values and measurement point dose heterogeneity were analyzed in 48 patients who underwent CyberKnife radiotherapy. Sixteen patients who received isocentric dose delivery were set as the control group, whereas 32 who received non-isocentric dose delivery were divided into two groups of smaller PE (SPE) and larger PE (LPE) by using their median PE value. The mean dose differences (± standard deviations) were 1.0 ± 0.9%, 0.5 ± 1.4% and 4.1 ± 2.8% in the control, SPE and LPE groups, respectively. We observed significant correlations of the dose difference with the PE value (r = 0.582, P < 0.001) and dose heterogeneity (r = 0.471, P < 0.001). We concluded that when determining a robust measurement point for CyberKnife point dose verification, PE evaluation was more effective than the conventional dose heterogeneity-based method that introduced optimal measurement point dose heterogeneity of <10% across the detector.

Dose-volume analysis of predictors for chronic gastrointestinal complications in patients with cervical cancer treated with postoperative concurrent chemotherapy and whole-pelvic radiation therapy.

The purpose of this study is to evaluate dose-volume histogram (DVH) predictors for the development of chronic gastrointestinal (GI) complications in patients with cervical cancer who have undergone postoperative concurrent chemotherapy and whole-pelvic radiation therapy (WPRT). The subjects were 135 patients who had undergone postoperative WPRT with concurrent nedaplatin-based chemotherapy between 2000 and 2014. Associations between selected DVH parameters and the incidence of chronic GI complications of G3 or higher were evaluated. Chronic GI complications of severity G3 occurred in 18 (13%) patients. Patients with GI complications had significantly greater V5-V45, mean dose and the generalized equivalent uniform dose (gEUD) of the small bowel loops, compared with those without GI complications. V30-V45, mean dose and gEUD of the bowel bag also showed significant differences between patients with and without GI complications. In contrast, no parameter for the large bowel loop was correlated with GI complications. Receiver operating characteristics curve analysis indicated that V30-V45 of the small bowel loops were better predictors than these respective parameters for the bowel bag. Next, patients were divided into four groups based on the median V15 and V40 of the small bowel loops. The group with both a high V15 and a high V40 showed a significantly higher probability of chronic GI complications. In conclusion, the small bowel loops are better predictors of chronic GI complications compared with the bowel bag, and a relatively high-dose volume (e.g. V40) of the small bowel loops is a useful predictor of chronic GI complications.

Involvement of resistin-like molecule ß in the development of methionine-choline deficient diet-induced non-alcoholic steatohepatitis in mice.

Resistin-like molecule ß (RELMß) reportedly has multiple functions including local immune responses in the gut. In this study, we investigated the possible contribution of RELMß to non-alcoholic steatohepatitis (NASH) development. First, RELMß knock-out (KO) mice were shown to be resistant to methionine-choline deficient (MCD) diet-induced NASH development. Since it was newly revealed that Kupffer cells in the liver express RELMß and that RELMß expression levels in the colon and the numbers of RELMß-positive Kupffer cells were both increased in this model, we carried out further experiments using radiation chimeras between wild-type and RELMß-KO mice to distinguish between the contributions of RELMß in these two organs. These experiments revealed the requirement of RELMß in both organs for full manifestation of NASH, while deletion of each one alone attenuated the development of NASH with reduced serum lipopolysaccharide (LPS) levels. The higher proportion of lactic acid bacteria in the gut microbiota of RELMß-KO than in that of wild-type mice may be one of the mechanisms underlying the lower serum LPS level the former. These data suggest the contribution of increases in RELMß in the gut and Kupffer cells to NASH development, raising the possibility of RELMß being a novel therapeutic target for NASH.

High-Dose-Rate Brachytherapy as Monotherapy for Intermediate- and High-Risk Prostate Cancer: Clinical Results for a Median 8-Year Follow-Up.

PURPOSE: To present mature results of high-dose-rate brachytherapy (HDR-BT) as monotherapy for intermediate- and high-risk prostate cancer. METHODS AND MATERIALS: From 1995 through 2012, 190 patients, 79 with intermediate-risk and 111 with high-risk prostate cancer, were treated with HDR-BT alone using 48 Gy/8 fractions, 54 Gy/9 fractions, or 45.5 Gy/7 fractions over 4 to 5 days. Neoadjuvant with or without adjuvant androgen deprivation therapy was administered to 139 patients, 35 intermediate- and 104 high-risk. RESULTS: Median follow-up time was 92 months (range, 10-227 months), with a minimum of 2 years for surviving patients. Respective rates of cause-specific survival, overall survival, metastasis-free survival, and biochemical no evidence of disease for the intermediate-risk patients were 100%, 100%, 96%, and 93% at 5 years, and 100%, 96%, 91%, and 91% at 8 years. Corresponding rates for the high-risk patients were 97%, 93%, 84%, and 81% at 5 years, and 93%, 81%, 74%, and 77% at 8 years. The cumulative incidence of late grade 2 to 3 genitourinary toxicity was 5% at 5 years and 10% at 8 years, and that of late grade 3 was 0 at 5 years and 1% at 8 years. The cumulative incidence of late grade 2-3 gastrointestinal toxicity was 4% at 5 years and 6% at 8 years, and that of late grade 3 was 0 at 5 years and 2% at 8 years. No grade 4 or 5 toxicity was detected. CONCLUSIONS: Our single-institution study with a median 8-year follow-up showed that HDR-BT as monotherapy was safe and effective for patients with intermediate- and high-risk prostate cancer.

Distinct Time Course of the Decrease in Hepatic AMP-Activated Protein Kinase and Akt Phosphorylation in Mice Fed a High Fat Diet.

AMP-activated protein kinase (AMPK) plays an important role in insulin resistance, which is characterized by the impairment of the insulin-Akt signaling pathway. However, the time course of the decrease in AMPK and Akt phosphorylation in the liver during the development of obesity and insulin resistance caused by feeding a high fat diet (HFD) remains controversial. Moreover, it is unclear whether the impairment of AMPK and Akt signaling pathways is reversible when changing from a HFD to a standard diet (SD). Male ddY mice were fed the SD or HFD for 3 to 28 days, or fed the HFD for 14 days, followed by the SD for 14 days. We examined the time course of the expression and phosphorylation levels of AMPK and Akt in the liver by immunoblotting. After 3 days of feeding on the HFD, mice gained body weight, resulting in an increased oil red O staining, indicative of hepatic lipid accumulation, and significantly decreased AMPK phosphorylation, in comparison with mice fed the SD. After 14 days on the HFD, systemic insulin resistance occurred and Akt phosphorylation significantly decreased. Subsequently, a change from the HFD to SD for 3 days, after 14 days on the HFD, ameliorated the impairment of AMPK and Akt phosphorylation and systemic insulin resistance. Our findings indicate that AMPK phosphorylation decreases early upon feeding a HFD and emphasizes the importance of prompt lifestyle modification for decreasing the risk of developing diabetes.

LUBAC Formation Is Impaired in the Livers of Mice with MCD-Dependent Nonalcoholic Steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is a disorder characterized by hepatic lipid accumulation followed by the inflammation-induced death of hepatocytes and fibrosis. In this process, oxidative stress contributes to the induction of several inflammatory cytokines including TNF-α andIL-1ß in macrophages, while, in hepatocytes, NF-κB reportedly induces the expressions of cell survival genes for protection from apoptosis. Recently, it was reported that the new ubiquitin ligase complex termed linear ubiquitin chain assembly complex (LUBAC), composed of SHARPIN (SHANK-associated RH domain-interacting protein), HOIL-1L (longer isoform of heme-oxidized iron-regulatory protein 2 ubiquitin ligase-1), and HOIP (HOIL-1L interacting protein), forms linear ubiquitin on NF-κB essential modulator (NEMO) and thereby induces NF-κB pathway activation. In this study, we demonstrated the formation of LUBAC to be impaired in the livers of NASH rodent models produced by methionine and choline deficient (MCD) diet feeding, first by either gel filtration or Blue Native-PAGE, with subsequent confirmation by western blotting. The reduction of LUBAC is likely to be attributable to markedly reduced expression of SHARPIN, one of its components. Thus, impaired LUBAC formation, which would result in insufficient NF-κB activation, may be one of the molecular mechanisms underlying the enhanced apoptotic response of hepatocytes in MCD diet-induced NASH livers.

Mosapride citrate improves nonalcoholic steatohepatitis with increased fecal lactic acid bacteria and plasma glucagon-like peptide-1 level in a rodent model.

Several lines of evidence have suggested a role of gut microbiota in the etiology of nonalcoholic steatohepatitis (NASH). NASH subjects reportedly showed a prolonged orocecal transit time coexistent with small intestinal bacterial overgrowth. We considered the possibility that enhanced gastrointestinal motility would influence gut microbiota and thus investigated the effects of the gastroprokinetic agent mosapride citrate (MC) on gut microbiota and the development of NASH using a methionine-choline deficient (MCD) diet-fed rodent model. Mice were divided into three groups, given the normal chow diet (NCD), the MCD diet, or the MCD diet containing 10 mg·kg(-1)·day(-1) of MC (MCD plus MC) for 6 wk. NASH development was evaluated based on hepatic histochemical findings, serum parameters and various mRNA and/or protein expression levels. MC treatment suppressed MCD diet-induced NASH development, with reduced serum lipopolysaccharide and increased plasma glucagon-like peptide-1 (GLP-1) concentrations. Calculation of the relative abundance of each strain based on gut microbiota analyses indicated lactic acid bacteria specifically, such as Bifidobacterium and Lactobacillus, in feces to be decreased in the MCD, compared with the NCD group. Interestingly, the reduction in lactic acid bacteria in the MCD diet group was reversed in the MCD plus MC group. In addition, colon inflammation observed in the MCD diet group was reduced in the MCD plus MC group. Therefore, MC showed a protective effect against MCD diet-induced NASH development in our rodent model, with possible involvements of increased fecal lactic acid bacteria, protection against colon inflammation and elevated plasma GLP-1.

Lactobacillus casei strain Shirota protects against nonalcoholic steatohepatitis development in a rodent model.

Gut microbiota alterations are associated with various disorders. In this study, gut microbiota changes were investigated in a methionine-choline-deficient (MCD) diet-induced nonalcoholic steatohepatitis (NASH) rodent model, and the effects of administering Lactobacillus casei strain Shirota (LcS) on the development of NASH were also investigated. Mice were divided into three groups, given the normal chow diet (NCD), MCD diet, or the MCD diet plus daily oral administration of LcS for 6 wk. Gut microbiota analyses for the three groups revealed that lactic acid bacteria such as Bifidobacterium and Lactobacillus in feces were markedly reduced by the MCD diet. Interestingly, oral administration of LcS to MCD diet-fed mice increased not only the L. casei subgroup but also other lactic acid bacteria. Subsequently, NASH development was evaluated based on hepatic histochemical findings, serum parameters, and various mRNA and/or protein expression levels. LcS intervention markedly suppressed MCD-diet-induced NASH development, with reduced serum lipopolysaccharide concentrations, suppression of inflammation and fibrosis in the liver, and reduced colon inflammation. Therefore, reduced populations of lactic acid bacteria in the colon may be involved in the pathogenesis of MCD diet-induced NASH, suggesting normalization of gut microbiota to be effective for treating NASH.

Par14 protein associates with insulin receptor substrate 1 (IRS-1), thereby enhancing insulin-induced IRS-1 phosphorylation and metabolic actions.

Pin1 and Par14 are parvulin-type peptidyl-prolyl cis/trans isomerases. Although numerous proteins have been identified as Pin1 substrates, the target proteins of Par14 remain largely unknown. Par14 expression levels are increased in the livers and embryonic fibroblasts of Pin1 KO mice, suggesting a compensatory relationship between the functions of Pin1 and Par14. In this study, the association of Par14 with insulin receptor substrate 1 (IRS-1) was demonstrated in HepG2 cells overexpressing both as well as endogenously in the mouse liver. The analysis using deletion-mutated Par14 and IRS-1 constructs revealed the N-terminal portion containing the basic domain of Par14 and the two relatively C-terminal portions of IRS-1 to be involved in these associations, in contrast to the WW domain of Pin1 and the SAIN domain of IRS-1. Par14 overexpression in HepG2 markedly enhanced insulin-induced IRS-1 phosphorylation and its downstream events, PI3K binding with IRS-1 and Akt phosphorylation. In contrast, treating HepG2 cells with Par14 siRNA suppressed these events. In addition, overexpression of Par14 in the insulin-resistant ob/ob mouse liver by adenoviral transfer significantly improved hyperglycemia with normalization of hepatic PEPCK and G6Pase mRNA levels, and gene suppression of Par14 using shRNA adenovirus significantly exacerbated the glucose intolerance in Pin1 KO mice. Therefore, although Pin1 and Par14 associate with different portions of IRS-1, the prolyl cis/trans isomerization in multiple sites of IRS-1 by these isomerases appears to be critical for efficient insulin receptor-induced IRS-1 phosphorylation. This process is likely to be one of the major mechanisms regulating insulin sensitivity and also constitutes a potential therapeutic target for novel insulin-sensitizing agents.

Integrator complex plays an essential role in adipose differentiation.

The dynamic process of adipose differentiation involves stepwise expressions of transcription factors and proteins specific to the mature fat cell phenotype. In this study, it was revealed that expression levels of IntS6 and IntS11, subunits of the Integrator complex, were increased in 3T3-L1 cells in the period when the cells reached confluence and differentiated into adipocytes, while being reduced to basal levels after the completion of differentiation. Suppression of IntS6 or IntS11 expression using siRNAs in 3T3-L1 preadipocytes markedly inhibited differentiation into mature adipocytes, based on morphological findings as well as mRNA analysis of adipocyte-specific genes such as Glut4, perilipin and Fabp4. Although Pparγ2 protein expression was suppressed in IntS6 or IntS11-siRNA treated cells, adenoviral forced expression of Pparγ2 failed to restore the capacity for differentiation into mature adipocytes. Taken together, these findings demonstrate that increased expression of Integrator complex subunits is an indispensable event in adipose differentiation. Although further study is necessary to elucidate the underlying mechanism, the processing of U1, U2 small nuclear RNAs may be involved in cell differentiation steps.

[A case of carcinoma associated with anal fistula effectively treated with preoperative chemoradiotherapy].

A 60-year-old man presented with anal pain. He was diagnosed as having perianal abscess and carcinoma associated with anal fistula. We performed chemoradiotherapy (radiation, total 50.4 Gy; capecitabine 2,000 mg/m2) followed by chemotherapy( XELOX, 2 courses: capecitabine 2,000 mg/m2, oxaliplatin 130 mg/m2). After chemoradiotherapy, the tumor significantly reduced in size. Laparoscopic abdominoperineal resection of the rectum, extended resection of the perianal region, and reconstruction of the perianal skin defect using a rectus abdominis musculocutaneous flap were performed. Histopathologically, the tumor was classified as tub2, pMP, ly0, v0, pN0 (0/3), pStage I, and the therapeutic efficacy was classified as Grade 2. Chemoradiation appears to be effective for the treatment of carcinomas associated with anal fistula.

[Neoadjuvant chemoradiotherapy with capecitabine and oxaliplatin for the treatment of locally advanced lower rectal cancer].

Chemoradiotherapy before surgical treatment of locally advanced lower rectal cancer is currently uncommon in Japan. We have treated 5 patients with T3 and/or N1 and 2 patients with rectal cancer using chemoradiotherapy including capecitabine and oxaliplatin( XELOX). The treatment consisted of concomitant administration of radiotherapy( 45 Gy/25 Fr), capecitabine (2,000 mg/m2/day; 2 weeks followed by 1 week off), and XELOX (2 courses). Surgery was performed 1 month after the final dose of chemotherapy was administered. The adverse events of Grade greater than 2 observed were radiation dermatitis (n=3), peripheral neuropathy (n=1), and rash (n=1). Either laparoscopic abdominoperineal resection( n=4) or open low anterior resection( n=1) was performed for surgical treatment. Histopathological regression grading revealed Grade 1a (n=1) and Grade 2 (n=4). The combined therapy resulted in downstaging in all patients. Preoperative chemoradiotherapy followed by XELOX might be effective for the treatment of locally advanced lower rectal cancer.