Laparoscopic sentinel node navigation surgery versus laparoscopic gastrectomy with lymph node dissection for early gastric cancer: short-term outcomes of a multicentre randomized controlled trial (SENORITA).

BACKGROUND: Sentinel node navigation surgery reduces the extent of gastric and lymph node dissection, and may improve quality of life. The benefit and harm of laparoscopic sentinel node navigation surgery (LSNNS) for early gastric cancer is unknown. The SENORITA (SEntinel Node ORIented Tailored Approach) trial investigated the pathological and surgical outcomes of LSNNS compared with laparoscopic standard gastrectomy (LSG) with lymph node dissection. METHODS: The SENORITA trial was an investigator-initiated, open-label, parallel-assigned, non-inferiority, multicentre RCT conducted in Korea. The primary endpoint was 3-year disease-free survival. The secondary endpoints, morbidity and mortality within 30 days of surgery, are reported in the present study. RESULTS: A total of 580 patients were randomized to LSG (292) or LSNNS (288). Surgery was undertaken in 527 patients (LSG 269, LSNNS 258). LSNNS could be performed according to the protocol in 245 of 258 patients, and a sentinel node basin was detected in 237 (96·7 per cent) Stomach-preserving surgery was carried out in 210 of 258 patients (81·4 per cent). Postoperative complications occurred in 51 patients in the LSG group (19·0 per cent) and 40 (15·5 per cent) in the LSNNS group (P = 0·294). Complications with a Clavien-Dindo grade of III or higher occurred in 16 (5·9 per cent) and 13 (5·0 per cent) patients in the LSG and LSNNS groups respectively (P = 0·647). CONCLUSION: The rate and severity of complications following LSNNS for early gastric cancer are comparable to those after LSG with lymph node dissection. Registration number: NCT01804998 ( http://www.clinicaltrials.gov).

ANTECEDENTES: La cirugía de navegación del ganglio centinela (sentinel node navigation surgery, SNNS) reduce la extensión de la resección gástrica y ganglionar, y puede mejorar la calidad de vida. Se desconoce el beneficio y el daño de la cirugía de navegación del ganglio centinela por vía laparoscópica (laparoscopic sentinel node navigation surgery, LSNNS) para el cáncer gástrico precoz. El ensayo clínico SENORITA investigó los resultados patológicos y quirúrgicos de LSNNS en comparación con la gastrectomía laparoscópica estándar (laparoscopic gastrectomy, LSG) con disección ganglionar (lymph node dissection, LND). MÉTODOS: El ensayo SENORITA fue un ensayo multicéntrico aleatorizado y controlado, iniciado por investigadores, abierto, con asignación a grupos paralelos y de no inferioridad llevado a cabo en Corea. El resultado primario fue la supervivencia libre de enfermedad a los 3 años. En el presente estudio, se describen los resultados secundarios correspondientes a morbilidad y mortalidad a los 30 días del postoperatorio. RESULTADOS: Un total de 580 pacientes fueron aleatorizados a LG (n = 292) o LSNNS (n = 288). La cirugía se realizó en 527 pacientes (LG 269, LSNNS 258). LSNNS pudo ser realizada de acuerdo con el protocolo en 245 de 258 pacientes y en 237 de 245 pacientes (96,7%) se detectó un ganglio centinela. La cirugía con preservación del estómago se realizó en 210 de 258 pacientes (81,4%). Las complicaciones postoperatorias se presentaron en 51 pacientes del grupo LSG (19,0%) y en 40 pacientes (15,5%) del grupo LSNNS (P = 0,294). Las complicaciones grado III o mayor de Clavien-Dindo se detectaron en 16 (5,9%) y 13 pacientes (5,0%) de los grupos LSG y LSNNS, respectivamente (P = 0,647). CONCLUSIÓN: El porcentaje y la gravedad de las complicaciones tras LSNNS para cancer gástrico precoz son comparables a la LSG con LND.

Comparative transcriptome analysis of the human endocervix and ectocervix during the proliferative and secretory phases of the menstrual cycle.

Despite extensive studies suggesting increased susceptibility to HIV during the secretory phase of the menstrual cycle, the molecular mechanisms involved remain unclear. Our goal was to analyze transcriptomes of the endocervix and ectocervix during the proliferative and secretory phases using RNA sequencing to explore potential molecular signatures of susceptibility to HIV. We identified 202 differentially expressed genes (DEGs) between the proliferative and secretory phases of the cycle in the endocervix (adjusted p < 0.05). The biofunctions and pathways analysis of DEGs revealed that cellular assembly and epithelial barrier function in the proliferative phase and inflammatory response/cellular movement in the secretory phase were among the top biofunctions and pathways. The gene set enrichment analysis of ranked DEGs (score = log fold change/p value) in the endocervix and ectocervix revealed that (i) unstimulated/not activated immune cells gene sets positively correlated with the proliferative phase and negatively correlated with the secretory phase in both tissues, (ii) IFNγ and IFNα response gene sets positively correlated with the proliferative phase in the ectocervix, (iii) HIV restrictive Wnt/ß-catenin signaling pathway negatively correlated with the secretory phase in the endocervix. Our data show menstrual cycle phase-associated changes in both endocervix and ectocervix, which may modulate susceptibility to HIV.

Environmental Escherichia coli: ecology and public health implications-a review.

Escherichia coli is classified as a rod-shaped, Gram-negative bacterium in the family Enterobacteriaceae. The bacterium mainly inhabits the lower intestinal tract of warm-blooded animals, including humans, and is often discharged into the environment through faeces or wastewater effluent. The presence of E. coli in environmental waters has long been considered as an indicator of recent faecal pollution. However, numerous recent studies have reported that some specific strains of E. coli can survive for long periods of time, and potentially reproduce, in extraintestinal environments. This indicates that E. coli can be integrated into indigenous microbial communities in the environment. This naturalization phenomenon calls into question the reliability of E. coli as a faecal indicator bacterium (FIB). Recently, many studies reported that E. coli populations in the environment are affected by ambient environmental conditions affecting their long-term survival. Large-scale studies of population genetics revealed the diversity and complexity of E. coli strains in various environments, which are affected by multiple environmental factors. This review examines the current knowledge on the ecology of E. coli strains in various environments with regard to its role as a FIB and as a naturalized member of indigenous microbial communities. Special emphasis is given on the growth of pathogenic E. coli in the environment, and the population genetics of environmental members of the genus Escherichia. The impact of environmental E. coli on water quality and public health is also discussed.

Dilute versus concentrated vasopressin administration during laparoscopic myomectomy: a randomised controlled trial.

OBJECTIVE: To determine if higher-volume, fixed-dose administration of vasopressin further reduces blood loss at the time of minimally invasive myomectomy. DESIGN: Randomised multicentre clinical trial. SETTING: Tertiary-care academic centres in the USA. POPULATION: Women undergoing conventional laparoscopic or robot-assisted laparoscopic myomectomy. METHODS: All participants received the same 10-unit (U) dose of vasopressin, but were randomly assigned to one of two groups: (i) received 200 ml of diluted vasopressin solution (20 U in 400 ml normal saline), and (ii) received 30 ml of concentrated vasopressin solution (20 U in 60 ml normal saline). MAIN OUTCOME MEASURES: The primary study outcome was estimated blood loss; the study was powered to detect a 100-ml difference. RESULTS: A total of 152 women were randomised; 76 patients in each group. Baseline demographics were similar between groups. The primary outcome of intraoperative blood loss was not significantly different, as measured by three parameters: surgeon estimate (mean estimated blood loss 178 ± 265 ml and 198 ± 232 ml, dilute and concentrated groups respectively, P = 0.65), suction canister-calculated blood loss, or change in haematocrit levels. There were no vasopressin-related adverse events. CONCLUSION: Both dilute and concentrated vasopressin solutions that use the same drug dosing demonstrate comparable safety and tolerability when administered for minimally invasive myomectomy; however, higher volume administration of vasopressin does not reduce blood loss. TWEETABLE ABSTRACT: This randomised trial failed to show benefit of high-volume dilute vasopression.

Profiling of rectal cancers MRI in pathological complete remission states after neoadjuvant concurrent chemoradiation therapy.

AIM: To fully characterise the magnetic resonance imaging (MRI) traits of rectal cancers in a large sample of patients, each experiencing pathological complete remission (pCR) after neoadjuvant concurrent chemoradiation therapy (CCRT). MATERIALS AND METHODS: A total of 120 patients (77 male, 43 female; median age, 59.5 years; range, 32-81 years) with rectal cancers in CCRT-induced pCR states who underwent pre- and post-CCRT MRI and eventual surgery between July, 2005 and September, 2014 were retrospectively reviewed. In most (n=100), diffusion-weighted imaging was also performed. Tumour volume, tumour regression grade (TRG), T-stage, mesorectal fascia (MRF) status, and T2 signal intensity (T2-SI) were analysed. Paired t-test and McNemar's test were applied for statistical comparisons. RESULTS: Tumour volume declined sharply after CCRT (pre-CCRT, 21.5 ± 22.4 cm(3); post-CCRT, 6.6 ± 8.4 cm(3); p<0.001). TRG distribution was as follows: G1 (clinical CR), 3; G2, 38; G3, 78; G4, 1; and G5 (marked progression), 0. Downstaging of T-stage (34%,16/47) and MRF status (19.7%,13/66) did occur; but on post-CCRT MRI, 25.8% (31/120) remained at T3 ≥ 5 mm or T4 stage, and 44.2% (53/120) were MRF-positive. A majority (88.3%, 106/120) of patients displayed intermediate T2-SI prior to CCRT. Most converted to dark T2-SI after CCRT, with 12.5% (15/120) unchanged. On post-CCRT MRI, 11% (11/100) of patients showed diffusion restriction. CONCLUSION: MRI findings in CCRT-induced pCR-status rectal cancers were highly variable. Tumour volume and T2-SI mostly decreased; however, such lesions occasionally presented with unexpected atypical features, such as large residual volume and/or intermediate T2-SI.

Transanal specimen extraction in robotic rectal cancer surgery.

BACKGROUND: The aim of this study was to identify the benefits of robotic transanal specimen extraction (RTSE) compared with minilaparotomy specimen extraction (MSE). METHODS: Patients who underwent totally robotic surgery with curative intent for treatment of adenocarcinoma of the rectum below 12 cm from the anal verge were selected from the authors' database. Patients were divided into RTSE and MSE groups according to the method of specimen delivery. Clinicopathological features and perioperative surgical outcomes were compared between the two groups. RESULTS: There were 53 patients in the RTSE group and 66 in the MSE group. No differences were observed in overall complications. Postoperative recovery was faster in the RTSE group in terms of resumption of a soft diet (mean(s.d.) 3·5(1·5) versus 4·6(1·7) days; P < 0·001) and length of hospital stay (9·0(4·8) versus 11·3(5·3) days; P = 0·016). Pain scores on a visual analogue scale were significantly lower in the RTSE group than in the MSE group from day 2 to day 5 after surgery (P = 0·021 to P < 0·001). CONCLUSION: RTSE in robotic rectal cancer surgery was associated with less pain and a faster recovery than MSE.

Adenosine triphosphate-based chemotherapy response assay-guided chemotherapy in unresectable colorectal liver metastasis.

BACKGROUND: This study aims to evaluate the effectiveness of adenosine triphosphate-based chemotherapy response assay (ATP-CRA)-guided neoadjuvant chemotherapy for increasing resectability in patients with unresectable colorectal liver metastasis. PATIENTS AND METHODS: Patients were randomised into two groups: Group A was treated by conventional chemotherapy regimen and Group B was treated by chemotherapy regimen according to the ATP-CRA. Three chemotherapeutic agents (5-fluorouracil, oxaliplatin and irinotecan) were tested by ATP-CRA and more sensitive agents were selected. Either FOLFOX or FOLFIRI was administered. Between Group A and B, treatment response and resectability were compared. RESULTS: Between November 2008 and October 2010, a total 63 patients were randomised to Group A (N=32) or Group B (N=31). FOLFOX was more preferred in Group A than in Group B (26 out of 32 (81.3%) vs 20 out of 31 (64.5%)). Group B showed better treatment response than Group A (48.4% vs 21.9%, P=0.027). The resectability of hepatic lesion was higher in Group B (35.5% vs 12.5%, P=0.032). Mean duration from chemotherapy onset to the time of liver resection was 11 cycles (range 4-12) in Group A and 8 cycles (range 8-16) in Group B. CONCLUSION: This study showed that tailored-chemotherapy based on ATP-CRA could improve the treatment response and resectability in initially unresectable colorectal liver metastasis.

Impact of tumor infiltration pattern into the surrounding tissue on prognosis of the subserosal gastric cancer (pT2b).

BACKGROUND: The aim of this study was to clarify the impact of infiltration pattern on prognosis in patients with gastric carcinoma invading subserosa. METHODS: Clinicopathologic findings in patients with ssgamma pattern (n = 144) were compared with those in patients with ssalpha/ssbeta cancers (n = 222). Prognostic factors of pT2b patients were analyzed by univariate and multivariate analysis. RESULTS: Compared with the ssalpha/beta group, ssgamma gastric cancer exhibited more frequent undifferentiated histology, disseminated lymph node metastasis and perineural invasion. Frequency of postoperative peritoneal recurrence was significantly higher in ssgamma gastric cancer (P < 0.05). The 5-year survival rate for patients with ssgamma gastric cancer was significantly lower compared with ssalpha/beta group (63.2% vs. 74.8%, respectively; P < 0.05). Lymph node metastasis, vein invasion and infiltrative pattern (ssgamma) were significant independent prognostic factors affecting survival in pT2b patients. CONCLUSION: In patients with gastric cancer invading the subserosa, infiltrative type growth pattern is closely related to carcinomatosis and poorer prognosis.

Improvement of the resolution in direct membrane integrity test by controlling solution surface tension.

Membrane-based treatment technologies have been introduced as a promising tool for the removal of water-borne pathogens. To ensure successful application of membrane processes, the integrity of the membrane system should be maintained. Related with evaluation of the membrane integrity, USEPA guidance recommends pressure-based membrane integrity (MIT). Based on the bubble point theory, the ability of detecting smallest integrity breakage during the MIT is defined as "Resolution". However, the response to remarkably small breach demands significantly high initial test pressure of the pressure decay test. In this study, the surface tension of the test liquid was controlled to improve the resolution without increasing the corresponding test pressure. Three common chemicals were chosen to control the solution surface tension. It is concluded that 0.1 M of the citric acid can decrease the initial test pressure significantly for the same pore size. Subsequently, the improvement of the resolution with controlled surface tension was confirmed by the results of pressure decay test and marker test.

Lymph node micrometastasis in node negative early gastric cancer.

AIMS: The clinical significance of lymph node micrometastasis for histologically node negative gastric cancer is not well documented. This study was to assess the incidence and to clarify the risk factors of lymph node micrometastasis in patients with node negative early gastric cancer (EGC). METHODS: We investigated the lymph node micrometastasis with using an anticytokeratin immunohistochemical stain in 90 patients with node negative EGC who underwent curative resection between 1991 and 2000. RESULTS: Among 3526 nodes from 90 patients, there were 17 cytokeratin immunohistochemical stain positive nodes from nine patients. The incidence of micrometastasis was higher in patients with lymphatic invasion (p=0.012), venous invasion (p=0.026) and larger tumor (p=0.003). The independent risk factors for lymph node micrometastasis were lymphatic invasion (p=0.004, RR=22.915, 95% CI = 2.709 ~ 193.828) and tumor size (p=0.029, RR=1.493, 95% CI = 1.042 ~ 2.138). Although there were 10 deaths during the follow-up period of mean 67.6 months (1 month ~ 147 months), there was no death from a cancer recurrence. CONCLUSIONS: The incidence of lymph node micrometastasis in patients with node negative early gastric cancer was 10%, and the independent risk factors for micrometastasis were lymphatic invasion and tumor size.

Cordycepin inhibits IL-1beta-induced MMP-1 and MMP-3 expression in rheumatoid arthritis synovial fibroblasts.

OBJECTIVE: MMP is a key enzyme in the degradation of extracellular matrices, and its expression plays important roles in inflammatory diseases. Cordycepin (3'-deoxyadenosine), a bioactive compound of Cordyceps militaris, has been shown to exhibit many pharmacological activities, such as anti-cancer, anti-inflammatory and anti-infection activities. In this study, we aimed at the inhibitory effect of cordycepin on IL-1beta-induced MMP-1 and MMP-3 expression as well as the molecular basis using RA synovial fibroblasts (RASFs). METHODS: RASFs were isolated from synovial tissue obtained from 12 patients with RA and cultured in monolayer. Expression of MMP-1 and MMP-3 was evaluated using western blotting and real-time PCR. Chemokines were analysed by ELISA. The phosphorylation of mitogen-activated protein kinase was measured by western blotting. Electrophoretic mobility shift assay was performed to evaluate binding activities of DNA to nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). RESULTS: Cordycepin inhibited IL-1beta-induced MMP-1 and MMP-3 expressions in RASFs in a dose-dependent manner. Among various chemokines [such as monocyte chemoattractant protein-1 (MCP-1), GRO-alpha, regulated upon activation, normal T-cell expressed and presumably secreted (RANTES) and epithelial neutrophil activating peptide 78 (ENA-78)], cordycepin specifically blocked IL-1beta-induced ENA-78 production in RASF. Moreover, cordycepin significantly inhibited IL-1beta-induced p38/JNK and AP-1 activation, but not extracellular signal-regulated kinase (ERK) and NF-kappaB activation. CONCLUSIONS: Cordycepin is a potent inhibitor of IL-1beta-induced chemokine production and MMP expression and strongly blocks the p38/JNK/AP-1 signalling pathway in RASFs.

Biodegradation of the insecticide N,N-diethyl-m-toluamide by fungi: identification and toxicity of metabolites.

Fungi (Cunninghamella elegans ATCC 9245, Mucor ramannianus R-56, Aspergillus niger VKMF-1119, and Phanerochaete chrysosporium BKMF-1767) were tested to elucidate the biologic fate of the topical insect repellent N,N-diethyl-m-toluamide (DEET). The elution profile obtained from analysis by high-pressure liquid chromatography equipped with a reverse-phase C-18 column, showed that three peaks occurred after incubation of C. elegans, with which 1 mM DEET was combined as a final concentration. The peaks were not detected in the control experiments with either DEET alone or tested fungus alone. The metabolites produced by C. elegans exhibited a molecular mass of 207 with a fragment ion (m/z) at 135, a molecular mass of 179 with an m/z at 135, and a molecular mass of 163 with an m/z at 119, all of which correspond to N,N-diethyl-m-toluamide-N-oxide, N-ethyl-m-toluamide-N-oxide, and N-ethyl-m-toluamide, respectively. M. ramannianus R-56 also produced N, N-diethyl-m-toluamide-N-oxide and N-ethyl-m-toluamide but did not produce N-ethyl-m-toluamide-N-oxide. For the biologic toxicity test with DEET and its metabolites, the freshwater zooplankton Daphnia magna was used. The biologic sensitivity in decreasing order was DEET > N-ethyl-m-toluamide > N,N-diethyl-m-toluamide-N-oxide. Although DEET and its fungal metabolites showed relatively low mortality compared with other insecticides, the toxicity was increased at longer exposure periods. These are the first reports of the metabolism of DEET by fungi and of the biologic toxicity of DEET and its fungal metabolites to the freshwater zooplankton D. magna.

Nitrogen and phosphorus removal from swine wastewater by intermittently aerated dynamic-flow system.

This study was performed to evaluate the effects of the volume fraction of an anaerobic reactor (VFAR) and SRT on the removal of T-N and T-P in both an intermittently aerated system (IAS) and intermittently aerated dynamic-flow system (IADS), respectively. When the VFAR in the total volume of reactor from both IAS and IADS are 13%, 7%, and 0% at 5 days of SRT, the removal efficiencies of T-P were 80-87%, 62-65% and <30%, respectively. However, it was observed from this study that the removal efficiencies of T-N and T-P were not correlated to VFAR at a predetermined SRT, producing greater than 5000 mg/L of MLVSS. Also, IADS was shown to have the greater buffer capacity and adaptability to resist the shock due to the loading of high concentration of N. Furthermore, IADS achieved over 80% of removal efficiency of N even at much lower C/N ratio of 4.7. Therefore, it seems that IADS has the significant advantages over other biological nutrients removal processes.

Response of the immune system of mammary tumor-bearing rats to cyclophosphamide and soluble low-molecular mass tumor-associated antigens: the spleen and lymph nodes.

In a previous study, we showed that soluble low-molecular-mass tumor-associated antigens (sTAA) promote the anti-tumor effect of the anticancer drug cyclophosphamide (CPA) on rat mammary carcinogenesis. In this report, we analyzed the underlaying mechanisms. Studies were performed on the spleen and lymph nodes from the following groups of mammary tumor-bearing rats: i) control rats, ii) rats treated with sTAA, iii) rats treated with CPA, i.v.) rats treated with CPA and sTAA. Different zones of the spleen and lymph nodes were measured and their T cell content (CD4(+) and CD8(+) cells) was analyzed immunohistochemically. CPA decreased the size and cell content of follicles, splenic areas related to the production of B cells, of the marginal zone and to a lesser extent of the periarterial lymph sheath, and decreased the number of CD4(+) and, at a lower rate, of CD8(+ )T cells in the spleen. Addition of sTAA restored activity in the splenic zones producing these cells. Similar effects of CPA and sTAA were found in lymph nodes with accumulation of B lymphocytes in the primary and secondary follicles and of T lymphocytes, including both CD4(+) and CD8(+) cells, in the paracortical zone. We suggest that inhibition of the functional activity of the immune system is one of the main reasons for the toxic effects of chemotherapeutic drugs such as CPA and that the tumor-suppressive antitoxic effects of sTAA result from their activation of B- and T-lymphocyte production in this system, particularly in the spleen and lymph nodes.

Soluble low-molecular-mass tumor-associated antigens promote the suppression of rat mammary tumors by tamoxifen and prevent its toxic effect.

This study examined whether the soluble tumor-associated antigens (sTAA) of 66 kDa and 51 kDa could promote suppression of chemically-induced rat mammary tumorigenesis by the hormone-related anticancer drug tamoxifen and prevent the drug's toxic side-effects. Dimethylbenzanthracene (DMBA, 10 mg/rat, 3 administrations) was used to induce mammary tumors in 8-week-old Wistar rats. Then, for 13-17 more weeks, preparations of sTAA (50 microg/rat) and tamoxifen (10 mg/rat) were administered, separately or in combination, on a weekly basis. The experiment was continued for 18 weeks and was terminated when the number of dead rats reached 50% in each group. Treatment with tamoxifen inhibited tumor growth and their malignance: the number of rats without malignant tumors significantly increased compared to controls, 27.3% and 5.6%, respectively. Treatment with sTAA resulted in a significant increase in the number of regressed tumors to 10.1% compared to 0% and 1.4% in control and tamoxifen-treated rats, respectively. Moreover, the period of 50% survival increased from 13 weeks in tamoxifen-treated rats to 17 weeks, and as a result, rats treated with sTAA were involved in the experiment for an average 14.3 weeks compared to 10 and 10.4 weeks in control and tamoxifen-treated groups. In rats treated simultaneously with tamoxifen and sTAA, the time of appearance of each new tumor increased from 4.5 weeks to 6.6 weeks with a significant increase to 14.3% in the number of regressed tumors. The period to 50% survival increased to 18 weeks, and these rats were involved in the experiment for up to 16.4 weeks. The number of rats without malignant tumors increased to 22.2% and the time of appearance of malignancy increased to 9.6 weeks, as compared to 7.3 weeks in controls. The results demonstrated that sTAA have tumor-suppressive properties, and also enhance the anticancer effects of tamoxifen and prevent its toxic side-effects.