Development of a risk-scoring system to evaluate the serosal invasion for macroscopic serosal invasion positive gastric cancer patients.

BACKGROUND: The status of serosal invasion is often discordance between pathological and intraoperative evaluation. Our study sought to develop a risk-scoring system (RSS) to predict the probability of pT4a for macroscopic serosal invasion (MSI) positive patients and reevaluate the serosal invasion status. PATIENTS AND METHODS: A total of 1301 pT3/pT4a gastric cancer patients with curative surgery were reviewed. We constructed the RSS to predict the probability of pT4a and assigned MSI-positive patients into different risk groups based on the risk scores. The prognostic significance of these risk groups was also evaluated. RESULTS: Univariate and multivariate analyses identified that tumor location, Lauren type, Borrmann type, tumor size, lymphovascular invasion and pN stage were risk factors related to pT4a. Survival analyses showed that pT3 MSI-positive patients in high-risk group had similar survival with pT4a patients. We incorporated these two groups into one stage and proposed a novel revised-T stage. Two-step multivariate analyses indicated that the revised-T stage showed better prediction ability for prognosis and peritoneal recurrence assessment than original pT stage and MSI status. CONCLUSIONS: In our present study, we developed a RSS to predict the probability of pT4a for MSI-positive patients. Based on our RSS, we proposed a treatment algorithm to reevaluate the tumor invasion for MSI-positive patients in clinical practice. Future studies should include other preoperative predictors to improve the clinical utility of our model.

Tanshinone IIA alleviates lipopolysaccharide-induced acute lung injury by downregulating TRPM7 and pro-inflammatory factors.

The study aimed to investigate the role of Tanshinone IIA (Tan IIA) in lipopolysaccharide (LPS)-induced acute lung injury (ALI) in its regulation of TRPM7. Wistar male rats were randomly divided into the normal saline (NS), LPS, knockout (KO) + LPS, low-dose Tan IIA (Tan-L), middle-dose Tan IIA (Tan-M), high-dose Tan IIA (Tan-H) and KO + high-dose Tan IIA (KO + Tan-H) groups. The level of tumour necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, TRPM7 protein expression, current density-voltage curve and Ca2+ concentration were detected through ELISA, Western blotting, electrophysiological experiment and a calcium-imaging technique, respectively. The rats in the KO + LPS, Tan-L, Tan-M, Tan-H and KO + Tan-H groups all displayed lower levels of TNF-α, IL-1ß and IL-6 than the LPS group. Rats in the KO + Tan-H group exhibited lower levels of NF-α, IL-1ß and IL-6 than rats in the Tan-H group. Elevated levels of TRPM7 protein expression in the LPS and Tan groups were detected in comparison with the NS group. However, TRPM7 protein expression in Tan-M and Tan-H groups was notably lower than in that of the LPS group. In comparison with the NS group, the LPS and Tan groups had a greater PIMs cell density and a higher concentration of Ca2+ . Contrary results were observed in the KO + LPS, Tan-H and KO + Tan-H groups. Tan IIA decreases calcium influx in PIMs and inhibits pro-inflammatory factors which provide an alleviatory effect in regards to LPS-induced ALI by suppressing TRPM7 expression.

Effect of a spray formulation on the reproductive parameters of a susceptible population of Rhipicephalus (Boophilus) microplus / Efeitos de uma formulação pulverização sobre os parâmetros reproductivos de uma população susceptível de Rhipicephalus (Boophilus) microplus

The number of studies emphasizing the possible damage that acaricidal spray formulations can cause on engorged female ticks' reproductive parameters is small. The present study evaluated the deleterious effects of a spray formulation (dichlorvos 60% + chlorpyrifos 20%) on the reproductive parameters of a susceptible population of Rhipicephalus (B.) microplus females, using the Stall Test. The ticks were allocated randomly to treatments according to the mean numbers of females detached from each cow on days -3, -2 and -1 and the cattle pen location. The numbers of engorged female ticks that naturally detached from the cattle were counted daily from day 1 to day 30. For each group, 20 detached engorged female ticks or the available number collected daily were evaluated regarding reproductive parameters. Associations of organophosphates demonstrated elevated acaricidal efficacy, as well as deleterious effects on the reproductive parameters of R. (B.) microplus females. The engorged female weight (days 1 to 7), weight of egg masses (days 5 to 10) and larval hatching percentage (days 5 to 19) were decreased (P ≤ 0.05). It is possible that a formulation can lead to deleterious effects on R. (B.) microplus females when the tick population analyzed shows elevated sensitivity towards a particular formulation. However, further studies need to be conducted.

É relativamente pequeno o número de estudos que enfatiza os danos que uma formulação acaricida spray pode desencadear sobre os parâmetros reprodutivos das teleóginas. O presente estudo teve como objetivo avaliar os efeitos deletérios de uma formulação spray comercial (dichlorvos 60% + Clorpirifós 20%), sobre os parâmetros reprodutivos de uma população susceptível de R. (B.) microplus, desprendidas de bovinos experimentalmente infestados, utilizandose o teste de estábulo. Os animais foram alocados aos grupos de tratamentos de acordo com a contagem média de fêmeas desprendidas dos bovinos nos dias -3, -2 e -1. O número de teleóginas desprendidas foi quantificado do dia 1 ao 30. Para cada grupo, diariamente 20 fêmeas, ou a quantidade disponível, foram selecionadas e submetidas à avaliação dos parâmetros reprodutivos. A associação de organofosforados demonstrou elevada eficácia acaricida e também apresentou efeitos deletérios sob os parâmetros reprodutivos de Rhipicephalus (B.) microplus, diminuindo (P≤0,05) o peso das teleóginas (dos dias 1 ao 7), o peso da massa de ovos (dos dias 5 ao 10) e a eclodibilidade das larvas (dos dias 5 ao 19). Talvez uma formulação pode apresentar efeitos deletérios sobre os parâmetros reprodutivos de fêmeas de R. (B.) microplus, quando existe um elevado grau de sensibilidade dessa cepa de carrapato a um determinado composto. De qualquer maneira, futuros estudos devem ser realizados.

Effect of growth hormone, hyperbaric oxygen and combined therapy on the gastric serosa.

AIM: To investigate the role of growth hormone (GH), hyperbaric oxygen therapy (HBOT) and combined therapy on the intestinal neomucosa formation of the gastric serosa. METHODS: Forty-eight male Wistar-albino rats, weighing 250-280 g, were used in this study. The rats were divided into four groups (n = 12): Group 1, control, gastric serosal patch; Group 2, gastric serosal patch + GH; Group 3, gastric serosal patch + HBOT; and Group 4, gastric serosal patch + GH + HBOT. Abdominal access was achieved through a midline incision, and after the 1-cm-long defect was created in the jejunum, a 1 cm × 1 cm patch of the gastric corpus was anastomosed to the jejunal defect. Venous blood samples were taken to determine the insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) basal levels. HBOT was performed in Groups 3 and 4. In Groups 2 and 4, human GH was given subcutaneously at a dose of 2 mg per kg/d for 28 d, beginning on the operation day. All animals were sacrificed 60 d after surgery. The jejunal segment and the gastric anastomotic area were excised for histological examination. The inflammatory process, granulation, collagen deposition and fibroblast activity at the neomucosa formation were studied and scored. Additionally, the villus density, villus height, and crypt depth were counted and recorded. The measurements of villus height and crypt depth were calculated with an ocular micrometer. New vessel growth was determined by calculatingeach new vessel in a 1 mm(2) area. RESULTS: In the histological comparison of groups, no significant differences were observed between the control group and Groups 2 and 3 with respect to epithelialization, granulation, fibroblastic activity and the inflammatory process, but significant differences were present between the control group and all others groups (Groups 2-4) with respect to angiogenesis (P < 0.01) and collagen deposition (P < 0.05, P < 0.01). Significant differences between the control group and Group 4 were also observed with respect to epithelialization and fibroblastic activity (P < 0.01 and P < 0.05, respectively). There were significant differences in villus density in all of groups compared with the control group (P < 0.05). Crypt depth was significantly greater in Group 4 than in the control group (P < 0.05), but no other groups had deeper crypts. However, villus height was significantly longer in Groups 2 and 4 than in the control group (P < 0.05). The comparison of groups revealed, significant difference between control group and Groups 2 and 4) with respect to the levels of IGF-1 and IGFBP-3 (P < 0.01) 3 wk after the operation. CONCLUSION: HBOT or GH and combined therapy augmented on neomucosal formation. The use of combined therapy produced a synergistic effect on the histological, morphological and functional parameters.

Benefits of hyperthermic intraperitoneal chemotherapy for patients with serosal invasion in gastric cancer: a meta-analysis of the randomized controlled trials.

BACKGROUND: In this meta-analysis we aimed to determine the effectiveness and safety of hyperthermic intraperitoneal chemotherapy (HIPC) for patients with advanced gastric cancer who underwent gastrectomy. METHODS: In accordance with standard meta-analysis procedures, our study included patients who underwent resection for advanced gastric cancer and were randomly allocated to receive either hyperthermic intraperitoneal chemotherapy or control. We searched PubMed (up to November 2011), EMBASE (up to November 2011), Cochrane Database of Systematic Reviews (CDSR), and Cochrane Central Register of Controlled Trials (CCTR) (up to November 2011). Both published and unpublished trials were included in the analysis, and no search restrictions were imposed. There was no language restriction. The results were analyzed using RevMan 5.1 software, which was provided by Cochrane Collaboration. RESULTS: There were ten randomized controlled trials included in the analysis. A total of 1062 patients with gastric cancer in these studies were divided into the HIPC group (n = 518) and control group (n = 544). A significant improvement in survival was observed in the HIPC groups compared to the control group in the mitomycin C (MMC) subgroup (RR = 0.75, 95%CI 0.65-0.86; P < 0.00001) and the 5-FU group (RR = 0.69, 95%CI 0.52-0.90; P < 0.00001); the total RR was 0.73 (95%CI 0.64-0.83; P < 0.00001). Our findings indicated that HIPC potentially exhibited a lower peritoneal recurrence rate in the HIPC group compared to the control group (RR = 0.45, 95%CI 0.28-0.72; P = 0.001). CONCLUSIONS: Our meta-analysis demonstrated that HIPC may improve the overall survival rate for patients who receive resection for advance gastric cancer potentially, and help to prevent peritoneal local recurrence among patients with serosal invasion in gastric cancer.

Randomized clinical trial of adjuvant chemotherapy with intraperitoneal and intravenous cisplatin followed by oral fluorouracil (UFT) in serosa-positive gastric cancer versus curative resection alone: final results of the Japan Clinical Oncology Group trial JCOG9206-2.

PURPOSE: To evaluate the survival benefit of adjuvant chemotherapy after curative resection in serosa-positive gastric cancer, a multicenter phase III clinical trial was conducted in Japan. PATIENTS AND METHODS: From January 1993 to March 1998, 268 patients were randomized to adjuvant chemotherapy (135 patients) or surgery alone (133 patients). All patients underwent gastrectomy with D2 or greater lymph node dissection. The chemotherapy regimen consisted of intraperitoneal cisplatin soon after abdominal closure, postoperative intravenous cisplatin (day 14) and 5-fluorouracil (day 14-16), and daily oral FU (UFT) starting 4 weeks after surgery for 12 months. The primary endpoint was overall survival. Relapse-free survival and site of recurrence were secondary endpoints. RESULTS: Fifty-two patients (38.5%) in the adjuvant chemotherapy arm completed the chemotherapy regimen. There were 4 (1.49%) treatment-related deaths, 1 in the surgery-alone and 3 in the adjuvant chemotherapy arm (2 did not receive chemotherapy). Grade 4 toxicity was observed in 3 patients in the surgery-alone and 2 patients in the adjuvant chemotherapy arm. There was no significant difference in 5-year overall survival (62.0% adjuvant chemotherapy vs. 60.9% surgery-alone, P = 0.482) and 5-year relapse-free survival rates (57.5% adjuvant chemotherapy vs. 55.6% surgery-alone; P = 0.512). CONCLUSION: There was no benefit in overall and relapse-free survival with this adjuvant chemotherapy regimen for patients with macroscopically serosa-positive gastric cancer after curative resection.

[Postoperative adjuvant immunochemotherapy using Lentinan for advanced gastric carcinoma patients with metastasis in the regional lymph nodes and serosal invasion].

Six patients with gastric cancer, stage IIIA to IV, received intraabdominal cisplatin (CDDP) at laporotomy. This was followed by postoperative intravenous infusion of mitomycin C (MMC), CDDP or fluorouracil (5-FU). When these patients recovered to the extent that permitted oral medication, an immunochemotherapeutic regimen containing either oral UFT (uracil and tegafur) or 5'-deoxy-5-fluorouridine (5'-DFUR), plus intravenous Lentinan (LNT) was administered for a period ranging from one and a half to two years. This postoperative immunochemotherapy was successful in all 6 patients. No relapse has been observed in any of them for at least 4 years. These findings indicate that the chemotherapeutic strategy of administering intraabdominal CDDP immediately after surgery, followed by postoperative immunochemotherapy with pyrimidine-fluoride products plus Lentinan on an outpatient basis may be useful in the treatment of T3 or T4 gastric carcinoma with metastasis in the regional lymph nodes.

Postoperative adjuvant chemotherapy is effective in gastric cancer with serosal invasion: significance in patients chosen for multivariate analysis.

There are few reports on overall usefulness of adjuvant chemotherapy in gastric cancer patients. We tried to clarify, using multivariate analysis, usefulness of postoperative adjuvant oral chemotherapy in advanced gastric cancer patients after curative resection. Four hundred and eighty-two gastric cancer patients enrolled in a randomized controlled trial were classified into 2 groups based on postoperative chemotherapeutic regimen: oral doxifluridine (5'-DFUR, an intermediate metabolite of capecitabine) (n=245) or oral 5-fluorouracil (5-FU) (n=237). The significant prognostic factors in patients with serosal invasion were chemotherapeutics (5'-DFUR vs. 5-FU) (risk ratio 1.649; 95% CI, 1.112-2.437), lymph node metastasis (no vs. yes) (2.823; 1.422-5.604), and tumor differentiation (differentiated vs. undifferentiated) (1.727; 1.068-2.791). Significant factors influencing peritoneal recurrence time were chemotherapeutics (1.756; 1.063-2.902), serosal invasion (no vs. yes) (2.237; 1.264-3.961), lymph node metastasis (2.541; 1.267-5.095), tumor differentiation (2.656; 1.374-5.136), and tumor location (others vs. total) (3.595; 2.006-6.443). There were no differences in the overall survival between chemotherapy. However, 5'-DFUR produced a better survival time of patients with serosal invasion than 5-FU, that might be attributed to the prevention of peritoneal recurrence in this subset.

[A simple alternative method in the treatment of idiopathic hydrocele in adults: vaginal "fenestration"]. / Une alternative technique simple dans le traitement de l'hydrocèle idiopathique de l'adulte: la "fenestration" vaginale.

The author describes a new, simple technique for the treatment of idiopathic hydrocele according to a "fenestration" procedure designed to correct the imbalance of intravaginal hydrostatic exchanges. The operation consists of initially hemming separately the deep fibrous layer and the parietal leaflet of the tunica vaginalis to form the margins of the "window", which is then applied by its fibrous layer to the dartos, continuous with the subcutaneous connective tissue, a site of rich lymphatic drainage. In a series of 108 patients treated by this technique since September 1982, with a follow-up of 6 years, the anatomical and functional results were excellent in 98 cases (90.7%), moderate in 6 cases (5.5%) and poor in 4 cases (3.7%). Compared to classical techniques, the fenestrated opening of the tunica vaginalis with preservation of the tunica vaginalis and limited opening of the serosa, preserves the testicular support and the protective role of the serosa on the testis. Lastly, suture of the margins of the window to the dartos, by facilitating deep lymphatic drainage towards the superficial connective tissue, reconstitutes a physiological equilibrium in the constant exchanges of intravaginal serous fluids. Experience has demonstrated the anatomical and functional efficacy and reliability of this extremely simple procedure, which is essentially indicated in adult patients with idiopathic hydrocele and a healthy tunica vaginalis.

Implantation of colon cancer cells on intact and damaged colon mucosa and serosa: an experimental study in the rat.

The ability of malignant colon cancer cells to implant on intact and damaged colonic mucosa and serosa was tested in a series of experiments using male WAG rats. The mucosa was damaged in an "acute" way by multiple biopsies and in a "chronic" way by means of a chemically induced colitis. The creation of an anastomosis provoked both mucosal and serosal damages. CC531 colon cancer cells injected intraluminally as an enema implanted at the serosal side of an anastomosis without invading the mucosa in 66% of the rats. An intact colon mucosa is 100% resistant to the implantation of viable CC531 cells. In contrast, tumour growth was noticed in 100% of the rats when the malignant cells were sprayed over the intact colon serosa at laparotomy. Mucosal damage by biopsies in the presence of viable colon cancer cells resulted in mucosal implantation and intraluminal tumour growth in one out of thirty rats. No tumour growth was observed when the CC531 cells were instilled on one week old mucosal ulcerations resulting from a chemical induced colitis.

Angiographic diagnosis of the degree of serosal invasion of carcinoma of the colon.

Angiography using Prostaglandin E1 was performed on 38 patients with carcinoma of the colon in order to diagnose the degree of serosal cancer invasion. The findings at angiography were classified into four groups: 1) AG-S3, abnormal change (irregularity and/or encasement) up to marginal vessels; 2) AG-S2, abnormality up to vasa recta; 3) AG-S1, abnormality of penetrating branches of vasa recta within the wall of the colon; and 4) AG-S0, no distinct findings of above-mentioned vessels. These angiographic findings were compared with both macroscopic and microscopic serosal cancer invasion. Angiographic diagnosis is in accord with the macroscopic findings in 84.2 percent of cases. Angiographic diagnosis is in accord with the microscopic findings in 32.4 percent of cases. Macroscopic findings confirm the angiographic diagnosis precisely but the conflict with microscopic findings should not be overlooked. This may be the result of inflammatory change, adhesion, and fibrosis around carcinoma of the colon.