Peritoneal lavage with Glycyrrhiza glabra is effective in preventing peritoneal adhesion in a rat model.

BACKGROUND: Intraperitoneal adhesion formation is a significant problem following surgeries, resulting in substantial clinical and economic consequences. Glycyrrhiza glabra has several pharmacological properties consisting of anti-inflammatory, anti-microbial, anti-oxidant, anti-cancer, and immunomodulatory activities. AIM: Therefore, we aimed to investigate the impacts of G. glabra on the development of post-operative abdominal adhesion in a rat model. METHODS: Male Wistar rats weighing 200-250 g were divided into six groups (n = 8): Group 1: normal group (non-surgical), and the surgical groups including Group 2: control group received the vehicle, Group 3: G. glabra 0.5% w/v, Group 4: G. glabra 1% w/v, Group 5: G. glabra 2% w/v, and Group 6: dexamethasone, 0.4% w/v. The intra-abdominal adhesion was performed utilizing soft sterilized sandpaper on one side of the cecum, and the peritoneum was slightly washed with 2 ml of the extract or vehicle. In addition, macroscopic examination of adhesion scoring and the levels of inflammatory mediators [interferon (IFN)-γ, prostaglandin E2 (PGE2)], fibrosis markers [interleukin (IL)-4, transforming growth factor (TGF)-ꞵ], and oxidative factors [malondialdehyde (MDA), nitric oxide metabolites (NO), and reduced glutathione (GSH)] were evaluated. In vitro toxicities were also done on mouse fibroblast L929 and NIH/3T3 cell lines. RESULTS: We found higher levels of adhesion (P < 0.001), IFN-γ(P < 0.001), PGE2(P < 0.001), IL-4(P < 0.001), TGF-ß(P < 0.001), MDA(P < 0.001), and NO(P < 0.001), and lower levels of GSH(P < 0.001) in the control group. In contrast, G. glabra concentration dependent and dexamethasone alleviated the levels of adhesion (P < 0.05), inflammatory mediators (P < 0.001-0.05), fibrosis (P < 0.001-0.05), and oxidative (P < 0.001-0.05) factors, while propagating the anti-oxidant marker (P < 0.001-0.05) in comparison to the control group. Results also showed that the extract did not significantly reduce cell viability up to 300 µg/ml (P > 0.05). CONCLUSION: G. glabra could concentration-dependently mitigate peritoneal adhesion formation through its anti-inflammatory, anti-fibrosis, and anti-oxidant properties. However, further clinical investigations are required to approve that G. glabra may be a promising candidate against post-surgical adhesive complications.

Long-term observation of gastric patients with positive immunocytochemistry of peritoneal washing.

Prognosis in gastric cancer patients is highly dependent on the tumor stage at presentation. Surgery still remains the main therapeutic option in gastric cancer patients. However, the efficacy of this treatment may be substantially limited by the risk of peritoneal dissemination. The introduction of hyperthermic intraperitoneal chemotherapy (HIPEC) may affect the long-term outcomes in this group of patients, but high morbidity associated with this procedure provides the rationale to identify the correct population of patients for HIPEC. The aim of the study was to evaluate a long-term prognostic value of peritoneal washing immunocytochemistry as a prognostic factor in patients with gastric cancer. This is a prospective, long-term analysis of patients who underwent peritoneal lavage with immunocytochemistry assessment in the Maria Sklodowska-Curie National Research Institute of Oncology, in Warsaw, Poland. Between January 2002 and November 2004, a total of 157 patients with histologically confirmed gastric cancer were enrolled in the study. Laparotomy and intra-operative peritoneal lavage for immunocytochemistry examination were performed prior to gastrectomy. All patients were followed up with endpoints of cancer recurrence and mortality. Positive peritoneal washing immunocytochemistry was associated with clinical staging of gastric cancer, overall survival, and progression-free survival. It is an independent poor outcome prognostic factor.

Evaluation of the Therapeutic Effects of the Hydroethanolic Extract of Portulaca oleracea on Surgical-Induced Peritoneal Adhesion.

OBJECTIVE: Peritoneal adhesion (PA) is an abnormal connective tissue that usually occurs between tissues adjacent to damaged organs during processes such as surgery. In this study, the anti-inflammatory and antioxidant effects of Portulaca oleracea (PO) were investigated against postoperative-induced peritoneal adhesion. METHODS: Thirty healthy male Wistar rats (220 ± 20 g, 6-8 weeks) were randomly divided into four groups: (1) normal, (2) control (induced peritoneal adhesion), and (3) and (4) PO extracts (induced peritoneal adhesion and received 100 or 300 mg/kg/day of PO extract for seven days). Finally, macroscopic and microscopic examinations were performed using different scoring systems and immunoassays in the peritoneal lavage fluid. RESULTS: We found that the levels of adhesion scores and interleukin- (IL-) 1ß, IL-6, IL-10, tumour necrosis factor- (TNF-) α, transforming growth factor- (TGF-) ß 1, vascular endothelial growth factor (VEGF), and malondialdehyde (MDA) were increased in the control group. However, PO extract (100 and 300 mg/kg) notably reduced inflammatory (IL-1ß, IL-6, and TNF-α), fibrosis (TGF-ß 1), angiogenesis (VEGF), and oxidative (MDA) factors, while increased anti-inflammatory cytokine IL-10, antioxidant factor glutathione (GSH), compared to the control group. CONCLUSION: Oral administration of PO improved postoperational-induced PA by alleviating the oxidative factors, fibrosis, inflammatory cytokines, angiogenesis biomarkers, and stimulating antioxidative factors. Hence, PO can be considered a potential herbal medicine to manage postoperative PA. However, further clinical studies are required to approve the effectiveness of PO.

Standardised pomegranate peel extract lavage prevents postoperative peritoneal adhesion by regulating TGF-ß and VEGF levels.

Peritoneal adhesion represents a severe complication following surgery. Punica granatum (pomegranate) possesses several anti-oxidative and anti-inflammatory properties. Pomegranate peel extract (PPEx) can alleviate the production of various inflammatory factors and cytokines. Thus, we sought to evaluate the anti-adhesion effects of pomegranate in rats. Thirty male Wistar rats (6-week-old, 220 ± 20 g) were divided into five groups (n = 6): normal group without any surgical procedures, control group, and experimental groups receiving 2 ml of 1%, 2%, and 4% w/v PPEx, respectively. Peritoneal adhesions were examined macroscopically. Furthermore, we evaluated inflammatory cytokines levels [interleukin 6 (IL-6), and tumour necrosis factor-α (TNF-α)], growth factors [transforming growth factor- ß1 (TGF-ß1), and vascular endothelial growth factor (VEGF)], and oxidative stress parameters [nitric oxide metabolites (NO), and malondialdehyde (MDA), and glutathione (GSH)] using biochemical methods. Our results showed that the adhesion score and IL-6, TNF-α, TGF-ß1, VEGF, NO, and MDA levels were increased in the control group. In contrast, the GSH level was diminished in the control group compared with the normal group (P < 0.001). PPEx (1 and 2% w/v) markedly reduced all measured parameters compared with the control group (P < 0.001-0.05). PPEx may reduce peritoneal adhesion by alleviating adhesion formation, IL-6, TNF-α, TGF-ß1, VEGF, NO, and MDA, and stimulating anti-oxidative factors. Therefore, PPEx may be considered an appropriate candidate for the treatment of postoperative peritoneal adhesion.

Anti-Inflammatory and Proresolving Effects of the Omega-6 Polyunsaturated Fatty Acid Adrenic Acid.

Polyunsaturated fatty acids (PUFAs) and their metabolites are potent regulators of inflammation. Generally, omega (n)-3 PUFAs are considered proresolving whereas n-6 PUFAs are classified as proinflammatory. In this study, we characterized the inflammatory response in murine peritonitis and unexpectedly found the accumulation of adrenic acid (AdA), a poorly studied n-6 PUFA. Functional studies revealed that AdA potently inhibited the formation of the chemoattractant leukotriene B4 (LTB4), specifically in human neutrophils, and this correlated with a reduction of its precursor arachidonic acid (AA) in free form. AdA exposure in human monocyte-derived macrophages enhanced efferocytosis of apoptotic human neutrophils. In vivo, AdA treatment significantly alleviated arthritis in an LTB4-dependent murine arthritis model. Our findings are, to our knowledge, the first to indicate that the n-6 fatty acid AdA effectively blocks production of LTB4 by neutrophils and could play a role in resolution of inflammation in vivo.

Prognostic factors of overall survival for patients with FIGO stage IIIc or IVa ovarian cancer treated with neo-adjuvant chemotherapy followed by interval debulking surgery: A multicenter cohort analysis from the FRANCOGYN study group.

INTRODUCTION: The aim of this study was to identify prognostic factors of overall survival in patients with FIGO stage IIIc or IVa ovarian cancer (OC) treated by neo-adjuvant chemotherapy (NAC) followed by interval debulking surgery. MATERIALS AND METHODS: Data from 483 patients with ovarian cancer were retrospectively collected, from January 1, 2000 to December 31, 2016, from the FRANCOGYN database, regrouping data from 11 centers specialized in ovarian cancer treatment. Median overall survival was determined using the Kaplan-Meier method. Univariate and multivariate analysis were performed to define prognostic factors of overall survival. RESULTS: The median overall survival was 52 after a median follow up of 30 months. After univariate analysis, factors significantly associated with decreased overall survival were; no pelvic and/or para-aortic lymphadenectomy (p = 0.002), residual disease (CC1/CC2/CC3) after surgery (p < 0.001), positive cytology after NAC (p < 0.001), omental disease after NAC (p = 0.002), no pathologic complete response (pCR) (p = 0.002). In multivariate analysis, factors significantly associated with decreased overall survival were; residual disease after surgery (HR = 1.93; CI95% (1.16-3.21), p = 0.01) and positive cytology after NAC (HR = 1.59; CI95% (1.01-2.55), p = 0.05). Patients with no residual disease after surgery had a median overall survival of 64 months versus 35 months for patients with residual disease. Patients with negative cytology after NAC had a median overall survival of 71 months versus 43 months for patients with positive cytology after NAC. CONCLUSION: In this first and largest French based retrospective study, complete cytoreductive surgery in ovarian cancer remains the main prognostic factor of overall survival.

Pattern of recurrence in patients with endometrial cancer: A retrospective study.

INTRODUCTION: Endometrial cancer (EC) known prognostic factors are not sufficient to predict either outcome or recurrence rate/site: to investigate EC recurrence patterns according to ESMO-ESGO-ESTRO risk classes, could be beneficial for a more tailored adjuvant treatment and follow-up schedule. METHODS: 758 women diagnosed with EC, and a 5-years follow-up, were enrolled: they were divided into the ESMO-ESGO-ESTRO risk classes (low LR, intermediate IR, intermediate-high I-HR, and highrisk HR) and surgically treated as recommended, followed by adjuvants therapies when appropriate. RESULTS: Higher recurrence rate (RR) was significantly detected (p < 0,001) in the HR group (40,3%) compared to LR (9,6%), IR (16,7%) and I-HR (17,1%). Recurrences were detected more frequently at distant sites (64%) compared to pelvic (25,3%) and lymph nodes (10,7%) recurrences (p < 0,0001): only in LR group, no differences were detected between local and distant recurrences. 5-Year distant-free (LR 99%, IR 94%,I-HR 86%, HR 88%) and local-free survivals (LR 99%, IR 100%,I-HR 98%, HR 95%) significantly differ between groups (p < 0,0001 and p = 0,003, respectively). Adjuvant therapy modifies RRs only in LR group (p = 0,01). CONCLUSION: To identify biological factors to stratify patients at higher risk of relapse is needed. Distant site relapse could be the main reason of endometrial cancer failure follow-up, independently or in addition to their risk class prognosis.

Evaluation of the Effects of Peritoneal Lavage with Rosmarinus officinalis Extract against the Prevention of Postsurgical-Induced Peritoneal Adhesion.

Postoperative adhesions are regarded as the major complication following abdominal surgery. Rosmarinus officinalis has shown antioxidative and anti-inflammatory effects. Therefore, we aimed to assess the influence of 70% v/v hydro-ethanolic extract of the aerial parts of R. officinalis against postoperative abdominal adhesions in a rat model. Forty-eight male Wistar rats (190 ± 20 g) were divided into six groups of eight: group 1 = normal group, without any surgical procedures, group 2 = control group, group 3 = vehicle group, and groups 3, 4, and 5 = experimental groups receiving 2 mL of 4, 2, or 1% w/v R. officinalis treatment. Adhesion levels were macroscopically examined. Additionally, the levels of inflammatory cytokines (interleukin-6, interleukin-1ß, and TNF-α), growth factors (transforming growth factor-ß1, and vascular endothelial growth factor), oxidative (NO, nitric oxide and MDA, malondialdehyde), and antioxidative (GSH, glutathione) factors were evaluated. Our results revealed that the adhesion score, interleukin-6, interleukin-1ß, TNF-α, transforming growth factor-ß1, vascular endothelial growth factor, NO, and MDA levels were significantly increased in the vehicle group, while the GSH level was diminished. R. officinalis treatment notably ameliorated the adhesion score following postoperative abdominal adhesions compared with the vehicle group. Our results also revealed that R. officinalis markedly reduced inflammatory cytokines, oxidative factors, fibrosis, and angiogenesis biomarkers, whereas it increased the antioxidative factor. Therefore, R. officinalis may be a potential candidate for the management of postoperative peritoneal adhesion.

Perforated Gastric Cancer: A Systematic Review.

Background: Although gastric carcinoma is the fifth most commonly diagnosed cancer, optimal treatment of perforated cancer remains debated. Materials and Methods: The study was conducted according to the guidelines from the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. An electronic systematic search was conducted using MEDLINE databases (PubMed, EMBASE, and Web of Science) by matching the terms "perforated gastric cancer," "gastric cancer perforated," "perforation AND gastric cancer," and "perforated gastric tumor." Results: Fifteen studies published between 1995 and 2018 and including 964 patients matched the inclusion criteria for this systematic review. There were 4 publications from Japan, 3 from Turkey, and 1 from China, Germany, Hong Kong, Italy, Nepal, Serbia, South Korea, and Taiwan, respectively. The sample size of the individual studies ranged from 8 to 514 patients. Perforated gastric carcinoma was rare and more prevalent in elderly males, preoperative diagnosis was uncommon, and the distal stomach was most frequently involved. Mortality was 11.4% and 1.9%, respectively, in one-stage versus two-stage gastrectomy (P = .010). Curative treatment by omental patch repair and staged gastrectomy yielded acceptable 5-year survival rates. There were no significant differences in the recurrence rate and pattern between perforated and nonperforated gastric cancer if a curative operation was performed. Use of laparoscopy was mentioned only in one study. Conclusions: Future studies should evaluate the role of laparoscopic surgery and clarify the indications for hyperthermic intraperitoneal chemotherapy and extensive peritoneal lavage protocols to decrease gastric cancer cell shed in the surgical field and increase long-term survival.

Could Araucaria heterophylla resin extract be used as a new treatment for toxoplasmosis?

Toxoplasmosis is a worldwide parasitic disease responsible for serious health problems to human. The currently available drugs used for toxoplasmosis treatment showed a limited efficacy and cause serious host toxicity. The in vitro screening for toxoplasmicidal activity of Araucaria heterophylla resin (AHR) extract and its major component 13-epi-cupressic acid (CUP) showed that both AHR (EC50 = 3.90) and CUP (EC50 = 3.69) have high toxoplasmicidal activity in comparison with standard cotrimoxazole (EC50 = 4.28). The antiprotozoal effects of AHR and CUP were investigated against acute and chronic toxoplasmosis using mice models. Two groups of Swiss albino mice were infected by RH Toxoplasma strain intraperitoneally and by Me49 strain orally. Both groups were treated with AHR and CUP in different doses. Their effects were evaluated by survival rate, peritoneal, spleen and liver parasite burdens, brain cyst burden, NO serum level and histopathological lesions. The ultrastructural changes of tachyzoites of acutely infected mice were studied using scanning electron microscopy (SEM). There is an evidence of toxoplasmicidal activity of AHR and CUP in acute and chronic experimental toxoplasmosis. In the acute model, mice treated with AHR and CUP showed prolonged survival rates, a significant decrease in the parasite density in peritoneal lavage and pathological insult in both liver and spleen compared with that of untreated ones. SEM results denote evident morphological alterations of treated tachyzoites. In chronic experimental toxoplasmosis, AHR and CUP treated groups could significantly reduce brain cyst burden by 96.05% and 98.02% respectively. This study indicates that AHR and CUP showed potent toxoplasmicidal activities experimentally and could be used as a potential natural nontoxic agent for treatment of toxoplasmosis.

Ocimum gratissimum L. leaf flavonoid-rich fraction suppress LPS-induced inflammatory response in RAW 264.7 macrophages and peritonitis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Ocimum gratissimum L. is a herbaceous plant that has been reported in several ethnopharmacological surveys as a plant readily accessible to the communities and widely used for the treatment of inflammatory diseases. The main goal of this study was to investigate the in vitro and in vivo anti-inflammatory activity and mechanism of action of the ethylacetate fraction of O. gratissimum leaf (EAFOg) and to chemically characterize this fraction. MATERIALS AND METHODS: EAFOg was obtained from a sequential methanol extract. The safety profile was evaluated on RAW 264.7 cells, using the alamarBlue® assay. Phenolic contents were determined by spectrophotometry, and metabolites quantified by high performance liquid chromatography. The anti-inflammatory activity of EAFOg and its ability to acts on leucocytes infiltration, inflammatory mediators as NO, IL-1ß, TNF-α, and IL-10 in lipopolysaccharide-induced peritonitis in mice and LPS-stimulated RAW 264.7 macrophage were evaluated. In addition, the anti-inflammatory activity of EAFOg was also investigated in arachidonic acid-related enzymes. RESULTS: Total phenolic and flavonoid contents of EAFOg were 139.76±1.07mg GAE/g and 109.95±0.05mg RE/g respectively. HPLC analysis revealed the presence of rutin, ellagic acid, myricetin and morin. The fraction exhibited no cytotoxic effects on the RAW 264.7 cells. The EAFOg (10, 50 and 200mg/kg) significantly reduced (p<0.05) neutrophils (38.8%, 58.9%, and 66.5%) and monocytes (38.9%, 58.0% and 72.8%) in LPS-induced peritonitis. Also, EAFOg (5, 20 and 100µg/mL) produced significant reduction in NO, IL-1ß, and TNF-α in RAW 264.7 cells. However, IL-10 level was not affected by the EAFOg, and it preferentially inhibits COX-2 (IC50 =48.86±0.02µg/mL) than COX-1 and 15-LO (IC50 >100µg/mL). CONCLUSION: The flavonoid-rich fraction of O. gratissimum leaves demonstrated anti-inflammatory activity via mechanisms that involves inhibition of leucocytes influx, NO, IL-1ß, and TNF-α in vivo and in vitro, thus supporting its therapeutic potential in slowing down inflammatory processes in chronic diseases.

[Integrated approach to correction enteral insufficiency in early postoperative period].

AIM: The purpose of the research was to study the effectiveness of enteral insufficiency correction at an acute peritonitis by applying minimally invasive techniques, electrical stimulation and rehabilitation of the bowel and abdominal intestine using Remaxol drug. MATERIAL AND METHODS: The analysis of the results of clinical and laboratory examination and treatment of 110 patients with acute diffuse peritonitis. In the comparison group (62 patients) in the early postoperative period applied standardized treatment, including software reorganization of the abdominal cavity, in the study group (48 patients) -- a comprehensive treatment that includes software laparoscopic sanation abdominal electrical stimulation of the duodenum, and intra-abdominal (single dose, 200 ml), and intracolonic (200 ml, 2 times daily) administration Remaxol. It was noted a significant improvement in treatment outcomes, including reduced mortality by 2.3 times, the shortening of hospital stay by 1.3 times. RESULTS: The major component of the positive effect of the developed scheme of therapy is its ability to promptly arrest the effects of enteral insufficiency, maintain the functional status of the liver. The relatively rapid recovery of motor and intestinal barrier function leads to a lowering of enteral insufficiency syndrome, which along with increased liver detoxification ability underlies the significant reduction of endogenous intoxication in three days. An important contribution to the effectiveness of the treatment makes intra and intracolonic administration Remaxol. The drug, possessing antioxidant, antihypoxic, hepatoprotective effects, contributes to the relatively rapid improvement of the barrier function of the peritoneum and intestines, detoxification ability of the liver recovery that significantly contributes to the relief of endogenous intoxication.

Flaxseed lignans enriched in secoisolariciresinol diglucoside prevent acute asbestos-induced peritoneal inflammation in mice.

Malignant mesothelioma (MM), linked to asbestos exposure, is a highly lethal form of thoracic cancer with a long latency period, high mortality and poor treatment options. Chronic inflammation and oxidative tissue damage caused by asbestos fibers are linked to MM development. Flaxseed lignans, enriched in secoisolariciresinol diglucoside (SDG), have antioxidant, anti-inflammatory and cancer chemopreventive properties. As a prelude to chronic chemoprevention studies for MM development, we tested the ability of flaxseed lignan component (FLC) to prevent acute asbestos-induced inflammation in MM-prone Nf2(+/mu) mice. Mice (n = 16-17 per group) were placed on control (CTL) or FLC-supplemented diets initiated 7 days prior to a single intraperitoneal bolus of 400 µg of crocidolite asbestos. Three days post asbestos exposure, mice were evaluated for abdominal inflammation, proinflammatory/profibrogenic cytokine release, WBC gene expression changes and oxidative and nitrosative stress in peritoneal lavage fluid (PLF). Asbestos-exposed mice fed CTL diet developed acute inflammation, with significant (P < 0.0001) elevations in WBCs and proinflammatory/profibrogenic cytokines (IL-1ß, IL-6, TNFα, HMGB1 and active TGFß1) relative to baseline (BL) levels. Alternatively, asbestos-exposed FLC-fed mice had a significant (P < 0.0001) decrease in PLF WBCs and proinflammatory/profibrogenic cytokine levels relative to CTL-fed mice. Importantly, PLF WBC gene expression of cytokines (IL-1ß, IL-6, TNFα, HMGB1 and TGFß1) and cytokine receptors (TNFαR1 and TGFßR1) were also downregulated by FLC. FLC also significantly (P < 0.0001) blunted asbestos-induced nitrosative and oxidative stress. FLC reduces acute asbestos-induced peritoneal inflammation, nitrosative and oxidative stress and may thus prove to be a promising agent in the chemoprevention of MM.

Soybean and Fish Oil Mixture With Different ω-6/ω-3 Polyunsaturated Fatty Acid Ratios Modulates Dextran Sulfate Sodium-Induced Changes in Small Intestinal Intraepithelial γδT-Lymphocyte Expression in Mice.

BACKGROUND: This study investigated the effect of different ω-6/ω-3 polyunsaturated fatty acid (PUFA) ratios on dextran sulfate sodium (DSS)-induced changes to small intestinal intraepithelial lymphocyte (IEL) γδT-cell expression. METHODS: Mice were assigned to 3 control and 3 DSS-treated groups and were maintained on a low-fat semipurified diet. One of the control (S) groups and a DSS (DS) group were provided with soybean oil; the other 2 control (Hω-3 and Lω-3) groups and 2 other DSS (DHω-3 and DLω-3) groups were fed either a soybean and fish oil mixture with a ω-6/ω-3 ratio of 2:1 or 4:1. After feeding the respective diets for 2 weeks, the DSS groups were given distilled water containing 2% DSS, and the control groups were given distilled water for 5 days. All groups were further provided distilled water 5 days for recovery, and the small intestinal IEL γδT-cell subset was isolated for analysis. RESULTS: DSS treatment resulted in a lower small intestinal IEL γδT-cell percentage and higher messenger RNA (mRNA) expressions of Reg IIIγ, keratinocyte growth factor (KGF), and complement 5a receptor (C5aR) by IEL γδT cells. Fish oil administration enhanced the proportion of small intestinal IEL γδT cells. Compared with the DLω-3 group, the DHω-3 group had lower Reg IIIγ, KGF, and C5aR mRNA expressions and higher expression of peroxisome proliferator-activated receptor (PPAR)-γ gene by small intestinal IEL γδT cells. CONCLUSIONS: Fish oil diets with a ω-6/ω-3 PUFA ratio of 2:1 were more effective than those with a ratio of 4:1 in improving DSS-induced small intestinal injury, and activation of PPAR-γ in IEL γδT cells may be associated with resolution of small intestinal inflammation.

Impact of guideline adherence on patient outcomes in early-stage epithelial ovarian cancer.

AIM: The aim of this study was to evaluate the effects of adherence to National Comprehensive Cancer Network (NCCN) guidelines on survival outcomes in patients with early-stage epithelial ovarian cancer. METHODS: Our institutional cancer registry data on 266 patients with Stage I epithelial ovarian cancer was reviewed retrospectively and compliance with treatment guidelines for surgery and adjuvant treatment was determined. Patients were categorized according to adherence or non-adherence. The primary endpoints were recurrence-free survival and disease-specific survival. Hazard ratios (HRs) for survival were estimated with a Cox proportional hazards model. RESULTS: Of the 266 patients, 71 (26.7%) underwent adequate surgical staging in accordance with the guidelines. The guidelines for adjuvant chemotherapy were followed adequately in all 71 patients that were adherent to surgical staging and in 163 of the 195 patients with non-adherence to surgical staging (83.6%). Multivariate analysis, adjusted for prognostic factors, identified higher recurrence-free survival (HR, 0.36; 95% CI, 0.15-0.88) and disease-specific survival (HR, 0.42; 95% CI, 0.16-1.12) among patients whose treatment adhered to both surgical and chemotherapy guidelines, although disease-specific survival was not statistically significant. When excluding clear cell histology from the cohort, the guideline-adherent group had significantly better disease-specific survival than the non-adherent group (HR, 0.13; 95% CI, 0.02-0.94). CONCLUSION: The results of this study suggest that adherence to NCCN guidelines may improve survival outcomes in patients with early-stage epithelial ovarian cancer, particularly in cases other than clear cell histology.

Efficacy and safety of strong acid electrolyzed water for peritoneal lavage to prevent surgical site infection in patients with perforated appendicitis.

PURPOSE: Our previous experimental study of perforated peritonitis in rats proved that peritoneal lavage with strong acid electrolyzed water (SAEW) has no adverse effects, reduces the bacteria count in the ascitic fluid more effectively than saline, and increases the survival rate significantly. Thus, we conducted a randomized controlled study, applying SAEW in the treatment of perforated appendicitis in children. METHODS: Forty-four patients, aged 3-14 years, were randomly divided into two groups: Group S (n = 20), in which the peritoneal cavity was lavaged with 100 ml/kg saline and the wound was washed out with 200 ml saline; and Group E (n = 24), in which the peritoneal cavity was lavaged with 100 ml/kg SAEW and the wound was washed out with 200 ml SAEW. RESULTS: No adverse effect of SAEW was observed in Group E. There was no difference in the bacterial evanescence ratio of ascitic fluid after lavage between Groups S and E (11.1 and 15.8%, respectively). A residual abscess developed in one patient from each group (5.0 and 4.2%, respectively). The incidence of surgical site infection (SSI) was significantly lower in Group E than in Group S (0 and 20%, respectively; P < 0.05). There was no difference in the duration of pyrexia, positive C-reactive protein, leukocytosis, or hospital stay between the groups. CONCLUSION: Peritoneal lavage and wound washing with SAEW have no adverse effects and are effective for preventing SSI.

[Opportunities of intraoperative hyperthermic perfusion application in treatment of peritoneal carcinomatosis].

Normothermic intraperitoneal perfusion (IPEP) and hyperthermic intraperitoneal perfusion (HIPEP) were performed in 44 Wistar female rats with transplanted ascites tumor of the ovary. Opportunities of intraoperative hyperthermic perfusion application in treatment of peritoneal carcinomatosis. Antineoplastic affects were evaluated according to increase of animals' survival. IPEP and HIPEP increase median survival time by 78% (p=0.307) and 150% (p=0.005) respectively in comparison with conventional intraperitoneal introduction of physiological solution. Thus HIPEP has statistically more significant antineoplastic affect in vase of peritoneal carcinomatosis.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for management of recurrent/relapsed ovarian granulosa cell tumor: a single-center experience.

AIM: The aim of this study was to retrospectively report our experience (efficacy/morbidity) with cytoreductive surgery+hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) for the management of recurrent/relapsed ovarian granulosa cell tumors (OGCT). MATERIAL AND METHODS: From 2010 to 2013, six patients underwent CRS+HIPEC. CRS was performed with standard peritonectomy procedures and visceral resections directed towards complete elimination of tumors from the abdominopelvic cavity. HIPEC was performed with cisplatin (50 mg/m²) and doxorubicin (15 mg/m²) and allowed to circulate in the abdominopelvic cavity for 90 min at 41.0-42.2°C. RESULTS: Cytoreduction completeness (CC-0) was achieved in all except one patient (CC-1). Five patients had OGCT recurrences in abdomen+pelvis and one patient in abdomen only. No grade V morbidity (Clavien-Dindo classification) occurred. Two patients developed lung atelectasis, which was managed by mere chest physiotherapy (grade I). One patient developed urinary tract infection (grade II) and another patient developed pneumonia (grade II) - both of which were managed by antibiotics. One patient developed splenic bed and anterior abdominal wall collections requiring ultrasound-guided aspiration without general anesthesia (grade III). One patient developed pulmonary embolism requiring intensive care-unit management (grade IV). Four chemo-naïve patients received adjuvant chemotherapy whereas the remaining two previously chemo-exposed patients received no adjuvant therapy. All patients were alive and disease-free without proof of recurrence/relapse at 40, 32, 27, 24, 20 and 16 months. The average interval of follow-up after CRS+HIPEC was roughly 27 months (range: 16-40 months). CONCLUSION: CRS+HIPEC appears to be an efficacious and morbidly well-tolerated therapeutic modality for recurrent/relapsed OGCT. Long-term follow-up data and further research are needed.

[Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis of colorectal and appendiceal origin].

BACKGROUND: We report our initial experience combining cytoreductive surgery (CRS) plus intraperitoneal chemotherapy with hyperthermia (HIPEC) in a selected group of patients presenting with disseminated peritoneal carcinomatosis (PC) of colorectaL or appendiceaL origin at a single tertiary referral institution. METHODS: The study included patients who underwent CRS with HIPEC at the Sheba Medical Center between April 2009 and December 2011. The HIPEC technique was administered with the open Coliseum technique reaching a steady state of mitomycin-C delivery at 410 C for perfusion duration of 90 minutes. RESULTS: AnaLysis included 45 patients (18 males) incorporating 42 cases of primary colorectal cancer (CRC) or appendiceal cancer and 3 cases of pseudomyxoma peritonei. Thirty-seven patients (82%) underwent CC-0 resections with a median overall hospital stay of 8 days (range 5-43). There was one perioperative death at 90 days. The perioperative complication rate was 31.1%. The median follow-up was 12 months (range 2-36) during which 13 patients died. Among the CRC and appendiceal cancer group the median overall survival was 20.2 months and the median progression free survival was 16.4 months (Kaplan-Meier analysis). During follow-up, 23 patients experienced disease progression. CONCLUSION: The selective use of cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for patients with peritoneal carcinomatosis from colorectal or appendiceal origin is safe with acceptable morbidity and low mortality.

Modified selection criteria for complete cytoreductive surgery plus HIPEC based on peritoneal cancer index and small bowel involvement for peritoneal carcinomatosis of colorectal origin.

BACKGROUND: Complete cytoreductive surgery (CCRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is on the verge of becoming the gold standard treatment for selected patients presenting peritoneal metastases (PM) of colorectal origin. PM is scored with the peritoneal cancer index (PCI), which is the main prognostic factor. However, small bowel (SB) involvement could exert an independent prognostic impact. AIM: To define an adequate cut-off for the PCI and to appraise whether SB involvement exerts an impact on this cut-off. PATIENTS AND METHODS: Patients (n = 139) treated with CCRS plus HIPEC were prospectively verified and retrospectively analyzed. One hundred presented with SB involvement of different extents and at different locations. RESULTS: All the patients with a PCI ≥ 15 exhibited SB involvement. Five-year overall survival was 48% when the PCI was <15 vs 12% when it was ≥ 15 (p < 0.0001. The multivariate analysis retained two prognostic factors: PCI ≥ 15 (p = 0.02, HR = 1.8), and the involvement of area 12 (lower ileum) (p = 0.001, HR = 3.1). When area 12 was invaded, it significantly worsened the prognosis: 5-year overall survival of patients with a PCI <15 and area 12 involved was 15%, close to that of patients with a PCI ≥ 15 (12%) and far lower than that of patients with a PCI <15 and no area 12 involvement (70%). CONCLUSION: A PCI greater than 15 appears to be a relative contraindication for treatment of colorectal PM with CCRS + HIPEC. Involvement of the lower ileum is also a negative prognostic factor to be taken into consideration.