Potential of Borojoa patinoi Cuatrecasas water extract to inhibit nosocomial antibiotic resistant bacteria and cancer cell proliferation in vitro.

Borojó (Borojoa patinoi Cuatrec.) is a fruit used in Colombian traditional medicine with supposed antihypertensive, antitumoral, diuretic, healing, immunological, anti-inflammatory and aphrodisiac effects. To explore the relative merits in terms of biological activities of borojó aqueous extract (BAE), we investigated in vitro its antimicrobial activity on nosocomial pathogenic and multidrug resistant (MDR) strains of Pseudomonas aeruginosa (6), Staphylococcus aureus (1) and Candida species (6), as well as its cytotoxicity on human conjunctive Wong-Kilbourne derivative (WKD) cells and Caco-2 cells from heterogeneous human epithelial colorectal adenocarcinoma. The bacteriostatic activity was observed overall on P. aeruginosa strains, as evidenced by the increase of the lag phase (43 hours) and reduction of the maximum growth rate detected using 187.5 mg BAE per mL. The bactericidal activity, instead, was observed at 375 mg BAE per mL. On the other hand, BAE showed an anti-proliferative effect against the Caco-2 cell line and was shown to be toxic on the WKD cell line at concentrations ranging from 0.05 to 187.5 µg mL-1. The analysis of the phenolic fraction of the fruit aqueous extract (BAE) using UHPLC-MS/MS showed the presence of 26 compounds, with vanillic, syringic and o-coumaric acids as the most abundant. Among these molecules, 7.81 ng mL-1 luteolin and myricetin, singly tested, were able to reduce bacterial growth. To the best of our knowledge, we are unaware of any previous studies demonstrating the anti-bacterial activity of borojó aqueous extract against antibiotic resistant strains of P. aeruginosa, and its anti-proliferative effect against WKD and Caco-2 cell lines. The latter result offers a potential base for new interest and investigations in relation to colon carcinoma models and borojó fruit consumption, since in Colombia this fruit is consumed also for its supposed antitumoral effects.

The role of metronomic capecitabine for treatment of recurrent hepatocellular carcinoma after liver transplantation.

The management of recurrent hepatocellular carcinoma untreatable with surgical options is based on systemic therapy with sorafenib. Due to the high rates of adverse events connected to the therapy with sorafenib, metronomic capecitabine seems a promising strategy for these patients. We analyzed the data of 38 patients with hepatocellular carcinoma recurrent after liver transplantation performed at our center. We compared the outcome of 17 patients receiving metronomic capecitabine versus 20 patients experiencing best supportive care and versus the data of the literature about treatment with sorafenib. In the group treated with metronomic capecitabine we observed an increased survival after tumor recurrence at the univariate and multivariate analysis compared to the group of best supportive care (median 22 months vs. 7 months, p < 0.01). Data from the literature on the use of sorafenib showed outcomes like our study group, with similar patient and tumoral features. The episodes of acute rejection and the tumor stage at the recurrence showed a correlation with patient survival at the univariate analysis. The metronomic capecitabine for hepatocellular cancer recurrent after liver transplantation seems effective without important adverse events and comparable results to sorafenib.

Plasmapheresis, Intravenous Immunoglobulins, and Autologous Serum Eyedrops in the Acute Eye Complications of Toxic Epidermal Necrolysis.

PURPOSE: Toxic epidermal necrolysis (TEN) is a rare, life-threatening, drug-induced, mucocutaneous disease, which can severely affect the ocular surface. The purpose of this study was to investigate the efficacy of plasmapheresis, human IV immunoglobulins (IVIg), and autologous serum (AS) eyedrops in the treatment of the severe acute ocular complications of TEN. METHODS: A retrospective chart review of all patients admitted to the Burn Unit, Azienda Ospedaliero-Universitaria-Sassari, Sassari, Italy, from 2009 to 2015, identified 9 patients (2 men, 7 women; mean age 63.8 ± 24.7 years) with TEN. Bilateral, acute ocular surface complications were observed in 7 (78%) patients; 3 showed catarrhal conjunctivitis, whereas 4 had severe pseudomembranous conjunctivitis and corneal ulcers. RESULTS: All patients with TEN were immediately treated with plasmapheresis and human IVIg, which produced a marked improvement in the patients' general condition. In the 3 with catarrhal conjunctivitis, preservative-free artificial tears and topical antibiotics were beneficial. In the 4 with severe pseudomembranous conjunctivitis and corneal ulcers, treatment with AS eyedrops resulted in corneal and conjunctival epithelium healing over 3-6 weeks. After a minimum follow-up of at least 12 months, there were minimal/mild residual signs and symptoms of dry eye. CONCLUSIONS: Plasmapheresis and IVIg may be life-saving and contribute to reduce ocular surface inflammation in TEN. Autologous serum eyedrops, prepared after plasmapheresis completion and IVIg infusion, may be helpful in the management of the severe acute ocular complications of TEN.

Liver transplantation is associated with good clinical outcome in patients with active tuberculosis and acute liver failure due to anti-tubercular treatment.

BACKGROUND: Active tuberculosis (TB) is commonly considered a contraindication for liver transplantation (LT). However, in patients with TB who develop acute liver failure (ALF) due to toxicity induced by anti-tubercular treatment (ATT), LT could be the only opportunity for treatment. The aim of this study was to evaluate the feasibility of LT in this scenario. METHODS: We described 2 cases and comprehensively reviewed the literature finding 26 cases of LT performed in patients having a concomitant active TB and liver failure secondary to ATT toxicity. RESULTS: TB was classified as pulmonary in 18/26 (69%), nodal in 3/26 (11%) TB cases, while the remaining 5/26 cases included disseminated, pleural, renal, ovarian, and vertebral TB localization (1 case each). ATT following LT consisted mainly of isoniazid or rifampin (RIF)-sparing regimens and included primarily fluoroquinolones and ethambutol. Rejection episodes and liver toxicity were reported in 19% and 8% of patients respectively. Graft rejection was more frequent among patients treated with RIF-containing regimens (P<.001). Mortality rate was 15% after a median follow up of 12 months. In only one case was death attributed to uncontrolled TB infection. CONCLUSION: Our findings suggest that LT is an effective therapeutic option for patients with active TB developing ALF following ATT and should be considered for patients failing medical treatment.

Cytoreduction (Peritonectomy Procedures) Combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Advanced Ovarian Cancer: Retrospective Italian Multicenter Observational Study of 511 Cases.

PURPOSE: The aim of this study was to help with the process of selecting patients with advanced ovarian cancer to undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) by analyzing outcome data at distinct clinical time points reflecting the natural history of the disease. METHODS: In a retrospective Italian multicenter study investigating patients with advanced ovarian cancer who underwent CRS plus HIPEC between 1998 and 2014, we analyzed data for consecutive patients at eight treatment time points: primary debulking surgery (PDS); interval debulking surgery after partial response, after no response, and after a pathologic complete response to neoadjuvant chemotherapy; first recurrence with a progression-free interval >12, <12 months, or >12 months in patients who underwent further chemotherapy before CRS and HIPEC; and patients who underwent two or more CRS procedures and chemotherapy lines before CRS and HIPEC. RESULTS: The 511 enrolled patients underwent 3373 procedures; 72.6% achieved complete cytoreduction, with an overall major morbidity of 17.4%. At a median follow-up of 53.8 months, overall survival (OS) was 54.2 months (95% confidence interval [CI] 44-58.4) and progression-free (PFS) survival was 16.6 months (95% CI 14.7-19.1). Outcome analysis in patients in whom CRS plus HIPEC was used for primary advanced cancer or recurrent ovarian cancer showed significant differences in OS and PFS according to the time points analyzed. Multivariate analysis identified completeness of CRS, Peritoneal Cancer Index, and the times when patients underwent CRS plus HIPEC as independent prognostic factors. CONCLUSIONS: This selective information on survival should help in interpreting the findings from ongoing randomized studies focusing on CRS plus HIPEC in patients with advanced ovarian cancer.

Essential oils in ocular pathology: an experimental study.

INTRODUCTION: The antimicrobial activity of essential oils (EOs) has been known for ages; in particular, the EOs of Melaleuca alternifolia, Thymus vulgaris, Mentha piperita, and Rosmarinus officinalis have been used for the treatment of fungal and bacterial infections. METHODOLOGY: This study focused on the in vitro cytotoxicity to normal human conjunctiva cells and antimicrobial activity of 20 EOs. RESULTS: The oils tested showed no cytotoxic effect at very low concentrations. Rosmarinus officinalis, Melaleuca alternifolia, and Thymus vulgaris L. red thyme geraniol sel oils had good antimicrobial activity against Gram-positive and Gram-negative strains. CONCLUSIONS: The results of this study are of great interest and may have a major impact on public health, providing useful tips to optimize the therapeutic use of some natural drugs.

Hyperthermic intraperitoneal chemotherapy with cisplatin and paclitaxel in advanced ovarian cancer: a multicenter prospective observational study.

OBJECTIVE: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been recently reported with favorable oncological outcomes as treatment of advanced epithelial ovarian cancer (EOC). The aim of this study was to demonstrate the feasibility of CRS+HIPEC with cisplatin and paclitaxel for the treatment of advanced EOC. METHODS: This is a prospective observational study of 54 patients, from April 2007 to October 2013, with primary or recurrent peritoneal carcinomatosis due to EOC. The mean age was 54.51±9.34. Thirty patients (59%) had primary EOC, and 24 patients (41%) had recurrent disease. RESULTS: Mean peritoneal cancer index was 10.11 (range, 0 to 28), complete cytoreduction (CC0) was achieved for 47 patients (87%), CC1 for seven patients (13%). Patients with suboptimal cytoreduction (CC2 and CC3) were not included in the study. The mean stay in intensive care unit was 4.73±5.51 days and the mean hospitalization time was 24.0±10.03 days. We did not observe any intraoperative death. Seven patients (13%) required additional operations. Three patients (5.6%) died within 30 days from the procedure. Severe complications were seen in 19 patients (35.2%). During the follow-up period, disease recurred in 33 patients (61.1%); the median disease-free survival time was 12.46 months and the median overall survival time was 32.91 months. CONCLUSION: CRS+HIPEC with cisplatin and paclitaxel for advanced EOC is feasible with acceptable morbidity and mortality. Additional follow-up and further studies are needed to determine the effects of HIPEC on long term survival.

Short-term outcome of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: preliminary analysis of a multicentre study.

AIM: To assess the incidence of morbidity and mortality of Cytoreductive Surgery plus Hyperthermic Intraperitoneal Chemotherapy. PATIENTS AND METHODS: A retrospective multicentric study was performed. Six hundred and eighty-three patients were recorded. Predictors of morbidity and mortality were evaluated with univariate and multivariate analysis. RESULTS: In univariate analysis, older age, Eastern Cooperative Oncology Group score, a greater value of Peritoneal Cancer Index (PCI) and sub-optimal cytoreduction were correlated with higher mortality, while older age, presence of ascites, ovarian origin of carcinomatosis, closed technique, a greater value of PCI, longer operative time and sub-optimal cytoreduction were predictors of higher morbidity. In multivariate analysis, older age and a greater value of PCI were correlated with higher mortality; older age, ovarian origin of tumor, presence of ascites, closed technique and longer operative time were predictors of higher morbidity. CONCLUSION: Careful patient selection has to be performed to improve clinical outcomes.

Adjuvant systemic chemotherapy after putative curative resection of colorectal liver and lung metastases.

OBJECTIVE: Marginal statistical evidence of efficacy of adjuvant and/or perioperative chemotherapy after resection of colorectal metastases exists, but formal recommendations are still lacking. The present study evaluated the adjuvant systemic chemotherapy after the first resection of liver and lung colorectal cancer metastases. PATIENTS AND METHODS: We retrospectively reviewed data of 181 consecutive unselected patients with R0 resection of colorectal metastases treated simultaneously at 2 institutions from 1997 to 2004. Patients > 75 years old, with an Eastern Cooperative Oncology Group Performance Status Score ≥ 2 or unfit for adjuvant chemotherapy were excluded from the analysis. The decision on chemotherapy after surgery was left to the patient in the absence of conclusive data on the efficacy of adjuvant chemotherapy in this setting. A total of 151 patients (131 with liver metastases, 20 with lung metastases), 78 of whom underwent adjuvant chemotherapy, were evaluable for disease-free survival (DFS) and overall survival. The main prognostic factors for DFS after resection of colorectal cancer metastases were investigated in univariate and multivariate analyses. RESULTS: At the univariate analysis, the number of resected lesions, lesion volume, disease-free interval and adjuvant systemic chemotherapy were the only significant prognostic factors. At multivariate analysis, only adjuvant chemotherapy and disease-free interval were independent prognostic factors (hazard ratios 1.66 and 1.62, respectively). The median DFS of patients who underwent systemic adjuvant chemotherapy was 16 months compared with 9.7 months for patients with observation alone (hazard ratio 1.56). Estimated 5-year DFS was 17.4% and 10.5% for treated and untreated patients, respectively. CONCLUSION: Adjuvant chemotherapy after metastasectomy in patients with colorectal cancer showed a significant benefit for DFS.

Evaluation of extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with advanced epithelial ovarian cancer.

OBJECTIVE: Although standard treatment for advanced epithelial ovarian cancer (EOC) consists of surgical debulking and intravenous platinum- and taxane-based chemotherapy, favorable oncological outcomes have been recently reported with the use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of the study was to analyze feasibility and results of CRS and HIPEC in patients with advanced EOC. MATERIALS/METHODS: This is an open, prospective phase 2 study including patients with primary or recurrent peritoneal carcinomatosis due to EOC. Thirty-nine patients with a mean (SD) age of 57.3 (9.7) years (range, 34-74 years) were included between September 2005 and December 2009. Thirty patients (77%) had recurrent EOC and 9 (23%) had primary EOC. RESULTS: For HIPEC, cisplatin and paclitaxel were used for 11 patients (28%), cisplatin and doxorubicin for 26 patients (66%), paclitaxel and doxorubicin for 1 patient (3%), and doxorubicin alone for 1 patient (3%). The median intra-abdominal outflow temperature was 41.5°C. The mean peritoneal cancer index (PCI) was 11.1 (range, 1-28); and according to the intraoperative tumor extent, the tumor volume was classified as low (PCI <15) or high (PCI ≥15) in 27 patients (69%) and 12 patients (31%), respectively. Microscopically complete cytoreduction was achieved for 35 patients (90%), macroscopic cytoreduction was achieved for 3 patients (7%), and a gross tumor debulking was performed for 1 patient (3%). Mean hospital stay was 23.8 days. Postoperative complications occurred in 7 patients (18%), and reoperations in 3 patients (8%). There was one postoperative death. Recurrence was seen in 23 patients (59%) with a mean recurrence time of 14.4 months (range, 1-49 months). CONCLUSIONS: Hyperthermic intraperitoneal chemotherapy after extensive CRS for advanced EOC is feasible with acceptable morbidity and mortality. Complete cytoreduction may improve survival in highly selected patients. Additional follow-up and further studies are needed to determine the effects of HIPEC on survival.