An analysis of patients with bulky advanced stage ovarian, tubal, and peritoneal carcinoma treated with primary debulking surgery (PDS) during an identical time period as the randomized EORTC-NCIC trial of PDS vs neoadjuvant chemotherapy (NACT)

Objective

The recent EORTC-NCIC randomized trial comparing primary debulking surgery (PDS) to neoadjuvant chemotherapy (NACT) in advanced epithelial ovarian carcinoma (EOC) reported a median progression-free survival (PFS) of 12 months and overall survival (OS) of 30 months for both arms. Due to the equivalent survival and decreased morbidity with NACT, many now consider it the preferred approach. We analyzed the outcomes of patients treated with PDS at our institution during the same time period in which the EORTC-NCIC trial was conducted, using identical inclusion criteria.

Methods

We identified all patients undergoing primary treatment for advanced EOC at our institution from 9/98-12/06. Study inclusion and exclusion criteria were identical to those of the EORTC-NCIC trial. Standard statistical tests were used.

Results

Of 316 eligible patients, 285 (90%) underwent PDS and 31 (10%) received NACT due to extra-abdominal disease, medical comorbidities, and/or advanced age (> 85 years). Of the 285 patients who underwent PDS, most had carcinoma of ovarian origin (248, 87%); stage IIIC disease (249, 87%); grade 3 tumors (237, 83%); and serous histology (249, 87%). Optimal cytoreduction (≤ 1 cm residual) was achieved in 203 patients (71%). Postoperative platinum-based chemotherapy was given to 281 of 285 patients (99%). The median PFS and OS were 17 and 50 months, respectively.

Conclusion

PDS should continue to be the preferred initial management for patients with bulky stages IIIC-IV ovarian carcinoma. NACT should be reserved for those who cannot tolerate PDS and/or for whom optimal cytoreduction is not feasible.     

Dendrimers as novel systems for delivery of neuropharmaceuticals to the brain

Most of the newly developed drugs fails to achieve sufficient bioavailability in to brain due to low water solubility and low permeability. Drug delivery systems are one method for achieving entry of molecules to their desired site of action within the body. Dendrimers are the customizable nanopolymers with uniform and well-defined particle size and shape. Dendrimers are of eminent interest for biomedical applications because of their ability to cross cell membranes. This potential pharmaceutical delivery system crosses the blood brain barrier (BBB) and other important target points. The high level of control over the dendritic architecture (size, branching density, surface functionality) make dendrimers ideal carriers in the field of brain drug delivery of anticancer, antiinflammatory, and antimicrobial agents. Examples of dendrimers such as poly(amidoamine) (PAMAM), poly(propylene imine) (PPI) and polyether-copolyester (PEPE), Glyco, PEGylated, peptide and pH dendrimers are of outmost significance. These dendrimers carry the drug molecules by physical interactions (encapsulation) or through chemical bonding (prodrug approach), while pH sensitive dendrimers are able to deliver drug molecules by alteration of ionic exchange in the brain microenvironment at the tumor site. Techniques employing dendrimers could be especially useful for drugs targeting to Alzheimer's and Prion's diseases. The present review should be of value to scientists who wish to work on the dendrimers for the delivery of molecules into the brain by systemic dosing.     

Targeting remyelination treatment for multiple sclerosis

Since disability in multiple sclerosis (MS) is a product of neurodegeneration and deficient remyelination, the ability to enhance neuroregeneration and myelin regeneration in MS is an enticing goal for MS drug development. In particular, remyelination treatments could promote return of neurological function and also prevent further axonal loss and neurodegeneration in MS due to trophic effects of myelin. The study of remyelination has advanced dramatically in the last several years such that a number of pathways inhibiting remyelination have been discovered, including those involving LINGO-1, Notch-1, hyaluronan, retinoid X receptor, and wnt/ß-catenin. Other approaches such as high throughput drug screening for remyelination drugs have caught fire, with identification of dozens of known drugs with oligodendrocyte maturation stimulatory effects. Several drugs identified through screens and other mechanisms are in the process of being further evaluated for remyelination in MS and MS models. We discuss the potential molecular targets and the variety of mechanisms towards drug identification and development in remyelination for MS.     

Health shock,catastrophic expenditure and its consequences on welfare of the household engaged in informal sector

Purpose

Despite significant contribution by India’s informal sector, tattered conditions have inflated the burden of health shocks in many ways. This study tries to examine the economic burden of health shocks and its associated consequences on households whose members are involved in informal sector. We primarily focus on three objectives for our analysis: (1) compute distribution and magnitude of health shocks and health expenditure between formal and informal workers; (2) evaluate the incidence and intensity of catastrophic health expenditure (CHE), and measure its impoverishment effect; (3) estimate the major determinants of CHE for informal sector households.

Methods

Underlying objectives have been estimated using standard catastrophic and impoverishment measures (poverty headcount and poverty gap) and Poisson, logit and Tobit multivariate regression models. For empirical analysis, data is exploited from the recent round of Indian Human Development Survey (IHDS-II), 2012.

Results

We find that around 27% of households engaged in the informal sector spends more than 5% threshold on their health payment. We also find that OOP health expenditure pushes 7.12% informal sector households in poverty. Moreover, we also find that the impoverishment effect mainly rests on outpatient health expenditure and poverty deepening for informal sector households.

Conclusion

Our findings indicate that informal sector workers are highly vulnerable to health shocks and economic burden in terms of high treatment costs and low insurance coverage. Further, we also show that workers engaged in the informal sector witness greater probability of incurring CHE and impoverishment. Results from the Tobit model suggests that various factors such as insurance coverage, severity of illness and others are crucial predictor of catastrophic spending.

     

Genetic analysis of four Pakistani families with achromatopsia and a novel S4 motif mutation of <Emphasis Type="Italic">CNGA3</Emphasis>

Background  

To identify the causative variants of achromatopsia (ACHM) in four Pakistani families presenting autosomal recessive ACHM.     

Pediatric radical abdominal trachelectomy for cervical clear cell carcinoma: a novel surgical approach

INTRODUCTION: Clear cell carcinoma of the cervix and vagina is rare in the pediatric population. Many of these tumors are associated with prior intrauterine diethylstilbestrol (DES) exposure. All DES-associated tumors are believed to contain microsatellite instability (MI). Historically, the recommended treatment is radical hysterectomy and pelvic lymphadenectomy, which result in infertility in all cases. Radical abdominal or vaginal trachelectomy and pelvic lymph node dissection is a new technique utilized in adult women with early cervical cancer who wish to retain fertility. This novel approach is also pertinent to the pediatric patient and is described in this report. A molecular analysis is also performed to determine if these are DES-associated tumors. METHODS: Due to the narrow vaginal anatomy in pediatric patients, a vaginal approach is not possible, and an abdominal approach is performed. The resection includes the cervix, upper vagina, parametrium, and paracolpos. Pelvic lymphadenectomy is performed in a similar manner to the adult patient. Matched pairs of normal and tumor DNA from both cases were examined for evidence of MI using a consensus panel of microsatellite markers. RESULTS: Two girls aged 6 and 8 years and without history of DES exposure presented with vaginal bleeding. Vaginoscopy revealed cervical polyp in both cases. Biopsies demonstrated clear cell cancer stage IB1 in both patients. They underwent radical abdominal trachelectomy and bilateral pelvic lymph node dissection along with anastomosis of uterine isthmus to upper vagina. Intraoperative frozen-section analysis confirmed negative uterine and vaginal margins. No adjuvant treatment was given and both girls remain disease free. Neither tumor showed evidence for MI, confirming that these are not DES-associated tumors. CONCLUSION: To our knowledge, this is the first report of radical abdominal trachelectomy in the pediatric age group and it is likely to include the youngest patient with clear cell carcinoma of the uterine cervix not associated with DES exposure. This novel approach is feasible and appears safe in the pediatric age group.     

En bloc resection of diaphragm with lung for recurrent ovarian cancer: a case report

INTRODUCTION: Multiple series have demonstrated the feasibility of full-thickness diaphragm resection for ovarian cancer metastatic to the diaphragm. However, direct extension of tumor into the lung is sometimes encountered, and successful resection of this type of implant has not been previously described in the gynecologic oncology literature. CASE REPORT: We present the first case of en bloc full-thickness diaphragm resection including a portion of lung tissue using the EndoGIA stapler with primary diaphragmatic closure. DISCUSSION: En bloc full-thickness diaphragm resection including a portion of lung tissue using the EndoGIA stapler is a safe, feasible, and effective method to optimize cytoreduction with disease-free margins in the context of invasive diaphragmatic ovarian cancer metastasis.     

Synthesis and anticonvulsant and anti inflammatory activities of new 3-aryl/alkylimino-1-methylindol-2-ones

Titled compounds have been synthesized by treating the 3-aryl/alkyliminoindol-2-ones with dimethyl-sulfate in presence of 10% sodium hydroxide and screened for their anticonvulsant and anti-inflammatory activities. The compounds having 1-naphthyl andp-chlorophenyl substituents are the most potent compounds in the series.