A phase 2 randomized controlled trial of oral resistant starch supplements in the prevention of acute radiation proctitis in patients treated for cervical cancer.

BACKGROUND: Radiation induced proctitis is frequently encountered during the radiation therapy of cervical and prostate cancers that causes pain and occasionally with bleeding and may affect the continuity of radiation therapy. AIMS AND OBJECTIVES: The purpose of the study is to look at the benefit of administration of an oral prebiotic amylase resistant starch in reducing the incidence of acute radiation proctitis, a distressing symptom in patients receiving radiation therapy for cancer of the cervix. MATERIAL AND METHODS: The study was conducted between 2011 and 2014 in 104 patients receiving radical chemo-radiotherapy for carcinoma cervix. Patients were randomized in to two arms, one receiving 30 gm of resistant starch and the other digestible starch on a daily basis throughout the course of the external radiotherapy. All patients received standard 4-field box radiation portals, 50 Gy in 25 fractions with 4 cycles of weekly concurrent Cisplatin. At completion of external beam radiotherapy, all patients underwent LDR/HDR brachytherapy. The study was double blinded and allocation was concealed from the investigators. The investigator recorded the radiotherapy related toxicity of the patients according to CTC V 3.0. The incidence and severity of grade 2-4 diarrhoea and proctitis were documented on a weekly basis and compared across the two groups and analyzed. Stool short chain fatty acid concentrations were measured at baseline at 2nd and 4th week and after 6 weeks of completion of radiotherapy in both study placebo arms and reported. The pattern of microbiota in the stool were also estimated in all patients at 4 time points. Two patients who progressed during therapy were not included in the analyses and two patients discontinued the intervention. A per protocol analyses was done. RESULTS: At analysis there were 50 patients in each arm. The severity of clinical proctitis was found to be similar in both groups of patients with 12.2 % of patients experiencing toxicity of grade 2 and above in digestible starch group versus 14.6% in the resistant starch group. Functional proctitis was similarly graded and it was found that 16.3 % patients in digestible starch group experienced toxicity against 10.2 % patients in the resistant starch group. This difference was seen at 4th week and continued in the subsequent weeks till the end of radiation. Both groups had similar reported toxicity at 6 weeks post intervention and similar incidence of grade 2 and above diarrhea. The resistant starch group was found to have 8% incidence as compared to 2% in the other group at the 5th and 6th week. The short chain fatty acid concentrations were not significantly different in the groups at any point. CONCLUSION: The study did not demonstrate a significant benefit in administering resistant starch over and above normal diet to patients receiving pelvic radiotherapy. The reasons may be attributed to concurrent use of chemotherapy and decrease in intestinal probiotics. The use of digestible starch in the control arm may have contributed to lower incidence of the toxicity endpoints as well.

Results of a Conservative Dose Plan Linear Accelerator-Based Stereotactic Radiosurgery for Pediatric Intracranial Arteriovenous Malformations.

OBJECTIVE: To evaluate the obliteration rate and clinical outcome following linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) for intracranial arteriovenous malformation (AVM) in pediatric patients (age ≤18 years). METHODS: Factors associated with the obliteration rate and neurologic complications were studied retrospectively in pediatric patients who underwent LINAC-based SRS for AVM between June 1995 and May 2014. RESULTS: The study cohort comprised 36 males and 33 females, with a median age at the time of SRS of 14 years (range, 7-18 years). The mean AVM volume was 8.5 ± 8.7 cc (range, 0.6-41.8 cc). The median marginal dose of radiation delivered was 15 Gy (range, 9-20 Gy). Magnetic resonance imaging (MRI) demonstrated complete obliteration of the AVM in 44 of the 69 patients (63.8%), at a mean follow up of 27.5 months (range, 12-90 months). On subgroup analysis, 41 of the 53 AVMs of ≤14 cc in volume (77.3%) were obliterated. AVMs with a modified AVM radiosurgery score <1 had significantly shorter obliteration times from the time of SRS (P = .006). On multivariate analysis, the mean marginal dose of radiation delivered to the AVM was the sole significant predictor of obliteration (odds ratio, 1.6; 95% confidence interval, 1 to 2.4). CONCLUSIONS: A modest median marginal dose of 15 Gy (16 Gy in the obliterated AVM group vs. 12 Gy in the nonobliterated group) resulted in an obliteration rate of 66.7% after LINAC-based SRS for intracranial AVM, with low rate.

Translating evidence into practice in low resource settings: cervical cancer screening tests are only part of the solution in rural India.

BACKGROUND: The majority of women in rural India have poor or no access to cervical cancer screening services, although one-quarter of all cervical cancers in the world occur there. Several large trials have proven the efficacy of low-tech cervical cancer screening methods in the Indian context but none have documented the necessary components and processes of implementing this evidence in a low-resource setting. METHODS: This paper discusses a feasible model of implementation of cervical cancer screening programme in low-resource settings developed through a pilot research project carried out in rural Tamilnadu, India. The programme used visual inspection of cervix after acetic acid application (VIA) as a screening tool, nurses in the primary care centres as the primary screeners and peer educators within Self-Help Women groups to raise community awareness. RESULTS: The uptake of screening was initially low despite the access to a screening programme. However, the programme witnessed an incremental increase in the number of women accessing screening with increasing community awareness. CONCLUSIONS: The investigators recommend 4 key components to programme implementation in low-resource setting: 1) Evidence-based, cost-effective test and treatment available within the reach of the community; 2) Appropriate referral pathways; 3) Skilled health workers and necessary equipment; and 4) Optimisation of health literacy, beliefs, attitudes of the community.

Squamous cell carcinoma cervix with metastasis to pyloroduodenal region.

Metastatic squamous cell carcinoma in the pyloroduodenal region is uncommon. Cases have been reported where carcinoma of the lung has presented with metastasis to the duodenum. We present here the case of a 57-year-old lady who was found to have a metastasis in pyloroduodenal region while on treatment for carcinoma cervix. The patient developed features of intestinal obstruction and endoscopy showed a growth extending from pyloric antrum to first part of duodenum up to the junction of first and second part. A biopsy was taken from the duodenal area and it was reported as metastatic squamous cell carcinoma. This is one of the few reported cases of hematogenous visceral metastasis from carcinoma cervix. Since the disease was found to be advanced and her performance status was poor, she was provided best supportive care.

Maximum tolerated dose and early response - results of a phase I trial of paclitaxel and cisplatin with radiation therapy in carcinoma of the cervix.

AIMS: Cisplatin-based chemotherapy with radiotherapy is currently the standard treatment for locally advanced carcinoma of the cervix. Recent studies have shown a better response with the addition of newer chemotherapeutic agents. The aim of this phase I study was to establish the maximum tolerated dose (MTD) of paclitaxel in combination with cisplatin as a radiosensitiser along with radiation therapy in the treatment of carcinoma of the cervix and to analyse the toxicity profile of the combination regimen. MATERIALS AND METHODS: In total, 21 newly diagnosed patients with squamous cell carcinoma of the cervix, International Federation of Gynecology and Obstetrics stage IB to IIIB were included in this trial. All patients received external beam radiation therapy to the pelvis (50 Gy in 25 fractions) delivered by conventional four-field box technique followed by low dose rate brachytherapy. Concurrent chemotherapy was administered with weekly cisplatin (30 mg/m(2)) and an escalating dose of weekly paclitaxel starting at 10 mg/m(2) up to 50 mg/m(2) (according to the modified Fibonacci series). RESULTS: The MTD of weekly paclitaxel was found to be 40 mg/m(2). The dose-limiting toxicity that occurred in our patients at a dose of 50 mg/m(2) weekly paclitaxel was grade 3 proctitis and vaginitis. CONCLUSION: In this phase I trial of concurrent radiation and combination chemotherapy with weekly paclitaxel and cisplatin (30 mg/m(2)/week), the MTD of paclitaxel was found to be 40 mg/m(2). This combination was feasible, with an acceptable toxicity profile.

Submandibular approach for tracheal intubation - a case report.

SUMMARY: Intubating a patient with panfacial fractures is always a challenge to the anaesthesiologist. In a 40-yr-old male patient with left Le Fort's III fracture with nasal bone and symphysis menti fracture, we successfully carried out oral endotracheal intubation which was then modified to submandibular approach to provide adequate surgical field. Initially oral endotracheal intubation was performed, then an incision was made in the submandibular region through which the endotracheal tube was brought out and maintained as submandibular approach throughout the surgery.

Capillary haemangioma involving the middle and external ear: radiotherapy as a treatment method.

Capillary haemangiomas rarely occur in the auditory canal and have mainly been managed with surgical excision or kept on close follow up for development of symptoms. Radiotherapy, as a treatment method, has not been reported previously in the published work. We describe a study of a capillary haemangioma in the auditory canal of a 26-year-old woman who presented with bleeding. She was treated with radiotherapy, after the lesion was found to be unsuitable for surgery and embolization. The patient remains well 5 years after completion of treatment.

Cyanobacterial toxins: a growing environmental concern.

Unusual blooms of toxic cyanobacteria in water bodies have drawn attention of environmentalists world over. Major blooms of Anabaena, Microcystis and Nodularia in water storage reservoirs, rivers and lakes leading to adverse health effects have been reported from Australia, England and many other parts of the world. An overview of the morphology and taxonomy of these toxic blue-green algae; their possible sources of contamination including dietary supplements and their potential to cause hepatotoxicity and neurotoxicity is given in this review. A detailed description of different cyanotoxins, and their mode of action has also been compiled. Reports of acute and chronic exposure to these toxic algae and their health effects on unsuspecting population along with a critical evaluation of efficacy of water treatment procedures to control them is presented here.

Convergence of clinical toxicology and epidemiology in relation to health effects of chemicals.

An integrated approach of clinical toxicology and epidemiology is an essential ingredient in environmental health risk management through molecular epidemiology and environmental genomics. The last decade has also seen the emergence of several biochemical markers useful in chemical risk assessment and in epidemiological studies. An appraisal of the concepts involved, the approaches required, and the potential scope of this approach is attempted here.

Effect of lindane on the growth and metabolic activities of cyanobacteria.

The effect of lindane was studied in Cyanobacteria (Anabaena) by estimating its growth pattern, biomass yield, chlorophyll content, and total starch and protein content. The results reveal that exposure of Anabaena with 0.5, 1.0, 1.5, and 2.0 ppm levels of lindane will have drastic effects on biomass production and photosynthetic rate. Since Cyanobacteria are a primary source of aquatic food web and important biofertilizer for rice cultivation, their protection from residual effects of lindane is essential for enriched soil fertility.

Agricultural produce in the dry bed of the River Ganga in Kanpur, India--a new source of pesticide contamination in human diets.

Vegetables grown in the dry bed field of the River Ganga in Kanpur, an important industrial city of North India, were analysed for the pesticides hexachlorocyclohexane (HCH), dichlorodiphenyl trichloroethane (DDT), their isomers and metabolites at three different sites. Residues of both the pesticides were found in all the samples. Mean levels of 109.35, 136.76 and 145.93 microg HCH/kg and 6.64, 49.3 and 46.70 microg DDT/kg were found in the rural upstream, city and downstream industrial areas, respectively. The mean total HCH and DDT levels were within safe limits as per the Indian Standard but some samples had HCH levels above the WHO/FAO limit. The pesticide residue level in vegetables was several fold higher than their surrounding sandy soil and could pose health problems since these popular vegetables are consumed regularly by the population.

Esophageal carcinoma with spread to mesenteric and iliac lymph nodes.

Carcinoma of the esophagus can metastasize to unusual sites. We report a patient with esophageal carcinoma with retrograde spread to the mesenteric and iliac lymph nodes from celiac nodes, demonstrated by magnetic resonance imaging and confirmed by FNAC.

Basaloid squamous carcinoma of the nasal cavity - a case report.

Basaloid squamous carcinoma is a rare variant of squamous carcinoma and is known for its aggressive behavior. Its presentation in the nasal cavity is uncommon . A case of this tumor arising from the nostril and showing good response to concomitant radiotherapy and cisplatinum is presented.

Effect of hexachlorocyclohexane on hsp26 expression in transgenic Drosophila melanogaster.

Hexachlorocyclohexane (HCH) at different concentrations (0.5 to 5.0 ng/ml) mixed with food was fed to third instar larvae of hsp26-lacZ transgenic Drosophila for 2 hr and hsp26 gene expression was examined by beta-galactosidase staining. Puffing in salivary gland polytene chromosomes was also studied. Brain and midgut of larvae showed dark blue staining at 2.0 and 5.0 ng/ml of HCH. Absence of induced puffing at 67B and 84D in the salivary gland polytene chromosomes indicated that these glands are not affected. The study suggests presence of the vulnerable sites in larvae to the higher concentrations of HCH.

Influence of antioxidants on the peroxidative swelling of mitochondria in vitro.

To clarify the role of prooxidative processes during in vitro swelling of freshly isolated rat liver mitochondria, the influence of different antioxidants and free-radical scavengers was tested. Ascorbate below 10 mmol/L without externally added Fe2+ acted as a prooxidant and enhanced swelling. Higher concentrations in the presence of Fe2+ showed antioxidant properties and a decrease in swelling and lipid peroxidation. Swelling was abolished by alpha-tocopherol and reduced to 50% by butylated hydroxytoluene. Glutathione supplementation decreased both swelling and lipid peroxidation. Oxidized glutathione caused swelling without any effect on peroxidation. Hydrogen peroxide, cumene hydroperoxide and t-butyl hydroperoxide caused progressive decreases in glutathione and reduced niacinamide coenzyme levels, suggesting prooxidative changes. Dithiothreitol was found to abolish this effect. Thus, antioxidants reverse superoxide-induced mitochondrial swelling and lipid peroxidation in vitro.

UVB-induced reduction in biomass and overall productivity of cyanobacteria.

Effect of middle wave ultraviolet radiation (UVB) was studied in three different species of cyanobacteria (Nostoc, Anabaena and Scytonema) by estimating their growth pattern, biomass yield, chlorophyll content, total starch and protein content. The results show that exposure of the cyanobacteria with UVB dose corresponding to an increase or decrease of 20% in its environmental flux will have drastic effects on biomass production, photosynthetic rate and nitrogen fixation. Cyanobacteria are primary sources of marine food web and an important biofertilizer; therefore, their protection from increasing threat of stratospheric ozone depletion will be necessary to maintain the ecological balance.

Toxicological considerations in environmental audit studies.

Environmental auditing has emerged as a new industrial management tool in recent years. It involves a careful examination of the organization, management procedures, product development, and equipment for environmental protection. The purpose of an environmental audit, from the toxicological point of view, is to assure that the total risk to humans, material, and environment should not increase as a result of a chemical process. The criteria to be adopted for such a safety audit are outlined.

Metastases to the hand from carcinoma of the lower alveolus.

A case of carcinoma of the lower alveolus metastasizing to the phalanges of the hand is reported. The possible mechanism of such metastases, the clinical and radiological features and the role of fine needle aspiration cytology are discussed.