Outcomes of surgical versus non-surgical treatment of resectable T4a laryngeal and hypopharyngeal carcinoma.

OBJECTIVE: Surgery is the recommended treatment for resectable T4a laryngeal and hypopharyngeal carcinoma. Non-surgical treatment is an option in a select few patients. METHOD: This retrospective study was undertaken to assess the treatment outcomes in patients with resectable T4a carcinoma of the larynx and hypopharynx who received either surgical or non-surgical treatment at our institute and to assess factors influencing these outcomes. RESULTS: A total of 120 patients were included in the study. They were divided into groups A, B and C based on the presence of extralaryngeal spread through laryngeal membrane, cartilage or both. The overall survival was better among patients who received surgery than those who received non-surgical treatment in the three groups. The factor influencing overall survival was the treatment given in the form of surgical versus non-surgical treatment. CONCLUSION: Surgery is the preferred treatment for T4a laryngeal and hypopharyngeal carcinoma, even in patients with extralaryngeal spread without cartilage erosion.

Incorporating Tumor Biology to Predict Hepatocellular Carcinoma Recurrence in Patients Undergoing Living Donor Liver Transplantation Using Expanded Selection Criteria.

Conventional selection criteria for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) are based on tumour size/number only, and do not consider vital surrogates of tumor biology such as alpha-fetoprotein (AFP) and tumor [18 F]fluorodeoxyglucose positron emission tomography ([18 F]FDG PET) avidity. We analyzed survival outcomes, and predictors of HCC recurrence in 405 patients with cirrhosis and HCC (HCC-cirr) who underwent living donor LT (LDLT) using our expanded selection criteria: no extrahepatic disease or major vascular invasion, irrespective of tumor size/number. Fifty-one percent patients had tumours beyond Milan, and 43% beyond the University of California San Francisco [UCSF] criteria. The 5-year overall survival (OS) and recurrence-free survival (RFS) were 64% and 70%, respectively. Three preoperatively available factors predicted recurrence: pre-LT AFP ≥100 ng/mL (P = 0.005; hazard ratio [HR], 2.190), tumor burden beyond the UCSF criteria (P = 0.001; HR, 2.640), and [18 F]FDG PET avidity (P = 0.004; HR, 2.442). A prognostic model based on the number and combination of the aforementioned preoperative risk factors was developed using a competing-risk RFS model. Three risk groups were identified: low (none or a single risk factor present, 9.3% recurrence), moderate (AFP ≥100 ng/mL and [18 F]FDG PET avidity, or beyond UCSF tumor and [18 F]FDG PET avidity, 25% recurrence), and high (AFP ≥100 ng/mL and beyond UCSF, or presence of all 3 risk factors, 46% recurrence). Acceptable long-term outcomes were achieved using our expanded selection criteria. Our prognostic model to predict recurrence based on preoperative biological and morphological factors could guide pretransplant management (downstaging versus upfront LDLT) with the aim of reducing post-LDLT recurrence.

Willingness to quit tobacco and its correlates among Indian tobacco users-Findings from the Global Adult Tobacco Survey India, 2016-17.

BACKGROUND: Willingness to quit in a tobacco user forms the basis for future quit attempts and quitting successfully. OBJECTIVE: To determine the prevalence and correlates of willingness to quit among tobacco users in India using the Global Adult Tobacco Survey (GATS), India, 2016-2017. METHODS: GATS, 2016-17 was a multistage geographically clustered sample survey done among 74,037 individuals aged 15 years and above across all the states and two of the Union Territories of India. Data of all those reported using any form of tobacco were studied for past attempts to quit tobacco, advised to quit by a health care provider, and exposure to anti-tobacco messages delivered through various media and the correlation of these with the willingness to quit using multivariate analysis. RESULTS: Of the 21,085 current tobacco users in the survey, 11,679 (52.2%), were willing to quit all forms of tobacco. Multivariate analysis showed that those in younger age groups (OR: 1.39 [1.23-1.56]), higher education levels (OR 1.15 [1.05-1.18]), time of first tobacco use in the day being more than 60 min after waking up in the morning (OR 1.11 [1.03-1.2]), history of attempts to quit in the past 12 months (OR 1.78 [1.69-1.87]), those advised to quit by health care provider in the past 12 months (OR 1.11 [1.06-1.17]), those using single form of tobacco (OR 1.1 [1.05-1.17]), those exposed to anti-tobacco messages in newspapers/magazines (OR 1.1 [1.05-1.17]), and cinemas (1.14 [1.08-1.20]) were more willing to quit compared to their counterparts. CONCLUSION: Enhanced publicizing of anti-tobacco messages through the currently employed media, and ensuring that doctors give a brief advice to quit during any contact with a tobacco user could improve the willingness to quit and the consequent quit rate, especially among those tobacco users who are in younger age groups and who have attempted to quit earlier.

Taxane-based Induction Chemotherapy Plus Concurrent Chemoradiotherapy in Nasopharyngeal Carcinoma: Prospective Results from a Non-endemic Cohort.

AIMS: To report the outcomes of induction chemotherapy (ICT) followed by chemoradiotherapy (CTRT) for a large cohort of locoregionally advanced nasopharyngeal cancer (LA-NPC) from a non-endemic region. MATERIALS AND METHODS: Between January 2008 and July 2015, 201 patients with histologically proven, non-metastatic NPC were treated with ICT followed by CTRT at our institute. All the patients received two to three cycles of a taxane-based ICT regimen. Radiotherapy was delivered using an intensity-modulated radiotherapy (IMRT) technique in all patients. RESULTS: After a median follow-up of 37 months (range: 7-110 months), the 3-year disease-free survival (DFS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival of the entire cohort was 72, 85, 83 and 87.4%, respectively. On multivariate analysis, histology was an independent predictor of DFS, LRFS and overall survival, with keratinising squamous cell carcinoma histologies predicting a worse outcome. The nodal stage was an independent predictor of DFS, DMFS and overall survival. Age, gender, ethnicity, tumour stage and response to ICT did not significantly affect any of the outcomes. Grade 2 or worse subcutaneous fibrosis was seen in 19% of patients at last follow-up and grade 2 or worse xerostomia was seen in 24% of patients. Thirty-nine per cent of patients developed clinical hypothyroidism at last follow-up. CONCLUSION: ICT followed by concurrent CTRT in the IMRT era provides excellent locoregional control, distant control and overall survival rates in patients with LA-NPC. However, distant failure continues to be a problem and may require further systemic intensification.

Squamous cell carcinoma of the tongue in a patient with dyskeratosis congenita: a rare entity.

Dyskeratosis congenita is a rare genetic disorder that results from progressive failure of the bone marrow. It presents with a classic triad of reticular pigmentations of the skin, dystrophic nails, and oral leukoplakia; patients rarely develop cancers. We report a patient with dyskeratosis congenita who presented with squamous cell carcinoma of the oral tongue.

The effect of probiotics and zinc supplementation on the immune response to oral rotavirus vaccine: A randomized, factorial design, placebo-controlled study among Indian infants.

BACKGROUND: Strategies are needed to improve oral rotavirus vaccine (RV), which provides suboptimal protection in developing countries. Probiotics and zinc supplementation could improve RV immunogenicity by altering the intestinal microbiota and immune function. METHODS: Infants 5weeks old living in urban Vellore, India were enrolled in a randomized, double-blind, placebo-controlled trial with a 4-arm factorial design to assess the effects of daily zinc (5mg), probiotic (1010Lactobacillus rhamnosus GG) or placebo on the immunogenicity of two doses of RV (Rotarix®, GlaxoSmithKline Biologicals) given at 6 and 10weeks of age. Infants were eligible for participation if healthy, available for the study duration and without prior receipt of RV or oral poliovirus vaccine other than the birth dose. The primary outcome was seroconversion to rotavirus at 14weeks of age based on detection of VP6-specific IgA at ≥20U/ml in previously seronegative infants or a fourfold rise in concentration. RESULTS: The study took place during July 2012 to February 2013. 620 infants were randomized equally between study arms and 551 (88.9%) completed per protocol. Seroconversion was recorded in 54/137 (39.4%), 42/136 (30.9%), 40/143 (28.0%), and 37/135 (27.4%) infants receiving (1) probiotic and zinc, (2) probiotic and placebo, (3) placebo and zinc, (4) two placebos. Seroconversion showed a modest improvement among infants receiving probiotic (difference between groups 1, 2 and 3, 4 was 7.5% (97.5% Confidence Interval (CI): -1.4%, 16.2%), p=0.066) but not zinc (difference between groups 1, 3 and 2, 4 was 4.4% (97.5% CI: -4.4%, 13.2%), p=0.272). 16 serious adverse events were recorded, none related to study interventions. CONCLUSIONS: Zinc or probiotic supplementation did not significantly improve the low immunogenicity of rotavirus vaccine given to infants in a poor urban community in India. A modest effect of combined supplementation deserves further investigation. TRIAL REGISTRATION: The trial was registered in India (CTRI/2012/05/002677).

Hepatic Venous and Inferior Vena Cava Morphology No Longer a Barrier to Living Donor Liver Transplantation for Budd-Chiari Syndrome: Surgical Techniques and Outcomes.

BACKGROUND: Living donor liver transplantation (LDLT) for Budd-Chiari syndrome (BCS) has been reported with <10 inferior vena cava (IVC) replacements with vascular/synthetic graft. The goal of this study was to review outcomes of LDLT for BCS at our center, with an emphasis on surgical techniques and postoperative anticoagulation therapy. METHODS: Between October 2011 and December 2015, a total of 1027 LDLTs were performed. Nine of these patients had BCS. We analyzed their etiologies, operative details, postoperative complications, and outcomes. RESULTS: The indication was chronic liver disease for all patients. Two patients required retrohepatic IVC replacement with a polytetrafluoroethylene graft due to severe adhesions and thrombosis, respectively. One patient required V-Y plasty for suprahepatic IVC narrowing. Five patients had portal venous thrombosis, 3 treated by thrombectomy, and 1 by renoportal anastomosis. The mean follow-up time was 18 ± 16 months. Only 1 early death occurred due to sepsis. The anticoagulation therapy involved heparin infusion from postoperative day 1, conversion to low-molecular-weight-heparin on postoperative days 3 to 6, followed by warfarin (postoperative days 9-16 to maintain an international normalized ratio of 2-3 long term), along with low-dose aspirin for 6 months. There was no recurrence of thrombosis. CONCLUSIONS: LDLT for BCS is well documented in literature. Prevention of recurrent thrombosis depends on meticulous surgical technique, perfect and wide outflow anastomoses, and a strict anticoagulation protocol. A synthetic (polytetrafluoroethylene) graft for IVC interposition is a safe and feasible option for reconstruction with good results. Low-dose aspirin with low-molecular-weight-heparin later converted to warfarin provides excellent results and prevents recurrence of thrombosis.

Modulation of host ubiquitin system genes in human endometrial cell line infected with Mycobacterium tuberculosis.

Endometrium is one of the most commonly affected sites in genital tuberculosis. The understanding of its interaction with the tubercle bacilli is of paramount importance for studying the pathogenesis of this disease. The main objective of this work was to study the interplay between Mycobacterium tuberculosis and host endometrial epithelial cell lines (Ishikawa cell lines), and to identify the differentially expressed genes upon tuberculosis infection. To study this, suppression subtractive hybridization library was constructed using M. tuberculosis H37Rv-infected Ishikawa cell line harvested 24 h post-infection. The subtracted cDNA library was screened, and 105 differentially expressed genes were identified and grouped based on their functions. Since ubiquitination process has gained importance in targeting M. tuberculosis to xenophagy, ubiquitin system genes obtained in the library were selected, and time course analysis of their gene expression was performed. We observed an upregulation of mkrn1 and cops5 and downregulation of zfp91, ndfip2, ube2f, rnft1, psmb6, and psmd13 at 24 h post-infection. From the results obtained, we surmise that ubiquitination pathway genes may have roles in combating tuberculosis which are yet uncharted.

Squamous cell carcinoma of the upper aerodigestive tract in exclusive smokers, chewers, and those with no habits.

BACKGROUND: Tobacco consumption is the major risk factor for developing head and neck squamous cell cancer (SCC). The site of development of HNSCC may depend on the way the tobacco is consumed. While laryngeal cancers are more common among smokers, oral cancers are more common among tobacco chewers. Since the use of smokeless tobacco is increasing, it is important to know whether this difference is restricted only to site wise distribution or it has other clinical and pathological implications. PATIENTS AND METHODS: We analyzed a prospectively collected dataset of HNSCC patients other than nasopharyngeal cancers attending our outpatient department at a single unit of the head and neck services at Tata Memorial Hospital, Mumbai, India, between January 2010 and September 2011. There were 747 eligible patients and were divided into three groups: Those with chewing as the only habit (chewers), those with smoking as the only habit (smokers), and those with no habits. Patients with regular use of alcohol were excluded from the study. The clinical and pathological parameters were analyzed. RESULTS: Of the 747 patients, the tobacco chewers formed 69.3% followed by smokers (19.5%) and patients with no habits (11.1%). Majority of smokers were men (98%). Site distribution revealed patients with chewing as the only habit had oral cancers (most commonly gingivobuccal complex cancers) as the most common site and those with smoking as the only habit had larynx as the most common site. In patients with no habits, oral tongue was found to be the most common site. No statistically significant pathological differences were observed in between these groups in patients who underwent surgery (n = 366) at the initial modality of treatment. CONCLUSIONS: There is a direct relationship between the form of tobacco use and site of appearance of HNSCC. However, there are no differences in clinical or pathological parameters between HNSCC caused by tobacco chewing or tobacco smoking.

Skin involvement and ipsilateral nodal metastasis as a predictor of contralateral nodal metastasis in buccal mucosa cancers.

CONTEXT: In view of low incidence of contralateral nodal metastasis and increase in the morbidity, the opposite neck is not routinely addressed. However, contralateral nodal metastasis is seen frequently in a certain group of patients. Identifying those factors associated with higher chances of contralateral nodal metastasis may help in optimizing the treatment. AIMS: The aim of this study was to identify prognostic factors associated with contralateral nodal metastasis in cases of buccal mucosa cancers. SETTINGS AND DESIGN: A retrospective audit of 125 patients with squamous cell carcinoma of buccal mucosa at a tertiary cancer center. SUBJECTS AND METHODS: Those cases in which lesions were reaching or crossing midline were included in this study. All cases underwent surgery as primary modality of treatment and had bilateral neck dissection. STATISTICAL ANALYSIS USED: Chi-square test is used for evaluating the variables predicting contralateral nodal metastasis. Finally, a multivariate analysis was performed using binomial logistic regression to identify those variables that were independently associated with the risk of contralateral nodal metastasis. RESULTS: Among 125 patients, 53 cases were node negative. Ipsilateral nodal metastasis was seen in 44/125 (35.2%) patients, 26/125 (20.8%) had bilateral neck node metastasis, and 2/125 (1.6%) had isolated contralateral nodal metastasis. Among these 28 patients with contralateral nodal metastasis, 26 patients had ipsilateral nodal metastasis. Ipsilateral nodal metastasis and skin involvement were independently predictive of contralateral nodal metastasis. CONCLUSIONS: Contralateral nodal metastasis in the absence of ipsilateral nodal metastasis is very rare and frozen section of ipsilateral neck dissection specimen can be an important pointer for addressing contralateral neck.

Thrombocytosis and Raised CRP Levels Predicts Advanced Stage in Esophageal Carcinoma.

PURPOSE: The significance of thrombocytosis and raised C-reactive protein (CRP) as prognostic markers in esophageal cancer is unclear. METHODS: We prospectively studied 50 consecutive patients with esophageal cancer and analyzed the relation of preoperative platelet count and CRP levels with the clinico-pathological characteristics and stage of the disease. The platelet count of 319 × 10(9)/L for thrombocytosis and CRP level >6 mg/dl were taken as cut-off values. RESULTS: The incidence of thrombocytosis as well as raised CRP level was 50 %. Eighty percent of patients with thrombocytosis had raised CRP levels. None of patients with early disease (stage I) had thrombocytosis while patients with advanced stage were associated with thrombocytosis, 81.81 % in stage III and 100 % in stage IV (p < 0.001). The incidence of elevated CRP levels has shown progressive linear co-relation with the stage of carcinoma, i.e., 0 % in pathological stage I, 16.67 % in stage II, 45.45 % in stage III, and 100 % in stage IV disease (p = 0.011). Patients with thrombocytosis and patients with raised CRP were associated with pathological nodal metastases in 84.61 % cases (p 0.005) and 61.53 % (p 0.030), respectively. CONCLUSION: Thrombocytosis alone or in combination with raised CRP had progressive linear relation with the stage of esophageal carcinoma.

Locoregional recurrences after post-operative volumetric modulated arc radiotherapy (VMAT) in oral cavity cancers in a resource constrained setting: experience and lessons learned.

OBJECTIVE: The conformal nature of dose distribution produced by volumetric modulated arc radiotherapy (VMAT) increases the risk of geographic miss. Data regarding patterns of failure after VMAT in oral cavity cancers in resource-constrained settings are scarce. The aim of the present study was to ascertain the patterns of failure in patients receiving adjuvant VMAT intensity-modulated radiotherapy (IMRT) for oral cavity cancer in Malabar Cancer Center, Kerala, India. METHODS: Data of patients with oral cavity cancer receiving adjuvant VMAT IMRT between April 2012 and March 2014 were collected. Recurrent volumes were delineated on the treatment planning images and classified as defined by Dawson et al (Dawson LA, Anzai Y, Marsh L, Martel MK, Paulino A, Ship JA, et al. Patterns of local-regional recurrence following parotid-sparing conformal and segmental intensity-modulated radiotherapy for head and neck cancer. Int J Radiat Oncol Biol Phys 2000; 46: 1117-26). RESULTS: 75 patients with a median follow-up of 24 months were analysed. 41 (55%) patients had oral tongue cancers and 52 (69%) of the patients had Stage IVA cancers. The 2-year locoregional recurrence-free survival, disease-free survival and overall survival were 88.9%, 82.1% and 80.5%, respectively. With a median time to failure of 6.5 months, five infield and three outfield failures were identified. CONCLUSION: A relatively low rate of outfield failure and lack of marginal failure attests to the efficacy of VMAT in such patients. Modifications to our existing target delineation policy have been proposed. ADVANCES IN KNOWLEDGE: The use of standardized target delineation methods allows safe use of VMAT IMRT even in resource-constrained settings.

Head and neck cancer in geriatric patients: Analysis of the pattern of care given at a tertiary cancer care center.

BACKGROUND AND AIM: The percentage of elderly people with head and neck cancers (HNC) is on the rise. This makes HNC in this group of patients an important issue for healthcare providers. The present study was planned to analyze the patterns of care given to the geriatric patients and to identify the factors influencing the decision making process. MATERIALS AND METHODS: Data of all the elderly patients (≥65 years) registered in the year 2012, with histologically proven HNC (all sites, stages, histopathological types, except lymphoma, sarcoma and cervical metastasis of unknown origin) receiving treatment (definitive/palliative) were collected. RESULTS: A total of 270 patients were included in this study. The median age was 72 years (range: 65-101), with predominant male population (70%, n = 190). Oral cavity squamous cell carcinoma (SCC) was the most common cancer (57%, n = 154). Eastern Co-Operative Oncology Group performance status (PS) of 0-2 was seen in 91% of the patients. Co-morbidities were present in 139 (51.5%) patients. 50% (n = 134) of the patients received palliative intent treatment, 45% (n = 123) definitive treatment, whereas in 5% (n = 13) the intent was not mentioned. Age, a clinical stage and PS significantly influenced the decision making on the intent of treatment. 208 (77%) patients completed their treatment irrespective of the intent. Age was the only factor influencing treatment completion irrespective of the intent. CONCLUSION: Geriatric HNC patients frequently present with advanced disease, having multiple co-morbidities. Hence, a multidisciplinary team management of these patients is essential, also taking into account of the social and financial support available to these patients.

Haim Munk syndrome and Papillon Lefevre syndrome--allelic mutations in cathepsin C with variation in phenotype.

Papillon-Lefevre syndrome and Haim Munk syndrome are palmoplantar keratodermas associated with premature periodontal destruction. The additional findings of Haim Munk Syndrome include onychogryphosis, arachnodactyly, acral osteolysis and pes planus. Both are associated with mutations in the lysosomal protease cathepsin C. We describe a patient with phenotype for Haim Munk Syndrome and genetic analysis revealed a homozygous point mutation in exon 1 of the gene encoding cathepsin C.

Improvement of xylanase production in solid state fermentation by alkali-tolerant Aspergillus fumigatus MKU1 using a fractional factorial design.

Optimization of media for the maximum production of xylanase by Aspergillus fumigatus MKUI was carried out using De Meo's fractional factorial design with seven components such as NaNO3, K2HPO4, MgSO4, FeSO4. KCl, peptone and yeast extract. A. fumigatus produced a maximum of 700 U/gds of enzyme after 48 hr of incubation (before optimization). After two steps of optimization, the medium designed favoured a 2.8 fold (1950 U/gds) increase in xylanase production by A. fumigatus. Optimized medium for Aspergillus fumigatus contained (g/l) NaNO3, 15; K2HPO4, 15; MgSO4, 5; FeSO4, 0.009; KCI, 0.5; peptone, 20; and yeast extract, 10.

Improvement of xylanase production in solid-state fermentation by alkali tolerant Aspergillus versicolor MKU3.

AIMS: To optimize the media components for xylanase production by Aspergillus versicolor MKU3 in solid-state fermentation (SSF). METHODS AND RESULTS: Medium optimization was carried out using De Moe's fractional factorial design with seven components. Maximum production of xylanase 3249.9 U g(-1) was obtained in SSF with an optimized medium containing (g l(-1)): NaNO(3), 20; K(2)HPO(4), 20; MgSO(4), 10; FeSO(4), 0.001; KCl, 1; peptone, 10 and yeast extract, 10. Four components namely NaNO(3), MgSO(4), peptone and K(2)HPO(4) significantly increased the xylanase production by A. versicolor MKU3. CONCLUSIONS: Fractional factorial design was used to optimize the seven components in the fermentation medium for SSF. The optimized media increased xylanase production by 3.4-fold. SIGNIFICANCE AND IMPACT OF THE STUDY: Aspergillus versicolor MKU3 produced maximum xylanase after two steps of media optimization under alkaline condition. This medium will be significant value for xylanase production in SSF.

Design of 20 MHz wideband piezoelectric transducers for close proximity imaging.

Quarter wave matching of ultrasonic transducers with two layers (glass and parylene) were studied with computer simulation. These layers are located between the piezoelectric transducer and the acoustic load. The purpose is to achieve a short impulse response and high efficiency broadband transfer in a practical manner for high frequency transducers. The acoustic impedances of these layers were chosen based on transmission line theory. A method to measure acoustic properties of the matching layers and a method to choose the material are discussed. The advantages in using a quarter wavelength of glass and parylene as the matching layers are given. The 6 dB fractional bandwidth of the simulated transmission-reception transfer was found to be 0.75, which is a factor of at least 6 improvement over a nonmatched transducer.