Change in CD3ζ-chain expression is an independent predictor of disease status in head and neck cancer patients.

CD3ζ has emerged as a clinically important immunological marker in head and neck squamous cell carcinoma (HNSCC) with reduced level of expression reported in both tumor infiltrating lymphocytes and peripheral blood lymphocytes. In this prospective study (power = 0.99, α = 0.05), CD3ζ expression was compared in 47 HNSCC patients and 53 controls using standardized flow cytometric method. There was no statistical difference in the percentages of the CD3 ε+ T-cell subset present in the peripheral blood mononuclear cells of the HNSCC patients and the healthy controls; however, T cells from the HNSCC patients produced a significantly weaker IFN-γ response in comparison to the healthy controls, when they were stimulated by the recall viral CEF peptide antigen. All patients were followed up for at least 3 years with a median follow-up of 45 months. Levels of CD3ζ-chain expression were measured at 117 follow-up visits at six-month intervals. Receiver operating characteristic curve identified the optimal cut off as a 12% increase in post treatment CD3ζ-chain expression from the baseline levels to confirm absence of HNSCC with the area under curve of 0.81 (95% CI = 0.68-0.94) for predicting absence of HNSCC. The specificity, sensitivity and positive predictive value were 81.25% 79.21% and 97.56%, respectively. Three-year disease specific survival (DSS) was significantly lower (p = 0.007) at 63.2% for patients who showed <12% increase in CD3ζ-chain level as compared to 96.2% for patients who had ≥12% increase. Our results indicate that the change in CD3ζ-chain expression from the baseline is an independent predictor of residual and recurrent HNSCC.

Role of four-dimensional computer tomography (4D-CT) in non-localising and discordant first-line imaging in primary hyperparathyroidism.

BACKGROUND: Accurate preoperative localisation of parathyroid adenoma is imperative for the success of minimally invasive parathyroidectomy (MIP). OBJECTIVE: Our study aimed to evaluate the role of four-dimensional computer tomography (4D-CT) scan as an imaging modality in patients with failed and discordant localisation reported in the first-line imaging modalities (ultrasonography and 99mTc-MIBI-SPECT/CT). METHODS: This is a prospective cohort study performed at a university teaching centre from March 2013 to July 2021. All patients with primary hyperparathyroidism who had failed localisation by ultrasonography and 99mTc-MIBI-SPECT/CT (SpCT), or discordance between them, had 4D-CT performed in this study. RESULTS: One hundred and two sporadic cases of pHPT with failed/discordant first-line imaging had 4D-CT imaging prior to parathyroidectomy. In 102 patients, 105 parathyroid adenomas were reported on histopathology. 4D-CT was able to localise 78% of them to the correct side and 64% to the correct quadrant in 102 patients, as compared with US (correct side 21%, correct quadrant 16%) and 99mTc-MIBI-SPECT/CT (correct side 36%, correct quadrant 31%). 4D-CT had a sensitivity, precision, accuracy and F1 score for correct quadrant localisation as 79%, 81%, 66% and 80%; and for correct side localisation as 82%, 98%, 80% and 89%, respectively. 4D-CT was able to identify three ectopic adenomas (two in superior mediastinum and one in the oesophageal wall) which were not detected on US or SpCT. CONCLUSION: 4D-CT was found to be sensitive and accurate in preoperative localising of the diseased parathyroid glands after failed/discordant US and SpCT. This led to more patients being offered MIP as the primary surgery and improved operative outcomes.

Effect of storage temperature on physico-chemical and sensory attributes of purple passion fruit (Passiflora edulis Sims).

Physico-chemical and sensory quality of juice from purple passion fruit under different storage temperature and time were assessed. The maximum loss in fruit weight was recorded under room temperature (25 ± 1°C) followed by at 11 ± 1°C. There was an increase in juice percentage up to 9 and 13 days under room temperature and storage at 11 ± 1°C respectively. The optimum flavour in juice was up to 5 days at 25 ± 1°C and up to 21 days at 8 ± 1°C. A significant reduction in sourness was recorded on 5th day under all treatments and the scores for sourness became almost constant after 17 days. The maximum increase in the mean scores of sweetness on 5th day was observed at 25 ± 1°C followed by at 11 ± 1°C. The optimum level of juice sweetness was maintained up to 21 days at 8 ± 1°C. Total soluble solids content increased in initial stage followed by reduction. There was a reduction in the titrable acidity up to 21 days at 8 ± 1°C. A decreasing trend in the reducing and non-reducing sugar of passion fruit was observed under all the treatments. Fruits stored at 25 ± 1°C, developed off-flavour in juice after 5 days, while storage at 8 ± 1°C produced no off-flavor even up to 21 days. Fruits can be stored for 5 days only at 25 ± 1°C as the overall sensory quality of juice reduced significantly afterwards, while juice maintained the optimum overall quality up to 21 days at 8 ± 1°C.

Human oral cancers have altered expression of Bcl-2 family members and increased expression of the anti-apoptotic splice variant of Mcl-1.

Expression of Bcl-2 family proteins in tumours can modulate apoptosis, influencing tumour behaviour and treatment. To investigate their role in oral tumourigenesis, nine Bcl-2 family transcripts were examined in three oral cell lines and 25 oral tumours, using ribonuclease protection assay. Since Mcl-1 mRNA was elevated in these samples, Mcl-1 splice variants were assessed by RT-PCR and Mcl-1 protein was studied in normal, premalignant and malignant oral tissues and cell lines, by immunohistochemistry and/or immunoblotting. The cell lines exhibited significantly higher levels of 7/9 Bcl-2 family transcripts as compared to those in normal tongue, and significantly higher (p=0.030, p=0.004) anti-apoptotic versus pro-apoptotic transcripts. Elevated Mcl-1 mRNA was observed in 11/25 (44%) tumours as compared to normal tissues with a five- to ten-fold higher expression of full-length anti-apoptotic Mcl-1 transcript versus the pro-apoptotic short isoform. Strong cytoplasmic Mcl-1 immunoreactivity was detected predominantly in differentiated epithelia in 27/33 (82%) oral tumours, 18/20 (90%) leukoplakia, 25/30 (83%) submucous fibrosis and 3/3 oral cell lines, with weak staining in 8/15 (53%) normal mucosa samples. Mcl-1 positivity in malignant and premalignant tissues was comparable but significantly higher (p<0.01) than that in normal mucosa. The expression of bcl-2 family genes, including Mcl-1 in tumours, did not correlate significantly with clinicopathological parameters. This is the first report delineating the in vivo expression patterns of Mcl-1 protein and Mcl-1 transcripts in oral cancers and premalignant lesions. The observed imbalance between expression of anti-apoptotic and pro-apoptotic Bcl-2 family genes may promote survival in the oral cell lines. Since the majority of oral tumours associated with tobacco-chewing evolve from premalignant lesions, the sustained expression of full-length anti-apoptotic Mcl-1 protein in these tissues suggests an important role for Mcl-1, early in oral cancer pathogenesis in protecting cells from apoptosis via neutralization of pro-apoptotic members and could be a potential therapeutic target for oral cancers.

Head and neck squamous cell cancers: need for an organised time-bound surveillance plan.

Optimal care of patients with head and neck squamous cell cancer (HNSCC) involves a pre-determined period of post-treatment follow-up for the detection of recurrent or persistent disease, metastases and second primaries at the earliest opportunity. There is little evidence in literature as to whether the surveillance schemes should be based on patient survival, quality of life or cost-adjusted parameters. This article aims at highlighting some of the issues pertinent to the optimization of surveillance strategies in HNSCC.

Soil-plant-animal continuum in relation to macro and micro mineral status of dairy cattle in subtropical hill agro ecosystem.

The purpose of the present study was to study the soil-plant-animal continuum in subtropical hilly areas. Soil (n = 96), fodder (n = 96), and blood serum samples from dairy cattle (n = 120) were collected from eight districts of Mizoram, a hilly state in India. The samples were digested using diacid mixture (HNO(3):HClO(4); 10:4) and analyzed for macro (Ca, P, Mg, Na, and K) and micro (Cu, Co, Mn, Fe, and Zn) mineral concentrations. The macro and micro mineral concentrations varied among the different districts. The correlation values between fodder and cattle were significant for all the minerals studied except for P and K. The correlation value between fodder and cattle was highly significant (P < 0.01) for Ca (0.878), Mg (0.88), Cu (0.885), and Zn (0.928). However, such correlations were not observed between the mineral levels in cattle and mineral levels in soil except for Ca (0.782). Equations developed in the present study for prediction of Ca (R(2) = 0.797), Mg (R(2) = 0.777), Zn (R(2) = 0.937), Fe (R(2) = 0.861), and Cu (R(2) = 0.794) had significant R(2) values. Further, it is inferred that dairy cattle reared under smallholder production system were deficient in most of the minerals and supplementation of required minerals is essential for optimum production.

Integrated resource-driven pig production systems in a mountainous area of Northeast India: production practices and pig performance.

Data on pig production system was derived through structured household interviews from a total number of 320 rural households and performance of pigs was assessed. Results revealed that the pig production system represented mixed farming based mainly on the common property resources. Majority of the pigs were reared in intensive system and fed with home made cooked feed (kitchen waste and locally available plants). The body weight of crossbred, Burmese and local pigs were 67, 65.4 and 45.6 kg, respectively at 12 months of age with average daily body weight of 184, 179 and 125 g, respectively. The overall mortality among the pigs was 17.96%. The major causes of mortality in pigs were Swine fever, Swine erysipelas, digestive disorders, nephritis and respiratory disorders. The body weight gain in pigs subjected to deworming and mineral mixture supplementation (218 g/day) was significantly (p < 0.05) higher than the control group (178 g/day). The input output ratio was 1:1.7 for both crossbred and Burmese pigs, while the corresponding ratio for local pigs was 1:1.2. It is inferred that the smallholder resource driven pig production system is economically viable and sustainable at household level and there is enough scope to improve the smallholder resource driven pig production system.

In vitro chemosensitivity profile of oral squamous cell cancer and its correlation with clinical response to chemotherapy.

CONTEXT: Oral cancers represent a disparate group of tumors with diverse clinical behavior and chemosensitivity profile. Currently, it is difficult to predict whether a tumor will respond to chemotherapy and which drug(s) will achieve the maximum clinical response. AIMS: To study in vitro chemosensitivity profile of oral cancers and to correlate the in vitro chemosensitivity of oral cancer to clinical response to chemotherapy. SETTINGS AND DESIGN: Prospective study in a tertiary cancer care center. METHODS AND MATERIAL: We prospectively studied the chemosensitivity profile of 57 untreated, advanced, unresectable oral cancers to cisplatin, methotrexate, 5-fluorouracil and their combinations by using histoculture drug response assay (HDRA) and correlated them to the clinical response to chemotherapy. STATISTICAL ANALYSIS USED: Chi Square test. RESULTS: Biopsy samples were successfully histocultured in 52/57 (91%) cases. Of these 52 evaluable patients, 47 had primary gingivo-buccal cancers and five had tongue / floor of mouth cancers. Based on the assay, 27 (52%) tumors were sensitive to cisplatin, 27 (52%) to methotrexate, 24 (46%) to 5-fluorouracil, 38 (73%) to combination of cisplatin and methotrexate and 36 (69%) to combination of cisplatin and 5-fluorouracil. Of these, 31 patients with good performance status received two cycles of chemotherapy using one or more of these test drugs. There was a significant correlation (p=0.03) between the in vitro chemosensitivity and the clinical response. Negative predictive value of the test was 80%, positive predictive value-69%, sensitivity-79% and specificity -71%. The overall accuracy of the assay was 74%. CONCLUSIONS: We found HDRA to be a fairly good predictor of chemo-response of oral cancer.

Comparing a thyroid prognostic nomogram to the existing staging systems for prediction risk of death from thyroid cancers.

OBJECTIVE: Thyroid prognostic nomogram can be applied across different histological types for predicting the individualized risk of death from thyroid cancer. The objective of this study was to compare the strength of our recently published thyroid prognostic nomogram with 12 existing staging systems to predict the risk of death from thyroid cancer. METHOD: This study included 1900 thyroid cancer patients, from a population based cohort of 2296 patients, on whom adequate staging information was available. Competing risk sub-hazard models were used to compare 12 pre-existing prognostic models with the nomogram model. Their relative strengths for prediction of patients' individualized risks of death from thyroid cancer were compared using Akaike information criterion (AIC), delta AIC, and concordance index. R version 3.2.2 was used to analyze the data. RESULTS: Our cohort of 450 males and 1450 females included 1796 (93.4%) differentiated thyroid cancers. Amongst the compared models, thyroid prognostic nomogram model appeared to be better than other models for predicting the risk of death from all non-anaplastic thyroid cancer (concordance index = 94.4), differentiated thyroid cancer (concordance index = 94.1) and papillary thyroid cancer (concordance index = 94.7). The difference from next best staging systems was most pronounced in non-anaplastic thyroid cancer (delta AIC = 114.8), followed by differentiated thyroid cancer (delta AIC = 35.6) and papillary thyroid cancer (delta AIC = 8.4). CONCLUSIONS: Thyroid prognostic nomogram model was found to be better than the other models compared for predicting risk of death from thyroid cancer.

Regional Variation across Canadian Centers in Radioiodine Administration for Thyroid Remnant Ablation in Well-Differentiated Thyroid Cancer Diagnosed in 2000-2010.

Background. Use of radioactive iodine (RAI) ablation has been reported to vary significantly between studies. We explored variation in RAI ablation care patterns between seven thyroid cancer treatment centers in Canada. Methods. The Canadian Collaborative Network for Cancer of the Thyroid (CANNECT) is a collaborative registry to describe and analyze patterns of care for thyroid cancer. We analyzed data from seven participating centers on RAI ablation in patients diagnosed with well-differentiated (papillary and follicular) thyroid cancer between 2000 and 2010. We compared RAI ablation protocols including indications (based on TNM staging), preparation protocols, and administered dose. We excluded patients with known distant metastases at time of RAI ablation. Results. We included 3072 patients. There were no significant differences in TNM stage over time. RAI use increased in earlier years and then declined. The fraction of patients receiving RAI varied significantly between centers, ranging between 20-85% for T1, 44-100% for T2, 58-100% for T3, and 59-100% for T4. There were significant differences in the RAI doses between centers. Finally, there was major variation in the use of thyroid hormone withdrawal or rhTSH for preparation of RAI ablation. Conclusion. Our study identified significant variation in use of RAI for ablation in patients with well-differentiated thyroid cancer both between Canadian centers and over time.

Simultaneous reconstruction of large skin and mucosal defect following head and neck surgery with a single skin paddle pectoralis major myocutaneous flap.

The pectoralis major myocutaneous (PMMC) flap is commonly used for head and neck reconstruction especially in impoverished nations. PMMC is a sturdy pedicled flap with relatively fewer complications, the learning curve is short and no specialized training in microvascular surgery is needed in order to use this flap. In a defect that requires a large skin and mucosal lining the authors routinely use either a bi-paddle PMMC or a combination of PMMC (for the mucosal lining) and a delto-pectoral flap (for the skin defect). It is indisputable that free tissue transfer is a better way of reconstruction for the majority of most such defects. Unfortunately, not all patients can be offered this form of reconstruction due to the cost, time, expertise and infrastructural constraints in high volume centres such as ours. Bi-paddling of PMMC is hazardous in obese males and most female patients. In such patients the skin defect is reconstructed usually by the delto-pectoral (DP) flap but this, for obvious reasons, is less welcomed by the patients. The authors suggest a technique wherein mucosal lining is created by the myofascial lining (inner surface) of the flap and the skin defect is reconstructed by the skin paddle of the single paddle PMMC. It should be considered wherever a DP flap is unacceptable, or bi-paddling or free tissue transfer is not possible.

Quality of life of head and neck cancer patient: validation of the European organization for research and treatment of cancer QLQ-C30 and European organization for research and treatment of cancer QLQ-H&N 35 in Indian patients.

AIMS: To present the first cross-culture validation of the European organization for research and treatment of cancer (EORTC) quality of life questionnaires, the EORTC-QLQ-C30, and the QLQ-H&N 35 in India. SETTINGS AND DESIGN: These questionnaires were translated into two vernacular languages and pilot test was done on 15 patients. Two hundred head and neck cancer patients completed the QLQ-C30 and the QLQ-H&N 35 at two time points during their treatment. Psychometric evaluation of the structure, reliability, and validity of the questionnaire was undertaken. RESULTS: The data supports the reliability of the scales. Validity was tested by item-scale, scale--scale correlation and by performing known group comparisons. The results demonstrated that the items correlated with their respective scale and no significant correlation was found between scales. The questionnaire was responsive to change over a period of time. SUMMARY: This data suggests that the EORTC QLO-C30 and the QLQ-H&N 35 are reliable and valid questionnaires when applied to a sample of head and neck cancer patients in India.

Identifying the most appropriate age threshold for TNM stage grouping of well-differentiated thyroid cancer.

OBJECTIVE: Age is integrated in most risk stratification systems for well-differentiated thyroid cancer (WDTC). The most appropriate age threshold for stage grouping of WDTC is debatable. The objective of this study was to evaluate the best age threshold for stage grouping by comparing multivariable models designed to evaluate the independent impact of various prognostic factors, including age based stage grouping, on the disease specific survival (DSS) of our population-based cohort. METHODS: Data from population-based thyroid cancer cohort of 2125 consecutive WDTC, diagnosed during 1970-2010, with a median follow-up of 11.5 years, was used to calculate DSS using the Kaplan Meier method. Multivariable analysis with Cox proportional hazard model was used to assess independent impact of different prognostic factors on DSS. The Akaike information criterion (AIC), a measure of statistical model fit, was used to identify the most appropriate age threshold model. Delta AIC, Akaike weight, and evidence ratios were calculated to compare the relative strength of different models. RESULTS: The mean age of the patients was 47.3 years. DSS of the cohort was 95.6% and 92.8% at 10 and 20 years respectively. A threshold of 55 years, with the lowest AIC, was identified as the best model. Akaike weight indicated an 85% chance that this age threshold is the best among the compared models, and is 16.8 times more likely to be the best model as compared to a threshold of 45 years. CONCLUSION: The age threshold of 55 years was found to be the best for TNM stage grouping.

Marginal mandibulectomy for lateral sulcus tumours.

OBJECTIVE: To report a retrospective series of marginal mandibulectomy for cancers of oral cavity, with special reference to squamous cancers of gingival buccal complex. METHODS: Retrospective record review of 107 patients who underwent marginal mandibulectomy between 1994 and 2001. RESULTS: Eighty-three marginal mandibulectomies were done for gingivo-buccal complex cancers. Local failure rate was 16%. The 2-year and 5-year disease free survival rates were 69 and 60%, respectively. The local recurrence free survival at the end of 2 and 5 years were 79 and 70%, respectively. CONCLUSION: In carefully selected patients, marginal mandibulectomy is an oncologically safe procedure to achieve good local control.

Upfront submandibular salivary gland transfer in pharyngeal cancers.

Head and neck irradiation results in salivary dysfunction and subsequent xerostomia. Twenty two patients with squamous cancer of oropharynx or hypopharynx underwent contralateral submandibular salivary gland transfer (SMSGT) to submental triangle to shield it from subsequent radiotherapy. Resting salivary outputs of transferred and untransferred gland (control) were measured before and after SMSGT and following radiotherapy, by cannulating individual submandibular duct. They were compared by paired samples t-test. Following radiation therapy transferred gland retained 73% and untransferred gland (control) retained 27% of baseline salivary output. This significant difference in post-radiation salivary outputs suggests preservation of function of transferred salivary gland.

Neoadjuvant chemotherapy with ifosfamide and cisplatin combination in advanced head and neck cancer: a retrospective analysis of 519 patients: a single institution experience.

Advanced head and neck cancer is a major therapeutic problem in India. Ifosfamide has shown significant activity as a single agent in head and neck squamous carcinoma. In this study, we present our experience with two cycles of ifosfamide and cisplatin in the neoadjuvant setting given to a total of 519 patients. The complete response rate was 20% and the overall response rate was 80%. The treatment was well tolerated, there was no need for dose reduction, and there were no life-threatening side effects. We feel that this high response rate is sufficient to warrant more studies using ifosfamide-based combinations in a neoadjuvant setting for squamous carcinoma of the head and neck.

Two- vs three-drug combination chemotherapy in advanced or recurrent head and neck cancer: a single institution experience of 361 patients.

Head and neck squamous cancer is a major concern in India. The proportion of advanced cases is significantly high, and these patients have dismal survival prospects despite aggressive therapy. Often surgical resection and/or radiotherapy are not feasible in these patients. Hence, we decided to explore the option of neoadjuvant chemotherapy using effective agents like ifosfamide and paclitaxel in combination with cisplatin in these patients. A total of 361 patients were evaluable at the end of study. Of these, 207 had received ifosfamide and cisplatin and 154 had received taxanes (paclitaxel or docetaxel) in addition to ifosfamide and cisplatin. The ifosfamide-cisplatin group had an overall response rate of 66.67% (CR, 16.42%; PR, 50.24%) and the median duration of response was 5.5 mo; whereas the group in which taxanes were added, showed an overall response rate of 73.37% (CR, 7.79%; PR, 65.58%) with a median duration of response of 10 mo. The toxicity in both the groups was acceptable and there was no mortality. We conclude that taxane-based combinations have a significant activity in advanced head and neck squamous cancer and warrant further studies.

Lateral thyrotomy for neurilemmoma of the larynx.

We present a rare case of neurilemmoma of the larynx, which was excised through a lateral thyrotomy approach with resulting restoration of laryngeal function. The advantage of the lateral thyrotomy approach for submucous tumours of the larynx is discussed.

Mesenteric fibromatosis: a report of three cases and literature review.

Fibromatosis is a group of relatively uncommon benign diseases showing proliferation of fibrous tissues and is liable to be confused with fibrosarcoma, thereby causing diagnostic as well as therapeutic dilemmas. Even after the correct diagnosis is made, one is not sure about the most effective treatment is in a given setting. Surgery seems to provide the best results but is not feasible at many times due to the extent of the disease, hence the need for non-surgical modalities for unresectable and incompletely resected tumors. Mesenteric fibromatosis is one of the rarer forms of fibromatosis. Three such cases are being presented here with a brief review of the literature.