Clinical outcomes for microvascular reconstruction in oral cancers: experience from a single surgical centre.

INTRODUCTION: Reconstruction of a surgical defect is an important part of the management of oral cancers. Microvascular free flap construction provides better functional and cosmetic outcomes. METHODS: Between 2014 and 2020, some 524 patients underwent microvascular reconstruction. Comorbidity variables were scored using the Charlson Comorbidity Index (CCI). Complications were recorded using Clavien-Dindo criteria. RESULTS: Eighty-three (15.84%), 339 (64.69%) and 102 (19.47%) patients underwent free radial forearm flap, free anterolateral thigh flap and free fibula osteocutaneous flap (FFOCF), respectively. Clavien-Dindo complications of grade III and above were seen in 39 (7.44%) patients. Total flap loss was seen in 18 patients and of these, 16 were salvaged using alternative free flaps or pedicled flaps. On univariate analysis, overall and major complication rates were higher in FFOCF (p=0.171). Major complications significantly more common in patients with a CCI score >4 (p=0.001). Patients aged >65 years had higher rates of complications (p=0.03). CONCLUSION: Microvascular free tissue transfer is a reliable, safe and gold standard modality in surgical reconstruction and can be replicated in non-institutional settings.

Molecular modeling, docking and dynamic simulations of growth hormone receptor (GHR) of Labeo rohita.

Growth hormones (GH) have diverse functions like growth promotion, metabolism, appetite, reproduction and social behavior in vertebrates, which is mediated through the growth hormone receptor (GHR). This work was aimed to analyze structural features, homology modeling and molecular docking of Labeo rohita GHR protein. A physicochemical characteristic, like molecular weight was 67.2 kDa and hydropathicity was 0.336. Protein modeling and structure confirmation of L. rohita GHR protein showed 92.7% residues are in the favored region. Selection of ligands and molecular docking shown Melengestrol and Riboflavin ligand showed uppermost binding energy values -7.8 and -7.3 kcal/mol. Molecular interactions describe conventional hydrogen bonding of Melengestrol was observed with VAL94, GLU97, GLU95, TRP57, PHE33, THR34, PRO35, ASP36, PRO37, ARG49, GLY292, LYS291, ILE290, ALA287, LYS289 residues. Riboflavin hydrogen bonds interaction was at PRO37, ASP36, PRO35, THR34, ARG49, SER144, VAL443, GLN442, PRO284, ASP294, ILE285, PRO286, SER408, ALA287, GLY292, LYS291, ILE290, PRO288, LYS287. Molecular dynamics simulation outcomes revealed that complex 2 (Riboflavin and GHR protein) is better than complex1 (Melengestrol and GHR protein). Overall, the results of the present work lead identification of novel molecules that may be agonistic of growth hormone receptor protein and can be used to surge growth in fish. Communicated by Ramaswamy H. Sarma.

Microvascular reconstruction for head and neck cancers in high risk population: clinical outcomes and complications.

INTRODUCTION: Microvascular reconstruction is the gold standard for reconstruction in oral cavity cancers. Age and comorbidities determine the type of reconstruction. We aimed to analyse the impact of high-risk comorbidities on perioperative morbidity. METHODS: This is a retrospective study of 317 patients undergoing microvascular reconstruction from January 2014 to December 2017. High risk patients were based on age, American Society of Anaesthesiologists (ASA) grade (III/IV) and Charlson comorbidity index (CCI) score >4; overall, 73 out of 317 patients were evaluated. RESULTS: Median age was 59 years. Five patients (6.8%) had complete flap failures and seven (9.5%) had minor complications (wound breakdown, bleeding, wound dehiscence, partial flap loss). ASA score of IV was significantly associated with morbidity while age >65 years and CCI >4 was not associated. The overall flap success rate was 93.2%. CONCLUSIONS: A high-risk population has nearly similar outcomes for microvascular reconstruction as a younger age group. High ASA score adversely affects surgery-related outcomes.

Oncological outcomes in patients undergoing major glossectomy for advanced carcinoma of the oral tongue.

INTRODUCTION: Major glossectomy is the treatment of choice in locally advanced tongue cancer. It remains the only option in the presence of recurrent or residual disease. The long-term outcomes for patients undergoing major glossectomy have traditionally been poor, with significant morbidity and poor oncological outcomes. The aim of this study was to report on oncological outcomes in patients undergoing major glossectomy. METHODS: All patients undergoing major glossectomy between 2014 and 2018 were included in the study. The data of 85 patients with advanced carcinoma of the oral tongue were evaluated. All were under the care of a single surgical and reconstructive team at two hospitals in Mumbai. RESULTS: The median patient age was 45 years. At the most recent follow-up, 55 patients (65%) were alive, 47 of whom were disease free. Twenty-nine patients (34%) had locoregional recurrence and twenty-five (29%) had distant metastasis. At a median follow-up of 19 months, rates for 2-year locoregional control, disease free survival (DFS) and overall survival (OS) were 69%, 61% and 62% respectively. Perinodal extension demonstrated a trend towards poor DFS (p=0.060), as did perineural invasion (p=0.055). Node positivity was a significant factor for poor OS, DFS and locoregional control. Multiple node involvement was significantly associated with poor OS on multivariate analysis (p=0.002). CONCLUSIONS: Node positivity and multiple node involvement were associated with poor outcomes. Major glossectomy may be offered as a curative option for selected patients with advanced carcinoma of the oral tongue with node negative or limited neck nodal disease (N1).

Impact of comorbidities on perioperative outcomes for carcinoma of oral cavity.

INTRODUCTION: Surgical management of oral cavity carcinoma involves composite resection with reconstruction. Comorbidities increase the risk of perioperative complications. Objective stratification is important for uneventful recovery. The Charlson Comorbidity Index and the Washington University Head and Neck Comorbidity Index were used to assess perioperative morbidity and mortality. MATERIALS AND METHODS: This was a prospective study of 531 patients with head and neck squamous cell carcinoma who were treated between January 2014 and December 2017. Patients' comorbidity scores on the Charlson Comorbidity Index and Washington University Head and Neck Comorbidity Index were recorded. RESULTS: The median age of the cohort was 49 years. Median Charlson Comorbidity Index score was 3 and Washington University Head and Neck Comorbidity Index was 0. There were five mortalities with a Charlson Comorbidity Index score of 4 or more. Fifteen patients had either infection, leak or postoperative bleeding. A Charlson Comorbidity Index of 4 or more was associated with higher event rate and poor overall survival (p=0.001). CONCLUSION: Higher Charlson Comorbidity Index score is associated with increased incidence of peri-operative morbidity and mortality, while the Washington University Head and Neck Comorbidity Index is a poor predictor of the same.

Pattern of infection, therapy, outcome and risk stratification of patients with febrile neutropenia in a tertiary care oncology hospital in India.

CONTEXT: Indian febrile neutropenia (FN) data are limited, especially in adult solid tumor patients. AIMS: The aim was to study patterns of presentation, source of infection, management and outcome and to evaluate the factors which may correlate with outcome. MATERIALS AND METHODS: A retrospective analysis of prospective data of FN patients at a tertiary care oncology teaching hospital in India between 2007 and 2012. A standardized form was filled for each patient. Patient management was at the discretion of the treating physician. Multinational Association for Supportive Care in Cancer (MASCC) score was retrospectively calculated. Failure of therapy was defined as death, organ failure, shifting from outpatient to inpatient or requirement of intensive care support. SPSS version 16 was used for analysis. RESULTS: A total of 388 FN episodes were included: 256 in hematolymphoid and 132 in solid tumor patients. 156 episodes were high-risk by MASCC score. Focus of infection was clinical in 45% and radiologic in 16%. Blood cultures were positive in 18% cases, most commonly Gram-negative organisms (72%). 93% patients were treated with an antibiotic combination of third-generation cephalosporin/beta-lactamase inhibitor, with aminoglycoside or fluoroquinolone. Antibiotic sensitivity to ceftriaxone was low at 38% while sensitivity to cefoperazone/sulbactam and piperacillin/tazobactam ranged between 50% and 55% and for carbapenems 75%. Failure of therapy occurred in 156 episodes, most commonly due to the need for second line antibiotics. Mortality was 5.5%. On univariate analysis, MASCC score, age, type of malignancy, prophylactic growth factors, presence of focus of infection, hemoglobin and nadir platelet count correlated with FN complications. CONCLUSION: Gram-negative bacteremia continues to be the predominant cause of FN in our setup.

Is There a Limitation of RECIST Criteria in Prediction of Pathological Response, in Head and Neck Cancers, to Postinduction Chemotherapy?

This study studied the coorelation between radiological response to induction chemotherapy and acheivement of pCR or near pCR. It was a retrospective analysis in which all patients who received NACT from 2008 till april 2012 were subjected to inclusion criteria. Coorelation analysis was performed between CR + PR and acheivement of pCR or near pCR. Twenty four patients were identified.The primary site of tumor was oral cavity in 19 patients (79.2%), maxilla in 2 patients (4.2%), laryngopharynx in 2 patients (4.2%) and oropharynx in 1 patient (4.2%). The clinical stage was stage IVA in 16 patients ( 66.7%) and IVB in 8 patients (33.3%). The overall response rates ie a combination of CR and PR was seen in 11patients (45.8%). The pCR was seen in 15 patients (62.5%) and rest had near pCR. There was no linear coorelation between radiological size decrement and tumor response. On coorelation analysis the spearman correlation coefficent was -0.039 (P = 0.857). This suggest that presently used radiological response criterias for response assesment in head and neck cancers severly limit our ability to identify patients who would have pCR or near pCR.

Sunitinib in metastatic renal cell carcimoma: a single-center experience.

INTRODUCTION: Historically, metastatic renal cell carcinoma (RCC) has had poor prognosis; the outcomes have improved with the introduction of tyrosine-kinase inhibitors, such as sunitinib. There is no reported literature from India on the use of sunitinib in metastatic RCC. We present an analysis of sunitinib at our institute over 4 years. MATERIALS AND METHODS: An unselected population of patients with metastatic or relapsed metastatic RCC receiving sunitinib was analyzed with respect to patient characteristics, response, toxicity, and outcomes. RESULTS: Fifty-nine patients (51 males, 8 females) with a median age of 55 years were included in the study. Lungs and bones were the most common site of metastases. The patients received a median number of 4 cycles, with 23 patients requiring dose-modification and 12 discontinuing therapy due to toxicity. Overall, 38 patients (65%) had CR, PR, or standard deviation while 14 had progression or death at initial evaluation. The median progression-free survival (PFS) was 11.4 months and overall survival was 22.6 months. Hand-foot syndrome, fatigue, mucositis, skin rash, and vomiting were seen more often among our patients, whereas hypertension was not as common compared with previously published reports. CONCLUSION: Sunitinib is a viable option for the treatment of metastatic RCC and shows a comparable PFS in Indian patients. Although toxicity remains a concern, most of the adverse effects can be managed conservatively. Careful patient selection, tailoring the dose of therapy, adequate counseling, and careful follow-up is essential for optimum therapy.

Metronomic weekly paclitaxel in advanced unresectable esophageal cancer.

CONTEXT: Advanced esophageal cancer is aggressive with an expected median survival of 6-7 months. Combination chemotherapy regimens provide effective palliation, but result in substantial toxicity. MATERIALS AND METHODS: Retrospective analysis of prospectively collected data of patients with advanced esophageal cancer, not amenable to definitive intent therapy who were treated with intravenous weekly paclitaxel. RESULTS: Between October 2010 and August 2011, 51 patients were included. Median age was 56 years, with a male: female ratio of 2.9:1. 29% were mid esophageal and 55% were lower third and gastroesophageal junction tumors. 65% of the tumors had squamous histology. Performance status was > 2 in 45%. 61% patients had received prior therapy, either definitive or palliative. 51% patients were platinum-pre-treated and 29% had received prior 3 weekly paclitaxel. 76% patients had distant metastases. Median number of cycles of weekly paclitaxel delivered was 11. 71% of patients had improvement in dysphagia, with a median time to symptom improvement of 9 days. In 72% patients, the feeding nasogastric tube could be removed. Overall response rate was 49% (complete remission: 4%, partial remission: 45%, stable disease: 13%). Median progression free survival was 4.7 months (confidence interval [95% CI: 3.7-5.7 months]) and median overall survival was 7.5 months (95% CI: 3.1-11.8 months). Histopathology, performance status and pre-treatment albumin significantly affected survival. The most common grade 3/4 toxicities included hyponatremia (14%), fatigue (16%), diarrhea (12%), anemia (31%), neutropenia (10%) and febrile neutropenia (4%). CONCLUSIONS: Metronomic weekly paclitaxel chemotherapy may provide palliative benefit in advanced unresectable metastatic esophageal cancer with minimal toxicity.

Can combination metronomic therapy overcome chemoresistance in cholangiocarcinoma? A literature review.

Cholangiocarcinoma (CCa) is relatively resistant to chemotherapy as well as radiation therapy, and complete resection is the main curative therapy for these patients. The prognosis for patients with unresectable intrahepatic CCa (iCCa) is extremely poor. A 55-year-old woman presented at our hospital with abdominal pain. After evaluation, she was diagnosed to have multifocal iCCa. She did not opt for standard chemotherapy and therefore received oral metronomic therapy with a combination of celecoxib, etoposide, and cyclophosphamide for a total of 30 months. Presently, she is 57 months post diagnosis and 27 months post cessation of all treatment and continues to be in complete radiological remission. In the present report, we review the literature and discuss whether metronomic scheduling of biologic agents and anticancer drugs will be able to overcome chemoresistance and improve the outcome in cholangiocarcinoma. References for the review were identified through searches of Pubmed for the last 10 years as well as searches of the files of the authors themselves. The final list was generated on the basis of originality and relevance to this review.

Induction chemotherapy in technically unresectable locally advanced oral cavity cancers: does it make a difference?

BACKGROUND: Locally advanced and unresectable oral cavity cancers have a poor prognosis. Induction might be beneficial in this setting by reducing tumor bulk and allowing definitive surgery. AIM: To analyze the impact of induction chemotherapy on locally advanced, technically unresectable oral cavity cancers. MATERIALS AND METHODS: Retrospective analysis of patients with locally advanced oral cavity cancers, who were treated with neoadjuvant chemotherapy (NACT) during the period between June 2009 and December 2010. Data from a prospectively filled database were analyzed for information on patient characteristics, chemotherapy received, toxicity, response rates, local treatment offered, patterns of failure, and overall survival. The statistical analysis was performed with SPSS version 16. RESULTS: 123 patients, with a median age of 42 years were analyzed. Buccal mucosa was the most common subsite (68.30%). Three drug regimen was utilized in 26 patients (21.10%) and the rest received two drug regimen. Resectability was achieved in 17 patients treated with 3 drug regimen (68.00%) and 36 patients receiving 2 drug regimen. Febrile neutropenia was seen in 3 patients (3.09%) receiving 2 drug regimen and in 9 patients (34.62%) receiving 3 drug regimen. The estimated median OS was not reached in patients who had clinical response and underwent surgery as opposed to 8 months in patients treated with non-surgical modality post NACT (P = 0.0001). CONCLUSION: Induction chemotherapy was effective in converting technically unresectable oral cavity cancers to operable disease in approximately 40% of patients and was associated with significantly improved overall survival in comparison to nonsurgical treatment.

Micropropagation and production of camptothecin form in vitro plants of Ophiorrhiza mungos

Objective: To explore the biotechnological potential of Ophiorrhiza mungos for micropropagation and camptothecin (CPT) production from in vitro grown plants.Methods: Surface sterilized explants of O. mungos were transferred aseptically in MS media containing various combinations of phytohormones for callus initiation and multiple shoot proliferation. The content of CPT was quantified in the methanolic extract of O. mungos plants and in in vitro grown plants by using high performance liquid chromatography (HPLC). Results: Maximum fresh weight and dry weight biomass of O. mungos callus was obtained from MS medium supplemented with IAA (2 ppm)+ BAP (2 ppm) + GA (1 ppm). The maximum shoot proliferation (25) and elongation (6.5 cm) was found in MS medium supplemented with Picloram + Thidiazuron + Gibberellic Acid in 1:2:1 ratio after four weeks of incubation. The maximum content of CPT (0.0768 % w/w) was found in wholein vitro plants whereas the minimum CPT was observed in adventitious buds (0.0026 % w/w) as compared to the naturally grown O. mungos plants (0.0030% w/w).Conclusions: Present findings indicate that O. mungos plants respond favourably for in vitro propagation and also produce higher amount of CPT as compared to naturally grown plants.

Studies on assessment of traffic noise level in Aurangabad city, India.

With the rapid rate of urbanization of Aurangabad city due to the expanding industrialization, the problem of noise pollution has become a concern for urban dwellers and government authority too. Noise pollution due to vehicular traffic is one of the growing environmental problems of urban centers. The study deals with the assessment of traffic noise levels in Aurangabad city. With respect to the total number of vehicles passing the road in unit time, which was surveyed by direct count method, six different sites from Aurangabad city, viz., Nagar Naka, Kranti Chowk, CIDCO bus stand, Railway station area, Dhoot Hospital and Baba petrol pump were selected to study the vehicular noise level. Noise measurements were carried out at these six locations on both working day and holiday during the peak traffic hours, i.e. 8:00 a.m. - 11:a.m., 1:00 p.m. - 4:00 p.m. and 5:00 p.m. - 8:00 p.m., in the morning, afternoon and evening sessions, respectively, after 5 minutes time interval. The noise level was monitored using noise level meter. The results obtained from this investigation showed that the Nagar Naka, Kranti chowk and CIDCO bus stand area have dense traffic zones when compared with the Railway station area, Dhoot Hospital and Baba petrol pump. The minimum and the maximum noise levels are 74 and 86 dB, respectively, on working day and 70 and 81 dB, respectively, on holiday. The measured noise level values exceed the prescribed noise level.

Dose-dependent response of central dopaminergic systems to metoclopramide in mice.

Metoclopramide (5 to 40 mg/kg, i.p.) induces catalepsy and antagonised apomorphine induced cage climbing behaviour in mice. This further indicate its postsynaptic striatal and mesolimbic D 2 dopamine (DA) receptor blocking activity. Metoclopramide at 1.25 and 2.5 mg/kg, i.p. induced stereotyped cage climbing behaviour in mice. Pretreatment with haloperidol and alpha-methyl-p-tyrosine significantly antagonised metoclopramide (1.25 and 2.5 mg/kg)-induced stereotyped cage climbing behaviour. Metoclopramide at these doses induces stereotyped cage climbing behaviour by releasing DA from the mesolimbic dopaminergic neurons with resultant activation of the postsynaptic mesolimbic D 2 DA receptors by the released DA. DA releasing action of metoclopramide (1.25 and 2.5 mg/kg, i.p.) and the subsequent induction of the stereotyped cage climbing behaviour by these doses of metoclopramide is explained on the basis of selective blockade of the presynaptic D 2 DA autoreceptors by these doses of metoclopramide.

Effects of pentazocine on dopamine-dependent behaviours in mice.

Pentazocine, a kappa opioid receptor agonist, induced catalepsy in mice suggesting thereby that it might possess postsynaptic striatal D 2 dopamine (DA) receptor blocking activity. However, our other findings, that pentazocine pretreatment did not antagonise the cage climbing behaviour induced by the directly acting DA agonist apomorphine in mice and actually potentiated the stereotyped behaviour induced by the indirectly acting DA agonist methamphetamine in mice, indicate that pentazocine does not possess postsynaptic striatal and mesolimbic D 2 DA receptor blocking activity. Pretreatment with naloxone, an antagonist of opioid receptors, antagonised pentazocine-induced catalepsy. This suggests the possible involvement of opioid mechanisms in the induction of catalepsy by pentazocine in mice.

Involvement of dopaminergic mechanisms in racemate pentazocine induced stereotyped behaviour in rats.

Racemate pentazocine was found to induce stereotyped behaviour (SB) in rats. Pretreatment with haloperidol and alpha-methyl-p-tyrosine significantly antagonised dl-pentazocine induced SB. This indicates that dl-pentazocine induces SB by releasing dopamine (DA) from the nigrostriatal and mesolimbic dopaminergic neurones with resultant activation of the postsynaptic striatal and mesolimbic D2 DA receptors by the released DA. However, pretreatment with naloxone failed to significantly modify dl-pentazocine induced SB indicating thereby that opioid mechanisms are not involved in the DA releasing action of dl-pentazocine. Our findings are explained on the basis of recent reports that the d-isomer of pentazocine releases DA by stimulating sigma receptors located on the nigrostriatal and mesolimbic dopaminergic neurones.