Outcomes of Elective Major Cancer Surgery During COVID 19 at Tata Memorial Centre: Implications for Cancer Care Policy.

BACKGROUND: Overburdened systems and concerns of adverse outcomes have resulted in deferred cancer surgeries with devastating consequences. In this COVID pandemic, the decision to continue elective cancer surgeries, and their subsequent outcomes, are sparsely reported from hotspots. METHODS: A prospective database of the Department of Surgical Oncology was analysed from March 23rd to April 30th, 2020. FINDINGS: Four hundred ninety-four elective surgeries were performed (377 untested and 117 tested for Covid 19 before surgery). Median age was 48 years with 13% (n = 64) above the age of 60 years. Sixty-eight percent patients were American Society of Anaesthesiology (ASA) grade I. As per surgical complexity grading, 71 (14·4%) cases were lower grade (I-III) and 423 (85.6%) were higher grade complex surgeries (IV - VI).Clavien-Dindo ≥ grade III complications were 5.6% (n = 28) and there were no postoperative deaths. Patients >60 years documented 9.3% major complications compared to 5.2% in <60 years (P = 0.169). The median hospital stay was 1 to 9 days across specialties.Postoperatively, 26 patients were tested for COVID 19 and 6 tested positive. They all had higher grade surgeries but none required escalated or intensive care treatment related to COVID infection. INTERPRETATION: A combination of scientific and administrative rationale contributed to favorable outcomes after major elective cancer surgeries. These results support the continuation of elective major cancer surgery in regions with Covid 19 trends similar to India.

Myeloid-derived suppressor cells impede T cell functionality and promote Th17 differentiation in oral squamous cell carcinoma.

Oral tumor microenvironment is characterized by chronic inflammation signified with infiltrating leukocytes and soluble mediators which cause immune suppression. However, how immunosuppressive cells like myeloid-derived suppressor cells (MDSCs) maintain the immunosuppressive tumor microenvironment and influence T cell function in oral squamous cell carcinoma (OSCC) patients remains poorly understood. In the present study, we found that percentages of MDSCs were higher in oral cancer patients compared to healthy individuals and correlated with cancer stage. Monocytic MDSCs (M-MDSCs) were prevalent in the periphery, while granulocytic/polymorphonuclear subset dominated the tumor compartment. M-MDSCs suppressed the lymphocyte proliferation and decreased the CD3-ζ (zeta) chain expression and interferon gamma production. The percentage of M-MDSCs in peripheral blood correlated inversely with CD3-ζ chain expression in T cells of these patients. Interleukin 6 (IL-6)-induced phosphorylated STAT3-regulated programmed cell death ligand 1, CCAAT/enhancer-binding proteins alpha and beta and Interleukin 10 expression in MDSCs. MDSCs inhibited TGF-ß-driven generation of induced regulatory T cells in vitro. M-MDSCs secreted interleukins IL-6, IL-1ß, IL-23 and PGE2 and facilitated T-helper 17 (Th17) cell differentiation which utilizes nitric oxide synthase and cyclooxygenase 2 enzyme activity. Interestingly, OSCC patients showed increased levels of Th17 cells in peripheral blood and tumor tissue. Thus, increased frequency of MDSCs, Th17 cells and decreased expression of CD3-ζ chain portray T cell tolerance and chronic inflammatory state facilitating tumor growth.

Extracellular 2'5'-oligoadenylate synthetase 2 mediates T-cell receptor CD3-ζ chain down-regulation via caspase-3 activation in oral cancer.

Decreased expression of CD3-ζ chain, an adaptor protein associated with T-cell signalling, is well documented in patients with oral cancer, but the mechanistic justifications are fragmentary. Previous studies in patients with oral cancer have shown that decreased expression of CD3-ζ chain was associated with decreased responsiveness of T cells. Tumours are known to induce localized as well as systemic immune suppression. This study provides evidence that oral tumour-derived factors promote immune suppression by down-regulating CD3-ζ chain expression. 2'5'-Oligoadenylate synthetase 2 (OAS2) was identified by the proteomic approach and our results established a causative link between CD3-ζ chain down-regulation and OAS2 stimulation. The surrogate situation was established by over-expressing OAS2 in a HEK293 cell line and cell-free supernatant was collected. These supernatants when incubated with T cells resulted in down-regulation of CD3-ζ chain, which shows that the secreted OAS2 is capable of regulating CD3-ζ chain expression. Incubation of T cells with cell-free supernatants of oral tumours or recombinant human OAS2 (rh-OAS2) induced caspase-3 activation, which resulted in CD3-ζ chain down-regulation. Caspase-3 inhibition/down-regulation using pharmacological inhibitor or small interfering RNA restored down-regulated CD3-ζ chain expression in T cells induced by cell-free tumour supernatant or rh-OAS2. Collectively these results show that OAS2 leads to impairment in CD3-ζ chain expression, so offering an explanation that might be applicable to the CD3-ζ chain deficiency observed in cancer and diverse disease conditions.

Real world data on long term outcome of neoadjuvant chemotherapy in locally advanced esthesioneuroblastoma and sinonasal tumor with neuroendocrine differentiation - Results from a single centre study.

INTRODUCTION: Esthesioneuroblastoma and sinonasal neuroendocrine carcinoma (SNEC) are the most common histological subtypes of non-squamous Sinonasal Tumors. A multidisciplinary approach is preferred for locally advanced unresectable esthesioneuroblastoma and SNEC. METHODS: From June 2010 to October 2021, 59 patients with esthesioneuroblastoma and SNEC received NACT. NACT consists of 2-3 cycles of Etoposide-Platinum based chemotherapy. Depending upon response and performance status, subsequent therapy was planned. SPSS descriptive statistics were performed for analysis. Kaplan Meir methods were used for the estimation of Progression Free Survival (PFS) and Overall Survival (OS). RESULTS: 45 (76.3 %) Esthesioneuroblastoma and 14 (23.7 %) SNEC patients received NACT. The median age of the population was 45 years (range 20-81 years). The majority of patients received 2-3 cycles of Platinum (Cisplatin or Carboplatin) + Etoposide as NACT. 28 patients (47.5%) underwent surgery and 20 patients (33.9%) received definitive chemoradiotherapy after NACT. The most common grade 3 or above adverse events were anemia (13.6%), neutropenia (27.1), and hyponatremia (45.8%). At the time of analysis, the median PFS was 56 months (95% CI 31 months to 77 months), and the median OS was 70 months (95% CI 56 months to 86 months). The most common late toxicities noticed were metabolic syndrome (42.4%), hyperglycemia (39%), nasal bleeding (33.9%), hypertension (17%), dyslipidemia (8.5%), and hypothyroidism (5.1%). CONCLUSION: The study shows that NACT is safe, and can be easily delivered without any life-threatening toxicities, with a favorable response and improved survival in this subset of patients.

Neoadjuvant chemotherapy in a rare type of very locally advanced sinonasal carcinomas - long-term results from a tertiary care centre.

Introduction: Sinonasal carcinomas are a rare type of head and neck malignancy with various histologies. The outcomes of patients with unresectable locally advanced sinonasal carcinomas are poor. Hence, we performed this analysis to study the long-term outcomes of sinonasal adenocarcinoma (SNAC) and sinonasal undifferentiated carcinomas (SNUC) where neoadjuvant chemotherapy (NACT) has been given followed by local therapy. Methods: 16 patients with SNUC and adenocarcinoma who received NACT were found eligible for the study. Descriptive statistical analysis was performed for baseline characteristics, adverse events and treatment compliance. Kaplan Meir methods were used for the estimation of progression-free survival (PFS) and overall survival (OS). Results: Seven (43.75%) adenocarcinoma and nine (56.25%) SNUC patients were identified. The median age of the whole cohort was 48.5 years. The median number of cycles delivered was 3 (IQR 1-8). The incidence of grade 3-4 toxicity (CTCAE version 5.0) was 18.75%. The response was partial response or better in seven patients (43.75%). Post-NACT 11 patients (n = 15, 73%) were eligible for definitive therapy. The median PFS was 7.63 months (95% CI, 3.23 - NA months) and the median OS was 10.6 months (95% CI, 5.2-51.5 months). Median PFS and OS for those who underwent surgery post-NACT versus those who did not undergo surgery were 36.267 versus 3.7 months (p = 0.012) and 51.5 versus 10.633 months (p = 0.190), respectively. Conclusion: The study shows a favourable role of NACT in improving resectability, significant improvement in PFS and non-significant improvement in OS after surgery.

Fascin overexpression promotes neoplastic progression in oral squamous cell carcinoma.

BACKGROUND: Fascin is a globular actin cross-linking protein, which plays a major role in forming parallel actin bundles in cell protrusions and is found to be associated with tumor cell invasion and metastasis in various type of cancers including oral squamous cell carcinoma (OSCC). Previously, we have demonstrated that fascin regulates actin polymerization and thereby promotes cell motility in K8-depleted OSCC cells. In the present study we have investigated the role of fascin in tumor progression of OSCC. METHODS: To understand the role of fascin in OSCC development and/or progression, fascin was overexpressed along with vector control in OSCC derived cells AW13516. The phenotype was studied using wound healing, Boyden chamber, cell adhesion, Hanging drop, soft agar and tumorigenicity assays. Further, fascin expression was examined in human OSCC samples (N = 131) using immunohistochemistry and level of its expression was correlated with clinico-pathological parameters of the patients. RESULTS: Fascin overexpression in OSCC derived cells led to significant increase in cell migration, cell invasion and MMP-2 activity. In addition these cells demonstrated increased levels of phosphorylated AKT, ERK1/2 and JNK1/2. Our in vitro results were consistent with correlative studies of fascin expression with the clinico-pathological parameters of the OSCC patients. Fascin expression in OSCC showed statistically significant correlation with increased tumor stage (P = 0.041), increased lymph node metastasis (P = 0.001), less differentiation (P = 0.005), increased recurrence (P = 0.038) and shorter survival (P = 0.004) of the patients. CONCLUSION: In conclusion, our results indicate that fascin promotes tumor progression and activates AKT and MAPK pathways in OSCC-derived cells. Further, our correlative studies of fascin expression in OSCC with clinico-pathological parameters of the patients indicate that fascin may prove to be useful in prognostication and treatment of OSCC.

Surgical Management of Parapharyngeal Tumors: Our Experience.

Context Tumors of parapharyngeal space (PPS) are rare and histologically diverse. The management of these tumors requires diligent assessment and planning with due consideration of various anatomical and pathological aspects of the lesion. Aims This retrospective study aims to present our experiences in the clinical and pathological aspects of PPS tumors with a critical evaluation of management. Settings and Design Retrospective analytical study. Methods and Material The electronic medical records of 60 cases of PPS tumors, managed surgically from 2007 to 2017, were reviewed and analyzed using SPSS 22 software. The mean follow-up duration was 44 months. Results The mean age was 45 years with a male-to-female ratio of 1.7 (38:22). The majority of the tumors were benign (71.7%) and the most common presentation being upper neck mass or oropharyngeal mass. Histologically, neurogenic tumors were most common (43.3%) PPS tumors, followed by tumors of salivary gland origin. Magnetic resonance imaging was used as a diagnostic modality in 70% of cases, and computed tomography scan and positron emission tomography/CT were used in 26.7 and 3.3% of cases, respectively. In our study, the diagnostic accuracy of fine-needle aspiration cytology was 71% for benign and 47% for malignant lesions. The most common approach for surgery used was transcervical (72%). Conclusion The study reveals that cranial nerve palsy is the most common complication associated with PPS tumors. Completely resected, malignant tumors originating within PPS have a good prognosis, as compared with tumors extending or metastasized to PPS.

Prognostic factors for loco-regional failure in early stage (I and II) squamous cell carcinoma of the gingivobuccal complex.

The objective of the article is to study the prognostic indicators of loco-regional failure in patients with early stage cancers of the gingivobuccal complex (GBC) treated at a single institution. The study design is based on retrospective chart review. A review of 2,275 patients diagnosed with GBC was conducted from January 1997 to December 1999, wherein 207 patients who fulfilled our inclusion criteria were analyzed. Univariate analysis, multivariate analysis, and disease-free survival are reported. During a median follow-up of 2.85 years there were 85 (43%) loco-regional failures of which 64% could be salvaged. As much as 80% of all failures occurred within the first 24 months and the mean survival for patients with recurrences was 9.6 months. Two and five-year disease-free survival for the entire cohort was 65% and 52%, respectively. Nodal metastasis, soft tissue infiltration, and pathological bone involvement correlated with poor disease-free survival on multivariate analysis. Early stage tumors of the GBC as evaluated clinically are often upstaged pathologically due to a high rate of occult nodal metastasis and local failure as they tend to invade bone and infiltrate adjacent soft tissue. Consequently, we recommend aggressive surgical therapy as we would recommend for advanced stage cancers of the GBC which includes a wide three-dimensional resection to account for soft tissue and bony infiltrations and adjuvant therapy in the presence of adverse features since salvage rates for recurrent tumors are poor.

Masseter Flap for Reconstruction of Defects After Excision of Buccal Mucosa Cancers with Intact Mandible.

Among the reconstructive options available for buccal mucosa defects with an intact mandible, free flap with microvascular anastomosis is the best option. However, in the developing world, with poor resources, limited in- frastructure, and high patient load, this cannot be offered to all patients. We report on the success of the masseter flap for reconstruction of such defects in carefully selected patients. Despite some known limitations, this flap is easy to learn and carries acceptable complications. The results of this flap may not be comparable to those of microvas- cular reconstructions, but they are better than those from other options such as skin graft, nasolabial flap, submental flap, etc. in terms of surgical time required, no donor site morbidity, and minimal aesthetic deformity.

Quality of life in head and neck cancer survivors: a cross-sectional survey.

PURPOSE: Head and neck cancer (HNC) survivors have substantial psychological distress in addition to treatment-related side effects. This study examines the long-term quality of life (QOL) of HNC survivors in a busy tertiary care center. MATERIAL AND METHODS: A prospective, cross-sectional survey was conducted studying 212 HNC survivors 1 year after completion of their treatment at a tertiary cancer center. Quality of life assessments were performed using the 2 standardized health-related QOL questionnaires: The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 and The Quality of Life Questionnaire Head and Neck Cancer Module. RESULTS: The overall global QOL rating for the study cohort was satisfactory. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 scores showed that the domains where most patients faired poorly included financial difficulties (54%), appetite loss (36%), fatigue (33%), and cough (30%). The Quality of Life Questionnaire Head and Neck Cancer Module scale identified the domains with poor scores to be dry mouth (64%), dental problems (42%), sticky saliva (40%), cough (39%), and problems with mouth opening (32%). Patients with early-stage tumors and those treated with surgery alone had significantly better QOL scores when compared with advanced stage tumors and patients receiving either radiation alone or multimodality treatment, respectively. CONCLUSIONS: Quality of life questionnaires provide a medium for patients to effectively communicate with their physician in a busy tertiary care facility and provide an insight into the physical, psychological, and social problems affecting our patients which can then direct future interventions.

Extensive tubercular neck lymphadenopathy in a man with early-stage tongue cancer.

BACKGROUND: A 66-year-old Asian man presented with a tongue ulcer and without palpable metastases to the neck nodes. A thorough clinical examination of the head and neck region did not reveal any other primary lesion. To assess the status of the neck, PET-CT imaging was advised. INVESTIGATIONS: Physical examination, punch biopsy, PET-CT imaging, blood tests, chest radiograph, fine-needle aspiration biopsy, tumor biopsy, neck incision, tuberculin test, sputum culture and histopathology. DIAGNOSIS: Carcinoma of the tongue of pathologic stage T2 N0 M0, with tubercular lymphadenitis and no nodal metastases. MANAGEMENT: Surgical excision and multidrug antitubercular therapy.

Squamous cell carcinoma of the superior gingival-buccal complex.

Squamous cell carcinoma of the superior gingival-buccal complex are rare and few English-language data have been published on their biological behaviour. Reported in this paper are the clinical behaviour and treatment outcomes of squamous cell carcinoma of the upper gingival-buccal complex. We reviewed the charts of 110 patients with squamous cell carcinoma restricted to the upper gingiva, superior gingival-buccal sulcus and adjoining buccal mucosa, seen between 1997 and 2001. Separate outcome analyses were carried out among 86 patients who had undergone surgery, and 24 patients treated by radiotherapy or chemo-radiation. Disease-free survival at 2 and 5 years was 48.9% and 36%, respectively, and was independent of epicentre of disease. Five-year, disease-free survival was 48.8% and 0% for surgical treatment and non-surgical treatment groups. T stage (p=0.024) and extra-capsular spread of disease (p=0.036) were independent predictors of disease-free survival on multivariate analysis. Adequate surgical resection and adjuvant treatment, in the first instance, offers the best chance of disease control.

Selective neck dissection (I-III) for node negative and node positive necks.

Selective neck dissection (I-III) for oral cancers offers similar regional control rates with less morbidity as compared with modified radical neck dissection. Charts of 414 patients with oral cancer, who underwent selective neck dissection (I-III) during 1994-2001, were analysed retrospectively. Seventy nine percent of the patients had a primary tumour in the gingivo-buccal complex. Cancer of tongue showed a trend towards higher regional failure (12.3%) as compared to gingivo-buccal cancers (6.5%). Primary tumour was staged as T1-8%, T2-47%, T3-19% and T4-26%. Sixty five percent of the patients were clinically node negative. Isolated neck failure was observed in 4.8% of patients at 2 years and in 5.8% at 5 years. De-differentiation of primary tumour and perineural spread were associated with regional failures. Eighty three percent of the neck recurrences were in the ipsilateral neck and only 16% of these were at levels IV or V. In all, 30% of all regional failures were outside the field of dissection.

Urinary bladder metastasis--an unusual presentation of distant spread from a primary pyriform sinus cancer: a case report.

Hypopharyngeal cancers have a high propensity to distant metastasis. However, metastasis to the urinary bladder as an initial presentation of distant spread has not been reported in literature. We present a report of a patient with a treated and controlled pyriform sinus cancer who presented with complaints of dysuria, 8 months after completion of treatment. Cystoscopy revealed a bladder mass and biopsy confirmed it to be a metastatic squamous cell carcinoma. On further investigation, the patient was found to have disseminated disease for which chemotherapy was instituted. A relevant review of literature is also presented.

Squamous cell carcinoma of the maxillary sinus: a Tata Memorial Hospital experience.

BACKGROUND: The optimal treatment of maxillary sinus carcinoma remains to be defined and there is a paucity of Indian studies on the subject. AIMS: To present experience of management of squamous cell carcinoma of the maxillary sinus treated with curative intent at a single institution. SETTINGS AND DESIGN: Retrospective study of patients with squamous cell carcinoma of the maxillary sinus who presented between 1994 to 1999. MATERIALS AND METHODS: The records of 73 patients with squamous cell carcinoma of the maxillary sinus were analyzed. Sixty-two patients were evaluable. Forty patients (65%) were treated with surgery followed by postoperative radiotherapy, five patients (8%) were treated with radiotherapy alone, five patients (8%) were treated with surgery alone; 12 patients (19%) received chemotherapy. STATISTICAL ANALYSIS USED: Statistical analysis was done using Kaplan-Meier method. RESULTS: The majority of patients presented with locally advanced disease (52, 84%); nodal involvement was observed in five patients (8%). The most common site of recurrence was at the primary site, which was observed in 28 patients (45%) and regional failures occurred in 10 (16%). The 3 and 5-year overall survival was 38% and 35% and the disease free survival was 29% and 26% respectively. The 5-year overall survival after surgery and postoperative radiotherapy was 42%. CONCLUSIONS: The majority of patients present with advanced disease resulting in poor outcomes to conventional treatment modalities. Locoregional tumor progression remains a significant pattern of failure. New approaches such as neoadjuvant or concomitant chemoradiotherapy with aggressive surgery need to be considered and evaluated in prospective studies.

Does tranexamic acid reduce blood loss during head and neck cancer surgery?

BACKGROUND AND AIMS: Transfusion of blood and blood products poses several hazards. Antifibrinolytic agents are used to reduce perioperative blood loss. We decided to assess the effect of tranexamic acid (TA) on blood loss and the need for transfusion in head and neck cancer surgery. METHODS: After Institutional Review Board approval, 240 patients undergoing supramajor head and neck cancer surgeries were prospectively randomised to either TA (10 mg/kg) group or placebo (P) group. After induction, the drug was infused by the anaesthesiologist, who was blinded to allocation, over 20 min. The dose was repeated every 3 h. Perioperative (up to 24 h) blood loss, need for transfusion and fluid therapy was recorded. Thromboelastography (TEG) was performed at fixed intervals in the first 100 patients. Patients were watched for post-operative complications. RESULTS: Two hundred and nineteen records were evaluable. We found no difference in intraoperative blood loss (TA - 750 [600-1000] ml vs. P - 780 [150-2600] ml, P = 0.22). Post-operative blood loss was significantly more in the placebo group at 24 h (P - 200 [120-250] ml vs. TA - 250 [50-1050] ml, P = 0.009), but this did not result in higher number of patients needing transfusions (TA - 22/108 and P - 27/111 patients, P = 0.51). TEG revealed faster clot formation and minimal fibrinolysis. Two patients died of causes unrelated to study drug. Incidence of wound complications and deep venous thrombosis was similar. CONCLUSION: In head and neck cancer surgery, TA did not reduce intraoperative blood loss or need for transfusions. Perioperative TEG variables were similar. This may be attributed to pre-existing hypercoagulable state and minimal fibrinolysis in cancer patients.

Masseter flap for reconstruction of defects after excision of buccal mucosa cancers with intact mandible.

Among the reconstructive options available for buccal mucosa defects with an intact mandible, free flap with microvascular anastomosis is the best option. However, in the developing world, with poor resources, limited infrastructure, and high patient load, this cannot be offered to all patients. We report on the success of the masseter flap for reconstruction of such defects in carefully selected patients. Despite some known limitations, this flap is easy to learn and carries acceptable complications. The results of this flap may not be comparable to those of microvascular reconstructions, but they are better than those from other options such as skin graft, nasolabial flap, submental flap, etc., in terms of surgical time required, no donor site morbidity, and minimal aesthetic deformity.

Prospective study of ultrasound-guided fine-needle aspiration cytology and sentinel node biopsy in the staging of clinically negative T1 and T2 oral cancer.

BACKGROUND: The purpose of this study was to compare sentinel node biopsy (SNB) and ultrasound-guided fine-needle aspiration cytology (FNAC) for preoperative evaluation of the N0 neck in T1 to T2 oral cavity squamous cell carcinoma (SCC). METHODS: Fifty-one consecutive patients with T1 to T2 N0 oral cavity SCC were included in this study. Preoperative ultrasound was performed in all patients. Ultrasound-guided FNAC was performed in patients in whom the ultrasound result was reported as indeterminate or positive. SNB was done in all patients followed by elective neck dissection (END). Histopathology of END was considered as the gold standard for all statistical analysis. RESULTS: The incidence of occult metastasis was 26.4%. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 71.4%, 100%, 100%, and 90.2% for SNB and 14.3%, 100%, 100%, and 76.5% for ultrasound-guided FNAC. CONCLUSION: Ultrasound-guided FNAC lacked sufficient accuracy to detect occult metastases. SNB is a reliable method to detect occult metastasis that has potential to replace END.

Hemangioma of base of tongue.

Although vascular malformations of the tongue comprise a significant portion of head and neck angiodysplastic lesions, hemangioma of base of tongue is rare. We report a case of hemangioma of base of tongue extending to the supraglottis, which necessitated an extended supraglottic laryngectomy. Patient had an uneventful recovery and at three year, follow-up has a normal speech and no difficulty in swallowing or aspiration. More importantly, there was no recurrence of hemangioma or bleeding. Although hemangiomas may be treated by various conservative methods, occasionally patient may require surgical excision as in the present case due to the repeated bleeding episode and difficult access. A high index of suspicion and radiological investigations should be performed if the clinical presentation is atypical for malignancy, as in our case.

International Federation of Head Neck Oncology Society 5(th) World Congress/American Head Neck Society 2014 update.

Head neck cancer is an important health problem with high morbidity and mortality. Early detection and adequate treatment improve prognosis significantly. Thus creating awareness among clinicians is an important step toward control of head neck cancer and reducing its overall burden. We here provide an update on the International Federation of Head Neck Oncology Society/American Head Neck Society 2014 held between July 26, 2014 and July 30, 2014 in New York.