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.

Anti-Proliferation Effect of Theasaponin E1 on the ALDH-Positive Ovarian Cancer Stem-Like Cells.

Ovarian cancer has the highest mortality rate of all gynecological malignancies and the five-year death rate of patients has remained high in the past five decades. Recently, with the rise of cancer stem cells (CSCs) theory, an increasing amount of research has suggested that CSCs give rise to tumor recurrence and metastasis. Theasaponin E1 (TSE1), which was isolated from green tea (Camellia sinensis) seeds, has been proposed to be an effective compound for tumor treatment. However, studies on whether TSE1 takes effect through CSCs have rarely been reported. In this paper, ALDH-positive (ALDH+) ovarian cancer stem-like cells from two platinum-resistant ovarian cancer cell lines A2780/CP70 and OVCAR-3 were used to study the anti-proliferation effect of TSE1 on CSCs. The ALDH+ cells showed significantly stronger sphere forming vitality and stronger cell migration capability. In addition, the stemness marker proteins CD44, Oct-4, Nanog, as well as Bcl-2 and MMP-9 expression levels of ALDH+ cells were upregulated compared with the original tumor cells, indicating that they have certain stem cell characteristics. At the same time, the results showed that TSE1 could inhibit cell proliferation and suspension sphere formation in ALDH+ cells. Our data suggests that TSE1 as a natural compound has the potential to reduce human ovarian cancer mortality. However, more research is still needed to find out the molecular mechanism of TSE1-mediated inhibition of ALDH+ cells and possible drug applications on the disease.

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.

Reactive oxygen species-caspase-3 relationship in mediating blood-brain barrier endothelial cell hyperpermeability following oxygen-glucose deprivation and reoxygenation.

OBJECTIVE: Microvascular hyperpermeability that occurs due to breakdown of the BBB is a major contributor of brain vasogenic edema, following IR injury. In microvascular endothelial cells, increased ROS formation leads to caspase-3 activation following IR injury. The specific mechanisms, by which ROS mediates microvascular hyperpermeability following IR, are not clearly known. We utilized an OGD-R in vitro model of IR injury to study this. METHODS: RBMEC were subjected to OGD-R in presence of a caspase-3 inhibitor Z-DEVD, caspase-3 siRNA or an ROS inhibitor L-AA. Cytochrome c levels were measured by ELISA and caspase-3 activity was measured fluorometrically. TJ integrity and cytoskeletal assembly were studied using ZO-1 immunofluorescence and rhodamine phalloidin staining for f-actin, respectively. RESULTS: OGD-R significantly increased monolayer permeability, ROS formation, cytochrome c levels, and caspase-3 activity (p < 0.05) and induced TJ disruption and actin stress fiber formation. Z-DEVD, L-AA and caspase-3 siRNA significantly attenuated OGD-R-induced hyperpermeability (p < 0.05) while only L-AA decreased cytochrome c levels. Z-DEVD and L-AA protected TJ integrity and actin cytoskeletal assembly. CONCLUSIONS: These results suggest that OGD-R-induced hyperpermeability is ROS and caspase-3 dependent and can be regulated by their inhibitors.

Regulation of tumor necrosis factor-α-induced microvascular endothelial cell hyperpermeability by recombinant B-cell lymphoma-extra large.

BACKGROUND: Tumor necrosis factor-α (TNF-α), a cytotoxic cytokine, induces endothelial cell barrier dysfunction and microvascular hyperpermeability, leading to tissue edema, a hallmark of traumatic injuries. The objective of the present study was to determine whether B-cell lymphoma-extra large (Bcl-xL), an antiapoptotic protein, would regulate and protect against TNF-α-mediated endothelial cell barrier dysfunction and microvascular hyperpermeability. METHODS: Rat lung microvascular endothelial cells were grown as monolayers on Transwell membranes, and fluorescein isothiocyanate-bovine albumin flux (5 mg/mL) across the monolayer was measured fluorometrically to indicate changes in monolayer permeability. The rat lung microvascular endothelial cell adherens junctional integrity and actin cytoskeleton was studied using ß-catenin immunofluorescence and rhodamine phalloidin dye, respectively. Pretreatment of caspase-8 inhibitor (Z-IETD-FMK, 100 µM) for 1 hour and transfection of Bcl-2-homology domain 3-interacting domain death agonist small interfering RNA (10 µM) for 48 hours were performed to study their respective effects on TNF-α-induced (10 ng/mL; 1-hour treatment) monolayer permeability. Recombinant Bcl-xL protein (2.5 µg/ml) was transfected in rat lung microvascular endothelial cells for 1 hour, and its effect on permeability was demonstrated using a permeability assay. Caspase-3 activity was assayed fluorometrically. RESULTS: Z-IETD-FMK pretreatment protected the adherens junctions and decreased TNF-α-induced monolayer hyperpermeability. Bcl-2-homology domain 3-interacting domain death agonist small interfering RNA transfection attenuated the TNF-α-induced increase in monolayer permeability. Recombinant Bcl-xL protein showed protection against TNF-α-induced actin stress fiber formation, an increase in caspase-3 activity, and monolayer hyperpermeability. CONCLUSIONS: Our results have demonstrated the protective effects of recombinant Bcl-xL protein against TNF-α-induced endothelial cell adherens junction damage and microvascular endothelial cell hyperpermeability. These findings support the potential for Bcl-xL-based drug development against microvascular hyperpermeability and tissue edema.

Prolonged generalized immune response on 18F-FDG PET/CT following COVID-19 vaccination.

The Coronavirus disease 2019 (COVID-19) pandemic continues to be a major public health concern affecting millions of people globally. The COVID-19 vaccination has implications in medical assessment of cancer patients especially undergoing diagnostic imaging such as 18F-fluoro-deoxyglucose (FDG) positron emission tomography with computed tomography (PET/CT). The inflammatory changes following vaccination can cause false positive findings on imaging. We present a case of a patient with esophageal carcinoma who had 18F-FDG PET/CT scan, 8 weeks following booster dose of Moderna COVID-19 vaccination, which showed widespread FDG avid reactive lymph nodes and intense splenic uptake for prolonged duration of approximately 8 months (34 weeks) probably representing generalized immune response. It is important from radiological/nuclear medicine perspective to recognize imaging features of such rare effect of COVID-19 vaccination, which can pose a challenge in assessing 18F-FDG PET/CT scans in cancer patients. It has also opened new avenues for future research evaluating such COVID-19 vaccine-related prolonged systemic immunological response in cancer patients.

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 peripheral artery pseudoaneurysm following orthopedic trauma: a report of 14 cases.

PURPOSE: Purpose of this study was to report the etiology, diagnosis, surgical management, and outcome of pseudoaneurysm associated with orthopedic trauma. METHODS: A retrospective review was conducted of all patients presenting to a Level 1 trauma center between 2013 and 2019. Clinical records were reviewed for the mechanism of primary injury, associated fracture pattern, time of presentation, site of involvement, etiology of the pseudoaneurysm, diagnosis, management, and complications. We identified 14 patients with pseudoaneurysm of peripheral arteries following orthopedic trauma. RESULTS: The mean interval between primary injury and the manifestation of clinical symptoms was 88.5 days (range, 16-304 days). There were 3 upper limb injuries and 11 lower limb injuries. The presenting symptoms were pain associated with excessive extremity swelling in most of the patients. A significant drop in hemoglobin (mean fall- 2.9 g/dL) was noted in nine patients. Most common artery involved was the superficial branch of femoral artery and posterior tibial artery followed by the brachial artery. Fractured bone spike was the cause of injury in eight patients and iatrogenic injury in six patients. Diagnosis was confirmed by CT angiography with duplex scan in eight patients, duplex scan alone in one patient, MRI along with duplex scan in one patient. The remaining four patients were diagnosed intraoperatively. Excision of the pseudoaneurysm and ligation of the involved minor arteries was done in eight patients. Surgical repair of the major artery with critical vascular injury was done in six patients. One patient underwent secondary amputation following the anastomotic blowout. CONCLUSION: Early diagnosis of pseudoaneurysm requires knowledge and a high index of suspicion. Surgical reconstruction of major arteries should always be done and ligation of major vessels can lead to catastrophes. Excision of pseudoaneurysm can be done when minor arteries are involved with the presence of good collateral circulation. LEVEL OF STUDY: Level IV Study.

Reconstruction of Massive Segmental Distal Femoral Metaphyseal Bone Defects After Open Injury: A Study of 20 Patients Managed with Intercalary Gamma-Irradiated Structural Allografts and Autologous Cancellous Grafts.

BACKGROUND: Our aim was to examine the outcome of gamma-irradiated intercalary structural allografts combined with autologous cancellous grafts in treating large metaphyseal bone defects of the distal femur following open injuries. METHODS: We prospectively included 20 consecutive patients with large metaphyseal bone defects of >4 cm located in the region of the distal femur following open injuries treated between 2010 and 2018, with a mean follow-up of 2 years (range, 2 to 10 years). Of these patients,18 were men and 2 were women. The mean age was 39 years (range, 22 to 72 years). The mean length of the bone defects was 10.1 cm (range, 5.5 to 14.5 cm), and all were in the metaphysis of the distal femur. The surgical technique included initial early debridement and external fixation followed by reconstruction of the bone defect using structural allograft combined with autologous cancellous bone graft harvested from the iliac crest and locking plate fixation. Definitive fixation was performed at an average period of 22.5 days (range, 3 to 84 days) after injury. Osseous union, rate of infection, complications, need for secondary procedures, and functional outcome using the Lower Extremity Functional Scale (LEFS) at the final follow-up were assessed. RESULTS: After excluding 1 patient who was lost to follow-up, 19 patients with complete follow-up were available for analysis. Of those, 13 patients (68%) achieved complete union at both ends of the allograft with host bone without any further intervention. Three patients (16%) developed aseptic nonunion of the proximal end of the allograft requiring 1 additional procedure each to achieve union. Four patients (21%) developed a deep surgical site infection. Of those, 1 elderly patient required above-the-knee amputation following uncontrolled diabetes and infection. A second patient required 2 additional procedures, and a third patient needed 4 additional procedures to achieve union. The fourth patient developed infection after achieving union, and the infection subsided after debridement and implant removal. The mean LEFS score for all 19 patients was 55 (range, 41 to 75). CONCLUSIONS: Use of allograft was a reasonable single-stage alternative solution for massive distal femoral bone defects, which united without additional surgery in two-thirds of the patients and without limb-length discrepancy. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Inhibition of VE-cadherin proteasomal degradation attenuates microvascular hyperpermeability.

OBJECTIVE: VE-cadherin, an integral component of the adherens junction complex, is processed through the endosome-lysosome pathway and proteasome system for degradation. Our objective was to determine if inhibition of this pathway would protect against microvascular hyperpermeability. METHODS: To induce VE-cadherin degradation, we utilized a mutant VE-cadherin protein that lacks the extracellular domain (rVE-cad CPD). Intravital microscopy was employed to study the changes in microvascular permeability in rat mesenteric postcapillary venules. Rat lung microvascular endothelial cell (RLMEC) monolayers were utilized in parallel studies. The adherens junction integrity was determined using VE-cadherin and ß-catenin immunofluorescence. TOPflash/FOPflash transfection and luciferase reporter assay were performed to study ß-catenin-mediated transcriptional activation. RESULTS: rVE-cad CPD (2.5 µg/mL of blood volume) increased hyperpermeability significantly (p < 0.05). The VE-cadherin siRNA as well as rVE-cad CPD induced significant increase in monolayer hyperpermeability (p < 0.05). Transfection of rVE-cad CPD disrupted adherens junctions evidenced by discontinuity in ß-catenin and VE-cadherin immunofluorescence (p < 0.05). Proteasome inhibitor MG132 attenuated rVE-cad CPD induced monolayer hyperpermeability and adherens junction damage. CONCLUSIONS: VE-cadherin disruption in animals results in hyperpermeability. Parallel studies in RLMEC demonstrated similar results. In addition, inhibition of proteasomal degradation attenuated microvascular hyperpermeability. These findings have significance in understanding the role of VE-cadherin in regulating vascular hyperpermeability.

Role of ß-catenin in regulating microvascular endothelial cell hyperpermeability.

BACKGROUND: Paracellular microvascular hyperpermeability occurs mainly because of the disruption of the endothelial adherens junction complex. Vascular endothelial-cadherin that consists of an extracellular and intracellular domain to confer cell-cell contact is linked to the actin cytoskeletal assembly through ß-catenin. Our objective was to determine the functional role of ß-catenin during paracellular hyperpermeability and to evaluate whether exogenous ß-catenin would protect against vascular leak. METHODS: ß-Catenin siRNA (2.5 µg/mL) was administered to Sprague-Dawley rats through tail vein. FITC-albumin extravasation of the mesenteric postcapillary venules was evaluated after 48 hours using intravital microscopy. Parallel studies using rat lung microvascular endothelial cell monolayers were transfected with ß-catenin siRNA, and hyperpermeability was determined using monolayers after 48 hours. The effectiveness of ß-catenin siRNA was tested using immunofluorescence and Western blot. To study the protective effect of ß-catenin, rat lung microvascular endothelial cell monolayers were transfected with a ß-catenin gene expression construct for 48 hours or a recombinant ß-catenin protein (1 µg/mL) for 2 hours, followed by transfection with proapoptotic BAK peptide (5 µg/mL), a known inducer hyperpermeability. RESULTS: ß-Catenin siRNA induced a significant increase in vascular hyperpermeability in vivo (p<0.05) and monolayer permeability (in vitro; p<0.05). ß-Catenin siRNA significantly altered the adherens junction complex and decreased ß-catenin protein levels. ß-Catenin gene expression construct or recombinant ß-catenin protein attenuated BAK-induced monolayer hyperpermeability significantly (p<0.05). CONCLUSION: Posttranscriptional gene silencing of ß-catenin leads to vascular hyperpermeability in vivo and monolayer hyperpermeability in vitro. The enhancement of ß-catenin gene expression at the adherens junction or exogenous introduction of ß-catenin protein shows protection against vascular hyperpermeability.

Current updates in management of extremity injuries in polytrauma.

Injury-related morbidity and mortality have been one of the most common causes of loss in productivity across all geographic distributions. It remains to be a global concern despite a continual improvement in regional and national safety policies. The establishment of trauma care systems and advancements in diagnostics and management have improved the overall survival of severely injured. A better understanding of the physiopathological and immunological responses to injury led to a significant shift in trauma care from "Early Total Care" to "Damage Control Orthopedics." While most of these algorithms were tailored to the philosophy of "life before limb," the impact of improper fracture management on disability and societal loss is increasingly being recognized. Recently, "Early Appropriate Care" of extremities has gained importance; however, its implementation is influenced by regional health care policies, available resources, and expertise and varies between low and high-income countries. A review of the literature was performed using PubMed, Embase, Web of Science, and Scopus databases on articles published from 1990 to 2020 using the Mesh terms "Polytrauma," "Multiple Trauma," and "Fractures." This review aims to consolidate on guidelines and available evidence in the management of extremity injuries in a polytraumatized patient to achieve better clinical outcomes of these severely injured.

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.

Management of Tibial Shaft Fractures Distal to TKA Prosthesis by Intramedullary Nail: A Report of Three Cases.

INTRODUCTION: Diaphyseal tibial fractures distal to a well-fixed tibial component although rare present a significant challenge and optimal treatment remains controversial. Displaced periprosthetic tibial shaft fractures are ideally treated with open reduction internal fixation with plate osteosynthesis. However, this treatment method is associated with weight-bearing restrictions, which can be difficult for elderly patients with multiple comorbidities and balance impairment. We present our experience of internal fixation with an intramedullary nail that uses an inferior entry point, standard intramedullary tibial nail, and conventional instrumentation. MATERIALS AND METHODS: Between 2017 and 2018, three patients with acute tibial shaft fractures distal to a TKA (Felix Type 3A) were treated with an intramedullary nail. Preoperative planning involved assessing proximal tibia to ensure adequate room for implant and instrumentation. The average patient age was 66.3 years (range 59-72 years) and all patients were males. All the patients sustained fractures of distal tibial and fibula diaphysis, after a road traffic accident. There were no complications intraoperatively, and all procedures were completed uneventfully. One patient underwent additional fixation of the fibula. RESULTS: All patients achieved a radiological fracture union after an average of 20.6 weeks. There were no fixation failures, or nonunions postoperatively. There were no new symptoms relative to the TKA that could be attributed to the tibial nailing procedure. CONCLUSION: We recommend that this technique can be used primarily for this fracture pattern distal to a TKA, provided there is adequate space to accommodate the nail and instrumentation proximally anterior to the tibial tray.

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.