Can cell-free DNA (cfDNA) in pleural lavage serve as a predictive and prognostic biomarker among surgically treated Stage I-III a nonsmall cell lung cancer (NSCLC)? A pilot study.

BACKGROUND AND OBJECTIVES: The role of cell-free DNA (cfDNA) in operable nonsmall cell lung cancer (NSCLC) is unclear. This study was aimed to evaluate the feasibility for identification of cfDNA in pleural lavage fluid and its correlation with plasma in resectable NSCLCs. METHODS: Consecutively resected NSCLCs were evaluated for cfDNA levels in preoperative plasma (PLS1), intraoperative pleural-lavage (PLV) and postoperative (at 1 month) plasma sample (PLS2). CfDNA was isolated and measured quantitatively by qPCR in a TaqMan probe-detection approach using the human ß-actin gene as the amplifying target. RESULTS: All (n = 34) except one were negative for malignant cells in PLV cytology. CfDNA could be isolated from all the three samples (PLS1, PLV, and PLS2) successfully in each patient. The median cfDNA levels in PLS1, PLV and PLS2 were 118 ng/mL (IQR 61-158), 167 ng/mL (IQR 59.9-179.9) and 103 ng/mL (IQR 66.5-125.4) respectively. The median follow-up was 34.1 months (IQR 25.2-41.6). A significant overall-survival (OS) and disease-free survival (DFS) were recorded for patients with cfDNA level cut-offs at 125, 170, and 100 ng/mL, respectively for PLS1, PLV, and PLS2. Patients with raised cfDNA in PLS1 (>125 ng/mL) and PLV (>170 ng/mL) had significantly poorer 2-year OS, p = 0.005 and p = 0.012, respectively. The hazards (OS) were also higher for those with raised cfDNA in PLV (HR = 5.779, 95% CI = 1.162-28.745, p = 0.032). PLV (>170 ng/mL) had increased pleural recurrences (p = 0.021) and correlated significantly with poorer DFS at 2-years (p = 0.001) with increased hazards (HR = 9.767, 95% CI = 2.098-45.451, p = 0.004). Multivariable analysis suggested higher cfDNA in PLV as a poor prognostic factor for both OS and DFS. CONCLUSIONS: Among patients with operable NSCLC, it is feasible to identify cfDNA in pleural lavage and correlate PLV cfDNA with pleural recurrences and outcomes.

Malignant Chest Wall Tumors: Complex Defects and Their Management-A Review of 181 Cases.

BACKGROUND: Chest wall tumors are a heterogeneous group of tumors that are managed by surgeons from diverse specialties. Due to their rarity, there is no consensus on their diagnosis and management. MATERIALS: This retrospective, descriptive analysis includes patients with malignant chest wall tumors undergoing chest wall resection. Tumors were classified as primary, secondary, and metastatic tumors. The analysis includes clinicopathological characteristics, resection-reconstruction profile, and relapse patterns. RESULTS: A total of 181 patients underwent chest wall resection between 1999 and 2020. In primary tumors (69%), the majority were soft tissue tumors (59%). In secondary tumors, the majority were from the breast (45%) and lung (42%). Twenty-five percent of patients received neoadjuvant chemotherapy, and 98% of patients underwent R0 resection. Soft tissue, skeletal + soft tissue, and extended resections were performed in 45%, 70%, and 28% of patients, respectively. The majority of patients (60%) underwent rib resections, and a median of 3.5 ribs were resected. The mean defect size was 24 cm2. Soft tissue reconstruction was performed in 40% of patients, mostly with latissimus dorsi flaps. Rigid reconstruction was performed in 57% of patients, and 18% underwent mesh-bone cement sandwich technique reconstruction. Adjuvant radiotherapy and chemotherapy were given to 29% and 39% of patients, respectively. CONCLUSIONS: This is one of the largest single-institutional experiences on malignant chest wall tumors. The results highlight varied tumor spectra and multimodality approaches for optimal functional and survival outcomes. In limited resource setting, surgery, including reconstructive expertise, is very crucial.

MicroRNA-3692-3p is overexpressed in lung tumors but may not serve as a prognostic biomarker in lung cancer patients.

BACKGROUND: We previously reported overexpression of miR-3692-3p in the serum of non-small cell lung cancer patients. However, the expression profile and clinical utility of miR-3692-3p in the tumor tissues of lung cancer patients are not yet reported. METHODS AND RESULTS: We quantified the expression levels of miR-3692-3p in the tumors and adjacent normal lung tissues of early-stage (n = 29) and tissue biopsies of locally advanced and metastatic (n = 85) lung cancer patients using TaqMan advanced miRNA assay. We correlated miR-3692-3p expression with survival outcomes, therapeutic response, and other clinicopathological variables. We also predicted the target genes of miR-3692-3p, constructed a protein-protein interaction network, and performed functional enrichment analysis using various in silico tools. We found significant overexpression of miR-3692-3p in the tumors (Log2 fold change = 3.672; p < 0.0001) and tissue biopsies (Log2 fold change = 2.08; p = 0.0001) compared to normal lung tissues of lung cancer patients. The expression of miR-3692-3p did not correlate with overall survival (OS), progression-free survival (PFS), and response to therapy. In multivariate analysis, therapeutic response emerged as an independent prognostic biomarker of OS (HR = 3.47; p = 0.022) and PFS (HR = 19.86; p < 0.001). Our in silico analysis predicted 238 target genes of miR-3692-3p. CONCLUSIONS: Overexpression of miR-3692-3p could contribute to the development of lung cancer. However, mechanistic studies are warranted to shed further light on its role in lung carcinogenesis.

Analysis of miR-375-3p, miR-197-3p, and miR-15a-5p Expression and Their Clinical Relevance as Biomarkers in Lung Cancer.

Background: MicroRNAs (miRNAs) play an important regulatory role and serve as biomarkers in various human cancers. However, their role in the prognosis and predicting response to therapy in Indian lung cancer patients is not fully explored. Methods: We collected surgically resected tumors and paired adjacent normal lung tissues from 29 early-stage and tissue biopsies from 103 locally advanced and metastatic lung cancer patients in this prospective study. We quantified the expression levels of miR-375-3p, miR-197-3p, and miR-15a-5p using TaqMan Advanced miRNA Assays. We correlated miRNAs expression with response to therapy and survival outcomes. Results: The median age of lung cancer patients was 60 years. We found significant overexpression of miR-375-3p and miR-197-3p in the tumors compared to paired normal lung tissues. Higher expression of miR-375-3p was observed more frequently in responders compared to nonresponders. The expression of miR-375-3p and miR-197-3p was able to differentiate patients of lung adenocarcinoma from lung squamous cell carcinoma. We did not find any correlation between miRNAs expression and survival outcomes. Conclusion: Overexpression of miR-375-3p and miR-197-3p might contribute to lung carcinogenesis. The expression of miR-375-3p may assist in predicting therapeutic response. More prospective studies are warranted to evaluate the potential of miR-375-3p as a predictive biomarker of response to therapy.

A systematic review of the current management approaches in leiomyosarcoma of inferior vena cava-Results from analysis of 118 cases.

INTRODUCTION: Primary intravenous leiomyosarcomas are rare vascular tumors with aggressive disease biology. The diagnosis and management have been challenging as little data exist from large databases. METHODS: A literature search was done to identify all cases of primary leiomyosarcomas in the last five years. Clinicopathological features and management strategies were evaluated. RESULTS: The median age was 53 years, predominantly females (2.5:1), presenting as metastases in up to 12.1% cases. Most tumors were locally advanced with a median size of 10cm. Inferior vena cava involvement from renal veins to infrahepatic veins remains the most frequent site (57.1%cases) while nearly half (52.8%) proceeded for surgery without histological proof. Most patients could undergo upfront resection (88.0%) with few patients receiving neoadjuvant chemotherapy (4.3%) or neoadjuvant radiotherapy (2.2%). Significant multivisceral resections included right nephrectomy (41.3%), liver resection (25.7%) and left nephrectomy (2.2%). Most patients (91.8%) needed an inferior vena cava graft placement with remarkable microscopically negative margins (85.5% cases). Doxorubicin and ifosfamide were the most frequently used combination chemotherapy regimens in both pre and postoperative settings with partial responses. The median overall and disease free survival among operated patients was 60 months and 28 months respectively. In multivariate analysis large tumor, extensive inferior vena cava involvement, and need for adjuvant chemotherapy appeared significant predictors for overall survival. CONCLUSIONS: Aggressive upfront surgical resection with clear margin remains the key for long-term survival. Doxorubicin-based regimens were preferred as neoadjuvant chemotherapy while adjuvant treatment with chemotherapy, radiotherapy, or both may be considered in high-risk patients.

Evaluation of the programmed death-ligand 1 mRNA expression and immunopositivity and their correlation with survival outcomes in Indian lung cancer patients.

The presence of membranous immunopositivity of programmed death-ligand 1 (PD-L1) in tumors serves as a key determinant of response to immune checkpoint inhibitors. However, there are very limited studies on the evaluation of the PD-L1 mRNA expression and immunopositivity and their correlation with therapeutic response and survival outcomes, especially in Indian lung cancer patients. In this prospective study, conducted between 2017 and 2020, we collected biopsies and surgically resected tumors from 173 lung cancer patients. PD-L1 immunopositivity and mRNA expression were determined by immunohistochemistry using SP263 assay and qRT-PCR, respectively. PD-L1 expression was correlated with various clinicopathological variables, response to therapy, and survival outcomes using appropriate statistical methods. The median age was 60 years (range 33-81 years) with the majority of patients being male (86.5%) and smokers (83%). Histologically, the majority of patients were non-small cell lung cancer (89.4%) and of squamous cell carcinoma histology (64.3%). PD-L1 immunopositivity in tumor cells (tumor proportion score (TPS) ≥ 1%) was detected in 37.6%, while high immunopositivity (TPS ≥ 50%) was detected in 16.8% of lung cancer patients. Almost 76% of lung cancer patients with PD-L1 TPS ≥ 50% belonged to PD-L1 mRNA high-expression group. PD-L1 mRNA expression and immunopositivity did not correlate with response to therapy and survival outcomes. We conclude that PD-L1 immunopositivity and mRNA expression do not seem to serve as a prognostic biomarker for lung cancer patients treated with chemotherapy. More prospective studies should be planned to evaluate the predictive and prognostic relevance of PD-L1 expression in Indian lung cancer patients being treated with immune checkpoint inhibitors.

Impact of COVID-19 Pandemic on Cancer Surgical Services-AIIMS, New Delhi Experience.

COVID pandemic has impacted cancer care delivery and cancer surgical services globally. There is an urgent need to study the extent of the impact of COVID on cancer surgery and individual institutional response and strategies adopted to counter the adverse impact. A review of administrative and clinical policy changes adopted at the tertiary cancer center to combat COVID pandemic and resume cancer surgical services were performed. A retrospective comparative analysis of cancer out-patient census during COVID pandemic affected year and the preceding normal year along with cancer surgery data audit for the same periods was performed to assess the impact of the pandemic on cancer surgery. In addition, COVID infection rates among cancer surgery patients and healthcare workers were evaluated. There was approximately a 50% reduction in cancer outpatient registrations during COVID pandemic affected year. A trend of increasing footfalls was noted with decreasing COVID intensity and opening of lockdowns. There was a 33% reduction in major elective surgery and a 41% reduction in emergency surgery performed during the COVID period. As far as cancer surgeries are concerned, there was a 12-50% reduction in volumes involving different subsites. Overall COVID positivity rates among cancer surgery patients was low (8.17%), and approximately 30% of healthcare workers involved in cancer surgery were tested positive for COVID during the study period. Results of the current study indicate a significant impact of COVID pandemic on cancer surgical services. There was a significant impact on outpatient visits and cancer surgery volumes. However, a multidisciplinary-coordinated team approach, effective administrative and policy implementation, adoption of revised surgical safety and anesthesia protocols, COVID screening, and testing protocols facilitated resumption of cancer surgical services without adverse impact on surgical outcomes.

Clinical outcomes and technical description of unstented end to side pancreaticogastrostomy by small posterior gastrotomy.

BACKGROUNDS/AIMS: Morbidity following Whipple's surgery largely depends upon the pancreatic stump anastomosis leak. Pancreaticogastrostomy is one of the techniques of pancreatic stump reconstruction and is described variously in the literature. Duct to mucosa pancreaticogastrostomy is described either by a large 3-4 cm posterior gastrotomy or by small gastrotomy of 2-3 mm with the use of internal stents along with. We describe clinical outcomes and technique of 2 layer end to side pancreatico-gastrostomy by a small posterior gastrotomy without the use of internal stents. METHODS: Hospital records of 35 patients where the technique of, small posterior gastrotomy end to side duct to mucosa pancreatico-gastrostomy without internal stents, was used for pancreatic stump reconstruction were studied retrospectively. The data were analyzed for demographic details, stage of the disease, and short term outcomes related to surgical procedure. RESULTS: The mean duration of surgery was 7.4 hours. Grade A, B, and C POPF were observed in 10 (28.5%), 3 (8.5%), and 1 (2.8%) of patients respectively. The mean time to remove pancreatic drain was 9 days, and the mean time to start oral feeds was 8.9 days. The mean hospital stay was 12.9 days (07-26). Thirty days mortality was 2.8%. CONCLUSIONS: Unstented duct to mucosa end to side pancreatico-gastrostomy technique is comparable with other pancreatico-gastrostomy techniques in outcomes in terms of POPF, morbidity, mortality, and hospital stay. However, to establish the superiority or inferiority of this technique, a larger study is recommended.

Hyperthermic intraperitoneal chemotherapy in locally advanced and recurrent ovarian carcinoma: surgical and oncological outcomes in the Indian public healthcare system.

This study analyzed the surgical outcomes after initial implementation of a cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) program in government settings in India. Methods: Ovarian cancer patients undergoing cytoreductive surgery and HIPEC from May 2015 to April 2019 were identified from a prospectively maintained database. Treatment characteristics and surgical outcomes were analyzed. Results: The study identified 101 patients. The mean peritoneal cancer index (PCI) was 7 ± 6, with higher PCI scores in primary and recurrent cases. Major morbidities were recorded in 24.7% of patients. High PCI score, completeness of cytoreduction and major morbidities were independent predictors of overall survival in multivariate analysis. Conclusion: The application of HIPEC in limited-resource settings is feasible with acceptable major morbidities. This program should receive similar priority in government systems.

Vulvar cancer: surgical management and survival trends in a low resource setting.

BACKGROUND: This study aims to analyze risk factors, clinical profiles, treatment protocols, and disease outcomes in histologically proven resectable vulvar cancer (VC) patients according to tumor stage. This is a retrospective analysis of a prospectively collected database of 20 VC patients from May 2014 to June 2019. RESULTS: The mean age of VC diagnosis was 55 years, with a range of 38-84 years. The incidence was four cases per year. The disease incidence was significantly more in post-menopausal (65%) and multiparous (90%) women. According to FIGO staging of vulvar cancer, stages I, II, and III were assigned to 6, 1, and 11 patients respectively. Two patients suffered from stage IVa vulvar melanoma. All patients had undergone surgical interventions. Patients treated with only nonsurgical (chemotherapy/radiotherapy/chemo-radiotherapy) treatment modalities were excluded from the study. Fifteen patients were treated with wide local excision (WLE), bilateral inguinofemoral dissection (B/L IFLND), and primary repair. Four and one patients were treated with radical vulvectomy (RV) and modified radical vulvectomy (MRV) [with or without B/L IFLND and PLND] respectively. Reconstruction with V-Y gracilis myocutaneous and local rotation advancement V-Y fasciocutaneous flaps were done in two patients. Therapeutic groin nodal dissection was performed in 19 patients except in one patient who was treated by palliative radical vulvectomy. In the final histopathology reports, tumor size varies from 0.5 to 6.5 cm (mean 3.35 cm) with the predominance of squamous cell carcinoma (18 out of 20 patients). Only 10 out of 18 eligible patients received adjuvant treatment. Poor patient compliance has been one of the major reasons for adjuvant treatment attrition rate. Systemic and loco-regional metastasis occurred in 3 patients each arm respectively. Poor follow up of patients is the key limitation of our study. CONCLUSION: Vulvar cancer incidence was significantly high in post-menopausal and multiparous women. The most important prognostic factors were tumor stage and lymph node status. Oncological resection should be equated with functional outcome. The multidisciplinary team approach should be sought for this rare gynecological malignancy.

Neoadjuvant chemotherapy followed by surgery in lung cancer: Indian scenario.

A vast majority of the patients with lung cancer in India present as advanced stage disease and a significant number among them have nonmetastatic locally advanced tumors which require multimodality management with curative intent. We analyzed the treatment outcome of the patients treated with of neoadjuvant chemotherapy followed by surgery approach. This was a retrospective analysis of institutional database of all non-small cell lung cancer patients who underwent neoadjuvant chemotherapy followed by curative intent surgery with/without adjuvant therapy from 2012 to 2018. Patients included were those with N2 disease; T4 or T3 disease requiring pneumonectomy or extensive adjacent structures resection. Mediastinal staging was done by PET-CT (Positron Emission Tomography - Computed Tomography) along with Endobronchial ultrasound in most cases. All the patients received platinum-based doublet chemotherapy for 3-6 cycles before surgery. Response to neoadjuvant chemotherapy and survival were analyzed. A total of 44 patients fulfilled the eligibility criteria. Majority were males (81.8%) and smokers (75%). Squamous cell carcinoma (50%) was the most common subtype. Total 43.2% patients had either T3 or T4 tumors. N2 disease (either single station or multistation) was observed in 67.2% cases. A complete pathologic response was observed in 22.7% cases. In addition, 6.8% patients had ≤10% viable tumor in the resected specimen. Residual disease in N2 nodes were found in 25% cases. Median follow-up was 35.9 months. Patients with residual N2 disease showed a trend toward inferior survival. In multivariate analysis smoking, pretreatment tumor category and final pathologic stage were significant factors for disease free but not for overall survival. This study shows that neoadjuvant chemotherapy is a feasible and effective modality for downstaging locally advanced cases of non-small cell lung cancer among the Indian patients. Patients with less than 10% residual tumor burden had a better survival. The role of surgery in those with persistently N2 needs further evaluation.

Video assisted thoracoscopic surgery in paediatric mediastinal tumors.

Video assisted thoracoscopic surgery (VATS) is an emerging tool for approaching childhood mediastinal tumors in a minimally invasive way. The magnified visibility and availability of smaller instruments has allowed to explore even areas close to the great vessels and other vital structures. The safety and feasibility of this technique has been described for a wide range of these tumors. In spite of that the literature is deficient in use of this modality in paediatric mediastinal tumors. Although widely practiced in adults, various controversies have been set forward in application of this technique in children. This article aims to explore reasons for the underutilisation of VATS in these patients and tries to explain the areas of controversy with this technique. Various ways of comparison have been attempted for a broad understanding of the finer details (comparisons between open and VATS in children, VATS in children and adults, VATS in mediastinal tumors and lung surgeries).