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Introduction Ovarian cancer is the third most common cancer among Indian women. The data on the hereditary predisposition of these cancers and the clinical outcomes of those with pathogenic mutations is meager in India. Objective The aim of the current study was to analyze the germline-genetic profile, clinicopathological characteristics, and outcomes of patients with ovarian cancer who were referred for genetic counseling at our Institute. Materials and Methods It was a cross-sectional observational study. Patients with histological diagnosis of carcinoma ovary at our institute who were referred for genetic counseling from July 2017 to June 2020 were included in the study. All patients underwent pretest counseling. Most patients underwent multigene panel testing with reflex multiplication ligation-dependent probe amplification for large genomic rearrangements, while some received testing for BRCA1 and BRCA2 only. The variants were classified as pathogenic or benign based on American College of Medical Genetics (ACMG) guidelines. Data regarding the demographic profile, clinical characteristics, histopathological findings, family history, treatment received, and outcomes were extracted from the medical record system files. Results One hundred and one patients were referred to the genetic clinic and underwent genetic counseling. All patients were advised for genetic testing; however, only 72 (71%) underwent testing. A multigene panel testing was done in 51 (70%) patients, and only BRCA1 and BRCA2 genes were tested in 21 (30%). Among the 72 patients who underwent a genetic test, the median age was 47 years (range, 28–82). The most common histopathology was serous (90%), while 85% were diagnosed having stage 3 and 4 ovarian cancer. A pathogenic/likely pathogenic (P/LP) BRCA or non-BRCA mutation was detected in 32 (44%) patients. Six patients (8%) had a variant of unknown significance (VUS). Among P/LP mutations, 85% were in the BRCA gene (75% in BRCA1 and 10% in BRCA2), while 15% were in non-BRCA gene mutations (RAD51, PALB2, MER11, HMMR). Disease-free survival and overall survival were not different in mutation-positive and mutation-negative cohorts. Conclusions We report 44% P/LP mutations in this selected cohort of patients with carcinoma ovaries. BRCA mutations constituted 85% of all the mutations, while 15% of mutations were in non-BRCA genes.

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.

Cancer is emerging as a major public health challenge globally. Recently, IARC (International Association of Research on Cancer) published global cancer burden using GLOBOCAN 2020 estimates for 36 cancers in 185 countries of the world. As per the estimates of the World Health Organization (WHO) in 2019, cancer is the first or second leading cause of death in 112 of 183 countries. The major takeaways of the GLOBOCAN 2020 report relevant to the surgical oncology community include the rising global burden of cancer, global disparity in cancer incidence and mortality in different geographic regions, and the impact of the human development index (HDI) on cancer incidence and projected global cancer burden by 2040. In this article, we discuss the implications of the GLOBOCAN report on future global cancer control strategies and the role of surgical oncologists in the fight against cancer.

The spectrum and significance of Variants of Uncertain Significance (VUS) mutations in breast cancer predisposition genes is poorly defined in the Indian population.All new female breast cancer patients from 1 March 2019 to 28 February 2020 were screened. Those providing informed consent and without previous genetic testing were recruited. Multigene panel testing (107 genes) by next-generation sequencing was performed for all patients. Descriptive statistics was used to describe the spectrum of VUS mutations.Out of 236 patients recruited in the study, a VUS was detected in 89 patients (37.71%). VUS pathogenic ratio was 2.02. A total of 121 different VUS mutations in 40 different genes were detected. Fourteen patients (15.7%) had a VUS in high penetrance genes and 36 VUS mutations (29.8%) were detected in one of the genes involved in homologous recombination repair pathway. No therapeutic interventions were done based on VUS.In this large prospective study of genetic determinants of breast cancer from India, a high prevalence of VUS (37.71%) was detected with 15.7% patients having a VUS in high penetrance genes. More evidence needs to be generated from larger multicentric studies to better understand the implications of these genetic variants and enable their reclassification.

Oral cavity squamous cell carcinoma (OSCC) is the most common type of head and neck cancer worldwide. Smokeless tobacco (SLT) has been well proven for its role in oral carcinogenesis due to the abundance of several carcinogens. However, the role of inhabitant microorganisms in the oral cavity of smokeless tobacco users has not yet been well explored in the context of OSCC. Therefore, the present investigation was conceived to analyze the oral bacteriome of smokeless tobacco users having OSCC (CP group). With the assistance of illumina-based sequencing of bacterial-specific V3 hypervariable region of 16S rDNA gene, 71,969 OTUs (operational taxonomic units) were categorized into 18 phyla and 166 genera. The overall analysis revealed that the oral bacteriome of the patients with OSCC, who were smokeless tobacco users, was significantly different compared to the healthy smokeless tobacco users (HTC group) and non-users (HI users). The appearance of 14 significantly abundant genera [FDR (false discovery rate) adjusted probability value of significance (p value) 0.05] among the CP group showed the prevalence of tobacco-specific nitrosamines forming bacteria (Staphylococcus, Fusobacterium, and Campylobacter). The functional attributes of the oral bacteriome of the CP group can also be correlated with the genes involved in oncogenesis. This study is the first report on the oral bacteriome of Indian patients with OSCC who were chronic tobacco chewers. The results of the present study will pave the way to understand the influence of smokeless tobacco on the oral bacteriome of OSCC patients. KEY POINTS: • Oral bacteriome of OSCC patients differ from healthy smokeless tobacco (SLT) users and SLT non-users. • Smokeless tobacco influences the oral bacteriome of OSCC group. • Oral bacteriome specific diagnostics may be developed for pre-diagnosis of oral cancer.

Background: A clinical audit provides the framework to improve the quality of patient care in a systematic way. In this study, we intensively audited our 250 advanced epithelial ovarian cancer (EOC) patients aiming to improve our patient care.Methods: Ambispective study of 250 patients of advanced EOC was done from our prospectively maintained computerized database in the department of surgical oncology, AIIMS, New Delhi from 2013 to 2020.We audited the demographic profile, treatment patterns, perioperative and survival outcomes in different subgroups.Results: In this study, 83.6% stage III and 16.4% stage IV A. There was 62 (24.8%) upfront, 112 (44.8%) interval and 76 (30.4%) secondary group. 126 underwent cytoreductive surgery (CRS) and 124 CRS and hyperthermic intraperitoneal chemotherapy (HIPEC). There was 24.8% early and 8.4% late postop complications. Median follow up 50 months. Overall, the median disease-free survival (DFS) 39 months. PFS was 12 months among 68 patients with recurrence. Attrition rate 4%. In the upfront setting, the median DFS 44 months in CRS only group and DFS not reached (p=0.032) in CRS and HIPEC group still. In the interval setting, the median DFS 39 months in CRS only group and 44 months in CRS and HIPEC group (p=0.06). In recurrent setting, the median DFS 14 months in CRS group and 23 months in CRS and HIPEC group (p=0.02)Conclusions: Audit is an integral part of any clinical practice. It teaches us to improve the quality of care and thereby better outcomes. We recommend 6 monthly clinical audits in any cancer treatment for better outcomes in future.

Meta-analysis of transcripts in colon adenocarcinoma patient tissues led to the identification of a DNA damage responsive miR signature called DNA damage sensitive miRs (DDSMs). DDSMs were experimentally validated in the cancerous colon tissues obtained from an independent cohort of colon cancer patients and in multiple cellular systems with high levels of endogenous DNA damage. All the tested DDSMs were transcriptionally upregulated by a common intestine-specific transcription factor, CDX2. Reciprocally, DDSMs were repressed via the recruitment of HDAC1/2-containing complexes onto the CDX2 promoter. These miRs downregulated multiple key targets in the DNA damage response (DDR) pathway, namely BRCA1, ATM, Chk1 (also known as CHEK1) and RNF8. CDX2 directly regulated the DDSMs, which led to increased tumor volume and metastasis in multiple preclinical models. In colon cancer patient tissues, the DDSMs negatively correlated with BRCA1 levels, were associated with decreased probability of survival and thereby could be used as a prognostic biomarker. This article has an associated First Person interview with the first author of the paper.

Phthalates are known endocrine-disrupting chemicals used indiscriminately as constituents in consumer products including food processing, and packaging, cosmetics, personal care and household items. Although, few studies have assessed the risk of breast cancer on exposure to phthalates, their association with breast cancer risk in Indian women have not yet been evaluated.We conducted a case-control study involving 171 participants. Urinary concentrations of six phthalate dieters; DMP (Dimethyl phthalate), DEP (Diethyl phthalate), DBP (Dibutyl phthalate), BBP (benzyl butyl phthalate), DEHP (Di-2-ethyl-hexyl phthalate), DINOP (Di-n-octyl phthalate) were estimated by GC-MS and geometric means were calculated. Univariate and multivariable logistic regression was performed to assess breast cancer risk on exposure to phthalates. Genes responsive to phthalates were identified through literature search and matched with NGS data, and gene-enrichment analysis was performed.Significant associations were observed between urinary phthalate concentrations and increased risk of breast cancer for di-butyl phthalate (OR=1.5, 95% CI; 1.06, 2.11, p = 0.002) and di-2-ethyl-hexyl phthalate (median vs ≤ median; OR=2.97, 95% CI; 1.18, 7.47, p = 0.005) in multivariable analyses. We also found several phthalate-responsive gene mutations in paired breast tumor tissues, which include PTPRD (76.19%), AR (42.86%), CYP1A1 (42.86%), CYP19A1 (23.81%), AHRR (19.05%), PIK3CA (19.05%), CYP1B1 (9.52%), RB1 (9.52%) and MMP9 (9.52%). Gene-enrichment analysis revealed that these genes form a major part of ER/PR, PPAR and HIF-1α-TGF-β signaling cascades involved in breast cancer CONCLUSION: Although the sample size is small, in this first case-control study from India, DBP and DEHP were found to be associated with increased risk of invasive breast cancer and tumor tissues revealed mutations in several phthalate-responsive genes. It is, therefore suggested that human biomonitoring in India and larger studies evaluating the early life genetic and epigenetic alterations on phthalates exposure are required to establish their role in breast carcinogenesis.

Among percutaneous biopsy techniques, the vacuum assisted breast biopsy (VAB) obtains large tissue samples to alleviate some of the limitations associated with conventional percutaneous biopsy techniques. We aimed to determine the efficacy of VAB in previous equivocal biopsies using the mammotome device.A prospective non-randomized efficacy study was planned and executed on 43 patients (42 women, 1 man) whose previous FNAC and/or CNB of breast masses yielded inconclusive results or were suspicious for cancer.VAB revealed malignancy in 31 (72%) of the 43 patients. Among them, 23 were diagnosed as infiltrative ductal carcinoma (IDC) on VAB, 20 underwent surgery and the final histopathological diagnosis was the same in 19 of them. One patient showed ductal carcinoma-in-situ (DCIS) only in the surgical specimen. Other malignancies included infiltrating lobular carcinoma (ILC) in 5 patients and one each of DCIS, non- Hodgkin lymphoma (NHL) and metastasis from lung cancer. Benign lesions were detected in 12 (28%) patients. These included 8 fibroadenomas, 2 fibrocystic disease and 1 each of mastitis and breast abscess. Four patients with fibroadenoma underwent surgical excision.

Data on patients with localized Ewing sarcoma family of tumors (ESFT) who have received a uniform chemotherapy protocol are minimal.This is a single institutional review of patients with ESFT treated between June 2003 and November 2011.224/374 (60%) patients with ESFT presented with localized disease; median age was 15 years (range: 0.1-55). Ninety-nine patients underwent surgery of which 50 received adjuvant radiotherapy; 80 patients received radical radiotherapy following neoadjuvant chemotherapy. At median follow-up of 40.2 months (range: 1.3-129), 5-year EFS, OS, and local-control-rate, were 36.8 ± 3.6%, 52.4 ± 4.3%, and 63 ± 4.3%, respectively. In multivariate analysis, tumor diameter8 cm (P = 0.03), symptom duration4 months (P = 0.04), and WBC11 × 10(9) /L (P = 0.003) predicted inferior EFS; spine/abdomino-pelvic primary (P = 0.009) and WBC11 × 10(9) /L (P = 0.003) predicted inferior OS. Tumor size8 cm (P = 0.03) and radical radiotherapy as local treatment (P = 0.01) predicted inferior local-control-rate.Prognostic hazard models for EFS and OS based on significant prognostic factors suggested that patients with combination of ESFT of spine/abdomino-pelvic region and baseline WBC11 × 10(9) /L had inferior OS (hazard ratio 4.44, P0.001) while patients with combination of ESFT with symptom duration4 months, tumor diameter8 m and baseline WBC11 × 10(9) /L had inferior EFS (hazard ratio 3.89, P = 0.002).

Data on extraosseous Ewing sarcoma (EES) with uniform chemotherapy protocol are minimal. We aimed to examine this aspect in our patients, identify prognostic factors and compare the same with osseous Ewing sarcoma.A single institutional data review of patients with EES treated between June 2003 and November 2011 with uniform chemotherapy and evaluated on intent-to-treat analysis was done.Of 374 patients with Ewing sarcoma, 60 (16%) were EES with median age 16 years; 20 (33%) had metastases. After median follow-up of 25 months (range: 1.7-104.4), 5-year event free survival (EFS), OS, and local-control-rate were 47.1 ± 7.9%, 61.6 ± 7.8%, and 77.9 ± 8.6%, respectively for entire EES cohort. In multivariate analysis, hemoglobin ≤ 10 g/dl (P = 0.03), and white blood cell count (WBC)11 × 10(9) /L (P = 0.009) predicted inferior EFS for the entire EES cohort. Low hemoglobin (P = 0.05) and high LDH (P = 0.01) predicted inferior OS for the entire EES cohort on multivariate analysis. As compared to the cohort of skeletal primary (n = 314), higher proportion of patients underwent surgery in the cohort of EES (P = .003); EFS (P = 0.004) and OS (P = 0.08) were superior for patients with EES than patients with skeletal Ewing sarcoma.These data of EES suggests that low hemoglobin and high WBC count adversely affect EFS. Overall outcome was significantly better for EES than skeletal primary tumors.

Breast cancer is the commonest cancer among women worldwide. Surgery plays an important role in its management. Axillary lymph node dissection has been the standard of care for staging, prognostication and control of axillary disease for almost a century. However, this time-tested paradigm is shifting gradually in the western world, because of the increasing use of screening mammography resulting in the detection of a large proportion of node-negative early breast cancers and a significant incidence of axillary lymph node dissection-related arm morbidity. Minimally invasive and less morbid procedures such as sentinel lymph node biopsy are being used more commonly in the West. However, the western experience cannot be directly extrapolated to the Indian scenario because of the differences in patient profile, treatment standards and expertise available. There is a need to critically analyse these issues before the Indian medical community advocates sentinel lymph node biopsy as a routine procedure for managing patients with breast cancer.

Breast conservation therapy is a well-established treatment modality for early breast cancer. It is not widely practised in developing countries because of a lack of awareness and treatment facilities, and physician and patient bias. We analysed our experience of breast conservation therapy.We retrospectively reviewed 102 patients who had undergone breast conservation surgery and axillary dissection for breast cancer. Surgery was followed by 45 Gy of radiation to the whole breast and 15-20 Gy of tumour bed boost. All high risk patients received adjuvant systemic therapy. The disease profile, morbidity and treatment outcome were analysed.Out of 902 patients, 102 underwent breast conservation therapy (90 had early breast cancer and 12 had locally advanced breast cancer). Only 19.6% of patients with early breast cancer received breast conservation therapy. One-third of the patients had had a prior surgical intervention. The mean tumour size was 2.8 cm, 44% had nodal involvement and 29% were oestrogen- and progesterone-receptor negative. At a mean follow up of 32 months, only 1 patient had local recurrence, and the 5-year projected disease-free and overall survival were 82% and 88%, respectively.Breast conservation therapy should be offered to suitable breast cancer patients. Strict adherence to protocol-based therapy and active multidisciplinary coordination are crucial for a successful breast conservation therapy programme. Education of the patient as well as the physician population is necessary for increasing the breast conservation therapy rates in India.

Postoperative fistula involving upper gastrointestinal tract surgery is a rare but troublesome occurrence. Reoperation on these patients is challenging and needs to be individualised. Various methods are described including primary closure, bypass procedures, serosal patch repair and Roux-en-Y repair. We present a new technique of repair using afferent loop that provided a vascularized bowel segment, which used in an anatomical fashion for closure of fistula.

Early detection and multimodality therapy has resulted in an overall improvement of survival among breast cancer patients. Despite a significant shift in the treatment approach from radical mastectomy to breast conservation a significant number of patients develop lymphedema. This study was conducted to evaluate the prevalence and risk factors for development of lymphedema.Retrospective analysis for prevalence of lymphedema in a tertiary care regional cancer centre.Three hundred treated breast cancer patients with a minimum follow up of one year were evaluated for the prevalence and risk factors for lymphedema. Lymphedema was assessed using a serial circumferential measurement method. More than 3 cm difference in circumference is considered as clinical significant lymphedema. Univariate and multivariate analysis were performed for evaluating the risk factors by using the Chi square test and Cox logistic regression analysis.The prevalence of clinically significant lymphedema was 33.5 % and 17.2 % had severe lymphedema. The prevalence of lymphedema was 13.4 % in patients treated with surgery only where as the prevalence was 42.4% in patients treated with surgery and radiotherapy. Stage of the disease, body surface area1. 5 m2, presence of co-morbid conditions, post operative radiotherapy and anthracycline based chemotherapy were significant risk factors in univariate analysis where as axillary irradiation and presence of co-morbid conditions have emerged as independent risk factors in multivariate analysis (P0.001).Post treatment lymphedema continues to be a significant problem following breast cancer therapy. Presence of co-morbid conditions and axillary radiation significantly increases the risk of lymphedema. A combination of axillary dissection and axillary radiation should be avoided whenever feasible to avoid lymphedema.

Isolated ipsilateral supraclavicular lymph nodal (IISCLN) metastasis was considered part of locally advanced breast cancer (LABC) previously but the recent staging system categorised this group to metastatic disease (stage IV). There is no clear consensus on intent of therapy in patients with IISCLN. A retrospective comparative analysis of IISCLN and LABC patients treated with a curative multimodality approach was performed to evolve guidelines on treatment approach in patients with IISCLN spread.A total number of 670 patients with breast cancer treated in the Department of Surgical Oncology, IRCH, AIIMS, during the period between January, 1993 to December, 2000 were studied retrospectively. Out of these 16 (2.4%) patients with cytology proven isolated metastasis to ipsilateral SCLN without any other distant disease and 299 LABC patients were analysed. All patients received neoadjuvant anthracycline based chemotherapy, surgery, postoperative radiotherapy (50 Gy) including supraclavicular fossa. The relapse patterns and survival in both the groups were compared.At a median follow up of 36 months (range 9-72 months) the total recurrence in the IISCLN group was 31% and in the LABC group was 26%, the systemic recurrence was equal at 25% in each group while the locoregional recurrence was 12% and 7% in the IISCLN and LABC groups respectively. The overall survival (OS) was 81% and 91% whereas the disease-free survival (DFS) was 12% and 7% in the IISCLN and LABC groups, respectively.Intent of therapy in metastatic breast cancer is palliative. However, patients with IISCLN metastasis have a relatively less aggressive biologic behaviour as compared to patients with spread to other distant sites. Results of the current study shows that the relapse patterns and survival of IISCLN group and LABC are comparable. Hence, despite being staged as metastatic disease, patients with IISCLN spread should be treated with combined modality approach for prolonged survival.

Adenocarcinoma of the stomach is usually advanced at presentation, and local or distant spread may preclude the option of primary curative resection. Neoadjuvant chemotherapy (NAC) has shown promise in downstaging initially unresectable disease. This pilot study was planned to assess the utility of NAC using Cisplatin and 5-Fluoro uracil in the management of initially unresectable gastric cancer.Ten patients with unresectable gastric adnocarcinoma were included. They received two cycles of cisplatin, 30 mg/m2 intravenously in combination with 5-Fluoro Uracil, 1000 mg/m2. They were restaged using Endoscopy and CT scan and taken up for exploratory laparotomy.Eight of 10 patients (80%) had an objective response to chemotherapy. Six patients (60%) with initially unresectable disease could be offered curative surgery. The median survival was 10 months (range 1-60 months). There were two long term survivors (48 and 60 months respectively).Neoadjuvant chemotherapy (NAC) is an effective option in downstaging initially unresectable gastric carcinoma. Complete response to chemotherapy also predicts long term survival.

The harmonic scalpel is recently emerging as an alternative surgical tool for dissection and haemostasis and has been extensively used in the field of minimally invasive surgery. We studied the utility and advantages of this instrument over electrocautery for performing modified radical mastectomy.The operative and morbidity details of twenty-three breast cancer patients who underwent modified radical mastectomy using the harmonic scalpel were compared with 23 matched controls operated with electrocautery by the same surgical team.There was no significant difference in the operating time between the harmonic scalpel and electrocautery group (104 and 100 mins, p0.05). The blood loss (60 +/- 35 ml and 294 +/- 155, p0.001) and drainage volume (590 +/- 430 ml and 1,085 +/- 690 ml, p0.001) were significantly lower in the harmonic scalpel group. There was a significant reduction of drain days in harmonic scalpel group (mean five and nine days, p0.05). There was no significant difference in the seroma rate between two groups (16% and 22%).Modified radical mastectomy using harmonic scalpel is feasible and learning curve is short. Harmonic scalpel significantly reduces the blood loss and duration of drainage as compared to electrocautery.

Venous access is crucial for cancer management for administration of drugs blood products, antibiotics and periodic sampling.To review our experience of long-term venous access devices used over a ten-year period and to analyse the outcome in cancer patients in Indian setting.A retrospective analysis of data in a tertiary care Regional cancer centre.A total of 110 patients with various malignancies requiring long-term venous access were included in the study. A uniform open cut down procedure under local anaesthesia was used and silastic Hickman catheters were inserted in the cephalic or external jugular or internal jugular veins. A record of all complications and catheter loss and final out come were analysed.A total of 111 catheters were used in 110 patients. Sixty-nine catheters were placed in cephalic, 40 in external jugular, and 2 in internal jugular vein. Duration of catheter indwelling period ranged from 7 to 365 days with a median of 120 days. In 90% of the cases the catheter tip was located either in superior vena cava or in right atrium. Total catheter related complications were observed in 37 (34.54%) patients and catheter loss rate due to complications was 15.4% (17/111).Long-term venous access using Hickman catheter insertion by open cut down method is a simple, safe and reliable method for administration of chemotherapeutic agents, antibiotics and blood products. The incidence of various complications and catheter loss was acceptable and overall patient satisfaction was good.