Upfront cytoreductive surgery versus neoadjuvant chemotherapy in advanced epithelial ovarian cancer in Indian patients.

In cases of ovarian carcinoma, primary cytoreductive surgery (CRS) is the standard treatment up to stage IIIB, but patient selection for neoadjuvant chemotherapy (NACT) in selected cases is controversial. A total of 200 patients with advanced ovarian cancer were analyzed retrospectively, according to specific selection criteria. Primary CRS was performed in 95 patients (47.5%) and interval CRS after 3-6 cycles of NACT was performed in 105 patients (52.5%). After median follow-up of 35 months, 5-year overall survival was 53.7% in the upfront CRS group and 42.2% in the NACT group. Primary CRS is the standard in advanced stages of ovarian carcinoma, but in certain subset of patients, NACT is preferred. Identifying that group is challenging but feasible. Proper selection of patients is key to successful outcomes.

Adjuvant radiation therapy for malignant tumours of the eyelid: Experience from a tertiary cancer centre in India.

Background: . Tumours of the eyelid are a rare subgroup of neoplasms with varied histology and inherent differences in clinical behaviour. Surgery is the standard of care, and adjuvant radiation therapy (RT) is given in the presence of features suggesting a high risk of local recurrence. The treatment of lymph nodes in the neck is debatable. We reviewed the utility of RT for lymph nodes in the neck in patients with malignant tumours of the eyelid. Methods: . We reviewed medical records of all patients with tumours of the eyelid treated at our centre from July 2006 to December 2014 for their demographic, clinical profile, treatment details and outcome. Results: . The records of 37 patients were included for analysis, of these 34 underwent surgery and 21 received adjuvant RT. Their median age was 60 (range 30-85) years. Sebaceous cell carcinoma was the most common (50.4%). The median disease-free survival (DFS) was 35 months (95% CI 17.9-52.0). The 1- and 3-year DFS were 82.7% and 45%, respectively. Univariate analysis showed a superior outcome with early stage (T1) tumours (p=0.01), RT dose of ≥60 Gy and those underwent lymph node dissection (p=0.03). The presence of high-risk factors including close or positive margin had an inferior outcome with a trend towards statistical significance (p=0.06). Conclusion: . We found a favourable outcome with early T stage, RT dose of ≥60 Gy and lymph node dissection. High-risk histopathological features including close margins and positive lymph nodes merit adjuvant RT including regional lymph nodes.

Role of S100 A7 as a diagnostic biomarker in oral potentially malignant disorders and oral cancer.

Background: S100 proteins have been implicated in the tumorigenesis of different human cancers and in oral dysplasia, as they are keratinocytes. Materials and Methods: In the present study, we have attempted to compare the expression of S100-A7 within young-onset (age ≤45 years, Group 1) oral squamous cell carcinoma (OSCC), OSCC in older age groups (age >45 years Group 2), oral potentially malignant disorders (OPMDs, Group 3) and inflammatory lesions (Group 4). The tissue sections were scored based on the percentage of immunostained cells and staining intensity. Nuclear, cytoplasmic and membrane immunoreactivity were also scored. Results: The present study comprised 153 histopathologically diagnosed case subjects of OSCC >45 years (n = 41), OSCC <45 years (n = 36), OPMD (n = 40) and inflammatory lesions (n = 36). The present study revealed a statistically significant difference of distribution with regard to S100A7 staining (cytoplasmic and nuclear) between OPMDs and OSCC (P < 0.05). The nuclear, cytoplasmic and membrane staining as well as the staining intensity had significantly different scoring patterns among the OSCC group, OPMD group and the inflammatory lesions with the OSCC group having the highest scoring of the S100A7 staining (irrespective of the age). Conclusions: The present study concludes that S100A7 can be used as a diagnostic biomarker to differentiate between OPMDs and OSCC lesions. However, the marker is unable to distinguish between OSCCs in younger and older patients as the molecular pathogenesis of tumors in either of these age groups is probably similar.

Occupational Hazards of Surgical Smoke and Achieving a Smoke Free Operating Room Environment: Asia-Pacific Consensus Statement on Practice Recommendations.

Background: Surgical smoke generated through energy devices may present detrimental effects on individuals present in the operating room (OR). Despite the concerns possibly associated with surgical smoke, there may be no mandatory policies that suggest protective measures and limited firm standards are committed yet to address the same. Aim: The aim of this paper is to present recommendations for surgeons and OR personnel by taking a consensus approach based on available literature and its interpretation by a multi-national panel of experts. Methods: The Asia-Pacific (APAC) group was established with the aims of reviewing literature evidence, discussing key issues regarding surgical smoke and its hazards, and offering a summary of statements in achieving a smoke-free OR environment. Eleven expert surgeons from the international APAC region were gathered with the purpose of coming to a consensus on engineering, best work-practices, and administrative controls in minimizing surgical smoke exposure. A two-phase consensus method was used to obtain opinions from the expert panel of specialists. Statements with an agreement of more than 80% were accepted. Findings: For twenty-one statements, the panel achieved consensus on 17 statements; another 5 were dropped due to lack of consensus. The consensus was obtained on statements that address the need for the implementation of administrative policies, training and awareness, standard procedure for the continued use of engineering controls, stringent work practice controls and preventive controls. Conclusion: The statements presented may guide surgeons and OR personnel in the practical management of surgical smoke safety, mitigating the risks associated with it. The consensus statement also provides a series of recommendations that can be used with other stakeholders, such as policymakers, hospital administrators and professional societies, to highlight and motivate the implementation of meaningful policies.

Role of rebiopsy in metastatic breast cancer at progression.

Alteration of biomarkers is well-documented in breast cancer at locoregional recurrence or metastasis attributed to tumor heterogeneity and change in biology. There is a lack of literature on alteration of biomarkers in metastatic breast cancer (MBC) at progression. We included 32 patients of upfront MBC. Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2/neu documented at baseline and at progression. Median age was 46 (range 26-72) years. Estrogen receptor altered in 6 (18.75%) patients [4 (12.5%) positive to negative and 2 (6.25%) from negative to positive], progesterone receptor altered in 8 (25.3%) patients (6 [18.75%] positive to negative and 2 [6.25%] negative to positive) and human epidermal growth factor receptor 2/neu altered in 5 (15.6%) patients (all were positive to negative). Therapy was changed as per new receptor status. Documentation of change in receptor status may be justified to determine further therapy and prognosis in MBC at progression.

Alveolar soft part sarcoma of orbit: A rare diagnosis.

OBJECTIVE: Alveolar soft part sarcoma (ASPS) is an aggressive, rare tumour with unique morphological and histopathological features. METHODS: We report a rare case of orbital ASPS and its management in a young male who presented with painless proptosis and progressive loss of vision. RESULT: Twenty-two year male presented with a history of gradually increasing proptosis with loss of vision since 12months. He underwent radical re-excision of mass with right orbital exenteration and reconstruction using temporalis muscle flap. Adjuvant radiotherapy to a dose of 64Gy in 32 fractions over 6.5weeks was planned in view of positive surgical margins. Patient is free of disease and currently under follow up in multidisciplinary clinic. CONCLUSION: Function preserving surgery remains the standard treatment approach in localised disease however the complex anatomy and locally aggressive nature makes it difficult to achieve clear surgical margin. Adjuvant radiotherapy has shown to improve local control in patients with positive surgical margins.

Circulating cell-free DNA and its integrity as a prognostic marker for breast cancer.

The aim of our study was to look for alternative predictive biomarkers for breast cancer management in limited resource setup. A comprehensive analysis of circulating cell-free DNA (CCFD) in serum at baseline was performed to assess its prognostic potential. Quantitative polymerase chain reaction (qPCR) of ALU sequences using ALU115 and ALU247 primers was carried out in patients (N: baseline 148, postoperative 47) and 51 healthy controls. Mean serum DNA integrity, levels of ALU 247 and levels of ALU 115 were significantly higher in patients than in healthy females. No significant differences were observed in the levels ALU 247 and ALU 115 between stage IV and earlier stages of the disease. The DNA integrity was significantly higher in stage IV than earlier stages. A significant decrease in DNA integrity was observed after surgery (pre: 0.55 ± 0.23 vs post: 0.43 ± 0.30; P = 0.002) while no such change could be observed for ALU 247 and ALU 115. Baseline DNA integrity was significantly higher in relapsed patients than in patients who were free of disease (P = 0.005). Higher baseline DNA integrity was also indicated, though statistically not significant, in patients who died (P = 0.14). In contrast, ALU 247 and ALU 115 levels were decreased in died patients as compared to survivors (24.8 ± 34.80 vs 73.5 ± 170.83, P = 0.02 for ALU 247 and 41.0 ± 47.99 vs 159.5 ± 299.54, P = 0.005 for ALU 115). Baseline levels of ALU 115 and ALU 247 were lower in relapsed patients, though statistically not significant. In univariate analysis, the only clinic-pathological parameter associated with disease prognosis was tumor size. The hazards of 5-year overall mortality was 3.60 (95 % CI: 1.03 12.53, P = 0.03) among patients with lower baseline serum levels of CCFD (ALU 247 < 21 and ALU 115 < 41). Similarly the 4 year hazards for recurrence was 2.30 (95 % CI: 0.96 5.52, P = 0.05) among patients with higher DNA integrity. Baseline serum levels of CCFD and its integrity were found to be potential prognostic biomarkers in patients of primary breast cancer at our centre.

BRCA1 germline mutations in Indian familial breast cancer.

Germline mutation analysis of BRCA1 gene has demonstrated significant allelic heterogeneity. These differences represent historical influences of migration, population structure and geographic or cultural isolation. To date, there have been no reports of Indian families with mutations in BRCA1. We have screened for mutations in selected coding exons of BRCA1 and their flanking intron regions in three breast or breast and ovarian cancer families with family history of three or more cases of breast cancer under age 45 and/or ovarian cancer at any age. We have also analyzed 10 female patients with sporadic breast cancer regardless of age and family history, as well as 50 unrelated normal individuals as controls. Thus a total of 90 samples were analyzed for BRCA1 mutations using polymerase chain reaction-mediated site directed mutagenesis (PSM) and single stranded conformation polymorphism (SSCP) analysis for various selected exons followed by sequencing of variant bands. Eight point mutations were identified. Two deleterious pathogenic, protein truncating non-sense mutations were detected in exon 11 (E1250X) and exon 20 (E1754X) and six novel and unique amino acid substitutions (F1734S, D1739Y, V1741G, Q1747H, P1749A, R1753K). One complex missense mutation of exon 20 [V1741G; P1749A] was seen in two out of three families and another complex combination of missense and non-sense mutations of the same exon [V1741G; E1754X] was observed in only one family. These complex mutations exist only in breast cancer families but not in control populations of women. Three splice site variants (IVS20+3A>C, IVS20+4A>T, IVS20+5A>T) and two intronic variants (IVS20+21_22insG, IVS20+21T>G) were also detected. In the group of 10 sporadic female patients no mutations were found.

Novel germline mutations in the BRCA1 and BRCA2 genes in Indian breast and breast-ovarian cancer families.

The two major hereditary breast/ovarian cancer predisposition tumor suppressor genes, BRCA1 and BRCA2 that perform apparently generic cellular functions nonetheless cause tissue-specific syndromes in the human population when they are altered, or mutated in the germline. However, little is known about the contribution of BRCA1 and BRCA2 mutations to breast and/or ovarian cancers in the Indian population. We have screened for mutations the entire BRCA1 and BRCA2 coding sequences, and intron-exon boundaries, as well as their flanking intronic regions in sixteen breast or breast and ovarian cancer families of Indian origin. We have also analyzed 20 female patients with sporadic breast cancer regardless of age and family history, and 69 unrelated normal individuals as control. Thus a total of 154 samples were screened for BRCA1 and BRCA2 mutations using a combination of polymerase chain reaction-mediated site directed mutagenesis (PSM), polymerase chain reaction-single stranded conformation polymorphism assay (PCR-SSCP) and direct DNA sequencing of PCR products (DS). Twenty-one sequence variants including fifteen point mutations were identified. Five deleterious pathogenic, protein truncating frameshift and non-sense mutations were detected in exon 2 (c.187_188delAG); and exon 11 (c.3672G>T) [p.Glu1185X] of BRCA1 and in exon 11 (c.5227dupT, c.5242dupT, c.6180dupA) of BRCA2 (putative mutations - four novel) as well as fourteen amino acid substitutions were identified. Twelve BRCA1 and BRCA2 missense variants were identified as unique and novel. In the cohort of 20 sporadic female patients no mutations were found.

Pulmonary metastasectomy: review of experience at a tertiary cancer care center.

BACKGROUND: Thirty to 40% of all extra thoracic cancers lead to secondary pulmonary lesions and approximately 20% of these cases feature metastases that are confined to the lungs. There is benefit of pulmonary metastasectomy in a select subset of patients. AIMS: The goal of this study was to evaluate the patient profile, treatment patterns, and outcomes following surgical treatment of lung metastasis and to identify prognostic factors for long-term survival. MATERIALS AND METHODS: Retrospective analysis of a prospectively maintained computerized database at a tertiary cancer care centre was done. 36 patients underwent curative resection for isolated pulmonary metastasis from January 1999 to December 2009. All metastasis were detected by non-contrast CT scan of the chest. Lung function tests were performed in all patients. Posterolateral thoracotomy was performed for resection of pulmonary metastasis by lung sparing procedures. A routine protocol of complete resection of all visible and palpable lung metastasis with a margin of 0.5 to 10 mm was followed in all patients. Staged thoracotomy was done for bilateral metastases. All palpable nodules were resected by wedge resection except in one case where pneumonectomy was done to achieve R0 resection. All patients underwent complete resection. CONCLUSIONS: Disease-free interval of more than 1 year along with less than 2 malignant nodules in patients with non-visceral pulmonary metastasis are variables identified in the present study which have enabled pulmonary metastasectomy to be offered as a safe therapeutic lifeline to patients.