A proposal for changing nomenclature from pseudomyxoma peritonei (PMP) to abdomino-peritoneal mucinous carcinoma (APM) based on its long journey and experience from tertiary oncology center in India.

INTRODUCTION: Pseudomyxoma peritonei (PMP) is a generalized term, usually known as "jelly belly" since 1884. Incidence is very low, 1-3 per million people per year. Because of its indolent nature, it is usually diagnosed at an advanced stage, thereby impacting the quality of life. The 5-year survival rate varies from 23 to 86% in world literature. Even 10 years and 20 years of survival have been described. With our experience, we like to propose rename of PMP as abdomino-peritoneal mucinous carcinoma (APM) as we strongly feel the time has come to specify the term and standardize the management strategy. METHODOLOGY: In the premier institute of India and as a tertiary referral center, we experienced the maximum number of advanced cases of APM. From 2012 to 2021, we analyzed all the APM patients based on a prospectively maintained computerized database in the department of surgical oncology and found the reasons for renaming from this traditional one. RESULTS: We included a total of 87 patients who underwent surgical intervention. Thirty-five patients underwent cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC), and 52 patients underwent debulking. In CRS-HIPEC patients, CC-0 was achieved in 28 patients (80%), CC-1 in 4 patients (11.4%), and CC-2 in 3 patients (8.6%). Palliative intent HIPEC was done in 3 patients (8.6%). Clavien-Dindo grade III and IV morbidity was observed in 18.8% of patients with 90 days mortality of 5.7%. CONCLUSION: With our long-term experience and advancement of scientific evidence, we like to propose a new name for PMP as APM. We strongly believe this paper will give a clear picture of this rare disease and standard management outlines.

Learning Curve of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy - an Analysis of Critical Perioperative and Surgical Outcomes among 155 Peritoneal Surface Malignancy Patients Treated at a Tertiary Care Cancer Centre.

AIMS: Various factors can influence the learning curve of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Initiating CRS and HIPEC programmes in low- and middle-income countries is challenging due to resource constraints and limited availability of expertise. We present our experience of CRS and HIPEC from a learning curve perspective among a cohort 155 peritoneal surface malignancy patients. MATERIALS AND METHODS: Patients undergoing CRS and HIPEC between May 2015 and February 2019 were included in the study. Patients were divided into two consecutive cohorts: the first 73 cases comprised the learning phase, group 1; the subsequent cohort of 82 patients were considered as the implementation phase, group 2. A comparative analysis of clinical and surgical outcome parameters was carried out between the two groups. RESULTS: The clinical spectrum was comparable among group 1/group 2. Most were ovarian (56.8%), colorectal (13.5%) and appendiceal (11.0%) malignancies. Group 2 had a higher number of moderate to high peritoneal cancer index patients (34.1% versus 19.1%), total peritonectomies (48.8% versus 45.2%), multi-visceral resections (colonic 41.5% versus 27.4%, small bowel 25.6% versus 19.1%, diaphragmatic 8.5% versus 6.5% and hepatic resections 8.5% versus 2.7%) and completeness of cytoreduction 0/1 rates (97.6% versus 93.1%). A lower incidence of intraoperative urological injuries (2.6% versus 12.3%) was noticed in group 2 (P = 0.007). Non-significant improvements seen in group 2 included surgery duration (6.0 ± 1.3 h versus 6.4 ± 1.7 h), intensive care unit stay (1.3 ± 1.1 days versus 1.8 ± 1.5 days), overall hospital stay (8.1 ± 0.9 days versus 8.8 ± 1.4 days) and reduction in Clavien-Dindo grade 3-4 complications (25.4% versus 36.9%). CONCLUSIONS: The results of the current study indicate that by implementing standard protocols and mentoring by an experienced team, a learning curve of CRS and HIPEC can be achieved in fewer than 75 cases. The baseline expertise of the treating team can also influence the learning curve.

Profile of Pathogenic Mutations and Evaluation of Germline Genetic Testing Criteria in Consecutive Breast Cancer Patients Treated at a North Indian Tertiary Care Center.

BACKGROUND: The burden of hereditary breast cancer in India is not well defined. Moreover, genetic testing criteria (National Comprehensive Cancer Network [NCCN] and Mainstreaming Cancer Genetics [MCG] Plus) have never been validated in the Indian population. METHODS: All new female breast cancer patients from 1st March 2019 to 28th 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. The frequency of pathogenic/likely pathogenic (P/LP) mutations between patients qualifying and not qualifying the testing criteria was compared and their sensitivity was computed. RESULTS: Overall, 275 breast cancer patients were screened and 236 patients were included (median age 45 years); 30 patients did not consent and 9 patients previously underwent genetic testing. Thirty-four (14%) women had a positive family history and 35% had triple-negative breast cancer. P/LP mutations were found in 44/236 (18.64%) women; mutations in BRCA1 (22/47, 46.8%) and BRCA2 (9/47, 19.1%) were the most common, with 34% of mutations present in non-BRCA genes. Patients qualifying the testing criteria had a higher risk of having a P/LP mutation (NCCN: 23.6% vs. 7.04%, p = 0.03; MCG plus: 24.8% vs. 7.2%, p = 0.01). The sensitivity of the NCCN criteria was 88.6% (75.4-96.2) and 86.36% (72.65-94.83) for MCG plus. More than 95% sensitivity was achieved if all women up to 60 years of age were tested. Cascade testing was performed in 31 previous (16/44 families), with 23 testing positive. CONCLUSIONS: The frequency of P/LP mutations in India is high, with significant contribution of non-BRCA genes. Testing criteria need modification to expand access to testing.

A new definition of health? An open letter of autochthonous peoples and medical anthropologists to the WHO.

Currently, for many practitioners (hospital and liberals) and researchers (including public health), the WHO definition of health is outdated: first it seems more utopian than pragmatic; then, it proves unsuitable for a large part of the world population. There is clearly a need to refine this definition or propose additional criteria to be more relevant or discriminating. In this perspective, what can indigenous people offer in the elaboration of a new definition of health? In this article, leaders or representatives of autochthonous peoples, anthropologists and physicians from many cultural origins (Amazonia, Patagonia, Papua New-Guinea, Inuit, North-American Indian, sub-Saharan Africa, India, China, Melanesia and Polynesia) have tried to identify and explain several key concepts that WHO should reintegrate into its new definition of health: human equilibrium in nature, accepted spirituality and adaptation. On the sidelines of the application of COP21 decisions that should give back to man his place into the environment, autochthonous people leaders, anthropologists and MDs explain why these three concepts are fundamental and universal health determinants, and need to be included in a new WHO definition of health.

Young breast cancer: A single center experience.

BACKGROUND: Breast cancer in women aged less than 35 years is uncommon and accounts for 1-2% of all breast cancer in the West. There is a paucity of data on young breast cancer from India. The aim of this study was to analyze the clinical, pathological, prognostic factors and outcome in young breast cancer patients. MATERIALS AND METHODS: This analysis was performed in 251 patients aged <35 years or less (defined as breast cancer in the young), who were registered at our institute over an 11 year period between 2001 and 2011. RESULTS: The median age was 31 years (range 18-35). Positive family history (siblings and parents) was elicited in only 10 patients. The TNM stage distribution was: Stage I was 2.5%, stage II - 20.5%, stage III - 55% and stage IV - 22%. The median clinical tumor size was 5.1 cm. Modified radical mastectomy was the most common surgical procedure and this was done in 79% of cases. 40% of tumors were high grade and 60% had pathological node positive disease. Estrogen and Progesterone and human epidermal growth factor receptor 2/neu positivity were 33% and 29% respectively. Triple negative breast cancer constituted 31% of patients. With a median follow-up of 30 months, 3 years relapse free survival and overall survival was 51% and 66%. CONCLUSION: Young women constituted 8% of breast cancer cases. Advanced disease at presentation and triple negativity (nearly one third of patients) results poor outcome.

Randomized trial comparing neo-adjuvant versus adjuvant chemotherapy in operable locally advanced breast cancer (T4b N0-2 M0).

BACKGROUND AND OBJECTIVES: Locally advanced breast cancer (LABC) remains a major problem in developing countries. While trials utilizing neo-adjuvant chemotherapy demonstrate superior survival rates compared to historic controls, randomized studies evaluating the precise role of neo-adjuvant chemotherapy in LABC are lacking. In the present trial, neo-adjuvant chemotherapy was compared against adjuvant chemotherapy to assess survival advantage in operable T4b N0-2 M0 breast cancer. METHODS: A total of 101 women with operable LABC (T4b N0-2 M0) were randomized. In arm A, 50 patients received 3 cycles of CEF chemotherapy before and 3 cycles following surgery. In arm B, 51 patients had primary surgery followed by 6 cycles of CEF chemotherapy. In both arms, loco-regional radiotherapy was given after completion of CEF. RESULTS: The response of primary tumor to neo-adjuvant chemotherapy was 66%, complete response (CR) 14% and partial response (PR) 52%. Clinical nodal response occurred in 95% of node positive patients. Only two (4%) patients had pathologic CR both in tumor and axilla. There was a significant (P = 0.02) increase in incidence of pathologically negative nodes in arm A. At a median follow up of 25 months, there was no significant difference in overall and disease free survival (DFS) in both arms (P = 0.42 and 0.18). Patients showing a response to neo-adjuvant chemotherapy had better DFS (P = 0.04) compared to those who had no response. CONCLUSIONS: Early results of the study indicate no survival benefit with the inclusion of neo-adjuvant chemotherapy in LABC (T4b N0-2 M0). Neo-adjuvant chemotherapy resulted in significant down staging; good responders had a better DFS compared to those who did not respond.

Luminescent proteins from Aequorea victoria: applications in drug discovery and in high throughput analysis.

Recent progress in generating a vast number of drug targets through genomics and large compound libraries through combinatorial chemistry have stimulated advancements in drug discovery through the development of new high throughput screening (HTS) methods. Automation and HTS techniques are also highly desired in fields such as clinical diagnostics. Luminescence-based assays have emerged as an alternative to radiolabel-based assays in HTS as they approach the sensitivity of radioactive detection along with ease of operation, which makes them amenable to miniaturization. Luminescent proteins provide the advantage of reduced reagent and operating costs because they can be produced in unlimited amounts through the use of genetic engineering tools. In that regard, the use of two naturally occurring and recombinantly produced luminescent proteins from the jellyfish Aequorea victoria, namely, aequorin and the green fluorescent protein (GFP), has attracted attention in a number of analytical applications in diverse research areas. Aequorin is naturally bioluminescent and has therefore, virtually no associated background signal, which allows its detection down to attomole levels. GFP has become the reporter of choice in a variety of applications given that it is an autofluorescent protein that does not require addition of any co-factors for fluorescence emission. Furthermore, the generation of various mutants of GFP with differing luminescent and spectral properties has spurred additional interest in this protein. In this review, we focus on the use of aequorin and GFP in the development of highly sensitive assays that find applications in drug discovery and in high throughput analysis.