Evolving utility of exosomes in pancreatic cancer management.

Despite the development of newer oncological treatment, the survival of patients with pancreatic cancer (PC) remains poor. Recent studies have identified exosomes as essential mediators of intercellular communications and play a vital role in tumor initiation, metastasis and chemoresistance. Thus, the utility of liquid biopsies using exosomes in PC management can be used for early detection, diagnosis, monitoring as well as drug delivery vehicles for cancer therapy. This review summarizes the function, and clinical applications of exosomes in cancers as minimally invasive liquid biomarker in diagnostic, prognostic and therapeutic roles.

STIL Endows Oncogenic and Stem-Like Attributes to Colorectal Cancer Plausibly by Shh and Wnt Signaling.

The discovery of a potent gene regulating tumorigenesis and drug resistance is of high clinical importance. STIL is an oncogene; however, its molecular associations and role in colorectal oncogenesis are unknown. In this study, we have explored the role of STIL gene in tumorigenesis and studied its molecular targets in colorectal cancer (CRC). STIL silencing reduced proliferation and tumor growth in CRC. Further, STIL was found to regulate stemness markers CD133 and CD44 and drug resistant markers thymidylate synthase, ABCB1, and ABCG2 both in in-vitro and in-vivo CRC models. In addition, high expression of STIL mRNA was found to be associated with reduced disease-free survival in CRC cases. Interestingly, we observed that STIL-mediated regulation of stemness and drug resistant genes is not exclusively governed by Sonic hedgehog (Shh) signaling. Remarkably, we found STIL regulate ß-catenin levels through p-AKT, independent of Shh pathway. This partially answers Shh independent regulatory mechanism of cancer stem cell (CSC) markers by STIL. Our study suggests an instrumental role of STIL in molecular manifestation of CRC and progression.

Adaptations and Safety Modifications to Perform Safe Minimal Access Surgery (MIS: Laparoscopy and Robotic) During the COVID-19 Pandemic: Practice Modifications Expert Panel Consensus Guidelines from Academia of Minimal Access Surgical Oncology (AMASO).

The pandemic of COVID-19 across the globe triggered national lockdowns hampering normal working for all the essential services including healthcare. In order to reduce transmission and safety of patients and healthcare workers, the elective surgeries have been differed. The visits to the hospitals for follow-ups and consultations received temporary halt. However, we cannot halt the treatment for cancer patients who may or may not be COVID-19 positives. These are emergencies and should be treated ASAP. Conducting emergency surgeries during pandemic like COVID-19 is challenge for surgeons and the entire hospital infrastructure. The available information about COVID-19 and its propensity of contamination through droplets and aerosol need some modifications for conducting surgeries successfully without contaminating the hospital buildings, protecting healthcare teams and the patient. With these objectives, some modifications in the operating theater including surgical techniques for minimal access, laparoscopy, and robotic surgery are proposed in this review article. This review article also discusses the safety measures to be followed for the suspected or confirmed COVID-19 patient and the guidelines and recommendations for healthcare teams while treating these patients. Although there is little evidence of viral transmission through laparoscopic or open approaches, modifications to surgical practice such as the use of safe smoke evacuation and minimizing energy device used to reduce the risk of exposure to aerosolized particles to healthcare team are proposed in this review article.

Validation of Malayalam Translation of the European Organization for the Research and Treatment of Cancer Quality of Life Instrument OG25 for Esophagogastric Junction Cancers.

BACKGROUND: Quality of life questionnaire (QLQ) OG25 is the questionnaire used for measuring quality of life (QOL) of patients with esophago-gastric junction (OG) cancers. QLQ-OG 25 is a disease-specific tool to capture the QOL parameters of patients with OG junction cancers. OG 25 was developed by the European Organization for the Research and Treatment of Cancer (EORTC) using inspiration from their questionnaires for carcinoma stomach (STO22) and carcinoma esophagus (OES18). It is usually used along with QLQ-C30, which is a general tool applicable for all cancers. This questionnaire is in the English language. In order to use this questionnaire in a non-English speaking population, the English questionnaire has to be initially translated to the local languages. Malayalam is the language spoken by 38.5 million people residing in the South Indian state, Kerala, India. We have translated and validated the QLQ-OG 25 to Malayalam language in an attempt of enabling it to be used for future studies at this geographic region. METHODS: The translation was done by the standard protocol adopted by EORTC. QLQ-C30 and QLQ-OG25 questionnaires were then filled in by patients with OG junction cancers. These patients had cancers of various subsites of the OG junction and were at different stages of treatment, at the time of interview. The interview was done twice, at an interval ranging from 48 h to 1 week between the two interviews. RESULTS: A total of 46 patients with OG junction tumors at varying stages of treatment completed the questionnaire. There were no missing data. The average time to finish the interview was 12.12 min. The Cronbach's alpha, which signifies the internal consistency of the questionnaire, was found to be >0.7 in all the domains studied, except in cognitive function. The intraclass correlation coefficients varied from 0.63 to 0.93. CONCLUSION: The Malayalam translation of the QOL tool QLQ-OG25 has been found to be an acceptable and valid tool in assessing the QOL parameters of patients with OG junction cancers.

Recommendations for Surgery During the Novel Coronavirus (COVID-19) Epidemic.

The whole world is going through an unprecedented period during the pandemic of COVID-19. This pandemic has affected all aspects of daily life with far-reaching implications, especially in most aspects of healthcare. Practice of surgery across the globe is in a standstill as of now. When we restart surgical practices across world, we have to bring new protocols and practices in place to combat the transmission. This article discusses the major changes in surgical practice, which need to be brought in. This article is based on scientific information about transmission of virus and experiences of some of the authors from China, a country which successfully dealt with and contained the virus outbreak.

The City of Hope Quality of Life Stoma Questionnaire: Malayalam Translation and Validation.

BACKGROUND: Malayalam is the language spoken by 38.5 million people worldwide. There is no specific instrument to measure stoma-related quality of life (QOL) in Malayalam language. AIM: This study was designed to translate and validate the city of hope QOL (COH-QOL) Ostomy Questionnaire, which is a robust tool developed in English language. MATERIALS AND METHODS: The instrument was translated to Malayalam, abiding by internationally accepted translation methodology. Trained interviewer (first author) administered the questionnaire to patients with stoma, who were visiting the stoma clinic. The reliability of the subscales and the total scores were established by calculating correlation coefficients. Convergent and divergent validity were evaluated by calculating Pearson's correlations of each item with its own scale and other scales. RESULTS: Cronbach's alpha coefficients for all subscales were 0.70 or more. Similarly, split-half coefficients also were more than 0.70, which were acceptable. All subscales met the minimum acceptable standards of convergent and discriminant validity. Discriminant validity of all scores was less than convergent validity which suggests that there was no overlap between various constructs in measuring the same traits. The validation study of Malayalam translation of COH stoma questionnaire has shown that the tool is valid and reliable. CONCLUSION: The validation study of Malayalam translation of City of Hope Stoma questionnaire has shown the tool is valid and reliable.

Palatal swelling in a young adult.

The presence of numerous minor salivary gland tissues in the posterior part of hard palate increases the possibility of salivary gland neoplasms. Minor salivary gland tumor accounts for about 15% of all the salivary gland neoplasms, of which mucoepidermoid carcinoma (MEC) accounts for about 35.9%. Although a wide range of the differential diagnosis is made by the clinicians toward a single palatal swelling without any other specific changes on inspection, a prompt "histopathological" diagnosis is of utmost importance in case of lesions like "MEC." By taking the case study of a 23-year-old male patient who was complaining of difficulties in eating and speaking due to a swelling in the palate that was not associated with pain, etc., this case report highlights the need for an early clinical examination and prompt histopathological diagnosis of such clinically benign looking lesions, as such an action can play an ameliorating role in reducing the chances of postoperative morbidity.

Augmented CD133 expression in distal margin correlates with poor prognosis in colorectal cancer.

Pathological assessment of excised tumour and surgical margins in colorectal cancer (CRC) play crucial role in prognosis after surgery. Molecular assessment of margins could be more sensitive and informative than conventional histopathological analysis. Considering this view, we evaluated the distal surgical margins for expression of cancer stem cell (CSC) markers. Cellular and molecular assessment of normal, tumour and distal margin tissues were performed by flow cytometry, real-time q-PCR and immuno-histochemical analysis for CRC patients after tumour excision. CRC patients were evaluated for expression of CSC markers in their normal, tumour and distal tissues. Flow cytometry assay revealed CD133 and CD44 enriched cells in distal margin and tumour compared to normal colorectal tissues, which was further confirmed by immunohistochemistry. Most importantly, immunohistochemistry also revealed the enrichment of CSC markers expression in pathologically negative distal margins. Patients with distal margin enriched for CD133 expression showed an increased recurrence rate and decreased disease-free survival. This study proposes that although distal margin seems to be tumour free in conventional histopathological analysis, it could harbour cells enriched for CSC markers. Further CD133 could be a promising molecule to be used in molecular pathology for disease prognosis after surgery in CRC patients.

Immunocytochemistry on Sputum Samples Predicts Prognosis of Lung Cancer.

CONTEXT: Despite sputum cytology being accepted as a simple and noninvasive diagnostic method for lung cancer, the clinical usefulness of sputum for evaluation of prognosis is yet to be explored. Validation of some of the markers in sputum for prognosis prediction will be highly useful for selective therapy. AIMS: This study was aimed to evaluate a reliable panel of immunocytochemical markers for their significance to predict survival. MATERIALS AND METHODS: We have analyzed the expression of p53, p16, galectin-3, and epidermal growth factor receptor (EGFR) proteins in sputum samples processed in a mucolytic agent/cellblock and compared the same with that of the corresponding tissue samples. RESULTS: Overexpression of p16 and EGFR was found to have a better survival benefit, whereas positive p53 and galectin-3 expressions had shorter period of survival. Expression patterns of all these four proteins were more or less similar in smears, cellblocks of sputum, and tissue samples except for slight changes in staining intensity which was not found to be statistically significant. No significant difference was found in the association of these proteins with survival pattern between sputum and tissue samples. CONCLUSION: This is the first report of immunocytochemistry of a panel of markers on cells exfoliated in sputum samples which suggests that analysis of immunocytochemical markers in sputum samples can be attempted as a cost-effective and reliable predictor of prognosis and survival. Accumulation of mutated p53, overexpression of galectin-3, and lower expression of p16 and EGFR proteins were found to predict poor prognosis for lung cancer.

Identification and Quantification of Drug-Resistant Cells in Colorectal Tumor and Distal Margin.

Cancer stem cells are cellular subpopulations in tumor, which are highly tumorigenic and drug resistant due to their adaptive molecular mechanism. In the recent years, these cells have attracted researchers' focus because of their unique properties which makes them biologically well evolved than other proliferating tumor cells. We have studied the presence of cancer stem cells in colorectal cancer (CRC) and its surgical margins. We report for the first time the presence of drug-resistant cells in distal resection margins in CRC and showed that a closer distal margin of less than 2 cm could have higher possibility of drug-resistant cells to spread.

Aggressive Angiomyxoma of Inguinoscrotal Region Mimicking Inguinal Hernia: a Case Report.

Aggressive angiomyxoma (AAM) is a rare mesenchymal tumour of pelvis and perineum, almost exclusively occurring in females. We are reporting a case of a 53-year-old gentleman who presented with a long standing inguinoscrotal swelling misdiagnosed as inguinal hernia, for which he underwent incomplete excision at local hospital and then was referred to our centre for completion surgery.

A Prospective Study of Distal Microscopic Spread in Rectal Cancer After Neoadjuvant Chemoradiation in Pinned and Unpinned Specimen.

The most important margin in determining the prognosis of rectal cancer is circumferential resection margin (CRM). But, the type of surgery is determined by distal rectal margin (DRM), whether sphincter saving procedure is possible or patient needs an abdominoperineal resection. There are no standardized uniform guidelines for measurement of DRM. The purpose of this study is to assess the distal microscopic spread beyond gross margin after neoadjuvant concurrent chemoradiation (CCRT) in rectal cancers, the factors influencing the distal microscopic spread, the shrinkage of the distal margin in pinned and unpinned fresh and fixed specimen, and to find out the best method of measurement of distal rectal margin. A prospective analytical study was conducted from May 2013 through February 2015 in 47 cases of carcinoma rectum (both AR and APR) who had received neoadjuvant CCRT. Fresh specimen was collected within 30 min of specimen retrieval and a longitudinal cut was made in the distal margin of all specimens. One side of the specimen was pinned onto a cork board and the other side was left unpinned. Measurements were made from the distal end of clinical gross tumor. DRM was determined in both pinned and unpinned sides in fresh and fixed specimen. Of the 47 patients, 2 patients (4.2%) had small focus of tumor beyond gross margins, 1 at 6 mm and another at 3.5 mm on the unpinned side. The average margin for fresh and fixed pinned specimens was 3.67 and 3.47 cm, respectively, with percentage shrinkage of 5.4% for the pinned specimens. The average margin for fresh and fixed unpinned specimens was 3.32 and 2.84 cm, respectively, with percentage shrinkage of 14.4% for the unpinned specimens. Six patients (12.7%) had complete pathological response. Correlation of distal margin was better in pinned specimen. A correction factor of 15% for shrinkage needs to be taken into account while assessing unpinned specimen. Only in 4.2% of patients, there was distal submucosal spread beyond gross margin. Long-term follow up is required for assessing adequacy of DRM post neoadjuvant CCRT.

Radical Treatment of Rectal Cancer in Elderly Is Feasible than Feared: Results from a Tertiary Care Centre.

The thought of subjecting an elderly patient with rectal cancer to protocol-based neoadjuvant chemoradiation (NACTRT), surgery and adjuvant chemotherapy is sought with fear due to their multiple comorbidities and impaired functional status associated with the process of ageing. Hence, many a times the treatment is compromised and it is a fact that this subgroup of patients is underrepresented in most of the clinical trials. This study was aimed at analysing the perioperative and oncologic outcomes after protocol-based treatment of rectal cancer in the elderly patients, defined here as those with age ≥70 years. Prospective analysis of medical records of rectal cancer patients was done who were ≥70 years of age and were diagnosed and treated at Regional Cancer Centre (RCC), Thiruvanathapuram from 2008 to 2012. In this 5-year period, a total of 339 rectal cancer patients underwent surgery as part of multimodality treatment with curative intent. Of them, 75 patients were ≥70 years of age. Half of them had one or more comorbidities (54%) and majority were locally advanced at presentation (77%). Forty-seven (62%) cases received NACTRT and all of them tolerated RT dose (50.4 Gy) without modification. Anterior resection (AR) was performed in 48 (64%) and abdominoperineal resection (APR) in remaining. Diverting stoma was made in four; of which three remained permanent. Two colostomies were performed for delayed leaks. Three patients (4%) died within 30 days due to leak, sepsis and cardiopulmonary causes. Two thirds (49/75) received adjuvant chemotherapy (ACT) but only 55% of them (27/49) could complete all the cycles without dose modification. The median survival was 28 months. The 3-year disease-free survival (DFS) and overall (OS) were 80.1 and 83.9%, respectively. There were 11 distant recurrences including two locoregional recurrences. The morbidity and mortality of multimodality therapy is reasonable to proceed with radical treatment with curative intent in the elderly patients with rectal cancer.

Triple Test-a Predictor of Anastomotic Integrity in Patients Undergoing Low Anterior Resection After Neoadjuvant Chemoradiotherapy.

Anastomotic leak after low anterior resection for rectal cancer is a dreaded complication. Diversion stoma helps tiding over this crisis and it is routinely practised in most centres, especially in post chemoradiotherapy setting. But a diversion stoma has got its own problems. In this study, we attempt to use the triple test as a predictor of anastomotic integrity and thereby avoid a diverting stoma, and patients undergoing low anterior resection after neoadjuvant chemoradiotherapy were spared the trouble of a diverting stoma if the on table triple test was negative. Two hundred such consecutive patients were prospectively followed up in the postoperative period. The incidence of anastomotic leak and the factors predicting the same were analysed in this group of patients. The incidence of anastomotic leak in our study was 7%, which is much less when compared to published literature. The triple test was a reliable predictor of the integrity of anastomosis and if the test is negative, a diverting stoma can be avoided. Age more than 60 years and end-to-end anastomosis were found to be associated with increased incidence of leak, and patients with a negative triple test need not routinely undergo diversion stoma after a low anterior resection even in post chemoradiotherapy setting.

Pneumocytoma: a Case Report and Review of Literature.

Pneumocytoma is a rare benign neoplasm which was described over 50 years ago. Over the years its nomenclature and histogenesis has been a subject of much debate and controversy. We would like to report a case of a lady who presented with complaints of cough and hemoptysis. X-ray chest and computerized tomography (CT) scan showed a solitary pulmonary nodule. Biopsy was inconclusive. She underwent a left lower lobectomy. Her postoperative period was uneventful. Her final diagnosis was of pneumocytoma. She is on regular follow-up and is asymptomatic at present.

Oncological Safety of Breast Conservation Surgery in Young Females.

Breast conservation surgery (BCS) is the standard of care in early breast cancer. The oncological safety of this procedure has been proven beyond doubt in several randomised control trials. But there are concerns regarding the safety of this procedure in young females. The concern is regarding increased risk of local recurrence. This issue has not been addressed in any major trial. In this prospective study we intend to look into the oncological safety of BCS in young patients who are less than forty years of age.

Role of frozen section in the intra-operative margin assessment during breast conserving surgery.

BACKGROUND: Breast conserving surgery (BCS) is increasingly done for early breast cancers in many countries since it has been demonstrated by randomized trials that survival rates after BCS followed by adjuvant therapy are equivalent to those obtained after mastectomy. Frozen section analyses (FSA) is a technique used for intra-operative assessment of margin status in BCS. The aim of this study was to assess the concordance of margin status assessment by FSA and permanent sections and to assess correlation with local recurrence. MATERIALS AND METHODS: A total of 162 patients underwent BCS for in situ or invasive carcinoma with FSA of margins during the year 2008 at our center. The inclusion criteria in this study were patients with intact tumor at the time of surgery. After application of the inclusion criteria, 60 patients could be included in this study. RESULTS: After frozen section, 20 patients had an initial negative margin. 40 subjects underwent additional excisions at the time of initial surgery because of close or positive margins. Of these 40 patients, in 32 patients a negative margin could be achieved with re-excisions. Pathological analyses of frozen section showed concordance to permanent sections in all cases. At a median follow-up of 40 months, there were no local recurrences. CONCLUSION: Intra-operative FSA allows resection of suspicious margins at the time of primary conservative surgery and results in low rates of local recurrence and second surgeries. There is good concordance between results of FSA and the final paraffin section in assessing margin status.

Dr. Thomas cherian; father of cancer surgery in kerala.

Dr. Thomas Cherian (1940-2014) is one of the first surgical oncologists from State of Kerala, India. A humble human being, dexterous surgeon, untiring worker, and a dynamic personality that was Dr. Thomas Cherian. His vision, hardworking abilities and indomitable spirit were exemplary. He has paved path for the development of surgical oncology in Kerala. This article portrays not only the life of a selfless man, but also the beginning of a new speciality of Surgical Oncology in Kerala.