Prognostic Implications of Various Surgical Procedures and Postoperative Margin Status in Gastroesophageal Junction Tumors.

Esophagogastric junction (EGJ) carcinomas often require access to two compartments of the body for good margin and lymphadenectomy. Whether it is required to do so in all patients is debatable. We analyzed outcomes of patients who underwent surgeries for EGJ carcinomas in terms of margin status and survival. This is a retrospective analysis of a prospectively maintained database of patients with EGJ adenocarcinomas operated between January 2014 and December 2016. Type of surgery performed and its impact on margin status and survival were assessed. Follow-up was for a minimum of 5 years. Ninety-four patients with EGJ carcinomas were operated on during the study period. Eight (8.51%) had involved proximal margin, and 2 of these had positive distal margin also. None had distal margin alone involved. Seventeen (18.09%) and 5 (5.32%) had a close proximal and distal margin, respectively. Radial margin was close/involved in 6 (6.38%) patients. Five-year overall survival and disease-free survival for the cohort was 38% and 30.8%, respectively. Proximal gastrectomy had a higher proximal margin positivity. Positive proximal or distal margin and a close/involved radial margin were detrimental to disease free survival and overall survival. Proximal gastrectomy is associated with a higher likelihood of proximal margin positivity. Positive margin leads to lower survival. Whether involvement of margins is just a surrogate marker of aggressive tumor or is an error in assessing extent tumor needs to be studied. Large-scale prospective studies in this regard are desirable.

Sacral Resections for Primary Sacral Tumor - an Experience from a Tertiary Care Cancer Center in India.

Primary sacral tumors are uncommon and sacrectomy is a complex surgical procedure with substantial risk of morbidity. We conducted a retrospective study of patients who had undergone sacral resections for primary sacral tumors between 2010 and 2020. Ten sacral resections including five type 1 sacrectomy (S1 resected), four type 2 (S1 spared), and one type 3 (S3 spared) were performed during the above period. The median age was 47 years and the most common histologic diagnosis was chordoma (50%). The median operating time was 705 min (range 180-960 min) with a median blood loss of 3400 ml (range 500-7000 ml) and a median duration of hospital stay of 13.5 days (range 7-68 days). All patients who underwent type 1 sacrectomy experienced major complications (Clavien-Dindo grade 3 or above) including one death in the immediate perioperative period. Microscopically positive margins (R1) were noted in two patients (20%). All patients with type 1 sacrectomy had R0 resection. The median follow-up period was 31 months. The median MSTS score was 12 (range 4-27). A total of seven patients (70%) had a minimum follow-up of 2 years without disease recurrence. Sacral resection for primary tumors of the sacrum with oncologically safe margins is feasible. Although associated with substantial perioperative morbidity, a detailed preoperative planning and execution of the surgery by a team of orthopedic oncosurgeon, surgical oncologist, and plastic surgeon offer a hope for survival in patients with acceptable functional outcome.

Co-expression of galectin-3 and vimentin in triple negative breast cancer cells promotes tumor progression, metastasis and survival.

BACKGROUND: Lack of druggable targets and complex expression heterogeneity of known targets is common among TNBC subtypes. An enhanced expression of galectin-3 in TNBCs has already been documented. We have observed a tumor progression-dependent galectin-3 expression in TNBCs compared to adjacent epithelium and non TNBCs. OBJECTIVE: To unravel the association of galectin- 3 in tumor progression, aggressiveness and drug resistance in TNBC patients. METHODS: Galectin-3 expression in 489 breast cancer tissues was correlated with clinicopathological features and the results were validated in cell lines and mouse model by silencing galectin-3 using shRNA and the proteins were profiled by western blot and qRT-PCR. Protein interaction was analyzed by GFP Trap and Mass spectrometry. RESULTS: Galectin-3 expression correlated with tumor stage in TNBC and a lower galectin-3 expression was associated with poor patient survival. The positive correlation between galectin-3, vimentin and CD44 expression, pinpoints galectin-3 contribution to epithelial to mesenchymal transition, drug resistance and stemness. Vimentin was found as an interacting partner of galectin-3. Duplexing of galecin-3 and vimentin in patient samples revealed the presence of tumor cells co-expressing both galectin-3 and vimentin. In vitro studies also showed its role in tumor cell survival and metastatic potential, elementary for tumor progression. In vivo studies further confirmed its metastatic potential. CONCLUSIONS: Tumor progression dependent expression pattern of galectin 3 was found to indicate prognosis. Co-expression of galectin-3 and vimentin in tumor cells promotes tumor dissemination, survival and its metastatic capability in TNBCs.

Morbidity of Temporary Loop Ileostomy in Patients with Colorectal Cancer.

Leakage of low colorectal anastomoses after total mesorectal excision is a dreaded complication. Hence, an ileostomy is commonly performed during anterior resection especially in patients who have received neoadjuvant radiation. The aim of this study was to quantify the temporary loop ileostomy-related benefits as well as morbidity in patients with colorectal cancer. We did a retrospective study including all patients who underwent anterior resection with diversion ileostomy for biopsy-proven rectal carcinoma at our institute from 1 Jan 2016 to 31 Dec 2017 with follow-up of 2 years. A total of 104 patients were included in the study. In our series, 6.7% patients had an anastomotic dehiscence which precluded patients from stoma reversal. 12.5% of the patients had a stoma-related complication. 5.7% patients had complications following a stoma reversal. Eighty percent of the patients who developed clinically evident dehiscence in the immediate postoperative period were managed conservatively because of the presence of stoma. We did not have any mortality related to the stoma. 18.3% patients did not have their stomas reversed. The stoma non-reversal due to anastomotic dehiscence or stricture could be attributed to in 7.7% patients. 3.8% had to have their ileostomies converted to a permanent colostomy due to either a rectovaginal fistula or dehiscence or stricture. The complications associated with ileostomy are not insignificant. In our study, the tumor location in lower rectum was the only significant factor for non-reversal. We have to objectively identify patients who are at low risk for leakage and avoid ileostomy in them, and also try to minimize the morbidity of ileostomy by methods like early closure.

Effects of Revision Surgery and Surgical Margins on Outcome of Peripheral Soft Tissue Sarcomas: Experience from a Tertiary Cancer Care Centre.

INTRODUCTION: The purpose of this study is to assess the impact of revision surgery, after unplanned excision, on oncological outcome and surgical morbidity in soft tissue sarcomas and also to assess the relation between margin status and oncologic outcome. MATERIALS AND METHODS: We undertook a retrospective analysis of prospectively maintained database of 153 patients with peripheral soft tissue sarcomas treated in our institute from 2006-2010. RESULTS: Postoperatively, 111(72.5%) patients had negative margins, 20(13.1%) had close margins and 22(14.4%) had planned positive margins. Local recurrence rate was 19.8% in patients with negative margins and 28.6% for patients with close or positive margins (p= 0.007). There was no statistically significant difference in rates of distant metastases (18.9% vs 21.4%, p value 0.56) and five-year overall survival (82.5% Vs 79.8%, p value 0.41) between margin negative and close/positive groups. The five-year overall survival rates were 80.4 vs 77.8% (p =0.42) and five-year disease-free survival rates were 72.4% vs 70.2% (p=0.3), in the revision surgery group and primary surgery group respectively. CONCLUSION: Margin status after excision of soft tissue sarcoma is not a direct predictor for overall survival or distant metastasis. Revision surgery after an unplanned excision does not carry worse survival compared to primary surgery group.

Pattern of Lymph Node Metastasis in Endometrial Cancer: a Single Institution Experience.

Surgical staging remains the standard primary treatment of endometrial cancer. Lymph node metastasis is the most important prognostic factor which helps in deciding adjuvant treatment. Extensive lymphadenectomy is associated with increased incidence of morbidity. The role of lymphadenectomy in surgical staging is still controversial especially in early stage disease. The surgico-pathological pattern of 155 patients with apparently stage 1 cancer endometrium who had undergone pelvic alone or pelvic and para-aortic lymph node dissection and its correlation to the grade of the tumour, myometrial infiltration and presence of peritoneal disease and incidence of peri-operative morbidity are analysed and described.

CT reporting of relevant vascular variations and its implication in pancreatoduodenectomy.

Pancreatoduodenectomy (PD) also known as Whipple procedure is done for malignant lesions involving the distal CBD, duodenum, ampulla and pancreatic head. In the absence of peritoneal and distant metastases, resectability of the lesion is mainly determined by the relationship of the lesion with the vascular structures in the vicinity. Vascular variations of the celiac artery branches are common and PD, a complex surgical procedure, becomes more challenging if the vascular variations are present. In borderline resectable lesions advances in neoadjuvant therapies and refined surgical techniques are pushing the boundaries of resection. Extended PD is done in borderline resectable lesions when resection and reconstruction of portal vein involved by the primary mass and dissection of extended lymph nodal stations are intended. In this era where more borderline cases are undergoing surgery, it is essential for the radiologist to understand the procedure and the implications of variations in vascular anatomy. Though there are many radiology literatures available on the diagnostic and resectability criteria related to normal vessel anatomy there are very few on the importance of the variant arterial anatomy. The purpose of this review is to familiarize the readers with these variant vessels which can help the surgeons in their intraoperative identification and consequently improve surgical outcomes.

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.

ß-hCG-induced mutant BRCA1 ignites drug resistance in susceptible breast tissue.

ß-hCG expression in breast cancer is highly controversial with reports supporting both protective and tumorigenic effects. It has also been reported that risk of breast cancer at an early age is increased with full-term pregnancies if a woman is a BRCA1 mutation carrier. We have already demonstrated that BRCA1-defective cells express high levels of ß-hCG and that when BRCA1 is restored, ß-hCG level is reduced. Also, BRCA1 can bind to the promoter and reduce the levels of ß-hCG. ß-hCG induces tumorigenicity in BRCA1-defective cells by directly binding to TGFBRII and induces TGFBRII-mediated cell proliferation. In this study, we analyzed the mechanism of action of ß-hCG on BRCA1 expression and its influence on drug sensitivity in breast cancer cells. We demonstrate that ß-hCG induces mutant BRCA1 protein expression in BRCA1 mutant cells; however, in BRCA1 wild-type cells, ß-hCG reduced wild-type BRCA1 protein expression. Transcriptionally, ß-hCG could induce Slug/LSD1-mediated repression of wild-type and mutant BRCA1 messenger RNA levels. However, ß-hCG induces HSP90-mediated stabilization of mutant BRCA1 and hence the overexpression of mutant BRCA1 protein, resulting in partial restoration of homologous recombination repair of damaged DNA. This contributes to drug resistance to HSP90 inhibitor 17AAG in BRCA1-defective cancer cells. A combination of HSP90 inhibitor and TGFBRII inhibitor has shown to sensitize ß-hCG expressing BRCA1-defective breast cancers to cell death. Targeting the ß-hCG-HSP90-TGFBRII axis could prove an effective treatment strategy for BRCA1-mutated breast tumors.

Brcal Defective Breast Cancer Cells Induce in vitro Transformation of Cancer Associated Fibroblasts (CAFs) to Metastasis Associated Fibroblasts (MAF).

It is known that Cancer Associated Fibroblast (CAFs) from the primary tumor site can accompany cancer cells to a secondary site during the process of metastasis. We hypothesize that these CAFs could be transformed to an altered cell type, which can be called as Metastasis Associated Fibroblasts (MAF) in turn can support, and convoy cancer cells for metastasis. There are no published reports that have characterized and distinguished CAFs from MAF. It is well established that some of the cancer cells within the tumor mass accumulate novel mutations prior to metastasis. Hence, we speculated that mutations in the tumor suppressor gene, BRCA1, which is already reported to induce metastasis via abnormal expression of Ezrin, Radixin and Moesin (ERM), could generate MAF. In the present study, we demonstrate for the first time that CAFs isolated from primary breast cancer tissues when co-cultured with BRCA1 mutated HCC1937 cells transform CAFs to MAF in vitro. As expected, MAF augmented proliferation, migration and invasion along with over-expression of epithelial mesenchymal transition (EMT) markers, Ezrin and CCL5, thereby facilitating metastasis. Therefore, we inhibited Ezrin and CCL5 in vitro in MAF and observed that the migration and invasion abilities of these cells were attenuated. This highlights the intriguing possibilities of combination therapy using MAF inhibitors as anti-metastatic agents along with anticancer drugs, to control the metastatic spread from primary tumor site.

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.

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.

Salvage Surgery for Cervical Cancer Recurrences.

Cervical cancer usually presents in advanced stages and is treated with chemoradiation. About 15-20 % patients present with local recurrence after chemoradiation. Radical surgical resection is the only treatment modality offering long term survival benefit in recurrent cervical cancer. The most common surgical option for these patients is pelvic exenteration. Radical hysterectomy may be done for patients with a small centrally located recurrence in the cervix with no infiltration of adjacent structures. The aim of this study was to evaluate the morbidity and survival outcome following radical hysterectomy and pelvic exenteration for recurrent cancer cervix. We retrospectively reviewed the medical records of our patients who underwent surgery for cancer cervix recurrence from January 2010 to December 2014. The postoperative morbidity was considered early if it happened in the initial 30 days of surgery and late if it occurred after 30 days. All patients were followed up till February 2015. Survival analysis was done using Kaplan- Meir method. Between January 2010 and December 2014, 20 patients with recurrent cervical cancer underwent radical surgical resection. The median age of the study group was 43 years (range 28-63 years). Seventeen patients had squamous cell carcinoma and 3 had adenocarcinoma. 13 underwent pelvic exenteration and 7 patients underwent radical type 2 hysterectomy with bilateral pelvic lymphnode dissection. In the exenteration group, 8 patients had anterior exenteration, 4 had total exenteration and one had posterior exenteration. Urinary diversion was done by ileal conduit in 8 patients, double barrel colostomy in two and wet colostomy in two patients. There were no immediate postoperative deaths. Operating time, blood transfusions needed and hospital stay was more in the exenteration group compared to radical hysterectomy patients. After pelvic exenteration post-operative complications were seen in 76.9 % of which the most common was of the urinary tract including 3 patients with pyelonephritis, 5 had renal insufficiency and 2 patients developed urinary fistulae. Post-operative morbidity was lower in radical hysterectomy patients. There were two patients in the hysterectomy group who developed vault recurrence while none in the exenteration group had local recurrence. The median follow up time was 19 months (range 9-53 months).Three year overall survival for the entire cohort was 43 %. Median survival time for the exenteration group was 28 months which was significantly higher than 14 months for the radical hysterectomy group. This study shows that radical surgical resection is feasible with good survival outcome and acceptable morbidity in recurrent cancer cervix patients. Radical hysterectomy can be done in selected patients but pelvic exenteration has better long-term survival but with the potential for both short- & long-term complications.

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.

Extramedullary plasmacytoma of the trachea.

Extramedullary plasmacytomas are plasma cell tumors that occur outside the bone marrow. They constitute around 4 % of all plasma cell neoplasms. The most common site of extramedullary plasmacytoma is the upper aerodigestive tract-nasal cavity, paranasal sinuses and oronasopharynx. We are presenting a case of extramedullary plasmacytoma of the trachea. Trachea is an extremely rare site of plasmacytoma. When extraosseous plasmacytoma occur in uncommon sites, the distinction from B cell lymphomas showing extensive plasmacytic differentiation can be difficult and diagnostically challenging.

Rhodococcus equi granulomatous mastitis in an immunocompetent patient.

A 37-year-old immunocompetent woman was evaluated for progressive swelling of her left breast. Magnetic resonance imaging (MRI) showed multiple hypo-intense solid lesions and could not exclude breast cancer. Tissue biopsy was suggestive of granulomatous mastitis without any evidence of malignancy. Culture of the specimen in brain heart infusion broth grew Rhodococcus equi. The patient responded well to combination therapy with ciprofloxacin and azithromycin, and the lesions regressed in follow-up MRI. To the best of our knowledge, this is the first report of R. equi granulomatous mastitis. Accurate identification of this rare pathogen is necessary to provide appropriate treatment in granulomatous mastitis.