Laparoendoscopic hybrid procedure - Oncologically safe and feasible option for gastrointestinal stromal tumours of the stomach.

Minimally invasive resection of gastrointestinal stromal tumours of the stomach is a feasible alternative to the traditional open approach, without the need for advanced laparoscopic training, as lymph node dissection is not necessary and excision with a negative margin is the only requirement. The loss of tactile feedback is a known drawback of laparoscopic surgery, causing difficulty in assessing the margin of resection. Earlier described laparoendoscopic techniques require advanced endoscopic procedures, which are not readily available in all places. We present a novel method wherein we use an endoscope to guide the resection margins during laparoscopic surgery. In our experience of five patients, we were able to successfully use this technique to get the negative margins pathologically. This hybrid procedure can thus be used to ensure adequate margin, keeping all the benefits of laparoscopic surgery.

Factors predicting perioperative outcomes in patients with myasthenia gravis or thymic neoplasms undergoing thymectomy by video-assisted thoracoscopic approach.

BACKGROUND: The purpose of this study was to identify the factors which predict the perioperative outcomes after video-assisted thoracoscopic surgery (VATS) thymectomy in patients with myasthenia gravis (MG) or thymic neoplasms. PATIENTS AND METHODS: Data of consecutive patients who had undergone VATS thymectomy in our institution from August 2016 to April 2018 were collected retrospectively from a prospectively maintained database followed by prospective recruitment of patients who underwent VATS thymectomy from April 2018 to February 2020. RESULTS: A total of 31 patients were included. Females were more common (51.6%), and 29 patients (93.5%) had MG. The most common indication for thymectomy was the presence of both MG and thymoma (51.6%). Most MG patients had moderate disease (55.2%) or severe (24.1%) disease preoperatively. Mean operative time and blood loss were 196.9 ± 63.5 min and 122.5 ± 115.3 ml, respectively. Mean hospital stay was 7.9 ± 6.7 days. The rate of major and minor complications was 16.18% and 35.4%, respectively. Multivariate linear regression analysis established that MG symptoms >12 months, prolonged invasive ventilation (intubation ≥24 h), and complications were associated significantly with a prolonged hospital stay. Adjusting for outliers, pre-operative disease severity (MG Foundation of America class), and intubation ≥24 h were the only factors that had a significant impact on perioperative outcomes. CONCLUSION: Pre-operative disease severity and post-operative invasive ventilation are strong determinants of perioperative outcomes. Pre-operative optimisation and early extubation protocols can further reduce morbidity in patients undergoing thymectomy by the VATS approach.

RRBP1 rewires cisplatin resistance in oral squamous cell carcinoma by regulating Hippo pathway.

BACKGROUND: Chemoresistance is one of the major factors for treatment failure in OSCC. Identifying key resistance triggering molecules will be useful strategy for developing novel treatment methods. METHODS: To identify the causative factors of chemoresistance, we performed RNA sequencing and global proteomic profiling of human OSCC lines presenting with sensitive, early and late cisplatin-resistance patterns. RESULTS: From the common set of dysregulated genes from both the analysis, RRBP1 was identified to be upregulated in both early and late cisplatin-resistant cells with respect to the sensitive counterpart. Analysis of OSCC patient sample indicates that RRBP1 expression is upregulated in chemotherapy-non-responder tumours as compared to chemotherapy-responder tumours. Genetic (knockout) or pharmacological (Radezolid, represses expression of RRBP1) inhibition of RRBP1 restores cisplatin-mediated cell death in chemo-resistant OSCC. Mechanistically, RRBP1 regulates Yes-associated protein1 (YAP1), a key protein in the Hippo pathway to induce chemoresistance. The PDC xenograft data suggests that knockout of RRBP1 induces cisplatin-mediated cell death and facilitates a significant reduction of tumour burden. CONCLUSION: Overall, our data suggests that (I) RRBP1 is a major driver of cisplatin-resistance in OSCC, (II) RRBP1 regulates YAP1 expression to mediate cisplatin-resistance, (III) Radezolid represses RRBP1 expression and (IV) targeting RRBP1 reverses cisplatin-induced chemoresistance in advanced OSCC.

Laparoscopic resection for low rectal cancer in a patient with horseshoe kidney - Technical considerations to prevent iatrogenic injuries.

Horseshoe kidney (HSK) is a rare congenital malformation of the kidneys and is commonly associated with other anomalies of the renovascular and ureteropelvic systems. These anomalies present a surgical challenge, especially for surgeries involving the retroperitoneum. We present the case of a 56-year-old male patient with biopsy-proven rectal cancer who had completed neoadjuvant chemoradiation and was planned for curative resection. Contrast-enhanced computed tomography (CECT) of the abdomen and pelvis revealed the presence of an HSK. Reconstructed three-dimensional (3D) images of the renal vasculature revealed the presence of an accessory renal artery originating directly from the aorta and supplying the isthmus of the HSK without any other venous or ureteral anomalies. Laparoscopic abdominoperineal resection with total mesorectal excision was done without any untoward complications. The presence of HSK per se is not a contraindication for laparoscopic operations involving the retroperitoneum. Pre-operative 3D CECT helps to identify the presence of anatomical variations and guides surgical resection.

Minimally invasive esophagectomy: Preservation of arch of Azygos vein in prone position.

Minimally invasive esophagectomy (MIE) for oesophageal cancer has gained wide popularity in recent years due to its improved morbidity and mortality outcomes. We describe our modified technique of MIE in prone position with preservation of the arch of azygos vein. In our experience with 14 patients, the mean operative duration was 378 min (standard deviation [SD] 378 ± 59 min) and the mean blood loss was 390 ml (SD 390 ± 142 ml). The mean lymph node count was 28 (range 17-54). The Visick score was I in 12 (85.7%) patients and II in 2 (14.3%) patients at follow-up. The preservation of azygos vein arch is a technically feasible procedure and may be associated with a better quality of life outcome.

DDX3 modulates cisplatin resistance in OSCC through ALKBH5-mediated m6A-demethylation of FOXM1 and NANOG.

Platinum based drugs alone or in combination with 5FU and docetaxel are common regimen chemotherapeutics for the treatment of advanced OSCC. Chemoresistance is one of the major factors of treatment failure in OSCC. Human RNA helicase DDX3 plays an important role in cell proliferation, invasion, and metastasis in several neoplasms. The potential role of DDX3 in chemoresistance is yet to be explored. Enhanced cancer stem cells (CSCs) population significantly contributes to chemoresistance and recurrence. A recent study showed that m6A RNA regulates self-renewal and tumorigenesis property in cancer. In this study we found genetic (shRNA) or pharmacological (ketorolac salt) inhibition of DDX3 reduced CSC population by suppressing the expression of FOXM1 and NANOG. We also found that m6A demethylase ALKBH5 is directly regulated by DDX3 which leads to decreased m6A methylation in FOXM1 and NANOG nascent transcript that contribute to chemoresistance. Here, we found DDX3 expression was upregulated in both cisplatin-resistant OSCC lines and chemoresistant tumors when compared with their respective sensitive counterparts. In a patient-derived cell xenograft model of chemoresistant OSCC, ketorolac salt restores cisplatin-mediated cell death and facilitates a significant reduction of tumor burdens. Our work uncovers a critical function of DDX3 and provides a new role in m6 demethylation of RNA. A combination regimen of ketorolac salt with cisplatin deserves further clinical investigation in advanced OSCC.

Impact of the initial phase of COVID-19 pandemic on surgical oncology services at a tertiary care center in Eastern India.

BACKGROUND: The COVID-19 pandemic has caused a global health emergency and affected the resources in both the public and private health sectors significantly. The present study aims to assess the impact of the pandemic on the services by the department in the first 3 months since the first COVID case in the region. METHODS: The study period was from 16 March to 15 June 2020. We queried the database for data on site of the tumor, diagnosis, stage, tumor board decisions and planning, surgical procedures, adjuvant treatment, and follow-up details. The change in tumor board decision and actual treatment taken by the patient were all recorded, taking into consideration the COVID-19 pandemic. RESULTS: Among the 1567 patient contacts, 1306 were out-patient visits and 261 teleconsultations. Fifty-four patients underwent surgery from the 87 admitted to the hospital. Ten preoperative patients and two postoperative patients were tested for COVID and reported to be negative. CONCLUSIONS: The dilemma of providing cancer surgery services to the patients in this pandemic has been global. Strict measures and guidelines can help to overcome the COVID pandemic time, keeping in mind the locoregional logistics.

STAT3- and GSK3ß-mediated Mcl-1 regulation modulates TPF resistance in oral squamous cell carcinoma.

Cisplatin alone or in combination with 5FU (5-fluorouracil) and docetaxel (TPF) are common regimen chemotherapeutics for treatment of advanced oral squamous cell carcinoma (OSCC). Despite the initial positive response, several patients experience relapse due to chemoresistance. The potential role of Bcl-2 antiapoptotic members in acquired chemoresistance is yet to be explored. To address this, we designed two different relevant OSCC chemoresistant models: (i) acquired chemoresistant cells, where OSCC lines were treated with conventional chemotherapy for a prolonged period to develop chemoresistance, and (ii) chemoresistant patient-derived cells, where primary cells were established from tumor of neoadjuvant-treated OSCC patients who do not respond to TPF. Among all Bcl-2 antiapoptotic members, Mcl-1 expression (but not Bcl-2 or Bcl-xL) was found to be upregulated in both chemoresistant OSCC lines and chemoresistant tumors when compared with their respective sensitive counterparts. Irrespective of all three chemotherapy drugs, Mcl-1 expression was elevated in OSCC cells that are resistant to either cisplatin or 5FU or docetaxel. In chemoresistant OSCC, Mcl-1 mRNA was upregulated by signal transducer and activator of transcription 3 (STAT3) activation, and the protein was stabilized by AKT-mediated glycogen synthase kinase 3 beta (GSK3ß) inactivation. Genetic (siRNA) or pharmacological (Triptolide, a transcriptional repressor of Mcl-1) inhibition of Mcl-1 induces drug-mediated cell death in chemoresistant OSCC. In patient-derived xenograft model of advanced stage and chemoresistant OSCC tumor, Triptolide restores cisplatin-mediated cell death and facilitates significant reduction of tumor burdens. Overall, our data suggest Mcl-1 dependency of chemoresistant OSCC. A combination regimen of Mcl-1 inhibitor with conventional chemotherapy deserves further clinical investigation in advanced OSCC.

Invasive micropapillary carcinoma of the breast and bilateral ovarian mature cystic teratoma with benign Brenner tumor in a postmenopausal woman - An uncommon occurrence.

The synchronous occurrence of bilateral ovarian tumors and breast malignancy often raise the suspicion of a Krukenberg tumor or a hereditary breast and ovarian cancer syndrome, both of which are uncommon in clinical practice. A 58-years-old postmenopausal woman had a right breast lump and was diagnosed as infiltrating duct carcinoma, no special type, and incidentally detected bilateral adnexal mass with the clinical suspicion of Krukenberg tumor. However, following the radical surgical excision of the right breast and bilateral ovaries, the right breast showed invasive micropapillary carcinoma (IMPC) while the ovaries showed mature cystic teratoma (MCT) with benign Brenner tumor. IMPC of the breast along with bilateral ovarian MCT with benign Brenner tumor is an unusual clinical occurrence in a postmenopausal female and thus worthy of documentation. It should be categorized as a non-hereditary synchronous tumor. The histomorphology augmented by immunohistochemistry and appropriate clinical context is pivotal in rendering a correct diagnosis.

Essential cancer protein identification using graph-based random walk with restart.

Protein-protein interaction (PPI) network analysis holds significant promise for cancer diagnosis and drug target identification. This paper introduces a novel random walk-based method called essential cancer protein identification using graph-based random walk with restart (EPI-GBRWR) to address this gap. This proposed method incorporates local and global topological features of proteins, enhancing the accuracy of essential protein identification in PPI networks. Starting with meticulous preprocessing of cancer gene datasets from NCBI, including breast, lung, colorectal, and ovarian cancers, and identifying a core set of common genes. The proposed method constructs PPI networks to capture complex protein interactions from these common cancer genes. Topological analysis, including a centrality measures matrix, is generated to perform the analysis to identify essential nodes. The study revealed that 40 essential proteins among breast, colorectal, lung and ovarian cancer showcase the potency of integrative methodologies in unravelling cancer complexity, signalling a transformative era in cancer research and treatment. The strength of the findings from the study has direct clinical relevance in cancer diseases. It contributes to the field of precision medicine to guide personalized treatment strategies.

CK7+/CK20+/CDX2+ mucinous carcinoma, arising in a mature cystic teratoma of ovary, presenting with disseminated metastasis and pseudomyxoma peritonei.

ABSTRACT: Mucinous carcinomas arising within an ovarian dermoid tumor are rare. Most of the cases reported in the literature show morphological features resembling an appendiceal mucinous neoplasm. They exhibit CK7-/CK20+ immunophenotype similar to carcinomas of the lower gastrointestinal tract. In this report, we have described a case of a well-differentiated mucinous carcinoma arising within a mature cystic teratoma. The mucinous carcinoma showed a spectrum of morphological patterns, including cystadenoma-like areas, proliferative/borderline areas, villous adenoma-like areas, and areas of invasive carcinoma. In addition, our case showed some unusual findings, namely, diffuse CK7 positivity, associated pseudomyxoma peritonei, and metastasis to lungs. These features were not demonstrated in any of the previously reported cases. Our case shows that the teratomatous mucinous neoplasm of the ovary may show CK7+/CK20+/CDX2 + immunoprofile making it immunohistochemically indistinguishable from a primary ovarian mucinous neoplasm or a metastatic mucinous carcinoma of the lower gastrointestinal tract.

Primary invasive squamous cell carcinoma of the nipple in an adult male: A case report and brief review of literature.

This is a case report of a rare and uncommon primary invasive squamous cell carcinoma (SCC) of the nipple in a male patient. The patient presented with an ulcerated growth over the left nipple for the last 20 years, which progressed over the last 6 months. He underwent wide local excision with level II axillary lymph node dissection, and one out of 42 lymph nodes harvested showed metastatic deposit. The patient was planned for follow-up with no adjuvant treatment, and had no evidence of local-regional or distant recurrence at 24 months follow-up. The primary invasive SCC of male nipple is very rare, and its diagnosis is challenging as it can be confused with other clinical conditions. However, a histopathological examination with immunohistochemistry can differentiate primary SCC nipple from other differential diagnoses. The treatment options for cutaneous SCC include surgical excision, cryotherapy, electrosurgery, topical ointments, definitive radiation therapy, and photodynamic therapy. Regional lymph node dissection in SCC nipple could potentially have therapeutic and prognostic significance.

Usefulness of Combined Advanced Dynamic Contrast-Enhanced and Diffusion-Weighted MRI Over Ultrasonography in Differentiating Cancer From Benign Lesions in Dense Breasts.

Aim To evaluate the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) in characterizing suspicious lesions in dense breasts compared to ultrasonography (USG). Materials and methods Eighty-two consecutive female patients with suspicious lesions in dense breast parenchyma showing the American College of Radiology Breast Imaging Reporting And Data System (ACR BI-RADS) c/d composition on mammography underwent USG, where 63 lesions of 63 patients were suspicious. They underwent multiparametric MRI, followed by histopathological evaluation (HPE) of the lesions. Statistical analysis was done to calculate the sensitivity, specificity, and accuracy of USG and MRI in lesion characterization and the combined accuracy of DCE-MRI with DWI. The receiver operating characteristic (ROC) curve analysis provided the cut-off for the apparent diffusion coefficient (ADC) value. Results The sensitivity, specificity, and accuracy of USG were 91.7%, 63%, and 79.4%, respectively. Kinetic curve analysis on DCE-MRI showed a type I curve only in benign lesions. Malignant lesions predominantly showed a type III curve. The sensitivity, specificity, and accuracy of DCE-MRI were 95.8%, 78.5%, and 85.7%, respectively. The optimum cut-off ADC value was 1.05x10-3 mm2/s with sensitivity, specificity, and accuracy of 83.3 % each. The specificity and accuracy of combined DCE-MRI with DWI were 94.4% and 88.1%, respectively. Conclusion Advanced MRI, including a combination of DCE-MRI kinetics and DWI, would be more effective and accurate for lesion characterization in dense breasts and act as a superior problem-solving tool compared to USG in differentiating carcinoma from benign lesions.

Triple Positive Oral Squamous Cell Carcinoma Patients Predict Poor Survival Outcomes: Multiple Factor Positivity Warrants the Need for Modified Treatment Approaches.

Objectives: The presence of lymphovascular invasion (LVI), perineural invasion (PNI) and extranodal extension (ENE) have shown adverse outcomes in oral squamous cell carcinoma (OSCC). This study evaluated the impact of LVI, PNI and ENE, individually and in combination, on survival outcomes in OSCC. Material and Methods: A retrospective analysis of a prospectively maintained oral cancer database was done from January 2017 to March 2023. All consecutive OSCC patients who underwent curative intent surgery were included. The triple-positive group was defined by the presence of all three features (LVI/PNI/ENE), while the double-positive group had the presence of two features. The disease-free survival (DFS) and overall survival (OS) analysis was done between different study groups. Results: A total of 255 patients were included in the analysis. The LVI, PNI and ENE positivity was 13%, 26% and 11%, respectively. There were 19 patients (7%) with double-positive and ten patients (4%) with triple-positive disease. The triple-positive group had lower DFS than non-triple-positive (0% vs 57%, p-value 0.001) and lower OS (0% vs 72%, p-value 0.003). The median DFS and OS of the triple-positive group were eight months and 24 months, respectively. Similarly, the double-positive group also had statistically significant inferior DFS (p-value 0.007) and OS (p-value 0.002) compared to the single-positive/triple-negative group. Conclusion: The triple-positive disease had poor outcomes, with no patients achieving disease-free or overall survival at the 5-year follow-up. The presence of multiple adverse factors necessitates modification of adjuvant therapy and therapeutic strategy, which may enhance survival outcomes.

Effect of Preoperative Body Mass Index on Postoperative and Long-Term Outcomes in an East Indian Gastric Cancer Cohort.

BACKGROUND: Gastric cancer is a global health concern with varying clinical outcomes. This study aims to investigate the influence of preoperative Body Mass Index (BMI) on survival in patients who underwent curative resection for gastric cancer in Eastern India. METHODS: Data from a prospectively maintained Surgical Oncology database were analysed for patients who underwent curative resection for primary gastric adenocarcinoma between May 2016 and March 2022. Patients with incomplete data were excluded. Preoperative BMI was categorised into three groups: Underweight (< 18.5 kg/m2), Normal (18.5-22.9 kg/m2), and Overweight/Obese (=23 kg/m2). Clinicopathological details, short-term outcomes, and long-term oncological outcomes were assessed. Statistical analysis included survival estimates, Cox proportional hazard models, and subgroup analysis. RESULT: Of 162 patients, 145 met the inclusion criteria. Patients were predominantly male (68%) with middle or lower socioeconomic status. No significant differences amongst BMI groups were observed in performance score, tumour grade, clinical stage, or short-term outcomes. Postoperative complications and 30-day mortality were similar. However, underweight patients had poorer 4-year disease-free survival (DFS) compared to overweight/obese patients (14.3% vs. 39.7%, p = 0.03). Overweight/obese patients showed significantly better 4-year overall survival (OS) than underweight patients (47.8% vs. 20.4%, p = 0.03). CONCLUSIONS: In Eastern Indian gastric cancer patients undergoing curative resection, preoperative higher BMI (overweight/obese) was associated with better long-term survival. Understanding these findings could guide tailored interventions to improve outcomes in this population.

Correlation of 18-fluorodeoxyglucose uptake values on PET-CT scan with histological prognostic markers in breast cancer.

BACKGROUND: Positron emission tomography-computed tomography (PET-CT) scan utilizes 18-fluorodeoxyglucose (18-FDG), based on the principle of higher glycolytic activity and reduced glucose-6-phosphatase levels in cancer cells. This imaging modality is usually advised in the metastatic evaluation of stage III breast cancer patients. The correlation of maximum standard uptake values of primary lesion with different pathological and molecular markers has not been studied extensively. METHODS: Retrospective analysis of the data was performed from our prospectively maintained breast cancer database. All the patients who had undergone 18-FDG PET-CT scan at initial evaluation for staging between June 2017 and April 2020 were included in the study. One-way ANOVA test or Student's t-test as appropriate was performed to assess the difference of means in maximum standard uptake values (SUVmax) of the primary lesion and axillary nodes with clinical stage, histological grade, molecular subtype. Bonferroni post hoc test was also applied. RESULTS: Out of 388 patients in the breast cancer database, 45 patients met inclusion criteria. There was a significant correlation of molecular subtype (p = 0.029) with SUVmax of the primary lesion. Higher primary SUVmax was associated with higher T stage (p = 0.01) and higher histological grade (p = 0.06). In each molecular subtype, there was an increase in mean SUVmax of the primary lesion with increasing histological grade and vice versa. CONCLUSIONS: SUVmax of the primary lesion in breast cancer patients reflects tumor biology. Higher SUVmax can predict patients with triple-negative breast cancers and higher grades in primary tumors. However, further large-scale validatory studies are essential.

Margin to Depth of Invasion Ratio: A Significant Predictor of Survival in Patients With Oral Cancer.

PURPOSE: A common definition of a clear margin (≥5 mm) in oral squamous cell carcinoma (OSCC) for all stages is a subject of controversy. Studies have shown that even 1- and 2-mm margins are adequate, and few studies have identified dynamic resection margin as a criterion. We aimed to study the margin to depth of invasion ratio (MDR), margin to tumor thickness ratio (MTR), and margin to tumor size ratio (MSR) as prognostic markers for survival. Notably, to our knowledge, this is the first study to evaluate the role of MDR in OSCC. METHODS: A prospectively maintained head and neck cancer database was analyzed from January 2017 to February 2023. The MDR, MTR, and MSR were calculated for each patient. Survival outcomes were analyzed using the Cox proportional model and the Kaplan-Meier method. Akaike's information criterion (AIC) and Bayesian information criterion (BIC) were used to compare different ratio models. X-tiles software was used to identify the optimal cutoff value of MDR. RESULTS: Two hundred eighty patients in the database were assessed, of which 123 eligible patients were enrolled in the study. MDR was an independent predictor of disease-free survival (DFS) on multivariate analysis. The MDR model had the lowest values on AIC and BIC analyses. A cutoff value of 0.5 for MDR showed a significant correlation with DFS and overall survival. CONCLUSION: MDR was the best predictor of recurrence of all the three ratios studied. The minimum safe surgical margin can be calculated by multiplying the depth of invasion by 0.5. This study signifies the role of dynamic resection margin criteria on the basis of MDR in defining clear margins.

Inclusion of Perineural Invasion with AJCC-TNM Staging: Outcomes from a South Asian Cohort of Curatively Treated Gastric Cancer Patients.

BACKGROUND: The incidence of perineural invasion (PNI) in patients with gastric cancer (GC) is high, and patients with PNI positive disease have a poor prognosis compared to PNI-negative disease. The present study aims to study the incidence and evaluate the impact of PNI on the survival outcome of a cohort of South Asian GC patients. MATERIAL AND METHODS: All consecutive patients undergoing curative gastrectomy were included in the study. The incidence of PNI and correlation with different clinico-pathological features and overall survival was performed. RESULTS: A total of 59.54% had PNI-positive disease and the median OS of PNI + ve patients was 29.3 months, while it was not reached in PNI-ve patients. The PNI positivity was a significant prognostic factor for overall survival both on univariate and multivariate analysis. On TNM-PNI staging, those with TNM stage I/II patients with PNI + ve disease had similar OS to all stage III patients (p = 0.835) and were worse than that of PNI-ve patients (p < 0.05). CONCLUSION: The incidence of PNI in gastric cancer is high. The inclusion of PNI with AJCC-TNM staging may better stratify prognostic staging in curatively treated gastric cancer patients.