PD-L1 Expression in Colorectal Carcinoma Correlates with the Immune Microenvironment.

INTRODUCTION/BACKGROUND: Colorectal carcinoma (CRC) is a common malignancy, with its diverse clinical, pathological, and molecular features. The immune microenvironment of a tumor comprises of interplay between various cells and molecules, and has a significant role in deciding the tumor behavior and overall prognosis. PD-L1 (programmed cell death ligand-1) has been implicated in the regulation of the tumor immune microenvironment (TIME). There is limited data regarding the correlation of PD-L1 expression with immune cell profile in CRCs, especially in the Indian setting. The study aimed to assess the PD-L1 expression in CRC tumor cells and its association with TIME, mismatch repair (MMR), and various other clinicopathological parameters. METHODS: This is a hospital-based, cross-sectional observational study. PD-L1 expression was assessed at the protein level by immunohistochemistry and mRNA level by qRT-PCR. Immune cell markers (CD4, CD8, CD20, FOXP3, and CD163) were interpreted using the ImageJ Fiji platform. RESULTS: Of the 104 cases, 21% were PD-L1 positive and were more common in right-sided CRCs. PD-L1 positive cases showed significantly higher concentrations of all T-cell subsets (CD4+ , CD8+ , and FOXP3+), CD20+ B-cells, and CD163+ macrophages were noted. No statistical significance was seen between PD-L1 expression with clinical profile, pathological subtype, grade or stage, mismatch repair status (proficient vs deficient), and survival. CONCLUSIONS: The present study showed a relatively lower frequency of PD-L1 in CRC from the Eastern Indian cohort. The immune cell concentration in the present study was calculated using image analysis-based objectivised methods. Significant correlation of PD-L1 expression in tumor cells with the tumor-infiltrating immune cells indicated its crucial role in the pathobiology of CRC especially by regulating the TIME. Considering the therapeutic implication of PD-L1 in various malignancies, it may be one of the crucial therapeutic targets in a proportion of cases.

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.

Demographic and clinical profile of 1106 adult soft tissue sarcoma patients: A single institutional prospective database experience from India.

BACKGROUND: Adult soft tissue sarcomas (STS) are rare and diverse. Current management is based on limited literature from the West. Therefore, data from different geographical regions is required, including the low-middle-income countries. This is our experience managing adult sarcomas in the tertiary cancer center of North India. MATERIALS AND METHODS: This is a retrospective analysis of the structured sarcoma database of patients treated in the surgical oncology department between 1992 and 2020. The descriptive analysis includes demography, site distribution, diagnosis, histopathology variations, prior surgical interventions, and stage. RESULTS: A total of 1106 soft tissue sarcoma patients were treated in three decades. Age distribution was 13%, 43%, 31%, and 11% in <20, 21-40, and 41-60 and >60 years, respectively. The male-to-female ratio was 1.73. The anatomical distribution was 17%, 42%, 23%, 7%, 7%, and 3% in upper extremity, lower extremity, trunk, retroperitoneum, head and neck, and viscera, respectively. Overall, 49% of patients had undergone prior suboptimal surgeries at community hospitals. Common histology subtypes were synovial sarcoma (18%), undifferentiated pleomorphic sarcoma (UPS) (13%), dermatofibrosarcoma protuberans (12%), and liposarcoma (9%). A pathological discordance of 13% was identified between the initial and the final histologies. Overall, 61% of tumors were high-grade. Memorial Sloan Kettering Stages II and III were present in 33% and 35% of patients, respectively. CONCLUSIONS: This is one of the largest single institutional experiences of STS from the Asian population. Mostly young adults were affected with male preponderance. The lower extremity and trunk were common subsites. Frequent histologies were synovial sarcoma and UPS. A high rate of suboptimal surgical intervention at the community level and pathological discordance was noted. This study highlights the need to establish prospective structured databases for capturing quality information related to rare malignancies and providing insights for future research.

The rhabdoid variant of adrenocortical carcinoma-Report of three cases and literature review.

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy. Extensive rhabdoid morphology in ACC has been described recently in very few cases. The proportion of rhabdoid morphology and the role of SMARCB1/ INI1 expression in these tumor cells to diagnose the specific variant is not described in the literature. We reviewed the clinicopathological features of nine cases of adrenocortical neoplasm. Out of which, three cases of ACC showed predominant rhabdoid morphology. Large discohesive cells with abundant cytoplasm containing eosinophilic inclusions, eccentric vesicular nucleus, and prominent nucleoli. INI1 immunostain was retained in all cases. We reported the rhabdoid variant of ACC, a novel entity, and its diagnostic approach from their histological mimickers. Identifying more cases of this entity will help to clearly understand the pathogenesis, biologic behaviour, and any specific molecular alterations in the future.

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.

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.

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.

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.

Metronomic Therapy in Palliation of Oral Cancer Patients-A Home Based Approach at the End of Life.

INTRODUCTION: Despite the development of targeted therapies for the management of oral cancer patients, the cost of treatment is a concern in middle- and low-income countries. The present study assessed the feasibility of low-cost metronomic therapy as an alternative treatment modality in patients with unresectable or inoperable oral cancers. METHODOLOGY: The study was a prospective, single-arm study. Unresectable, inoperable, and metastatic lip and oral cavity cancers were started on metronomic therapy, a combination of oral methotrexate 15 mg/m2 once a week and oral celecoxib 200 mg twice daily, as palliative therapy. The primary endpoint was overall survival. The secondary endpoints were a response to metronomic therapy, compliance, and toxicity. RESULTS: From June 2018 to May 2020, 25 patients were started on metronomic therapy. The median age was 60 years. The median overall survival was 8.8 months. At eight weeks of therapy, 11 patients (44%) had a partial response, ten patients had stable disease (40%), and four patients had progressive disease (16%). The compliance with the therapy was 100%, and one patient (4%) developed grade III toxicity. CONCLUSIONS: Considering the resource constraints and cost limitations in low and middle-income countries, oral metronomic therapy in the form of methotrexate and celecoxib should be regarded as a suitable regimen in the palliative treatment of patients with unresectable, metastatic, or advanced, recurrent cancers.

Prophylactic Drain Versus No Drain in Curative Gastric Cancer Surgery-A Randomized Controlled Trial.

BACKGROUND: The adoption of enhanced recovery after surgery protocols has questioned the placement of prophylactic drain after curative gastrectomy. A 2015 Cochrane meta-analysis did not find convincing evidence of routine drain placement in gastrectomy, but the quality of evidence was questioned. The present study compared short-term outcomes of prophylactic drain placement versus no drain in gastrectomy. METHODOLOGY: The study is a prospective, non-inferiority, and randomized controlled trial. Histologically proven adenocarcinoma of the stomach undergoing curative gastrectomy with D2 lymphadenectomy was included in the study. Randomization was done intra-operatively. The primary outcome was a postoperative hospital stay. Secondary outcomes included the return of bowel function, achieving adequate enteral feeding, re-surgery, morbidity, and mortality. RESULTS: One hundred fifty-seven patients were registered, of which 108 patients underwent curative surgery, and were randomized to 54 patients in each group. The median age was 55 years (range: 23-78) and 58.5 years (range: 35-80) in the drain and no drain group. No significant difference was noticed in primary or secondary outcomes in both groups. CONCLUSION: Avoid placing a prophylactic drain is not inferior to drain placement following gastrectomy with D2 lymphadenectomy for stomach adenocarcinoma. So, routine prophylactic drain placement can be avoided.

Signet ring cell lymphoma of follicular type with BCL2 gene rearrangement: A rare case with a short review of literature.

A case of signet ring cell lymphoma of presacral lymph node is reported. The patient was diagnosed as follicular lymphoma on the basis of clinical and laboratory features, including immunohistochemistry (IHC) and gene rearrangement studies. Light microscopy examination showed neoplastic atypical cells with signet ring cell morphology in core biopsy of lymph node that stained for B-cell markers by IHC. In addition, the neoplastic cells expressed CD20, CD10, BCL-2, and BCL-6, indicating follicular center origin. Fluorescence in situ hybridization study demonstrated BCL2 gene arrangement. Especially in the case of deep-seated intra-abdominal lymph nodes with atypical presentation, the differential diagnosis arises with nonhemopoietic tumors, and this needs to be distinguished by specific immunostaining and gene arrangement studies.

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.

Elevated Expression of DNA Methyltransferases and Enhancer of Zeste Homolog 2 in Helicobacter pylori - Gastritis and Gastric Carcinoma.

AIM: The aim of this study was to study the role of key epigenetic regulators pertaining to DNA methylation and histone-modification systems in Helicobacter pylori (HP)-associated gastritis and gastric carcinogenesis. METHODS: The expression of DNA methyltransferase (DNMT-1, 3A, and 3B) and the catalytic subunit of polycomb repressive complex-2 (enhancer of zeste homolog 2 [EZH2]) in gastric carcinomas (n = 104), mucosa adjacent to carcinoma (n = 104), HP-associated gastritis (n = 95), and histologically normal mucosa (n = 31) was assessed by immunohistochemistry and qRT-PCR. RESULTS: The expression of all 3 DNMTs and EZH2 was significantly higher in HP-associated gastritis and carcinoma cases than in those with adjacent and normal mucosa. The expression of DNMT-1 and 3B was maximum in HP-associated gastritis. DNMT-3A showed higher expression in carcinoma-adjacent mucosa than in normal mucosa. Interestingly, the expression of EZH2 was higher in cases of HP-associated gastritis with metaplasia than in those without metaplasia and also in cases of intestinal type of adenocarcinoma. Significant positive correlation of EZH2 was identified with DNMT-1, DNMT-3A, and DNMT-3B. However, none of these markers was associated with survival outcome. CONCLUSION: This study establishes an important role of the key epigenetic regulators in the pathogenesis of both HP-associated gastritis and gastric carcinoma. Higher expression of all the epigenetic markers in the gastritis and their persistence in the carcinoma point toward their implications in HP-driven gastric carcinogenesis. Further, an inter-relation between the 2 arms of epigenetics, namely, DNA methylation and histone-modification in the pathogenesis of gastric carcinoma, is also documented. Given the reversibility of epigenetic phenomenon, these molecules may be of important therapeutic use.

Role of metronomic therapy for advanced oral cancers and predictors of response: Multi-institutional feasibility study.

BACKGROUND: In an era of targeted therapies, patients with cancer in resource-constraint countries continue to struggle to find affordable care. METHODS: The present study is a multicenter prospective single-arm study. Patients with expected delay in surgery, unresectable or metastatic cancers, and patients not suitable for surgery or conventional chemotherapy were included. Oral methotrexate 15 mg/m2 once a week and oral celecoxib 200 mg twice daily was used for metronomic therapy. RESULTS: At 8 weeks, a clinically complete response was seen in 2.5%, partial response in 46.6%, stable disease in 39.8%, and disease progression in 11%. Size less than 4 cm, alveolobuccal subsite, and well-differentiated histology were significantly associated with no disease progression. CONCLUSION: Constraint-adapted approach of using methotrexate and celecoxib is economical with good compliance, minimal toxicity, and good efficacy. It is feasible for use in diverse settings. Individualized selection of patients based on response predictors may maximize metronomic therapy's benefit.

Ergotamine Induced Retroperitoneal Fibrosis.

Retroperitoneal fibrosis (RPF) is an uncommon disease characterised by the presence of fibroinflammatory reaction which starts around the infrarenal portion of the abdominal aorta in the retroperitoneum and frequently entrap the ureter causing obstructive uropathy. Approximately, two thirds of the cases are idiopathic, where aetiopathogenesis is not known. Ergotamine-induced RPF, although rare, is considered under secondary group. The fibrogenic process here is thought to be due to serotonergic activity. We report a case of RPF in a young female with obstructive uropathy who had history of long-term ergotamine intake for migraine. Histopathological evaluation revealed different evolving stages of necrotising vasculitis. In addition, the patient has responded to withdrawal of offending drug along with immunosuppressive therapy. We believe, apart from serotonergic activity, ergotamine can lead to RPF through a vasculitic process which has not been reported earlier.

Primary malignant giant cell tumor of the sternum.

Primary malignant giant cell tumor (PMGCT) is a diagnosis based on the presence of a high-grade sarcomatous component along with a typical benign giant cell tumor (GCT). We report the first case of PMGCT of the sternum in a 28-year-old male with painless swelling over the manubrium sterni. The differential diagnoses of PMGCT and giant cell-rich osteosarcoma were considered. Surgical resection was performed, and the reconstruction was done with a neosternum using polymethyl methacrylate and prolene mesh. At 30 months follow-up, the patient is disease-free.