Impact of Perioperative Systemic Chemotherapy on Survival for Patients Who have Diffuse Malignant Peritoneal Mesothelioma Treated with CRS-HIPEC.

BACKGROUND: The available data on the role of perioperative systemic chemotherapy (SC) for diffuse malignant peritoneal mesothelioma (DMPM) patients undergoing (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is heterogeneous and unstandardized. This study aimed to evaluate the impact of SC on the survival outcomes of DMPM patients undergoing CRS-HIPEC and to identify prognostic factors that affect the decision to administer SC. METHODS: Patients who underwent CRS-HIPEC in the National Cancer Institute Milan (1995-2020) were retrospectively analyzed using propensity score-matching of known covariates. The patients were grouped into three groups: group A (neoadjuvant chemotherapy [NACT] and no-SC), group B (no-SC and adjuvant chemotherapy [ACT]), and group C (NACT and ACT). Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meir method, and prognostic factors were calculated using the Cox-regression method. RESULTS: After a median follow-up period of 45 months (95% confidence interval [CI], 6.348-83.652 months) for group A, 115 months (95% CI, 44.379-185.621 months) for group B, and 88 months (95% CI, 3.296-172.704 months) for group C, the study analyzed 154 DMPM patients consisting of matched group A (NACT: 60 + no-SC: 52 = 112), group B (ACT: 38 + no-SC: 38 = 76), and group C (NACT: 31 + ACT: 31 = 62). The patients undergoing ACT had better 5-year OS and PFS than the patients undergoing NACT. In the multivariate analysis, ACT was significantly associated with improved OS by 48% (hazard ratio [HR], 0.52; 95% CI, 0.280-0.965, p = 0.038). For PFS, the association of ACT did not reach statistical significance (HR, 0.531; 95% CI, 0.266-1.058; p = 0.072). CONCLUSION: The optimum treatment sequence for DMPM is CRS-HIPEC followed by adjuvant chemotherapy for high-risk patients. Upfront surgery appears preferable to NACT for patients amenable to complete CRS.

Outcomes of radical surgical resections for nonmetastatic anorectal melanomas: Experience from a tertiary care centre.

AIM: The outcome of radical surgery in nonmetastatic anorectal melanoma (AM) patients is studied infrequently. Here, we aimed to explore the stage-wise outcomes and the impact of radical resections in these patients. METHODS: In this single-centre retrospective study, data of 154 eligible patients were recorded and analysed. Data were obtained from November 2010 to September 2019 with follow-up until November 2020. Overall survival (OS) and disease-free survival (DFS) was calculated by Kaplan Meir method and univariate analysis of prognostic factors by Cox regression. RESULTS: Of 154 patients, 110 were metastatic (stage III) and 44 were nonmetastatic (stage I:22, stage II:22) and underwent curative resections. Median follow-up was 48 months (14-119 months). A total of 39 patients underwent total mesorectal excisions (TME) and five transanal excision (TAE) were performed. Seven patients underwent extended resections. Stage I and II patients had 3- and 5-year OS of 40% and 36%; and DFS of 45% and 33.2%, respectively. Median OS and DFS were 31 and 24 months, respectively. Stage II (node-positive) patients had better median OS compared to stage III (21 vs. 4 months; p = 0.000), and 54.5% patients had recurrences, most commonly both systemic and nodal (45.83%). Median OS of patients without recurrence was 34 months. CONCLUSION: In this large surgical series of AMs, outcome in stage I and II patients was significantly better than stage III and patients with stage II disease can have acceptable oncological outcomes. Radical surgical resections with or without lymphadenectomy could be considered in these patients. The role of adjuvant systemic therapy and radiation needs to be explored as part of multimodality treatment.

Perioperative therapy in muscle invasive bladder cancer.

Radical cystectomy with bilateral pelvic lymph node dissection is the standard of care for muscle invasive bladder cancer (MIBC). The role of neoadjuvant and adjuvant therapy has evolved over the last 3-4 decades, and neoadjuvant chemotherapy (NACT) has now become the standard recommended treatment. However, there are many nuances to this and the utilization of chemotherapy has not been universal. The optimum chemotherapy regimen is still debated. Adjuvant radiation has a role in high-risk patients although not established and immunotherapy has shown promising results. We reviewed the evidence on NACT and adjuvant chemotherapy (ACT) regimens, NACT versus ACT, and the role of adjuvant radiotherapy and immunotherapy in MIBC.

Rare Variants of Malignant Peritoneal Mesothelioma: a Literature Review.

Primary peritoneal mesothelioma (PM) is a rare and aggressive malignancy that arises from the peritoneum and classified into diffuse malignant peritoneum mesothelioma (DMPM) and borderline variants, viz. multicystic peritoneal mesothelioma (MCPM) and well-differentiated papillary peritoneal mesothelioma (WDPPM). The borderline variants are rarer than conventional DMPM, are less aggressive form accounting for 3-5% of all cases of peritoneal mesothelioma. In this narrative review article, we have discussed the pathogenesis, clinical presentation, natural history, and management of these rarer variants of PM, viz. MCPM and WDPPM. Histologically, MCPM typically consists of small cysts composed of mesothelial epithelium with benign bland cuboidal cells with clear fluids; cells lack cellular atypia and have increased number of mitoses. WDPPM has specific papillary component with myxoid plump cores and single layer of bland mesothelial cells. Both the variants commonly present as incidental finding or symptoms of chronic abdominal pain, chronic pelvic inflammatory disease, pelvic mass, and infertility. In the absence of treatment, these diseases are slow growing with major concerns being that both the variants have malignant transformation capabilities and a high rate of recurrence. In the light of current evidences, it is recommended that MCPM and WDPPM patients should be offered a complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy consisting of cisplatin and doxorubicin. Collaborative multi-institutional studies are needed to generate more data and formulate robust guidelines.

Bidirectional Chemotherapy in Advanced Colorectal Cancer Peritoneal Metastases.

Colorectal cancer (CRC) patients with extensive peritoneal metastases who are not candidates for CRS-HIPEC have poor prognoses. We evaluated the role of systemic and intra-peritoneal (IP) chemotherapy in these patients. CRC patients with confirmed peritoneal metastasis were enrolled. After implantation of IP chemoport patients received weekly IP paclitaxel in incremental doses of 20 mg/m2 with systemic chemotherapy. The primary end-points were the feasibility, safety, and tolerance (perioperative complications), and the secondary end-point was the clinico-radiological response. Patients included in the study were registered between January 2018 and November 2021. IP chemoport was implanted in 18 patients of which 14 patients underwent successful instillation of IP chemotherapy. Four patients did not receive IP chemotherapy in view of port-site infection for which IP ports were removed. The median age was 39 years (range: 19-61 years). The site of the primary tumor was equal in the colon and rectum. Fifty percent of patients had signet ring-cell adenocarcinoma, and 21% had poorly differentiated adenocarcinoma. The median serum of CEA level was 12.27 ng/mL (1.63-116.16 ng/mL). The median PCI score was 25 (18-35). The median number of IP chemotherapy cycles (weekly) was 3.5 (1-12 cycles). In 14.3% of patients, IP chemoport had to be removed due to block and infection. Three, five, and four patients had clinico-radiologically disease progression, stable disease, and partial response, respectively. One patient underwent subsequent successful CRS-HIPEC. There were no grade 3-5 (CTCAE 3.0) complications. Incremental doses of IP paclitaxel with systemic chemotherapy is safe and feasible in selected colorectal adenocarcinoma patients with peritoneal metastases without any serious adverse events.

Management of Abdominal Ewing's Sarcoma: A Single Institute Experience.

Ewing's sarcoma (ES)/primitive neuroectodermal tumors (PNETs) are a rare group of tumors commonly arising from bones, uncommonly from soft tissues, and rarely from abdomen. The aim of the study was to analyze the outcome (recurrence-free survival[RFS]), patient characteristics, role of FDG-PET (fluorodeoxyglucose positron emission tomography) computerized scan, chemotherapy and radiation, and prognostic factors. We retrospectively studied patients diagnosed with abdominal ES/PNET and treated surgically between June 2005 and November 2019. Ten patients were included in the study, with a median age of 36.5 years (19-46 years). The median follow-up was 25 months (3-178 months). The site of origin was the retroperitoneum, small bowel, and abdominal wall in six, two, and two patients, respectively. 70% of patients were treated with induction chemotherapy. R0 resection was achieved in 90% of patients. With chemotherapy, there was significant reduction in tumor size (p = 0.034) with non-significant reduction in SUV max (p = 0.31). The 1- and 2-year RFS were 88.90% and 76.20%, respectively. Pathological peritoneal metastasis and ability to achieve R0 resection were prognostic factors affecting RFS. These patients must be offered multimodality treatment. Induction chemotherapy significantly reduces the tumor size. Pathological peritoneal metastasis and ability to achieving R0 resection significantly affect survival.

Demographics, Pattern of Care, and Outcome Analysis of Malignant Melanomas - Experience From a Tertiary Cancer Centre in India.

BACKGROUND: Treatment of malignant melanoma has undergone a paradigm shift with the advent of immune checkpoint inhibitors (ICI) and targeted therapies. However, access to ICI is limited in low-middle income countries (LMICs). PATIENTS AND METHODS: Histologically confirmed malignant melanoma cases registered from 2013 to 2019 were analysed for pattern of care, safety, and efficacy of systemic therapies (ST). RESULTS: There were 659 patients with a median age of 53 (range 44-63) years; 58.9% were males; 55.2% were mucosal melanomas. Most common primary sites were extremities (36.6%) and anorectum (31.4%). Nearly 10.8% of the metastatic cohort were BRAF mutated. Among 368 non-metastatic patients (172 prior treated, 185 de novo, and 11 unresectable), with a median follow-up of 26 months (0-83 months), median EFS and OS were 29.5 (95% CI: 22-40) and 33.3 (95% CI: 29.5-41.2) months, respectively. In the metastatic cohort, with a median follow up of 24 (0-85) months, the median EFS for BSC was 3.1 (95% CI 1.9-4.8) months versus 3.98 (95% CI 3.2-4.7) months with any ST (HR: 0.69, 95% CI: 0.52-0.92; P = 0.011). The median OS was 3.9 (95% CI 3.3-6.4) months for BSC alone versus 12.0 (95% CI 10.5-15.1) months in any ST (HR: 0.38, 95% CI: 0.28-0.50; P < 0.001). The disease control rate was 51.55%. Commonest grade 3-4 toxicity was anemia with chemotherapy (9.5%) and ICI (8.8%). In multivariate analysis, any ST received had a better prognostic impact in the metastatic cohort. CONCLUSIONS: Large real-world data reflects the treatment patterns adopted in LMIC for melanomas and poor access to expensive, standard of care therapies. Other systemic therapies provide meaningful clinical benefit and are worth exploring especially when the standard therapies are challenging to administer.

Management of locally advanced primary mediastinal synovial sarcoma.

Primary mediastinal synovial sarcoma (PMSS) is a relatively rare disease, and patients are treated predominantly with surgery for resectable disease. Management of locally advanced borderline resectable and unresectable PMSS is not only challenging but also lacks standard guidelines. We present three patients with PMSS, who were unresectable or borderline resectable at presentation and were treated with neoadjuvant chemotherapy followed by surgery and postoperative radiotherapy.

POSSUM: A Scoring System for Perforative Peritonitis.

BACKGROUND AND OBJECTIVES: Perforative peritonitis carries considerable morbidity and mortality with the postoperative period unpredictable most of the times. It therefore becomes necessary for a scoring system that predicts the post-operative outcome. POSSUM (Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity) helps in predicting the post-operative morbidity and mortality in these patients. POSSUM scores are based on 12 physiological factors and 6 operative factors. In our study, we included two more factors, which are specifically important in perforative peritonitis; they are, perforation to operation time and the presence of co-morbidity. The presence of these factors significantly affects the post-operative status. Through this prospective study, we can predict which patients are at a higher risk of death or complication and give appropriate management as necessary. MATERIALS AND METHODS: Our sample size was 50 patients with perforative peritonitis. The study was conducted in single unit from September 2013 to August 2014. Data was collected based on POSSUM scoring system. Outcome of the patients was recorded as death / alive; complicated / uncomplicated and statistical analysis was done by comparing the expected and observed outcomes. RESULTS: By applying linear analysis, an observed to expected ratio of 1.005 was obtained for mortality and 1.001 for morbidity. There was no statistically significant difference between the observed and expected mortality rates (χ(2) = 3.54, p = 0.316) and morbidity rates (χ(2) = 2.40, p = 0.792). It was found to be comparable with other studies. The factors independently studied; perforation to operation time and presence of co-morbidity were statistically significant with respect to outcome (p<0.05). CONCLUSION: Although a small sample size is the limitation of this study, POSSUM scoring system is a good indicator of postoperative outcome in patients with perforative peritonitis and was applicable in our setup. It is useful in identifying high risk patients and give preferential care to them for better outcome. Inclusion of factors like perforation to operation time and co-morbid status can improve the scoring system and better care can be provided.

Splenic Injury in Situs Inversus Totalis - A Surgical Challenge.

Situs inversus totalis is a rare congenital anomaly in which position of the heart and all abdominal viscera is reversed. Situs abnormalities usually go unnoticed but may be recognized by radiography or ultrasonography as an incidental finding or during evaluation for congenital heart diseases. We present such an extremely rare and to the best of our knowledge the third reported case of an injured spleen in the right hypochondrium, following seemingly trivial blunt trauma in a patient with situs inversus totalis who underwent splenectomy. The presence of associated congenital heart defects, visceral anatomical variations and mirror imaging makes the anaesthetic management as well as the surgical exercise a challenging one in such cases.