Clinical and Immunological Features, Genetic Variants, and Outcomes of Patients with CD40 Deficiency.

PURPOSE: Inherited deficiencies of CD40 and CD40 ligand (CD40L) reflect the crucial immunological functions of CD40-CD40L interaction/signaling. Although numerous studies have provided a detailed description of CD40L deficiency, reports of CD40 deficiency are scarce. Herein, we describe the characteristics of all reported patients with CD40 deficiency. METHODS: The PubMed, Embase and Web of Science databases were searched for relevant literature published till 7th August 2023. Study deduplication and identification of relevant reports was performed using the online PICO Portal. The data were extracted using a pre-designed data extraction form and the SPSS software was used for analysis. RESULTS: Systematic literature review revealed 40 unique patients with CD40 deficiency. Respiratory tract and gastrointestinal infections were the predominant clinical manifestations (observed in 93% and 57% patients, respectively). Sclerosing cholangitis has been reported in nearly one-third of patients. Cryptosporidium sp. (29%) and Pneumocystis jirovecii (21%) were the most common microbes identified. Very low to undetectable IgG levels and severely reduced/absent switch memory B cells were observed in all patients tested/reported. Elevated IgM levels were observed in 69% patients. Overall, splice-site and missense variants were the most common (36% and 32%, respectively) molecular defects identified. All patients were managed with immunoglobulin replacement therapy and antimicrobial prophylaxis was utilized in a subset. Hematopoietic stem cell transplantation (HSCT) has been performed in 45% patients (curative outcome observed in 73% of these patients). Overall, a fatal outcome was reported in 21% patients. CONCLUSIONS: We provide a comprehensive description of all important aspects of CD40 deficiency. HSCT is a promising curative treatment option for CD40 deficiency.

Modality of Radiotherapy and Overall Survival in Pediatric Diffuse Brainstem Gliomas: Implications for Resource-Constrained Settings.

BACKGROUND: Childhood diffuse brainstem glioma (dBSG) is a rare tumor with a poor prognosis. Any tumor-directed surgical intervention is difficult. Magnetic resonance imaging forms the mainstay of diagnosis and radiation therapy has remained the backbone of therapy. In this study, we compare the outcomes of conformal radiotherapy with conventional therapy in the context of resource-constrained settings. METHODS: In this retrospective analysis, conducted between 2010 and 2019, all pediatric patients with a diagnosis of dBSG were analyzed. The survival data were calculated in months from the date of diagnosis. Survival differences between variables were compared using the Log-rank test and the risk of death was calculated using Cox regression analysis. RESULTS: A total of 20 patients (11 males, 55%) with a diagnosis of dBSG were included. Median age at diagnosis was 6.5 years. No surgical resection or biopsy was done in any patient. Fifteen (75%) patients received radiotherapy and only 4 (20%) patients received additional chemotherapy. Five (25%) patients did not receive any form of anti-cancer therapy. Median overall survival (OS) was 8 months (95% CI 5.2-10.8). Females were at a higher risk of death than males. Children treated with radiotherapy had a longer OS than untreated children; however, the modality of radiotherapy employed or the addition of chemotherapy did not affect the OS. CONCLUSION: Radiotherapy, irrespective of the modality, increases the survival of children with dBSG in resource-poor settings. Additionally, socioeconomic concerns need to be addressed in the management of these tumors, especially in the case of female children. Lay summaryChildhood diffuse brainstem glioma (dBSG) is a rare tumor with a poor prognosis. Any tumor-directed surgical intervention is difficult. Magnetic resonance imaging forms the mainstay of diagnosis and radiation therapy has remained the backbone of therapy. In this 10-year retrospective study, we compare the outcomes of conformal radiotherapy with conventional therapy in the context of resource-constrained settings. A total of 20 patients with a diagnosis of dBSG were included with a median age at diagnosis of 6.5 years (5.25-8.75). No surgical resection or biopsy was done in any patient. Fifteen (75%) patients received radiotherapy and only 4 (20%) patients received additional chemotherapy. Five (25%) patients did not receive any form of anti-cancer therapy. Median overall survival (OS) was 8 months (95% CI 5.2-10.8). Females were at a 3.4-fold (95% CI 1.0-12.1) higher risk of death than males. Children treated with radiotherapy had a longer OS than untreated children; however, the modality of radiotherapy employed or the addition of chemotherapy did not affect the OS. Radiotherapy, irrespective of the modality, increases the survival of children with dBSG in resource-poor settings. Additionally, socioeconomic concerns need to be addressed in the management of these tumors, especially in the case of female children.

Impact of the Interval between Neoadjuvant Chemotherapy and Gastrectomy on Pathological Response and Survival Outcomes for Patients with Locally Advanced Gastric Cancer: A Meta-analysis.

Background: It is still unknown what is the appropriate time between neoadjuvant chemotherapy (NACT) and gastrectomy in cases of gastric cancer. To comprehend the relationship more clearly between waiting time after NACT before having a gastrectomy and survival results, a meta-analysis was done. Methods: Retrospective and prospective research from the PubMed, Embase, and Cochrane Library databases were thoroughly reviewed. Research examining the impact of delays of 4, 4-6, and above 6 weeks between the conclusion of NACT and surgery in patients with locally advanced gastric cancer qualified as eligible studies. The pathologic complete response (pCR) rate served as the main outcome indicator. Additional outcome metrics were overall survival (OS) and survival free of illness. Results: The meta-analysis showed that patients with locally advanced gastric cancer with a waiting time for surgery of above 4 weeks compared to those with a waiting time for surgery of below 4 weeks saw a significantly higher pCR rate (pCR) [odds ratio (OR): 1.67; 95% confidence interval (CI): 1.07-2.60; p = 0.02]. The meta-analysis found no appreciable OS differences [hazard ratio (HR): 0.93; 95% CI: 0.76-1.13; p = 0.44). Conclusions: Time to surgery (TTS) had no effect on the survival results, according to our data. Only in the group where delaying surgery by more than 4 weeks after the end of NACT improved pathological response, but had no effect on survival. How to cite this article: Naveed S, Banday SZ, Qari H, et al. Impact of the Interval between Neoadjuvant Chemotherapy and Gastrectomy on Pathological Response and Survival Outcomes for Patients with Locally Advanced Gastric Cancer: A Meta-analysis. Euroasian J Hepato-Gastroenterol 2022;12(2):81-91.

Patterns of Treatment and Outcomes in Epithelial Ovarian Cancer: A Retrospective North Indian Single-Institution Experience.

PURPOSE: Ovarian cancer (OC) is ranked as the third most common gynecologic cancer in various Indian cancer registries. In India, OC is seen in the younger age group, with a median age < 55 years being reported by most of the studies. The majority of patients are diagnosed in advanced stage (70%-80%), where the long-term (10-year) survival rate is poor, estimated at 15%-30%. The aim of this study was to evaluate clinical epidemiology, treatment patterns, and survival outcomes in patients with epithelial OC. METHODS: This was a retrospective analysis of patients with epithelial OC who were treated at Sher-i-Kashmir Institute of Medical Sciences, Srinagar, over a period of 9 years, from January 2010 to December 2018. RESULTS: OC constituted 2.94% of all cancers registered. Epithelial OC constituted 88.4% of all OCs, with a median age 50 years. More than two third of patients belonged to rural background and the majority (76.9%) of the patients were in stage III or IV at the time of diagnosis. The main presenting symptoms were abdominal distension/bloating (46.5%) and gastrointestinal disturbances (35.2%). The most common histologic types were serous (65.9%) followed by mucinous carcinoma (15%). Median overall survival for the whole study cohort was 30 months (95% CI, 28.0 to 31.9). Median overall survival for stage I, II, III, and IV was 72, 60, 30, and 20 months, respectively. CONCLUSION: Most of the patients presented in advanced stage of the disease and have poor outcome. Delay in diagnosis and improper management before registering in tertiary cancer center and lack of tertiary care facilities are the root causes of poor outcomes. The general population and primary care physicians need to be made aware of OC symptoms.

ABO Blood Group and the Risk of Esophageal Squamous Cell Carcinoma in Kashmir, a High Risk Region.

BACKGROUND: ABO blood group has been linked with a number of diseases including cancer. Association of ABO blood type with esophageal squamous cell carcinoma (ESCC) has been sparsely reported and the results are inconsistent. We undertook this study to analyze if any association exists between the ABO and Rh blood groups and ESCC risk. METHODS: We conducted a hospital-based case control study to analyze ABO and Rh blood groups in patients with histologically proven diagnosis of ESCC and compared them with healthy donors from the same population. ABO and Rh blood group status of general population was obtained from the blood bank at Sher-i-Kashmir Institute of Medical Sciences (SKIMS) and from original articles published from time to time. Chi-Square test was performed to look for statistical significance. RESULTS: For this study, 206 patients were prospectively enrolled. Seventy-four (35.9%) patients had blood group O. Blood groups type A and type B was found each in 59 (28.6%) patients. In 108,014 healthy donors, 35.3% had blood type O followed by type B (33.66%). There was no significant difference in any of the blood types between patients with ESCC and donors (P = 0.31). CONCLUSION: No association exists between ABO blood type and the risk of ESCC.