Tumor burden score as a prognostic factor in patients with intermediate and locally advanced hepatocellular carcinoma undergoing liver resection: an attempt to extend resectability criteria.

BACKGROUND: Surgery is currently recommended as a curative treatment option for hepatocellular carcinomas (HCC) belonging to Barcelona Clinic Liver Cancer (BCLC) stage A only. This study aims to classify various BCLC groups as per Tumor Burden Score (TBS) in an attempt to identify patients who could benefit from resection. MATERIALS AND METHODS: A retrospective analysis of a prospectively maintained database of all patients operated for HCC between January 2010 and July 2022 was performed. TBS was defined as, TBS2 = (maximum tumor diameter)2 + (number of tumors)2. RESULTS: Two hundred and ninety-one patients who underwent resection were staged as per the latest BCLC (A = 219, B = 45, C = 27) staging. Patients were segregated into low (<7.3) and high (>7.3) TBS. With a median follow-up of 36.2 months, the median OS for stages, A and B in the low TBS group was 107.4 and 42.7 months respectively. Median OS was not reached for patients in the BCLC C stage. In patients with high TBS, the median OS for BCLC A, B and C was 42.3, 25.72, and 16.9 months respectively. CONCLUSION: TBS is a significant factor influencing survival in patients of HCC. TBS can be used to stratify patients in BCLC B and C stages and help select patients who would benefit from surgical resection to achieve good long-term survival with acceptable morbidity.

CA 19-9 Surveillance Detects Recurrences Early and Contributes to Improvement in Survival in Resected Ampullary Cancers: Analysis of 572 cases.

OBJECTIVE: To determine the clinical utility of serum CA 19-9 surveillance for detecting recurrences in resected ampullary carcinomas (ACs). INTRODUCTION: Although an established prognostic marker for pancreatic ductal adenocarcinoma, the value of CA 19-9 in resected ACs during follow-up is unknown. METHODS: Retrospective analysis of ACs undergoing pancreaticoduodenectomy at Tata Memorial Centre-Mumbai, from January 2012 to January 2020 was performed. Survival, recurrence patterns, factors associated with recurrences and the utility of CA 19-9 surveillance were assessed. RESULTS: The 5-year OS of 572 included patients with ACs, was 56.4%. There were 251(43.88%) recurrences, majority being distant (n=223). Higher 'T' & 'N' stage, margin involvement, perineural invasion, poor tumour differentiation and pancreatobiliary subtype were associated with poor outcomes. Optimal CA 19-9 level to predict recurrence was 77.85 U/mL (sensitivity-61.22%, specificity-76.67%, AUC-0.711); however, a serial rise was a more accurate predictor (sensitivity-71.05%, specificity-91.67%). The median duration between the first rise in CA 19-9 (>37 U/mL) and radiological evidence of recurrence was 4.04 months. The optimal level of relative rise in CA 19-9 in diagnosing a recurrence was established at 2.79x (sensitivity-46.26%, specificity-83.33%, AUC-0.614). A serial rise and absolute value of >200 U/mL was associated with recurrence in 87% & 92.9% of cases. Recurrence detection & treatment after serum CA 19-9 elevation was associated with superior median survival as compared to recurrence detection without elevation (12.8 mo vs. 7.6 mo, P=0.005). CONCLUSION: Serum CA 19-9 testing during follow-up evaluation detects recurrences early and improves survival in resected ACs, and therefore should be recommended as a routine surveillance test.

Study on disease activity of immunological disorders to correlate with thyroid function and other associated correlations.

Background: Organ-specific immunological disorders involving organ/gland like the thyroid, liver, muscles, pancreas, etc., is a result of autoimmunity which can be with or without association with systemic immunological disorders. The thyroid gland is most commonly involved. We evaluated thyroid dysfunction and ESR among various immunological disorders and their correlation with disease activity and hemoglobin respectively. Material and Methods: A cross-sectional/observational study was conducted by including 110 patients with different immunological disorders who came in as in-patients and outpatients in our institute for 18 months and various data were collected and evaluated to analyze the targeted parameters among the study group. Results: We found a positive correlation between disease activity and thyroid dysfunction in different immunological disorders (only in Rheumatoid arthritis [P = 0.004) and Systemic lupus erythematosus (0.009) and not in other immunological disorders] among the study group. A positive correlation was found between ESR (Mean value - 19.63 and Standard Deviation (SD) - 09.473) and disease activity (only in Rheumatoid arthritis P = 0.0001) where a negative correlation was found between ESR and Hemoglobin (Mean value - 11.07 and SD - 01.91 (P = 0.001) in patients under study. Conclusion: Our study demonstrated a positive correlation between thyroid dysfunction and ESR with disease activity, whereas demonstrated a negative correlation between ESR and Hemoglobin in patients with various immunological disorders under study.

A prospective study to assess cervical scar satisfaction following conventional open thyroidectomy for thyroid cancer.

BACKGROUND: Conventional open thyroidectomy (COT) remains a common method of thyroidectomy in many parts of the world for various reasons. METHODS: In this prospective (cross-sectional) study, we evaluated the scar satisfaction among patients and surgeons following COT using the Patient and Observer Scar Assessment Scale (POSAS) and the Patient Scar Assessment Questionnaire (PSAQ). RESULTS: A total of 116 patients were included. The median age of the patients was 44 years and the majority were women. The median scar length overall was 12.2 cm. On POSAS, the median score for surgeon 1 was 1 (range 1-5), for surgeon 2, it was 2 (range 1-6), and for the patient, it was 1 (range 1-6) suggesting good scar satisfaction. The patient's response in the PSAQ was also echoing similar outcomes with scar satisfaction. CONCLUSIONS: Overall, both the patients and the surgeons seem to be satisfied with the overall scar appearance following COT despite the scar length.

Clinical characteristics, outcomes and prognostic factors in KRAS mutant lung cancers: experience from a tertiary care cancer center in India.

Objectives: Kirsten rat sarcoma viral oncogene homologue (KRAS) mutations in lung cancers, long considered untargetable, have had a recent rise in interest due to promising data of agents targeting KRAS p.G12C. As Indian data are scarce, we sought to identify baseline clinical characteristics, prognostic factors and outcomes of lung cancer patients with KRAS mutations at our hospital. Methods: Patients with KRAS mutant lung cancers treated at our institute from 2016 to 2022 were analysed. Results: 133 patients with KRAS mutant lung cancers were identified. Median age was 57 (interquartile range 28-78) years, and 58 (43.6%) were smokers. 17 (12.7%) had brain metastases. The commonest variant was p.G12C, seen in 53 (39.8%) patients. Six (4.5%) had programmed death ligand 1 (PDL-1) expression >50% by Ventana SP263 PDL-1 assay, and 13 (9.7%) had epidermal growth factor mutation. Of 92 patients with available treatment details, the majority received intravenous chemotherapy, nine (9.8%) received tyrosine kinase inhibitors and four (4.4%) received immunotherapy (pembrolizumab). Median progression-free survival (PFS) with first-line therapy was 6 (95% confidence interval (CI) 2.8-9.2) months and median overall survival (OS) was 12 (CI 9.2-14.8) months. The incidence of brain metastases was higher in patients with G12C mutations (p = 0.025). Brain metastases (HR: 3.57, p < 0.001), Eastern Cooperative Oncology Group performance status (PS) ≥ 2 (HR: 2.13, p = 0.002) and G12C mutation (HR: 1.84, p = 0.011) were associated with inferior PFS, while brain metastases (HR: 4.6, p < 0.001), PS ≥ 2 (HR: 2.33, p = 0.001) and G12C mutation (HR: 1.93, p = 0.01) were associated with inferior OS. Conclusion: This is the largest dataset of KRAS mutant lung cancers from India. Brain metastases were higher in patients with G12C mutations and associated with poorer PFS and OS. G12C mutation and PS ≥ 2 were also associated with inferior PFS and OS. Experience with targeted therapy for KRAS mutations remains an area of future exploration due to the unavailability of these agents in India.

Clinico-Radiological Outcomes in WNT-Subgroup Medulloblastoma.

Medulloblastoma (MB) comprises four broad molecular subgroups, namely wingless (WNT), sonic hedgehog (SHH), Group 3, and Group 4, respectively, with subgroup-specific developmental origins, unique genetic profiles, distinct clinico-demographic characteristics, and diverse clinical outcomes. This is a retrospective audit of clinical outcomes in molecularly confirmed WNT-MB patients treated with maximal safe resection followed by postoperative standard-of-care risk-stratified adjuvant radio(chemo)therapy at a tertiary-care comprehensive cancer centre. Of the 74 WNT-MB patients registered in a neuro-oncology unit between 2004 to 2020, 7 patients accrued on a prospective clinical trial of treatment deintensification were excluded, leaving 67 patients that constitute the present study cohort. The median age at presentation was 12 years, with a male preponderance (2:1). The survival analysis was restricted to 61 patients and excluded 6 patients (1 postoperative mortality plus 5 without adequate details of treatment or outcomes). At a median follow-up of 72 months, Kaplan-Meier estimates of 5-year progression-free survival and overall survival were 87.7% and 91.2%, respectively. Traditional high-risk features, large residual tumour (≥1.5 cm2), and leptomeningeal metastases (M+) did not significantly impact upon survival in this molecularly characterized WNT-MB cohort treated with risk-stratified contemporary multimodality therapy. The lack of a prognostic impact of conventional high-risk features suggests the need for refined risk stratification and potential deintensification of therapy.

Study on Assessing Serum Lactate as an Early Prognostic Determinant in Sepsis Outcome.

BACKGROUND: Apart from being one of the main causes of death, sepsis has recently been considered a chronic critical illness. This has resulted in the implementation of standard treatment recommendations for management, with a focus on the initial phases of treatment. Early detection of sepsis and prognostic grading are now crucial for management. Despite the fact that sequential organ failure assessment score (SOFA), acute physiology, and chronic health evaluation II score (APACHE II) have been widely used in sepsis, there have been shortcomings such as feasibility and many lab parameters involved. As a result, this study was conducted to evaluate the role of serum lactate as an early marker and to compare it to current scoring systems for determining the outcome of sepsis. METHODS AND MATERIAL: This was an observational hospital-based study with 60 individuals recruited over a one-year period from July 2021 to June 2022. Serum lactate, as well as the other laboratory tests required for the computation of SOFA and APACHE II, were performed. The baseline data and the trend of lactate vs standard scores were examined in the first 48 hours, as well as their impact on outcomes in sepsis patients (as measured by mortality rates- patients were followed up for 28 days). The diagnostic accuracy of these scores was calculated using the area under the receiver operating characteristic (ROC) curve (AUROC). RESULTS: The study enrolled 60 people out of a total of 162 people who were screened. The mean age was 48.4 years, with the highest mortality occurring between the ages of 41 and 60 years. Of the total 60 participants, 34 (56.6%) were male, with the respiratory tract being the most common source of infection for sepsis (36.67%). In our study, 46 patients survived while 14 patients died. The mean lactate on admission was 3.1 mmol/L in survivors and 4 mmol/L in non-survivors, whereas APACHE II was 9 and 12.36, and SOFA was 3.63 and 7.79, respectively, in survivors and non-survivors. Serum lactate and prognosis scores were compared in the survivor and non-survivor groups, and the difference in diagnostic accuracy was found to be statistically significant. CONCLUSIONS: Serum lactate can be used as an early recognition marker in patients with a probability of sepsis and serial lactate monitoring has a similar diagnostic accuracy in predicting outcomes as the traditional prognostic scoring systems SOFA and APACHE II.

Treatment Response to Neoadjuvant Therapy in Squamous Esophageal Cancer-Correlation Between Metabolic Response and Histopathology.

PURPOSE: Esophageal cancer is among the leading causes of cancer-related mortality worldwide. Patients presenting with localized and loco-regionally advanced cancer without distant metastases have reasonable survival with multimodality management. Adequate and comprehensive staging is the backbone for proper selection of patients fit for curative treatment. Positron emission tomography (PET) in combination with contrast-enhanced computed tomography (CECT) is utilized as the standard staging modality. Multimodality treatment has been able to achieve evaluable tumor responses including pathological complete response (pCR). It is, therefore, necessary to understand whether the impact of neoadjuvant therapy can be evaluated on imaging, i.e., standardized uptake value (SUV) on PET scan done for response assessment and if this can be correlated with histopathological response and later, with survival. Squamous cell carcinoma (SCC) is more common globally and in the Indian subcontinent; hence, we chose this subgroup to evaluate our hypothesis. METHODS: This is a single institution, retrospective study. Out of the 1967 patients who were treated between 2009 and 2019, 1369 (78.54%) patients had SCC. Out of these, 44 received NACTRT, whereas 1325 received NACT followed by curative surgery. The standardized uptake value (SUV) of 18-fluorodeoxyglucose was recorded during pre- and post-neoadjuvant treatment (NAT) using positron emission tomography (PET). The histopathology of the final resection specimen was evaluated using the Mandard tumor regression grade (TRG) criteria with response being graded from 0 to 5 as no residual tumor (NRT), scanty residual tumor (SRT), and residual tumor We attempted to find a cut-off value of the post neoadjuvant SUV of the primary tumor site which correlated with achievement of better histopathological response. RESULTS: Out of 1325 patients of SCC esophagus who underwent surgery, 943 patients had available data of TRG, and it was categorized into the 0-2 category which had 325 patients (34.5%) and 3-5 category, 618 patients (65.5%). The SUV was taken only from the PET scans done at our institution, so as to achieve a more homogenous cohort, and this was available for 186 patients, 151 from the NACT group and 35 from the NACTRT group. The ROC method was used to find the cut-off for SUV (5.05) in the NACT cohort, which depicted significant difference in the outcome. Out of these, 93 patients who underwent NACT had SUV > 5.05 and 58 had SUV < 5.05. It was found that the subjective and objective histopathological scores correlated at a p value of < 0.0001. Specifically, the majority of cases with SRT tended to be in the 3-5 category of TRG, whereas cases with NRT are predominantly in the 0-2 category. In the ≥ 5.05 category of SUV, there were 76 cases with SRT. In the NACT cohort, the < 5.05 category of SUV, there are 26 cases with SRT and 32 cases with NRT. Among cases with SRT, 74.5% had SUV ≥ 5.05, while 25.5% had SUV < 5.05. Among cases with NRT, 34.7% had SUV ≥ 5.05, while 65.3% had SUV < 5.05 (p value 0.007). No significant association was found in the radio-pathological correlation in the NACTRT group. CONCLUSION: Our study confirms the correlation of post neoadjuvant chemotherapy PET SUV with histopathological response, the cut-off of SUV being 5.05 in our cohort. This confirms the predictive value of FDG PET as demonstrated in other studies. Furthermore, its prognostic value with respect to survival has been verified in multiple other studies. With larger scale randomized studies, we may be able to identify the group of patients who have borderline operability anatomically as well as physiologically, where alternative treatment regimens may be indicated to improve outcomes.

Low-dose versus standard-dose olanzapine with triple antiemetic therapy for prevention of highly emetogenic chemotherapy-induced nausea and vomiting in patients with solid tumours: a single-centre, open-label, non-inferiority, randomised, controlled, phase 3 trial.

BACKGROUND: Olanzapine is an effective antiemetic agent but it results in substantial daytime somnolence when administered at the standard dose. Our aim was to compare the efficacy of low-dose versus standard-dose olanzapine after highly emetogenic chemotherapy in patients with solid tumours. METHODS: This was a single-centre, open-label, non-inferiority, randomised, controlled, phase 3 trial done in a tertiary care referral centre in India (Tata Memorial Centre, Homi Bhabha National Institute, Mumbai). Patients aged 13-75 years with an Eastern Cooperative Oncology Group performance status of 0-2, who were receiving doxorubicin-cyclophosphamide or high-dose cisplatin for a solid tumour were eligible. Patients were randomly assigned (1:1), with block randomisation (block sizes of 2 or 4) and stratified by sex, age (≥55 or <55 years), and chemotherapy regimen, to receive low-dose (2·5 mg) oral olanzapine or standard-dose (10·0 mg) oral olanzapine daily for 4 days, in combination with a triple antiemetic regimen. Study staff were masked to treatment allocation but patients were aware of their group assignment. The primary endpoint was complete control, defined as no emetic episodes, no rescue medications, and no or mild nausea in the overall phase (0-120 hours), assessed in the modified intention-to-treat (mITT) population (ie, all eligible patients who received protocol-specified treatment, excluding those who had eligibility violations and who withdrew consent after randomisation). Daytime somnolence was the safety endpoint of interest. Non-inferiority was shown if the upper limit of the one-sided 95% CI for the difference in the complete control proportions between the treatment groups excluded the non-inferiority margin of 10%. This study is registered with the Clinical Trial Registry India, CTRI/2021/01/030233, is closed to accrual, and this is the final data analysis. RESULTS: Between Feb 9, 2021, and May 30, 2023, 356 patients were pre-screened for eligibility, of whom 275 patients were enrolled and randomly assigned (134 to the 2·5 mg olanzapine group and 141 to the 10·0 mg olanzapine group). 267 patients (132 in the 2·5 mg group and 135 in the 10·0 mg group) were included in the mITT population, of whom 252 (94%) were female, 15 (6%) were male, and 242 (91%) had breast cancer. 59 (45%) of 132 patients in the 2·5 mg olanzapine group had complete control in the overall phase versus 59 (44%) of 135 in the 10·0 mg olanzapine group (difference -1·0% [one-sided 95% CI -100·0 to 9·0]; p=0·87). In the overall phase, there were significantly fewer patients in the 2·5 mg olanzapine group than in the 10·0 mg olanzapine group with daytime somnolence of any grade (86 [65%] of 132 vs 121 [90%] of 135; p<0·0001) and of severe grade on day 1 (six]5%] vs 54 [40%]; p<0·0001). INTERPRETATION: Our findings suggest that olanzapine 2·5 mg is non-inferior to 10·0 mg in antiemetic efficacy and results in reduced occurrence of daytime somnolence among patients receiving highly emetic chemotherapy and should be considered as a new standard of care. FUNDING: Progressive Ladies Welfare Association.

Iron Deficiency Anemia Presenting With Pancytopenia: A Study From India.

INTRODUCTION: Iron deficiency anemia (IDA) is the most common cause of anemia worldwide. IDA is commonly associated with thrombocytosis and normal or slightly decreased leukocyte count. Sometimes it can present with thrombocytopenia, but rarely present with pancytopenia. Here we are presenting six cases of severe iron deficiency presenting with pancytopenia, which responded to iron replenishment. METHODS:  This 12-month observational study was conducted in the Department of General Medicine at a tertiary care Centre in India. All cases of pancytopenia (after exclusion of other causes) with IDA were included. IDA was established with the help of a complete blood count (CBC), peripheral smear examination, serum iron studies, and serum ferritin.  Results: In our study, CBC at four weeks later of iron transfusion without other supplementation showed significant improvement in hematological parameters. CONCLUSION:  Severe iron deficiency is a reversible etiology of pancytopenia. It should be kept as a differential diagnosis of pancytopenia if common causes of pancytopenia are ruled out.

Melioidosis as a Mystique Infection: A Study From Central India.

INTRODUCTION: Melioidosis is caused by the Gram-negative bacilli Burkholderia pseudomallei, which is found in contaminated water and soil and spreads via inhalation, inoculation, and ingestion. Melioidosis manifests diversely in immunocompetent and immunocompromised patients, ranging from asymptomatic to life-threatening respiratory distress, septic shock, localized tissue infection, necrotizing pneumonia, and soft organ abscesses.  Methods: An 18-month observational study was conducted at a tertiary center in central India among various confirmed melioidosis cases, with data gathered and analyzed. Aerobic culture and sensitivity were performed in all studied cases, either in blood/body fluid/localized collection - using blood agar media for the culture and disc diffusion method on Mueller Hinton agar for sensitivity. Other tests, such as radiological imaging, were conducted according to symptoms and signs of localized infection. RESULTS: The melioidosis cases under study were compared on various clinical/presenting parameters. Melioidosis has a variety of risk factors, but we found that, in India, diabetic patients are at a higher risk of this infection, particularly fatal forms, as all of the patients in our study were diabetic. Melioidosis is known to have joint involvement, either as a source of infection or later in the course of the disease. All cases were successfully treated with antibiotics and surgical procedures, demonstrating the significance of determining disease etiology, early diagnosis, and rapid early management. CONCLUSION:  Melioidosis is a potentially fatal disease, particularly in diabetics, with a wide range of symptoms and complications. Physicians face a variety of challenges, including clinical symptoms resembling other chronic illnesses, such as tuberculosis, delays in laboratory confirmation, underdiagnosis, reduced reporting, and a lack of suspicion. Because there are very little data and it is a seldom reported infection from central India, we are publishing a study on seven melioidosis patients.

An Assessment of Thyroid Dysfunction and Related Parameters in Patients With Systemic Autoimmune Disorders.

Background and objective Systemic autoimmune disorders involve abnormal immune responses leading to tissue damage. Dysfunction of the thyroid gland due to autoimmune mechanisms is common in such disorders, which can cause either hypofunctioning or hyperfunctioning of the gland. This study aimed to investigate the prevalence of thyroid dysfunction among patients with various systemic autoimmune disorders. Material and methods This cross-sectional observational study included 110 adult patients either diagnosed with or having clinical/biological features of systemic autoimmune diseases. The patients underwent a detailed clinical history assessment, physical examination, and necessary investigations. Data were analyzed using IBM SPSS Statistics for Windows, Version 26.0. (IBM Corp., Armonk, NY). Results Among the 110 autoimmune disorder patients, 22.7% had thyroid dysfunction, specifically hypothyroidism, while 77.3% were euthyroid. Hypothyroidism was prevalent among patients with rheumatoid arthritis (RA, 20.3%), systemic sclerosis (SSc, 20%), ankylosing spondylitis (AS, 15.8%), and systemic lupus erythematosus (SLE, 54.5%). Moreover, 60% of patients were anemic, and the prevalence of anemia was higher among female patients and younger individuals. Conclusions This study showed a higher prevalence of thyroid dysfunction, particularly hypothyroidism, in patients with systemic autoimmune disorders. Female patients and younger individuals were more susceptible to autoimmune disorders, thyroid dysfunction, and anemia. These findings highlight the need for simultaneous screening and evaluation for thyroid dysfunction and anemia in systemic autoimmune disease patients, particularly in female patients and those of younger age groups.

An Immunocompetent Adult Male Presented with a Liver Abscess Caused by the Mycobacterium tuberculosis: A Case Report from India.

A liver abscess is a collection of purulent fluid in the liver parenchyma caused by a variety of etiological organisms such as bacteria, protozoa, and in rare occasions fungi. Mycobacterium tuberculosis (MTB) is a frequent and widespread infection in underdeveloped nations such as India, which can manifest in many ways. Tuberculosis mostly affects the lungs, although it can also affect any organ in the body. We are reporting a case of liver abscess caused by MTB infection in order to raise general awareness among physicians about the importance of suspecting and ruling out tuberculosis as a cause of liver abscess. To the best of our knowledge, there have been very few such cases reported from India/the rest of the world.

Identification of key gene signatures for the overall survival of ovarian cancer.

BACKGROUND: The five-year overall survival (OS) of advanced-stage ovarian cancer remains nearly 25-35%, although several treatment strategies have evolved to get better outcomes. A considerable amount of heterogeneity and complexity has been seen in ovarian cancer. This study aimed to establish gene signatures that can be used in better prognosis through risk prediction outcome for the survival of ovarian cancer patients. Different studies' heterogeneity into a single platform is presented to explore the penetrating genes for poor or better survival. The integrative analysis of multiple data sets was done to determine the genes that influence poor or better survival. A total of 6 independent data sets was considered. The Cox Proportional Hazard model was used to obtain significant genes that had an impact on ovarian cancer patients. The gene signatures were prepared by splitting the over-expressed and under-expressed genes parallelly by the variable selection technique. The data visualisation techniques were prepared to predict the overall survival, and it could support the therapeutic regime. RESULTS: We preferred to select 20 genes in each data set as upregulated and downregulated. Irrespective of the selection of multiple genes, not even a single gene was found common among data sets for the survival of ovarian cancer patients. However, the same analytical approach adopted. The chord plot was presented to make a comprehensive understanding of the outcome. CONCLUSIONS: This study helps us to understand the results obtained from different studies. It shows the impact of the heterogeneity from one study to another. It shows the requirement of integrated studies to make a holistic view of the gene signature for ovarian cancer survival.