Safety and Efficacy of Modified FOLFIRINOX in Unresectable or Metastatic Gallbladder Cancer: A Phase II Pilot Study.

PURPOSE: For unresectable gallbladder cancer (GBC), gemcitabine and platinum is standard combination; however, outcome is poor. We conducted this study to find feasibility of modified flourouracil, oxaliplatin, and irinotecan in this group. MATERIALS AND METHODS: We conducted a prospective, phase II single-arm pilot study. Inclusion criteria were histologically proven GBC and Eastern Cooperative Oncology Group 0-1. Primary end points were overall response rates and overall survival. The following treatment was given: oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, and irinotecan 150 mg/m2, all once on day 1, fluorouracil 2,400 mg/m2 continuous intra-venous infusion over 46 hours repeated every 2 weeks, and maximum 12 doses, with primary granulocyte colony-stimulating factor prophylaxis. RESULTS: Between February 2019 and July 2020, 29 patients with unresectable GBC were enrolled. The median age was 52 years, and 18 were females. The Eastern Cooperative Oncology Group was 0 in 4. Five had bilirubin > normal, and 15 each had high serum alkaline phosphatase and carbohydrate antigen 19-9. Twenty-five patients had stage IV disease, and remaining unresectable locally advanced disease. A median of 8.5 cycles was given, and 11 completed treatment. Nine stopped chemotherapy because of progression, and one because of toxicity, and treatment is ongoing in three. Twenty-two required dose reduction. A treatment delay of 1-2 weeks was seen in 25 patients. Best response was complete response 1, partial response 13 (overall response rate 48.2%), and stable disease 9. Four patients with metastatic disease underwent R0 resection. As on cutoff date, nine are surviving (three without disease). Eighteen died of PD, and in two, cause was unknown. There was no toxic death. The median overall survival and progression-free survival were 309 and 252 days, respectively. Twenty-three patients experienced grade III or IV toxicity, and common were diarrhea (13), vomiting (12), and anemia (7). CONCLUSION: First-line modified flourouracil, oxaliplatin, and irinotecan is feasible in unresectable GBC with encouraging responses. Toxicities are higher but manageable. Higher response rates make this an option to explore in borderline resectable cases.

Molecular targets in GI malignancies - A pathologist's perspective.

Newer molecular diagnostics and improved understanding of cancer pathogenesis have identified multiple pathways that can be potentially targeted with the use of novel therapeutics in development. These developments have ushered cancer therapeutics in newer era of personalized medicine. Same is reflected on current management strategies for advanced gastrointestinal malignancies. Molecular profiling for BRAF and RAS is standard for colorectal cancer while Her2 and PDL1 status is needed for planning therapy of advanced gastroesophageal cancers. Tissue agnostic markers like MSI, TMB and NTRK are making headways in therapeutic armamentarium. While newer targeted therapies against FGFR, EGFR, PI3K-AKT, DDR pathways are showing promising results in initial studies. Here we review traditional as well as upcoming molecular markers in field of GI malignancies, methods of testing and evidence for rational use in clinical practice.

High degree of fluoroquinolone resistance among extrapulmonary tuberculosis patients at a tertiary care center in North India.

Background: The treatment of drug-resistant tuberculosis (TB) involves various regimens. Among them, the most promising antibiotic regimens are fluoroquinolone (FQ) drugs. Drug susceptibility testing (DST) for FQs is not included as routine assessment for baseline TB diagnosis. Limited resources are available about FQ resistance among extrapulmonary TB (EPTB) cases. Methods: A total of 447 culture-positive specimens were subjected to DST for first-line anti-TB drugs (FLDs) and second-line anti-TB drugs. DST was performed using automated mycobacterium growth indicator tube-960 liquid culture techniques. The study was carried out during the period of April 2016 to March 2017. In addition, DST of FQs was also performed in FLD-sensitive strains. Results: Mycobacterium tuberculosis was isolated from 447 specimens. Of the 447 culture-positive EPTB specimens, 54 were rifampicin-resistant (RR)/multidrug-resistant TB (MDR-TB) isolates, 45 isolates were resistant to any drug, and the remaining 348 were sensitive to FLDs. Monoresistance of FQs was observed in 20.4% (11/54) among RR/MDR-TB isolates and 4.3% (15/348) among FLD-sensitive isolates. Conclusion: The high degree of FQ resistance observed in EPTB specimens among drug-sensitive and MDR-TB isolates is alarming. This study reflects the need to expand culture and DST for EPTB cases and include FQs within first-line DST in such settings. Furthermore, there should be a rational use of FQs for the treatment of other diseases.

Induction Therapy with Novel Agents and Autologous Stem Cell Transplant Overcomes the Adverse Impact of Renal Impairment in Multiple Myeloma.

We investigated the impact of renal impairment (RI) on the outcome in multiple myeloma (MM) patients following induction and autologous stem cell transplantation (ASCT). Among 349 patients who received a first ASCT for MM, 86 (24.6%) had RI at diagnosis, defined as estimation of glomerular filtration rate (eGFR) <40 mL/min/1.73 m2 according to the modification of diet in renal disease (MDRD) formula. Post induction reversal of renal function occurred in 68 (79%) patients including complete renal response in 37.2%. Two hundred and fifty-one patients had received novel agents for induction; posttransplant complete response (CR) rates were 71.4% for patients with renal impairment (RI) versus 67.2% in those without RI, p = 0.23. The quality of stem cell collection and days to engraftment were similar except that patients with RI required higher transfusion numbers of packed red cells (p < 0.002) and platelets (p < 0.007). The median overall survival (OS) was 96 months (95% confidence interval [CI] 72.80-119.20) for patients with eGFR ≥40 mL/min, n = 195) versus 62 months (95% CI 28.7-95.3) for 56 patients with RI (eGFR <40 mL/min), p = 0.15. The 5-year OS was 64.6% versus 54.4%, respectively. The median progression-free survival (PFS) was 52 months (95% CI 36.3-67.7) for patients with eGFR ≥40 mL/min versus "not reached" for those with eGFR <40 mL/min p = 0.87; and the 5-year PFS was 48.1% versus 51%, respectively. We conclude that induction with novel agents results in reversal of renal dysfunction in the majority of patients. Consolidation with Hemopoietic Stem Cell Transplantation (HSCT) overcomes the adverse impact of RI on survival.

Pulmonary Cryptococcoma Masquerading as Lung Cancer.

We report a case of pulmonary cryptococcoma, in an adult with recently detected diabetes, mimicking as lung cancer. A 45-year-old gentleman with past history of pulmonary tuberculosis presented with fever, cough with expectoration, pleuritic chest pain and hemoptysis. Chest radiograph and computed tomography revealed right lower lobe mass which significantly enhanced on contrast administration. Ultrasound guided biopsy was done which on histopathological examination showed non-necrotizing granulomas with narrow-based budding yeast cells suggestive of cryptococcosis. Detailed work-up for dissemination of infection was negative. A dramatic response to anti-fungal treatment was observed and the patient is doing fine on follow-up.

Unique Triad of 'Pregnancy, Kala Azar and Hemophagocytic Lymphohistiocytic Syndrome from a Non-Endemic Region'.

India and neighboring Nepal, Bangladesh along with Sudan and Brazil are the four largest foci of visceral leishmaniasis and account for 90% of the world's visceral leishmaniasis (VL) burden, with India being the worst affected. High degree of suspicion is usually based on patient presenting from endemic area with features of pancytopenia hepatosplenomegaly. Hemophagocytic lymphohistiocytic (HLH) syndrome also presents with similar clinical features. Visceral leishmaniasis leading to secondary HLH syndrome is in itself a rare entity while both of these presenting in pregnant patient, to the best knowledge of the authors, is yet to be described in literature.

Disseminated Tuberculosis Masquerading as Metastatic Pancreatic Carcinoma.

Tuberculosis (TB) is highly prevalent in India, but TB of pancreas is rare. It is usually seen in patients with miliary TB and often in immunocompromised host as like in HIV positive patients. Pancreatic TB can present as pancreatic mass, pancreatic abscess or acute or chronic pancreatitis. Pancreatic involvement in tuberculosis can occur via haematological route by contiguity from the adjacent organs. In certain clinical settings, presence of pancreatic mass should alert clinicians regarding possibility of pancreatic TB, especially in endemic areas. With use of appropriate diagnostic tests and proper treatment it is potentially curable.

An Interesting Case of Bilateral Lung Consolidation.

Organising pneumonia is a histopathological entity characterised by intra-alveolar buds of granulation tissue, intermixed myofibroblasts and connective tissue. Cryptogenic organising pneumonia (COP) is characterised by this particular histopathological pattern, along with typical clinical and imaging features, when no other underlying aetiology is found. COP (previously known as bronchiolitis obliterans organising pneumonia [BOOP]) is one of the rare variants of interstitial pneumonias. This condition is characterised by a rapid clinical and radiological improvement with steroid treatment. Here we are reporting a case of COP in adult female with discussion on approach and basic pathophysiology of this type of pneumonia.