An eye-opening case of periorbital oedema: a clinicodiagnostic dilemma.

Cutaneous metastasis (CM), a rare occurrence, can produce a variety of skin lesions. Signet-ring cell carcinoma (SRCC) is a very aggressive tumour with low survival rate irrespective of location. We report a case of SRCC with CM presenting with asymptomatic progressive unilateral angio-oedema-like findings. A high index of suspicion and low threshold for biopsy are crucial for early diagnosis of CM as the prognosis is poor, especially when the primary cancer is SRCC.

Constitutional mismatch repair deficiency syndrome: Do we know it?

Constitutional mismatch repair deficiency syndrome is a rare autosomal recessive syndrome caused by homozygous mutations in mismatch repair genes. This is characterized by the childhood onset of brain tumors, colorectal cancers, cutaneous manifestations of neurofibromatosis-1 like café au lait spots, hematological malignancies, and occasionally other rare malignancies. Here, we would like to present a family in which the sibling had glioblastoma, and the present case had acute lymphoblastic lymphoma and colorectal cancer. We would like to present this case because of its rarity and would add to literature.

Immunohistochemical study of Programmed Cell Death Ligand 1 (PDL1) expression by combined positive score using 22C3 clone in head and neck squamous cell carcinomas, its correlation with clinicopathological features and outcome.

Context: Programmed cell death ligand 1 (PD L1) is a transmembrane protein that is highly expressed in neoplastic cells. Therapy with immune checkpoint inhibitors target PD-1/PD-L1 blockade-inducing tumour regression. Immunohistochemistry (IHC) for PD-L1 expression enables patient selection for immunotherapy and can be considered as a potential predictive biomarker for immunotherapy in head and neck squamous cell carcinoma (HNSCC). Aims: To determine the PDL1 expression in HNSCC, to correlate with clinicopathological features and outcome. Settings and Design: We retrospectively analysed 59 cases of HNSCC at our Tertiary Hospital between January 2017 and November 2018 and followed up until death/Nov 2022 for Overall survival. Methods and Material: IHC analysis of PD-L1 using Combined Positive Score (CPS) with antibody clone 22C3 in 59 cases of HNSCC was performed. PD-L1 expression was correlated with clinicopathological features and outcomes. Statistical Analysis Used: Pearson Chi-square test was used to analyse the correlation between PD-L1 expression and clinicopathological parameters using SPSS20.0. Survival curves were calculated by Kaplan-Meier method, and differences were analysed by log-rank test. Results: A total of 25 cases (42.4%) had positive PDL expression (CPS ≥1). 16/25 cases (27.1%) belonged to CPS (≥1, <10). An almost-perfect interobserver agreement was noted by two pathologists for PD-L1 IHC expression. No statistically significant correlation was noted between PD-L1 score and clinicopathologic features. Conclusions: Detection of PD-L1 status gives further insight into frequency of PD-L1 expression in Indian HNSCC patients to possibly improve clinical treatment strategies, ensuring that our patients get the maximum therapeutic benefit of immunotherapy.

A Randomized, Double-Blind, Phase III Study in India for Comparing Efficacy, Safety, and PK of ZRC-3277 (Pertuzumab Biosimilar) With Perjeta® in Patients With HER2-Positive Metastatic Breast Cancer.

INTRODUCTION: To evaluate the efficacy, safety, pharmacokinetics (PK), and immunogenicity of ZRC-3277 (pertuzumab biosimilar) with Perjeta® (pertuzumab) in previously untreated patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). PATIENTS AND METHODS: This phase III, multicenter, double-blind study across 38 sites in India randomized (1:1) patients with HER2-positive MBC in either the ZRC-3277 or Perjeta® group. Both groups also received trastuzumab and docetaxel. Of 268 enrolled patients, mITT population had 243 patients (119 and 124 in the ZRC-3277 and Perjeta® groups, respectively). The primary objective was to compare the between-group objective response rate (ORR) after 6 cycles of treatment. ORR was determined by evaluating scans of computed tomography or magnetic resonance imaging following Response Evaluation Criteria in Solid Tumor (RECIST 1.1). Two-sided 95% confidence interval (95% CI) for the difference in ORR was determined to evaluate the noninferiority of ZRC-3277 to Perjeta®. The secondary outcomes included the assessment of PK, immunogenicity, and safety between the 2 groups. RESULTS: In the mITT population, 104 (87.39%) and 114 (91.94%) participants achieved the ORR in the ZRC-3277 and Perjeta® groups, respectively. For predefined -15% noninferiority margin, obtained 2-sided 95% CIs (-12.19%, 3.11%) for the difference in ORR (-4.55%) between the 2 groups demonstrated the noninferiority of ZRC-3277 to Perjeta®. PK, immunogenicity, and safety were not significantly different between the 2 groups. CONCLUSION: Efficacy, PK, immunogenicity, and safety profiles of ZRC-3277 was found to be similar to those of Perjeta®.

Febrile Neutropenia in Hematological Malignancies: Clinical and Microbiological Profile and Outcome in High Risk Patients.

BACKGROUND AND OBJECTIVES: Febrile neutropenia (FN) is considered a medical emergency. Patients with hematological malignancies (HM) commonly experience FN. Broad spectrum antibiotics have to be started empirically to prevent complications. This study depicts the clinical profile, microbiological profile, antibiotic sensitivity pattern, and outcome in high risk HM. MATERIALS AND METHODS: In this prospective study, 72 patients with hematologic malignancies, diagnosed and treated for 108 high risk febrile neutropenic episodes from August 2011 to January 2013 at a Regional Cancer Center, in South India were analyzed. Cefoperazone-sulbactum was used as a first-line empiric antibiotic. RESULTS: Majority of the patients with FN episodes had acute myeloid leukemia. Overall culture positivity was 29.62%. The most common organisms isolated were Gram-negative bacilli (63.64%), with Escherichia coli being the most frequent pathogen. All Gram-negative organisms were sensitive to imipenem, whereas sensitivity pattern to other antibiotics were as follows: 85.71%, 78.26%, 69.52%, 63.64%, 41.66% and 47.05% for pipercillin-tazoactum, meropenem, cefoperazone-sulbactum, amikacin, ceftazidime, ciprofloxacin respectively. Overall mortality was 13.5%. Most of the patients responded to empiric antibiotic cefoperazone-sulbactum. CONCLUSIONS: In the hematologic malignancies particularly in acute leukemia, there is high risk of developing FN. Empiric therapy with cefoperazone-sulbactum as a first line leads to satisfactory outcome in high risk FN and therapy should be tailored to the most appropriate antibiotics according to the bacterial culture results.

Management of febrile neutropenia in solid organ malignancies following chemotherapy.

BACKGROUND: Febrile neutropenia is a medical emergency and it requires immediate hospitalization for evaluation and administration of empiric broad-spectrum antibiotics. The present study was undertaken to analyze the infectious agents, choice of empiric antibiotics, and outcome in high-risk febrile neutropenia in the solid organ malignancies. MATERIALS AND METHODS: In this study, 92 high risk febrile neutropenic episodes were analyzed in 72 patients with solid organ malignancies. We used cefoperazone-sulbactum as an initial empiric antibiotic. Piperacillin/tazobactum or carbapenems were added to the patients who did not respond to initial antibiotic. RESULTS: Among the 92 episodes treated, most patients received first-line chemotherapy for locally advanced disease. Microbes were isolated in 25% of febrile neutropenic episodes. Gram-negative organism (61.70%) constituted the most common isolates. The most common microbes identified were E. coli and Staphylococcus aureus in blood, Klebsiella pneumonia in sputum and E. coli in urine culture. Patients who had been treated with cefoperazone-sulbactum improved clinically in 70.6% of febrile neutropenic episodes. Second- line antibiotics (piperacillin-tazobactum with amikacin) were required in 24% episodes, while another 5.4% episodes required third-line antibiotics (carbapenems). In this study, mortality was seen in 12% of febrile neutropenic episodes. Staphylococcus aureus was 100% sensitive to linezolid, teicoplanin, and vancomycin, whereas Gram-negative organisms were 100% sensitive to imepenem and meropenem. CONCLUSION: Cephaperazone-sulbactum is a reasonable initial choice for empirical therapy in high risk febrile neutropenic patients in solid organ malignancies.