FOLFOX-4 as second-line therapy after failure of gemcitabine and platinum combination in advanced gall bladder cancer patients.

OBJECTIVE: There is no standard second-line chemotherapy after progression on first-line therapy including gemcitabine and platinum combination in advanced gall bladder cancer patients. So this study was undertaken to assess the efficacy and safety of FOLFOX-4 regimen in this setting. METHODS: In this observational study, patients with performance status ≤2, who progressed on first-line therapy, were enrolled from May 2010 to June 2014. FOLFOX-4 based treatment was administered until progression, unacceptable toxicity or up to 12 cycles. RESULTS: A total of 66 patients were enrolled in this study. The median age of patients was 52.5 years (32-66 years),of which 24 (36.36%) were males and 42 (63.63%) were females. The median number of cycles could be given were 9.5 (2-12). Only 43.93% patients in this study completed full 12 cycles of chemotherapy. Sixteen patients (24.24%) in this study required the dose reduction at least in one cycle of chemotherapy due to toxicities. Disease control rate was seen in 39 (59.09%) patients, with complete response in none, partial response in 16 (24.24%), stable disease in 23 (34.84%) and progressive disease in 27 (40.90%) patients. The median progression free survival was 3.9 months; median overall survival was 7.6 months. The main Grade 3/4 side effects seen were hematological in 31.81% (n = 21) and gastrointestinal in 25.75% (n = 17) patients. Majority of patients (46%) had Grade 1/2 peripheral neuropathy. CONCLUSIONS: FOLFOX-4 is an effective and well-tolerated regimen as a second-line treatment in advanced gall bladder cancer patients. Further studies are required, especially in the Indian subcontinent.

Transoral Robotic Surgery for a Rare Case of Venolymphatic Malformation in Parapharyngeal Space.

Venous malformations are low flow endothelial malformations with aberrant and ectatic venous channels. They are defects in vascular growth which causes functional and cosmetic impairment. Gradual growth in size of the lesion occurs due to venous congestion or thrombosis. Venous malformations in parapharyngeal space are a rare entity and are difficult to diagnose. Case Report. 13 year old boy presented with a history of hyposmia and progressive difficulty in breathing for a duration of 2.5 years. MRI face and neck with contrast showed a 4.5 × 4.3x3.6 cm lesion in the left parapharyngeal space. CT angiogram of brain and neck demonstrated a heterogeneously enhancing mass in the left parapharyngeal region. PET scan illustrated an ill-defined mass in the left pre styloid parapharyngeal space. Biopsy from the lesion showed features consistent with venolymphatic malformation. Flexible laryngoscopy showed a bulge over the left soft palate region with narrowing of nasopharyngeal lumen. Patient underwent transoral robotic surgery for complete excision of the mass. Post-operative period was uneventful. He has been on follow up for the past 1 year with no evidence of any residual or recurrent disease. Venolymphatic malformation is a rare lesion in the parapharyngeal space which is difficult to diagnose pre operatively. Surgical excision is the preferred modality of treatment for deep seated lesions in the parapharyngeal space. The advent of transoral robotic surgery have reduced the morbidity and improved clearance for such cases.

Study of Efficacy and Toxicity of Capecitabine Maintenance After Response to Docetaxel, Cisplatin, and 5-Fluracil-Based Chemotherapy in Advanced Carcinoma Stomach.

BACKGROUND: Advanced gastric cancer is associated with poor survival despite chemotherapy. Maintenance chemotherapy has been successfully tried in lung cancer and colorectal cancers however there is scarce literature on maintenance therapy in advanced gastric cancer. We report a prospective non-randomized single-arm trial of capecitabine maintenance after response to docetaxel, cisplatin, and 5-Flurouracil-based chemotherapy. METHODS: 50 patients with advanced gastric cancer, who had achieved response or had stable disease after 6 cycles of Docetaxel, Cisplatin, and 5-Flurouracil (D 75 mg/m2, C 75 mg/m2, FU 750 mg/m2/d d1-d5, q3 weeks) chemotherapy were prospectively selected to receive maintenance chemotherapy with capecitabine (1000mg/ m2 bid d1-d14 q21 days) until progression. RESULTS: During the median follow-up period of 18 months all patients had progressed, however, there was no treatment-related death, the median time to tumor progression was 10.3 months, with grade 3 and 4 toxicities in 10-15% of patients, and treatment delays in 75% of patients. CONCLUSIONS: Our study has shown that maintenance chemotherapy with capecitabine post-first-line docetaxel, cisplatin, and 5-FU-based chemotherapy is effective and delays tumor progression. However, toxicity was a concern in our study which led to treatment-related delays but without any treatment-related death. Most patients continued therapy till progression.

Analysis of Spatial Heterogeneity of Responses in Metastatic Sites in Renal Cell Carcinoma Patients Treated with Nivolumab.

Background: The purpose was to determine whether tumor response to CPI varies by organ and to characterize response patterns in a group of surgically treated metastatic RCC patients treated with Nivolumab. Methods: A retrospective analysis was undertaken between January 2016 and March 2020 on patients receiving Nivolumab for metastatic RCC, following first-line therapy and having at least one baseline and two follow-up scans. A Fisher's exact test was used to compare categorical variables, and a Kruskal-Wallis test was used to compare continuous variables. Results: Twenty-one out of thirty patients evaluated were eligible, and they were divided into two groups: responders (n = 11) and non-responders (n = 10). According to all iRECIST standards, 18 (85.7 percent) of the 21 patients had PD (10 patients), PR (3 patients), or SD (8 patients). At baseline, 7, 15, 4, 13, 7, and 7 patients, respectively, had detectable hepatic metastasis and lung, brain, lymph node, soft tissue, and other intra-abdominal metastases; these patients were evaluated for organ-specific response. The ORRs for hepatic metastasis and lung, brain, lymph node, soft tissue, adrenals, and other intraperitoneal metastases were correspondingly 10%, 20%, 35%, 0%, and 25%. In total, 13 (61.9%) of them demonstrated varied responses to CPI therapy, with 6 (28.5%) demonstrating intra-organ differential responses. The lymph nodes (35%) had the best objective response (BOR), followed by the adrenals and peritoneum (both 25%), the brain (20%), and the lung (20%). The response rate was highest in adrenal gland lesions (2/4; 50%), followed by lymph nodes (13/19; 68.4 percent) and liver (5/10; 50%), whereas rates were lowest for lesions in the lung (9/25; 36%), intraperitoneal metastases (1/4; 25%), and brain (1/5; 20%). Conclusions: In renal cell carcinoma, checkpoint inhibitors have a variable response at different metastatic sites, with the best response occurring in lymph nodes and the least occurring in soft tissue.

Combined Diagnostic Accuracy of Diffusion and Perfusion MR Imaging to Differentiate Radiation-Induced Necrosis from Recurrence in Glioblastoma.

We aimed to use quantitative values derived from perfusion and diffusion-weighted MR imaging (PWI and DWI) to differentiate radiation-induced necrosis (RIN) from tumor recurrence in Glioblastoma (GBM) and investigate the best parameters for improved diagnostic accuracy and clinical decision-making. Methods: A retrospective analysis of follow-up MRI with new enhancing observations was performed in histopathologically confirmed subjects of post-treated GBM, who underwent re-surgical exploration. Quantitative estimation of rCBV (relative cerebral blood volume) from PWI and three methods of apparent diffusion coefficient (ADC) estimation were performed, namely ADC R1 (whole cross-sectional area of tumor), ADC R2 (only solid enhancing lesion), and ADC R3 (central necrosis). ROC curve and logistic regression analysis was completed. A confusion matrix table created using Excel provided the best combination parameters to ameliorate false-positive and false-negative results. Results: Forty-four subjects with a mean age of 46 years (range, 19−70 years) underwent re-surgical exploration with RIN in 28 (67%) and recurrent tumor in 16 (33%) on histopathology. rCBV threshold of >3.4 had the best diagnostic accuracy (AUC = 0.93, 81% sensitivity and 89% specificity). A multiple logistic regression model showed significant contributions from rCBV (p < 0.001) and ADC R3 (p = 0.001). After analysis of confusion matrix ADC R3 > 2032 × 10−6 mm2 achieved 100% specificity with gain in sensitivity (94% vs. 56%). Conclusions: A combination of parameters had better diagnostic performance, and a stepwise combination of rCBV and ADC R3 obviated unnecessary biopsies in 10% (3/28), leading to improved clinical decision-making.

Study of Gemcitabine Plus Nab-Paclitaxel-Based Chemotherapy Regimen as First-Line Treatment in Metastatic Pancreatic Carcinoma.

Varun GoelBackground The purpose of this study was to study the effectiveness of gemcitabine and nab-paclitaxel combination as first-line chemotherapy regimen for the treatment of metastatic pancreatic cancer. There is scarcity of data regarding efficacy and toxicity profile of this combination in Indian population. Aims and Objectives The primary aim of this study was to assess efficacy of this regimen, for which evaluation done in terms of the objective response rate, progression-free survival (PFS), and overall survival. Safety data were also evaluated. Materials and Methods In this prospective study, gemcitabine plus nab-paclitaxel combination chemotherapy was given as first line in metastatic pancreatic carcinoma patients till progression or appearance of grade 3/4 toxicities with treatment. Results The study was performed in 30 patients comprising 18 (60%) males and 12 (40%) females. The median age was 60 years. Median number of cycles administered were six cycles per patient. Seventeen patients (56.67%) had a partial response and 0% had complete response. A total of seven (23.3%) patients progressed on chemotherapy and six (20%) had stable disease (SD). The disease control rate (responses and SD) was 76.7%. The median PFS was 5.75 months. There was no statistically significant difference in terms of response rates and baseline CA 19-9 levels. Most common toxicities were hematological toxicities with rates of grade 3/4 anemia and neutropenia of 20%. Among nonhematological toxicities, nausea (46.67%) and fatigue (30%) were the commonest. Conclusion Combination of gemcitabine and nab-paclitaxel is active and well tolerated in advanced pancreatic carcinoma. To the best of our knowledge, this is the first such study conducted in India.

Primitive neuroectodermal tumor of the kidney in a young male: Case report and review of literature.

Primitive neuroectodermal tumor of the kidney is a rare tumor. A total of approximately 79 primary renal cases have been reported to date. Primitive neuroectodermal tumors occur preferentially in the soft-tissues of the paravertebral region and chest wall, less frequently in extremities, with a slight male predominance. We report a case of primitive neuroectodermal tumor of the kidney in a 17-year-old male with a pre-operative diagnosis of renal cell carcinoma-stage 4. The patient underwent radical nephrectomy and histopathological examination revealed a highly aggressive tumor of monotonous sheets of round cells with focal areas of rosette formations and high mitotic rate with Ki67 index of 25-30%. Tumor cells were positive for CD 99 confirming the diagnosis of primitive neuroectodermal tumor. Primitive neuroectodermal tumor of the kidney needs to be kept in mind as a differential diagnosis in young adults presenting with a large kidney mass.

Evaluation of apoptosis in skin biopsies of patients of borderline leprosy and lepra type 1 reaction.

BACKGROUND: The role of apoptosis is not clear in leprosy and lepra reactions. OBJECTIVES: To evaluate frequency of apoptosis in skin lesions of borderline leprosy and Type 1 lepra reaction. METHODS: Sixty patients with borderline leprosy (30 with clinically diagnosed Type 1 reaction (T1R) (Group I) and 30 without clinical evidence of reaction (Group II)) were analyzed in this prospective study. Apoptosis was detected by two different methods for comparison, that is, histopathologic examination (HPE) and deoxyribonucleic acid (DNA) fragmentation and electrophoresis. Quantification of apoptotic bodies/10 high power fields (HPF) was also done. RESULTS: Out of 30 cases, apoptosis was detected in 29 cases in Group I and 24 cases in Group II by HPE (P = 0.103), whereas, with the use of DNA electrophoresis it was detected in 24 cases in Group I and 18 cases in Group II (P = 0.091). On quantitative estimation it was found that number of apoptotic bodies are higher in Group I in comparison to Group II (2.77 vs 1.99), which is statistically significant. CONCLUSIONS: There was moderate agreement (κ = 0.47) between the two methods of apoptosis detection. Apoptosis was seen more in patients with T1R both qualitatively (statistically nonsignificant) and quantitatively (statistically significant). Clinical significance of this novel finding is that apoptosis can be used as one of the variables for diagnosis of T1R to increase detection rate.

Evaluation of key histologic variables in skin biopsies of patients of borderline leprosy with type 1 lepra reaction.

BACKGROUND: Leprosy remains an important health problem mainly in the African and South-East Asia regions. Type 1 reaction is an immune-mediated phenomenon known to complicate at least 30% of patients of leprosy. Diagnosing type 1 reaction correctly is important for timely institution of therapy to prevent and treat neuropathy-associated disability and morbidity. There is paucity of literature on definitive criteria for histologic diagnosis of type 1 reaction. This study was conducted to determine the key histologic variables for diagnosing type 1 reaction. METHODS: This was a prospective study recruiting 104 patients with borderline leprosy. Three pathologists blinded to the clinical diagnosis independently assessed the cases. The agreement between each histological variable and clinical diagnosis was then calculated by using Cohen's kappa (Κ) coefficient. RESULTS: Histological diagnosis of type 1 reaction was given to 27 (67.5%) of 40 clinically diagnosed cases of type 1 reaction cases. Histological variables chosen as key variables for histological diagnosis of type 1 reaction were presence of giant cells, dermal edema, intragranuloma edema, granuloma fraction 31-50%, and presence of medium to large giant cells. CONCLUSION: This study has shown that T1R are still underdiagnosed histologically in comparison with clinical assessments. The key variables for diagnosing type 1 reaction were proposed.

Trichomegaly of eyelashes after treatment with erlotinib in carcinoma pancreas.

Epidermal growth factor receptor (EGFR) inhibitors have been widely used for the treatment of epithelial malignancies. A wide spectrum of skin toxicities have been described in patients receiving EGFR inhibitors. Trichomegaly, especially of the eyelashes is a rare side effect of this therapy. We report a case of trichomegaly of eyelashes in a 39-year-old male, a case of carcinoma pancreas. This side-effect of these medications gives prospects as a therapy to stimulate the growth of hair.