Bioactive nutraceutical ligands and their efficiency to chelate elemental iron of varying dynamic oxidation states to mitigate associated clinical conditions.

The natural bioactive or nutraceuticals exhibit several health benefits, including anti-inflammatory, anti-cancer, metal chelation, antiviral, and antimicrobial activity. The inherent limitation of nutraceuticals or bioactive ligand(s) in terms of poor pharmacokinetic and other physicochemical properties affects their overall therapeutic efficiency. The excess of iron in the physiological compartments and its varying dynamic oxidation state [Fe(II) and Fe(III)] precipitates various clinical conditions such as non-transferrin bound iron (NTBI), labile iron pool (LIP), ferroptosis, cancer, etc. Though several natural bioactive ligands are proposed to chelate iron, the efficiency of bioactive ligands is limited due to poor bioavailability, denticity, and other related physicochemical properties. The present review provides insight into the relevance of studying the dynamic oxidation state of iron(II) and iron(III) in the physiological compartments and its clinical significance for selecting diagnostics and therapeutic regimes. We suggested a three-pronged approach, i.e., diagnosis, selection of therapeutic regime (natural bioactive), and integration of novel drug delivery systems (NDDS) or nanotechnology-based principles. This systematic approach improves the overall therapeutic efficiency of natural iron chelators to manage iron overload-related clinical conditions.

Pre-phase strategy to mitigate first cycle effect in diffuse large B cell lymphoma.

CONTEXT: Treatment-related toxicities in DLBCL (diffuse large B cell lymphoma) patients are higher in the initial phase of treatment (first cycle effect). Implementation of pre-phase treatment before definitive chemotherapy had been shown to alleviate some of these side-effects in a non-randomized study conducted earlier in our institute (Lakshmaiah et. al., Eur J Haematol 100:644-8, 2018). AIMS: This study was aimed at validating the role of pre-phase treatment in newly diagnosed DLBCL patients. SETTINGS AND DESIGN: All newly diagnosed patients with DLBCL above the age of 18 years were evaluated for eligibility and prospectively enrolled. A single-arm prospective study was conducted at the Department of Medical Oncology, in our institute from July 2015 to December 2019. METHODS AND MATERIAL: Patients received vincristine and prednisolone as pre-phase treatment for 7 days after which definitive chemotherapy was instituted on day 1. They were followed up for 30 days post-first cycle chemotherapy. STATISTICAL ANALYSIS USED: Paired Student's t tests and Wilcoxon signed-ranks test were used for comparison of various clinical variables as appropriate. P value of less than 0.05 was considered significant. RESULTS: Among the 180 patients who were included in study, performance status improvement was noted in significant number of patients (p < 0.001). 38.4% achieved an ECOG (Eastern Cooperative Oncology Group) performance status of 0 post-pre-phase therapy. Febrile neutropenia was observed in 12.8% in the present cohort as compared to the historical non-pre-phase cohort (34%). CONCLUSIONS: Pre-phase therapy significantly improves the performance status and diminishes neutropenia rates in DLBCL patients.

Comparison Between CHOP and DAEPOCH with or Without Rituximab in Adult High Grade B Cell Lymphoma, Not Otherwise Specified; A Retrospective Study From a Tertiary Cancer Hospital in South India.

Lymphoma that on morphology appear blastoid or intermediate between DLBCL and BL but who lack myc and bcl-2 and/or bcl-6 rearrangements are grouped under high grade B-cell lymphoma, not otherwise specified (HGBL, NOS). Only a few studies have yet compared the outcome of HGBL, NOS treated with different chemo-immunotherapy regimens. HGBL, NOS patients were analyzed retrospectively, who were treated with CHOP or DAEPOCH regimens every 21 days for six cycles with or without rituximab. The primary clinical objective was progression free survival. One and two year PFS rates were 29.4% and 20.6% for the CHOP arm and, 65.2% and 47.8% for the DAEPOCH arm respectively. There was statistically significant difference in mean PFS between the arms (DAEPOCH vs CHOP: 19.7 months vs 12.8 months; HR = 0.44, p = 0.02, 95% CI: 0.22-0.88). One and two year OS rates were 91.1% and 20.5% for the CHOP arm and 95.6% and 60.8% for the DAEPOCH arm respectively. Mean OS was significantly better for DAEPOCH arm (28.1 months vs 20.7 months: HR = 0.43, p = 0.03, 95% CI: 0.20-0.92). Grade 3 and 4 hematological and non-hematological toxicities were more common in DAEPOCH arm. There were 2 treatment related deaths, 1 in each arm (4.3% for DAEPOCH vs 2.9% for CHOP). HGBL, NOS is a heterogeneous group of aggressive lymphoma associated with early relapse in nearly half of the cases. Intensive regimens like DAEPOCH is associated with improved outcome in terms of PFS and OS. Though toxicities are more with DAEPOCH, they are manageable and treatment related mortality is low.

Candida albicans biofilm formation and growth optimization for functional studies using response surface methodology.

AIM: Optimization of Candida albicans growth and biofilm formation is essential for understanding the recalcitrance of this pathogen to advance functional analysis on hospital tools and material surfaces. Optimization and quantification of biofilm have always been a challenge using the conventional one variable at a time (OVAT) method. The present study uses central composite design-based response surface methodology for optimization of conditions to induce growth and biofilm formation in Candida albicans on polystyrene microtiter plates. METHODS AND RESULTS: Statistical software package, Stat Soft®, STASTICA version 12.6 was used for data analysis. The variables considered in the design matrix were media pH, temperature, incubation period, shaker speed and inoculum size. A four-pronged quantification approach with XTT assay (cell viability), crystal violet assay (biofilm), calcofluor white assay and wet/dry weight measurements (cell mass) was used to understand different aspects of biofilm formation. Cell viability and cell mass were inversely related; however, biofilm was independent of these two factors. The study also highlighted the fact that foetal bovine serum does not significantly contribute to cell adhesion and in turn in vitro biofilm formation in some of the cultures. CONCLUSIONS: A high-throughput optimization of C. albicans growth and biofilm formation on polystyrene microplate has been developed and validated. SIGNIFICANCE AND IMPACT OF STUDY: This is a first time approach to optimize the interaction of parameters for C. albicans biofilm formation using RSM. Heterogeneity in growth conditions for local strains of C. albicans clinical isolates was observed. This microtiter plate-based method can be used for future screening of therapeutics for the control of C. albicans.

Discordance in clinical versus pathological staging in breast cancer: Are we undermining the significance of accurate preoperative staging in the present era?

BACKGROUND: The present era of individualized treatment for breast cancer is influenced by the initial disease status including the anatomical extent, grade, and receptor status. An accurate preoperative staging is the basis of treatment planning and prognostication. Our study aims to determine the discordance between the preoperative clinical and the postoperative pathological stages of breast cancer patients. METHODOLOGY: The medical records of all non-metastatic breast cancer patients from January 2017 to December 2018 who underwent upfront surgery were reviewed. They were staged as per the eighth AJCC and the concordance between the clinical (c) and pathological T (tumor), N (nodal), and final AJCC stage was studied. A Chi-square test was used to determine factors that significantly correlate with disease discordance. RESULTS: A total of 307 breast cancer patients were analyzed. Among these, 43.3% were hormone receptor-positive, 30.6% were Her2 positive and 26% were triple-negative. Overall stage discordance was seen in 48.5% (n = 149) patients (upstaging in 22.1%, downstaging in 26.4%). The discordance rate was 48.9% for T stage (cT versus pT) and 57.4% for N stage (cN versus pN). Among patients with clinically node-negative disease, 53.4% were found to have positive nodes on histopathology, while 27.2% had vice versa. Overall, the factors associated with upstaging were ER-positive, Her2 positive and triple-negative status (all p < 0.05), while none of the factors showed significant association with downstaging. CONCLUSIONS: About half of breast cancer patients had discordance between clinical and pathological staging with higher discordance in the nodal stage. This changes the disease prognosis, and may also affect the offered surgical treatment and radiotherapy. Thus highlighting the need for a precise pre-operative staging. Also, this information will aid clinicians in discussions with patients, keeping in mind the likelihood of change in disease staging and management.

Rapidly Progressing Plasma Cell Leukemia with Underlying Plasmablastic Morphology: A Rare Case Report of a 25-Year Old Male.

Multiple myeloma constitutes a wide spectrum of diseases, ranging from slow-growing monoclonal gammopathy of undetermined significance to rapidly progressing plasma cell leukemia. It is a very rarely diagnosed hematological malignancy in those less than 30 years of age. A 25-year-old male presented with complaints of fatigue and low-grade fever. On investigation, he was found to have bicytopeina and features of tumor lysis syndrome. Initially, this was thought to be indicative of acute leukemia. However, upon further analysis with bone marrow biopsy, serum protein electrophoresis, and immunofixation, it was determined that the patient had an IgG myeloma with plasmablastic morphology. It rapidly progressed and the peripheral smear started showing clusters of plasma cells suggesting a picture of plasma cell leukemia. The patient succumbed to this aggressive disease despite treatment. This case illustrates that myeloma should also be included in the differential diagnosis for young patients, especially the rare plasmablastic variant, which can be misdiagnosed as acute leukemia. The aggressive morphology also tends to show rapid progression to plasma cell leukemia, which has a poor prognosis.

A Pilot Study on the Addition of Tramadol or Eutectic Mixture of Local Anesthetics (Prilocaine Plus Lignocaine) to Local Lignocaine Infiltration for Prevention of Bone Marrow Aspiration/Biopsy Associated Pain.

Objectives Bone marrow aspiration although being a common procedure is associated with significant pain and its reduction remains an unmet need. We evaluated the use of tramadol and eutectic mixture of local anesthetics (prilocaine plus lignocaine) (EMLA) for reducing the severity of pain. Materials and Methods In this pilot study, we compared the addition of either tramadol 50 mg per oral (T) or EMLA local application (E) or no intervention (L) in addition to the usual procedure of local infiltration with lignocaine 2% before bone marrow aspiration and biopsy (BMAB) in adults suspected/confirmed with malignancy. Both, tramadol and EMLA were administered 1 hour prior to the procedure. Primary end point was reduction in pain intensity with these interventions compared with local infiltration alone. Pain was assessed using numerical FACES pain scale, a visual analogue scale. Secondary end points were to see the effect on pre procedure apprehension and to find out the other factors associated with increased pain related to the procedure. Statistical Analysis and Results A total of 300 patients were included in the study, 100 each in tramadol (T), EMLA (E), and only lignocaine local infiltration (L) arms, respectively. The mean pain intensity on the visual scale was significantly lower in the tramadol arm (T, E, L-3.4, 4.4, 4.7, respectively) ( p < 0.0005). There was a significant reduction in percentage of patients who experienced moderate/severe pain (four or more) in the tramadol arm (T, E, L-45, 77, 82%, respectively) ( p < 0.0005). Duration of procedure >10 minutes, body mass index >30, ECOG (Eastern Oncology Group) performance status ≥3, and age >50 years were positively correlated with more pain. Leukemia patients experienced significantly more pain compared with patients with lymphoma and other solid malignancies. Tramadol was well tolerated. No significant effect on pre-procedure apprehension was noted in any of the arms. Conclusion Tramadol appears to have a preventive effect on bone marrow aspiration/biopsy-associated pain and appears to be well tolerated, whereas EMLA was not associated with such an effect. Larger studies may be done to ascertain the same.

Follicular Lymphoma in Young Adults: Study from a Regional Cancer Center in South India.

Objective Follicular lymphoma (FL) is a disease of the elderly. It is postulated that younger patients have distinct tumor biology and treatment outcomes. Various lymphoma groups across the world have studied this to understand if young adults (YAs) need a different treatment approach. Our study fills the void in data from an Asian country on YA population with FL. Patients and Methods We retrospectively analyzed young patients (age ≤40 years) diagnosed with FL at our center from 2012 to 2018. Their disease characteristics, treatment details, and outcomes were studied to examine any association between various parameters and survival. Results There were 28 young FL patients included in our study that constituted 14.6% of FL cases (males: 53.5% and females: 46.5%). The median age at diagnosis was 36.5 years. Most of the patients presented in an advanced stage, 57% had extranodal involvement, and 39.3% had bone marrow involvement at the time of presentation. The most common chemotherapy regimen used was cyclophosphamide, vincristine, and prednisone. Half of them received chemoimmunotherapy and only 18% continued rituximab as maintenance therapy. The overall response rate was 92.9% ( n = 26), and the remaining two patients had progressive disease while on treatment. The median progression free survival (PFS) was 6.1 years and median overall survival (OS) was not reached. On univariate analysis, extranodal disease was associated with a lower PFS ( p = 0.06) and low hemoglobin showed a significant association with OS ( p = 0.005). On multivariate analysis, none of the factors showed a significant association with survival. Conclusion Most YAs present with advanced disease with a good response to treatment and favorable outcomes.

Primary mucinous carcinomas of the lung: Clinical characteristics and treatment outcomes.

INTRODUCTION: Invasive mucinous adenocarcinoma (IMA) of the lung is a distinct histologic variant of adenocarcinomas comprising about 2%-10% of lung adenocarcinomas. A large proportion of IMAs carry KRAS mutations and only rarely epidermal growth factor receptor (EGFR) mutations or ALK/ROS translocations; thus, most cases are not amenable for targeted therapy at present. This study was conducted to elicit the unique clinicopathological characteristics of IMA. MATERIALS AND METHODS: Medical records of patients diagnosed with IMA by needle biopsy at Kidwai Cancer Institute, Bangalore, from 2013 to 2018, were retrieved and reviewed. Statistical analysis was performed using SPSS version 23.0 (IBM Corp., Armonk, NY, USA). RESULTS: Four hundred and ninety cases of needle biopsy of the lung were diagonosed at our institute between January 2013 and December 2018. Nine cases (1.8%) were diagnosed as IMA. The median age of presentation was 59 years. Six (66.7%) were current smokers with pack-year > 20. Three (33.3%) of the cases were initially misdiagnosed as pneumonia in view of computed tomography findings. The lung was the most common site of metastasis (77.8%). Serum Carcinoembryonic Antigen (CEA) was elevated in six cases (66.7%). None of the cases had any driver mutations in EGFR gene or ALK and ROS1 translocations. All cases were treated with pemetrexed-carboplatin doublet followed by pemetrexed maintenance till progression. The median progression-free survival (PFS) was 15 months (range: 5-18 months). Docetaxel was given as the second-line chemotherapy in all progressed patients. Best response noted was stable disease, seen in 4 (57.1%) cases. The median PFS for docetaxel was 6 months (range: 3-8 months). The median overall survival was 22 months (range: 9-27 months). Patients with initially raised CEA at progression had a serial rise in serum CEA. CONCLUSIONS: IMA is rarely diagnosed on needle biopsies due to insufficient tissue. They mimic pneumonia on imaging, thus delaying diagnosis. EGFR mutations, ALK, and ROS1 translocations are usually negative making them ineligible for tyrosine kinase inhibitors. Response to chemotherapy is modest.

Socioeconomic and administrative factors associated with treatment delay of esophageal and gastric carcinoma: Prospective study from a tertiary care centre in a developing country.

This study was aimed to analyze the spectrum of time intervals, from the onset of symptoms to the commencement of treatment in esophagogastric cancers. Factors influencing these time delays and correlation between these time points with variables including socioeconomic strata, educational level, histopathology, location of tumor and the initial modality of treatment were assessed. STUDY SETTING AND METHODS: A prospective analysis of patients with esophagogastric cancer presenting to a single tertiary care unit over a period of 12 months was performed. Histopathology other than adenocarcinoma and squamous cell were excluded. RESULTS: 202 patients were enrolled in the study. Most patients presented with advanced disease, i.e. 91.5 % of esophageal and 90 % of gastric malignancies belonged to either stage 3 or stage 4 as per American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system. The median delay from the appearance of the first symptoms to initiation of treatment was 15 weeks (range 4-64). Patient related factors contributed to a significant delay [median of 5 weeks (range 1-24)]. Administrative factors were responsible for median delay of 3 weeks (range 0.5-20). Curative multimodality treatment was administered in 62.5 % of patients. Significant longer delay was influenced by socioeconomic strata, educational level, evaluation by non-specialist (p < 0.05). No relationship was noted between histopathology, location of tumor or initial modality of treatment. CONCLUSIONS: Delays in our setting is much more than that is seen in Western and even some Asian countries. An important component of delay is administrative related factors. These may be intervened at the hospital level compared to other factors which may need long term community oriented approaches.

Evolution of the treatment of primary central nervous system lymphoma in a Regional Cancer Center of South India: Impact of high-dose methotrexate on treatment outcome.

OBJECTIVE: Primary central nervous system lymphoma (PCNSL) is a rare form of aggressive extranodal non-Hodgkin lymphoma. This study attempts to delineate the clinicopathological and radiological profile of PCNSL cases at our center. MATERIALS AND METHODS: All the pathologically confirmed PCNSL cases between January 2007 and July 2016 were analyzed retrospectively. The influence of potential prognostic parameters and therapeutic strategies on survival was investigated by log-rank test and Cox regression analysis. RESULTS: Of the 53 PCNSL patients, 34 (64%) patients were males. Median age at diagnosis was 44 years (range 22-65 years). The most common location in the brain was the cerebral hemispheres in 32 patients (60%), and 16 patients (30%) had multiple intracranial lesions. Histologically, all patients were diffuse large B-cell lymphomas, except one case of anaplastic large-cell lymphoma. The median survival of the patients received whole-brain radiation alone ( n = 6), standard CHOP chemotherapy + radiation ( n = 14), and DeAngelis protocol ( n = 31) was 8 months, 13 months, and 23 months, respectively. Among the 31 patients treated with DeAngelis protocol, Memorial Sloan Kettering Cancer Center Class 1 ( n = 23) and Class 2 ( n = 8) patients had a median overall survival (OS) of 25 months and 13 months, respectively. The incidence of treatment-related neurotoxicity was significantly higher with DeAngelis protocol, in comparison to CHOP + whole-brain radiation therapy (26% vs. 14%, P < 0.05). CONCLUSION: None of the potential prognostic factors had a statistically significant influence on OS in our patients. High-dose methotrexate-based chemotherapy combined with radiation was the only factor, which had a significant impact on survival (log-rank P = 0.000) but at the cost of increased neurotoxicity.

Clinical profile, cytogenetics and treatment outcomes of adult acute myeloid leukemia.

INTRODUCTION AND AIMS: Acute myeloid leukemia (AML) in adults has poor prognosis. The epidemiologic profile of patients varies greatly in different geographic locations and so do the cytogenetic abnormalities and the FAB subtype of the AML. We intended to study the clinical profile, cytogenetics, and outcomes with standard of care treatment on our population in India. METHODS: This was a retrospective study with systematic review of 203 case records. Primary objectives were to know the demographic profile of AML, prevalence of various FAB subtypes, cytogenetic abnormalities, and treatment outcomes at our center, which is a referral center of oncology. Two treatment outcomes considered in study for patients of AML were achievement of remission status of the bone marrow postintensive induction chemotherapy and sustenance of the remission for 6 months, once remission is achieved. Secondary objective was to study these outcomes in non-M3 AML in relation to cytogenetics. RESULTS: Median age was 39 years. The most common FAB subtype observed was AML M2. About 65.6% patients achieved complete remission (CR), and 42.4% patients could sustain it for next 6 months. Cytogenetics correlated with prognosis but not age. CONCLUSIONS: Our population differs from the Western population regarding lower age, lower prevalence of adverse cytogenetics, and higher prevalence of favorable cytogenetic abnormalities. Cytogenetics had a good correlation with CR rates after chemotherapy as well as its sustenance.

Follicular lymphoma transforming to DLBCL and reverting back to follicular lymphoma at relapse-a case report.

BACKGROUND: Transformation of low-grade follicular lymphoma to high-grade diffuse large B cell lymphoma (DLBCL) is known. However, the opposite is not commonly reported. In this report, we present a case of follicular lymphoma that underwent transformation to DLBCL. Three years after treatment for histologic transformation, the patient presented again with low-grade follicular lymphoma at the same site which is unusual in the natural history of follicular lymphoma. CASE PRESENTATION: A 50-year-old female patient presented to us with complaints of slowly progressing swelling in the neck on the left side for a duration of 1 year. Past history of the patient revealed a diagnosis of follicular lymphoma in 2004 for which the patient had taken prednisolone and chlorambucil. Details of staging were not available with the patient. After a complete work-up, she was diagnosed as DLBCL, stage IIIE. She was treated with 6 cycles of CHOP regimen. She had very good response to chemotherapy. However, she defaulted and was lost to follow-up. She presented again after 3 years with history of painless progressive swelling in the right side of the neck for the last 1 year. Examination revealed cervical lymph nodes and ascites. This time, a repeat biopsy and immunohistochemistry was suggestive of follicular lymphoma. In view of significant ascites, she was started on chemotherapy with CVP regimen. After 6 cycles, she has good partial response and resolution of ascites. She is currently on follow-up. CONCLUSIONS: We have presented a case of FL that has transformed to DLBCL after 10 years of diagnosis. After HT, she was treated with CHOP chemotherapy and the patient relapsed again after 3 years with follicular lymphoma histology. This case highlights the unique and varied natural history of follicular lymphoma that may be attributed to different subclones of malignant cells that may have arisen from a common progenitor FL cell and differential effect of chemotherapy on these subclones.

HIV/AIDS-related lymphoma: perspective from a regional cancer center in India.

BACKGROUND: India has the third largest population of people living with HIV/AIDS (PLHA). Lymphoma is the second most common malignancy among PLHA. However, data are lacking regarding HIV/AIDS-related lymphoma (ARL) in India. This study evaluated the epidemiology and clinical outcomes of ARL from a regional cancer center in India. METHODS: This retrospective analysis included cases of ARL between March 2011 and September 2017. Data were obtained from patient record files for the assessment of epidemiology and clinical outcomes. Statistical analysis was performed using GraphPad Prism 6. Comparisons of subtype-specific survivals were performed using log-rank tests. RESULTS: Of 1,226 lymphoma cases, 80 (6.5%) were ARL. Details were available for 70 patients. The median age at diagnosis was 40.5 (9-74) years with a male:female ratio of 2:1. AIDS-defining lymphomas (ADL) constituted 78.6% of cases, while 21.4% had non-AIDS defining lymphoma (NADL). The mean CD4 counts were 193.15±92.85 and 301.93±107.95 cells/µL, respectively (t-test; P=0.0002). Extranodal involvement was present in 55.7%, B symptoms were reported in 60%, and lactate dehydrogenase (LDH) was elevated in 64.3% of patients. The median overall survival times were 6 months for plasmablastic lymphoma (PBL), 23 months for diffuse large B-cell lymphoma (DLBCL), and was not reached for Hodgkin's lymphoma (log-rank test; P=0.0011). Other histological subtype cases were too few to draw meaningful survival outcomes. CONCLUSION: ARL is a heterogeneous disease. Histologic subtype is a major determinant of the clinical outcome. ADL has significantly lower CD4 counts than those of NADL. There is an urgent and unmet need for uniform management guidelines for improving outcomes in this under-represented patient population.

Modified Epirubicin, cisplatin, and 5-FU regimen as first-line chemotherapy in metastatic gastric or gastroesophageal junction adenocarcinoma: A Phase II study.

BACKGROUND: Epirubicin, cisplatin, and 5-FU (ECF) is one of the most commonly used first-line chemotherapy regimens in metastatic gastric cancer. However, due to protracted infusion schedule, need for special infusion pumps, and catheter-related complications, the practical utility and acceptability of standard ECF regimen are limited, particularly in resource-constrained settings including India. MATERIALS AND METHODS: In the present study, we have used a more convenient modification of the standard ECF protocol (using 5 days intravenous infusion of 5-FU at a dose of 750 mg/m2/day, given over 6 h through a peripheral venous line), in Indian patients with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. The primary endpoint was overall survival (OS). The secondary endpoints were overall response rate (ORR), progression-free survival (PFS), and toxicity profile. RESULTS: Between January 2014 and December 2017, 107 patients were assigned and treated with this modified ECF regimen. The median age was 52 years (range, 34-62); 66.3% were males and 36.5% of the patients had ≥ 3 metastatic disease site involvement at baseline. Dose reductions due to toxicity were required in 14.9% of the patients. The ORR was 32.7%; median PFS and OS were 5.9 months (95% confidence interval [CI]: 4.7-6.9) and 10.4 months (95% CI: 8.4-11.8), respectively. Both the hematological and nonhematological toxicities were manageable, and there was no toxicity-related death. The most frequent Grade 3-4 adverse events were neutropenia (18.7%), febrile neutropenia (13.1%), mucositis (5.6%), and diarrhea (5.6%). CONCLUSIONS: In the present study, the modified ECF regimen demonstrated significant efficacy with an acceptable toxicity profile in Indian patients with metastatic gastric and GEJ adenocarcinoma. The survival outcomes of this modified schedule were comparable with those of the standard ECF regimen, as reported earlier. Clearly, this modified and more convenient ECF protocol should be explored and validated through large prospective randomized trials.

Every distant deposit is not a metastasis: Synchronous primaries do exist.

BACKGROUND: Synchronous occurrence of two malignant tumors is a rare event. With increasing use of sophisticated imaging modalities for staging, synchronous multiple tumors are more commonly detected now. Assuming the second primary malignancy as metastasis will change the intent of treatment from curative to palliative, greater awareness among oncologists is of paramount importance. This study is an example where thorough clinical examination and proper judgment resulted in correct diagnosis and appropriate treatment. MATERIALS AND METHODS: This is a prospective descriptive study. Patients diagnosed with synchronous primary tumors from January 2016 to November 2017 at our center were reviewed. RESULTS: Ten cases of synchronous primary malignancies were detected during this period. A total of 20 primary tumors were diagnosed. Lung carcinoma and gastrointestinal malignancies were the most common (five patients each). The median age was 59.5 years. Seven patients were male. Second primary tumor was suspected in four patients during clinical examination, while in six patients it was suspected on imaging. Even in the presence of two primary tumors, three patients were treated with curative intent. CONCLUSION: Possibility of synchronous second primary malignancy should always be kept whenever a distant deposit is detected at an unusual site. Histopathological evaluation of the lesion before assuming a metastasis will lead to accurate diagnosis, staging, and appropriate treatment.

A prospective study to compare the measured glomerular filtration rate compared to estimated glomerular filtration rate in patients undergoing definitive chemoradiation, with platinum agents for various malignancies.

CONTEXT: Renal function assessment is of paramount importance before using the platinum agents especially cisplatin. Glomerular filtration rate (GFR) estimation by diethyl-triamine-penta-acetic acid (DTPA) scan (measured GFR [mGFR]) is considered gold standard. AIMS: The aim of this study is to know if we can replace the mGFR with the GFR estimation with Cockcroft-Gault formula (eGFR) in patients undergoing chemoradiation. SETTINGS AND DESIGN: This is a prospective, descriptive study. SUBJECTS AND METHODS: Patients who are planned for definitive chemoradiation will be eligible for the study. Renal function will be measured DTPA scan and Cockcroft-Gault (CG) formula. Subgroup analysis based on the weight, age, and sex will be done. STATISTICAL ANALYSIS USED: Demographic and renal function parameters were analyzed using summary measures. To test the significance of the difference between mGFR and cGFR, a paired t-test will be used; to look for an association between various estimates of renal function, the Pearson's correlation coefficient will be calculated using a two-tailed test. RESULTS: Median mGFR of patients was 82.7 (range: 65-125 ml/min, standard deviation [SD] =14.0 ml/min) while the median eGFR as per the CG formula was 83.9 ml/min (range: 37-137 ml/min, SD = 24.4 ml/min). The median mGFR was only 1.2 ml/min lesser when measures by the CG formula with no significance difference between them (P = 0.66, 95% confidence interval: -4.5-6.3). CONCLUSIONS: We concluded that in resource-limited setting eGFR using CG formula can replace mGFR, especially in patients with age <60 years. Although weight did not showed a significant difference by two methods, a study with large sample is needed to confirm the result.

Synchronous primary cancers: Renal cell carcinoma and rectal cancer.

Although cancers of rectum and kidney are common malignancies, the occurrence of primary synchronous neoplasms of these organs has been reported rarely. Very few case reports are available in literature till date. The relationship between these two events remains unclear, probably because of the rarity of the association. In this report, we describe incidentally detected renal cell carcinoma in an elderly man, during staging workup of rectal adenocarcinoma and both malignancies were surgically managed simultaneously with curative intent.

Primary gastrointestinal diffuse large B-cell lymphoma: A prospective study from South India.

BACKGROUND: Gastrointestinal tract (GIT) is the most common extranodal site for non-Hodgkin's lymphoma (NHL) and constitutes about 10%-15% of all NHL. This was a prospective study to evaluate the epidemiological, clinicopathological characteristics, and treatment outcome of primary GIT diffuse large B-cell lymphoma (PGIL). MATERIALS AND METHODS: Newly diagnosed patients of PGIL with DLBCL histology were eligible. Lugano staging system was used. All patients were treated with prephase treatment (1 mg vincristine and 100 mg prednisolone) followed by CHOP-based chemotherapy (with or without rituximab) as definitive treatment. RESULTS: A total of 21 patients of PGIL were diagnosed. The median age was 46 years (range: 27-69 years) with male:female ratio of 2:1. Dull aching abdominal pain was the most common presenting complaint. Stomach was the most common site involved (52.4%, n = 11) followed by the colon (23.8%, n = 5). The estimated median survival in patients with Stage IV disease was significantly lower as compared to patients with localized disease (Stage I and II) (6.23 months vs. 23.4 months; P = 0.04). Patients, who did not achieve complete response (CR), had 15.5 times higher risk of death, as compared to those who achieved CR (P = 0.01). CONCLUSIONS: Stomach was the most common site for PGIL. Localized disease and CR after first-line chemotherapy were associated with better survival. A higher cost of rituximab was the prohibitive factor for cure in these patients.

Clinical profile and treatment outcomes of metastatic neuroendocrine carcinoma: A single institution experience.

BACKGROUND: Neuroendocrine carcinoma (NEC) is a rare tumor arising from the diffuse neuroendocrine system. Most of these present in the advanced stage and palliative chemotherapy remains the only option. The prognosis remains poor with the standard chemotherapy regimen of platinum and etoposide (EP) providing modest survival benefit. METHODS: The study was done for 3 years at a tertiary cancer center in South India. Patients with a diagnosis of metastatic NEC were analyzed for clinical and pathological characteristics. The treatment outcomes and prognostic factors were evaluated using appropriate statistical test. RESULTS: A total of 114 patients of metastatic NEC satisfied the inclusion criteria and were analyzed. Gastrointestinal including hepatobiliary tract (33%) was the most common site of primary disease followed by lung (26%), genitourinary (15%), head and neck (14%), and unknown primary (9%). On analysis of pattern of metastasis, liver (65%) was the most common site followed by bone (54%) and lung (42%). The median overall survival was 11 months with a statistically significant difference between pulmonary and extrapulmonary disease (8 vs. 13 months; P = 0.003). Ki67% value was strongly associated with prognosis (hazard ratio 0.517, 95% confidence interval; 0.318-0.840, P = 0.008) whereas age, sex, and lactate dehydrogenase level did not show any relation with survival. CONCLUSION: The outcome of advanced NEC with standard chemotherapy remains poor. Larger studies with other therapeutic and novel agents are warranted to improve the treatment outcomes.