Fumarate hydratase-deficient renal cell carcinoma: an oncology care institutional experience.

Renal cell carcinoma (RCC) accounts for 2% of all cancer cases worldwide, and majority are sporadic. The latest World Health Organization (WHO) classification of renal cell tumors (fifth edition, 2022) has molecularly defined renal tumor entities, which includes fumarate hydratase (FH)-deficient RCC. FH-deficient RCC is an aggressive carcinoma caused by pathogenic alterations in FH gene, seen in 15% of patients with hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) syndrome. These tumors occur more frequently at a younger age and present at an advanced stage, carrying a dismal prognosis. We report a series of 10 cases of FH-deficient RCC. The mean age was 49.8 years, and all cases presented in advanced stages (III and IV). Morphologically, the cases had varied architectural patterns with characteristic eosinophilic macronucleoli and perinucleolar halo. On immunohistochemistry (IHC), all showed diffuse nucleo-cytoplasmic expression of S-(2-succino)-cysteine (2-SC), with loss of FH in seven cases. FH-deficient RCCs are aggressive neoplasms and can be diagnosed using specific IHC markers (FH and 2-SC). These patients should undergo germline testing for FH gene mutation, genetic counseling, and surveillance of family members.

Robot-Assisted Video Endoscopic Inguinal Lymph Node Dissection for Penile Cancer: An Indian Multicenter Experience.

Objective: To report outcomes of multicenter series of penile cancer patients undergoing robot-assisted video endoscopic inguinal lymph node dissection (RA-VEIL). Materials and Methods: In this retrospective analysis from 3 tertiary care centers in India, consecutive intermediate-/high-risk carcinoma penis (CaP) patients with nonpalpable inguinal lymphadenopathy and/or nonbulky (<3 cm) mobile inguinal lymphadenopathy undergoing RA-VEIL were included. Patients with matted/bulky (>3 cm) and fixed lymphadenopathy were excluded. Demographic, clinical, and intraoperative data were recorded. Perioperative complications were graded by the Clavien-Dindo classification (CDC). The International Society of Lymphology (ISL) {0-III} grading was used for the assessment of lymphedema. Incidence and pattern of recurrences were assessed on follow-up. Results: From January 1, 2011, to September 30, 2023, 115 patients (230 groins) underwent bilateral RA-VEIL for CaP. The median age of the cohort was 60 (50-69) years. Clinically palpable (either unilateral or bilateral) inguinal lymphadenopathy was seen in 54 patients (47%). The "per groin" median operative time was 120 (100-140) minutes with median lymph node yield of 12 (9-16). No complications were recorded in 87.8% groins operated, with major complications (CDC 3) seen in 2.6% groins. At a median follow-up of 13.5 months, 13 patients had documented recurrences and there were 10 cancer-related deaths. No port-site recurrences were observed. No/minimal lymphedema (ISL 0/I) was seen in 94% legs. Conclusion: RA-VEIL demonstrates safety and oncologic efficacy in penile cancer patients presenting with clinically nonpalpable and/or nonbulky inguinal lymphadenopathy, with favorable functional outcomes.

Surgical and oncological outcomes of robot-assisted versus laparoscopic radical nephroureterectomy for upper-tract urothelial carcinoma: A single-center comparative analysis.

Introduction: We retrospectively compared surgical and oncological outcomes of robot-assisted (RA) radical nephroureterectomy (RNU) in patients of upper-tract urothelial carcinoma with a cohort of patients who underwent the same procedure using a laparoscopic approach. Methods: Data of 63 consecutive patients who underwent RNU with bladder cuff excision (BCE) from 2011 to 2022 at a single tertiary care institution was retrospectively retrieved from the electronically maintained institutional database. Twenty-six cases underwent RNU with a laparoscopic approach, whereas 37 were done by RA approach. Demographic, clinical, surgical, and pathologic details and survival analyses were reported and compared. The tetrafecta of RNU, which include the performance of a BCE, lymphadenectomy, no positive surgical margin, and no major surgical complication, was also reviewed. Results: The mean age and body mass index of the robotic and laparoscopic groups were 61.5 years versus 62.7 years and 23.8 versus 24.9 kg/m2, respectively (P = 0.710 and 0.309). The Charlson Comorbidity Index and upper-tract tumor site distribution were comparable between the groups. There was no significant difference in the distribution of T stage, N stage, presence of multifocality, or lymphovascular invasion between the two groups. Although the rate of concomitant carcinoma in situ was higher in laparoscopic cohort, 42.8% versus 10.8% in robotic cohort (P = 0.004). The laparoscopic group had higher blood transfusion rates (50 vs. 13.5%, P = 0.002) and longer median hospital stays (7 vs. 4 days, P = 0.000). The median follow-up time was 21.5 versus 27 months in the laparoscopic and robotic groups. The RA group was significantly better in the achievement of the tetrafecta outcomes. The 5-year urinary bladder recurrence-free survival (UB RFS) and elsewhere RFS between the laparoscopic and robotic cohorts were 65% versus 72% and 56% versus 70%, respectively (P = 0.510 and 0.190). The laparoscopic cohort had worse 5-year cancer-specific survival and overall survival (64% vs. 90% and 58% vs. 74%, P = 0.04 and 0.08). Conclusion: The robotic approach to RNU and BCE has significantly lower transfusion rates, lower hospital stays, and significantly better cancer-specific survival rates.

Prostate cancer detection using magnetic resonance imaging-transrectal ultrasound fusion biopsy: A retrospective cohort study.

Introduction: Transrectal ultrasound (TRUS) guided systematic prostate biopsy is conventionally used for the diagnosis of carcinoma prostate (CaP). However, magnetic resonance imaging (MRI) guided biopsies have been shown to have superior diagnostic performance. MRI-TRUS fusion biopsy improves the detection by combining the systematic and the targeted biopsies (TB). In this study, we evaluated the role of fusion biopsy in the detection of CaP as well as clinically significant carcinoma prostate (CsCaP). Methods: In this retrospective study, the patients who underwent fusion biopsy from January 2016 to July 2022 were evaluated. Patients underwent multiparametric MRI and the suspicious lesions were reported as per the Prostate Imaging Reporting and Data System (PIRADS) version 2. The clinical, imaging, and biopsy parameters were recorded and evaluated. Results: A total of 330 patients with PIRADS ≥3 underwent MRI-TRUS fusion biopsy and prostate cancer was detected in 187 patients (56.67%). With an increase in the PIRADS score, there was a significant rise in the detection of CaP (P < 0.001) and CsCaP (P < 0.0000001). Prostatitis was observed in 13%-18.1% of the patients with a lesion on MRI irrespective of the PIRADS score. The systematic and TB were comparable for the detection of CaP (P = 0.88) and CsCaP (P = 0.26). With a prostate-specific antigen density (PSAD) cutoff of 0.15 ng/mL/cc and 0.22 ng/mL/cc, biopsy could be safely avoided in 14.2% and 20.3% of the patients, missing only 0.3% of CaP and 0.9% of CsCaP, respectively. Different subgroups based on PSA levels, prostate volume, lesion dimension, and PIRADS score did not show a significant difference between the systematic and the targeted cores for the detection of CsCaP. Conclusion: This single center study of MRI-TRUS fusion prostate biopsy shows that in men with clinical suspicion of prostate cancer a pre-biopsy MRI and MRI-TRUS fusion combined systematic and targeted prostate biopsy improves the detection of prostate cancer and CsCaP. Patients with a PIRADS 3 lesion with a PSA density <0.22 can safely avoid prostate biopsy, without a significant risk of missing clinically significant prostate cancer.

Recent advances and future directions in etiopathogenesis and mechanisms of reactive oxygen species in cancer treatment.

A class of exceptionally bioactive molecules known as reactive oxygen species (ROS) have been widely studied in the context of cancer. They play a significant role in the etiopathogenesis for cancer. Implication of ROS in cancer biology is an evolving area, considering the recent advances; insights into their generation, role of genomic and epigenetic regulators for ROS, earlier thought to be a chemical process, with interrelations with cell death pathways- Apoptosis, ferroptosis, necroptosis and autophagy has been explored for newer targets that shift the balance of ROS towards cancer cell death. ROS are signal transducers that induce angiogenesis, invasion, cell migration, and proliferation at low to moderate concentrations and are considered normal by-products of a range of biological activities. Although ROS is known to exist in the oncology domain since time immemorial, its excessive quantities are known to damage organelles, membranes, lipids, proteins, and nucleic acids, resulting in cell death. In the last two decades, numerous studies have demonstrated immunotherapies and other anticancer treatments that modulate ROS levels have promising in vitro and in vivo effects. This review also explores recent targets for therapeutic interventions in cancer that are based on ROS generation or inhibition to disrupt the cell oxidative stress balance. Examples include-metabolic targets, targeted therapy with biomarkers, natural extracts and nutraceuticals and targets developed in the area of nano medicine. In this review, we present the molecular pathways which can be used to create therapy plans that target cancer by regulating ROS levels, particularly current developments and potential prospects for the effective implementation of ROS-mediated therapies in clinical settings. The recent advances in complex interaction with apoptosis especially ferroptosis and its role in epigenomics and modifications are a new paradigm, to just mechanical action of ROS, as highlighted in this review. Their inhibition by nutraceuticals and natural extracts has been a scientific challenging avenue that is explored. Also, the inhibition of generation of ROS by inhibitors, immune modulators and inhibitors of apoptosis and ferroptosis is explored in this review.

Cutaneous Radiation-Associated Angiosarcoma After Treatment of Carcinoma Penis: First Report from Tertiary Cancer Centre of North India.

Cutaneous radiation-associated angiosarcoma (cRAA) is a rare and aggressive secondary cutaneous angiosarcoma (cAS) with poor survival. cRAA has been mostly reported in breast carcinoma patients. Owing to its rarity, there is scanty literature available and no treatment guidelines. To the best of our knowledge, this is the first report of cRAA after multimodality treatment of carcinoma penis. A sixty-eight-year-old gentleman, a known case of carcinoma penis, underwent total penectomy with perineal urethrostomy and bilateral radical inguinopelvic lymph node dissection 6 years ago. He received adjuvant radiotherapy to the pelvis and bilateral groin. He presented with a bleeding plaque-like lesion with ulceration over the left lower abdomen (within previous radiation field) which rapidly progressed in size over the past 2 months. On examination, the lesion bled profusely on touch. Contrast MRI was suggestive of lobulated exophytic enhancing cutaneous lesion free from underlying muscle. Wedge biopsy was suggestive of cutaneous angiosarcoma. He underwent wide local excision with local perforator flap reconstruction from the right lower abdomen. Histopathology was suggestive of cutaneous angiosarcoma which showed immunoexpression of CD31, ERG1, cMYC suggestive of cRAA. cRAA is a very aggressive disease with 5-year survival of 15-34%. To the best of our knowledge, this is the first ever reported case of cRAA of lower abdomen after multimodality management of carcinoma penis. It masquerades with other benign and less aggressive radiation-induced skin lesions. cMYC immunoexpression is specific for secondary cAS. Wide local resection with negative margin provides the best outcome.

Enzalutamide-Induced Acute Maculopapular Rash in Treatment of Metastatic Prostate Cancer: First Case Report from a Tertiary Cancer Care Center of North India.

Enzalutamide is a new potent inhibitor of the signaling pathway for the androgen receptor with a half-life of 5.8 days. It has been on the market for the treatment of metastatic castration-resistant prostate cancer since November 2013. We report a case of acute generalized exanthematous maculopapular rash induced by enzalutamide. In summary, newer androgen receptor blockers have a propensity to cause skin related adverse effects. Most common among these are apalutamide. Enzalumatamide, per se, is a safe drug and has not been associated frequently in causing maculopapular rash. Few cases has been reported. In all these cases, the drug was discontinued and 2nd line therapy was instituted. In this report, Enzalutamide was withheld for 10 days and anti-histaminics was instituted. After a full recovery, Enzalutamide was reinstituted in treatment. A 62-year-old male patient with no significant medical history, was diagnosed in March 2020 with metastatic prostatic adenocarcinoma. Baseline PSA was 456 ng/ml. PSMA PET scan showed evidence of multiple bony metastasis. He was started on Degarelix subcutaneous injection with oral abiraterone initially. PSA level showed initial decreasing trend till September 2021 followed by sudden increase. Intramuscular Injection leuprolide was started and initial responses were good followed by later rise of PSA from January. Tab Xtandi (Enzalutamide) was added to the regimen from 31.1.22. Three days after starting enzalutamide treatment, the patient experienced an acute skin reaction. It is about of the plaques covered with widespread millimetric non-follicular papules. Enzalutamide was stopped after appearance of rashes to avoid further serious adverse effects. Anti-histaminics were started. Complete resolution of skin lesions occurred within 10 days. Tab Enzalutamide was reinstituted on 11th day after stoppage and on complete resolution of skin resolutions. According to the CTCAE 5.0 criteria, these skin rash was graded as grade 2. In view of evidence in literature and clinical improvement after stoppage, the acute drug reaction was attributed to enzalutamide. Uro oncologist can be confronted with adverse skin drug reactions attributable to new therapeutic molecules. The slow resolution of symptoms seems be due to the long half-life of enzalutamide. It should not be withdrawn from therapy owing to these effects. Rather, it should be with stopped for 10-14 days. Basic treatment with anti-histaminics or topical steroids may be enough to warranty the resolution of symptoms, and the drug (Enzalutamide) can be continued thereafter.

Diagnostic Utility of Galactomannan Enzyme Immunoassay in Invasive Aspergillosis in Pediatric patients with Hematological Malignancy.

OBJECTIVE: This study aims to determine the diagnostic utility of galactomannan enzyme immunoassay (GM EIA) in invasive aspergillosis (IA) in children with hematological malignancy (high risk population) in terms of sensitivity, specificity, negative predictive value (NPV) and positive predictive values (PPV) at various cut offs while validating the revised EORTC/MSG 2019 criteria in order to obtain the best cut-off. MATERIAL AND METHODS: For 100 pediatric patients, serum and respiratory samples were collected. Clinical, mycological workup (potassium-hydroxide mount, fungal culture) and GM EIA was done to classify proven, probable, and possible IA as per EORTC-MSG guidelines,2019. Sensitivity, specificity, PPV and NPV were calculated of GM indices at cut-off 0.5, 0.7 and 1, and validated with revised EORTC -MSG, 2019. RESULTS: Of 100 patients enrolled, 75 were diagnosed with ALL, 14 with AML, two with Hodgkin's, three had non-Hodgkin lymphoma, and six had undifferentiated leukemia. With routine mycological findings, 51 were classified as probable IA, 11 as possible IA, and 38 as no IA. Aspergillus flavus was the most prevalent on culture (56.9%, 29/51) followed by A. fumigatus (29%, 15/51) A. niger (7.8%, 4/51), A. terreus (3.9%, 2/51) and A. nidulans (2%, 1/51). GM EIA demonstrated sensitivity 82.3%, specificity 97.4%, PPV 98.1%, and NPV 77.1% at cut-off 0.67 when comparing probable/possible IA v/s no IA groups. The GM EIA had the best sensitivity (82.4%), specificity (81.8%), PPV (95.5%), and NPV (50%) at cut off 0.78 when the probable IA group was compared to the possible IA. Seven patients succumbed of whom 5 had GMI ≥ 2. CONCLUSION: This study deduces the optimal cut-off for serum GM EIA to be 0.67 obtained by ROC analysis when comparing possible and probable IA versus no IA and reinforces the definition of probable category of EORTC-MSG criteria, 2019. At 0.5 ODI the sensitivity (87.1%) and NPV (80.5%) are high, thus making it the most suitable cut-off for detecting true positive and ruling out IA respectively, in pediatric patients with hematological malignancy. GM EIA when performed adjunctive to clinico-radiological findings can prove to be screening, diagnostic and prognostic test for IA in pediatric hematological malignancy patients.

Prognostic relevance of surface expression of cytokine receptor-like factor 2 in pediatric B-lineage acute lymphoblastic leukemia.

Overexpression of cytokine receptor-like factor 2 (CRLF2) resulting from its genomic rearrangement is the most frequent genetic alteration found in Philadelphia chromosome-like (Ph-like) B-cell acute lymphoblastic leukemia (B-ALL), a high-risk leukemia. Detection of CRLF2 expression by multiparameter flow cytometry has been proposed as a screening tool for the identification of Ph-like B-ALL. However, the prognostic relevance of flow cytometric expression of CRLF2 in pediatric B-ALL is not very clear. Additionally, its association with common copy number alterations (CNA) has not been studied in detail. Hence, in this study, we prospectively evaluated the flow cytometric expression of CRLF2 in 256 pediatric B-ALL patients and determined its association with molecular features such as common CNAs detected using Multiplex ligation-dependent probe amplification and mutations in CRLF2, JAK2 and IL7RA genes. Further, its association with clinicopathological features including patient outcome was assessed. We found that 8.59% (22/256) pediatric B-ALL patients were CRLF2-positive at diagnosis. Among CNAs, CRLF2 positivity was associated with presence of PAX5 alteration (P=0.041). JAK2 and IL-7R mutations were found in 9% and 13.6% CRLF2-positive patients, respectively. IGH::CRLF2 or P2RY8::CRLF2 fusions were each found in 1/22 individuals. CRLF2-positive patients were found to have inferior overall (hazard ratio (HR) =4.39, P=0.006) and event free survival (HR=2.62, P=0.045), independent to other clinical features. Furthermore, concomitant CNA of IKZF1 in CRLF2 positive patients was associated with a greater hazard for poor overall and event free survival, compared to patients without these alterations or presence of any one of them. Our findings demonstrate that the surface CRLF2 expression in association with IKZF1 copy number alteration can be used to risk stratify pediatric B-ALL patients.

Infections Associated Hemophagocytosis-Secondary HLH Mimics in Children!"

Infection-associated hemophagocytosis is a diagnostic challenge. The varied presentation makes timely diagnosis difficult. We report two cases with unusual presentation of well-established secondary triggers for hemophagocytic lymphohistiocytosis.

Severity and mortality associated with COVID-19 among children hospitalised in tertiary care centres in India: a cohort study.

Background: It is critical to identify high-risk groups among children with COVID-19 from low-income and middle-income countries (LMICs) to facilitate the optimum use of health system resources. The study aims to describe the severity and mortality of different clinical phenotypes of COVID-19 in a large cohort of children admitted to tertiary care hospitals in India. Methods: Children aged 0-19 years with evidence of SARS-CoV-2 infection (real time polymerase chain reaction or rapid antigen test positive) or exposure (anti-SARS-CoV-2 antibody, or history of contact with SARS-CoV-2) were enrolled in the study, between January 2021 and March 2022 across five tertiary hospitals in India. All study participants enrolled prospectively and retrospectively were followed up for three months after discharge. COVID-19 was classified into severe (Multisystem Inflammatory Syndrome in Children (MIS-C), severe acute COVID-19, 'unclassified') or non-severe disease. The mortality rates were estimated in different phenotypes. Findings: Among 2468 eligible children enrolled, 2148 were hospitalised. Signs of illness were present in 1688 (79%) children with 1090 (65%) having severe disease. High mortality was reported in MIS-C (18.6%), severe acute COVID-19 (13.3%) and the unclassified severe COVID-19 disease (12.3%). Mortality remained high (17.5%) when modified MIS-C criteria was used. Non-severe COVID-19 disease had 14.1% mortality when associated with comorbidity. Interpretation: Our findings have important public health implications for low resource settings. The high mortality underscores the need for better preparedness for timely diagnosis and management of COVID-19. Children with associated comorbidity or coinfections are a vulnerable group and need special attention. MIS-C requires context specific diagnostic criteria for low resource settings. It is important to evaluate the clinical, epidemiological and health system-related risk factors associated with severe COVID-19 and mortality in children from LMICs. Funding: Department of Biotechnology, Govt of India and Department of Maternal, Child and Adolescent Health and Aging, WHO, Geneva, Switzerland.

Robot-assisted retroperitoneal lymph node dissection for post-chemotherapy residual mass in testicular cancer: Long-term experience from a tertiary care centre.

Objectives: To present our intermediate to long-term oncological and functional outcomes of robot-assisted retroperitoneal lymph node dissection (RA-RPLND) in post-chemotherapy (PC) residual mass in testicular cancers. To the best of our knowledge, this is the largest single-centre experience of RA-RPLND for in such setting. Methods: Prospectively maintained database of carcinoma testis patients undergoing RA-RPLND from February 2012 to September 2021 was reviewed. Patient demographics, tumour stage and risk groups and chemotherapy details were recorded. Intraoperative details and post-operative complications were also noted. Pathological outcomes included were lymph node yield and histopathology report. Further, follow-up was done for recurrence and antegrade ejaculation status. Results: Total of 37 cases were done for PC residual masses. International germ cell cancer collaborative group good, intermediate and poor risk proportion was 18 (48.6%), 14 (37.8%) and 5 (13.5%), respectively. Bilateral full template dissection, unilateral modified template dissection and residual mass excision was performed in 59.5% (22/37), 35.1% (13/37) and 5.4% (2/37) patients, respectively. The median size of the excised residual mass was 3.45 cm interquartile range (IQR 2-6 cm), with the largest being 9 cm. The median lymph nodal yield was 19. The most common histology was necrosis (n = 24, 65%), followed by teratoma (n = 11, 30%) and viable malignancy (n = 2, 5%). Antegrade ejaculation was reported in 32 patients (86.4%). After a median follow-up of 41 (IQR 14-64) months, only one patient had a recurrence. Conclusions: RA-PC-RPLND is thus a safe, feasible and oncologically effective option for selected patients. With increasing experience, larger masses can also be dealt with efficiently.

Inguinal lymph node dissection in the era of minimally invasive surgical technology.

BACKGROUND: Inguinal lymph node dissection (ILND) is an essential step in both treatment and staging of several malignancies including penile and vulvar cancers. Various open, video endoscopic, and robotic-assisted techniques have been utilized so far. In this review, we aim to describe available minimally invasive surgical approaches for ILND, and review their outcomes and complications. METHODS: The PubMed, Wiley Online Library, and Science Direct databases were reviewed in February 2020 to find relevant studies published in English within 2000-2020. FINDINGS: There are different minimally invasive platforms available to accomplish dissection of inguinal nodes without jeopardizing oncological results while minimizing postoperative complications. Video Endoscopic Inguinal Lymphadenectomy and Robotic Video Endoscopic Inguinal Lymphadenectomy are safe and achieve the same nodal yield, a surrogate metric for oncological adequacy. When compared to open technique, Video Endoscopic Inguinal Lymphadenectomy and Robotic Video Endoscopic Inguinal Lymphadenectomy may offer faster postoperative recovery and fewer postoperative complications including wound dehiscence, necrosis, and infection. The relatively high rate and severity of postoperative complications hinders utilization of recommended ILND for oncologic indications. Minimally invasive approaches, using laparoscopic or robotic-assisted platforms, show some promise in reducing the morbidity of this procedure while achieving adequate short and intermediate term oncological outcomes.

Robotic re-exploration for post-operative in house complications following robotic pelvic uro-oncologic surgery: Initial experience, tips and tricks.

Purpose: Despite widespread acceptance of robotics in urology, literature on using the minimally invasive approach for management of post robotic surgical complications is limited. Here we describe our experience with tips and tricks for robotic re-exploration of post-operative in house complications following robotic pelvic uro-oncologic surgery. Methods: A retrospective query of prospectively maintained database was done for all patients who underwent robotic - radical cystoprostatectomy (RCP, 437 patients) and radical prostatectomy (RP, 649 patients), from Jan 2015 or March 2021. Clinical details were collected for all who underwent a second robotic procedure during the same hospital admission for any complication related to the primary surgery. Results: Following RCP, 5 patients were re-explored for intestinal obstruction. Surgery was successfully completed in all with a median console time of 80 minutes. Median time to the passage of flatus and discharge from hospital following relook surgery was 3 and 6 days, respectively. Following RP, 3 patients underwent robotic re-exploration (two for reactionary hemorrhage, one for rectal injury). All three cases were managed with a median console time of 75 minutes. Robotic re-exploration was accomplished without extending the skin incision of the index surgery and we did not find an increased incidence of infectious or wound related complications. Conclusion: Robotic re-exploration for select post robotic urologic pelvic oncology surgery complications in the immediate and early post-operative period is feasible in the hands of experienced surgeons. Our experience can help others adopt robotics in such scenarios.

Early prognosis prediction in acute myeloid and acute lymphoid leukemia patients using cell-free DNA concentration ratios.

Background: Cell-free DNA (cfDNA) is a promising biomarker for disease prediction in many cancers, including acute leukemia (acute myeloid leukemia [AML] and acute lymphoblastic leukemia [ALL]). This study investigated the role of cfDNA in predicting relapse or unfavorable outcomes in acute leukemia patients upon initial diagnosis. Methods: Paired peripheral blood samples of 25 patients with ALL and AML were compared at baseline and induction/follow-up and clinically correlated with clinicopathological and outcome variables according to the risk category. cfDNA was isolated using commercial cfDNA extraction kits. The probability of poor outcomes in high-risk groups and a cut-off value for risk stratification minimal residual disease (MRD) positivity and outcome prediction were derived. Results: Twenty-five patients diagnosed with AML and ALL were risk-stratified based on NCI risk stratification, and of these 25 patients, 4 patients were of standard risk (SR) and 1 patient was of intermediate risk (IR), while a majority of patients (80%) were of high risk (HR). Of these, four HR patients passed away. The ratio of cfDNA reduction at baseline and the end of induction was a strong predictor of poor outcomes in high-risk patients, regardless of the MRD status. A cfDNA ratio score of 2.6 or higher at diagnosis/remission predicted poor outcomes, with higher accuracy than conventional MRD detection by flow cytometry. Conclusion: A higher cfDNA ratio at diagnosis/remission or at baseline predicts poor outcomes in acute leukemia patients. This pilot study suggests that cfDNA ratio scoring may be a useful tool for predicting prognosis in acute leukemia patients, regardless of the MRD status.

2/1 dose schedule of sunitinib is superior than the 4/2 regimen for the first-line therapy of clear cell metastatic renal cell carcinoma - An Indian experience.

BACKGROUND: Sunitinib remains the first-line treatment for favorable risk metastatic clear cell renal cell cancer (mccRCC). It was conventionally given in the 4/2 schedule; however, toxicity necessitated trying the 2/1 regimen. Regional variations in treatment response and toxicity are known, and there is no data from the Indian subcontinent about the outcomes of the alternative dosing schedule. METHODS: Clinical records of all consecutive adult patients who received sunitinib as first-line therapy for histologically proven mccRCC following cytoreductive nephrectomy from 2010-2018 were reviewed. The primary objective was to determine the progression-free survival (PFS), and the secondary objectives were to evaluate the response rate (objective response rate and clinical benefit rate), toxicity, and overall survival. A list of variables having a biologically plausible association with outcome was drawn and multivariate inverse probability treatment weights (IPTW) analysis was done to determine the absolute effect size of dosing schedules on PFS in terms of "average treatment effect on the treated" and "potential outcome mean." RESULTS: We found 2/1 schedule to be independently associated with higher PFS on IPTW analysis such that if every patient in the subpopulation received sunitinib by the 2/1 schedule, the average time to progression was estimated to be higher by 6.1 months than the 4/2 schedule. We also found 2/1 group to have a lower incidence than the 4/2 group for nearly all ≥ grade 3 adverse effects. Other secondary outcomes were comparable between both treatment groups. CONCLUSION: Sunitinib should be given via the 2/1 schedule in Indian patients.

Robot-Assisted Video Endoscopic Inguinal Lymph Node Dissection for Carcinoma Penis.

Inguinal lymph node status is the single most important prognostic factor for survival in patients with carcinoma penis. Various modifications and alternatives to open inguinal lymph node dissection have been developed as the same is associated with high postoperative morbidity such as wound infection, skin flap necrosis, lymphorrhea, and lymphedema. Robot-assisted video endoscopic inguinal lymph node dissection (RA-VEIL) has the potential to accomplish thorough inguinal lymph node dissection with definitively reduced postoperative morbidity. In this video, we demonstrate our technique of RA-VEIL: The fascia lata first approach and highlight our technical modifications of the conventionally described procedure.