Supraclavicular block evaluation in oncoorthopedic patients under general anesthesia using perfusion index: A prospective cohort study.

Background: Supraclavicular brachial plexus blocks (SCBPB) are routinely placed prior to anaesthetic induction for post-operative pain relief after prolonged orthopaedic oncosurgery, since patients are required to remain awake for sensorimotor evaluation of block. If the window period after surgery but before anesthesia-reversal is employed for administering SCBPB, it bestows the quadruple advantage of being painless, not augmenting surgical bleed, longer post-operative analgesia and reduced opioid-related side effects. The problem spot is assessing SCBPB-efficacy under general anesthesia. Methods: This prospective, single-centric, observational cohort study included 30 patients undergoing upper limb orthopaedic oncosurgery under general anesthesia. Perfusion index (PI) was assessed using two separate units of Radical-7™ finger pulse co-oximetry devices simultaneously in both the upper limbs and PI ratios calculated. Skin temperature was noted. Results: After successful block, PI values in blocked limb suddenly increased after 5 min, progressively increasing for next 10 min, whereas PI failed to increase further above that attained post anaesthetic-induction in unblocked limb. PI values in the blocked limb were 4.32, 4.49, 4.95, 7.25, 7.71, 7.90, 7.94, 7.89, and 7.93 at 0, 2, 3, 5, 10, and 15 min post block-institution at reversal and 2 min, 5 min post-reversal, respectively. PI ratios at 2, 3, 5, 10, and 15 min post block-administration in the blocked limb, taking PI at local anaesthetic injection as denominator were 1.04, 1.15, 1.67, 1.78, and 1.83, respectively. Correlation between PI and skin temperature in the blocked limb gave a repeated measures correlation coefficient of 0.79. Conclusion: Monitoring trends in PI and PI-ratio in the blocked limb is a quantitative, non-invasive, inexpensive, simple, effective technique to monitor SCBPB-onset in anaesthetised patients.

Circulating Chromosome Conformation Signatures Significantly Enhance PSA Positive Predicting Value and Overall Accuracy for Prostate Cancer Detection.

BACKGROUND: Prostate cancer (PCa) has a high lifetime prevalence (one out of six men), but currently there is no widely accepted screening programme. Widely used prostate specific antigen (PSA) test at cut-off of 3.0 ng/mL does not have sufficient accuracy for detection of any prostate cancer, resulting in numerous unnecessary prostate biopsies in men with benign disease and false reassurance in some men with PCa. We have recently identified circulating chromosome conformation signatures (CCSs, Episwitch® PCa test) allowing PCa detection and risk stratification in line with standards of clinical PCa staging. The purpose of this study was to determine whether combining the Episwitch PCa test with the PSA test will increase its diagnostic accuracy. METHODS: n = 109 whole blood samples of men enrolled in the PROSTAGRAM screening pilot study and n = 38 samples of patients with established PCa diagnosis and cancer-negative controls from Imperial College NHS Trust were used. Samples were tested for PSA, and the presence of CCSs in the loci encoding for of DAPK1, HSD3B2, SRD5A3, MMP1, and miRNA98 associated with high-risk PCa identified in our previous work. RESULTS: PSA > 3 ng/mL alone showed a low positive predicted value (PPV) of 0.14 and a high negative predicted value (NPV) of 0.93. EpiSwitch alone showed a PPV of 0.91 and a NPV of 0.32. Combining PSA and Episwitch tests has significantly increased the PPV to 0.81 although reducing the NPV to 0.78. Furthermore, integrating PSA, as a continuous variable (rather than a dichotomised 3 ng/mL cut-off), with EpiSwitch in a new multivariant stratification model, Prostate Screening EpiSwitch (PSE) test, has yielded a remarkable combined PPV of 0.92 and NPV of 0.94 when tested on the independent prospective cohort. CONCLUSIONS: Our results demonstrate that combining the standard PSA readout with circulating chromosome conformations (PSE test) allows for significantly enhanced PSA PPV and overall accuracy for PCa detection. The PSE test is accurate, rapid, minimally invasive, and inexpensive, suggesting significant screening diagnostic potential to minimise unnecessary referrals for expensive and invasive MRI and/or biopsy testing. Further extended prospective blinded validation of the new combined signature in a screening cohort with low cancer prevalence would be the recommended step for PSE adoption in PCa screening.

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.

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.

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.

Analysis of Clinical Outcomes of Patients with Soft Tissue Sarcoma.

The aim of this study was to evaluate the outcome of patients with soft tissue sarcoma of the extremity and abdominal wall. This is the retrospective analysis of patients from a prospectively maintained data base from a single institute. We identified 79 patients with intermediate- to high-grade soft tissue sarcomas who were treated at our institute between Jan 2015 and July 2018. Low-grade tumors were excluded. There were 60 males and 19 females with a mean age of 44.6 years. Of the 79 sarcomas, 50 were in the lower limb and 24 in the upper limb and 5 were in abdominal wall. The commonest subtypes were undifferentiated pleomorphic sarcoma (n = 21) and synovial sarcoma (n = 19). Only 9 patients had metastatic disease at presentation. All 79 patients underwent surgical resection with an intent to achieve clear margins. Amputation was done in 19 patients while wide excision of the tumor was done in 60 patients. Adjuvant radiotherapy was given in 49 patients while adjuvant chemotherapy was given in 35 patients. At last follow-up (73 patients), 48 patients are alive without disease, 9 are alive with disease, 12 patients had died of disease, and 4 patients died due to other causes. Overall survival (OS) for 3 year is 77.6%, and estimated mean survival is 55.05 months. Relapse-free surviva (RFS)l at 3 year is 74.3%, and estimated mean RFS is 51.78. The only independent factor that affected the OS was the dimension of primary tumor (p = 0.02). For disease-free survival, the independent factors that affected outcome were stage at presentation (p = 0.04) and dimension of the tumor (p = 0.04). Short-term results shown by this study shows good outcome in patient with intermediate- to high-grade sarcomas when multidisciplinary approach is utilized for the management. Patients who had metastatic disease at presentation did worse than patients who did not.

Clinical and pathologic characteristics to select patients for focal therapy or partial gland ablation of nonmetastatic prostate cancer.

PURPOSE OF REVIEW: Focal therapy or partial gland ablation for nonmetastatic prostate cancer is gaining popularity not just as an alternative to active surveillance, but as an acceptable alternative to whole gland therapy in appropriate cases. This review summarizes recent evidence to help select patients for optimal outcomes. RECENT FINDINGS: Recommendations by expert panels have become less conservative with each meeting. As experience with older modalities for focal therapy grows, newer modalities continue to be introduced. We are now in a position to offer personalized treatment pathway considering nuances of each focal therapy modality. SUMMARY: The ideal case for focal therapy should be an MRI visible significant lesion (PIRADS score ≥ 3), with a positive biopsy for significant cancer (Gleason grade group 2-3) in the corresponding targeted biopsy area, and insignificant or absent disease in the nontarget random biopsy areas. Multifocal disease can also be selectively treated. Salvage focal ablation is an attractive treatment option for radio-recurrent or index focal therapy failure cases.

Efficacy of the three-point cuff palpation technique in preventing endobronchial tube migration during positioning in robotic pelvic surgeries.

Background and Aims: During robotic pelvic surgeries, the shortening of endotracheal tube (ETT) tip-to-carina distance (DTC) during pneumoperitoneum with 45° Trendelenburg position can result in endobronchial tube migration. In the three-point ETT cuff palpation (TPP) technique, maximal ETT cuff distension is felt over the tracheal segment located between the cricoid-thyroid membrane and suprasternal notch, which is likely to provide optimal placement. However, the reproducibility and reliability of the TPP technique in preventing endobronchial tube migration are yet to be evaluated. Hence, we compared three ETT placement techniques: TPP technique, intubation guide mark (IGM) technique and Varshney's formula (VF) for the prevention of endobronchial tube migration during robotic pelvic surgeries. Methods: ETT placement by TPP was compared with IGM and VF techniques in 100 American Society of Anesthesiologists physical class II-III patients, by assessing the serial changes in DTC and incidence of endobronchial tube migration throughout the different phases of pneumoperitoneum and Trendelenburg position using t-test and Chi-square test. Changes in the DTC during various phases were also measured. Results: DTC (mean ± standard deviation) at baseline and during pneumoperitoneum was significantly better in TPP technique (2.80 ± 0.62 cm and 1.96 ± 0.66 cm) as compared to both IGM (2.50 ± 1.27 cm and 1.41 ± 1.29 cm) and VF techniques (1.83 ± 1.13 cm and 0.98 ± 1.18 cm), P < 0.001. During pneumoperitoneum, the mean shortening of DTC was 0.84 ± 0.20 cm, and no endobronchial tube migration was found in TPP technique compared to 20% in IGM and 25% in VF techniques, P < 0.001. Conclusion: TPP is a simple and reliable technique, which provides optimal ETT placement and prevents endobronchial tube migration throughout the different phases of robotic pelvic surgeries.

Utility of lung ultrasound for extravascular lung water volume estimation during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND AND AIMS: Rising extravascular lung-water index (ELWI) following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC), if not timely intervened, can progress to pulmonary oedema. Transpulmonary thermodilution (TPTDL) is a standard technique to estimate ELWI (T-ELWI score), and track ongoing changes. Lung ultrasound (LUS) is another technique for ELWI (L-ELWI score) estimation. However, reproducibility and reliability of LUS for tracking serial L-ELWI changes during CRS + HIPEC remains to be validated. METHODS: This prospective observational study included 360 L-ELWI and T-ELWI measurements at 12 peri-operative time-points. Cohen's Kappa test was used to assess reproducibility, Inter-rater agreement (between the anaesthetist and radiologist), and agreement between LUS and TPTDL for classifying the severity of pulmonary oedema. Reliability of LUS for 'tracking serial changes' in ELWI over time in individual patients was assessed by determining the repeated measures correlation (z-rrm) between weighted L-ELWI and T-ELWI scores. The ability of both techniques to discriminate pulmonary oedema was compared by analysing the area under ROC curves. RESULTS: Excellent inter-rater agreement for assigned L-ELWI scores was observed (linear weighted κ = 0.95 for both). Both techniques had a good agreement in classifying the severity of pulmonary oedema (linear weighted κ = 0.63, 95% CI 0.51-0.79). T-ELWI and weighted L-ELWI scores correlated strongly (z-rrm = 0.88, 95% CI 0.80-0.92, P < 0.0001). Both techniques had comparable ability to discriminate pulmonary oedema (difference in area under ROC curve = 0.0014, 95%CI -0.0027 to 0.0055, P = 0.5043). CONCLUSION: We found the utility of LUS as a reliable and reproducible technique for ELWI estimation and tracking its changes over time in CRS + HIPEC.

Pitcher pot neourethral modification of ileal orthotopic neobladder achieves satisfactory long-term functional and quality of life outcomes with low clean intermittent self-catheterization rate.

Objective: To describe a decade of our experience with a neo-urethral modification of ileal orthotopic neobladder (pitcher pot ONB). Multiple investigators have reported similar modifications. However, long-term longitudinal functional and quality of life (QOL) outcomes are lacking. Methods: Prospectively maintained hospital registry for 238 ONB patients comprising a mix of open and robotic surgery cohorts from 2007 to 2017, and minimum of 2 years of follow-up was retrospectively queried. QOL was evaluated using Bladder Cancer Index (BCI). Longitudinal trends of QOL domain parameters were analysed. List of perioperative variables that have a biologically plausible association with continence, potency, and post-operative BCI QOL sexual, urinary, and bowel domain scores was drawn. Variables included surgery type, Body Mass Index (BMI), T and N stage, neurovascular bundle (NVB) sparing, age, and related pre-operative BCI QOL domain score. Prognostic associations were analysed using multivariable Cox proportional hazard models and multilevel mixed-effects modeling. Results: The study comprised 80 and 158 patients who underwent open and robotic sandwich technique cohorts, respectively. Open surgery was associated with significantly higher "any" complication (40% vs 27%, P-value .050) and "major" complication rate (15% vs 11%, P-value .048). All patients developed a bladder capacity >400 cc with negligible post-void residual urine, and all but one patient achieved spontaneous voiding by the end of study period (<1% clean intermittent self-catheterization [CISC] rate). By 15 months, QOL for all three domains had recovered to reach a plateau. About 45% of patients achieved potency, and the median time to achieve day and night time continence was 9 and 12 months respectively. Lower age and NVBs spared during surgery were found to be significantly associated with the earlier achievement of potency, day and night time continence, as well as better urinary and sexual summary QOL scores. Conclusions: Pitcher pot neobladder achieves satisfactory long-term functional and QOL outcomes with negligible CISC rate. Results were superior with incremental nerves spared during surgery.

CSF cell-free DNA EGFR testing using DdPCR holds promise over conventional modalities for diagnosing leptomeningeal involvement in patients with non-small cell lung cancer.

BACKGROUND: EGFR mutant NSCLC patients have leptomeningeal (LM) involvement in more than 9% cases. MATERIAL & METHODS: We conducted a study evaluating the diagnostic utility of cfDNA EGFR testing in CSF using DdPCR while comparing it against MRI and CSF cytology. We also looked for known EGFR mutations in the CSF sample. These mutations were also tested in paired plasma samples. We further compared which constituent of CSF (pellet/supernatant) had better yield. RESULTS: 21 patients comprised the study. Of these 17 patients were diagnosed to have LM involvement based on conventional criteria. All modalities had 100 % specificity and positive predictive value. However, MRI and CSF cytology had a poor negative predictive value. cfDNA had the highest sensitivity (92.3 %), negative predictive value (75 %), accuracy (94.1 %), and net comparative benefit. Paired plasma samples were available for 19 patients. Primary EGFR mutation was detectable in the CSF sample in 16/19 patients; however, the plasma sample was positive only in 7/19 patients. 3 samples were negative for primary EGFR mutation in both CSF and plasma. None of the CSF samples showed positivity for T790M mutation which could however be observed in two patients in plasma samples. Both supernatant and pellet were analysed for cfDNA mutation analysis in 18/21 patients. The intraclass correlation coefficient regarding the percentage fraction tumor-derived DNA of cfDNA observed was 0.83(95 % CI 0.29 to 0.95) between both samples. CONCLUSION: EGFR detection in CSF has a potential role in diagnosing LM involvement. T790 M resistance mutations are uncommon in CSF post first and second-generation TKIs. Both supernatant and pellet samples can be used for the extraction of cell-free DNA in CSF.

Uro-oncology in times of COVID-19: The available evidence and recommendations in the Indian scenario.

The Corona Virus Disease-2019 (COVID-19), one of the most devastating pandemics ever, has left thousands of cancer patients to their fate. The future course of this pandemic is still an enigma, but health care services are expected to resume soon in a phased manner. This might be a long drawn process and we need to have policies in place, to be able to fight both, the SARS-CoV-2 virus and cancer, simultaneously, and emerge triumphant. An extensive literature search for impact of delay in management of various urological malignancies was carried out. Expert opinions were sought wherever there was paucity of evidence, in order to reach a consensus and come up with recommendations for directing uro-oncology services in the times of COVID-19. The panel recommends deferring treatment of patients with renal cell carcinoma by 3 to 6 months, except for those with ongoing hematuria and/or inferior vena cava thrombus, which warrant immediate surgery. Metastatic renal cell cancers should be started on targeted therapy. Low grade non-muscle invasive bladder cancers can be kept on active surveillance while high risk non-muscle invasive bladder cancers and muscle invasive bladder cancers should be treated within 3 months. Neoadjuvant chemotherapy should be avoided. Management of low and intermediate risk prostate cancer can be deferred for 3 to 6months while high risk prostate cancer patients can be initiated on neoadjuvant androgen deprivation therapy. Patients with testicular tumors should undergo high inguinal orchiectomy and be treated according to stage without delay, with stage I patients being offered surveillance. Penile cancers should undergo penectomy, while clinically negative groins can be kept on surveillance. Neoadjuvant chemotherapy should be avoided and adjuvant therapy should be deferred. We need to tailor our treatment strategies to the prevailing present conditions, so as to fight and defeat both, the SARS-CoV-2 virus and cancer. Protection of health care workers, judicious use of available resources, and a rational and balanced outlook towards different malignancies is the need of the hour.

Adjuvant radiation compares favorably to chemotherapy in patients with carcinoma penis and nodal positivity restricted to groin.

OBJECTIVES: To compare overall survival (OS) between adjuvant radiation, chemotherapy and chemoradiation (CCRT) postsurgery for node-positive patients with carcinoma penis. METHODS: Prospectively maintained registry for 45 patients receiving adjuvant treatment following lymph node dissection from 2011 to 2017, having minimum 6 months follow-up and more than 2 positive inguinal nodes was analyzed. Patients without pelvic nodal positivity (n= 32) were treated by radiotherapy (RT) (n = 25) or chemotherapy (n = 7); CCRT (n = 6) or chemotherapy (n = 7) was used in patients with positive pelvic nodes (n = 13). Data was collected for age, comorbidities, body mass index, tobacco exposure, treatment modality, tumor grade, pathological T and N stage, and extra-nodal extension. OS was compared between different treatment modalities stratifying patients with and without pelvic nodal positivity. Multivariate cox proportional hazard analysis was used to narrow down remaining variables and Inverse Probability Treatment Weights modeling was used to determine average treatment effect. RESULTS: About 12 of 14 patients in the chemotherapy group received both cisplatin and paclitaxel. Pathological T stage, N stage and extra-nodal extension had significant association with OS on multivariate analysis. Among patients with nodal positivity restricted to groin the estimated average OS when all patients received adjuvant RT was 1,438 days (95% confidence interval [CI] 1,256-1,619 days, Pvalue <0.0001). The estimated average OS if all patients received chemotherapy was lower by 1,007 days (95% CI 810-1,202 days, P value <0.0001). Among patients with positive pelvic nodes the estimated average OS when all patients received adjuvant CCRT was 467 days (95% CI 368-566 days, P value <0.0001). The estimated average OS difference if all patients received chemotherapy was 17 days (95% CI -144 to 178 days, Pvalue 0.21). CONCLUSION: In patients with nodal positivity limited to groin, adjuvant RT proved superior to chemotherapy. Among patients with pelvic nodal positivity, CCRT offers no significant OS advantage over combination chemotherapy.

Droplet digital polymerase chain reaction offers an improvisation over conventional immunohistochemistry and fluorescent in situ hybridization for ascertaining Her2 status of breast cancer.

BACKGROUND: Droplet digital polymerase chain reaction (DDPCR) is a recent modality for detecting Her2 expression which is quantitative, cheaper, easier to standardize, and free from interobserver variation. PURPOSE: The purpose of this study is to incorporate DDPCR in the current diagnostic paradigm with clinical benefit. MATERIALS AND METHODS: Fifty-four consecutive patients were tested by immunohistochemistry (IHC), fluorescent in situ hybridization (FISH), and DDPCR. With FISH result as gold standard, receiver operating characteristic curves for DDPCR ratio were analyzed to label Her2-negative, equivocal, and positive cases as DDPCR score 1, 2, and 3, respectively. Proportion of patients labeled unequivocally as Her2 positive or negative was defined to have "clinically benefitted" from the test. Drawing parallel to inter-relationships between DDPCR, IHC, and FISH in the test cohort, four diagnostic pathways were defined - (1) initial IHC followed by FISH, (2) initial DDPCR followed by FISH, (3) initial IHC followed by DDPCR followed by FISH, and (4) initial DDPCR followed by IHC followed by FISH. RESULTS: Clinical benefit of DDPCR as an initial test in the test cohort was 57%, while it was 65% if used as a second-line test among those with an initial inconclusive IHC result. Sensitivity analysis in the simulation cohort revealed that if DDPCR cost was ≤0.6 times the cost of IHC, then a three-step pathway with DDPCR upfront would near certainly prove most cost beneficial. If DDPCR cost was >0.6 but ≤2 times the cost of IHC, then a three-step pathway with DDPCR as second-line test had a higher probability to prove most cost beneficial. If DDPCR cost was >2 times the cost of IHC, then conventional pathway had a higher probability to prove most cost-effective. CONCLUSION: Incorporating DDPCR in the current clinical diagnostic paradigm has the potential to improve its cost-effectiveness and benefit.

Number of positive nodes - Current relevance in determining prognosis of oral cavity cancer after the recent AJCC staging update.

INTRODUCTION: Lymph node involvement and the number of positive nodes is a significant prognosticator in oral cavity cancers and current staging system does not incorporate it as an integral part. MATERIAL AND METHODS: This was a retrospective study of oral cavity cancer patients who were operated during the time period of 2009-2017. The data was collected and analysed to assess the impact of increase in the number of positive nodes on survival and its comparison of survival statistics to current AJCC staging. RESULTS: A total of 1431 patients were included in this study and 32.5% of these patients had a node positive disease. Nodal positivity was a significant prognosticator on multivariate analysis. Number of positive nodes was modelled with restricted cubic spline function and it showed progressive worsening of survival functions with increase in number. On Kaplan Meier analysis there was a better separation of curves when number of positive nodes was used and Akaike information criterion (AIC) showed that it was a better prognosticator than existing AJCC staging. CONCLUSION: Number of positive nodes is a significant prognosticator of prognosis and hence should be considered in the AJCC staging system.

Functional analysis of vocal folds by transcutaneous laryngeal ultrasonography in patients undergoing thyroidectomy.

BACKGROUND: Transcutaneous laryngeal ultrasound (TCLUS) can assess Vocal folds (VF) by subjectively identifying mobility or objectively by calculating vocal fold displacement velocity (VFDV). Optimal diagnostic approach (subjective assessment, VFDV estimation or a combination of both) is unresolved; hence, we conducted this prospective study in patients undergoing thyroidectomy. METHOD: Two anaesthetists performed TCLUS pre- and post-operatively for functional assessment of 200 VFs on 100 patients. Their findings were compared with pre-operative flexible laryngoscope (FL) performed by surgeons and with post-operative C-Mac video laryngoscope (C-Mac VL) by another independent anaesthetist. Correlation between FL and TCLUS findings and inter-rater agreement between TCLUS findings of both anaesthetists was analysed. Decision curve analysis (DCA) was performed to compare clinical benefit of hoarseness, subjective VF movement, VFDV, and combined assessment for detecting disabled VFs. RESULTS: We found good correlation between VF mobility on TCLUS and FL (Spearman's r = 0.93, P < 0.0001) as well as C-Mac VL (Spearman's r = 0.83, P < 0.0001) with excellent inter-rater agreement between both anaesthetists. DCA showed combined assessment to have marginally higher clinical benefit than other diagnostic approaches at intermediate threshold probabilities while its benefit was similar to subjective evaluation at higher threshold probabilities. CONCLUSION: Provided achievement of optimal acoustic window, TCLUS can reliably assess disabled VFs with FL reserved for their confirmation or doubtful cases. Subjective assessment of VF mobility should suffice in most cases with additional VFDV estimation reserved pre-operatively for situations with higher risk of VFs disability, and post-operatively when subjective VF assessment findings are discordant from pre-operative status.

The detection of primary and secondary EGFR mutations using droplet digital PCR in patients with nonsmall cell lung cancer.

BACKGROUND: We share our experience of using droplet digital polymerase chain reaction (DdPCR) in liquid biopsy specimens for detecting primary and secondary epidermal growth factor receptor (EGFR) mutations among patients with nonsmall-cell lung cancer who had tissue biopsy initially analyzed for del19, L858R and T790M. MATERIALS AND METHODS: Three groups of patients were chosen: Group 1: patients positive for EGFR mutation (del 19 or L858R) by conventional tissue biopsy that were treatment naïve, Group 2: patients positive for EGFR mutation (del 19 or L858R) by conventional tissue biopsy with acquired resistance to tyrosine kinase inhibitor (TKI) therapy, documented by radiology, and Group 3: no known EGFR mutation detected on primary tissue biopsy and treatment naive. RESULTS: One hundred and thirty-three patients were included in the study. Group 1 had 40 cases, of which 21 (52.5%) and 19 (47.5%) were positive for del19 and L858R mutations, respectively, by tissue biopsy. DdPCR detected primary mutation in all but 5 cases. DdPCR additionally found four patients to have T790M mutation. Group 2 had 73 cases and DdPCR detected T790M mutation in 39 (53.4%) cases. Liquid biopsy also picked the original primary mutation in 56/73 cases. Secondary tissue biopsy for T790M mutation status was performed in 11 patients and while it detected mutation in 2 out of 11 cases, DdPCR detected the same in 7 cases, thus providing significantly superior yield (46% difference, McNemar's test, P value 0.063). Tissue biopsy additionally detected c-MET amplification in a patient who had T790M mutation on liquid biopsy. Group 3 had 20 patients and none were falsely positive for EGFR mutation on liquid biopsy. Overall, DdPCR had a Cohen's kappa of 0.82 (standard error 0.074, 95% CI 0.68-0.97) indicating "very good agreement" with conventional tissue biopsy. CONCLUSION: DdPCR demonstrated 87.5% sensitivity and 100% specificity in detecting primary EGFR mutations in patients who were treatment naïve with overall positive and negative predictive value of 100% and 80%, respectively. DdPCR demonstrated T790M mutation postprogression on TKI therapy in 53.4% patients.

Clinical utility of RT-PCR in assessing HER 2 gene expression versus traditional IHC and FISH in breast cancer patients.

BACKGROUND: IHC and FISH are used for categorizing HER 2 status in breast cancer at the protein and DNA level, respectively. HER 2 expression at the RNA level is quantitative, cheaper, easier to standardize and free from interobserver variation. METHODS: 115 consecutive patients were tested by IHC, FISH and RT-PCR (test cohort). Assuming FISH result to be the response variable, ROC curves for RT-PCR ratio were analyzed to label HER 2 negative, equivocal and positive cases as RT-PCR score 1, 2 and 3, respectively. Inter-relationships between RT-PCR, IHC and FISH were defined. 'Clinical benefit' of a test was defined as proportion of patients labeled unequivocally as HER 2 positive or negative. Population for 1 year was simulated constraint to previous reports of HER 2 positivity and IHC category distribution by a meta-analysis of previous studies that evaluated concordance between IHC and FISH to determine HER 2 status (simulation cohort). Four diagnostic pathways in the simulation cohort were defined-(1) initial IHC, followed by FISH (conventional pathway); (2) initial RT-PCR, followed by FISH; (3) initial IHC, followed by RT-PCR and then by FISH; (4) initial RT-PCR, followed by IHC and then by FISH. The clinical benefit of IHC and RT-PCR in the four pathways was analyzed and sensitivity analysis for incremental cost-effectiveness ratio and cost-benefit comapring RT-PCR against IHC, both as first-line tests and among those with IHC score 2 as a reflex second-line test was performed by the Monte Carlo technique. FINDINGS: 115 patients comprised the study population. While none with IHC score of 0 or 1 was FISH positive for HER 2, all cases with IHC score of 3 were FISH positive. 43 cases were assigned IHC score of 2. Thus, 72 patients benefited from the initial IHC testing [clinical benefit 62.6%], with the overall concordance between IHC and FISH being 100% for those with IHC score of 0, 1 and 3 (conclusive IHC categories). For RT-PCR with 100% concordance, 15.7% (115-97 = 18) patients would have benefited from RT-PCR testing if it was used as a first-line test. If RT-PCR would have been used as a second-line test among those with IHC score 2 (n = 43), then only 6 patients would have been assigned a conclusive RT-PCR category (category 1 or 3) translating to a clinical benefit of 14% (6/43) as a second-line test. As a second-line test it had 51% probability to prove more cost-effective than the conventional pathway, provided the cost of RT-PCR was 0.4 times the cost of IHC. Also in a three-step pathway, RT-PCR upfront would have 56% probability of higher cost-benefit provided the cost of RT-PCR was 0.1 times the cost of IHC. CONCLUSION: RT-PCR results were found to be suboptimal to IHC in terms of discriminative ability and clinical benefit; thus, it is unlikely to replace IHC as a first-line test in the near future.

Comparing Outcomes of Robotic and Open Inguinal Lymph Node Dissection in Patients with Carcinoma of the Penis.

PURPOSE: We compared outcomes between robot-assisted video endoscopic inguinal lymphadenectomy and open inguinal lymph node dissection in patients without bulky nodal metastasis in a tandem contemporary cohort. MATERIALS AND METHODS: We retrospectively analyzed a prospectively maintained hospital registry of 51 patients who underwent robot-assisted video endoscopic inguinal lymphadenectomy and 100 treated with open inguinal lymph node dissection from 2012 to 2016 for groins without bulky nodal metastasis and who had a minimum 9-month followup. Complications were graded by the Clavien-Dindo classification, and nodal yield and disease recurrence during followup were assessed. Elastic net regression was used to select variables associated with major complications (Clavien 3a or greater) for multivariable analysis of plausible factors, including patient age, diabetes, body mass index, smoking, nodal stage, surgery type, sartorius transposition, saphenous vein transection and adjuvant radiotherapy. Penalized likelihood logistic regression methods were used for multivariate analysis to ascertain final effect sizes while accounting for sparse data bias. RESULTS: Robot-assisted video endoscopic inguinal lymphadenectomy and open inguinal lymph node dissection had comparable median lymph node yields (13 vs 12.5). No patient experienced recurrence during the median followup of 40 months. Robot-assisted video endoscopic inguinal lymphadenectomy was associated with significantly lower hospital stay, days needing a drain in situ, incidence of major complications, edge necrosis, flap necrosis and severe limb edema. On multivariable analysis pathological nodal stage (OR 2.8, 95% CI 1.1-6.8, p = 0.027) and open inguinal lymph node dissection (OR 7.5, 95% CI 1.3-43, p = 0.024) emerged as independent risk factors associated with an increased risk of major complications. CONCLUSIONS: Robot-assisted video endoscopic inguinal lymphadenectomy is a feasible technique which allows for a similar nodal yield while being associated with lower morbidity than open inguinal lymph node dissection in patients without bulky groin adenopathy.