Immunohistochemical expression of PD-L1 and MDR1 in breast tumors: association with clinico-pathological parameters and treatment outcome.

Antitumor immune evasion is a hallmark for the development and progression of cancer. Tumor cells adopt various mechanisms to escape the host immune system recognition. One such mechanism is the over expression of programmed death ligand (PD-L1), a negative T cell regulatory molecule. Because PD-L1 overexpression causes resistance to chemotherapeutic response in many cancers, herein we explored the relationship between PD-L1 and multidrug resistance protein MDR1 in breast cancer. Immunohistochemical evaluation of PD-L1 and MDR1 proteins in 194 breast cancer tissue samples were carried out. The relationship between PD-L1 and MDR1 expression on cancer cells with clinicopathological factors and prognosis was investigated. IHC showed a significant correlation between PD-L1 and MDR1 expression on tumor cells. Increased PD-L1 expression was also associated with lymph node status and tumor grade of the patient. Our results also revealed that the expression of PD-L1 and MDR1 was higher in TNBC subtype compared to other breast cancer subtypes. Therefore, a better understanding of the molecular mechanism through which PD-1/PD-L1 pathway contribute to the chemoresistance might bring forth the prognostic significance of PD-L1 and selection of patients who may benefit from immunotherapy.

A randomized controlled trial to study the effect of intratracheal and intravenous lignocaine on airway and hemodynamic response during emergence and extubation following general anesthesia.

OBJECTIVE: Intratracheal (IT) and intravenous (IV) lignocaine suppress airway reflex and hemodynamic response during extubation, but studies regarding this are sparse. The primary aim was to compare the effect of IT and IV lignocaine on attenuation of airway reflex to endotracheal extubation and the secondary aim was to compare the hemodynamic responses to extubation, using lignocaine by the two different routes. METHODS: Seventy-five female patients with comparable age, body mass index, and American Society of Anesthesiologists Physical Status undergoing carcinoma breast surgery were randomized into three groups. Group A received 2% lignocaine 3 mg/kg intratracheally 5 min and Group B received 2% lignocaine 1.5 mg/kg intravenously 3 min before extubation. Group C was control group. The airway and hemodynamic responses were noted in terms of episodes of cough during emergence and extubation. Categorical variables assessed using Fisher's exact test and continuous variables assessed using one-way analysis of variance. RESULTS: Cough suppression was present in Groups A and B, with better results observed with IT than with IV lignocaine. In the control group, Grade III cough reflex was present predominantly. There was a statistically significant difference (p<0.001) in blood pressure and heart rate between Group A versus Group C and in Group B versus Group C, but not between Group A and Group B. CONCLUSION: IT lignocaine administered before extubation significantly attenuates post-extubation cough reflex than IV lignocaine. Both IT and IV lignocaine can effectively attenuate the airway and hemodynamic response to extubation.

Uterine Sarcoma: Retrospective Study From A Single institute.

Abstract: Uterine sarcomas are heterogeneous group of tumours comprising 1% of gynaecological malignancies. There is lack of concences on optimal treatment of uterine sarcomas. This is because of lack of randomised controlled trials due to rarity of these tumours. Surgical management without spill remains the standard primary treatment. Most of the times uterine sarcomas are diagnosed postoperatively from histopathology report of either myomectomy or hysterectomy. This retrospective study analysed the clinico pathological characteristics, prognostic factors, treatment details and survival outcome of different types of uterine sarcomas. Materials and methods: This is a retrospective analysis of 59 patients of uterine sarcomas. All patients underwent surgery. Adjuvant chemotherapy or radiation treatment were given according to histopathological report and FIGO stage. Patients were followed up every three months for first two years and then every six months. Disease free survival (DFS) and Overall survival (OS) were calculated. Statistical analysis: The data were summarized using descriptive statistics as mean, percent and range. Survival probabilities were estimated using Kaplan-Meier method and the significance of difference between the survival curves were calculate using log-rank test. Results: Uterine sarcomas are rare and aggressive tumours of uterus. Majority of these tumours present in early stage. Surgery remains the main treatment modality. Role of adjuvant radiation treatment remains controversial. Tumour stage is the most important prognostic factor.

Is Young Age an Independent Prognostic Factor in Carcinoma Breast? A Single-Institution Retrospective Comparative Study from South India.

Breast cancer is the most common cancer in women globally(1). It is usually a disease of old age. The incidence of breast cancer in females younger than 40 years is as low as 0.5%. Disease in patients with age less than or equal to 40 years at diagnosis is usually considered a young breast cancer(2). Occurrence of more adverse pathological features like triple negative and Her2 positive breast cancer as well as lacking reliable screening methods in young women leads to the poor prognosis in this group of patients(3). In the present study we aim to find the clinical and pathological characteristics of breast cancer in young women and their survival outcome for 5 years comparing the same with those characteristics of the older patients. Patients with nonmetastatic carcinoma breast who had registered at Regional Cancer Centre, Trivandrum, during the year 2012 were selected for the study. Patient's details including the clinicopathological features, treatment details, oncologic outcomes including recurrence, and survival data until 31 July 2019 were collected from treatment files kept in the hospital and via telephonic interview. Kaplan-Meier method was employed for survival analysis. Survival comparison was done using the log-rank test. Cox proportional hazards regression analysis was done for assessing the risk. Out of 1611 curatively treated patients with carcinoma breast, 281 (17.44%) were young breast cancer (equal to or less than 40 years). The median follow-up period was 82 months. Median age of diagnosis was 51.3 years. Young patients presented with larger tumour size, but nodal stage and composite stage, were not different. They had more TNBC status, 35% vs. 24%, p = 0.001. Young patient group had a drop in 5-year OS but statistically insignificant (75.9% vs. 82.5%, p = 0.179) and marginally significant drop in DFS (68.1% vs. 73.8%, p = 0.064). The proportion of young breast cancer is very high in the Indian population. Age is not an independent risk factor for worse prognosis. T and N stage, Her2nue status, and adequacy of nodal clearance are the most important independent risk factors deciding the 5-year OS.

Serum Free Light Chain Assay as a Prognostic Marker in Patients with Aggressive B-Cell Non-Hodgkin's Lymphoma: Impact on Survival Outcome.

T.M. AnoopBackground The role of serum free light chain (FLC) as a prognostic biomarker in lymphoproliferative diseases is being increasingly studied. In this study we present the 5-year survival outcome for patients with aggressive B-cell non-Hodgkin's lymphoma (NHL) and their relation to FLC and other known prognostic markers. Materials and Methods This is a prospective study conducted in patients diagnosed with aggressive B-cell NHL. Serum FLC level and ratio were estimated prior to initiation of treatment. Results A total of 100 patients were included in the study from December 2013 to December 2015 with a median age of 53 years. Thirty-eight patients (38%) had elevated FLC level of which 26% were polyclonal and 12% were monoclonal elevations. Abnormal FLC ratio was noted in 12% patients. Median follow-up duration of the study was 75 months. Five-year relapse-free survival (RFS) for the study population was 54.4%. Five-year RFS was 64.1% for early stage and 48.2% for advanced stage diseases ( p = 0.05). The RFS was significantly better in age less than 60 years (59.5% vs 43.8%, p < 0.001). Five-year overall survival (OS) was 61.3%. OS was significantly better in younger patients (73.6% vs 33.4%, p < 0.001), with International Prognosis Index score of 0 to 2 (87.4% vs 26.7%, p < 0.001). Patients with elevated FLC had inferior RFS (50% vs 71.4%, p = 0.04). Abnormal FLC ratio also strongly corresponded to inferior RFS (54.5% vs 66.2%, p = 0.001). OS was also significantly inferior in patients with abnormal FLC ratio (72.6% vs 63.6%, p = 0.001). Conclusion In patients with newly diagnosed aggressive B-cell NHL, elevated FLC levels and abnormal FLC ratio were significantly associated with inferior survival.

Evaluation of Factors Affecting Margin Positivity and Persistent Disease After Leep for Cervical Intraepithelial Neoplasia.

BACKGROUND: Cervical intraepithelial neoplasia (CIN) is the precursor lesion of cervical cancer. Untreated high-grade CIN significantly increases the risk of developing invasive cancer. Conization is the main treatment. Loop electrosurgical excision procedure (LEEP) is the most common conization method used. The study aims to assess the risk factors associated with positive margin and persistent disease after LEEP for CIN. MATERIALS AND METHODS: A total of 156 patients who underwent LEEP during 2011-2018 included in the study. We analyzed the socio-demographic characteristics, colposcopy details, dimensions of LEEP specimen (thickness, length, volume) and histopathology (margin positivity, grade). Persistent disease was histologically confirmed by repeat LEEP and hysterectomy. RESULTS: Margin positivity was noted in 33.3% (52) patients. Residual disease was noted in 26.2% (41) of the patients who had undergone a repeat LEEP or hysterectomy. There was a significant association between margin positivity and Swede score of 5 or more, a high-grade lesion on IFCPC score, inner margin involvement, LEEP done in a single pass. The cutoff for margin positivity was length of 0.513 cm and thickness of 0.35 cm. A significant association between residual disease and margin positivity, postmenopausal status, Swede score of 5 or more, high-grade lesion on IFCPC score, inner margin involvement was observed. The chance of residual disease was less if the cone specimen had minimum length of 0.775 cm and minimum thickness of 0.65 cm. CONCLUSION: When in doubt regarding the margins, it is always better to perform multiple passes for lesions with a high Swede score with an initial smear of HSIL. Postmenopausal women with inner margin positivity have a high chance of residual disease and should be either kept on close follow-up or consider a repeat procedure.

Prevalence and Risk Factors for Metabolic Syndrome Among Childhood Acute Lymphoblastic Leukemia Survivors: Experience From South India.

BACKGROUND AND OBJECTIVES: Improved survival of childhood acute lymphoblastic leukemia (ALL) has diverted attention to the long-term consequences of the treatment; metabolic abnormalities being one of the most important issues. METHODS: Children diagnosed with ALL at age 14 years and younger at Regional Cancer Centre in South India who completed treatment and who were on follow-up for >2 years were enrolled in the study between April 1, 2018 and March 31, 2019. They were prospectively evaluated for the presence of metabolic syndrome (MS) and associated risk factors. RESULTS AND DISCUSSION: A total of 277 survivors of pediatric ALL were recruited during the study period. MS was present in 8.3% (n=23) and 6% (n=13) survivors by National Cholesterol Education Programme Adult Treatment Panel III (NCEPATP III) and International Diabetes Federation (IDF) criteria, respectively. The prevalence of overweight and obesity in the survivors was 9% and 13%. The prevalence of increased waist circumference, low high-density lipoprotein cholesterol, elevated triglycerides, elevated fasting glucose, and increased blood pressure were 10.5%, 28.9%, 24.9%, 2.5%, and 9%, respectively. Overweight/obese survivors were at an increased risk for developing MS (odds ratio=17.66; 95% confidence interval=6.2-50.16, P=0.001). Survivors who received cranial radiotherapy were at an elevated risk for having low high-density lipoprotein cholesterol (P=0.001). CONCLUSIONS: In our study, the prevalence of MS was higher in childhood ALL survivors, as compared with the general population. The study points to the need for regular screening of pediatric ALL survivors for early detection of MS, along with lifestyle modification in those with metabolic abnormalities, to curb the growing incidence of coronary artery disease.

Prognostic factors and outcomes of nonseminomatous germ cell tumours of testis-experience from a tertiary cancer centre in India.

Germ cell tumour of the testis is the most common cancer in young men in the western world. India has the lowest incidence globally, and hence Indian data are sparse. We report the outcomes of patients with nonseminomatous germ cell tumours of testis treated at a tertiary cancer centre in South India over a period of 10 years. Patients with a histopathological diagnosis of nonseminomatous germ cell tumours of the testis from 1 January 2006 to 31 December 2016 were included in the study. Patient demographics, tumour characteristics and treatment details were retrieved from case records. Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS). Cox regression model was used to analyse the prognostic factors. One hundred and nineteen patients with nonseminomatous germ cell tumours of the testis were included in the study. The median follow-up was 81 months. The estimated 4-year OS and progression-free survival were 87.1% and 84.5%, respectively. The four-year OS for good, intermediate and poor-risk groups was 93.6%, 87.5% and 52.6%, respectively. The PFS at 4 years was 91.4%, 87.8% and 47.4% for good, intermediate and poor-risk groups, respectively. The presence of nonpulmonary visceral metastasis and biochemical response after chemotherapy were significant predictors for OS and PFS in multivariate cox proportional hazards regression. The survival figures are comparable to the rest of the world except in the poor prognostic risk group. The inferior survival noticed in this group of patients may be due to the lack of good salvage procedures. High-dose chemotherapy with stem-cell support may be considered more often for this group of patients.

Higher incidence of syndrome of inappropriate antidiuretic hormone secretion during induction chemotherapy of acute lymphoblastic leukemia in indian children.

BACKGROUND: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a well-known adverse effect of vincristine (VCR). Literature suggests that Asians are predisposed to develop SIADH following VCR administration. However, data regarding the occurrence of SIADH in children with malignancy are limited. This study aims to analyze the incidence, clinical picture, risk factors, management, and outcome of SIADH during induction chemotherapy for pediatric acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: A prospective study was conducted among the 166 newly diagnosed pediatric ALL patients who were treated at a tertiary cancer center in India between January 2015 and December 2015. Patients who developed hyponatremia during induction chemotherapy were further investigated for SIADH. RESULTS: The incidence of SIADH was 10.8% (n = 18) with a mean sodium level of 125 mEq/L (114-129 mEq/L). In the preceding 2 weeks, 72% of episodes were associated with the administration of two (n = 6) or three (n = 7) doses of VCR. One child presented with seizures. All the patients were managed with fluid restriction and only two patients required sodium correction with 3% saline. Girls older than 10 years of age showed a marginally significant correlation to develop SIADH (P-value = 0.059). CONCLUSION: We report a higher incidence of SIADH (10.8%) in Indian children, compared to that described in the literature, during induction chemotherapy for ALL. Regular monitoring of sodium levels during this period of chemotherapy is hence essential for the timely diagnosis and appropriate management of SIADH, which in turn will avert complications, including neurological symptoms secondary to SIADH.

Phase IIb trial comparing two concurrent cisplatin schedules in locally advanced head and neck cancer.

BACKGROUND: Concurrent chemoradiation with 3 weekly cisplatin (100 mg/m2) is the standard of care for locally advanced head and neck cancer. However, this regimen has been shown to be associated with lesser compliance and higher toxicities. Hence, there is a need to explore alternative concurrent cisplatin regimens. OBJECTIVES: The objective of this study was to compare the efficacy and toxicities of 3 weekly cisplatin (100 mg/m2) with weekly cisplatin (40 mg/m2) concurrently with radiation in patients with locally advanced head and neck cancer. PATIENTS AND METHODS: This phase IIb trial randomized 56 patients with Stage III and IV squamous cell carcinoma of oropharynx, hypopharynx, and larynx to Arm A or Arm B. Arm A received cisplatin 100 mg/m2 3 weekly and Arm B received cisplatin 40 mg/m2 weekly concurrently with radiation. The primary end point was disease-free survival (DFS) and secondary end points were overall survival (OS) and acute toxicity. DFS and OS were estimated using Kaplan-Meier method, and log-rank test was used to assess the difference in these distributions with respect to treatment. RESULTS: The 2-year DFS in Arm A and Arm B was 64.5% and 52.8%, respectively (P = 0.67). The OS at 2 years was 71% and 61.1% in Arm A and Arm B, respectively (P = 0.61). There were no significant differences in acute hematological, renal, or mucosal toxicities between the two arms. CONCLUSION: This study showed a nonsignificant improvement in DFS and OS in the 3 weekly cisplatin arm over the weekly arm with comparable toxicities. The trial is registered with Clinical Trial Registry of India (CTRI registration number: CTRI/2013/05/003703, URL-http://ctri.nic.in).

Role of laparoscopy in predicting surgical outcomes in patients undergoing interval cytoreduction surgery for advanced ovarian carcinoma: A prospective validation study.

OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of laparoscopy in detecting inoperable disease in patients undergoing interval cytoreduction (ICR) for advanced ovarian carcinoma (AOC). The primary outcome measured was the performance of laparoscopy-based predictive index value (PIV) score developed by Fagotti et al. The secondary outcomes measured were performance of individual parameters included in PIV score and optimal cytoreduction (OCR) rates in our population. PATIENTS AND METHODS: This is a single-arm, prospective validation trial. Patients undergoing ICR for AOC in our institution were evaluated prospectively with laparoscopy before planned attempt at debulking surgery. Seven laparoscopic parameters included in laparoscopic PIV score were evaluated. Laparoscopic findings were compared with the final outcomes of definitive surgery. OCR was defined as residual disease <1 cm. The efficiency of the individual laparoscopy score was analyzed using receiver operating characteristic (ROC) curves. RESULTS: A total of 73 patients planned for ICR for AEOC were included in the study. Laparoscopic PIV score could successfully predict inoperability in 12 (16.4% of total study population) out of 14 inoperable patients in the total population and thus could avoid 85% of unsuccessful surgeries at a PIV score cutoff of ≥8. Performance of individual parameters included in PIV score was also evaluated. Two parameters out of seven, that is, mesenteric retraction and stomach infiltration had poor performance on ROC curve. Modified PIV score was calculated for each patient after excluding these two parameters. Modified PIV score had similar performance as Fagotti's PIV score at cutoff ≥6 (P = 0.728, for difference in area under the curve). No staging laparoscopy-related serious adverse events were noted in any of the patients. CONCLUSIONS: Laparoscopy is a safe, effective, and accurate method for predicting inoperability in patients undergoing ICR for AEOC.