Current status of human papillomavirus vaccination in India's cervical cancer prevention efforts.

Efforts are being made to scale up human papillomavirus (HPV) vaccination for adolescent girls in India. Bivalent and quadrivalent HPV vaccines were licensed in the country in 2008, and a nonavalent vaccine was licensed in 2018. Demonstration projects initiated in Andhra Pradesh and Gujarat in 2009 introduced HPV vaccination in public health services in India. Following a few deaths in these projects, although subsequently deemed unrelated to vaccination, HPV vaccination in research projects was suspended. This suspension by default resulted in some participants in a trial evaluating two versus three doses receiving only one dose. Since 2016, the successful introduction of HPV vaccination in immunisation programmes in Punjab and Sikkim (with high coverage and safety), government-sponsored opportunistic vaccination in Delhi, prospects of a single dose providing protection, and future availability of an affordable Indian vaccine shows promise for future widespread implementation and evaluation of HPV vaccination in India.

Pregabalin in the treatment of postmastectomy chronic pain: Results of an open label, single-arm clinical study.

Postmastectomy chronic pain (PMCP) is one of the important survivorship issues faced by breast cancer patients. It is a chronic pain which persists for more than 3 months after mastectomy or quadrantectomy and is considered to be neuropathic in nature. An open label, single-arm, prospective study was conducted to evaluate the efficacy of Pregabalin in relieving clinically significant PMCP (pain score ≥3 on visual analogue scale). Pregabalin brought about significant reductions in pain (visual analogue scale [VAS] Scores; baseline 5.50 ± 1.197, end of 1 month 2.40 ± 1.430, end of 2 months 2.10 ± 1.370) and significant improvement in quality of life.

The Impact of Peritumoral Retraction Clefting & Intratumoral Eosinophils on Overall Survival in Oral Squamous Carcinoma Patients.

This retrospective study aimed to investigate the impact of peritumoral retraction clefts (RC) and tumor-associated tissue eosinophilia (TATE) as predictors of overall survival (OS) in oral squamous cell carcinoma (OSCC) patients. Their relationships with tumor-factors were also examined. Eighty-seven OSCC cases (pTNM: I + II/III + IV; 32/55), post-curative surgery, comprised the study cohort. Three observers independently estimated the percent RC semi-quantitatively in the selected tumor sections. Additionally, stromal eosinophils were counted in ten consecutive high-power fields of intratumoral and peritumoral regions to evaluate the corresponding TATE. The percent RC ranged between 0% -90% (Mean ± SD: 16 ± 24%; Median: 5%). The stromal eosinophils were greater in peritumoral as compared to intratumoral region. The events of death and tumor recurrence were reached in 16 (18.4%) and 36 (41%) cases respectively. The 3-years OS was 69% [Median OS: 1880 days; Mean follow up: 471(Range; 36-1880) days]. Increased percent RC exhibited relationship with pathologic stage (pTNM III&IV), primary tumor (pT III&IV), tumor depth > 4 mm and categorical tumor recurrence. Additionally, peritumoral eosinophilic infiltrates increased with increasing tumor depths and muscle invasion. Kaplan-Meier curves revealed significantly reduced OS in OSCC cases exhibiting: increased percent RC (>2.5%), mild -moderate/absent intratumoral TATE (versus intense TATE) or categorical tumor recurrence. In subsequent multivariate tests, all the three variables retained significance. Additionally, intraclass correlation coefficient demonstrated acceptable internal consistency for the observers who estimated percent RC. In conclusion, RC and intratumoral TATE proved to be independent predictors of OS in our OSCC cohort. Additionally, increased percent RC pointed towards aggressive tumor behaviour.

Comparison of the Seventh and Eighth Editions of the American Joint Committee on Cancer pT and pN Classifications as Predictors of Survival in Patients With Oral Squamous Cell Carcinoma.

Objectives: We retrospectively compared the seventh and eighth editions of American Joint Committee on Cancer (AJCC) TNM frameworks as disease-free survival (DFS) and overall survival (OS) predictors in oral squamous carcinomas (OSCCs). Methods: We restaged the 342 patients with the revised pT and pN criteria and performed survival analyses. Results: The 3-year DFS (mean follow-up, 364 days; recurrences, 99) was 50%, and the 5-year OS (mean follow-up, 615 days; deaths, 69) was 42%. The eight edition pN classification was an independent multivariate survival predictor. The revised TNM criteria upstaged pT, pN, and stage groupings in 99 (38.8%), 58 (37.3%), and 101 (29.5%) patients. The latter two groups revealed significantly worse DFS and OS compared with those whose categorizations had remained unaltered. In addition, their classification/staging criteria demonstrated superior discrimination, monotonicity, and accuracy for survival estimations. Conclusions: Of the competing AJCC staging criteria, the revised pN classification was the most powerful system to predict OSCC survivals.

Clinical significance of interleukin-6 in diagnosis of lung, oral, esophageal, and gall bladder carcinomas.

INTRODUCTION: Chronic inflammation predisposes to cancer. Cytokines play an essential role in cancer pathogenesis. Interleukin-6 (IL-6) is a pleiotropic cytokine that enables growth and differentiation of tumors. The effects of IL-6 are mediated by signal transducers and activators of transcription 3 (STAT3). STAT3 deficiency reduced tumor incidence and growth while STAT3 hyperactivation has an opposite effect; also it negatively regulates p53 gene. IL-6/STAT3 signaling is crucial in carcinogenesis linked to inflammation. Increased IL-6 levels are observed in cancer. Studies investigating the role of IL-6 is limited. AIM: This study aims at determining IL-6 levels in lung, oral, esophageal, and gallbladder cancer patients. MATERIALS AND METHODS: Subjects consisted of 175 patients with lung, oral, gall bladder, and esophageal cancers. The patients included 68 females and 107 males with an average age of 52 years. Fifty healthy individuals served as controls. IL-6 was detected by electrochemiluminescent immunoassay principle. RESULTS: IL-6 values were determined in 175 (21 lung, 55 oral, 17 esophageal and 82 gallbladder) cancer patients. Of these, 147/175 (18 lung, 43 oral, 13 esophageal and 73 gallbladder) cancer patients (84%) showed higher IL-6 levels as compared to control group (normal range: <7 pg/ml). CONCLUSION: This indicates a significant correlation between IL-6 overexpression and cancer development, highlighting the significance of IL-6 in oral, lung, esophageal, and gallbladder carcinomas. IL-6 may be used as a tumor marker for cancer diagnosis. It may be a clinically significant predictor and may represent a target for cancer treatment. However, to definitely conclude this, further extensive studies would be required.

Useful information provided by graphic displays of automated cell counter in hematological malignancies.

BACKGROUND: Automated cell counters have become more and more sophisticated with passing years. The numerical and graphic data both provide useful clues for suspecting a diagnosis especially when the workload is very high. AIM: We present our experience of useful information provided by graphic displays of an automated cell counter in hematological malignancies in a cancer hospital where a large number of complete blood count (CBC) requests are received either before or during chemotherapy. This study was conducted to assess the usefulness of hematology cell counter, viz. WBC-Diff (WBC differential), WBC/BASO (WBC basophil) and IMI (immature myeloid information) channel scatter plots, and the flaggings generated in various hematological malignancies. MATERIAL & METHODS: The graphic displays have been compiled over a period of 1 year (October 2015-September 2016) from blood samples of various solid and hematological malignancies (approximately 400 per day) received for routine CBC in the laboratory. Approximately 50 000 scattergrams have been analyzed during the study period. The findings were confirmed by peripheral blood smear examination. RESULTS: The scattergram analysis on XE-2100 is very sensitive as well as specific for diagnosing acute leukemia, viz. acute myeloid leukemia, acute lymphoblastic leukemia; chronic myeloproliferative disorders, viz. chronic myeloid leukemia; and chronic lymphoproliferative disorder especially chronic lymphocytic leukemia. CONCLUSION: It is suggested that the laboratories using the hematology analyzers be aware of graphic display patterns in addition to flaggings generated which provide additional information and give clue toward the diagnosis even before peripheral smear examination.

A semi-quantitative World Health Organization grading scheme evaluating worst tumor differentiation predicts disease-free survival in oral squamous carcinoma patients.

We investigated World Health Organization (WHO) grading and pattern of invasion based histological schemes as independent predictors of disease-free survival, in oral squamous carcinoma patients. Tumor resection slides of eighty-seven oral squamous carcinoma patients [pTNM: I&II/III&IV-32/55] were evaluated. Besides examining various patterns of invasion, invasive front grade, predominant and worst (highest) WHO grade were recorded. For worst WHO grading, poor-undifferentiated component was estimated semi-quantitatively at advancing tumor edge (invasive growth front) in histology sections. Tumor recurrence was observed in 31 (35.6%) cases. The 2-year disease-free survival was 47% [Median: 656; follow-up: 14-1450] days. Using receiver operating characteristic curves, we defined poor-undifferentiated component exceeding 5% of tumor as the cutoff to assign an oral squamous carcinoma as grade-3, when following worst WHO grading. Kaplan-Meier curves for disease-free survival revealed prognostic association with nodal involvement, tumor size, worst WHO grading; most common pattern of invasion and invasive pattern grading score (sum of two most predominant patterns of invasion). In further multivariate analysis, tumor size (>2.5cm) and worst WHO grading (grade-3 tumors) independently predicted reduced disease-free survival [HR, 2.85; P=0.028 and HR, 3.37; P=0.031 respectively]. The inter-observer agreement was moderate for observers who semi-quantitatively estimated percentage of poor-undifferentiated morphology in oral squamous carcinomas. Our results support the value of semi-quantitative method to assign tumors as grade-3 with worst WHO grading for predicting reduced disease-free survival. Despite limitations, of the various histological tumor stratification schemes, WHO grading holds adjunctive value for its prognostic role, ease and universal familiarity.

Staphylococcus hominis subsp. novobiosepticus, an emerging multidrug-resistant bacterium, as a causative agent of septicaemia in cancer patients.

Staphylococcus hominis subsp. novobiosepticus is a new sub-species of S. hominis, thus dividing S. hominis into subsp. hominis and novobiosepticus. This study was designed to identify subsp. novobiosepticus isolates amongst the S. hominis isolated from blood samples of patients with malignancy and septicaemia and to study their resistance profile. The identification was performed by using three simple tests which differentiated between the two sub-species. It was found that 22.8 per cent of S. hominis isolates belonged to subsp. novobiosepticus.

Identification of Specific miRNA Signature in Paired Sera and Tissue Samples of Indian Women with Triple Negative Breast Cancer.

Of several subtypes of breast cancer, triple negative breast cancer (TNBC) is a highly aggressive tumor that lacks expression of hormone receptors for estrogen, progesterone and human epidermal growth factor receptor 2 and shows a worst prognosis. The small noncoding RNAs (miRNAs) considered as master regulator of gene expression play a key role in cancer initiation, progression and drug resistance and have emerged as attractive molecular biomarkers for diagnosis, prognosis and treatment targets in cancer. We have done expression profiling of selected miRNAs in paired serum and tissue samples of TNBC patients and corresponding cell lines and compared with that of other subtypes, in order to identify novel serum miRNA biomarkers for early detection and progression of TNBC. A total of 85 paired tumor tissues and sera with an equal number of adjacent normal tissue margins and normal sera from age matched healthy women including tissue and sera samples from 15 benign fibroadenomas were employed for the study. We report for the first time an extremely high prevalence (73.9%) of TNBC in premenopausal women below 35 years of age and a significant altered expression of a panel of three specific oncogenic miRNAs- miR-21, miR-221, miR-210, and three tumor suppressor miRNAs- miR-195, miR-145 and Let-7a in both tissues and corresponding sera of TNBC patients when compared with triple positive breast cancer (TPBC) patients. While miR-21, miR-221 and miR-210 showed significant over-expression, miR-195 and miR-145 were downregulated and well correlated with various clinicopathological and demographic risk factors, tumor grade, clinical stage and hormone receptor status. Interestingly, despite being a known tumor suppressor, Let-7a showed a significant overexpression in TNBCs. It is suggested that this panel of six miRNA signature may serve as a minimally invasive biomarker for an early detection of TNBC patients.

Mucoepidermoid Carcinoma of Parotid as a Second Malignancy in Acute Lymphoblastic Leukemia.

BACKGROUND: Improved survival seen in Acute Lymphoblastic Leukemia (ALL) cases has led to increased reports of second malignant neoplasms. CASE CHARACTERISTICS: A 12-year-old female treated for ALL using UK ALL XI protocol nine years back presented with progressively increasing pre-auricular swelling. OBSERVATION: Investigations revealed it to be a Mucoepidermoid carcinoma. MESSAGE: Mucoepidermoid carcinoma should be a differential in any parotid swelling of treated case of pediatric ALL.

Antibodies from combinatorial libraries use functional receptor pleiotropism to regulate cell fates.

To date, most antibodies from combinatorial libraries have been selected purely on the basis of binding. However, new methods now allow selection on the basis of function in animal cells. These selected agonist antibodies have given new insights into the important problem of signal transduction. Remarkably, when some antibodies bind to a given receptor they induce a cell fate that is different than that induced by the natural agonist to the same receptor. The fact that receptors can be functionally pleiotropic may yield new insights into the important problem of signal transduction.

Achromobacter Xylosoxidans Bloodstream Infection in Elderly Patient with Hepatocellular Carcinoma: Case Report and Review of Literature.

Achromobacter xylosoxidansis a nonfermentative Gram-negative organism, known to cause opportunistic infection in humans. We report a case of septicemia in a 76-year-old male patient with underlying hepatocellular carcinoma due to A. xylosoxidans, which showed a different antimicrobial susceptibility pattern from what is usually reported. From aerobic blood culture of the patient, A. xylosoxidans was isolated which was found to be sensitive to amoxicillin-clavulanic acid, piperacillin-tazobactam, ceftazidime, cefoperazone-sulbactam, meropenem, minocycline, tigecycline, and trimethoprim/sulfamethoxazole. The patient recovered with amoxicillin-clavulanic acid treatment, which was given empirically to the patient. The present case highlights the possible role of amoxicillin-clavulanic acid for treatment of bloodstream infection with A. xylosoxidans.

Antibiotic Resistance Pattern of Uropathogens: An Experience from North Indian Cancer Patient.

Empirical treatment of urinary tract infections (UTIs) can be made evidence based if it is governed by the resistance pattern of common uropathogens. A retrospective study was carried out at a tertiary care cancer institute to identify the common uropathogens and to know their resistance profile. 20.82% of the outpatients' urine samples (community-acquired urinary tract infection (CA-UTI)) and 24.83% of the indoor patients' urine samples (hospital-acquired urinary tract infection (HA-UTI)) grew uropathogens. Escherichia coli was the predominant pathogen both in CA-UTI (68%) and HA-UTI (45%) followed by Klebsiella spp and Enterococcus spp. High level of resistance to fluoroquinolones and third generation cephalosporins was noted. Nitrofurantoin was found to be a reliable oral drug for treatment of most of the uropathogens.

Surgical Site Infection Caused by Aeromonas hydrophila in a Patient with Underlying Malignancy.

Aeromonas skin and soft tissue infections in cancer patients can lead to serious life threatening conditions such as cellulitis, necrotizing fasciitis and myonecrosis. We report here a case of surgical site infection, post radical mastectomy, in a 58-year-old female with carcinoma breast. Cultures of exudates from the wound grew Aeromonas hydrophila on repeated occasions. Recovery was uneventful following targeted antimicrobial therapy and regular dressing of the wound. Early suspicion, diagnosis, and treatment with potent antibiotics are needed to prevent any further complications resulting from infection by this emerging pathogen.

Case report and literature review of carbapenem resistant shewanella putrefaciens isolated from ascitic fluid.

Shewanella species are Gram-negative, non-fermentative, oxidase positive, motile bacilli with the major phenotypic characteristic of production of large amounts of hydrogen sulfide. Shewanella putrefaciens, primarily considered to be an environmental bacterium, is infrequently recovered from clinical specimens. Herein, we report a case of ascitic fluid infection with carbapenem resistant Shewanella putrefaciens in a patient with underlying liver disorder requiring repeated ascitic fluid tapping. Proper antibiotic therapy helped in complete recovery of the patient.

Multi-targeted approach to cancer treatment: an international translational cancer research symposium.

Whether it is chronic myeloid leukemia, ALK-expressing malignancies, or HER2-positive breast cancer, targeted-therapies for treatment of human cancers have shown great promise. However, as they hit a single molecule expressed in neoplastic cells, their use is frequently associated with development of resistance. In cancer cells many signaling pathways operate in parallel, hence the idea of multi-targeted therapy is prevailing. The Society of Translational Cancer Research held its biennial meeting in the capital city of India, Delhi from February 6th through 9th, 2014 to discuss 'Multi-targeted Approach to Treatment of Cancer'. Over 200 scientists, clinicians, trainees, and industry representatives from different countries gathered in Vigyan Bhavan, the hotspot of Delhi for four days to talk and discuss on a variety of topics related to multi-targeted therapeutic approaches. Talks were presented by leaders in the cancer research field from various countries. It became clear from this conference that coupling multiple targeted-agents or using an agent that hits an individual target in several independent locations in the disease-causing pathway(s) may be the best approach to treat different cancers.

Solitary bone plasmacytoma progressing into retroperitoneal plasma cell myeloma with no related end organ or tissue impairment: a case report and review of the literature.

Solitary bone plasmacytomas and plasma cell myeloma are clonal proliferations of plasma cells. Many patients with solitary bone plasmacytomas develop plasma cell myeloma on follow-up. We present a case of a 70-year-old man who presented with fracture and a lytic lesion in the subtrochanteric region of the left femur and was assigned a diagnosis of solitary bone plasmacytoma. He received local curative radiotherapy. However, 4 months later his serum M protein and ß2-microglobulin levels increased to 2.31 g/dL and 5.965 mg/L, respectively. He complained of abdominal fullness and constipation. Ultrasound and non-contrast CT imaging revealed multiple retroperitoneal masses. Colonoscopic examination was normal. Biopsy of the a retroperitoneal mass confirmed it to be a plasmacytoma. Repeat hemogram, blood urea, serum creatinine, skeletal survey, and bone marrow examination revealed no abnormalities. This is an unusual presentation of plasma cell myeloma, which manifested as multiple huge extramedullary retroperitoneal masses and arose from a solitary bone plasmacytoma, without related end organ or tissue impairment and bone marrow plasmacytosis. The patient succumbed to his disease 8 months after the appearance of the retroperitoneal masses. This case highlights the importance of close monitoring of patients diagnosed with solitary bone plasmacytoma with increased serum M protein and serum ß2-microglobulin levels, so that early therapy can be instituted to prevent conversion to plasma cell myeloma.