Analysis of patients with endometrial carcinoma using the ProMise classifier: a pilot study from India.

BACKGROUND: Molecular subtyping of endometrial carcinomas (EC) has been shown to classify tumors into prognostically relevant groups. Characterizing EC with a limited number of markers viz., POLE mutations, p53 mutations, and MMR status, can provide valuable information. DESIGN: Paraffin sections of a cohort of 48 EC from a tertiary care center were characterized for the above-mentioned molecular markers and analyzed in the context of survival. METHODS: Formalin fixed paraffin embedded tissues from 48 EC were characterized for POLE mutations by Sanger sequencing (exons 9-14), for MMR (MLH1, MH2, MSH6) using immunohistochemistry (IHC) and copy number (high/low) using p53 IHC. Mutational status was integrated along with the clinicopathological details and survival analysis performed. RESULTS: Eleven (22.9%) patients were MMR deficient, 3 (6.3%) had POLE mutation, while 2 (4.1%) had both POLE and P53 mutations (regarded as multiple classifiers). Twelve (25%) patients were found to have P53 mutations, while the remaining 20 (41.7%) had no specific molecular profile (NSMP). Median follow-up duration was 43.5 (2-62) months with 8 recurrences and 9 deaths. Tumors with POLE mutation had the most favorable prognosis followed by the NSMP and the MMR mutated group while the P53 and multiple classifier groups had the worst prognosis in terms of OS (Log-rank p: 0.006) and PFS (Log-rank p: 0.001). CONCLUSION: The integration of molecular-clinicopathologic data for endometrial cancer classification, through cost-effective, clinically applicable assays appears to be a highly objective tool that can be adopted even in resource-limited settings. It has the potential to cause a shift in the paradigm of EC pathology and management practice.

Vulval Intraepithelial Neoplasia 3: A Clinico-Pathological Review in a Tertiary Care Centre Over 10 Years.

Objectives: Vulval Intraepithelial Neoplasia 3 (VIN) is a chronic, premalignant condition affecting the vulval skin. The age standardised incidence is approximately one per 100,000 women, with a peak at 30-49 years of age, and has risen over recent decades. This study would analyse the pattern of presentation, diagnosis, treatment and follow up of patients diagnosed with VIN 3 over a period of ten years at a tertiary care centre in India. Materials and Methods: This was a retrospective study conducted on all patients diagnosed to have VIN 3 between 1 January 2010 to 30 November 2019 in the Department of Gynaecologic Oncology, Christian Medical College, Vellore were included in this study. The outpatient records of the patients were obtained from an electronic registry. Results: A total of 18 patients were diagnosed of VIN 3 during this time period. Sixteen patients were older than 50 years. Abnormal PAP was noted in 10 patients (HSIL-7, LSIL-2, ASC-H-1). Four patients had coexisting VAIN 3. About 16 patients underwent primary simple vulvectomy or wide local excision. Two patients were managed conservatively. Nine patients had recurrence with mean disease free interval of 12.5 months (4-36 months). Cryotherapy was used in 2 patients. Imiquimod was used in 3 patients. Surgical margins was achieved in 7 patients out of which 5 patients had recurrence. About 50% of patients with involved margins on biopsy had recurrence. Mean duration of follow up was 17 months (4-105 months). About 8 patients developed squamous cell carcinoma of genital tract on follow up. Conclusion: VIN 3 has a high rate of progression to invasive SCC. Regression of VIN is rare. Proper follow up and treatment of VIN 3 goes a long way in preventing the morbidity associated with vulval cancer.

ERAS: An Audit of Existing Practices.

Objectives: Enhanced recovery after surgery (ERAS) is a set of multidisciplinary, evidence proven guidelines which enhance perioperative recovery in various surgical branches. This study was planned as a pilot effort with the aim of evaluating the surgical team's compliance to ERAS, in the absence of a structured programme, in the department of gynaecologic oncology of a tertiary care hospital in India. Methods: This is a retrospective audit of patients who underwent elective surgery, in the department of gynaecologic oncology, in a tertiary care centre in India, between 15th August 2019 to 15th October 2019. Emergency operations and those surgeries with palliative intent were excluded from the study. Electronic outpatient and inpatient records of patients chosen by convenient sampling were examined. Adherence to 18 components (pre-operative, intra-operative and post-operative) from the ERAS guidelines pertaining to surgical care were analysed. Results: A total of 50 patients were included. Mean age group was 50 years (22-76 years). Majority of patients (60%) had a Charlson Deyo score of 0. Excellent compliance was noted with respect to preoperative counselling (94%), intraoperative management (86%) and post-operative factors such as early ambulation, thromboprophylaxis and early discharge. Practices which required improvement included reduction of period of pre-operative fasting, prehabilitation, carbohydrate loading, gum chewing and coffee consumption and early initiation of feeding in post-operative period. Conclusion: Dedicated and co-ordinated team effort will ensure that an ERAS protocol is enforced. Periodic auditing will reveal inconsistencies in compliance and guarantee benefit to patients.

Role of Hysterectomy in Gestational Trophoblastic Neoplasia.

Hysterectomy has a limited role in the management of gestational trophoblastic neoplasia because of the high effectiveness of chemotherapy and the young age of patients. In selected patients, it is believed to help in reducing the number of chemotherapy cycles, overcoming chemo-resistance, and treating acute haemorrhagic events. The present study aimed to evaluate the indications and outcomes of hysterectomy in patients with GTN at a tertiary care centre in India. Between 2012 and 2019, we identified all patients with GTN from the hospital database. Demographic, clinical, and follow-up details of patients who underwent hysterectomy were obtained from the electronic medical records. During the study period, 98 cases of GTN were treated at our centre of which 54% were low-risk and 46% were high-risk cases. Twenty-six patients (26%) underwent hysterectomy as part of their management for GTN. The patients belonging to the high-risk group had more hysterectomies (65%) with an odds ratio of 2.96. The common pathological diagnosis was choriocarcinoma in 44% and an invasive mole in 30% of patients. Bleeding, either intraperitoneal or vaginal, was the most common indication for hysterectomy (48%). The median number of chemotherapy cycles received was 5 in patients who had primary hysterectomy and 6 in patients who did not have hysterectomy. The majority of patients received EMACO (57.7%) chemotherapy. The mean duration of follow-up was 18 months (range 1-67). After treatment, complete remission was achieved in 94 out of 98 (95.9%) and also in all patients (100%) who had undergone hysterectomy as adjuvant procedure. Three patients died during treatment (3.06%), all belonging to the high-risk group, and one patient had a recurrence (0.01%). In selected cases of GTN, hysterectomy may be an effective means to reduce or eliminate tumour bulk, to overcome chemoresistance and manage acute bleeding events.

Treatment Outcomes of Early Carcinoma Cervix Before and After Sub-specialization.

This study aimed to compare the treatment outcomes in carcinoma cervix before and after gynecologic oncology sub-specialization at a tertiary care hospital, in India. This was a retrospective cohort study comparing women with operable cervical cancer who underwent radical hysterectomy before and after gynecologic oncology sub-specialization. Electronic medical records of women operated for early carcinoma cervix between 2001 and 2010 and 2011-2015 were reviewed and compared for treatment and oncological outcomes. Seventy-four patients were operated over 5 years after sub-specialization as against 59 over 10 years before sub-specialization, with similar clinical characteristics. After surgical-pathological examination, both cohorts were comparable with regard to mean tumor size, lymph nodes retrieved, deep stromal invasion, and involvement of lymph nodes, parametrium, and vaginal margins. After sub-specialization, the rate of intraoperative (3% versus 14%, p = 0.018) and postoperative complications (15% versus 46%, p < 0.001) was lower. Adjuvant radiation was used more after sub-specialization (50% versus 24%, p < 0.001). The follow-up rates were similar in both groups with comparable 5-year recurrence-free survival and overall survival rates. The hazard ratio for death after sub-specialization was 0.39 (95% CI 0.12 to 1.22) after adjusting for histology, stage, grade, and presence of intermediate or high risk factors. Gynecological oncologic sub-specialization decreased intraoperative and postoperative complications, improved pathological reporting, and enabled appropriate tailoring of adjuvant therapy.

Metastatic Tumors to the Ovary-a Surgeon's Dilemma.

The ovary is a common site of metastasis. Differential diagnosis of ovarian carcinomas, including secondary tumors, remains a challenging task. Clinical decision-making depends on an accurate diagnosis of the type of ovarian cancer. This study was done to evaluate the pattern of metastatic tumors to the ovary and clinical details and to analyze the survival outcomes over a period of 5 years. Patients who had metastatic tumors to the ovary are identified from the electronic database from 1 January 2015 to 30 September 2019. Clinical details are collected from the electronic charts. Survival data is collected over the phone. The total number of ovarian cancers treated during the time period was 720, of which primary high-grade mucinous tumors contributed 9 (1.2%), and metastatic tumors to ovary 70 (10%). The highest levels of CEA were seen in carcinoma rectum, colon, and cholangiocarcinoma. CA 19-9 was very high in carcinoma gall bladder, pancreas, and cholangiocarcinoma. Common primaries were stomach (23%), gall bladder (13%), and colon (13%). Adenocarcinoma with signet ring cells was found in 29% of the patients. The median follow-up was 7 months (range 1 to 40 months). The median overall survival was 10 months after diagnosis (95% CI,7.9-12.0). There was no statistically significant difference in survival between patients who had peritoneal carcinomatosis with enlarged ovaries and those who had metastasis confined to ovaries (p value 0.360). A diagnosis of metastatic tumors to the ovary is associated with a very poor prognosis and the focus of treatment should be to improve the quality of life. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13193-020-01267-4.

Complications and Outcomes of Diaphragm Surgeries in Epithelial Ovarian Malignancies.

To achieve optimal debulking, cytoreductive surgery often involves diaphragm stripping. We describe our complications and survival outcomes after diaphragm surgery in epithelial ovarian cancer. A retrospective analysis on patients with advanced stage epithelial ovarian cancer between January 2012 and September 2019. The details of the diaphragmatic resections and stripping and their complications were looked into. During the study period, 616 patients with epithelial ovarian cancers were operated of which, 81 (13.2%) had diaphragm surgery. The majority underwent diaphragm stripping (60%) while 33% had resection and 7% cases had diaphragmatic nodule excision. Optimal debulking was achieved in 89% of cases. The complexity of surgery was intermediate in 64% of patients and complex in 33% as per Aletti's scoring. Mean operating time was 300 min (SD113). Moderate to severe pleural effusion was seen in 26 (32. %) patients necessitating pleural tapping in 16% and single lumen pleurex catheter insertion in 11%. Median recurrence-free and overall survival were 22 (95% CI 16.9-27) and 32 months (95% CI 25.5-38) respectively. Diaphragm stripping and resection is an important step in achieving optimal debulking of advanced and recurrent ovarian cancer. Diaphragmatic disease clearance is a necessary skill to be acquired by the gynaecologic oncology surgeons. Choosing the patients correctly and anticipation of complications can reduce morbidity and mortality.

Abdominal Tuberculosis Mimicking Ovarian Cancer: A Diagnostic Dilemma.

AIMS: The objective of this study was to describe the clinicopathological details in patients referred to the Gynaecologic Oncology Department with possible ovarian or primary peritoneal cancer where the final diagnosis turned out to be abdominal tuberculosis. METHODOLOGY: Retrospective chart analysis of 23 cases diagnosed with abdominal tuberculosis who were admitted under the Division of Gynaecologic Oncology suspected to have disseminated peritoneal malignancy, during 2014-2017. RESULTS: There were 23 patients who were referred to the Gynaecologic Oncology outpatient for evaluation of ascites, to rule out malignancy. The mean age of this patient group was 35 years (SD 14.5, range 14-65). The mean CA 125 was 333.5 [400.7 (9.09-1568)]. Ascitic fluid analysis confirmed TB in 26%; omental biopsy revealed TB in 69%, and operative diagnostic procedures (laparoscopy and laparotomy) were done in 15 of the 23 patients which had a positive pick up rate of 100% to confirm the diagnosis of TB. Culture of ascitic fluid/omental tissue and PCR yields were poor with a pick up rate of 33% and 6%. CONCLUSIONS: Abdominal TB is common in India and can mimic ovarian malignancy, and hence, high degree of suspicion needed. The isolation of AFB is the gold standard for diagnosis of pulmonary tuberculosis but has a low yield in abdominal TB. Ultrasound-guided procedure is reasonable as an initial procedure. As much time can be lost in working up these patients through multiple diagnostic algorithms using ascitic tap, USG biopsy and then an operative procedure, diagnostic laparoscopy could be considered early in the work up. It is a simple, time-saving and cost-effective way of establishing a diagnosis sooner with least complications.

The Ionospheric view of the 2011 Tohoku-Oki earthquake seismic source: the first 60 seconds of the rupture.

Using the specific satellite line of sight geometry and station location with respect to the source, Thomas et al. [Scientific Reports, https://doi.org/10.1038/s41598-018-30476-9] developed a method to infer the detection altitude of co-seismic ionospheric perturbations observed in Global Positioning System (GPS) - Total Electron Content (TEC) measurements during the Mw 7.4 March 9, 2011 Sanriku-Oki earthquake, a foreshock of the Mw 9.0, March 11, 2011 Tohoku-Oki earthquake. Therefore, in addition to the spatio-temporal evolution, the altitude information of the seismically induced ionospheric signatures can also be derived now using GPS-TEC technique. However, this method considered a point source, in terms of a small rupture area (~90 km) during the Tohoku foreshock, for the generation of seismo-acoustic waves in 3D space and time. In this article, we explore further efficacy of GPS-TEC technique during co-seismic ionospheric sounding for an extended seismic source varying simultaneously in space and time akin to the rupture of Mw 9.0 Tohoku-Oki mainshock and the limitations to be aware of in such context. With the successful execution of the method by Thomas et al. during the Tohoku-Oki mainshock, we not only estimate the detection altitude of GPS-TEC derived co-seismic ionospheric signatures but also delineate, for the first time, distinct ground seismic sources responsible for the generation of these perturbations, which evolved during the initial 60 seconds of the rupture. Simulated tsunami water excitation over the fault region, to envisage the evolution of crustal deformation in space and time along the rupture, formed the base for our model analysis. Further, the simulated water displacement assists our proposed novel approach to delineate the ground seismic sources entirely based on the ensuing ionospheric perturbations which were otherwise not well reproduced by the ground rupture process within this stipulated time. Despite providing the novel information on the segmentation of the Tohoku-Oki seismic source based on the co-seismic ionospheric response to the initial 60 seconds of the event, our model could not reproduce precise rupture kinematics over this period. This shortcoming is also credited to the specific GPS satellite-station viewing geometries.

Mapping the Impact of Non-Tectonic Forcing mechanisms on GNSS measured Coseismic Ionospheric Perturbations.

Global Navigation Satellite System (GNSS) measured Total Electron Content (TEC) is now widely used to study the near and far-field coseismic ionospheric perturbations (CIP). The generation of near field (~500-600 km surrounding an epicenter) CIP is mainly attributed to the coseismic crustal deformation. The azimuthal distribution of near field CIP may contain information on the seismic/tectonic source characteristics of rupture propagation direction and thrust orientations. However, numerous studies cautioned that before deriving the listed source characteristics based on coseismic TEC signatures, the contribution of non-tectonic forcing mechanisms needs to be examined. These mechanisms which are operative at ionospheric altitudes are classified as the i) orientation between the geomagnetic field and tectonically induced atmospheric wave perturbations ii) orientation between the GNSS satellite line of sight (LOS) geometry and coseismic atmospheric wave perturbations and iii) ambient electron density gradients. So far, the combined effects of these mechanisms have not been quantified. We propose a 3D geometrical model, based on acoustic ray tracing in space and time to estimate the combined effects of non-tectonic forcing mechanisms on the manifestations of GNSS measured near field CIP. Further, this model is tested on earthquakes occurring at different latitudes with a view to quickly quantify the collective effects of these mechanisms. We presume that this simple and direct 3D model would induce and enhance a proper perception among the researchers about the tectonic source characteristics derived based on the corresponding ionospheric manifestations.

UV-B priming of Oryza sativa var. Kanchana seedlings augments its antioxidative potential and gene expression of stress-response proteins under various abiotic stresses.

Priming is one of the mechanisms for the induction of the antioxidant defense system and various stress-responsive proteins which help plants to survive under various abiotic stresses. Based on the observation that the rice seedlings primed with UV-B (low dose of UV-B irradiation-6 kJm-2) induced the acclimation against NaCl, PEG and UV-B stresses, it was of interest to see the augmentation of antioxidative potential and stress-responsive proteins accumulation in rice seedlings due to UV-B priming under these stresses. Various stresses result in production of ROS, which cause membrane degradation resulting in the accumulation of malondialdehyde. These negative impacts were observed exceedingly in rice seedlings from non-primed PEG stress (NP+P) condition than UV-B and NaCl stresses. The production of non-enzymatic antioxidants, activity/mRNA-level expressions of enzymatic antioxidants and stress-responsive proteins were effectively augmented in UV-B-primed rice seedlings subjected to NaCl stress (P+N) condition followed by UV-B stress (P+U) and PEG stress (P+P). The activation of stress-responsive proteins (HSP and LEA) in rice due to the UV-B priming of rice seedlings is being reported for the first time. The results revealed that the UV-B seedling priming was alleviating the effect of NaCl, PEG, and UV-B stresses in rice seedlings. The positive impacts of UV-B seedling priming were more prominent in rice seedlings subjected to NaCl stress, indicating the cross tolerance imparted by UV-B priming.

Diagnostic Accuracy of Frozen Section and Its Influence on Intraoperative Management of Indeterminate Epithelial Ovarian Tumors.

The objective of this study is to determine the diagnostic accuracy of frozen section in detecting epithelial ovarian tumor histological types and its effect on management. A retrospective review was done of all patients who had an intraoperative frozen section for an indeterminate ovarian tumor over a six-year period. The reference standard was final histology. The validity indices for frozen section in diagnosing benign, borderline, and malignant lesions were determined. One hundred thirty-five intraoperative frozen section-diagnosed epithelial ovarian tumors were reviewed. The mean age was 44.9 ± 14.2 years, the median parity was 2, and 57% (77/135) of patients were post-menopausal. The commonest histological subtype was mucinous 48.1% (65/135) on frozen section and 46.7% (63/135) on final histology. The overall concordance rate of frozen section to final histology was 81.5% (ƙ = 0.719, p = 0.0001). The accuracy, sensitivity, specificity, and positive predictive value of frozen section to diagnose benign lesions were 86.7%, 85.7%, 97.2%, and 79.2% respectively. In borderline tumors, the diagnostic test characteristics were 88.1%, 81.2%, 90.3%, and 72.2%. For malignant lesions, these values were 88.1%, 77.8%, 95.1%, and 91.3% respectively. The odds ratios for frozen section being correct were 40.9 (95% CI 14.8-113.5) for benign lesions, 40.3 (95% CI 13.4-121.3) for borderline tumors, and 67.4 (95% CI 20.5-222.0) for malignancy. Over-treatment or under-treatment occurred in 19.3% of patients. Intraoperative frozen section is useful in situations where the nature of the ovarian tumor is uncertain. However, borderline ovarian tumors are more likely to be over-diagnosed. About a fifth of patients received inappropriate treatments based on the frozen section report.

Amplification of abiotic stress tolerance potential in rice seedlings with a low dose of UV-B seed priming.

UV-B radiation is a major abiotic stress factor that adversely affects the growth and productivity of crop plants including rice (Oryza sativa L.). However, on the other hand, lower doses of UV-B radiation applied to seeds can have a priming effect on plants emerging from it. In this study, seeds of O. sativa var. kanchana were primed with UV-B radiation (6 kJ m-2) and were further subjected to NaCl, polyethylene glycol 6000 (PEG) and UV-B stress. The effects of UV-B priming in imparting NaCl, PEG and UV-B stress tolerance to rice seedlings were analysed through various photosynthetic features and antioxidative mechanisms. PSI and PSII activity levels as well as chl a fluorescence were found to be significantly higher in the UV-B primed and unstressed seedlings. When stress (NaCl, PEG and high UV-B) was imposed, increased PSI and PSII activity levels, chl a fluorescence and metabolite accumulation (proline, total phenolics and sugar) as well as nonenzymatic (ascorbate and glutathione) and enzymatic (superoxide dismutase, catalase, ascorbate peroxidase) antioxidants were recorded in UV-B primed and NaCl-stressed plants followed by UV-B primed and UV-B-stressed plants, and primed and PEG-stressed, compared with unprimed and stressed conditions. The results indicate that UV-B priming in rice seedlings effectively enhances the NaCl stress tolerance potential in rice to a greater extent than UV-B and PEG stress tolerance potential. The cost-effectiveness of UV-B seed priming is predominantly clear from the differing tolerance responses of rice seedlings exposed to different stress conditions.

Author Correction: Revelation of early detection of co-seismic ionospheric perturbations in GPS-TEC from realistic modelling approach: Case study.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Revelation of early detection of co-seismic ionospheric perturbations in GPS-TEC from realistic modelling approach: Case study.

GPS-derived Total Electron Content (TEC) is an integrated quantity; hence it is difficult to relate the detection of ionospheric perturbations in TEC to a precise altitude. As TEC is weighted by the maximum ionospheric density, the corresponding altitude (hmF2) is, generally, assumed as the perturbation detection altitude. To investigate the validity of this assumption in detail, we conduct an accurate analysis of the GPS-TEC measured early ionospheric signatures related to the vertical surface displacement of the Mw 7.4 Sanriku-Oki earthquake (Sanriku-Oki Tohoku foreshock). Using 3D acoustic ray tracing model to describe the evolution of the propagating seismo-acoustic wave in space and time, we demonstrate how to infer the detection altitude of these early signatures in TEC. We determine that the signatures can be detected at altitudes up to ~130 km below the hmF2. This peculiar behaviour is attributed to the satellite line of sight (LOS) geometry and station location with respect to the source, which allows one to sound the co-seismic ionospheric signatures directly above the rupture area. We show that the early onset times correspond to crossing of the LOS with the acoustic wavefront at lower ionospheric altitudes. To support the proposed approach, we further reconstruct the seismo-acoustic induced ionospheric signatures for a moving satellite in the presence of a geomagnetic field. Both the 3D acoustic ray tracing model and the synthetic waveforms from the 3D coupled model substantiate the observed onset time of the ionospheric signatures. Moreover, our simple 3D acoustic ray tracing approach allows one to extend this analysis to azimuths different than that of the station-source line.