Evaluation of factors influencing lymph node metastasis in endometrial cancers: A retrospective study.

OBJECTIVES: The role of lymphadenectomy in the management of early endometrial cancer remains controversial. The aim of our study was to evaluate risk factors associated with nodal metastases in endometrial cancer and to devise a predictive risk model based on the significant risk factors in predicting node metastasis. MATERIALS AND METHODS: A retrospective study was conducted on women diagnosed with uterus-confined endometrial cancer, and who underwent surgical staging with pelvic and/or paraaortic lymphadenectomy from our center during July 1, 2017 to June 30, 2019. Clinical details, Magnetic Resonance imaging (MRI)-detected myometrial invasion, and pre and post-operative histological details of tumor were correlated with pelvic and/or para-aortic lymph node metastasis. Risk factors were assessed using logistic regression model and risk models devised. RESULTS: 128 patients were included in the study. Paraaortic lymphadenectomy was done in 72.7% patients. Nodal metastasis was seen in 14.8% of patients. Logistic regression analyses revealed lymphovascular invasion (P = 0.002), parametrial involvement (P = 0.017) and nonendometrioid histology (P = 0.004) to be significant risk factors. Tumor size >2 cm, grade 3 and deep myometrial invasion had higher risk for nodal metastasis, although non-significant. Risk models were derived with sensitivity of 79-89.5%, specificity of 58.7-69.7%, Negative predictive value (NPV) of 95-97% and accuracy of 63-71%. CONCLUSION: Lymphovascular invasion, nonendometrioid histology and parametrial involvement are independent predictors of lymph node metastasis in endometrial cancer. Risk models using these risk factors can better predict the risk of nodal metastasis and thus avoid lymph node dissection in low risk patients. Our risk models had reasonably good sensitivity in nodal metastasis prediction and require further validation.

MPNST of Uterine Round Ligament: A Report of a Surgically Challenging Aggressive Rare Case and Literature Review.

MPNSTs (malignant peripheral nerve sheath tumours) arise rarely from the female genital tract, even more rarely from the uterus. A literature review showed 18 cases affecting the uterine cervix, but only four affecting the uterus per se, making our present case the fifth to be involving the uterus, specifically round ligament. It was the first time a uterine lesion (not uterine cervix) was defined in a neurofibromatosis patient. This was a young patient who initially underwent a uterus-sparing surgery for a round ligament tumour which was finally diagnosed to be MPNST. She received adjuvant chemotherapy but recurred with pelvic vascular involvement. A challenging surgery was performed, and the tumour was resected without morbidity. She was followed up with radiotherapy; however, she quickly developed extensive peritoneal disease and succumbed to the disease. High-grade nature of MPNST along with the background of NF could have made the tumour more aggressive, highlighting the importance of suspecting MPNST in spindle cell tumours of pelvis and performing total resection in the first setting.

Clinical Profile and Survival Outcome of Endometrial Cancer with p53 Mutation.

Clinicopathologic classification of endometrial cancer imperfectly reflects the tumor biology. Pathologic categorization - especially in high-grade tumors - results in an imprecise estimation of the risk of disease, recurrence, and death. Molecular subtyping is emerging as the standard of care in diagnosis and treatment of endometrial cancers. Molecular markers are important prognostic factors in tumor dissemination and early recurrence of endometrial cancers. TP53 mutation is an important prognostic factor for both serous and endometrioid cancers. The study aims to compare the clinical profile and overall survival of endometrial cancers with and without p53 mutation. Sixty-three patients who underwent surgical staging for carcinoma endometrium were included in the study.TP53 mutation status was determined based on p53 expression by immunohistochemistry (IHC) as a p53 wild or p53 mutant type. Data were analyzed for the clinical profile, p53 mutation status on IHC, histological pattern, tumor grade, stage of the disease, lymph node spread, recurrence pattern, treatment received, 2-year disease-free survival, and overall survival. Recurrence was noted in 12.7% patients after 2-year follow-up, of which 75% patients had p53 mutation. Significant association was seen between p53 expression and high-grade tumors, stage, cervical involvement, and adnexal involvement. The 2-year overall survival of the p53 wild type was 97.2% and the p53 mutant type was 91.7%. The 2-year disease-free survival for the p53 wild type was 94.3% and the disease-free survival of the p53 mutant variety was 83.5%. The 2-year disease-free survival for endometrioid carcinoma with p53 wild type was 100% and p53 mutant variety was 86.2% (p value 0.033). About 15.9% (10) patients were reassigned to the high-risk group needing chemotherapy and radiation according to the ESGO ESTRO 2021 consensus classification, due to their p53 mutation status. IHC to assess somatic p53 mutation may be done in endometrial biopsies irrespective of their histology. This may help to identify that the aggressive tumors thereby help in tailoring surgery, planning adjuvant treatment, and follow-up.

Feasibility of Sentinel Lymph Node Sampling in Early-Stage Carcinoma Endometrium: Single-Institution Experience.

Introduction: Accurate surgical staging is an essential component in the management of carcinoma endometrium to assess the stage of disease and to tailor adjuvant treatment. Sentinel node technique was introduced as an alternative for extensive lymphadenectomy in early stages to avoid complications associated with lymphadenectomy. Aims and Objectives: To assess the detection rate and diagnostic accuracy of SLN mapping in patients with early-stage carcinoma endometrium. Materials and Methods: Prospective validation study involving 30 patients diagnosed to have early-stage carcinoma endometrium. Sentinel nodes were detected by combined methods of radio colloid dye and isosulphan blue dye injection. Results: Sentinel lymph node was detected in 19 patients (63.4%). 11 patients had no sentinel nodes. Total number of sentinel nodes isolated was 68 with a mean of 2.26 per patient (range 0-4). Ten (33.33%) patients had single sentinel node location, while 9 (30%) had more than 1 sentinel lymph nodes. Twelve patients had bilateral sentinel nodes, and the most frequent location of sentinel node was obturator, 19 (63.3%) especially on right hemi-pelvis. One patient had a hot para-aortic node, while none had blue para-aortic sentinel node. Average number of lymph nodes obtained by lymphadenectomy was 13 per patient (range 7-22). All patients with sentinel node had negative frozen report as well as in histopathology. Two patients in whom no sentinel nodes were detected by either techniques had metastatic nodes in histopathology report. Conclusion: Detection rate was maximum with radiocolloid dye, and it is better to utilize the technique for less graded tumours and endometrioid variants.

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.

Impact of Surgery on Extramammary Paget's Disease Vulva: a Case Series.

Extramammary Paget's disease is a rare neoplasm that may affect the vulva. It usually presents as a pruritic red eczematous lesion with islands of hyperkeratosis that is often mistaken for other benign conditions. There are no specific guidelines for the management of this disease. Surgical excision is the standard treatment but recurrences are common in spite of extensive surgery with negative margins. We report here a series of 7 cases of Paget's disease vulva treated by primary surgery. The series highlights some of the challenges in the diagnosis and management of Paget's disease vulva.

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.

Pattern of Lymph Node Metastasis in Endometrial Cancer: a Single Institution Experience.

Surgical staging remains the standard primary treatment of endometrial cancer. Lymph node metastasis is the most important prognostic factor which helps in deciding adjuvant treatment. Extensive lymphadenectomy is associated with increased incidence of morbidity. The role of lymphadenectomy in surgical staging is still controversial especially in early stage disease. The surgico-pathological pattern of 155 patients with apparently stage 1 cancer endometrium who had undergone pelvic alone or pelvic and para-aortic lymph node dissection and its correlation to the grade of the tumour, myometrial infiltration and presence of peritoneal disease and incidence of peri-operative morbidity are analysed and described.

Evaluation of Computed Tomography Scan and CA 125 Response in Predicting Operability in Advanced Ovarian Cancer and Assessing Survival Outcome in Interval Cytoreductive Surgery.

The study aims at the prediction of optimal cytoreduction (OCR) in patients undergoing interval cytoreduction (ICR) in advanced epithelial ovarian cancer (AEOC) based on CT imaging and CA 125 values and assessing the survival pattern of these patients after ICR. This is a prospective observational study of patients with stage III C ovarian cancer who underwent ICR in our institution after neoadjuvant chemotherapy (NACT). All consecutive patients operated from April 2016 to October 2017 were included in the study. From their medical records, their demographic details and clinical variables were recorded. The CA 125 value and CT scan findings before and after chemotherapy were documented. A Bristow's predictive score (BS) was calculated based on the radiological parameters. After ICR, the outcome of the surgery was documented. Optimal cytoreduction (OCR) was defined as no gross residual disease after surgery. The surgical outcome was correlated with the CA 125 difference pre and post chemotherapy and Bristow's predictive score pre and post chemotherapy. The patients were followed up and their survival at 6 and 12 months was assessed. Univariate and multivariate analysis was done to identify factors predicting OCR. 51 patients were included in the study. Age group of the women ranged from 31 to 74 years with a mean of 52 years. Majority of the patients (70.6%) were postmenopausal. Of the 51 women, OCR could be achieved in 31 patients (60.8%). Post-chemotherapy, 36 patients had elevated CA125 above baseline of which 50% attained OCR. Forty six patients had CA 125 response post chemotherapy of which 67.4% attained OCR. Forty five patients had reduction in Bristow Score compared to the pre chemo values of which 64.4% attained OCR which was not found to be statistically significant. Overall survival was 100% survival at 6 months and 92.8% at 12 months in those who achieved OCR. Those with residual disease 0.1-1 cm had survival of 74.1% at 6 and 12 months. Those with residual disease > 1 cm had a survival of 50% at 6 and 12 months. CA125 response has a significant role in predicting OCR while CT evaluation using the BS was not useful in predicting OCR during ICR for AEOC.

Gynecological Cancers-the Changing Paradigm.

Outstanding research in the last few decades led to newer insights into the management of gynecological cancers. In the preventive arena, the efficacy and safety of HPV vaccination are well accepted and is now in addition to bi- and quadrivalent vaccines; there is a nonavalent vaccine against nine oncogenic HPV strains. Recent studies also looked into the dosaging schedules and age of vaccination against HPV to improve the vaccine efficacy and coverage. HPV testing is now approved as a primary screening test for cervical cancer in women aged more than 30 years with better sensitivity than the traditional cytology. Opportunistic salpingectomy for ovarian cancer prevention and neoadjuvant chemotherapy for advanced ovarian cancers are accepted practices. The role of personalized medicine in ovarian cancer and comprehensive genomic analysis of endometrial cancers are also covered in this review.

Salvage Surgery for Cervical Cancer Recurrences.

Cervical cancer usually presents in advanced stages and is treated with chemoradiation. About 15-20 % patients present with local recurrence after chemoradiation. Radical surgical resection is the only treatment modality offering long term survival benefit in recurrent cervical cancer. The most common surgical option for these patients is pelvic exenteration. Radical hysterectomy may be done for patients with a small centrally located recurrence in the cervix with no infiltration of adjacent structures. The aim of this study was to evaluate the morbidity and survival outcome following radical hysterectomy and pelvic exenteration for recurrent cancer cervix. We retrospectively reviewed the medical records of our patients who underwent surgery for cancer cervix recurrence from January 2010 to December 2014. The postoperative morbidity was considered early if it happened in the initial 30 days of surgery and late if it occurred after 30 days. All patients were followed up till February 2015. Survival analysis was done using Kaplan- Meir method. Between January 2010 and December 2014, 20 patients with recurrent cervical cancer underwent radical surgical resection. The median age of the study group was 43 years (range 28-63 years). Seventeen patients had squamous cell carcinoma and 3 had adenocarcinoma. 13 underwent pelvic exenteration and 7 patients underwent radical type 2 hysterectomy with bilateral pelvic lymphnode dissection. In the exenteration group, 8 patients had anterior exenteration, 4 had total exenteration and one had posterior exenteration. Urinary diversion was done by ileal conduit in 8 patients, double barrel colostomy in two and wet colostomy in two patients. There were no immediate postoperative deaths. Operating time, blood transfusions needed and hospital stay was more in the exenteration group compared to radical hysterectomy patients. After pelvic exenteration post-operative complications were seen in 76.9 % of which the most common was of the urinary tract including 3 patients with pyelonephritis, 5 had renal insufficiency and 2 patients developed urinary fistulae. Post-operative morbidity was lower in radical hysterectomy patients. There were two patients in the hysterectomy group who developed vault recurrence while none in the exenteration group had local recurrence. The median follow up time was 19 months (range 9-53 months).Three year overall survival for the entire cohort was 43 %. Median survival time for the exenteration group was 28 months which was significantly higher than 14 months for the radical hysterectomy group. This study shows that radical surgical resection is feasible with good survival outcome and acceptable morbidity in recurrent cancer cervix patients. Radical hysterectomy can be done in selected patients but pelvic exenteration has better long-term survival but with the potential for both short- & long-term complications.

Dietary probiotic supplementation improves growth and the intestinal morphology of Nile tilapia.

Probiotic administration can be a nutritional strategy to improve the immune response and growth performance of fish. The current study aimed to evaluate the effects of a probiotic blend (Bacillus sp., Pediococcus sp., Enterococcus sp., Lactobacillus sp.) as a dietary supplement on growth performance, feed utilization, innate immune and oxidative stress responses and intestinal morphology in juvenile Nile tilapia (Oreochromis niloticus). The probiotic was incorporated into a basal diet at three concentrations: 0 g/kg (A0: control), 3 g/kg (A1: 1.0×106 colony forming unit (CFU)/g) and 6 g/kg (A2: 2.3×106 CFU/g diet). After 8 weeks of probiotic feeding, weight and specific growth rate where significantly higher in fish-fed A1 diet than in fish-fed A0. Alternative complement in plasma was significantly enhanced in fish-fed A2 when compared with A0. The hepatic antioxidant indicators were not affected by probiotic supplementation. Villi height and goblet cell counts increased significantly in the intestine of fish-fed A1 and A2 diets compared with A0. The dietary probiotic supplementation was maintained until 20 weeks of feeding. Then the selected immune parameters, digestive enzymes and apparent digestibility of diets were studied. No effect of probiotic feeding was observed after that longer period supplementation. The dietary supplementation of mixed species probiotic may constitute a valuable nutritional approach towards a sustainable tilapia aquaculture. The improvement of the immune responses and intestinal morphology play an important role in increasing growth performance, nutrient absorption and disease resistance in fish, important outcomes in such a competitive and developing aquaculture sector.

Conservative Surgery for Early Cervical Cancer.

There is a rising incidence of early cervical cancer in young patients as a result of screening and early detection. Treatment of cervical cancer by surgery or radiotherapy results in permanent infertility which affects the quality of life of cancer survivors. Now with improved survival rates among early cervical cancer patients, conservative surgery aiming at fertility preservation in those desiring future pregnancy is an accepted treatment. Conservative surgery is possible in early cervical cancer including micro invasive cancer and stage IB cancers less than 2 cm. Stage IA1 cervical cancer is treated effectively by cervical conisation. In stage IA2 cancers and stage IB1 cancers less than 2 cm the fertility preservation surgery is radical trachelectomy. Radical trachelectomy removes the cervix with medial parametrium and upper 2 cm vaginal cuff retaining the uterus and adnexa to allow future pregnancy. Radical trachelectomy is a safe procedure in selected patients with cancer cervix with acceptable oncologic risks and promising obstetric outcome. It should be avoided in tumours larger than 2 cm and aggressive histologic types. This article focuses on the current options of conservative surgery in early cervical cancer.

Primary Malignant Melanoma of Vagina Treated by Total Pelvic Exenteration.

Primary malignant melanoma of vagina is a rare variant of melanoma and usually associated with a grave prognosis. Radical surgery is the only treatment option with reasonable loco regional control. A case of primary malignant melanoma involving whole of vagina infiltrating urethra and reaching up to vulva was treated by surgery and postoperative radiotherapy. The tumor was infiltrating bladder and rectum reaching the anal sphincter. Total pelvic exenteration was done to achieve tumor-free surgical margins. One year after treatment, patient is disease free.

Growth, immune responses and intestinal morphology of rainbow trout (Oncorhynchus mykiss) supplemented with commercial probiotics.

The influence of two commercial probiotics on the growth, innate immune parameters and intestinal morphology of rainbow trout (Oncorhynchus mykiss) juveniles (initial weight: 16.4 ± 0.4 g) was evaluated. Two probiotic types: A, multi-species (Bacillus sp., Pedicoccus sp., Enterococcus sp., Lactobacillus sp.) and B, mono-species (Pediococcus acidilactici) were tested at two levels each (A1: 1.5 g kg(-1), 8.6 × 10(5) CFU g(-1); A2: 3 g kg(-1), 1.6 × 10(6) CFU g(-1); B1: 0.1 g kg(-1), 2.6 × 10(4) CFU g(-1); B2: 0.2 g kg(-1), 7.2 × 10(4) CFU g(-1)) versus an unsupplemented diet (C). Diets were distributed to sextuplicate tanks, three times a day to visual satiation for 8 weeks. Growth performance and immune responses (plasma lysozyme, ACH50, peroxidase and head kidney respiratory burst) were determined at 4 and 8 weeks of feeding. Body composition and intestine morphology were determined at the end of the feeding trial. At 8 weeks, the lower dose of multi-species probiotic (A1) improved growth rate, while both probiotic types improved feed conversion rate compared to the control animals, at the lower dose of multi-species (A1) and at the higher dose of mono-species (B2) probiotics. Body composition did not vary between treatments. At 4 weeks, ACH50 activity was significantly higher in fish fed higher dose of B probiotic (B2, 123.7 ± 50.6 vs 44.1 ± 7.7 U.ml(-1) in control). At 8 weeks, lysozyme activity was higher in fish fed A1 (13.1 ± 5.2 µg ml(-1)) diet compared to fish fed control diet (7.8 ± 1 µg ml(-1)). Plasma peroxidase and head-kidney respiratory burst did not differ among the dietary treatments. Villi length and integrity and goblet cell counting of a cross section of the anterior intestine were not significantly different between groups. Results suggest benefits in zootechnical performance and immune humoral responses using both probiotic types, in a dose dependent manner, without apparent alterations in intestinal morphology.

Role of lymphadenectomy and its impact on survival in endometrial carcinoma - an institutional experience.

UNLABELLED: Pelvic and para aortic lymph nodes are the common sites of metastasis in endometrial carcinoma. The role of lymphadenectomy is widely discussed in literature with varying results. In this study we did a retrospective analysis of endometrial cancer patients to correlate lymphadenectomy with overall and disease free survival. METHODS: A retrospective review of 110 patients with carcinoma endometrium who underwent staging laparotomy at our institute during the period 2006-2010. Patients who underwent node dissections were categorized as group I and the rest as group II. Median lymph node count was 10. Grade of the tumor, nodal status and lymphadenectomy were correlated with overall and disease free survival. CONCLUSION: Lymph node metastasis and grade of tumor are significant predictors of survival. Lymphadenectomy did not show significant survival benefit. It has helped to upstage the disease so that appropriate adjuvant therapy could be planned. A prospective randomized control trial with complete pelvic and para aortic node dissection and uniform adjuvant therapy considering nodal status may help to answer the confusion regarding lymphadenectomy.