Should laparoscopy be revisited in the management of stage II endometrial cancer in the post-LACC era?

BACKGROUND: A recent randomized trial showed that laparoscopy had poorer outcomes compared with open surgery for early-stage cervical cancer. Whether this is of concern in endometrial cancer, when the cervix is involved has received little attention. This study aimed to investigate whether there is any difference on overall and cancer specific survival between patients treated with laparoscopy and laparotomy for stage II endometrial cancer. METHODS: Data from patients with histologically proven stage II endometrial cancer who were treated between 2010 and 2019 in a single cancer center were reviewed. Demographic, histopathological characteristics and treatment modalities were recorded. Recurrence rate, cancer specific and overall survival were compared between patients that were treated with laparoscopic and open surgery. RESULTS: From 47 patients with stage II disease, 33 (70%) were treated with laparoscopy and 14 (30%) with open surgery. There was no difference on age (P=0.86), BMI (P=0.76), Comorbidity Index Score (P=0.96), upstaging/upgrading after surgery (P=0.41), performance of lymphadenectomy (P=0.74), histological type (P=0.32), LVSI (P=0.15), depth of myometrial invasion (P=0.07), postoperative hospital stay (P=0.18) and administration of adjuvant treatment (P=0.11) between the two groups. Recurrence rate (P=0.756), overall (P=0.606) and cancer specific survival (P=0.564) were also comparable between laparoscopy and laparotomy groups. CONCLUSIONS: Laparoscopic and open surgery seem to have comparable outcomes for stage II endometrial cancer. The oncological safety of laparoscopy for stage II endometrial cancer should be further investigated with a randomized controlled trial.

The Major Constituent of Green Tea, Epigallocatechin-3-Gallate (EGCG), Inhibits the Growth of HPV18-Infected Keratinocytes by Stimulating Proteasomal Turnover of the E6 and E7 Oncoproteins.

Epigallocatechin-3-gallate (EGCG), the primary bioactive polyphenol in green tea, has been shown to inhibit the growth of human papilloma virus (HPV)-transformed keratinocytes. Here, we set out to examine the consequences of EGCG treatment on the growth of HPV18-immortalised foreskin keratinocytes (HFK-HPV18) and an authentic HPV18-positive vulvar intraepithelial neoplasia (VIN) clone, focusing on its ability to influence cell proliferation and differentiation and to impact on viral oncogene expression and virus replication. EGCG treatment was associated with degradation of the E6 and E7 oncoproteins and an upregulation of their associated tumour suppressor genes; consequently, keratinocyte proliferation was inhibited in both monolayer and organotypic raft culture. While EGCG exerted a profound effect on cell proliferation, it had little impact on keratinocyte differentiation. Expression of the late viral protein E4 was suppressed in the presence of EGCG, suggesting that EGCG was able to block productive viral replication in differentiating keratinocytes. Although EGCG did not alter the levels of E6 and E7 mRNA, it enhanced the turnover of the E6 and E7 proteins. The addition of MG132, a proteasome inhibitor, to EGCG-treated keratinocytes led to the accumulation of the E6/E7 proteins, showing that EGCG acts as an anti-viral, targeting the E6 and E7 proteins for proteasome-mediated degradation.

Does sites of recurrence impact survival in secondary cytoreduction surgery for recurrent epithelial ovarian cancer?

Outcomes of secondary cytoreduction surgery (SCS) were evaluated for morbidity, progression free survival (PFS) and overall survival (OS) and factors influencing results were explored. Retrospective analysis of all cases of SCS for epithelial ovarian cancer (EOC) was performed from October 2010 to December 2017. 62 patients were prospectively identified as candidates for SCS and 57 underwent SCS. 20(35%) patients required bowel resection/s, 24(42%) had nodal resections and 11(19%) had extensive upper abdominal surgery. 51(89%) achieved complete cytoreduction. After a median follow-up of 30 months (range 9-95 months), median PFS was 32 months (CI 17-76 months) and median OS has not reached. Seventeen patients have died and 32 have progressed. Three patients had Clavien-Dindo grade-3 and two had grade-4 morbidity. Patients who had multi-site recurrence had shorter median PFS (p = 0.04) and patients who required bowel resections had lower median OS (p = 0.009) compared to rest of the cohort.IMPACT STATEMENTWhat is already known on this subject? Retrospective studies have confirmed survival advantage for recurrence in epithelial ovarian cancer and recommend SCS for carefully selected patients. This finding is being evaluated in randomised control trials currently.What do the results of this study add? This study presents excellent results for survival outcomes after SCS and highlights importance of careful selection of patients with a goal to achieve complete cytoreduction. In addition, for the first time in literature, this study also explores various factors that may influence results and finds that there are no differences in survival outcomes whether these patients had early stage or advanced stage disease earlier. Patients who have multisite recurrence tend to have shorter PFS but no difference were noted for overall survival. Patients who have recurrence in bowels necessitating resection/s have a shorter median OS compared to rest of cohorts, however, still achieving a good survival time.What are the implications of these findings for clinical practice and/or further research? These findings will raise awareness for the clinicians and patients while discussing surgical outcomes and would set an achievable standard to improve cancer services. The pattern of recurrence and associated outcomes also point towards difference in biological nature of recurrent disease and could provide an opportunity for scientists to study the biological makeup of these recurrent tumours.

Revised FIGO staging for carcinoma of the cervix uteri.

OBJECTIVE: To revise FIGO staging of carcinoma of the cervix uteri, allowing incorporation of imaging and/or pathological findings, and clinical assessment of tumor size and disease extent. METHODS: Review of literature and consensus view of the FIGO Gynecologic Oncology Committee and related societies and organizations. RESULTS: In stage I, revision of the definition of microinvasion and lesion size as follows. Stage IA: lateral extension measurement is removed; stage IB has three subgroups-stage IB1: invasive carcinomas ≥5 mm and <2 cm in greatest diameter; stage IB2: tumors 2-4 cm; stage IB3: tumors ≥4 cm. Imaging or pathology findings may be used to assess retroperitoneal lymph nodes; if metastatic, the case is assigned stage IIIC; if only pelvic lymph nodes, the case is assigned stage IIIC1; if para-aortic nodes are involved, the case is assigned stage IIIC2. Notations 'r' and 'p' will indicate the method used to derive the stage-i.e., imaging or pathology, respectively-and should be recorded. Routine investigations and other methods (e.g., examination under anesthesia, cystoscopy, proctoscopy, etc.) are not mandatory and are to be recommended based on clinical findings and standard of care. CONCLUSION: The revised cervical cancer staging is applicable to all resource levels. Data collection and publication will inform future revisions.

Cancer of the ovary, fallopian tube, and peritoneum.

The Gynecologic Oncology Committee of FIGO in 2014 revised the staging of ovarian cancer, incorporating ovarian, fallopian tube, and peritoneal cancer into the same system. Most of these malignancies are high-grade serous carcinomas (HGSC). Stage IC is now divided into three categories: IC1 (surgical spill); IC2 (capsule ruptured before surgery or tumor on ovarian or fallopian tube surface); and IC3 (malignant cells in the ascites or peritoneal washings). The updated staging includes a revision of Stage IIIC based on spread to the retroperitoneal lymph nodes alone without intraperitoneal dissemination. This category is now subdivided into IIIA1(i) (metastasis ≤10 mm in greatest dimension), and IIIA1(ii) (metastasis >10 mm in greatest dimension). Stage IIIA2 is now "microscopic extrapelvic peritoneal involvement with or without positive retroperitoneal lymph node" metastasis. This review summarizes the genetics, surgical management, chemotherapy, and targeted therapies for epithelial cancers, and the treatment of ovarian germ cell and stromal malignancies.

Routine Intraoperative Frozen Section Examination to Minimize Bimodal Treatment in Early-Stage Cervical Cancer.

OBJECTIVE: In early-stage cervical cancer, single modality therapy is the main objective, to minimize patient morbidity while offering equivalent cure rates. Intraoperative frozen section examination (FSE) of lymph nodes (LNs) can facilitate this aim, ensuring that radical surgery is avoided in patients requiring adjuvant therapy for metastatic LN involvement. We aimed to evaluate the accuracy of routine intraoperative FSE of pelvic LNs during the surgical staging of early-stage cervical cancers and identify a group at low risk for nodal metastases. METHODS: A retrospective cohort study of 94 women aged 23 to 80 years who underwent primary surgery and planned intraoperative FSE of the pelvic LNs at the gynecological cancer center in Oxford was performed. The diagnostic value of FSE and the prediction of metastatic nodal disease were assessed by use of preoperative and intraoperative variables. RESULTS: A total of 1825 LNs were submitted for FSE. Of 94 women (13.8%), 13 had positive LNs at FSE. Two false-negative cases were reported with micrometastases but no false-positive cases. Frozen section examination as a diagnostic test reached a sensitivity of 86.7% and a specificity of 100%. A regression model including grade I to II and tumor size of less than 20 mm identified a low-risk group for LN involvement. CONCLUSIONS: In light of diverse practice patterns, FSE should be routinely offered to women with early-stage cervical cancer in a 1-step protocol. We equally devised a model to predict those patients at least risk of nodal disease, who may be spared of FSE.

Information and cervical screening: a qualitative study of women's awareness, understanding and information needs about HPV.

OBJECTIVES: To explore women's attitudes towards the information about human papilloma virus (HPV) provided during cervical screening and to describe women's HPV information needs. SETTING: Women with a range of screening results (normal, inadequate, borderline and abnormal) were identified by three screening centres in England. Two consecutive samples of women attending for colposcopy for the first time following screening were also approached. METHODS: Seven focus groups were conducted between May 2005 and April 2006 with 38 women who had recently been for cervical screening or had attended a colposcopy appointment. RESULTS: Most women had no prior awareness of HPV. Many women queried the importance of being informed about HPV as no preventive advice or treatment is available. The HPV information included in the UK national screening programme abnormal result leaflet left women with more questions than answers (a list of unanswered questions is included with the results). Further information was requested about HPV detection, infection and transmission as well as the natural history and progression of cervical cancer. No consensus was reached regarding the best time to provide HPV information. CONCLUSIONS: Clear communication of the complicated issues surrounding HPV infection and the natural history of cervical cancer is a considerable educational challenge for screening providers. As awareness of HPV becomes more widespread and HPV testing is explored as a triage during cervical screening, women are likely to require more information about the virus and the implications of infection. Consideration should be given to the production of a separate national screening programme HPV leaflet.

Advances in the management of cervical cancer.

This review presents key advances in the management of cervical cancer. Traditionally, cervical cancer is staged clinically and has been treated either by radical hysterectomy or by radiotherapy. Improvements in imaging have led to more accurate therapeutic decision making and treatment planning. The evidence on fertility-preserving surgery for cervical cancer and chemoradiotherapy for locally advanced cancer is summarized here. An improved understanding of the viral aetiology of cervical cancer has led to the development of therapeutic vaccination, with limited success. There is increasing recognition of the psychosexual needs of women who have survived cervical cancer.

The hypercoagulable state of malignancy: pathogenesis and current debate.

A hypercoagulable or prothrombotic state of malignancy occurs due to the ability of tumor cells to activate the coagulation system. It has been estimated that hypercoagulation accounts for a significant percentage of mortality and morbidity in cancer patients. Prothrombotic factors in cancer include the ability of tumor cells to produce and secrete procoagulant/fibrinolytic substances and inflammatory cytokines, and the physical interaction between tumor cell and blood (monocytes, platelets, neutrophils) or vascular cells. Other mechanisms of thrombus promotion in malignancy include nonspecific factors such as the generation of acute phase reactants and necrosis (i.e., inflammation), abnormal protein metabolism (i.e., paraproteinemia), and hemodynamic compromise (i.e., stasis). In addition, anticancer therapy (i.e., surgery/chemotherapy/hormone therapy) may significantly increase the risk of thromboembolic events by similar mechanisms, e.g., procoagulant release, endothelial damage, or stimulation of tissue factor production by host cells. However, not all of the mechanisms for the production of a hypercoagulable state of cancer are entirely understood. In this review, we attempt to describe what is currently accepted about the pathophysiology of the hypercoagulable state of cancer. We also discuss whether or not to screen patients with idiopathic deep venous thrombosis for an underlying malignancy, and whether this would be beneficial to patients. It is hoped that a better understanding of these mechanisms will ultimately lead to the development of more targeted treatment to prevent thromboembolic complications in cancer patients. It is also hoped that antithrombotic strategies may also have a positive effect on the process of tumor growth and dissemination.