Genetic variants associated with post-traumatic stress symptoms in patients with gynecologic cancer.

OBJECTIVE: Patients with cancer experience symptoms of post-traumatic stress disorder (PTSD) more commonly than the general population. The objective of this study was to identify single nucleotide polymorphisms (SNPs) associated with increased risk of post-traumatic stress disorder (PTSD) in patients with gynecologic cancer. METHODS: A prospective cohort study recruited 181 gynecologic cancer survivors receiving care at the University of Minnesota between 2017 and 2020 who completed PTSD DSM-V surveys to self-report their symptoms of PTSD and provided saliva samples. DNA samples were genotyped for 11 SNPs in 9 genes involved in dopaminergic, serotonergic, and opioidergic systems previously associated with risk of PTSD in populations without cancer. RESULTS: Most participants had either ovarian (42.5%) or endometrial (46.4%) cancer; fewer had cervical (7.7%) or vaginal/vulvar (3.3%) cancer. Two SNPS were identified as statistically significantly associated with higher PTSD scores: rs622337 in HTR2A and rs510769 in OPRM1. CONCLUSIONS: Genetic variation likely plays a role in development of PTSD. HTR2A is involved in the serotonin pathway, and OPRM1 is involved in the opioid receptor pathway. This information can be used by oncologic providers to identify patients at greater risk of developing PTSD and may facilitate referral to appropriate consultants and resources early in their treatment.

Mixed neuroendocrine/Non-neuroendocrine neoplasm (MiNEN) of gastrointestinal lineage arising in an ovarian mature cystic teratoma.

•Mixed neuroendocrine/non-neuroendocrine neoplasm (MiNEN) of gastrointestinal lineage arising in an ovarian mature cystic teratoma is extremely rare.•It is important to differentiate the gastrointestinal-type adenocarcinoma arising along with neuroendocrine tumor from a primary mucinous adenocarcinoma of the ovary. SATB2 and CDX2 Immunohistochemical stains play important role in differentiate these two.•This case highlights the careful morphologic evaluation and extensive sampling is crucial to make this rare diagnosis.

Superficial versus deep inguinal nodal dissection for vulvar cancer staging.

OBJECTIVE: The objective of this study was to compare the rate of groin recurrence among women undergoing superficial or deep inguinal lymph node dissections in suspected early-stage vulvar carcinoma. Secondary objectives included comparison of overall survival and post-operative morbidity between the study groups. METHODS: A retrospective cohort of 233 patients with squamous cell carcinoma (SCC) of the vulva who underwent an inguinal lymph node dissection at two major academic institutions from 1999 to 2017 were analyzed. Demographic, surgical, recurrence, survival, and post-operative morbidity data were collected for 233 patients, resulting in a total of 400 groin node dissections analyzed. RESULTS: Rates of overall primary recurrence of disease between superficial and deep inguinal LND (42.5 vs. 39.8%, p = 0.70) and rates of inguinal recurrence (3.4 vs. 8.3%, p = 0.16) were similar. Overall rates of postoperative morbidity were significantly higher in the cohort undergoing deep LND (70.3% vs 44.3%, p < 0.01). Rates of lymphedema (42.4 vs 15.9%, p < 0.01), readmission (26.3 vs 6.8%, p < 0.01), and infection (40.7 vs 14.8%, p < 0.01) were all significantly higher among patients undergoing deep LND. There was no significant difference noted in overall survival between the study groups when adjusting for stage and age (HR 1.08, p = 0.84). CONCLUSION: Superficial inguinal LND had no significant difference in rate of recurrence or overall survival when compared to deep inguinal LND in patients with vulvar SCC. Those who received a deep LND had a significant increase in overall morbidity, including lymphedema, readmission, and infection. For patients who cannot undergo or fail sentinel lymph node mapping, a superficial inguinal lymph node dissection may have similar outcomes in recurrence and overall survival with a reduction in overall morbidity as compared to a complete, or deep, lymph node dissection.

Robot-assisted versus laparoscopic minimally invasive surgery for the treatment of stage I endometrial cancer.

OBJECTIVE: Recent reports in both cervical and endometrial cancer suggest that minimally invasive surgery (MIS) had an unanticipated negative impact on long-term clinical outcomes, including recurrence and death. Given increasing use of robotic surgery since the LAP2 trial, we sought to compare the intermediate and long-term outcomes between those who underwent robotic surgery or laparoscopy for Stage I endometrial cancer. METHODS: We performed a retrospective review of patients from a single, large, academic, urban practice who underwent either laparoscopic or robot-assisted MIS (RA-MIS) for the treatment of endometrial carcinoma between 2006 and 2016, ensuring at least 5 years of potential follow-up. To adjust for differences in confounding variables between groups, propensity score-based inverse probability of treatment weighting (IPTW) was performed. Overall and recurrence-free survival were compared using Cox proportional hazards regression models adjusting for confounding weights. RESULTS: 1027 patients were included; 461 received laparoscopy and 566 received RA-MIS. RA-MIS use increased steadily during the study window, which resulted in longer mean surveillance in laparoscopy group (median 8.7 years versus 6.3 years, p < 0.001). RA-MIS was associated poorer recurrence-free (HR: 1.41, 95% CI: 1.12, 1.77) and overall survival (HR: 1.39, 95% CI: 1.06, 1.83). Disease-specific survival was also poorer in the RA-MIS group (HR: 3.51, 95% CI: 2.19, 5.63). Among those who recurred, median time to first recurrence was shorter in the RA-MIS group than the laparoscopy group (16.3 vs. 28.7 months, p = 0.07). CONCLUSION: RA-MIS was associated with poorer long-term patient outcomes. Our data in this lower-risk population indicate relevant clinical endpoints may be occurring during intermediate and long-term follow-up windows. These findings support a prospective evaluation of the long-term outcomes of RA-MIS.

Multimodal perioperative pain protocol for gynecologic laparotomy is associated with reduced hospital length of stay.

OBJECTIVES: The primary objective was to evaluate the impact of a multimodal perioperative pain regimen on length of hospital stay for patients undergoing laparotomy with a gynecologic oncologist. METHODS: We compared 52 patients who underwent laparotomy with a gynecologic oncologist at a single institution between 2017 and 2018, after implementation of a multimodal perioperative pain regimen, to a historic cohort of 94 patients (2016-2017). The multimodal pain regimen included pre- and post-operative administration of oral acetaminophen, gabapentin, and celecoxib, in addition to standard narcotics and optional epidural analgesia. Demographic, surgical, and post-operative data were collected. RESULTS: On multivariable analysis, bowel resection, stage, surgery length, age, and cohort group were retained as significant independent predictors of length of stay. Patients undergoing laparotomy prior to the pain protocol had a length of stay 1.26 times longer than patients during the post-implementation period (p < 0.01). For complex surgical patients, this translated into a reduction in length of hospital stay of 1.73 days. There was a significant reduction in pain scale score on post-operative day zero from 5 to 3 (p = 0.02) and a non-significant overall reduction of post-operative morphine equivalents, with similar adverse outcomes. CONCLUSION: Implementation of a multimodal perioperative pain regimen in patients undergoing gynecologic oncology laparotomy was associated with a significant reduction of length of hospital stay and improved patient-perceived pain, even in the absence of a complete Enhanced Recovery After Surgery (ERAS) protocol.

Minimally Invasive Robotic Surgery for Gynecologic Cancers: A Review.

Minimally invasive robotic surgery has become an effective surgical technique for the treatment of gynecologic malignancies. This article reviews the current utilization of robotic surgery and its role for future treatment in gynecologic oncology.

Differential DNA methylation in high-grade serous ovarian cancer (HGSOC) is associated with tumor behavior.

The epigenome offers an additional facet of cancer that can help categorize patients into those at risk of disease, recurrence, or treatment failure. We conducted a retrospective, nested, case-control study of advanced and recurrent high-grade serous ovarian cancer (HGSOC) patients in which we assessed epigenome-wide association using Illumina methylationEPIC arrays to characterize DNA methylation status and RNAseq to evaluate gene expression. Comparing HGSOC tumors with normal fallopian tube tissues we observe global hypomethylation but with skewing towards hypermethylation when interrogating gene promoters. In total, 5,852 gene interrogating probes revealed significantly different methylation. Within HGSOC, 57 probes highlighting 17 genes displayed significant differential DNA methylation between primary and recurrent disease. Between optimal vs suboptimal surgical outcomes 99 probes displayed significantly different methylation but only 29 genes showed an inverse correlation between methylation status and gene expression. Overall, differentially methylated genes point to several pathways including RAS as well as hippo signaling in normal vs primary HGSOC; valine, leucine, and isoleucine degradation and endocytosis in primary vs recurrent HGSOC; and pathways containing immune driver genes in optimal vs suboptimal surgical outcomes. Thus, differential DNA methylation identified numerous genes that could serve as potential biomarkers and/or therapeutic targets in HGSOC.

Profound sensorineural hearing loss after one cycle of intraperitoneal cisplatin in treatment of advanced ovarian cancer.

Few advances in the treatment of advanced epithelial ovarian cancer have improved patient overall survival. However, the incorporation of intraperitoneal administration of platinum based chemotherapy to standard treatment was one such advancement. It is understood that the intraperitoneal regimen is associated with increased toxicity when compared to intravenous administration alone; however, information regarding the specific risk of ototoxicity is lacking in the literature. We report a case of almost complete sensorineural hearing loss after one cycle of intraperitoneal cisplatin. Three days after receiving an intravenous 24 h paclitaxel at 135 mg/m2 and subsequent intraperitoneal infusion of cisplatin at 75 mg/m2, the patient presented with profound bilateral sensorineural hearing loss. The patient experienced no recovery of hearing despite an aggressive systemic steroid taper and change in chemotherapy regimen to alternative agents. She is currently under consideration for cochlear device implantation. Generally, cisplatin related ototoxicity during treatment of epithelial ovarian cancer is gradual, limited to high-frequency ranges and dose-related; however, the toxicity with only one standard dose can be profound and irreversible. This risk should be addressed when counseling patients prior to initiation of treatment.