Cancer risk management among female BRCA1/2, PALB2, CHEK2, and ATM carriers.

PURPOSE: Identification of inherited breast cancer may guide cancer risk management. We sought to compare risk management practices across women with inherited breast cancer genes. METHODS: Females with a pathogenic/likely pathogenic (P/LP) variant in BRCA1/2, PALB2, CHEK2, and/or ATM were surveyed about cancer risk management. Comparisons were made across genes. RESULTS: The 235 participants with P/LP variants (186 BRCA1/2, 28 PALB2, 15 CHEK2, and 6 ATM) had a median age of 54 and 61% had a prior breast cancer diagnosis. For women with P/LP variants in BRCA1/2, PALB2, and ATM/CHEK2, bilateral mastectomy (BM) rates were 79%, 61%, and 52%, and bilateral oophorectomy (BO) rates were 89%, 30%, and 37%, respectively. Among women with P/LP variants in PALB2 and ATM/CHEK2, 27% of those who had a BO had a family history of ovarian cancer. Contralateral mastectomy rates for women with P/LP variants in PALB2 and ATM/CHEK2 with unilateral breast cancer were 60% and 58%, and BM rates for those without breast cancer were 57% and 29%, respectively. CONCLUSION: These findings suggest high rates of both contralateral mastectomies among those with unilateral breast cancer and BM among those without a breast cancer diagnosis across women with P/LP variants in high and moderate penetrance breast cancer genes. BO was also often utilized for risk reduction across these women. These findings suggest potential overtreatment through risk-reducing surgery, and highlight the importance of promoting guideline-adherent, risk-appropriate care.

Small-Cell Carcinoma of the Ovary, Hypercalcemic Type-Genetics, New Treatment Targets, and Current Management Guidelines.

Small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and highly aggressive ovarian malignancy. In almost all cases, it is associated with somatic and often germline pathogenic variants in SMARCA4, which encodes for the SMARCA4 protein (BRG1), a subunit of the SWI/SNF chromatin remodeling complex. Approximately 20% of human cancers possess pathogenic variants in at least one SWI/SNF subunit. Because of their role in regulating many important cellular processes including transcriptional control, DNA repair, differentiation, cell division, and DNA replication, SWI/SNF complexes with mutant subunits are thought to contribute to cancer initiation and progression. Fewer than 500 cases of SCCOHT have been reported in the literature and approximately 60% are associated with hypercalcemia. SCCOHT primarily affects females under 40 years of age who usually present with symptoms related to a pelvic mass. SCCOHT is an aggressive cancer, with long-term survival rates of 30% in early-stage cases. Although various treatment approaches have been proposed, there is no consensus on surveillance and therapeutic strategy. An international group of multidisciplinary clinicians and researchers recently formed the International SCCOHT Consortium to evaluate current knowledge and propose consensus surveillance and therapeutic recommendations, with the aim of improving outcomes. Here, we present an overview of the genetics of this cancer, provide updates on new treatment targets, and propose management guidelines for this challenging cancer.

Transvaginal salpingo-oophorectomy with gasless laparoscopy - an optional pure natural orifice transluminal endoscopic surgery.

OBJECTIVES: To establish the appropriate technique for salpingo-oophorectomy via transvaginal natural orifice transluminal endoscopic surgery (NOTES), under gasless laparoscopy. MATERIAL AND METHODS: Ten patients with clinical indication underwent gasless laparoscopic transvaginal salpingo-oophorectomy with concurrent vaginal hysterectomy. An abdominal-wall lifting device was used after removal of the uterus, and the adnexa was removed trans-vaginally by gasless laparoscopy. The perioperative clinical data, such as operative duration, volume of blood loss, morbidity, intraoperative and postoperative complications, and length of hospital stay, were retrospectively analyzed. RESULTS: All procedures were successfully done, without any intraoperative or major postoperative complications, and no additional transabdominal ports were required. The salpingo-oophorectomy part of the procedure was completed in approximately 11-40 minutes, with minimal blood loss. All of the patients were discharged, scar-free, 2-4 days after surgery. CONCLUSIONS: Transvaginal NOTES with gasless laparoscopy is a feasible and safe surgical technique in cases involving difficult vaginal salpingo-oophorectomy, which avoids conversion to an abdominal route.

Risk-reducing Bilateral Salpingo-oophorectomy: Assessing the Incidence of Occult Ovarian Cancer and Surgeon Adherence to Recommended Practices.

STUDY OBJECTIVE: This study aimed to determine the incidence of ovarian cancer diagnosed at the time of risk-reducing bilateral salpingo-oophorectomy in a large cohort of patients with a BRCA mutation. In addition, we aimed to determine the adherence to the recommended practices for performing a risk-reducing bilateral salpingo-oophorectomy as described by the American College of Obstetricians and Gynecologists and the Society of Gynecologic Oncology. We sought to determine if adherence differed by the type of training (i.e., gynecologic oncologists vs benign gynecologists). DESIGN: Descriptive, retrospective analysis. SETTING: Academic medical center. PATIENTS: Two hundred sixty-nine patients with a known BRCA mutation. INTERVENTIONS: Prophylactic risk-reducing bilateral salpingo-oophorectomy performed either by a gynecologic oncologist or a benign gynecologist between July 2007 and September 2018. MEASUREMENTS AND MAIN RESULTS: Among 269 patients who underwent risk-reducing bilateral salpingo-oophorectomies, 220 procedures were performed by gynecologic oncologists, and 49 were performed by benign gynecologists. Washings were not performed in 5% of the procedures performed by gynecologic oncologists and 37% of the procedures performed by benign gynecologists (p <.001). Complete serial sectioning of the adnexa was not performed in 12% of the procedures performed by oncologists, and 13% of the procedures performed by benign gynecologists (p = .714). There were 8 cases (2.9%) of tubal or ovarian cancer diagnosed within this cohort. Of these cases, only 3 (1.1%) were diagnosed at the time of surgery and met the criteria for conversion to a staging procedure. CONCLUSION: Because the incidence of ovarian cancer diagnosis at the time of risk-reducing bilateral salpingo-oophorectomy is low and is often not diagnosed at the time of surgery owing to the presence of only microscopic disease, it may not be necessary for gynecologic oncologists to exclusively perform these procedures. However, this study also revealed that when this procedure is performed by benign gynecologic surgeons, some of the recommended practices are not routinely followed. If general gynecologic surgeons are to routinely perform risk-reducing bilateral salpingo-oophorectomies, it is important to promote better adherence to these practices.

Adnexal Torsion in Adolescents: ACOG Committee Opinion No, 783 Summary.

Adnexal torsion is the fifth most common gynecologic emergency. The most common ovarian pathologies found in adolescents with adnexal torsion are benign functional ovarian cysts and benign teratomas. Torsion of malignant ovarian masses in this population is rare. In contrast to adnexal torsion in adults, adnexal torsion in pediatric and adolescent females involves an ovary without an associated mass or cyst in as many as 46% of cases. The most common clinical symptom of torsion is sudden-onset abdominal pain that is intermittent, nonradiating, and associated with nausea and vomiting. If ovarian torsion is suspected, timely intervention with diagnostic laparoscopy is indicated to preserve ovarian function and future fertility. When evaluating adolescents with suspected adnexal torsion, an obstetrician-gynecologist or other health care provider should bear in mind that there are no clinical or imaging criteria sufficient to confirm the preoperative diagnosis of adnexal torsion, and Doppler flow alone should not guide clinical decision making. In 50% of cases, adnexal torsion is not found at laparoscopy; however, in most instances, alternative gynecologic pathology is identified and treated. Adnexal torsion is a surgical diagnosis. A minimally invasive surgical approach is recommended with detorsion and preservation of the adnexal structures regardless of the appearance of the ovary. A surgeon should not remove a torsed ovary unless oophorectomy is unavoidable, such as when a severely necrotic ovary falls apart. Although surgical steps may be similar to those taken when treating adult patients, there are technical adaptations and specific challenges when performing gynecologic surgery in adolescents. A conscientious appreciation of the physiologic, anatomic, and surgical characteristics unique to this population is required.

Adnexal Torsion in Adolescents: ACOG Committee Opinion No, 783.

Adnexal torsion is the fifth most common gynecologic emergency. The most common ovarian pathologies found in adolescents with adnexal torsion are benign functional ovarian cysts and benign teratomas. Torsion of malignant ovarian masses in this population is rare. In contrast to adnexal torsion in adults, adnexal torsion in pediatric and adolescent females involves an ovary without an associated mass or cyst in as many as 46% of cases. The most common clinical symptom of torsion is sudden-onset abdominal pain that is intermittent, nonradiating, and associated with nausea and vomiting. If ovarian torsion is suspected, timely intervention with diagnostic laparoscopy is indicated to preserve ovarian function and future fertility. When evaluating adolescents with suspected adnexal torsion, an obstetrician-gynecologist or other health care provider should bear in mind that there are no clinical or imaging criteria sufficient to confirm the preoperative diagnosis of adnexal torsion, and Doppler flow alone should not guide clinical decision making. In 50% of cases, adnexal torsion is not found at laparoscopy; however, in most instances, alternative gynecologic pathology is identified and treated. Adnexal torsion is a surgical diagnosis. A minimally invasive surgical approach is recommended with detorsion and preservation of the adnexal structures regardless of the appearance of the ovary. A surgeon should not remove a torsed ovary unless oophorectomy is unavoidable, such as when a severely necrotic ovary falls apart. Although surgical steps may be similar to those taken when treating adult patients, there are technical adaptations and specific challenges when performing gynecologic surgery in adolescents. A conscientious appreciation of the physiologic, anatomic, and surgical characteristics unique to this population is required.

Conservative surgery in stage I adult type granulosa cells tumors of the ovary: Results from the MITO-9 study.

OBJECTIVE: About 30% of Adult type granulosa cell tumors of the ovary (AGCTs) are diagnosed in fertile age. In stage I, conservative surgery (fertility-sparing surgery, FSS), either unilateral salpingo-oophorectomy (USO) or cystectomy are possible options. The aim of this study is to compare oncological outcomes of FSS and radical surgery (RS) in apparently stage I AGCTs treated within the MITO group (Multicenter Italian Trials in Ovarian cancer). METHODS: Survival curves were calculated using the Kaplan-Meier method and compared with log-rank test. The role of clinicopathological variables as prognostic factors for survival was assessed using Cox's regression. RESULTS: Two-hundred and twenty-nine patients were included; 32.6% received FSS, 67.4% RS. In the FSS group, 62.8% underwent USO, 16.7% cystectomy, 20.5% cystectomy followed by USO. After a median follow up of 84 months, median DFS was significantly worse in the FSS-group (10 yr DFS 50% vs 74%, in FSS and RS group, p = 0.006). No significant difference was detected between RS and USO (10 yr DFS 75% vs 70%, p = 0.5).Cystectomy-group showed a significantly worse DFS compared to USO (10 yr DFS 16% vs 70%, p < 0.001). Patients receiving cystectomy and subsequent USO showed a better prognosis, even though significantly worse compared to USO (10 yr DFS 41% vs 70%, p = 0.05). Between FSS and RS, no difference in OS was detected. At multivariate analysis, FIGO stage IC and cystectomy retained significant predictive value for worse survival. CONCLUSIONS: This study supports the oncological safety of FSS in stage I AGCTs, provided that cystectomy is avoided; USO should be the preferred approach.

Postoperative complications and owner assessment of single portal laparoscopic ovariectomy in dogs.

The aim of this retrospective study and owner survey was to record the postoperative complication rate, pain score and owners' satisfaction rates of single portal laparoscopic ovariectomy in dogs using an operating laparoscope and to compare our results with data in the veterinary literature on other laparoscopic methods. Therefore, the medical records of all bitches that were spayed using a laparoscopic single port ovariectomy with an operating laparoscope between November 2007 and November 2014 were reviewed. A minimum follow-up period of 12 months was required for study inclusion. One hundred and thirty two adult, healthy, femal dogs were included in our study. The information collected included breed, bodyweight, age at ovariectomy and postoperative complications detected during follow-up 9-14 days after surgery. Furthermore, an electronic questionnaire was implemented, and the owners of the dogs were asked to report on long-term complications and to retrospectively evaluate postoperative pain and overall satisfaction. Sixty-two different and mixed breed dogs with weights ranging from 1.9 to 50 kg and ages ranging from 0.5 to 10.8 years were included. Short-term complications were detected in 21 out of 132 cases, mostly at the surgical site (15.9 per cent). According to our questionnaire (n=65), 10 dogs developed urinary incontinence categorised as a major complication (15.4 per cent). The owner's evaluated pain score was less than 300 on a 1000-unit visual analogue scale for 56 out of 65 dogs (86.2 per cent) and less than 500 in 63 dogs (96.9 per cent). The dog owners' satisfaction rate was 95.3 per cent (87.5 per cent evaluated the surgery as excellent and 7.8 per cent as good). Altogether, our study suggests that single port access using an operating laparoscope for ovariectomy has minor complication rates comparable to other laparoscopic techniques but has the advantages of a low postoperative pain level as evaluated by the owner and a very high owner's satisfaction rate.

New Therapies for Ovarian Cancer.

In the latest NCCN Guidelines for Ovarian Cancer, the histologic subtypes of ovarian cancer are described in more depth as they vary by frequency, typical age and disease stage at presentation, treatment recommendations, and survival probabilities. The less common subtypes are also discussed. The update with the greatest impact on the treatment of ovarian cancer, however, is probably the use of maintenance therapy with poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors, and 3 PARP inhibitors are now included in the guidelines. These drugs have made a large difference in outcome, both for patients with BRCA mutations and in unselected patients.

Quality of life following prophylactic gynecological surgery: experiences of female Lynch mutation carriers.

Lynch syndrome (LS) is a genetic condition conferring an elevated risk of gastrointestinal, gynecologic and other malignancies, often before the age of 50. Current guidelines recommend prophylactic gynecologic surgery to manage inherited cancers for female mutation carriers. Data is lacking on women's quality of life following surgery. In this pilot study, we explored how women described their quality of life post-prophylactic gynecologic surgery and the factors that affected post-surgery experiences. A qualitative interview study was the chosen design. Ten female Lynch syndrome mutation carriers were interviewed by phone. Interviews were transcribed and analysed for themes relating to quality of life post-surgery using content analysis and constant comparison. Women largely reported doing well since their surgeries, though all described deleterious impacts on quality of life. Positive impacts of surgery included a reduction in cancer worry and an increase in healthy lifestyle behaviors, while negative impacts due to the sudden onset of menopause and impact on sexual function were common. Pre-surgical knowledge, drug and topical therapies, and post-surgical support all contributed to a positive quality of life. This small pilot study revealed increased endocrine symptoms and a negative impact on sexual health following prophylactic gynecological surgery. Women who were informed of potential symptoms pre-surgery coped better with surgical outcomes, as did women using some form of HRT. All women experienced reduced cancer worry post-surgery. Findings highlight areas for discussion in pre-operative settings (e.g., sexual health), as well as the need for better follow-up support post-surgery.

Evaluation of learning curves for ovariohysterectomy of dogs and cats and castration of dogs.

OBJECTIVE To define learning curves for fourth-year veterinary students performing ovariohysterectomy procedures in dogs and cats and castration in dogs. DESIGN Retrospective study. SAMPLE 3,196 ovariohysterectomies or castrations performed in dogs and cats by 88 veterinary students during a spay-neuter surgery and animal shelter rotation (n = 3,056) or by 1 experienced general practitioner (n = 140). PROCEDURES Data collected from medical records included patient signalment, type and duration of procedure, and sequence (by date and time) of the procedure within a list of procedures of the same type generated for each student. For each procedure type, geometric mean surgery time and 95% confidence intervals were determined for each number of surgeries completed by ≥ 10 students. Median surgery times for the same procedure types were determined for the experienced practitioner. The learning curve for each procedure was modeled with nonlinear (3-factor exponential equation with a nonzero asymptote) and linear regression. For each procedure, the asymptote (optimal surgery time) for students was compared with the experienced practitioner's median surgery time. RESULTS 2,945 surgeries (mean, 33/student) performed by ≥ 10 students were analyzed. Surgery time decreased in a nonlinear manner as student experience increased for castration of adult or pediatric dogs and ovariohysterectomy of pediatric dogs and adult or pediatric cats. Surgery time decreased in a linear manner as experience increased for ovariohysterectomy of adult dogs. CONCLUSIONS AND CLINICAL RELEVANCE To the authors' knowledge, this was the first study to map surgery times for common surgical procedures consecutively performed by veterinary students. Results clearly indicated the value of repetition to improve surgical skills (as measured by surgery time) during a 3-week period.

Quality control in ovarian cancer surgery.

The optimal surgical management of patients with ovarian cancer includes a thorough staging with peritoneal and retroperitoneal assessment for early disease stages and a complete debulking with the removal of all macroscopic tumor for advanced disease stages. Disparities across different institutions in terms of optimal surgical management have been described. Surgical quality control programs constitute a real possibility to ensure and improve the quality of the surgery performed. Guidelines for surgery in early and advanced disease stages have been recently reviewed by the National Comprehensive Cancer Network (NCCN), and several quality indicators (QIs) have been proposed. These QIs can be used as a powerful tool to monitor, compare, and improve the quality of surgery across different centers and institutions. Furthermore, a transparent report of surgical outcomes through the creation of National and International Networks, adherence to the NCCN guidelines, and the establishment of quality control programs with a strong training and education component are key factors in enhancing the quality of surgery for patients with ovarian cancer.

Ten Principles for Safe Surgical Treatment of Ovarian Endometriosis.

STUDY OBJECTIVE: To show a step-by-step laparoscopic approach for excision of an ovarian endometrioma following surgical principles for safety and maximal preservation of ovarian function. DESIGN: Video. Medical management of ovarian endometriomas is not recommended. Operative laparoscopy is the treatment of choice. Although considered a simple procedure, ovarian cystectomy requires a precise and correct technique in order to preserve ovarian function. SETTING: A private hospital. PATIENT: An asymptomatic, 27-year-old woman with ultrasound imaging suggesting a 6.2 × 5.4 cm left endometrioma. Additional findings of endometriotic implants were noted in the posterior aspect of the left broad ligament, retrocervical region, Douglas pouch, and left round ligament. INTERVENTIONS: After trocar insertion, standard inspection of the pelvic cavity with identification of endometriosis lesions and adhesions was performed. The endometrioma was drained with direct trocar puncture to avoid spillage of the endometriotic contents. Cyst aspiration and saline cleaning were executed. After drainage, a cold cut was performed at the puncture site for better identification of the cyst capsule. Through gentle traction and countertraction, the capsule was peeled from the ovarian cortex, preserving as much ovarian tissue as possible followed by careful hemostasis with a bipolar instrument. The ovary is fixed, anatomy re-established, and concomitant pelvic endometriosis resected. We aim for complete surgical excision in order to avoid leaving disease behind. The ovarian edges were reapproximated using simple interrupted stitches. MEASUREMENTS AND MAIN RESULTS: The total procedure time was 40 minutes. CONCLUSION: Laparoscopic endometrioma stripping offers an effective option for ovarian endometriosis treatment, reducing recurrence and being reproducible by gynecologic surgeons after proper training.

Effects of an optional clinical skills laboratory on surgical performance of third-year veterinary students.

OBJECTIVE: To determine whether addition of an optional clinical skills laboratory (OCSL) to the traditional surgery curriculum would affect total surgery time or incision closure time in veterinary students performing ovariohysterectomy of a dog during a third-year surgery course. DESIGN: Retrospective and prospective study of veterinary student attendance at OCSL sessions and student performance during the third-year surgery course. SAMPLE: Students from the classes of 2012, 2013, and 2014 at the Washington State University College of Veterinary Medicine. PROCEDURES: For all students, total surgery time and incision closure time were recorded when students performed an ovariohysterectomy of a dog during their third-year live-animal surgery course. Times were analyzed to identify differences among classes and determine whether times were associated with number of OCSL sessions attended, previous experience performing ovariohysterectomies, or enrollment in an elective clinical skills course. RESULTS: Total surgery and incision closure times were not significantly different between students in the class of 2012 (no access to the OCSL prior to the third-year surgery course) and students in the class of 2013 (ie, access to 4 OCSL sessions during the spring semester prior to the third-year surgery course). However, times were significantly shorter for students in the class of 2014 (ie, students who had access to OCSL sessions during the 3 semesters prior to the third-year surgery course) than for students in the other 2 classes. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that attendance in the OCSL sessions was associated with improvements in surgical performance, as reflected in faster total surgery and incision closure times while performing an ovariohysterectomy during the third-year surgery course.

Laparoscopy for the treatment of ovarian remnant syndrome in four dogs and two cats.

OBJECTIVE: To describe the clinical workup and laparoscopic treatment of ovarian remnant syndrome in dogs and cats. MATERIAL AND METHODS: After confirming the diagnosis with some or all of the following tests - vaginoscopy with cytology, hormonal tests, and ultrasound - laparoscopic removal of the ovarian remnants was performed. A three-portal technique was used in the four dogs and a two-portal technique in the two cats. RESULTS: All patients recovered well and were discharged the same day. No post-operative complications occurred in any patient. CONCLUSION AND CLINICAL RELEVANCE: Overall, in the hands of an experienced laparoscopic surgeon, laparoscopic removal of ovarian remnants appears to be a safe procedure in dogs and cats. In addition, laparoscopy offers the advantages of excellent visualization and a reduced morbidity for the patient. Careful case selection and complete pre-operative workup to rule out co-morbidities or underlying neoplasia are important. As with any laparoscopy the surgeon should always be prepared to convert to an open laparotomy if necessary.

[Feasibility of opportunistic salpingectomy at the time of vaginal hysterectomy for benign pathology and evaluation of occult tubal lesions prevalence: Preliminary study]. / Faisabilité de la salpingectomie prophylactique lors d'une hystérectomie d'indication bénigne par voie vaginale et évaluation de la prévalence des lésions tubaires occultes : étude préliminaire.

AIM: To assess the feasibility of prophylactic salpingectomy during vaginal hysterectomy for benign pathology and the prevalence of occult tubal lesions. MATERIALS AND METHODS: In this prospective study from 09/01/2013 to 11/01/2014, patients who underwent vaginal hysterectomy with salpingectomy or salpingo-oophorectomy were included. The prevalence of bilateral salpingectomy with or without ovariectomy and the prevalence of histopathological and immunohistochemical (p53 expression) abnormalities were evaluated. RESULTS: Bilateral salpingectomy was performed in 51/69 patients (73.9%). An elevated BMI was statistically associated with a failure of the salpingectomy (29.4 vs 25.8; P=0.01). There was only one case of postoperative hemorrhage in the salpingectomy group. On the 51fallopian tubes, there were 4 (12.9%) immunohistochemical abnormalities "p53 signature". CONCLUSION: The recent tubal origin of most ovarian cancer cases raised the question of the prophylactic salpingectomy in the population with genetic risk as well as in the general population. Bilateral salpingectomy may be performed during vaginal hysterectomy. However caution is needed because we do not know what is the exact evolution of the p53 signatures.

Comparison of the ability of veterinary medical students to perform laparoscopic versus conventional open ovariectomy on live dogs.

OBJECTIVE: To compare the feasibility of training veterinary medicine students to perform laparoscopic versus conventional open ovariectomy in live dogs. DESIGN: Randomized prospective parallel-group experiment. POPULATION: 25 students completing the second year of their veterinary curriculum. PROCEDURES: Students were randomly assigned to 2 groups to receive 14 hours of specific training in either open ovariectomy (n = 13) or laparoscopic ovariectomy (12). Confidence, basic surgical skills, and basic laparoscopic skills were evaluated before and after training, prior to live surgical procedures. RESULTS: Scores related to basic surgical skills were high in both groups and did not improve with either training program. Before live animal surgeries, student confidence and basic laparoscopic skills improved after training in laparoscopic ovariectomy and were higher than after training in open ovariectomy. Surgery time was higher for the students who received training in laparoscopic ovariectomy (129 minutes; range, 84 to 143 minutes), compared with students who received training in open ovariectomy (80 minutes; range, 62 to 117 minutes). On a 55-point scoring system, ovariectomy scores were similar between students who received training in open ovariectomy (34.5; range, 16.5 to 45) and students who received training in laparoscopic ovariectomy (34.5; range, 25 to 44.5). CONCLUSIONS AND CLINICAL RELEVANCE: The training programs were effective in improving student confidence and skills in laparoscopic ovariectomy. Results of this study suggested that veterinary medical students, with assistance from an instructor, may be taught to perform laparoscopic ovariectomies with performance equivalent to that for students performing open ovariectomies.