Syringe or mask? Loop electrosurgical excision procedure under local or general anesthesia: a randomized trial.

BACKGROUND: Loop electrosurgical excision procedure may be performed under local anesthesia or general anesthesia, and practice patterns differ worldwide. No randomized head-to-head comparison has been published to confirm or refute either practice. OBJECTIVE: This study aimed to compare loop electrosurgical excision procedure under local anesthesia vs general anesthesia regarding patient satisfaction and procedure-related outcomes such as rates of involved margins, complications, pain, and blood loss. STUDY DESIGN: Consecutive women referred to our colposcopy unit were recruited. Loop electrosurgical excision procedure was performed under local anesthesia with 4 intracervical injections of bupivacaine hydrochloride 0.5% or under general anesthesia with fentanyl, propofol, and a laryngeal mask with sevoflurane maintenance. The primary endpoint was patient satisfaction assessed on the day of surgery and 14 days thereafter using a Likert scale (score 0-100) and a questionnaire. Secondary endpoints included rates of involved margins, procedure-related complications, pain, blood loss, and surgeon preference. Results were compared using nonparametric and chi-square tests. RESULTS: Between July 2018 and February 2020, we randomized 208 women, 108 in the local anesthesia arm and 100 in the general anesthesia arm. In the intention-to-treat analysis, patient satisfaction did not differ between the study groups directly after surgery (Likert scale 100 [90-100] vs 100 [90-100]; P=.077) and 14 days thereafter (Likert scale 100 [80-100] vs 100 [90-100]; P=.079). In the per-protocol analysis, women in the local anesthesia arm had significantly smaller cone volumes (1.11 cm3 [0.70-1.83] vs 1.58 cm3 [1.08-2.69], respectively; P<.001), less intraoperative blood loss (Δhemoglobin, 0.2 g/dL [-0.1 to 0.4] vs 0.5 g/dL [0.2-0.9]; P<.001), and higher satisfaction after 14 days (100 [90-100] vs 100 [80-100]; P=.026), whereas surgeon preference favored general anesthesia (90 [79-100] vs 100 [90-100], respectively; P=.001). All other secondary outcomes did not differ between groups (resection margin status R1, 6.6% vs 2.1% [P=.26]; cone fragmentation, 12.1% vs 6.3% [P=.27]; procedure duration, 151.5 seconds [120-219.5] vs 180 seconds [117-241.5] [P=.34]; time to complete hemostasis, 60 seconds [34-97] vs 70 seconds [48.25-122.25] [P=.08]; complication rate, 3.3% vs 1.1% [P=.59]). In a multivariate analysis, parity (P=.03), type of transformation zone (P=.03), and cone volume (P=.02) and not study group assignment, age, body mass index, and degree of dysplasia independently influenced the primary endpoint. CONCLUSION: Loop electrosurgical excision procedure under local anesthesia is equally well tolerated and offers patient-reported and procedure-related benefits over general anesthesia, supporting the preferred practice in some institutions and refuting the preferred practice in others.

Chronic ectopic pregnancy: case report and systematic review of the literature.

BACKGROUND: Chronic ectopic pregnancy (CEP) is a variant of ectopic pregnancy (EP) characterized by low or absent serum human chorionic gonadotropin (hCG) levels, resistance to methotrexate (MTX), and an adnexal mass with fibrosis, necrosis, and blood clots due to repeated and gradual fallopian tube wall disintegration. CEP may complicate the course of patients with EP and is difficult to diagnose. CASE PRESENTATION: The case of a 36-year-old woman with EP, low serum hCG levels, a small echogenic adnexal mass, and resistance to MTX is presented. Salpingectomy was performed and histology demonstrated CEP with fibrosis, necrosis, and a hematocele within degenerated chorionic villi. SYSTEMATIC LITERATURE REVIEW: In a database search, 19 case reports, 3 case-control studies, and 3 case series describing 399 patients with CEP were identified. Serum hCG was negative in 40/124 cases (32%) with reported levels of serum hCG. The most common presenting symptom was abdominal pain (284/399 [71%]), followed by irregular vaginal bleeding (219/399 [55%]), and fever (20/399 [5%]). 73/399 (18%) women were asymptomatic. An adnexal mass was seen in 144/298 (48%) cases with perioperative ultrasound examination and with a mean largest diameter of 6.8 cm. Data on treatment modalities and outcomes were available for 297 women. Of these, 89% underwent surgery as first-line therapy. Laparoscopy was performed in most cases. MTX was the first-line therapy in a minority of cases. Complete resolution was achieved by first-line therapy in 287/297 (97%) cases. Adverse events were reported in 218 patients with CEP. Among those, adverse events ≥ grade 3 were seen in 186/218 (85%) cases. There was no case of treatment-related mortality. CONCLUSION: CEP is a variant of EP with low or absent trophoblast activity. A prolonged clinical course is typical and surgery is the mainstay of treatment.

Acute colonic pseudoobstruction (Ogilvie's syndrome) in gynecologic and obstetric patients: case report and systematic review of the literature.

BACKGROUND: Acute colonic pseudo-obstruction or Ogilvie's syndrome (OS) is a rare form of postsurgical or posttraumatic complication. OS rarely occurs in the postoperative course of gynecologic and obstetric patients and is difficult to diagnose. CASE PRESENTATION: We present the case of an 83-years-old patient with carcinosarcoma of the uterus who developed OS with non-obstructive dilation of the right hemicolon and intraabdominal compression after total abdominal hysterectomy, omentectomy, and lymphadenectomy. Laparotomy with colonic decompression and abdominal dressing was performed. Subsequently, the patient developed pneumonia and peritonitis and died due to septic shock. SYSTEMATIC LITERATURE REVIEW: We identified 49 case reports and 10 case series describing 17 gynecologic (cervical cancer, n = 2; carcinosarcoma of the uterus, n = 1; benign gynecologic condition, n = 14) and 76 obstetric patients (cesarean section, n = 66; OS during pregnancy or after vaginal delivery, n = 10). Outcome data were available for 59 patients. First-line treatment was conservative in 22/59 (37%) cases, laparotomy with decompression or colon resection was performed in 20/59 (34%) cases, endoscopic decompression in 12/59 (20%) cases, and i.v. neostigmine in 4/59 (7%) cases. Resolution was achieved in 22/59 (37%) of patients. The most common second-line treatment was right hemicolectomy. Adverse events grade 3 and 4 were observed in 8/59 and 31/59 patients (together 66%), respectively, mortality was 3/59 (5%). CONCLUSION: OS is a rare postoperative complication of gynecologic and obstetric patients with a good prognosis, but a high morbidity. Pregnancy seems to be a predisposing factor for OS. Conservative treatment is a successful first-line approach.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for endometrial cancer-derived peritoneal metastases: a systematic review.

Cytoreductive surgery (CRS) is an appropriate treatment for selected patients with endometrial cancer (EC)-derived peritoneal metastases (PM). Hyperthermic intraperitoneal chemotherapy (HIPEC) may enhance the therapeutic efficacy of CRS in these patients. We performed a systematic literature search of the databases PubMed and Cochrane Central Register of Controlled Trials to identify clinical trials and case reports reporting on the safety and efficacy of CRS and HIPEC in patients with EC-derived PM. Eight publications reporting on 68 patients were identified. The mean patient age was 57.1 years and the mean time from initial treatment of EC to CRS and HIPEC was 22.3 months. 41/64 patients had adenocarcinomas, type II cancers were present in 23/64 patients. The mean peritoneal carcinomatosis index (PCI) was 16.7. A complete surgical resection CC-0 was achieved in 44/63 (70%) patients. The chemotherapy regimens used for HIPEC were variable, but all included cisplatin, administered either alone (39/68 patients) or combined with doxorubicin or paclitaxel or mitomycin (29/68 patients). The duration of HIPEC was 60 min in 51/68 patients and 90 min in 17/68 patients. Mostly, the closed technique was used (55/68 patients). Adverse events grades 1/2, 3, and 4 were observed in 23/63, 12/63, and 6/63 patients, respectively. Treatment-associated mortality was 1% (1/63). After CRS and HIPEC, most patients received systemic chemotherapy (46/63 patients). Median disease-free and overall survival ranged from 7 to 18 and 12 to 33 months, respectively. In conclusion, CRS and HIPEC in EC with PM is safe and feasible. An additional therapeutic value of HIPEC is suggested, but prospective comparative trials are warranted.

Loop electrosurgical excision procedure with or without intraoperative colposcopy: a randomized trial.

BACKGROUND: Loop electrosurgical excision procedure is the standard surgical treatment for cervical dysplasia. Loop electrosurgical excision procedure is advised to be performed under colposcopic guidance to minimize adverse pregnancy outcomes. To date, there is no evidence from randomized trials for this recommendation. OBJECTIVE: We sought to assess the benefits of performing loop electrosurgical excision procedure under colposcopic guidance in women with cervical dysplasia. STUDY DESIGN: In a prospective, randomized trial, we compared loop electrosurgical excision procedure with loop electrosurgical excision procedure performed under direct colposcopic vision in a 1:1 ratio. The primary endpoint was resected cone mass; the secondary endpoints were margin status, fragmentation of the surgical specimen, procedure time, time to complete hemostasis, blood loss, and intraoperative and postoperative complications. A sample size of 87 per group (n = 174) was planned (with an assumed type I error of 0.05 and drop-out rate of 5%) to achieve 90% power to detect a 25% reduction in cone mass (with an assumed cone mass of 2.5 ± 1.6 g in the control group) using a nonparametric test (Mann-Whitney U). RESULTS: From October 2016 through December 2017, we randomized 182 women: 93 in the loop electrosurgical excision procedure group and 89 in the loop electrosurgical excision procedure-direct colposcopic vision group. Women undergoing loop electrosurgical excision procedure-direct colposcopic vision had significantly smaller cone specimens than those undergoing loop electrosurgical excision procedure (weight: median 1.86 [interquartile range 1.20-2.72] vs median 2.37 [interquartile range 1.63-3.31] g, respectively, P = .006). Secondary outcome measures did not differ significantly between groups: resection margin status involved vs free margin: 12 (13%) vs 75 (82%) and 11 (12.4%) vs 75 (84.3%); fragmentation no vs yes: 85 (92.4%) vs 7 (7.6%) and 84 (94.4%) vs 5 (5.6%); procedure time: 190 (interquartile range 138-294) and 171 (interquartile range 133-290) seconds; time to complete hemostasis: 61 (interquartile range 31-108) and 51 (interquartile range 30-81) seconds; intraoperative blood loss (Δhemoglobin): 0.4 (interquartile range 0.2-1.0) and 0.5 (interquartile range 0.1-0.9); complication rate: 6 (6.5%) and 2 (2.2%). In a multivariate analysis, study group allocation (P = .021) and parity (P = .028), but not age, body mass index, type of transformation zone, and dysplasia degree independently influenced the amount of resected cone mass. CONCLUSION: Loop electrosurgical excision procedure with intraoperative colposcopy leads to significantly smaller cone specimens without compromising margin status.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for peritoneal carcinomatosis: systematic review of clinical and experimental evidence with special emphasis on ovarian cancer.

BACKGROUND: Systemic chemotherapy is not effective in patients with peritoneal carcinomatosis (PC) and only a minority of affected patients is eligible for cytoreductive surgery. Intraperitoneal chemotherapy may provide a therapy alternative for these patients. METHODS: We performed a systematic review of clinical and experimental evidence on the safety and efficacy of pressurized intraperitoneal aerosol chemotherapy (PIPAC) in patients with PC and provide clinical recommendations based on the available evidence. RESULTS: Fifty-eight reports were identified, categorized as experimental (18 reports), clinical (28 reports), and other articles (14 reports). Experimental studies demonstrated improved tissue penetration and peritoneal coverage. The 28 clinical studies reported on 3515 procedures in 1547 patients with PC of various primary tumors with 16 of these studies reporting on patients with ovarian cancer. Toxicity was manageable. Based on 1197 patients in 22 studies, adverse events CTCAE grades 1, 2, 3, 4, and 5 were observed in 537 (45%), 167 (14%), 83 (7%), 10 (0.8%), and 19 (1.6%) cases, respectively. In a pooled analysis, the objective tumor response rate was 69% and the mean overall survival duration was 13.7 months. No significant hepatic, renal, or hematologic toxicity was described. PIPAC maintained and/or improved quality of life, as reported in 10 studies with 396 patients. CONCLUSIONS: Available evidence from controlled trials (phase I and phase II) and retrospective cohort studies in > 1500 patients unequivocally demonstrates that PIPAC is feasible, safe, and effective. PIPAC maintains quality of life in patients with recurrent cancer and PC. PIPAC is as evidence-based as any other treatment in women with ovarian cancer and PC beyond the third line of systemic chemotherapy and can be recommended in this indication.

Neuroendocrine carcinoma of the cervix: a systematic review of the literature.

BACKGROUND: Neuroendocrine carcinoma of the cervix (NECC) is a rare variant of cervical cancer. The prognosis of women with NECC is poor and there is no standardized therapy for this type of malignancy based on controlled trials. METHODS: We performed a systematic literature search of the databases PubMed and Cochrane Central Register of Controlled Trials to identify clinical trials describing the management and outcome of women with NECC. RESULTS: Three thousand five hundred thirty-eight cases of NECC in 112 studies were identified. The pooled proportion of NECC among women with cervical cancer was 2303/163470 (1.41%). Small cell NECC, large cell NECC, and other histological subtypes were identified in 80.4, 12.0, and 7.6% of cases, respectively. Early and late stage disease presentation were evenly distributed with 1463 (50.6%) and 1428 (49.4%) cases, respectively. Tumors expressed synaptophysin (424/538 cases; 79%), neuron-specific enolase (196/285 cases; 69%), chromogranin (323/486 cases; 66%), and CD56 (162/267; 61%). The most common primary treatment was radical surgery combined with chemotherapy either as neoadjuvant or adjuvant chemotherapy, described in 42/48 studies. Radiotherapy-based primary treatment schemes in the form of radiotherapy, radiochemotherapy, or radiotherapy with concomitant or followed by chemotherapy were also commonly used (15/48 studies). There is no standard chemotherapy regimen for NECC, but cisplatin/carboplatin and etoposide (EP) was the most commonly used treatment scheme (24/40 studies). Overall, the prognosis of women with NECC was poor with a mean recurrence-free survival of 16 months and a mean overall survival of 40 months. Immune checkpoint inhibitors and targeted agents were reported as being active in three case reports. CONCLUSION: NECC is a rare variant of cervical cancer with a poor prognosis. Multimodality treatment with radical surgery and neoadjuvant/adjuvant chemotherapy with cisplatin and etoposide with or without radiotherapy is the mainstay of treatment for early stage disease while chemotherapy with cisplatin and etoposide or topotecan, paclitaxel, and bevacizumab is appropriate for women with locally advanced or recurrent NECC. Immune checkpoint inhibitors may be beneficial, but controlled evidence for their efficacy is lacking.

A phase I, single-arm, open-label, dose escalation study of intraperitoneal cisplatin and doxorubicin in patients with recurrent ovarian cancer and peritoneal carcinomatosis.

OBJECTIVE: We performed a phase I, single-arm, non-randomized, open-label, dose-escalation trial to determine the dose-limiting toxicity of intraperitoneal cisplatin and doxorubicin applied as pressurized intraperitoneal aerosol chemotherapy (PIPAC) in women with recurrent ovarian cancer. METHODS: We used a standard 3 + 3 dose-escalation design with doxorubicin 1.5 mg/m2, cisplatin 7.5 mg/m2 q 4 to 6 weeks for 3 cycles and subsequent dose escalation steps (20% increment per step) in patients with recurrent ovarian cancer and peritoneal carcinomatosis. Toxicity and clinical efficacy were monitored. The primary endpoint was the maximum-tolerable dose. Secondary endpoints included histologic tumor regression and serum parameters. RESULTS: 15 evaluable patients (3, 7, and 5 in cohorts 1, 2, and 3, respectively) on average received 2.3 PIPAC cycles. No dose limiting toxicities were found. Adverse side effects were 1 grade 3 event (colon perforation) and 85 grade 1/2 events including fatigue (n = 19), abdominal pain (n = 18), nausea/vomiting (n = 14), sleep disorder (n = 8), diarrhea (n = 5), and fever (n = 2). Liver and renal toxicity was not observed in any of the 3 cohorts (AST 19.1 ±â€¯3.2, 25.8 ±â€¯6.5, and 22.1 ±â€¯4.5 IU/L, respectively; ALT 14.7 ±â€¯3.5, 18.5 ±â€¯5.6, and 23.3 ±â€¯13.0 IU/L, respectively; GGT 45.7 ±â€¯35.1, 25.2 ±â€¯10.3, and 43.9 ±â€¯26.4 IU/L, respectively; serum creatinine 1.06 ±â€¯0.23, 0.80 ±â€¯0.17, and 0.89 ±â€¯0.35 mg/dL, respectively). No systemic hematologic toxicity, alopecia, or neurotoxicity was noted. The maximum tolerable dose was not reached. Histologic tumor regression was observed in 7/11 (64%) patients who underwent ≥2 PIPAC cycles. CONCLUSIONS: PIPAC with cisplatin and doxorubicin may be safely used at an intraperitoneal dose of 10.5 mg/m2 and 2.1 mg/m2, respectively. Systemic toxicity of this therapy is low.

Concentrations of cisplatin and doxorubicin in ascites and peritoneal tumor nodules before and after pressurized intraperitoneal aerosol chemotherapy (PIPAC) in patients with peritoneal metastasis.

INTRODUCTION: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new means of delivering chemotherapy into the abdomen of patients with peritoneal carcinomatosis (PC). The amount of drug uptake in ascites and peritoneum after PIPAC is unknown. METHODS: Retrospective cohort study of women with PC from gynecological tumors comparing the concentrations of cisplatin and doxorubicin in ascites and peritoneum before and after PIPAC. Concentrations were measured using gas chromatography. Peritoneal tumor samples were assessed for histological tumor regression. RESULTS: 59 PIPAC procedures were performed in 32 women with PC. The concentrations of doxorubicin and cisplatin in ascites significantly increased after PIPAC (140.2 ± 671.5 vs 9035.7 ± 5328.6 ng/ml; p < 0.0001 and 95.2 ± 106.4 vs 24,770.8 ± 11,710.8 ng/ml; p < 0.0001, respectively). Concentrations of doxorubicin and cisplatin in peritoneal tissue also significantly increased after PIPAC (5.1 ± 0.7 vs 19.2 ± 38.6 ng/g; p = 0.007, and 81.9 ± 7.8 vs 131.5 ± 134.4 ng/g; p = 0.005, respectively). On an individual patient level, a significant uptake (>2-fold) of doxorubicin and cisplatin was observed in 57/59 (97%) and 58/59 (98%) of cases in ascites and in 23/59 (39%) and 13/59 (22%) of cases in the peritoneum. Uptake of cisplatin and doxorubicin were significantly correlated (Spearman correlation coefficient: 0.33; p = 0.011). After repeated PIPACs, doxorubicin uptake increased in peritoneal tumor tissue (p = 0.008). CONCLUSIONS: PIPAC leads to a significant chemotherapy uptake in both ascites and peritoneum, suggesting a bimodal cytotoxic effect of PIPAC via direct tissue uptake into peritoneal tumor nodules and via ascites. Consecutive PIPAC applications lead to peritoneal accumulation of doxorubicin, suggesting a cumulative cytotoxic effect of doxorubicin after repeated PIPACs.

Radiogenic angiosarcoma of the breast: case report and systematic review of the literature.

BACKGROUND: Radiogenic angiosarcoma of the breast (RASB) is a rare late sequela of local irradiation of the breast or chest wall after breast cancer. The prognosis of women with RASB is poor and there is no standardized therapy for this type of malignancy. CASE PRESENTATION: We present the case of a 54 year old woman with RASB (poorly differentiated angiosarcoma of the left breast; pT1, pNX, M0, L0, V0) and a history of invasive-ductal cancer of the left breast (pT1b, G2, pN0, ER positive, PR positive, HER-2/neu negative) treated in July 2012 with breast-conserving surgery, adjuvant chemotherapy with 6 cycles of epirubicin and cyclophosphamide, adjuvant irradiation of the left breast with 50 Gray, and adjuvant endocrine therapy with an aromatase inhibitor. In August 2016, a bilateral salpingo-oophorectomy was performed to remove a tumor of the left ovary, which was diagnosed as breast cancer recurrence. At the same time, a small, purple skin lesion of 1.2 cm in diameter was noted in the inner upper quadrant of the right breast. RASB was diagnosed by punch biopsy and the tumor was excised with clear margins. Imaging studies showed no evidence of further metastases. A systemic chemotherapy with 6 cycles of liposomal doxorubicin was initiated. Five months later, a local recurrence of RASB was diagnosed and mastectomy was performed. Six months later, the patient is alive with no evidence of disease. Three hundred seven cases of RASB were identified. The pooled incidence rate of RASB was 1/3754 women. The most common treatment of RASB was mastectomy in 83% of cases. Adjuvant radiotherapy or chemotherapy were rarely used with 6 and 4%, respectively, whereas in case of recurrence, chemotherapy was the mainstay of treatment, used in 58% of cases. Radiotherapy and repeated surgery were also common with 30 and 33% of cases, respectively. Overall, the prognosis of women with RASB was poor and the recurrence-free survival was short with a mean of 15.9 months. Mean overall survival was 27.4 months. CONCLUSION: RASB is a rare late complication of breast irradiation. The prognosis of women with RASB is poor. Surgery is the mainstay of treatment for localized disease while systemic chemotherapy and re-irradiation are appropriate for women with disseminated or recurrent RASB.

Identification of preterm birth in women with threatened preterm labour between 34 and 37 weeks of gestation.

The aim of this study was to assess whether serum markers would be useful as a new predictor of preterm birth in patients with spontaneous, late preterm labour. Patients diagnosed with late preterm labour were divided into preterm delivery (229 patients) and term delivery (178 patients) groups. The two groups were compared in terms of clinical characteristics and levels of serum markers (leukocyte subtypes, platelet, C-reactive protein [CRP], neutrophil to lymphocyte ratio [NLR] and platelet to lymphocyte ratio [PLR]), which were obtained at admission. The levels of leukocyte (p < .001), neutrophil (p < .001), CRP (p = .001), NLR (p < .001) and PLR (p = .003) were significantly higher, whereas lymphocytes (p = .012) were significantly lower in the preterm delivery group, compared to the term delivery group. On multivariate regression analysis, NLR positive was the most powerful predictive variable (OR = 1.41; 95%CI: 1.32-1.51; p = .005). NLR had the highest area under curve (0.711; 95%CI 0.662-0.760) in predicting preterm birth and a NLR >6.2 had the highest sensitivity (65.1%) and specificity (62.5%). High NLR at admission is an independent predictor of preterm birth in patients with spontaneous, late preterm labour. Impact statement What is already known on this subject: Preterm birth accounts for 5-12% of all births, and is a major factor associated with perinatal morbidity and mortality worldwide. However, more than 70% of preterm births occur at late preterm between 340/7 and 366/7 weeks of gestation. The central role of systemic and subclinical infections in preterm labour is well documented. Intrauterine infection leading to delivery can be measured by using a variety of laboratory parameters. What do the results of this study add: Neutrophil to lymphocyte ratio is an inexpensive, easily interpretable and promising haematologic parameter that is widely available. This study explored the association of high neutrophil to lymphocyte ratio with the risk of preterm birth in women with preterm labour between 34 and 37 weeks of gestation. What are the implications of these findings for clinical practice and/or further research: Neutrophil to lymphocyte ratio could be used in combination with existing markers to improve detection rates of preterm birth. Concomitant use of markers could be more powerful than measuring any of the individual markers alone.

Melanoma of the Vagina: Case Report and Systematic Review of the Literature.

BACKGROUND: Primary melanoma of the vagina (PMV) is a rare entity. The prognosis of women with PMV is poor and there is no standardized therapy for this type of malignancy. We present the case of a 72-year-old woman with PMV (cT2, pN0, M0). CASE REPORT: Imaging studies showed no evidence of regional or distant metastases. Molecular analysis demonstrated wild-type B-Raf proto-oncogene, serine/threonine kinase (BRAF). Staging laparoscopy with pelvic lymphadenectomy and subsequent radiotherapy with 60 Gy delivered as pelvic teletherapy and vaginal brachytherapy was applied. Systematic literature review: A total of 805 cases of PMV were identified. Most lesions were melanotic (65%) and localized (66%), whereas amelanotic (35%) and primary advanced lesions (34%) were only seen in a minority of patients. BRAF mutation was detected in none out of 33 cases, tumor protein 53 (TP53) mutations and mast/stem cell growth factor receptor CD117 (KIT) amplification were identified in one case each. The most common treatment was surgery, reported in 43% of cases. Surgery combined with adjuvant radiotherapy, adjuvant immunotherapy (mostly with interferon-alpha), or adjuvant chemotherapy were given in 35%, 8%, and 3% of cases, respectively. Radiotherapy or chemotherapy as sole treatments were used in 5% and 1% of patients, respectively. Among patients with recurrence, chemotherapy (mostly dacarbazine) alone or in combination with surgery, radiotherapy or immunotherapy was the most common treatment in 61% of cases. The mean durations of recurrence-free and overall survival were 16.4 and 22.2 months, respectively. CONCLUSION: PMV is a rare malignancy with a poor prognosis. Surgery, radiotherapy, and immunotherapy with interferon-alpha are the mainstay of treatment for localized disease, while chemotherapy with dacarbazine is mostly used for unresectable and recurrent disease. No data on the clinical value of immune checkpoint inhibitors in PMV have been published.

Accuracy of intrapartum fetal blood gas analysis by scalp sampling: A retrospective cohort study.

Fetal blood gas analysis (FBGA) using scalp blood is commonly used to identify serious fetal distress. However, there is a lack of data regarding its accuracy and reliability. The aim of this study was to determine the positive predictive value (PPV) and negative predictive value (NPV) of FBGA for predicting postpartum acidosis in case of nonreassuring fetal heart rate tracings (NRFHRT). To this end, we conducted a retrospective cohort study of singleton term deliveries with NRFHRT according to Fédération Internationale de Gynécologie et d'Obstétrique and Fisher cardiotocography scores undergoing FBGA in a university hospital. The PPV and NPV of FBGA regarding neonatal acidosis (defined as a pH value ≤ 7.15 in arterial or venous umbilical cord blood) and Apgar scores indicating neonatal depression (defined as a 5-min Apgar score ≤5) were evaluated. Multivariate analysis was used to determine the influence of cardiotocography variations and the time delay between FBGA and delivery on the accuracy of FBGA. We analyzed 343 deliveries with NRFHRT. In 32 (9%) of these cases, fetal acidosis was confirmed by a postpartum umbilical cord blood pH value ≤ 7.15. In 308/343 (90%) cases, FBGA identified NRFHRT as false positive (as confirmed by nonacidotic postpartum pH values) and thus avoided unnecessary interventions such as operative delivery. The overall test accuracy of FBGA was 91%. FBGA accurately predicted postpartum cord blood pH values with a margin of ±0.2 in 319/343 (93%) cases. On the other hand, the false negative rate of FBGA was 8% (29/343). The PPV and NPV of FBGA for predicting postpartum acidosis were 50% and 91%, respectively. The sensitivity was 9% and the specificity was 99%. In a multivariate logistic regression analysis, maternal body mass index (odds ratio [OR] 1.1; 95% confidence interval [CI] 1.01-1.17; P = .029) and cardiotocography variations (OR 0.80; 95% CI 0.66-0.98; P = .029) independently affected the predictive value of FBGA. The PPV of FBGA regarding neonatal depression according to Apgar scores was low with only 17%. We conclude that FBGA may be used in clinical practice to rule out, but not to rule in, neonatal acidosis in parturients with NRFHRT. It can avoid unnecessary interventions such as cesarean section or operative vaginal delivery in up to 90% of cases, but cannot reliably detect fetal acidosis.

Nutritional status, cachexia, and anorexia in women with peritoneal metastasis and intraperitoneal chemotherapy: a longitudinal analysis.

OBJECTIVE: To describe the nutritional status of women with peritoneal metastasis (PM) from recurrent ovarian, fallopian, or peritoneal cancer and to assess longitudinal variations of the cachexia-anorexia syndrome (CAS) during palliative pressurized intraperitoneal aerosol chemotherapy (PIPAC). METHODS: Nutritional assessment included body mass index (BMI), bioelectrical impedance analysis (BIA), and blood chemistry. CAS presence/absence was recorded before and during repeated cycles (1-11) of PIPAC. RESULTS: Eighty-four patients with peritoneal cancer (n=5) or PM from recurrent ovarian (n=77) or fallopian tube (n=2) cancer were included. At baseline, resting metabolism (RM) (1,432±172 kcal/day), visceral fat level (7.5±3.2), skeletal muscle mass (27.2%±4.6%), upper arm circumference (27.9±4.6 cm), lower leg circumference (35.1±3.9 cm), serum parameters (albumin [3.5±0.7 g/dL], total protein [6.3±0.9 g/dL], and transferrin [202±60 mg/dL]) were below normal limits. C-reactive protein (CRP) (4.3±6.8 mg/dL), caliper body fat (35.7%±6.3%), and total body fat mass (35.6%±8.5%) were above normal limits. Nineteen/84 (23%) patients had CAS at baseline. Deterioration or stabilization/improvement of CAS was observed in 9/55 (16.4%) and 46/55 (83.6%) patients with follow-up data, respectively. Baseline body fat mass, visceral fat level, skeletal muscle mass, caliper body fat, BMI, ascites, Karnofsky index, RM, and CRP, as well as tumor response were not predictive of CAS deterioration. CONCLUSION: Nutritional decline and onset or deterioration of CAS are difficult to predict. Careful measuring and monitoring of nutritional parameters and CAS in all patients seems to be necessary in order to identify those patients in need of enteral/parenteral nutrition support.

Thalidomide and lenalidomide for recurrent ovarian cancer: A systematic review of the literature.

The present review aimed to assess the safety and efficacy of thalidomide and lenalidomide, two immunomodulatory drugs with anti-angiogenic properties, in women with recurrent ovarian, fallopian tube, and primary peritoneal cancer. A systematic review of the literature was conducted whereby Medline and the Cochrane Central Register of Controlled Trials were searched using terms associated with thalidomide, lenalidomide, and recurrent ovarian, fallopian tube and primary peritoneal cancer. Published English language case reports, trials and studies that described the safety and efficacy of thalidomide or lenalidomide alone, or in combination with other drugs were reviewed. A total of 16 clinical studies involving 394 patients treated with thalidomide (n=188), lenalidomide (n=77) and 129 controls were identified, including five case reports (n=6), three case series (n=45), two phase I trials (n=27), four phase II trials (n=109), and two randomized phase III trials (n=207). In a pooled analysis of thalidomide investigated as a single drug, the overall clinical benefit rate was 43% (43/99) with a mean time to progression of 5.6 months. The response rate (complete response + partial response) was 25%. In a phase III trial, the combination of thalidomide and topotecan significantly increased the overall response rate compared with topotecan alone [14/30 (47%) vs. 8/39 (21%)]. In another phase III trial involving women with asymptomatic biochemical recurrence, compared with tamoxifen, thalidomide was not more effective. Lenalidomide was investigated in three phase I trials and in one phase II trial with an overall clinical benefit rate of 52% (34/65), and a mean time to progression of 4.6 months. The response rate (complete response + partial response) was 6%. Systemic toxicity of both drugs was noted in >77% of patients with pneumonitis/pneumonia, fatigue, neuropathy and venous thromboembolism reported as the most common side effects. Thalidomide and lenalidomide are moderately active in recurrent ovarian cancer. Thalidomide possesses synergistic effects with topotecan. The toxicity of both drugs is considerable and there is a greater amount of data available for thalidomide compared to lenalidomide.

Surgical performance of large loop excision of the transformation zone in a training model: A prospective cohort study.

Large loop excision of the transformation zone (LLETZ) is one of the most common procedures in operative gynecology and it is a routine part of the surgical training program of residents. There is, however, no established and standardized method of teaching residents how to perform LLETZ. Here, we present a surgical training model and assessed the improvement of surgical skills during repeated hands-on trainings of LLETZ in this model.Surgical novices and experts were recruited and were shown a LLETZ training video and then performed 3 LLETZ training sessions on consecutive days. Surgical skills were assessed by Objective Structured Assessment of Technical Skills (OSATS). Global rating scale (GRS), confidence (CON), fragmentation rate (FR), performance time (PT), and OSATS scores were calculated. Intra- and interobserver variabilities were determined. The construct validity of OSATS was assessed comparing metric scores of novices with those of experts.Sixty-eight probands (58 novices, 10 experts) were recruited. GRS, 2.3 ±â€Š1.3 (median ±â€ŠSD) versus 1.4 ±â€Š0.6, P < .001; CON, 2.7 ±â€Š0.9 versus 1.6 ±â€Š0.6, P < .001; FR, 81% versus 100%, P < .001; PT, 152 ±â€Š33 versus 120 ±â€Š27 seconds, P = .006; and OSATS scores, 18.8 ±â€Š1.3 versus 19.1 ±â€Š1.1, P = .16 of novices improved from session 1 to session 3. OSATS showed construct validity with metric scores (GRS, 1.1 ±â€Š0.3 vs 2.3 ±â€Š0.8, P < .001; CON, 1.0 ±â€Š0.0 vs 2.7 ±â€Š0.9, P < .001; PT 125 ±â€Š30 vs 152 ±â€Š33 seconds, P = .02; OSATS scores, 19.6 ±â€Š0.7 vs. 18.8 ±â€Š1.3, P = .02) reliably discriminating between experts and novices. Intra- and interobserver variabilities across probands were 0.99 ±â€Š0.03 and 0.64 ±â€Š0.10, respectively. OSATS scores were independent of handedness, sex, and regular sports activity in univariate and multivariate analyses.Repeated hands-on trainings improve surgical performance of LLETZ in a surgical training model with construct validity.

Synchronous Endometrial and Ovarian Cancer in Young Women: Case Report and Review of the Literature.

BACKGROUND: Young women with endometrial cancer (EC) have an increased risk of synchronous ovarian cancer. The prognosis of women with synchronous endometrial and ovarian cancer (SEOC) is good. A high proportion of affected women have hereditary non-polyposis colon cancer syndrome (HNPCC). CASE PRESENTATION: We present the case of a 45-year-old woman with histologically proven endometrioid adenocarcinoma of the endometrium (pT1B, G2, R0 without lymphovascular space invasion). She underwent laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy. Final histology revealed a synchronous bilateral endometrioid ovarian cancer (pT1A, G2, R0). HNPCC analysis by immunohistochemistry showed no microsatellite instability in MSH2, MSH6, MLH1, and PMS2. No adjuvant therapy was administered, clinical follow-up with regular gynecological examinations was recommended. In a systematic literature review, 2,904 cases of women with SEOC were identified with 1,035 (36%) of them being premenopausal or <50 years of age. The proportion of women with SEOC among all reported EC cases was 842/23,498 (3%) and the proportion of young women with SEOC among all reported EC cases was 261/23,498 (1%). In summary, microsatellite instability and subsequent mutations in mismatch repair genes compatible with HNPCC were identified in 6/15 (40%) women analyzed. The mean recurrence-free and overall survival times of young women with SEOC were 1.9 (min 0.2, max 3) and 4.0 (min 0.2, max 22.1) years, respectively. CONCLUSION: Young women with EC have a high risk of synchronous ovarian cancer. Thus, in young women with EC, bilateral salpingo-oophorectomy or careful histological assessment of both ovaries are recommended in order to confirm or rule out SEOC. HNPCC testing should be offered to all women.

Paget's Disease of the Vulva Treated with Imiquimod: Case Report and Systematic Review of the Literature.

BACKGROUND: Extramammary Paget's disease of the vulva (EPDV) is a rare adenocarcinoma in situ of the vulvar skin and is often resected with involved margins due to its reticular growth pattern. Adjuvant treatment with the immunomodulator imiquimod may be suitable to avoid repeated and mutilating surgery. CASE PRESENTATION: We present the case of a 73-year-old woman with EPDV, initially treated with surgical resection and re-resection for involved margins. Final histology revealed Paget's disease of the left vulva with 8 cm in the largest diameter and again involved margins. Subsequently, topical therapy with imiquimod 5% cream twice weekly was applied for 3 months. Vulvoscopy and local biopsies confirmed complete remission (CR). Based on a literature search using PubMed and the Cochrane Central Register of Controlled Trials, 21 reports on the therapeutic efficacy of imiquimod in 70 women with EPDV have been published. Pooled rates of CR and partial remission were 71% (50/70) and 16% (11/70), respectively. There were 4 cases of disease progression under imiquimod and the therapy was generally well tolerated with mild to moderate local reactions in >50% of cases. CONCLUSION: EPDV is a rare genital neoplasia and may be successfully treated with the topical immunomodulator imiquimod. Specifically, adjuvant imiquimod is a feasible and efficacious treatment option for women with involved resection margins after surgery.

Use of urea and creatinine levels in vaginal fluid for the diagnosis of preterm premature rupture of membranes and delivery interval after membrane rupture.

OBJECTIVE: To determine whether urea and creatinine measurements in vaginal fluid could be used to diagnose preterm premature rupture of membranes (PPROM) and predict delivery interval after PPROM. METHODS: A prospective study conducted with 100 pregnant women with PPROM and 100 healthy pregnant women between 24 + 0 and 36 + 6 gestational weeks. All patients underwent sampling for urea and creatinine concentrations in vaginal fluid at the time of admission. Receiver operator curve analysis was used to determine the cutoff values for the presence of PPROM and delivery within 48 h after PPROM. RESULTS: In multivariate logistic regression analysis, vaginal fluid urea and creatinine levels were found to be significant predictors of PPROM (p < 0.001 and p < 0.001, respectively) and delivery within 48 h after PPROM (p = 0.012 and p = 0.017, respectively). The optimal cutoff values for the diagnosis of PPROM were >6.7 mg/dl for urea and >0.12 mg/dl for creatinine. The optimal cutoff values for the detection of delivery within 48 h were >19.4 mg/dl for urea and >0.23 mg/dl for creatinine. CONCLUSION: Measurement of urea and creatinine levels in vaginal fluid is a rapid and reliable test for diagnosing and also for predicting delivery interval after PPROM.

What Characterizes Long-term Survivors of Recurrent Ovarian Cancer? Case Report and Review of the Literature.

BACKGROUND: Women with recurrent ovarian cancer have a poor prognosis and short survival. However, some women are long-term survivors and it is unclear whether they share specific common characteristics. CASE REPORT: We present the case of a 63-year-old woman with histologically-proven recurrent ovarian cancer and a survival time of 16 years after the diagnosis of recurrence. She underwent initial debulking surgery in 1994, followed by 6 cycles of adjuvant chemotherapy with cisplatin and paclitaxel. After recurrent disease was diagnosed by re-laparotomy in 2000, she underwent four lines of systemic chemotherapy from 2000 to 2009 (carboplatin/paclitaxel, topotecan, etoposide/treosulfan and liposomal doxorubicin) and four lines of endocrine therapy between 2002 and 2014 (tamoxifen, goserelin, tamoxifen and exemestane). In 2014, she underwent secondary debulking surgery and was tumor-free until 2015. Upon progression, she was then started on the fifth-line of endocrine therapy, fulvestrant, which was changed to the mTOR inhibitor everolimus in June 2016. In a PUBMED literature search, 360 cases of long-term survivors of recurrent ovarian cancer (LTSROC), defined as women with survival >5 years after the diagnosis of recurrence, were identified with a mean post-recurrence survival time of 7.5 years. Comparing the patient and therapy details of these women, we identified common characteristics of LTSROC, i.e. young age and optimal debulking at initial surgery, a long time span between first-line therapy and first recurrence and the combined use of optimal cytoreductive surgery and systemic chemotherapy. CONCLUSION: LTSROC are rare, with 360 cases described in the literature. LTSROC are characterized by young age, low tumor stage, long recurrence-free interval and combined modality treatment with optimal cytoreductive surgery and systemic chemotherapy.