Urine Protein to Creatinine Ratio for the Assessment of Bevacizumab-Associated Proteinuria in Patients with Gynecologic Cancers: A Diagnostic and Quality Improvement Study.

Proteinuria is a common adverse event arising from treatment with bevacizumab, requiring diagnostic testing via 24-h urine collection. However, this method is cumbersome. We assessed urine screenings in gynecologic cancer patients from February 2021 to May 2022. Along with a simple urine dipstick (UD), the urine microalbumin, total protein, and creatinine were measured and calculated as the urine albumin to creatinine ratio (UACR) and the urine protein to creatinine ratio (UPCR), which were further adjusted through the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations to be estimated and correlated with 24-h urine total protein content. The incremental cost-effectiveness ratio was used for cost analysis. There were 129 urine samples from 36 patients. The sensitivity and specificity for the UACR were 0.56 and 0.97, and for the UPCR, 0.71 and 0.88, respectively. The 24-h TP correlated strongly with the UACR (r = 0.75; p < 0.001) and UPCR (r = 0.79; p < 0.001) and fair for the simple UD (r = 0.35; p < 0.001). The UPCR saves one unnecessary 24-h urine test for less than a dollar compared to a simple UD. The results indicate that using the UPCR could enhance diagnostic accuracy, lower costs, and reduce unnecessary 24-h urine sampling.

Progression of fertility-sparing treatment for atypical endometrial hyperplasia in a woman with lynch syndrome: a case report and review of the literature.

Endometrial cancer in Lynch syndrome is characterized by a higher incidence, younger age at onset, and increased recurrence rates compared to sporadic cases, while the safety and efficacy of fertility-sparing treatments remain uncertain. This case report presents the oncology outcome of fertility-preserving treatment in a 39-year-old woman diagnosed with Lynch syndrome and atypical endometrial hyperplasia. Initially, she responded favorably to fertility-preserving treatment but subsequently experienced disease relapse and rapid progression during retreatment. Final pathology revealed endometrial cancer with metastasis to the right ovary, categorized as FIGO 2023 stage IIIA1. This population's unique molecular mechanisms and genetic mutations warrant special consideration when opting for fertility-sparing treatment. We have reviewed and summarized the oncology and pregnancy outcomes among Lynch syndrome and MMR-deficient patients through previous literature. However, no studies have investigated retreatment after recurrence in Lynch syndrome. Our case highlights the potential risks associated with retreatment following relapse. Vigilant monitoring and prompt consideration of surgical intervention are recommended upon disease relapse.

Dome-type extracorporeal manual morcellation during laparoscopic uterine surgery: Two years' experience in a teaching hospital.

OBJECTIVE: This study aims to describe the dome-type manual morcellation technique, a modified form of C-type incision, its comparative advantages over existing morcellation methods, the perioperative outcomes of trainees with varying experience levels, and the variables influencing morcellation speed based on our two years of experience. METHODS: This retrospective cohort study included women who underwent laparoscopic myomectomy or hysterectomy using dome-type morcellation for tissue extraction at a tertiary teaching hospital between May 2020 and September 2022. Morcellation was performed by either a single surgeon or a trainee (resident). Basic patient characteristics, perioperative outcomes, and morcellation time and speed were compared between the surgeon and trainee group. Regression models were employed to analyze variables influencing morcellation speed. RESULTS: A total of 41 women were enrolled. Among them, 20 procedures were performed by a surgeon alone, while the remaining 21 procedures were completed by trainees under the surgeon's supervision. The median weight of the specimens was 378 g (range 91-1345 g), and the median time for morcellation was 10 min (range 1-55 min). The median morcellation speed of surgeon and trainees was 70.25 and 31.7 g/min, respectively. Trainees' level of experience was found to be associated with morcellation speed, particularly for soft specimens. Additionally, both incision size and specimen stiffness were significantly associated with morcellation speed. No morcellation-related complications or bag ruptures were observed. CONCLUSION: Dome-type manual morcellation is an intuitive, efficient and safe method for specimen removal and is easy to learn for beginners.

TMTC1 promotes invasiveness of ovarian cancer cells through integrins ß1 and ß4.

Ovarian cancer is the most lethal gynecological malignancy and is characterized by peritoneal disseminated metastasis. Although O-mannosyltransferase TMTC1 is highly expressed by ovarian cancer, its pathophysiological role in ovarian cancer remains unclear. Here, immunohistochemistry showed that TMTC1 was overexpressed in ovarian cancer tissues compared with adjacent normal ovarian tissues, and high TMTC1 expression was associated with poor prognosis in patients with ovarian cancer. Silencing TMTC1 reduced ovarian cancer cell viability, migration, and invasion in vitro, as well as suppressed peritoneal tumor growth and metastasis in vivo. Moreover, TMTC1 knockdown reduced cell-laminin adhesion, which was associated with the decreased phosphorylation of FAK at pY397. Conversely, TMTC1 overexpression promoted these malignant properties in ovarian cancer cells. Glycoproteomic analysis and Concanavalin A (ConA) pull-down assays showed that integrins ß1 and ß4 were novel O-mannosylated protein substrates of TMTC1. Furthermore, TMTC1-mediated cell migration and invasion were significantly reversed by siRNA-mediated knockdown of integrin ß1 or ß4. Collectively, these results suggest that TMTC1-mediated invasive behaviors are primarily through integrins ß1 and ß4 and that TMTC1 is a potential therapeutic target for ovarian cancer.

Protein Glycosylation as Biomarkers in Gynecologic Cancers.

Gynecologic cancers are the leading cause of death in women. Endometrial, ovarian, and cervical cancer are the three main types of gynecologic cancers. Poor prognoses and high mortality rates of advanced-stage cancer are still challenges of all three types. Diagnostic tools for early cancer detection could be the cornerstone for further cancer treatment and prevention. Glycosylation plays a vital role in cell proliferation, adhesion, motility, and angiogenesis, and is aberrantly expressed in cancer cells. Alterations of glycosylation may represent promising biomarkers with potential diagnostic and monitoring applications, as well as disease prognosis. Many glycosylated biomarkers, including glycoprotein, glycan, and enzyme, were discovered and well-studied for application in gynecologic cancers. Some of them have been developed as targets for cancer treatment. The use of certain biomarkers for diagnostics and monitoring of gynecologic cancers has clinical advantages, as it is quantitative, comparable, convenient, and inexpensive. However, one of the single markers have sufficient sensitivity for the screening of gynecologic cancers. In this review, we introduced the details of glycosylation and the current application of glycosylated biomarkers in these three cancers. Moreover, we also reviewed the different roles of each biomarker in other cancers and aimed to understand these glycosylated biomarkers comprehensively.

Clinical outcome and urodynamic changes of tailored transvaginal mesh surgery for pelvic organ prolapse: A mid-term 40 Months follow-up.

PURPOSE: To evaluate the changes in clinical outcome and urodynamic parameters after tailored anterior transvaginal mesh (ATVM) surgeries in a mid-term follow-up. METHODS: Between November 2011 and December 2015, women with ≥stage II pelvic organ prolapse (POP) who underwent ATVM surgeries were retrospectively reviewed. The data-reviewing timeframe was until December 2021. Clinical and urodynamic diagnoses regarding urinary symptoms were evaluated before and after the operation. RESULTS: A total of 160 women were included. Stress urinary incontinence decreased significantly after the operation (99% (159/160) vs. 43% (68/160), p < 0.01), as well as the pad weight (20.5 ± 2.7 vs. 9.4 ± 2.0, p < 0.001) and diagnosis of urodynamic stress incontinence (83% (132/160) vs. 51% (82/160), p < 0.01). Overactive bladder syndrome increased significantly after the operation (18% (29/160) vs. 28% (45/160), p = 0.03), even though the objective parameters, such as first and strong desire to void, bladder oversensitivity, and detrusor overactivity, were all improved after the operation. The pad weight was mostly improved significantly within the first postoperative 2 years. Eighteen (11%) women had global recurrent POP, and only one (0.6%) woman had true recurrence of cystocele. Twenty-four (15%) women had mesh extrusion, and two-thirds of them could be managed in an office setting. CONCLUSION: In women with advanced cystocele, the ATVM surgery provides a favorable anatomic reduction outcome with an acceptable mesh extrusion rate. The ATVM provides an anti-incontinence effect, both in subjective symptoms and objective parameters, but this effect might decline after postoperative 2 years.

Early-stage granulosa cell tumor with pelvic recurrence and lung metastasis 16 years later: A case report and review of the literature.

OBJECTIVE: Only a few cases of early-stage ovarian granulosa cell tumor (GCT) with lung metastasis have been previously documented in the literature. We present a case of stage IA adult-type ovarian GCT with late pelvic recurrence and lung metastasis and review the relevant literature. CASE REPORT: A 71-year-old female who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy for an ovarian GCT in her early 50s presented with pelvic recurrence 16 years later. Lung metastasis was accidentally discovered during a preoperative computed tomography scan of the pelvic tumor. The patient received surgical resection and adjuvant chemotherapy. She remains alive and healthy without evidence of disease after 12 months of follow up. CONCLUSION: This case illustrates the importance of long-term follow-up for early-stage GCTs. It also highlights the requirement of extended examination for possible extra-abdominal/pelvic tumors.

Comparison of the vault prolapse rate after vaginal hysterectomy with or without residual uterine ligament ligations: A retrospective cohort study.

PURPOSE: To evaluate the post-hysterectomy vault prolapse (PHVP) rates performed using different methods of vaginal total hysterectomy (VTH). METHODS: A total of 251 women who underwent VTH with/without concomitant surgeries between January 1986 and December 2001 in a tertiary center. Thirty-eight women were excluded due to not only a vaginal approach. Of the remaining 213 women, 129 and 84 underwent VTH via the Tsuzi method with residual uterine ligament ligations (ligations group) and traditional VTH (without ligations group), respectively. The χ2 and Mann-Whitney U tests were applied appropriately. The cumulative percentages of women without PHVP were calculated over time and compared using Kaplan-Meier curves and log-rank tests. A p value of less than 0.05 was considered statistically significant. RESULTS: Compared to the without ligations group, women in the ligations group had longer operation time (115.9 ± 37.1 vs. 103.3 ± 41.4 min, p = 0.002) and more blood loss (217.4 ± 137.8 vs. 148.2 ± 149.0 mL, p < 0.001). When focusing on women with uterine prolapse, only operation time and grade of uterine prolapse were different between the groups (117.3 ± 24.8 vs. 107.9 ± 40.5 min, p = 0.025, and 21% vs. 41%, p = 0.018, respectively). The rate of PHVP was significantly lower in the ligation group than in the without ligations group (0 vs. 5, p = 0.005). CONCLUSION: VTH via the Tsuzi method with residual uterine ligament ligations resulted in fewer cases of PHVP than occurred in traditional VTH. If native tissue repair is planned in pelvic reconstruction surgery, VTH with residual uterine ligament ligations should be considered.

Comparison of clinical outcomes between tailored transvaginal mesh surgery and native tissue repair for pelvic organ prolapse.

BACKGROUND/PURPOSE: The most suitable surgical technique for pelvic organ prolapse (POP) remains undetermined. The aim of this study was to compare clinical outcomes of the tailored transvaginal mesh (TVM) surgery and vaginal native tissue repair (NTR) surgery for POP. METHODS: Between November 2011 and August 2014, medical records of 339 women receiving POP surgeries were reviewed. RESULTS: Compared with the NTR group (n = 169), the use of TVM surgery (n = 170) was a predictor for longer operation time (coefficient = 25.2 min, P < 0.001) and larger blood loss (coefficient = 79.9 mL, P < 0.001) by multivariable analysis. However, a higher recurrence rate of cystoceles (log-rank test, P = 0.001) was found in the NTR group, compared with the TVM group; but not apical prolapse (P = 0.32) or rectocele (P = 0.45). Multivariable analysis revealed that the TVM surgery (hazard ratio = 0.24, 95% confidence interval = 0.09-0.64, P = 0.004) and old age (hazard ratio = 1.07, 95% confidence interval = 1.02-1.11, P = 0.005) were independent predictors for the recurrence of cystoceles. Based on the receiver operating characteristic curve (ROC) analysis, the cut-off age value was 64 years with an ROC area of 0.65. In women with intact uterus (n = 162), the recurrence rate of cystoceles was lower in the TVM group (log-rank test, P = 0.0001), compared with the NTR group. However, there was no between-group difference in the recurrence rate of cystoceles in women with prior or concomitant hysterectomy (n = 177, P = 0.17). CONCLUSION: In women with intact uterus, the TVM group has a lower recurrence rate of cystoceles than the NTR group. In addition, old age, especially more than 64 years old, is a risk factor for cystocele recurrence.

Primary ovarian mucinous carcinoid tumor: A case report and review of literature.

OBJECTIVE: Only a few cases of primary ovarian mucinous carcinoid tumor have been documented in the literature till date. We present a case of primary ovarian mucinous carcinoid tumor, atypical type, and review the reported cases. CASE REPORT: A 33-year-old woman with a left ovarian tumor was diagnosed with primary ovarian mucinous carcinoid tumor, atypical type. She underwent left salpingo-oophorectomy and ipsilateral lymph node dissection. After 5 years, the tumor recurred on the right side, with large para-aortic lymphadenopathy that caused hydronephrosis. Complete surgical staging was performed, followed by nine cycles of weekly paclitaxel and gemcitabine. The tumor progressed after discontinuing the chemotherapy, and the patient died of disease 26 months after recurrence. CONCLUSION: Our patient demonstrated a more aggressive clinical course compared to that reported in previous literature. Based on this experience, complete surgical staging is highly recommended after the patient accomplished her fertility plan. Ovarian carcinoid tumors are relatively chemoresistant compared with epithelial ovarian cancers. The regimen of weekly paclitaxel and gemcitabine stabilized the disease but did not reach remission of the tumor. Further studies are required to determine the appropriate chemotherapy regimen.

Risk factors for coexistence of cervical elongation in uterine prolapse.

OBJECTIVE: To identify factors predicting cervical elongation in women with uterine prolapse. STUDY DESIGN: The medical records of women with uterine prolapse who underwent vaginal hysterectomy were reviewed. Multivariable logistic regression analysis was performed to identify predictors of cervical elongation. RESULTS: Of 295 women with uterine prolapse, 136 (46.1%) patients had cervical elongation, according to Berger et al. Classification (i.e., cervical length >3.38 cm and/or cervix-to-corpus lengths ratio >0.79). Multivariable analysis revealed that lower parity (odds ratio = 0.85, 95% confidence interval [CI] = 0.73 to 0.99, P = 0.04) and advanced stage of uterine prolapse (odds ratio = 1.97, 95% CI = 1.35-2.88, P < 0.001) were predictors for cervical elongation. Based on a receiver operating characteristic curve (ROC) analysis, the following optimum cut-off values were determined for cervical elongation: (1) parity ≤3, ROC area = 0.60 (95% CI = 0.53 to 0.66); (2) stage of uterine prolapse ≥3, ROC area = 0.63 (95% CI = 0.56 to 0.69). Thus, the predicted logit(p) for a given parity (a) and stage of uterine prolapse (b) can be denoted by logit(p) = -1.26 - 0.16 x a + 0.68 x b. The optimum cut-off values of logit(p) ≥-0.18 to predict cervical elongation were determined using ROC analysis (area = 0.66, 95% CI = 0.59 to 0.73). For women with parity ≤6, we can use either (1) stage 2 uterine prolapse and parity ≤1, or (2) ≥ stage 3 uterine prolapse as criteria to predict cervical elongation. CONCLUSIONS: Lower parity and advanced stage of uterine prolapse are predictors of cervical elongation in women with uterine prolapse. Thus, stage of uterine prolapse ≥3 or logit(p) ≥-0.18 may be useful for predicting cervical elongation.

C1GALT1 Seems to Promote In Vitro Disease Progression in Ovarian Cancer.

OBJECTIVE: Aberrant glycosylation affects many cellular properties in cancers. The core 1 ß1,3-galactosyltransferase (C1GALT1), an enzyme that controls the formation of mucin-type O-glycans, has been reported to regulate hepatocellular and mammary carcinogenesis. This study aimed to explore the role of C1GALT1 in ovarian cancer. METHODS: C1GALT1 expression was assessed in a public database based on microarray data from 1287 ovarian cancer patients and ovarian cancerous tissues. Lectin blotting and flow cytometry analysis were conducted to detect changes in O-glycans on ovarian cancer cells. Effects of C1GALT1 on cell growth, migration, and sphere formation were analyzed in C1GALT1 knockdown or overexpressing ovarian cancer cells in vitro. Expression of cancer stemness-related genes was analyzed by quantitative reverse transcription polymerase chain reaction. RESULTS: High C1GALT1 expression shows a trend toward association with poor survival in ovarian cancer patients. C1GALT1 modifies O-glycan expression on surfaces and glycoproteins of ovarian cancer cells. Knockdown of C1GALT1 decreased cell growth, migration, and sphere formation of ES-2 and OVTW59-p4 cells. Conversely, overexpression of C1GALT1 promoted such malignant properties of SKOV3 cells. Furthermore, C1GALT1 regulated the expression of several cancer stemness-related genes, including CD133, CD24, Oct4, Nanog, and SNAI2, in ovarian cancer cells. CONCLUSIONS: C1GALT1 modifies O-glycan expression and enhances malignant behaviors in ovarian cancer cells, suggesting that C1GALT1 plays a role in the pathogenesis of ovarian cancer and targeting C1GALT1 could be a promising approach for ovarian cancer therapy.

Radical trachelectomy for early stage cervical cancer: A case series and literature review.

OBJECTIVE: Radical trachelectomy (RT) is an alternative treatment for preserving fertility in patients with cervical cancer. Because women with operable cervical cancer opting for fertility preservation are scarce, few cases have been reported in Taiwan. Here we report our cases series. MATERIALS AND METHODS: We retrospectively evaluated seven patients who underwent vaginal RT and three patients who underwent abdominal RT in a single medical institute for a median follow-up period of 5 years. RESULTS: The oncological outcome was highly satisfactory. All patients survived and are currently disease-free, except for two who had recurrence and received additional concurrent chemoradiation therapy. Other complications included urinary tract infection, cervical stenosis, and unilateral hydronephrosis. All complications were manageable with little long-term effects. However, no pregnancy was observed during the 5-year follow-up period. CONCLUSION: RT is considered a complicated surgical procedure among gynecological operations. Here we review the literature and describe several factors associated with higher pregnancy rates.

GALNT6 expression enhances aggressive phenotypes of ovarian cancer cells by regulating EGFR activity.

Ovarian cancer is the most lethal of the gynecologic malignancies. N-acetylgalactosaminyltransferase 6 (GALNT6), an enzyme that mediates the initial step of mucin type-O glycosylation, has been reported to regulate mammary carcinogenesis. However, the expression and role of GALNT6 in ovarian cancer are still unclear. Here we showed that high GALNT6 expression correlates with increased recurrence, lymph node metastasis, and chemoresistance in ovarian endometrioid and clear cell carcinomas; and higher GALNT6 levels are significantly associated with poorer patient survivals. GALNT6 knockdown with two independent siRNAs significantly suppressed viability, migration, and invasion of ovarian cancer cells. Using phospho-RTK array and Western blot analyses, we identified EGFR as a critical target of GALNT6. GALNT6 knockdown decreased phosphorylation of EGFR, whereas GALNT6 overexpression increased the phosphorylation. Lectin pull-down assays with Vicia villosa agglutinin (VVA) indicated that GALNT6 was able to modify O-glycans on EGFR. Moreover, the GALNT6-enhanced invasive behavior was significantly reversed by erlotinib, an EGFR inhibitor. Our results suggest that GALNT6 expression is associated with poor prognosis of ovarian cancer and enhances the aggressive behavior of ovarian cancer cells by regulating EGFR activity.

Prognostic factors and adjuvant therapy on survival in early-stage cervical adenocarcinoma/adenosquamous carcinoma after primary radical surgery: A Taiwanese Gynecologic Oncology Group (TGOG) study.

OBJECTIVE: We aimed to identify prognostic factors of early-stage cervical adenocarcinoma (AC) and adenosquamous carcinoma (ASC) treated with primary radical surgery, and to evaluate the impact of postoperative adjuvant therapy on outcome. METHODS: The clinical-pathological data of all patients (n = 1132) with stages I-II cervical AC/ASC treated with primary radical surgery at the member hospitals of the Taiwanese Gynecologic Oncology Group were retrospectively reviewed. RESULTS: In multivariate analysis, stage II, deep stromal invasion (DSI), lymphovascular space invasion (LVSI), positive pelvic lymph node (PLN), and parametrial involvement (PI) were significant factors for recurrence-free survival (RFS), while only DSI, PI, and positive PLN were independent factors for cancer-specific survival (CSS). Low- and high-risk groups were defined by prognostic scores derived from the four factors (DSI, LVSI, positive PLN, PI) selected by internal validation. Postoperative adjuvant therapy significantly improved outcome for PLN-positive patients (RFS, p = 0.014; CSS, p = 0.016), but not for PLN-negative high-risk group because of higher mean prognostic score (p = 0.028) of adjuvant+ than adjuvant- patients. CONCLUSIONS: PLN metastasis, PI, DSI, and LVSI were independent prognostic factors. Prospective studies of postoperative adjuvant therapy with prognostic score and nodal status stratification for cervical AC/ASC are necessary.

Clinical and urodynamic effects of baclofen in women with functional bladder outlet obstruction: Preliminary report.

AIM: To investigate the efficacy and urodynamic effects of baclofen in women with functional bladder outlet obstruction. METHODS: Between January 2011 and December 2012, women who underwent baclofen treatment for functional bladder outlet obstruction, defined as <15 mL/s maximum flow rate and >20 cmH2 O detrusor pressure at maximum flow rate, but without significant anatomic causes, were retrospectively reviewed. Urodynamic variables at baseline and after 12 weeks of treatment were compared. RESULTS: Twenty women with functional bladder outlet obstruction underwent 12 weeks of baclofen treatment (oral baclofen 5 mg, three times daily). All patients reported improvement in voiding dysfunction symptoms after treatment, and no significant adverse effects were found on review of medical records. All patients underwent urodynamic studies after 12 weeks' treatment. Voided volume, voiding efficiency and maximum flow rate at voiding cystometry were significantly improved (mean, 273 vs. 368 mL, P = 0.002; 62.8% vs. 73.6%, P <0.001, and 10.3 vs. 11.6 mL/s, P = 0.046; respectively). Moreover, baclofen did not affect continence function, as indicated by non-significant changes in the parameters of urethral pressure profiles. CONCLUSIONS: Oral baclofen can improve symptoms of voiding dysfunction, voided volume, voiding efficiency and maximum flow rate in women with functional bladder outlet obstruction. None of the patients experienced intolerable side-effects. Thus, oral baclofen may be used as an initial treatment for women with symptoms of voiding dysfunction.

MUC20 promotes aggressive phenotypes of epithelial ovarian cancer cells via activation of the integrin ß1 pathway.

OBJECTIVE: Mucin (MUC) 20 has recently been implicated to play a role in human carcinogenesis. However, the role of MUC20 in epithelial ovarian cancer (EOC) remains to be elucidated. METHODS: MUC20 expression was assessed in tissue microarray and tumor specimens of EOC patients by immunohistochemistry. Effects of MUC20 on cell viability, adhesion, migration, and invasion were analyzed in MUC20 overexpressing or knockdown EOC cells. Western blotting was performed to analyze signaling pathways modulated by MUC20. RESULTS: MUC20 was overexpressed in EOC samples compared with benign tissues. High MUC20 expression was significantly associated with poor overall survival in patients with advanced-stage disease. MUC20 overexpression significantly enhanced EOC cell migration and invasion, but not viability. Mechanistic investigations showed that MUC20 increased cell adhesion to extracellular matrix (ECM) proteins and enhanced activation of integrin ß1 and phosphorylation of focal adhesion kinase (FAK). The enhancement of cell motility and the integrin ß1 signaling by MUC20 was significantly suppressed by integrin ß1 blocking antibody. Furthermore, these effects of MUC20 on EOC cells were also demonstrated in MUC20 knockdown cells. CONCLUSIONS: Our results suggest that MUC20 enhances aggressive behaviors of EOC cells by activating integrin ß1 signaling and provide novel insights into the role of MUC20 in ovarian cancer metastasis.