The Current Trend of Fertility Preservation in Patients with Cervical Cancer.

Although the incidence of most cancers increases with age, a considerable number of patients receive a diagnosis of cancer during their reproductive years. Young women wishing to get pregnant after cancer treatment should be provided consultation for fertility preservation and possible options. In patients with cervical cancer, hysterectomy is often inevitable because the uterus is located too close to the cervix. For young patients with cervical cancer who desire to get pregnant and whose lesion is confined to the cervix, sparing the uterus and, partially, the cervix should be prioritized as much as possible, while simultaneously ensuring favorable oncologic outcomes. In this review, we explore how to choose an adequate fertility-preserving procedure to achieve a balance between favorable oncologic outcomes and fertility and management during pregnancy after a radical trachelectomy in women with early-stage cervical cancer. For patients who require hysterectomy or radiation, evaluation of the ovarian condition and laparoscopic ovarian transposition followed by the use of artificial reproduction techniques and pregnancy by surrogacy should be discussed as options to achieve a successful pregnancy.

Comparison of outcomes of laparotomic and minimally invasive radical hysterectomy in women with early-stage cervical cancer.

OBJECTIVE: This study compared the outcomes of laparotomic radical hysterectomy (LRH) and minimally invasive radical hysterectomy (MISRH) in patients with early-stage cervical cancer. METHODS: The clinical data of patients with early-stage cervical cancer who underwent LRH or MISRH (laparoscopic/robotic) at Chang Gung Memorial Hospital, Linkou Branch, from 2002 to 2017 were retrospectively reviewed. The surgical safety (operation time, blood loss, blood transfusion rate, length of postoperative stay, and perioperative complications), overall survival (OS), disease-free survival (DFS), and recurrence pattern were analyzed. Propensity score matching (PSM) at a 3:1 ratio was performed to balance prognostic variables. RESULTS: Of the 760 patients (entire cohort), 614 underwent LRH and 146 underwent MISRH. After PSM, 394 and 140 patients were included in the LRH and MISRH groups, respectively. The 5-year OS rate was significantly lower in the MISRH group than in the LRH group (85.6% vs. 93.2%, p=0.043), and the 5-year DFS rate (p=0.21) did not differ significantly. After PSM, the 5-year OS rates did not differ significantly between the MISRH and LRH groups (87.1% vs. 92.1%, p=0.393). The MISRH group had a significantly shorter operation time (p<0.001), lower intraoperative blood loss (p<0.001), lower blood transfusion rate (p<0.001), and shorter postoperative stay (p<0.001) but a significantly higher rate of intraoperative bladder injury (p<0.001) than the LRH group. CONCLUSION: After PSM, MISRH is associated with nonsignificantly lower OS but a significantly higher risk of intraoperative urological complications than LRH.

Consistency in human papillomavirus type detection between self-collected vaginal specimens and physician-sampled cervical specimens.

With the rising need for accessible cervical cancer screening, self-sampling methods offer a promising alternative to traditional physician-led sampling. This study aims to evaluate the efficacy of the HygeiaTouch Self Sampling Kit for Women in detecting human papillomavirus (HPV) types and predicting cervical lesions. We studied the concordance in identifying high-risk HPV (hrHPV) types between samples collected by physicians and those self-collected by women using a self-sampling kit for validation. Women aged 21-65, fitting into specific categories based on their cervical health history were eligible. Cohen's kappa coefficient to gauge concordance between the two specimen types and relative accuracy metrics in identifying cervical intraepithelial neoplasia (CIN) were also calculated, with physician-sampled specimens serving as a reference. A total of 1210 participants from three institutes were involved. The self-sampling kit closely matched the physician-led method in terms of collecting valid specimens (100% vs. 100%), identifying hrHPV types (kappa: 0.75, 95% confidence interval [95% CI]: 0.72-0.79; agreement: 87.7%, 95% CI: 85.8-89.6) and predicting CIN grade 2 or worse (CIN2+) (relative sensitivity: 0.949, relative accuracy: 0.959). Kappa values varied between 0.71 and 0.83 for different hrHPV types and combinations, with an overall value 0.75 (95% CI: 0.72-0.79) signifying robust compatibility between the two methods. Our study underscores the potential of the HygeiaTouch Self Sampling Kit as a reliable, efficient, and user-friendly alternative to traditional sampling methods. This suggests that self-sampling could be pivotal in expanding cervical cancer screening accessibility and enhancing detection rates.

Origami Box Folding Exercise: A laparoscopic box simulation training and assessment method in facilitating laparoscopic psychomotor skills with minimal preparation.

OBJECTIVE: Laparoscopic box simulation training is widely recognized as an assessment tool to facilitate psychomotor skills especially for novice surgeons. However, current commercialized training modules including pegs, gauze, clips, pins etc. are generally costly and relatively inaccessible. We introduce a simple and pioneer surgical training drill, the Origami Box Folding Exercise (OBFE), based on the validated evaluating system of objective structured assessment of technical skills (OSATS) constructed with the scoring system of procedure-specific checklist (PSC) and global rating scale (GRS). MATERIALS AND METHODS: Face and content validation of the OBFE and OSATS are evaluated by five endoscopic experts from two medical centers in Taiwan. This is a prospective observational study analyzing the pre-test/post-test result of OBFE from 37 participants in two individual workshops as training and evaluating method for laparoscopic psychomotor skills. Both the pre and post tests are video recorded with a time limit of 5 min graded by two independent evaluators based on the OSATS scoring system. RESULTS: The reliability of PSC, GRS, and intergroup value between PSC and GRS were 0.923, 0.926 and 0.933, respectively. Inter-rater reliability of PSC, GRS, and both were 0.985, 0.932 and 0.977, respectively. Construct validity of PSC and GRS were statistically significant, with p-value 0.006 and 0.001, respectively. CONCLUSION: OBFE enhances laparoscopic psychomotor skills with requirement of a single piece of paper. The associated OSATS tool for a 5-min OBFE test was validated. OBFE training is an efficient training and assessment system to promote psychomotor skills in laparoscopic box simulation drill which requires simple and economical preparation.

Mutations in circulating tumor DNA detected in the postoperative period predict poor survival in patients with ovarian cancer.

BACKGROUND: We investigated whether mutations in plasma circulating tumor DNA (ctDNA) can provide prognostic insight in patients with different histological types of ovarian carcinoma. We also examined the concordance of mutations detected in ctDNA samples with those identified in the corresponding formalin-fixed paraffin-embedded (FFPE) tumor specimens. METHODS: Between July 2016 and December 2017, 29 patients with ovarian carcinoma were prospectively enrolled. FFPE tumor specimens were obtained from all participants. A total of 187 blood samples for ctDNA analysis were collected before surgery (C0), immediate after surgery before adjuvant chemotherapy (C1), and at six-month intervals. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. RESULTS: The study cohort consisted of 13 (44.8%) patients with high-grade serous carcinomas (HGSC), 9 (31.0%) with clear cell carcinoma, 2 (6.9%) with mucinous carcinomas, 4 (13.8%) with low-grade serous carcinomas, and 1 (3.4%) with endometrioid carcinoma. Twenty-four (82.8%) patients had at least one detectable ctDNA variant. The concordance rate between mutations identified in pretreatment ctDNA and corresponding FFPE tumor specimens was 92.3% for patients with HGSC and 58.6% for the entire cohort. The median follow-up time was 33.15 months (range: 0.79-46.13 months). Patients with an advanced stage disease more likely had detectable ctDNA mutations before surgery (C0) and after surgery at C1, while those with HGSC more likely had ctDNA mutations detected before surgery. The presence of ctDNA mutations at C1 was an independent predictor of worse OS with a hazard ratio of 6.56 (95% confidence interval, (1.07-40.17) for detectable versus undetectable C1 ctDNA variants, p = 0.042). CONCLUSIONS: ctDNA mutations are common in patients with ovarian carcinoma. The presence of ctDNA mutations after surgery was an independent predictor of less favorable PFS and OS.

Vaginal natural orifice transvaginal endoscopic surgery (vNOTES) surgical staging for endometrial carcinoma: The feasibility of an innovative approach.

OBJECTIVE: This study aims to describe the feasibility of treating early-stage endometrial cancer with hysterectomy, bilateral salpingo-oophorectomy, sentinel lymph node biopsy, and bilateral pelvic lymphadenectomy by vaginal Natural Orifice Transluminal Endoscopic Surgery (vNOTES). MATERIALS AND METHODS: A longitudinal study of prospectively registered patients was conducted at an academic tertiary care center. 15 patients who underwent vNOTES surgical staging of early endometrial carcinoma between January 2014 and December 2020 were included in the study. RESULTS: 15 patients between 20 and 80yrs of age with histologically proven Stage1 Gr1-2 endometrial cancer underwent vNOTES surgical staging. The mean age of the study population was 52.8 years (Standard Deviation [SD] 6.8) and the mean BMI was 27.8 kg/m2 (SD 6.4). The average operative time was 231.4 min (SD 41.0) with the mean estimated blood loss of 122.0 mL (SD 104.4). A total of 12 (80%) patients underwent SNL biopsy with ICG guided system, whereas 3 (20%) had pelvic lymph node dissection. There was one case with the surgical complication of bladder injury requiring conversion to conventional laparoscopy. CONCLUSION: With this study, we studied the feasibility of vNOTES surgery for early-stage endometrial cancer with minimal complications and the best long-term surgical outcome. The surgeries were performed by a single skilled endoscopist surgeon with previous experience with vNOTES surgery for adnexal tumors and hysterectomy. Our results showed the practicality of vNOTES in staging surgery for early-stage endometrial cancer. However, application to a larger cohort is required for more extensive surgical outcome studies.

An incidental diagnosis of endometrial cancer in a young and underweight female with isolated symptom of amenorrhea.

OBJECTIVE: We demonstrate a young woman with the incidental diagnosis of endometrial cancer, although all common risk factors of endometrial cancer were absent and endometrial lining in ultrasound was smooth either. CASE REPORT: A 23-year-old female was referral from local clinic for frequent lower abdominal pain, enlarged right adnexal cystic tumor and suspected adnexal torsion. A special symptom of annual menses (menses around every year) was also complained. The onset of the amenorrhea was 6 years ago just after a laparoscopic salpingostomy for right pyosalpinx. Her body mass index (BMI) was 16.8 kg/m2. Laboratory examination documented the level of prolactin, thyroid function, gonadotropins, estradiol and free testosterone were all within normal range. Pelvic ultrasound revealed the smooth endometrial lining with 1.2 cm in thickness. Laparoscopic surgery was arranged for the adnexal torsion. Besides, a diagnostic hysteroscopic was simultaneously planned for a further endometrial survey and endometrial sampling. Apart from a large functional cyst noted in right adnexa, the hysteroscopy disclosed diffuse polypoid endometrial lesions with neovascularity. The pathology showed atypical hyperplasia with focal endometrioid carcinoma. Postoperative magnetic resonance image revealed no residual tumor and FIGO IA status. Fertility preservation treatment with Mirena insertion was performed. CONCLUSION: Generally, the clues to detect endometrial neoplasm in a young female include family or genetic predisposition, menstrual patterns of abnormal spotting, obesity, risk of polycystic ovary syndrome and/or bizarre images of endometrial lining. However, the above conditions are all absent in the presenting case except the symptom of amenorrhea, in which the chronic anovulatory status may overstimulate the endometrium from the unopposed estrogen and potentially lead to the malignant transformation. Endometrial tissue assessment would be crucial for any young woman suspected to have prolonged exposure (≥6-12 months) of unopposed estrogenic stimulation. Endometrial tissue sampling in premenopausal group with amenorrhea for more than 6-12 months could not be ignored even for the young patient without common risk factors of endometrial cancer.

Neutrophil-to-lymphocyte-ratio-based perioperative prognosis prediction model on early mortality after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Combined cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) to treat peritoneal surface malignancy (PSM) has gained a positive result compared with palliative chemotherapy alone in several cancer types. However, its postoperative care could be challenging. We aimed to develop a predicting model on early mortality. METHODS: We retrospectively reviewed 132 PSM patients who had received CRS-HIPEC. The optimal cut-off value of the neutrophil-to-lymphocyte ratio (NLR) was determined as 4.4 by using the receiver operating characteristic curve analysis with an area under the curve (AUC) of 0.75. The impact of NLR on survival was elucidated by comparing the pre-operative low (NLR≤ 4.4, n = 101) and high (NLR> 4.4, n = 31) groups using the Kaplan-Meier method. The significant variables selected in multivariate analysis on early mortality were used in prediction model development. RESULTS: Multivariate analysis showed that incomplete CRS, major postoperative complications, higher pre-operative NLR, and dynamic NLR changes were significant predictors of early mortality. Our perioperative prediction of prognosis (triple P) model contained four independent risks, and the AUC after classification was 0.860 (95% confidence interval [CI]: 0.773-0.947). External validation confirmed positive discrimination ability (AUC: 0.808, 95% CI: 0.666-0.950). CONCLUSION: In conclusion, our triple P model provides great determination in outcomes prediction and it is easily obtained, reliable, and applicable in routine practice.

Hyperthermic intraperitoneal chemotherapy for recurrent epithelial ovarian cancer.

BACKGROUND: To investigate outcomes and morbidity of patients undergoing secondary cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent ovarian cancer. MATERIALS AND METHODS: Between April 2014 and January 2019, a total of 51 recurrent ovarian cancer patients receiving secondary CRS and HIPEC were retrospectively reviewed. RESULTS: Among the 51 patients, median peritoneal cancer index score was 13 (range 3-34), and completeness of cytoreduction (CC) score of 0/1 was achieved in 41 patients (78.8%). Regimen of HIPEC included cisplatin and paclitaxel in 39 (75%) cases. The median follow-up duration of survivors was 20.2 months. Sixteen (30.8%) patients remained free of recurrence after HIPEC. The median progression-free survival (PFS) and overall survival (OS) were 11.8 months and 34.5 months respectively. Multivariate analysis showed previous chemotherapy <2 lines (HR 0.24, 0.11-0.52; p = 0.001), chemotherapy-free interval ≥6 months (HR 0.19, 0.09-0.37; p < 0.001) and CA125 < 35 U/mL before HIPEC (HR 0.133, 0.021-0.0832; p = 0.031) were good prognostic factors for PFS. CC0/1 was not significant in multivariate analysis. The most common grade 3/4 toxicity was anemia (17.3%), pleural effusion (11.5%) and renal insufficiency (5.7%). Patients with age ≥50, peritoneal carcinomatosis index (PCI) ≥ 11, operation time ≥10 h and diaphragm surgery had significantly higher incidence of pleural effusion. CONCLUSIONS: The current study showed adding HIPEC to secondary CRS might prolong PFS especially in patients with previous chemotherapy <2 lines, chemotherapy-free interval ≥6 months and CA125 < 35 U/mL before HIPEC.

The Impact of Multidisciplinary Team Approach on Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is a therapeutic approach used to achieve curative treatment in intra-abdominal malignancy with peritoneal carcinomatosis (PC). However, it is a complicated procedure with high post-operative complication rates. Thus, we analyzed our preliminary data to establish whether multidisciplinary teamwork (MDT) implementation is beneficial for CRS-HIPEC outcomes. METHOD: A series of 132 consecutive patients with synchronous or recurrent PC secondary to gastrointestinal or gynecologic cancer who received CRS-HIPEC operation between May 2015 and September 2017 were included. Ninety-nine patients were categorized into the MDT group, with the 33 other patients into the non-MDT group. RESULTS: The mean PCI score was 16.3 ± 8.8. Patients in the MDT group more often presented a higher PCI score (p value = 0.038). Regarding CRS completeness (CCR 0-1), it was distributed 81.8% and 57.6% in the MDT and the non-MDT group, respectively (p value = 0.005). Although post-operative complications were common (n = 62, 47.0%), post-operative complication rates did not differ between the two groups. The cumulative OS survival rate at the first year was 75.5%. Older age (p = 0.030, HR = 4.58, 95% CI = 1.16-18.10), ECOG 2 (p = 0.030, HR = 6.41, 95% CI = 1.20-34.14), and incomplete cytoreduction (p = 0.048, HR = 2.79, 95% CI = 1.04-8.27) were independent prognostic factors for survival. CONCLUSIONS: Our experience suggests that the CRS-HIPEC performed under MDT cooperation may result in higher complete cytoreduction rates without increasing post-operative complications and hospital mortalities.

Metastatic Smooth Muscle Tumor of Uncertain Malignant Potential after Laparoscopic Presuming Myomectomy.

A 38-year-old para-2 female underwent laparoscopic myomectomy with uncontained morcellation. Three years later, she complained of epigastric pain. An intraperitoneal 3 cm mass beneath the umbilicus was showed on computed tomography (CT) scan. With the impression of gastrointestinal stromal tumor, she underwent open laparotomy at the general surgery department. A tumor was excised. Pathological examination showed that the tumor was consistent with a smooth muscle tumor of uncertain malignant potential smooth muscle tumors of uncertain malignant (STUMP). Six years postlaparoscopic myomectomy, during a regular follow-up, three parauterine masses were found on ultrasonography and CT scan. She underwent laparoscopic surgery for hysterectomy, bilateral salpingectomy, and excision of the masses. The masses were again diagnosed as STUMP. This case presents a recurrence of a rare type of smooth muscle tumor after uncontained morcellation. If myomas are to be removed with morcellation, it should only be used appropriately with a compatible containment system, and the risk of occult malignancy should be counseled.

Standardization and experience may influence the survival of laparoscopic radical hysterectomy for cervical cancer.

OBJECTIVE: Minimally invasive radical hysterectomy has been shown to be associated with poorer outcome in an influential prospective, randomized trial. However, many centers worldwide performing minimally invasive radical hysterectomy have data and experience that prove otherwise. We aim to review surgical and oncologic outcomes of patients operated by Laparoscopic Radical Hysterectomy in a tertiary hospital, by experienced surgeons and standardization in radicality, for cervical carcinoma Stage 1A1-1B1 from January 2009 to May 2014. MATERIALS & METHODS: Standardised surgical technique with Parametrium & Paracolpium resection approach was adopted by qualified and experienced Gynecologic/Gyne-Oncologic Endoscopic & Minimally Invasive Surgeons in performing Laparoscopic Radical Hysterectomy for Cervical Cancer stage 1A1-1B1 from January 2009-May 2014, involving 53 patients. Electronic Medical Record system (EMR) Of Chang Gung Memorial Hospital(Tertiary Referral Centre), Department of Obstetrics & Gynecology was accessed for surgical and oncologic outcomes. RESULTS: Fifty-Three patients operated from January 2009 to May 2014 were followed up for an average of 96.7 months with longest follow-up at 127 months. There were no cases of recurrence or death reported. 5 Year - Survival Rate and 5 Year Disease-Free Survival Rate were 100%. Two patients received post-operative pelvic radiation concurrent with chemotherapy using Cisplatin due to greater than 1/3 cervical stromal invasion. CONCLUSION: It is vital to standardize minimally invasive surgical techniques for early stage cervical cancer, with focus on adequate radicality and resection which may contribute to excellent survival outcomes. Further international multi-center randomized trial (Minimally Invasive Therapy Versus Open Radical Hysterectomy In Cervical Cancer) will provide justification for continued practice of MIS in early stage cervical cancer.

Postoperative adjuvant dose-dense chemotherapy with bevacizumab and maintenance bevacizumab after neoadjuvant chemotherapy for advanced ovarian cancer: A phase II AGOG/TGOG trial.

OBJECTIVE: The objective of this study is to evaluate the safety and efficacy of adding bevacizumab to dose-dense adjuvant chemotherapy with bevacizumab maintenance after neoadjuvant chemotherapy (NAC) and interval debulking surgery (IDS) for stage III/IV ovarian, tubal, and primary peritoneal cancer. STUDY DESIGN: This phase II clinical trial using Simon's minimax two-stage design was conducted. At the first stage, 13 subjects were enrolled, and the trial would proceed to second stage if ≤3 subjects discontinued treatment for study-defined significant adverse events (AEs). Patients with stage III/IV ovarian, tubal, and primary peritoneal cancer deemed not feasible for primary cytoreductive surgery were enrolled after 3-4 cycles of NAC and IDS without disease progression. NAC could be either weekly paclitaxel (80 mg/m2) (dose-dense) plus 3-weekly carboplatin (AUC5-6) or 3-weekly conventional schedule. After IDS, postoperative dose-dense adjuvant chemotherapy for 3 cycles at least (best to 6 cycles), and 3-weekly bevacizumab 15 mg/kg was given since postoperative cycle 2. Further 3-weekly maintenance bevacizumab 15 mg/kg was given intravenously for 17 cycles. RESULTS: Of the 22 enrolled subjects, 13 (59.1 %) had no gross lesion after IDS. Of the 13 subjects enrolled on the 1 st stage, one study-defined significant AE occurred, therefore the trial proceeded to the 2nd stage (n = 9). The median progression-free survival (PFS) was 22.1 months (95 % confidence interval [CI], 13.7-30.5), and the median overall survival (OS) was 49.2 months (95 % CI, 33.8-64.6). Peritoneal Cancer Index score at entering abdomen during IDS was significant for PFS (>12 vs ≤ 12: p = 0.003). One of the 22 subjects did not receive any study treatment. In the safety analysis (n = 21), grade 3/4 AEs included thrombocytopenia of 38.1 %, neutropenia 71.4 %, and anemia 28.6 %. Study-defined significant AEs of bowel perforation, poor-healing wound, and hypertension were found in 1 case each, respectively. CONCLUSION: This phase II trial demonstrated adding bevacizumab to dose-dense adjuvant chemotherapy with bevacizumab maintenance after NAC was feasible with tolerable toxicity and comparable PFS/OS as compared to other studies using bevacizumab in the NAC phase or dose-dense scheduling throughout.

Role of human papillomavirus status after conization for high-grade cervical intraepithelial neoplasia.

Human papillomavirus (HPV) is the well-established etiologic factor for cervical neoplasia. Cervical conization constitutes an effective treatment for high-grade cervical intraepithelial neoplasia (HG-CIN). We conducted an observational study for long-term outcomes and HPV genotype changes after conization for HG-CIN. Between 2008 and 2014, patients with newly diagnosed HG-CIN before conization (surveillance new [SN] group) and those who had undergone conization without hysterectomy (surveillance previous [SP] group) were enrolled. HPV testing and Pap smear were performed periodically for the SN and SP (collectively S) groups. All other patients receiving conization for HG-CIN during the study period were identified from our hospital database. Those eligible but not enrolled into our study were assigned to the non-surveillance (non-S) group. For the S group (n = 493), the median follow-up period was 74.3 months. Eighty-four cases had recurrent CIN Grade 2 or worse (CIN2+) (5-year cumulative rate: 14.8%), of which six had invasive cancer. Among the 84 patients, 65 (77.4%) exhibited type-specific persistence in the paired HPV results, whereas only 7 (8.3%) harbored new HPV types that belonged to the 9-valent vaccine types. Among the 7397 non-S patients, 789 demonstrated recurrent CIN2+, of which 57 had invasive cancer. The stages distribution of those progressed to invasive cancer in the non-S group were more advanced than the S group (P = .033). Active surveillance might reduce the severity of those progressed to cancer. Because a majority of the patients with recurrent CIN2+ had persistent type-specific HPV infections, effective therapeutic vaccines are an unmet medical need.