[Reducing the Time Before the Console in Robotic-Assisted Laparoscopic Hysterectomy].

Robotic-assisted surgery enables precise manipulations with magnified vision, stereoscopic vision, and forceps with multi-joint functions. It requires unique procedures such as position setting, port placement, roll-in, and docking, which lead to prolonged operation and anesthesia time. Five conditions described below were established at our institution to reduce the time to the initiation of console: (1) changing the patients' position from the flat lithotomy position to the spread legs position; (2) attaching a Hasson cone to hold the umbilical cannula stable; (3) changing the cannula's obturator (inner tube) from blunt to bladeless; (4) fixing the team, and (5) conducting regular docking training. These outcomes were examined in this study. The study included 77 patients who underwent robotic-assisted total hysterectomy for benign uterine disease and stage IA uterine cancer at our individual institution between April 2019 and July 2022. We compared the median time from anesthesia to console initiation between the first half group (cases 1-40) and the second half group (cases 41-77). The former required 91.5 (53-131) minutes, whereas the latter required 59 (37-126) minutes. Appropriate equipment selection and team education can reduce the time to console initiation.

Uterine Tumor Resembling Ovarian Sex Cord Tumor: A Case Report.

Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) are extremely rare, occurring in less than 1% of uterine stromal tumors, and they are considered to have a low malignant potential. Due to the small number of cases, no standard treatment has been defined. A 77-year-old woman with postmenopausal bleeding was admitted to our department. Imaging studies revealed a substantial mass around 30 mm in size on the anterior uterine wall. A total hysterectomy and bilateral salpingo-oophorectomy were performed for further diagnosis and treatment. The tumor revealed histopathological findings of a sex cord-like growth pattern in the form of fascicles, cords, or small nests. Immunohistochemical findings revealed that the tumor cells were positively reactive to alpha-SMA, calretinin, CD99, estrogen receptor, and progesterone receptor, collectively diagnosed as UTROSCT. No recurrence was observed over 12 months after treatment. We experienced the treatment of UTROSCT, an extremely rare tumor that occurs in elderly women. Although most cases of UTROSCT have a benign clinical course, several cases of recurrence and metastasis have been reported. It should be followed up for a long term after treatment.

Retrospective analysis of prognosis using the Gynecology Oncology Group score of stage IB-IIA node negative uterine cervical cancer after radical hysterectomy and trachelectomy.

There is currently controversy regarding the criteria for low and intermediate risk of cervical cancer (CC) after surgery. In the present study, the Gynecology Oncology Group (GOG) score was used to detect intermediate risk. Adjuvant radiotherapy was applied in the case of a GOG score >120. The present study aimed to evaluate the validity of the recurrence risk classification using the GOG score for stage IB-IIA node-negative CC. All cases of stage IB-IIA node-negative CC who underwent radical surgery between February 2007 and December 2015 were retrospectively reviewed. The GOG scores were determined from clinical and pathological findings and accordingly, subjects were divided into 4 groups: A, ≤40; B, >40 and ≤70; C, >70 and ≤120; and D, >120. Overall survival (OS) and recurrence-free survival (RFS) curves were generated using the Kaplan-Meier method. The log-rank test produced an estimated P-value by comparing the OS and RFS of group A (low-score group) with those of others. The present study included 61 patients (mean age, 47.82 years; age range, 22-76 years) and the median follow-up was 79 (39-149) months. Of these, 60 patients were observed for at least 60 months. During the follow-up period, the OS and RFS rates of group C were 94.7 and 84.2%, respectively, while those of group D were 100 and 91.7%, respectively; the OS and RFS of groups A and B were 100%. Log-rank tests for all OS and RFS indicated no significant differences compared to group A. It was indicated that a GOG score ≤70 does not require adjuvant therapy; however, a GOG score >70 requires consideration of adjuvant therapy based on the risk factors which constitute the score.

Surgical skill and oncological outcome of laparoscopic radical hysterectomy: JGOG1081s-A1, an ancillary analysis of the Japanese Gynecologic Oncology Group Study JGOG1081.

OBJECTIVES: We investigated whether surgical skill and procedure were related to oncological outcomes in cervical cancer patients who underwent Laparoscopic Radical Hysterectomy (LRH). METHODS: We previously assessed data of LRH from 251 patients with FIGO stage (2009) IA2, IB1and IIA1 cervical cancer collected for JGOG 1081s study. 1) The JGOG 1081s cohort study was re-examined to refine the surgical details and extend the follow-up period as chart review. 2) Unedited videos for recurrent cases and matched non-recurrent control cases were newly compared by experts for various surgical skills and surgical procedures using the modified Objective Structured Assessment of Technical Skills (OSATS) tool, without awareness of the recurrence status as video review. RESULTS: After a median follow-up of 46 months, tumors had recurred in 31 of the 251 patients. The five-year Recurrence-Free Survival rate was 86.9% (81.8-90.6) and five-year Overall Survival rate was 93.7% (87.5-96.8). Multivariate analysis from chart reviews found that an experience with LRH of less than 20 cases per institution was an independent prognostic factor for recurrence (Hazard Ratio (HR) 2.49, 95%CI 1.12-5.53, p = 0.025). For the surgical video review, we compared 23 videos of recurrent cases with 23 background-matched non-recurrent controls. Lower modified OSATS scores from the video review were consistently trended to have a higher risk of recurrence. CONCLUSIONS: Our new study has found that LRH surgical experience and skill trended to have better oncological outcomes.

Prognostic significance of intra-tumoral budding in high-grade serous ovarian carcinomas.

Intra-tumoral budding (ITB) has been well demonstrated to be an independent risk factor for adverse outcomes in colorectal carcinoma. This study investigated the prognostic significance of ITB in high-grade serous ovarian carcinomas (HGSOCs). The medical records and slides of 84 SOCs, including 13 with neoadjuvant chemotherapy (NAC), were retrospectively reviewed. The histopathologic examination with scoring of p53 expression showed them to be 80 HGSOCs and 4 low-grade serous ovarian carcinomas (LGSOCs). ITB was found in 64 (80.0%) of the 80 HGSOCs and 1 (25.0%) of 4 LGSOCs. The presence of ITB in HGSOC was significantly correlated with a higher level of CA125, an advanced 2014 FIGO stage, the presence of Lymph node metastasis, and the presence of lymphovascular space invasion (LVSI). The median progression-free survival (PFS) was 18 months in patients with HGSOC with ITB and 36 months in patients with HGSOC without ITB (P = 0.006), and their median overall survival (OS) was 50 months and 60 months (P = 0.060). The multivariate analysis revealed that ITB was not an independent prognostic factor. ITB is a cost-effective prognostic indicator for patients with HGSOC and ITB in ovarian tumor tissue is considered a useful histological biomarker of the progression of HGSOCs.

Synchronous Occurrence of Ovarian Seromucinous Carcinoma and Endometrial Mucinous Carcinoma: A Case Report.

Endometrioid carcinoma is the most common histological type of concurrent synchronous cancers of the uterus and ovary. Here we report a case of synchronous seromucinous carcinoma of the ovary and mucinous carcinoma of the endometrium with a literature review. A 51-year-old multiparous female complained of irregular bleeding and shortness of breath. Computed tomography revealed a large pelvic mass that consisted of cystic and solid components, a tumor of the endometrium, and a large amount of pleural effusion. An endometrial biopsy indicated adenocarcinoma, and adenocarcinoma cells were found in the pleural fluid. The patient with advanced ovarian cancer or endometrial cancer with massive pleural effusion received three courses of neoadjuvant chemotherapy (NAC) with paclitaxel and carboplatin followed by interval debulking surgery (IDS). The NAC was effective, and IDS was performed with no gross residual lesions. The post-operative diagnosis was seromucinous carcinoma of the ovary in FIGO (2014) stage IVA (ypT3cNxM1a) and mucinous carcinoma of the endometrium in FIGO (2008) stage IA (ypT1aNXM0). Three courses of postoperative TC therapy were performed, and maintenance therapy with Bevacizumab is ongoing. The patient is well without evidence of recurrence, sixteen months after surgery.

Hypersensitivity Reaction to Carboplatin in Gynecologic Cancer: A Case Report and a Review of the Literature.

A combination chemotherapy of paclitaxel plus carboplatin (TC) is the most frequently used regimen for gynecological malignancies. As long as it is effective, a carboplatin-containing combination chemotherapy is used for every relapse. This implies that the number of platinum administrations and the frequency of hypersensitivity reaction (HSR) increase as the prognosis improves. When a patient develops HSR to carboplatin, we have three options: 1) desensitizing and continuing to use carboplatin, 2) switching to other platinum drugs, or 3) changing to a non-platinum drug. Here we report an experience of an HSR to carboplatin in a patient with recurrent uterine carcinosarcoma. The patient was treated by surgery and TC therapy initially, resulting in no residual disease. The patient relapsed 18 months after the completion of the first-line chemotherapy and was treated with TC therapy again as second-line. An HSR to carboplatin occurred at the 10th cycle of TC in total. We replaced the carboplatin with cisplatin. A chemotherapy including cisplatin and adriamycin was repeated without further HSR. We reviewed the literature regarding HSR to carboplatin and in this paper we summarize the management for dealing with it.

Surgical margin status and recurrence pattern in invasive vulvar Paget's disease: A Japanese Gynecologic Oncology Group study.

OBJECTIVE: To examine the association between surgical margin status and recurrence pattern in invasive vulvar Paget's disease. METHODS: This is a preplanned secondary analysis of a previously organized nationwide retrospective study in Japan (JGOG-1075S). Women with stage I-IV invasive vulvar Paget's disease who received surgical treatment from 2001-2010 were examined (n=139). Multivariable analysis was performed to assess local-recurrence, distant-recurrence, and all-cause mortality based on surgical margin status. RESULTS: The median age was 70 years. The majority had stage I disease (61.2%), and the median tumor size was 5.0cm. Nodal metastasis was observed in 15.1%. Simple vulvectomy (46.0%) was the most common surgery type followed by radical vulvectomy (28.1%). More than half received vulvar reconstructive surgery (59.0%). Positive surgical margin was observed in 35.3%, and close margin <1cm was observed in 29.5%. Vulvectomy type was not associated with surgical margin status (P=0.424). The median follow-up was 5.8 years. Positive surgical margin was associated with increased local-recurrence (5-year cumulative rates for positive versus negative margin: 35.8% versus 15.0%, P=0.010) but not distant-recurrence (18.3% versus 16.0%, P=0.567). Positive surgical margin was also associated with increased all-cause mortality (5-year overall survival rates for positive versus negative margin: 72.6% versus 88.2%, P=0.032). In multivariable analysis, positive surgical margin remained an independent factor associated with increased risk of local-recurrence (hazard ratio 2.80, 95% confidence interval 1.18-6.63) and all-cause mortality (hazard ratio 2.87, 95% confidence interval 1.20-6.83). CONCLUSION: Positive surgical margin appears to be common in invasive vulvar Paget's disease that is associated with increased local-recurrence and all-cause mortality risks. Role of alternative surgical technique or adjuvant therapy merits further investigation to improve local disease control.

Laparoscopically Resected Venous Adventitial Cystic Disease that was Difficult to Distinguish from an Ovarian Tumor.

Adventitial cystic disease (ACD) is a rare condition in which a mucinous cyst forms within the adventitia, usually in arteries but rarely in veins. A 79-year-old patient presented with stomachache and nausea. Computerized tomography showed pelvic cysts on either side of the pelvis. The right tumor was 120×100 mm, and the left tumor was 45×35 mm. Our diagnosis was bilateral ovarian tumors and we performed laparoscopic tumor resection. In the abdominal cavity, we saw that the left ovary was swollen by about 3-4 cm and the right ovary was normal size. There was a mucous cyst located in the right retroperitoneal cavity that adhered around and bordered the right external iliac vein and the right obturator nerve. We peeled the adhesion away carefully and resected the tumor but the operation caused temporary obturator nerve paralysis. From pathological examination, we diagnosed the right retroperitoneal cyst to be venous ACD originating from the right external iliac vein. We found that venous ACD can grow as large as a pelvic tumor and is difficult to distinguish from an ovarian tumor, which is why we chose laparoscopic surgery. In this case, we performed the operation laparoscopically and no sequelae or recurrent tumor appeared during a 1-year follow-up. However, graft replacement is sometimes necessary for ACD, thus venous ACD should be considered a differential diagnosis and a surgical strategy should be developed when pelvic tumors are observed.

Acute arteritis after G-CSF administration.

Granulocyte colony-stimulating factor (G-CSF) is commonly used in clinical practice to accelerate neutropenia recovery after chemotherapy. G-CSF is a myeloid growth factor produced by monocytes, macrophages, fibroblasts and endothelial cells. Generally, aortitis and arteritis are not a known side effect of G-CSF and is thought to be extremely rare. Here, we present a case of a 77-year-old woman who underwent adjuvant chemotherapy (combined paclitaxel and carboplatin) for ovarian cancer, and then developed acute arteritis after receiving G-CSF. She developed grade 4 neutropenia on day 7 of the third chemotherapy cycle and received six G-CSF administrations. Two days after G-CSF administration, she came down with a high-grade fever that persisted for 2 weeks. Laboratory tests revealed a white blood cell count of 8700 UI, neutrophilic sequestration of 61.5%, and C-reactive protein of 8.43 mg/dl at the highest point of her fever. Considering that we were initially treating neutropenia, we diagnosed a bacterial infection, and she was treated with a course of antibiotics. However, her blood and urinalysis cultures were negative, and antibiotics were ineffective; thus, we performed a computed tomography scan to search for the cause of her persistent fever. The computed tomography scan showed remarkable thickness of the bilateral common carotid artery and the left subclavian artery consistent with arteritis. With cessation of the antibiotics course, she was followed closely without therapy, and her condition resolved in a few days. We conclude that G-CSF induced arteritis due to our exclusion of other probable etiologies.

Expression of N-Acetylgalactosaminyltransferase-6 Is Related to Expression of Cell Adhesion Molecules in Endometrial Cancer.

BACKGROUND: The aberrant glycosylation of mucin type O-glycans is thought to be associated with functional alteration of cancer cells, including adhesive properties, as well as their potential for invasion and metastasis. Positive expression of N-acetylgalactosaminyltransferase-6 (GalNAc-T6) may also be a marker for aberrant O-glycans in carcinogenesis. We previously reported that over-expression of GalNAc-T6 had a strong association with endometrial cell invasion ability in vitro. MATERIALS AND METHODS: This study investigated the relationship between GalNAc-T6 expression and cell adhesion molecules in 218 endometrial carcinomas by immunohistochemistry. RESULTS: Expression of GalNAc-T6 was found to be significantly related to expression of E-cadherin. Positive expression of GalNAc-T6 was significantly associated with better histological grade and good clinical prognosis of patients, but positive E-cadherin and ß-catenin expression were not significantly associated with improved overall survival. CONCLUSION: GalNAc-T6 might be related to cell-cell adhesion in the early phase of cancer invasion in endometrial carcinoma.

Expression of Polypeptide N-Acetylgalactosaminyltransferase-6 in Epithelial Ovarian Carcinoma.

BACKGROUND: The family of polypeptide N-acetylgalactosanimyltransferases (GalNAc-Ts) are important factors in glycosylation in carcinomas. The purpose of this study was to investigate the clinical significance of GalNAc-T6 and its correlation with the prognosis of epithelial ovarian carcinoma. MATERIALS AND METHODS: A total of 150 patients with epithelial ovarian carcinoma were enrolled and the relationship between GalNAc-T6 expression by immunohistochemistry and long-term survival was evaluated. RESULTS: The expression of GalNAc-T6 was positive in 57.6% (34/59) of those with serous carcinoma, 85.3% (29/34) in mucinous carcinoma, 15.6% (5/27) in clear cell carcinoma, and 44% (14/25) in endometrioid carcinoma. In a Kaplan-Meier analysis of patients with grade 1 or 2 serous carcinoma, the 10-year overall survival rates were 47.4% in the GalNAc-T6-positive and 9.1% in the GalNAc-T6-negative groups (p=0.047). CONCLUSION: GalNAc-T6 expression in epithelial ovarian carcinoma was different according to pathological type. In low-grade serous carcinoma, GalNAc-T6 expression may contribute to improved long-term survival.

GalNAc-T6 in the relationship with invasion ability of endometrial carcinomas and prognostic significance.

O-glycosylation in the field of carcinogenesis has been a critical topic of concern for several decades. The abnormal function of enzymes catalyzing the first step of this process, named polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts) has been determined to play an important role in cancer development and metastasis. Accordingly, we investigated the expression of GalNAc-T6 in endometrial carcinoma and evaluated the relationship between invasion characteristics and the cellular level of GalNAc-T6. The results suggested that positive GalNAc-T6 expression is significantly associated with histological grade of tumors and myometrial invasion characteristic. In vitro experiments showed that the over expression of GalNAc-T6 had strong association with the decrease of endometrial cell invasiveness. Taken together, our data support the use of GalNAc-T6 as a potential indicator of good prognosis and noninvasive tumor in patients with endometrial carcinoma.

Effect of menopause on hormonal receptors in ampullae of the fallopian tube with a special reference to the p53 signature.

OBJECTIVES: Age-related changes in the expression of hormonal receptors have not been well examined in the fallopian tube (FT). We herein report the effect of menopause on the hormone receptors in ampullae of the FTs (AFTs), in comparison with cortical inclusion cysts (CICs) of the ovary. METHODS: A total of 84 AFTs and 16 fimbriae of FTs, which were obtained from 26 premenopausal and 58 postmenopausal women; and 27 postmenopausal CICs were immunohistochemically studied for the expression of p53, Ki-67, estrogen receptor-alpha (ER-α), and progesterone receptor A (PRA). Apoptotic cells were identified using a TUNEL assay. RESULTS: Postmenopausal AFTs showed a significantly lower labeling index (LI) for Ki-67 (P<0.001), apoptosis (P=0.03), and PRA (P<0.001) than premenopausal AFTs. No significant correlation with immunohistochemical markers was found in premenopausal AFTs, but the LI for PRA was positively correlated with that for Ki-67 (P=0.004) and inversely with that for p53 (P=0.023) in postmenopausal AFTs. The expression of immunohistochemical markers was closely correlated between ampullae and fimbriae of the FT. The p53 signature (p53S) was detected in five postmenopausal AFTs (mean age: 70.2 years) and was not detected in any CICs. The immunohistochemical profile of p53S was low expression of Ki-67, apoptosis, and PRA, and high expression of ER-α. The expression of PRA in CICs was significantly higher than that in AFTs (P=0.001). CONCLUSION: The expression of PRA was significantly lower in postmenopausal AFTs than in premenopausal AFTs, whereas the expression of PRA was well preserved in postmenopausal CICs.

Immunohistochemical Analysis of the Effect of Dienogest on Ovarian Endometriotic Cysts.

Dienogest is a novel progestin with potent oral progestational activity that inhibits the clinical symptoms of endometriosis. We herein evaluated the effect of dienogest on ovarian endometriotic cysts via immunohistochemistry. Ovarian endometriotic cyst specimens were collected from 12 patients treated with dienogest and 20 patients not treated with hormones (controls). The expression of estrogen receptor (ER)-α, progesterone receptor A (PRA), and Ki-67 was studied by immunohistochemistry. As compared with the controls, the cell proliferation index was significantly reduced in both epithelial and stromal cells of the endometriotic cysts following the use of dienogest (P = 0.022 and P = 0.004, respectively). However, there was no significant difference between endometriotic cysts with and without the use of dienogest in the expressions of ER-α and PRA in the epithelial and stromal cells. Irrespective of the use of dienogest, the expression levels of ER-α and PRA in the epithelial cells were low (median: 32% and 8%, respectively). Conversely, the expression levels of ER-α and PRA in the stromal cells were well preserved (median: 68% and 92%, respectively). In the controls, there was no significant difference between endometriotic cysts in the expression levels of Ki-67, ER-α and PRA in epithelial and stromal cells during the proliferative and secretory phases. The finding of a reduction in the cell proliferation index by the use of dienogest with no change in the expressions of hormonal receptors may not support the direct progestational effect of dienogest on ovarian endometriotic cysts.

Expression of p53 in endometrial polyps with special reference to the p53 signature.

We herein examined the significance of the p53 expression in endometrial polyps (EMPs). A total of 133 EMPs, including 62 premenopausal and 71 postmenopausal women with EMP, were immunohistochemically studied for the expression of estrogen receptor (ER)-alpha, Ki-67 and p53. Apoptotic cells were identified using a TUNEL assay. A DNA sequence analysis of TP53 exons 5 to 9 was performed. Among the premenopausal EMPs, a multivariate analysis showed the labeling index (LI) for Ki-67 to correlate significantly with that for p53 (P<0.001), but not that for apoptosis. On the contrary, among the postmenopausal EMPs, the LI for Ki-67 correlated significantly with that for apoptosis (P<0.001). The p53 signature (p53S) was defined by endometrial epithelial cells, which are morphologically benign in appearance but display 12 or more consecutive epithelial cell nuclei with strong p53 immunostaining. The p53S was found in nine (12.7%) postmenopausal EMPs (mean age: 70.2 years). The median Ki-67 index for the p53S was 7%, with no significant difference from that of the glands of the postmenopausal EMPs without the p53S (P=0.058). The median apoptotic index for the p53S was 0%, which was significantly lower than that of the postmenopausal EMPs without the p53S (P=0.002). Two of four p53Ss showed TP53 mutations according to the DNA sequence analysis. The presence of the p53S is not rare in postmenopausal EMPs with an advanced age. Among postmenopausal EMPs, the LI of Ki-67 significantly correlates with that of apoptosis. However, such a positive correlation between the LI of Ki-67 and apoptosis is not observed in p53S.

The Relationship between Positive Peritoneal Cytology and the Prognosis of Patients with Uterine Cervical Cancer.

OBJECTIVE: We investigated the association of positive peritoneal cytology with prognosis in uterine cervical cancer. STUDY DESIGN: We reviewed the medical records and cytologic materials of 225 Japanese patients with FIGO IB1-IVB uterine cervical cancer who had undergone surgery at our University Hospital between 1993 and 2012. Univariate and multivariate regression analyses were performed for statistical analysis. RESULTS: Positive peritoneal cytology was noted in 6 of 225 patients (2.7%). Positive peritoneal cytology was found in 4 of 149 patients (2.6%) with squamous cell carcinoma (SCC) and in 2 of 70 patients (2.8%) with non-SCC (p = 0.9434). The 5-year survival rate of patients with positive peritoneal cytology was significantly lower than that of patients with negative cytology (50 vs. 84.6%, p = 0.001) in univariate survival analysis. However, peritoneal cytology no longer remained significant in multivariate analysis. CONCLUSION: Although we conclude that positive peritoneal cytology in uterine cervical cancer is a poor prognostic factor, further investigation and multi-institutional studies are necessary.

Significance of p53 expression in background endometrium in endometrial carcinoma.

The p53 signature (p53S) has been proposed to be a marker of the earliest phase of development of endometrial serous carcinoma. We examined the presence of p53S in the background endometrium in cases of endometrial carcinoma. From a series of 351 endometrial carcinomas, 225 (64.1 %) lesions, for which slides of the adjacent noncancerous endometrium were available for review, were included. Expression of estrogen receptor (ER)-alpha, Ki-67, and p53 in the adjacent endometrium was studied by immunohistochemistry. The p53S was defined as the presence of morphologically benign endometrial epithelial cells with moderate to strong intensity of p53 immunostaining. Of the 225 noncancerous endometrium samples, 34 consisted of hyperplastic and 191 of non-hyperplastic endometrium. A p53S was found in 22 cases (mean age 64.2 years), 2 in hyperplastic, and 20 in non-hyperplastic background endometrium. All p53S-positive cases also expressed ER-alpha; their median Ki-67 labeling index (LI) was 4.0 % (range 0.0 to 21.0 %). The two cases with hyperplastic p53S-positive background endometrium were in association with a grade 1 endometrioid tumor in a premenopausal woman with Lynch syndrome. Of the 152 cases of endometrioid adenocarcinomas with non-hyperplastic endometrium, 12 (8 %) were p53S positive, none of which associated with EIC. Of the 21 cases of serous carcinoma, five (24 %) were p53S positive, 4 of which (19 %) associated with EIC while in 5 others (24 %) EIC was found without p53S. Of three clear cell adenocarcinomas, none were p53S positive while two contained EIC without p53S. Of 15 carcinosarcomas, 3 (20 %) were p53S positive, all of which with EIC while 6 others (40 %) were associated with EIC but without p53S. Of the 8 non-endometrioid tumors with p53S, 7 (88 %) were associated with EIC. p53S is thought to be associated with precancerous lesions of non-endometrioid tumors, including carcinosarcomas.