Positive Ascites Cytology, Postoperative Chemotherapy and Prognosis of Stage I Ovarian Clear Cell Carcinoma.

BACKGROUND/AIM: Ovarian clear cell carcinoma (CCC) is associated with a poor prognosis and is resistant to chemotherapy. The aim of this study was to investigate the prognosis of CCC in Mie prefecture and to identify poor prognostic factors. PATIENTS AND METHODS: In this multi-center retrospective study, we analyzed the data of patients with CCC between February 2012 and December 2020. Patients were staged according to the International Federation of Gynecology and Obstetrics (FIGO) 2014 system. Statistical analyses were performed using the Kaplan-Meier method and compared between the two groups using the log-rank test. RESULTS: A total of 112 patients were included and the median follow-up time was 48 months. There was no difference in the prognosis between stages IA, IC1, and IC2. For patients at stages IA, IC1, and IC2, there was no difference in progression-free survival (PFS) and overall survival between the adjuvant chemotherapy and no chemotherapy groups. Median postrecurrent survival was 18 and 20 months in the stages I-II and III-IV groups, respectively. Multivariate analysis revealed that positive ascites cytology (p=0.006) was associated with PFS for patients at stages I-II and that the stage (p=0.039) was associated with PFS for patients at stages III-IV. CONCLUSION: Positive ascites cytology was a poor prognostic factor for patients at an early stage of CCC. Postoperative chemotherapy could be omitted for patients in stages IA and IC1. Relapsed patients did not respond to the standard treatment and had a poor prognosis regardless of the primary stage.

Does Vaginal Cuff Creation and Avoidance of a Uterine Manipulator Improve the Prognosis of Total Laparoscopic Radical Hysterectomy for Early Cervical Cancer? A Retrospective Multicenter Study.

Our goal was to compare the treatment outcomes of open-abdominal radical hysterectomy (O-RH) and total laparoscopic hysterectomy (TLRH) with vaginal cuff creation and without using a uterine manipulator in stage IB1-B2 (tumor size < 4 cm) cervical cancer cases. In this retrospective multicenter analysis, 94 cervical cancer stage IB1-B2 patients who underwent O-RH or TLRH in six hospitals in Japan between September 2016 and July 2020 were included; 36 patients underwent TLRH. Propensity score matching was performed because the tumor diameter was large, and positive cases of lymph node metastases were included in the O-RH group due to selection bias. The primary endpoint was progression-free survival (PFS) and recurrence sites of TLRH and O-RH. PFS and OS (overall survival) were not significant in both the TLRH (n = 27) and O-RH (n = 27) groups; none required conversion to laparotomy. The maximum tumor size was <2 and ≥2 cm in 12 (44.4%) and 15 (55.6%) patients, respectively, in both groups. Reportedly, the TLRH group had lesser bleeding than the O-RH group (p < 0.001). Median follow-up was 33.5 (2−65) and 41.5 (6−75) months in the TLRH and O-RH groups, respectively. PFS and OS were not significantly different between the two groups (TLRH: 92.6%, O-RH: 92.6%; log-rank p = 0.985 and 97.2%, 100%; p = 0.317, respectively). The prognosis of early cervical cancer was not significantly different between TLRH and O-RH. Tumor spillage was prevented by creating a vaginal cuff and avoiding the use of a uterine manipulator. Therefore, TLRH might be considered efficient.

Association of CXC chemokine receptor type 4 expression and clinicopathologic features in human vulvar cancer.

OBJECTIVE: Although CXC chemokine receptor type 4 (CXCR4) is known to be expressed in various solid tumors and plays an integral role in cancer invasion and metastasis, expression of CXCR4 in human vulvar cancer has not yet been investigated. We examined distribution and expression of this chemokine receptor in specimens of invasive and noninvasive human vulvar neoplasms to elucidate its clinical significance. METHODS: Study patients were 38 consecutive patients (31 with primary vulvar cancers and 7 with intraepithelial neoplasms) treated at one of our hospitals. Sections of all specimens were evaluated for CXCR4 expression by means of immunohistochemistry. Relations between CXCR4 expression and clinicopathologic features including prognosis were investigated. RESULTS: None of the 7 vulvar intraepithelial lesions expressed CXCR4. Of the 31 invasive vulvar tumor samples examined, 19 (61%) stained positively for CXCR4; 15 (68%) of 22 squamous cell carcinomas and 2 (29%) of 7 Paget tumors were CXCR4 positive. The difference in expression between invasive cancers and intraepithelial neoplasms was significant (P = 0.003). FIGO (International Federation of Gynecology and Obstetrics) stage III-IV cancers, in comparison to FIGO stage I-II cancers, were more likely to be positive for CXCR4 (82% vs 50%, P = 0.08). In terms of disease-free survival, prognosis of cancers that expressed CXCR4 was poorer than that of CXCR4-negative cancers (P = 0.013), but in terms of disease-specific survival, prognosis did not differ significantly between CXCR4-positive and -negative cancers (P = 0.111). CONCLUSIONS: More than half of invasive squamous cell vulvar cancers can be expected to express CXCR4, and CXCR4 expression correlates with poor disease prognosis.

Large or persistent lymphocyst increases the risk of lymphedema, lymphangitis, and deep vein thrombosis after retroperitoneal lymphadenectomy for gynecologic malignancy.

PURPOSE: This retrospective study examined the incidence of lymphocyst formation after retroperitoneal lymphadenectomy in patients with gynecologic malignancy as well as the relation between lymphocyst formation and such complications as lymphedema, lymphangitis, ileus, and deep vein thrombosis (DVT). METHODS: Three hundred twenty-one patients who underwent primary surgery with pelvic (90 patients) or combined pelvic and paraaortic lymphadenectomy (231 patients) for gynecologic malignancy between January 2001 and December 2009 were enrolled. The incidences of lymphocyst identified by computed tomography at 3 weeks and 1 year after surgery were analyzed in relation to the types of surgery and types of complications. RESULTS: At 3 weeks after surgery, lymphocysts were observed in 282/321 patients (88 %). At 1 year after surgery, lymphocysts persisted in 69 patients (21 %). Lymphedema was observed in 34/321 (11 %) patients, lymphangitis in 36/321 (11 %), ileus in 14/321 (4 %), and DVT in 24/321 (7 %). The incidence of lymphedema was significantly greater in patients with persistent lymphocyst than in those with without (17 vs. 9 %) (p = 0.038); the incidences of lymphangitis (20 vs. 9 %) (p = 0.007) were also greater in this group. Multivariate analysis showed a large lymphocyst (>50 mm) at 3 weeks after surgery to be an independent risk factor for lymphedema (odds ratio 2.76, p = 0.009). CONCLUSIONS: A large lymphocyst at 3 weeks after surgery or persistent lymphocyst increases the risk of lymphedema, lymphangitis, and DVT.

Torsion of a hydrosalpinx in a virgin patient with Mayer-Rokitansky-Küster-Hauser syndrome: report of a rare condition and its possible etiology.

BACKGROUND: To describe a rare case of hydrosalpinx torsion in a virgin patient with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. CASE: A 25-year-old woman with previously diagnosed MRKH syndrome in whom lower abdominal pain led to discovery and resection of a hydosalpinx of unusual origin in a university hospital department of obstetrics and gynecology, Japan. RESULTS AND CONCLUSIONS: Laparoscopy revealed a twisted left-sided hydrosalpinx, and the mass was resected laparoscopically. Results of the blood test for Chlamydia trachomatis were positive, but results of the PCR test were negative. Our case was unusual in that hydrosalpinx is rare in virgin patients with MRKH. The cause of the hydrosalpinx was unclear, but one possibility is excess tubal secretions from the fallopian tube.

Preoperative management of patients with gynecologic malignancy complicated by existing venous thromboembolism.

OBJECTIVES: In treating gynecologic malignancies, we sometimes encounter patients in whom venous thromboembolism (VTE) has developed before surgery. Few reports exist on preoperative management of VTE. We conducted a study to determine the optimum preoperative management strategy for patients with gynecologic malignancy and existing VTE. STUDY DESIGN: We reviewed the clinical records of patients treated between April 2004 and March 2010 in the Department of Obstetrics and Gynecology at Mie University Hospital. During this period, 654 exploratory or therapeutic laparotomies were performed for gynecologic malignancy. All patients were assessed by ultrasound for VTE before and after surgery. Twenty-five of the 654 patients (3.8%) had preoperative VTE. We reviewed the 25 cases and evaluated the management method and outcomes in terms of VTE. RESULTS: Most preoperative VTEs were located in a crural vein (23 cases; 92%); only 2 (8%) were in a pelvic vein. Three patients were excluded from the study because they had only a small organized thrombus and were treated with VTE prophylaxis according to American College of Chest Physicians (ACCP) guidelines. The other 22 patients were given graduated compression stockings and began anticoagulation therapy with heparin (unfractionated heparin or heparin calcium) immediately after the VTE diagnosis. Anticoagulation therapy was continued until a mean 8.5h before surgery and then restarted 10h (mean) after surgery. Sixteen of the 22 patients were treated by intermittent pneumatic compression during and after surgery. This management strategy resulted in six cases (27%) of diminished VTE, 10 cases (46%) without remarkable change, and six cases (27%) of deterioration. Clinical deterioration occurred in two of the 22 cases (9%), i.e., PE or pelvic VTE developed. CONCLUSIONS: Our preoperative management of existing VTE appears to be insufficient. Shorter or no interruption of antithrombotic therapy and/or another intervention such as inferior vena cava filter placement may be necessary in patients with preoperative VTE.

A case of usual (basaloid)-type vulvar intraepithelial neoplasia that failed to respond to imiquimod cream: clinical implications.

The authors report a case of usual-type (basaloid-type) vulvar intraepithelial neoplasia (VIN) 3 that failed to respond to imiquimod cream. A 51-year-old Japanese woman visited her local gynecologist complaining of vulvar itching. Atypical cells were noted in cytology smears, but nine vulvar biopsy specimens showed benign proliferation of epithelial tissue. The patient was placed under careful observation for 8 months, when the vulvar smears once again showed atypical cells and biopsy specimens revealed VIN3. The patient was then referred to our hospital where she was given a diagnosis of VIN 3, basaloid type of usual type. The biopsy specimens were positive for p16 and the lesions were confirmed to be human papilloma virus (HPV)-related. We recommended simple vulvectomy but the patient requested conservative treatment with imiquimod cream. With her written informed consent, we prescribed imiquimod cream to be self-administered 3 times a week. Colposcopy and pap smear test were performed every 2 weeks. Four weeks after the start of treatment, a fingertip-sized papule was detected at the patient's vaginal introitus. By 6 weeks, the lesion had enlarged, and biopsy specimens revealed invasive squamous cell carcinoma. At 7 weeks, we performed simple vulvectomy. The surgical specimen showed stage pT1b keratinizing-type squamous cell carcinoma. HPV-16 DNA was detected in the specimen.

Efficacy of a sodium hyaluronate-carboxycellulose membrane (seprafilm) for reducing the risk of early postoperative small bowel obstruction in patients with gynecologic malignancies.

OBJECTIVE: To evaluate the effect of a sodium hyaluronate and carboxymethylcellulose membrane (Seprafilm) on early postoperative small bowel obstruction (EPSBO) in patients with gynecologic malignancies. METHODS: One hundred forty-five patients who had Seprafilm placed during gynecological surgery between April 2002 and March 2007 (Seprafilm group) were compared with a historical control group of patients managed without Seprafilm between January 1997 and March 2002. All patients undergoing primary surgery with pelvic or combined pelvic and para-aortic lymphadenectomy for gynecological malignancies were retrospectively assessed for EPSBO and surgical infections. RESULTS: The incidence of EPSBO was significantly lower (P < 0.05) in the Seprafilm group (3.1%, 6/191) than in the control group (13.9%, 25/180). According to logistic regression analysis, the use of Seprafilm (odds ratio, 0.18; 95% confidence interval, 0.07-0.47; P < 0.0005) and the performance of pelvic lymphadenectomy alone (odds ratio, 0.27; 95% confidence interval, 0.09-0.78; P < 0.02) were independent predictors of a lower rate of EPSBO. The incidence of surgical infection showed no significant difference between the Seprafilm group (3.6%) and the control group (6.7%). CONCLUSIONS: Placement of Seprafilm helped to prevent EPSBO and had no significant adverse effect on surgical infections in patients who underwent lymphadenectomy for gynecological malignancy.

Case of mature cystic teratoma of the greater omentum misdiagnosed as ovarian cyst.

The teratoma of the greater omentum is a very rare entity. We present a case of mature cystic teratoma of the greater omentum misdiagnosed as ovarian cyst. The patient was a 36-year-old woman with an omental teratoma of 5 x 4 x 4 cm and an atrophic left ovary. The histopathologic diagnosis was mature cystic teratoma of the greater omentum and no evidence of immaturity or malignancy was noted. Preoperative tumor marker tests revealed moderate elevation of cancer antigen (CA)125, CA19-9 and carcinoembryonic antigen. The left ovary of the patient was atrophic and possible autoamputation of the ovarian tissue might be suggested.

A pilot study of neoadjuvant chemotherapy with mitomycin C, etoposide, cisplatin, and epirubicin for adenocarcinoma of the cervix.

BACKGROUND: To evaluate the efficacy and toxicity of the combination of mitomycin C, etoposide, cisplatin, and epirubicin (MEPA) as neoadjuvant therapy for patients with cervical adenocarcinoma. METHODS: Fourteen patients with cervical adenocarcinoma received neoadjuvant MEPA therapy followed by radical hysterectomy. The International Federation of Gynecology and Obstetrics stage was: IB1 in 2 patients, IB2 in 5, and IIB in 7. The MEPA regimen consisted of mitomycin C (15 mg/m2) on day 1, etoposide (70 mg/m2) on days 1 to 3, cisplatin (15 mg/m2) on days 1 to 5, and epirubicin (30 mg/m2) on day 1, with this course being repeated every 4 weeks. After two or three courses of chemotherapy, all patients underwent radical hysterectomy. Postoperative radiotherapy was given to 6 patients who showed risk factors at surgery. RESULTS: Of the 14 patients, 7 had complete remission (CR) clinically, 6 had partial remission, and only 1 showed no change. Examination of surgical material revealed no residual disease in 6 patients, and microscopic residual disease (<5 mm) in 2 patients. The patients who had no residual disease or microscopic disease in their hysterectomy specimens showed a significantly longer survival than those with macroscopic residual disease (P = 0.012). The dose-limiting toxicity was myelosuppression. Of the 33 treatment cycles administered, leukopenia of grade 3 or more occurred in 70%,and thrombocytopenia of grade 3 or more occurred in 79%. There were no therapy-related deaths. CONCLUSION: Although severe myelosuppression was also observed, there was a satisfactory response rate to MEPA therapy, which showed a good pathological CR rate.

Presentation of a major histocompatibility complex class 1-binding peptide by monocyte-derived dendritic cells incorporating hydrophobized polysaccharide-truncated HER2 protein complex: implications for a polyvalent immuno-cell therapy.

Recognition of the essential role of dendritic cells (DCs) as professional antigen-presenting cells has prompted investigators to search for methods to use DCs as natural adjuvants in immunotherapy. A number of antigenic oligopeptides, recognized by CD8(+) cytotoxic T lymphocytes (CTLs) specific for cancer cells, have been applied in clinical trials using DCs. Such a monovalent vaccine with a single epitope for a particular type of HLA class 1 molecule would be effective. However, a polyvalent vaccine might be more potent. We designed a novel protein delivery system consisting of hydrophobized polysaccharides complexed with target proteins. The truncated HER2 protein encompassing 147 N-terminal amino acids, including the 9-mer HER2p63-71 peptide (HER2p63), TYLPTNASL, the human homologue of an antigenic murine tumor rejection peptide, was prepared. We report here that HLA-A2402(+) DCs could incorporate hydrophobized polysaccharide-truncated HER2 protein complexes and process the protein to present major histocompatibility complex class 1-binding HER2p63 peptide. The complexes enter DCs by phagocytosis, and then the truncated protein is processed through a pathway similar to that for endogenous proteins. DCs sensitized by these complexes primed and boosted HER2p63-specific CD8(+) T cells in the context of HLA-A2402. Vaccination with DCs incorporating these complexes completely suppressed lung metastases in a HER2-expressing murine tumor model. We also generated 3 CD4(+) clones reactive with different HER2- derived 25-mer peptides from lymph node cells in mice treated with CHP/HER2-147. Thus, hydrophobized polysaccharide-protein complexes are promising candidates for the construction of polyvalent vaccines.