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Introduction: The mortality due to uterine cervical cancer has been gradually increasing in women under 40 years of age (U40) in Japan. We investigated the effect of high-risk human papillomavirus (HR-HPV) on U40 subjects without any overt cytological abnormalities. Materials and Methods: We retrospectively examined the clinical data, including the findings of a cobas 4800 HPV test that was approved in Japan in 2013 to triage women with atypical squamous cells of undetermined significance (ASC-US) and a histological examination in 589 Japanese women. Results: The overall prevalence rate of HR-HPV was 34.5%. Biopsy-confirmed cervical intraepithelial neoplasia (CIN) 2, or worse (CIN2+) was identified in 45.1% (23/51) of HR-HPV-positive women with ASC-US, who underwent colposcopy immediately. The mean period from the HPV test to the diagnosis of CIN2+ was 3.7 months. CIN2+ was more common (69.6%) in U40 patients. The rates of single or multiple infections of HPV-16, HPV-18, and 12 other HR-HPV (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) in CIN2+ U40 patients were 31.3%, 0%, and 81.3%, respectively. The relative risk for CIN 2+ among U40 women with HPV-16 was not significantly different from that of the patients with infection of any of the 12 other HR-HPVs. Conclusion: The results of this study suggest that the 12 other HR-HPVs have a potential to generate high-grade cervical lesions among young women, and the examination rate of colposcopy should be increased.

Introduction: The mortality due to uterine cervical cancer has been gradually increasing in women under 40 years of age (U40) in Japan. We investigated the effect of high-risk human papillomavirus (HR-HPV) on U40 subjects without any overt cytological abnormalities. Materials and Methods: We retrospectively examined the clinical data, including the findings of a cobas 4800 HPV test that was approved in Japan in 2013 to triage women with atypical squamous cells of undetermined significance (ASC-US) and a histological examination in 589 Japanese women. Results: The overall prevalence rate of HR-HPV was 34.5%. Biopsy-confirmed cervical intraepithelial neoplasia (CIN) 2, or worse (CIN2+) was identified in 45.1% (23/51) of HR-HPV-positive women with ASC-US, who underwent colposcopy immediately. The mean period from the HPV test to the diagnosis of CIN2+ was 3.7 months. CIN2+ was more common (69.6%) in U40 patients. The rates of single or multiple infections of HPV-16, HPV-18, and 12 other HR-HPV (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) in CIN2+ U40 patients were 31.3%, 0%, and 81.3%, respectively. The relative risk for CIN 2+ among U40 women with HPV-16 was not significantly different from that of the patients with infection of any of the 12 other HR-HPVs. Conclusion: The results of this study suggest that the 12 other HR-HPVs have a potential to generate high-grade cervical lesions among young women, and the examination rate of colposcopy should be increased.

HPV16 Asian variant (HPV16As) containing E6D25E oncogene, is commonly associated with cervical cancers of Asian populations. To explore a mechanism of E6D25E oncoprotein in carcinogenesis, we compared protein profiles in human keratinocytes expressing E6D25E with E6 of HPV16 prototype (E6Pro). A human cervical keratinocyte cell line, HCK1T, was transduced with retroviruses containing E6D25E or E6Pro genes. Biological properties of E6D25E or E6Pro transduced HCK1T cells were characterized. Protein profiles of the transduced HCK1T cells were analyzed using 2D-PAGE and characterized by mass spectrometry and western blotting. Reactomes of modulated proteins were analyzed by using the Reactome Knowledgebase. The E6D25E and E6Pro oncoproteins were comparable for their abilities to degrade p53 and suppress the induction of p21, and induce cell proliferation. Interestingly, the protein profiles of the HCK1T cells transduced with E6D25E showed specific proteomic patterns different from those with E6Pro. Among altered proteins, more than 1.5-fold up- or down- regulation was observed in E6D25E-expressing cells for gp96 and keratin7 which involved in activation of TLR signaling and transformation of squamocolumnar junction cells, respectively. This report describes new cellular proteins specifically targeted by E6D25E oncoprotein that may contribute to impair immune response against viral infection and cell transformation associated with oncogenic property of HPV16As variant.

Background and Objectives The aim of this study was to compare the clinical efficacy of paclitaxel/cisplatin (TP) as an adjuvant chemotherapy to adjuvant radiotherapy (RT) after radical hysterectomy and systematic lymphadenectomy for patients with cervical cancer. Methods A total of 125 patients with early-stage cervical cancer, who underwent radical hysterectomy, and received adjuvant therapy due to recurrent risk factors were retrospectively analyzed. Forty-nine patients were treated with RT, and 32 received paclitaxel/cisplatin (TP) for three to six cycles at 4-week interval. Survival and postoperative complications were compared between two modalities. Results There was no significant difference of 3-year disease-free survival between two groups (P = 0.23), while significantly better 3-year overall survival in TP group than RT group (P = 0.02). Seven of 32 patients (21.9%) treated with adjuvant TP, 16 of 49 patients (32.7%) treated with RT showed disease recurrence. Median of survival time after recurrence in RT group and TP group was 8.5 months, 12.0 months, respectively. Postoperative bowel obstruction was significantly more frequent in the RT group compared to the TP group (P = 0.01). Conclusions Postoperative chemotherapy using TP might be more beneficial for survival than adjuvant RT and can reduce postoperative complications for cervical cancer patients treated with radical hysterectomy. J. Surg. Oncol. 2012; 105:612–616. © 2011 Wiley Periodicals, Inc.

Growing teratoma syndrome (GTS) is defined as enlarging masses during or after chemotherapy for germ cell tumors, and containing only mature teratoma components. A surgical resection is important to confirm a diagnosis and thereby result in the resection of the most appropriate therapeutic management. GTS is a rare event in association with ovarian germ cell tumors. This report presents a case of a 36-year-old female treated surgically for GTS found during the follow-up after chemotherapy and the primary surgical resection of a malignant immature teratoma. Those masses showed fluorodeoxyglucose positron emission tomography positivity and elevated serum CA19-9 prior to the second operation. The histology revealed a mature teratoma. The patient has been disease free for 6 months after the second operation.

Objective: Considered to be a cause of unexplained chronic pelvic pain, appendiceal endometriosis is relatively rare, accounting for only 3% of all pathologic lesions of this disorder. In this study, we analyzed the clinicopathologic findings of resected appendices with an abnormal appearance discovered during laparoscopic surgery for endometriosis.Patients and Methods: We performed laparoscopic surgery on 309 patients with endometriosis between January 2006 and December 2008 in Hokkaido University Hospital and its affiliated hospitals. Nineteen patients underwent laparoscopic appendectomy after careful pathologic inspection of their appendices.Results: An abnormal appendiceal appearance was found in 17 of 19 patients; the remaining 2 patients possessed no superficial appendiceal abnormalities but had chronic pelvic pein. Of 17 cases with abnormal appendiceal appearance, 16 (94.1%) had pathological abnormalities: appendiceal endometriosis was found in 12 cases and appendicitis in 4 cases. Two patients affected by chronic pelvic pain with normal appendiceal appearances had appendices with no pathological abnormalities. The prevalence of appendiceal endometriosis in this study was 3.9% (12/309). All patients with appendiceal endometriosis had endometriomas. Neither conversion to open surgery nor treatment for surgical complication was necessary.Conclusion: Laparoscopic appendectomy is an appropriate procedure for patients with endometriosis if they have abnormal appendiceal appearances. During laparoscopic surgery for endometriosis, especially in the case of endometrioma, close observation of the appendix may allow surgeons to remove endometriotic lesions more thoroughly.

Objective: To evaluated the utility and safety of the Cavitron ultrasonic surgical aspirator (CUSA) for laparoscopic paraaortic lymphadenectomy in gynecologic malignancies.Methods: Between January 2007 and January 2008, we performed laparoscopic treatment of gynecologic cancer in 22 patients. In all patients, laparoscopic lymphadenectomy was included in the surgical procedures. In 10 of 22 patients, CUSA was used for the dissection of the left-sided para-aortic lymph nodes. The range of lymphadenectomy was up to the renal vein for patients with endometrial and ovarian cancers, and up to the inframesentric artery for patients with cervical cancer. We analyzed the number of removed lymph nodes and the time needed for the procedure. The results in the group with CUSA and those without CUSA were compared.Result: The number of lymph nodes removed was equivalent between the groups, irrespective of the range of lymphadenectomy. However, the operative time was shortened in the group with CUSA. We had no particular complications in either group.Conclusion: We safely performed laparoscopic lymphadenectomy using CUSA. There is a possibility that by using CUSA, the time required for laparoscopic lymphadenectomy may be shortened.

Growing teratoma syndrome (GTS) is defined as enlarging masses during or after chemotherapy for germ cell tumors, and containing only mature teratoma components. A surgical resection is important to confirm a diagnosis and thereby result in the resection of the most appropriate therapeutic management. GTS is a rare event in association with ovarian germ cell tumors. This report presents a case of a 36-year-old female treated surgically for GTS found during the follow-up after chemotherapy and the primary surgical resection of a malignant immature teratoma. Those masses showed fluorodeoxyglucose positron emission tomography positivity and elevated serum CA19-9 prior to the second operation. The histology revealed a mature teratoma. The patient has been disease free for 6 months after the second operation.

2020