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To develop a new therapeutic strategy for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancers, we evaluated the feasibility and efficacy of irinotecan and gemcitabine combination chemotherapy.Patients with taxane/platinum-resistant/refractory cancer received escalating doses of irinotecan and gemcitabine (level 1: 80 and 800 mg/mA total of 35 patients were enrolled. The recommended dose was defined as 100 mg/mCombination chemotherapy with irinotecan and gemcitabine represents a safe and effective treatment combination for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancers.

Background Finding ways to improve the cervical cancer screening rates among young women has been seen as a critical national health problem in many countries, including Japan. The aim of the present study was to evaluate the effects of a free-coupon program for cervical cancer screening conducted by a local government under financial support from the Japanese national government. Methods The personal cervical cancer screening information was analyzed for all female residents of Toyonaka City, including any past screening history and clinical results since the year 2009, when a free-coupon program for screening was started. These results were compared to results from 2008, prior to implementation of the free-coupon screening program. Results The screening rates of women eligible for the free-coupon peaked dramatically compared to women of similar age who paid for their screening; however, the rates for the ineligible-age population also increased significantly in parallel to those in the free-coupon program, possibly by indirect peer and publicity effects. In women aged 20 to 25 years, the consecutive screening rate after a free-coupon screening was significantly lower than for those women who received a regular residential screening. After a free-coupon screening, the rate for participating in consecutive screenings depended significantly on the institution where the participant received her first screening test. Conclusions These results suggest that, for a generation of young women 20–25 years of age, a free-coupon program for cervical cancer screening was effective in increasing the first-time participation rate for screening; however, the increase in first-time participation did not lead to the expected increase in consecutive screenings.

Patients with Swyer syndrome, which is also known as 46,XY pure gonadal dysgenesis, are at an increased risk of gonadoblastoma and germ cell tumor. Prophylactic gonadectomy is recommended for these patients. We report a case of stage IIA dysgerminoma arising in a streak gonad in a patient with Swyer syndrome, which was not diagnosable preoperatively and intraoperatively. The patient was primarily amenorrheic and identified as female phenotypically. She underwent gonadectomy at 27 years of age. Preoperative image analysis showed a relatively small uterus without adnexal masses. Laparoscopic findings showed bilateral streak gonads. Postoperatively, histopathological examination revealed that the patient had dysgerminoma in her left streak gonad. Preoperative and intraoperative diagnosis of dysgerminoma in normal size ovaries is thought to be difficult. Although it is rare, considering the occurrence of dysgerminoma in streak gonad with extension to the mesosalpinx, prompt prophylactic gonadectomy is strongly recommended for these patients regardless of the size of the ovaries.

Background In 2014–2015, 242 individuals aged 2–89 years were newly diagnosed with human immunodeficiency virus type 1 (HIV-1) in Roka, a rural commune in Cambodia. A case-control study attributed the outbreak to unsafe injections. We aimed to reconstruct the likely transmission history of the outbreak. Methods We assessed in 209 (86.4%) HIV-infected cases the presence of hepatitis C virus (HCV) and hepatitis B virus (HBV). We identified recent infections using antibody (Ab) avidity testing for HIV and HCV. We performed amplification, sequencing, and evolutionary phylogenetic analyses of viral strains. Geographical coordinates and parenteral exposure through medical services provided by an unlicensed healthcare practitioner were obtained from 193 cases and 1499 controls during interviews. Results Cases were coinfected with HCV (78.5%) and HBV (12.9%). We identified 79 (37.8%) recent ( Conclusions Unsafe injections in Cambodia most likely led to an explosive iatrogenic spreading of HIV, associated with a long-standing and more genetically diverse HCV propagation.

Objective To analyze the efficacy and safety of combination chemotherapy of docetaxel and irinotecan for paclitaxel and carboplatin (TC) -refractory or -resistant ovarian carcinomas and for first treatment of primary clear cell and mucinous ovarian carcinomas. Study design Between 2002 and 2009, we conducted a prospective Phase II study of the efficacy and safety of combination chemotherapy using docetaxel and irinotecan in 62 patients with TC-refractory or -resistant ovarian carcinoma cases (GOGO-OV2) and 15 patients with primary clear cell and mucinous ovarian carcinoma cases (GOGO-OV3). The dose of docetaxel and irinotecan was determined during our previous Phase I study. Results A docetaxel plus irinotecan regimen provided a 53% response rate, 6 months progression-free survival (PFS), and 12 months overall survival (OS) for primary clear cell and mucinous ovarian carcinomas (similar to TC therapy). The differences of anti-tumor and survival effects between refractory and resistant cases were not statistically significant. The regimen also provided a 15% response rate, 5 months PFS, and 15 months OS for TC-refractory or TC-resistant cases, when used as a second-line chemotherapy. These data are similar to previous reports, however, our study provides the first data exclusively for the cases refractory or resistant to a gold standard TC therapy as a second-line chemotherapy. The regimen was demonstrated to be well tolerable. Conclusion Combination chemotherapy of docetaxel and irinotecan may be a useful option to treat TC-refractory/resistant cases and primary clear cell and mucinous adenocarcinoma cases of ovarian carcinoma.

Antiretroviral therapy (ART) retention and 5 early-warning indicators (EWIs) of HIV drug resistance (HIVDR) were abstracted at 27 adult and 4 pediatric clinics in Vietnam in 2009. Of 4531 adults and 313 children, 81.2% and 84.4% respectively were still on ART at 12 months. More than 90% of the clinics monitored achieved the World Health Organization (WHO) targets for lost-to-follow-up (LTFU), ART prescribing practices, and ARV supply continuity. Only 83.9% of the clinics met the target for first-line ART retention and 79.3% met the target for clinic appointment-keeping. Clinic factors (i.e. number of patients, administrative level, and geographical region) were associated with ART retention and LFTU. Data were useful in guiding public health action to optimize ART services.

Purpose Recently a combination of paclitaxel and carboplatin (TC) (without an anthracycline) has begun to be used as an adjuvant or remission induction therapy, without any critical supportive evidence of its efficacy relative to a combination chemotherapy of taxane, platinum and anthracycline such as TEC (paclitaxel, epirubicin and carboplatin). The aim of our present study was to conduct the required clinical evaluations of the relative effectiveness of TC compared to TEC. Methods A retrospective comparison between the efficacy of TEC and TC regimens used for endometrial carcinoma at the Osaka University Hospital and the Osaka Medical Center for Cancer and Cardiovascular Diseases in Osaka, Japan, respectively, from 1999 to 2009 was performed. The clinical characteristics of the patients who received either TEC or TC were not significantly different, and TEC and TC therapies were initiated based on similar indications for chemotherapy. TEC regimen was paclitaxel (150 mg/m2), epirubicin (50 mg/m2) and carboplatin (AUC 4). TC regimen consisted of paclitaxel (175 mg/m2) and carboplatin (AUC 5). Results TEC was demonstrated to provide significantly better survival than TC as an adjuvant therapy for resected Stage III/IV diseases (p = 0.017 for progression-free survival and p = 0.014 for overall survival, by the log-rank test). However, in recurrent or more advanced cases, TC and TEC demonstrated similar effects on survival (p = 0.55 for progression-free survival and p = 0.63 for overall survival). Conclusions TEC should be offered as an adjuvant therapy to Stage III/IV patients. TC may be considered for recurrent or unresectable cases as a remission induction therapy.

The aim of the present study was to analyze the long-term outcome of cervical intraepithelial neoplasia 3 (CIN 3) after treatment with the Shimodaira-Taniguchi conization procedure, based on the status of the resection margins.In the Osaka University Hospital, conization using the Shimodaira-Taniguchi procedure has been routinely performed for CIN 3. Medical records of patients during the period from 2001 to 2008, whose post-conization diagnosis was CIN 3, were retrospectively analyzed for outcome versus margin status.During the median follow-up period of 565 days (range 34-3,013), CIN disease was again detected in 14 of 243 patients; it was found in 7 patients among 198 margin-negative cases, and in 7 patients among 45 margin-positive cases. There was a significant difference in the reappearance rate demonstrated between the cases with positive and negative margins (p = 0.0018). Among the patients whose first follow-up post-conization cytology was normal, recurrence-free probability was significantly higher in margin-negative cases than in margin-positive ones (hazard ratio, 5.19; 95% CI, 1.175-22.994; p = 0.0041).For the first time, we demonstrate that after treatment of CIN 3 lesions by Shimodaira-Taniguchi conization the status of the resection margin was a significant predictor for long-term outcome.

A primary retroperitoneal mucinous cystadenocarcinoma (PRMC) is an extremely rare lesion. To date, only 49 cases have been reported. The presence of mural nodules in a PRMC may indicate a worse prognosis. We report the case of a 40-year-old Japanese woman with a PRMC with mural nodules. Microscopic examination revealed that the stromal cells of the nodules were spindle-shaped and varied in size. The nodules were immunoreactive for vimentin but negative for cytokeratin and EMA, and the nuclei of the stromal cells were pleomorphic and strongly Ki-67 immunoreactive. The nodules were diagnosed as true sarcoma. To the best of our knowledge, this is 11th published case report of a PRMC with mural nodules.

Katsuya Suzuki1, Shigekazu Tsubaki2, Masami Fujita3, Naoto Koyama1, Michio Takahashi1, Kenji Takazawa41Research Institute for Health Fundamentals, Ajinomoto Co., Inc., Kawasaki; 2Samoncho Clinic, Tokyo; 3Shinanozaka Clinic, Tokyo; 4Tokyo Medical University Hachioji Medical Center, Tokyo, JapanAbstract: Safflower seed extract (SSE) contains characteristic polyphenols and serotonin derivatives (N-(p-coumaroyl) serotonin and N-feruloylserotonin), which are reported to inhibit oxidation of low-density lipoprotein (LDL), formation of atherosclerotic plaques, and improve arterial stiffness as assessed by pulse wave analysis in animal models. The effects of long-term supplementation with SSE on arterial stiffness in human subjects were evaluated. This double-blind, placebo-controlled study was conducted in 77 males (35–65 years) and 15 postmenopausal females (55–65 years) with high-normal blood pressure or mild hypertension who were not undergoing treatment. Subjects received SSE (70 mg/day as serotonin derivatives) or placebo for 12 weeks, and pulse wave measurements, ie, second derivative of photoplethysmogram (SDPTG), augmentation index, and brachial-ankle pulse wave velocity (baPWV) were conducted at baseline, and at weeks 4, 8, and 12. Vascular age estimated by SDPTG aging index improved in the SSE-supplemented group when compared with the placebo group at four (P = 0.0368) and 12 weeks (P = 0.0927). The trend of augmentation index reduction (P = 0.072 versus baseline) was observed in the SSE-supplemented group, but reduction of baPWV by SSE supplementation was not observed. The SSE-supplemented group also showed a trend towards a lower malondialdehyde-modified-LDL autoantibody titer at 12 weeks from baseline. These results suggest long-term ingestion of SSE in humans could help to improve arterial stiffness.Keywords: safflower, serotonin derivatives, antioxidants, augmentation index, pulse wave velocity

Objective To clarify the frequency of pregnancy complicated by ovarian endometriosis and to investigate the size change and outcome of ovarian endometriosis during pregnancy. Design Retrospective study. Setting Departments of obstetrics and gynecology of the Osaka University and Izumiotsu Municipal Hospitals of Osaka, Japan. Patient(s) Women who delivered between 1996 and 2007. Intervention(s) None. Main Outcome Measure(s) The frequency of pregnancies complicated by ovarian endometriosis and the size change of the lesions during pregnancy. Result(s) The frequency of ovarian endometriosis-complicated pregnancy has almost quadrupled over the last 12 years, to become the most common adnexal mass detected during pregnancy; it was 0.14% (five cases among 3558 deliveries) during the 6-year period from 1996 to 2001, but has increased to 0.52% (19 cases among 3599 deliveries) during the 6-year period from 2002 to 2007, a statistically significant increase of 3.8-fold. Among 25 ovarian endometriotic lesions observed during pregnancy in 24 women (one case had two lesions), the size of the cyst decreased in 13 lesions (52%), went unchanged in 7 (28%), and increased in 5 (20%), that demonstrated decidualization, abscess and rupture. Conclusion(s) Ovarian endometriosis during pregnancy can be safely observed conservatively; however, further investigation is required to predict the occurrence of abscess formation or rupture of ovarian endometriosis, and to distinguish the enlargements due to malignant transformation from those related to decidualization.

The aim of this study was to evaluate the efficacy of paclitaxel-carboplatin (TC) for recurrent cervical cancer after definitive radiotherapy and to compare the results with non-taxane containing platinum-based chemotherapies (NTP).The records of 59 consecutive women who had undergone salvage chemotherapy with TC (n=28) or NTP (historical control, n=31) for recurrence after definitive radiotherapy were retrospectively reviewed. Primary disease and recurrence data was collected. The activity and toxicity of TC were compared with those of NTP. The response rate and progression-free survival (PFS) after recurrence were the main endpoints. Multivariate analysis of prognostic factors for response was performed using the Cox proportional hazards regression model. Survival was calculated using the Kaplan-Meier methods and compared by the log-rank test.Overall, TC was well tolerated with a response rate of 67.9% (5 CR and 14 PR). The median PFS was 7 months for all patients and 10 months for responders. Myelosuppression was the most common toxicity (grade 3 in 16 patients, grade 4 in 5 patients). On the contrary, NTP showed a response rate of 22.6% with median and mean PFS of 0 month and 2 months, respectively. When compared, TC was significantly superior to NTP with regard to its response rate (p=0.001) and PFS (p0.0001). Moreover, TC showed significantly higher activity in patients with adenocarcinoma histology.Carboplatin-paclitaxel is active and well tolerated in patients with recurrent cervical cancer after definitive radiotherapy. This combination should be considered as an alternative regimen to cisplatin-paclitaxel in this patient population.

BackgroundA lymphocyst (lymphocele) is a common complication of lymphadenectomy, which is a widely used surgical method for gynecologic cancers. In cases of infected lymphocysts, therapeutic strategies, including the timing and duration of antibiotics administration and cyst drainage, may vary depending on the physician. The aim of this study was to determine the optimal timing for drainage of lymphocysts infected with bacteria resistant to antibiotic treatment.Materials and MethodsClinical data for 1175 patients who underwent a lymphadenectomy as part of surgery for a gynecologic malignancy between April 2000 and August 2012 at Osaka University Hospital, Osaka, Japan, were analyzed.ResultsOf the 282 patients who developed a lymphocyst (24%), 35 with infected lymphocysts (12%) were analyzed. Lymphocyst infection was not associated with tumor origin, type of hysterectomy, or region of lymphadenectomy (P = 0.81, P = 0.59, and P = 0.86, respectively). The total treatment period of cases treated only with antibiotics tended to be shorter than that of cases treated with combined antibiotics and drainage, but the difference was not significant (P = 0.061). However, for severe cases which needed drainage, initiating the drainage by day 5 significantly shortened the total treatment period compared with cases started on or after day 6 (P = 0.042).ConclusionsThe appropriate time point for initiating lymphocyst drainage has been difficult to determine. The present study implies that for severe lymphocyst infections, where drainage is required in addition to antibiotics, the earlier the drainage is performed, the shorter the treatment period is. Further studies may be required to decide other optimal treatment strategies for infected lymphocysts.

The present study aimed at evaluating the usefulness and adverse effects of duloxetine treatment for paclitaxel-induced peripheral neuropathy in gynecological cancer patients.Medical records of gynecological cancer patients treated with duloxetine were retrospectively studied to evaluate the drug's efficacy for paclitaxel-induced peripheral neuropathy.RESULTS from 25 patients showed that an improved response was observed in 14 (56%). By univariate and multivariate analysis, the patient's age, tumor origin, regimen of chemotherapy, accumulated doses of paclitaxel or carboplatin, previous medication, maintenance dosage and timing of treatment with duloxetine were found not to be associated with the effectiveness of duloxetine treatment. Adverse effects with duloxetine were mild and well-tolerated.As an option, duloxetine can be effectively used for paclitaxel-induced peripheral neuropathy in patients with gynecological cancers, irrespective of patients' age, origin of the tumor, regimen of chemotherapy, or previous medication.

To analyze clinical characteristics of venous thromboembolisms (VTE) in gynecological malignancies, and to find a cost-effective prophylaxis procedure for post-operative VTE.We analyzed clinical characteristics of 751 patients who underwent definitive surgery for gynecologic malignancies, and cost-effectiveness of VTE prophylaxis.VTE was diagnosed preoperatively in 4.5% of ovarian cancer cases, more frequently than any other type (p0.005). Older age and greater length of operation were independent risk factors for postoperative VTE. To prevent eight VTEs in 738 malignant cases, which occurred during day 2 to 10, $617,783, $726,185, or $994,222 were necessary for continuous VTE prophylaxis, using either unfractionated heparin (UFH), low-molecular weight heparin or fondaparinux, respectively.A strategy which might be cost-effective for post-surgical management of gynecological malignances is use of UFH three times combined with graduated compression stockings and intermittent pneumatic compression, thorough SpO2 monitoring, and perioperative measurements of the circumference of both sides of thighs and calves.

We retrospectively analyzed oncologic and reproductive outcomes of fertility-seeking premenopausal women with complex atypical hyperplasia (CAH) or Grade 1 endometrial adenocarcinoma (G1EA) who underwent medical management with high-dose medroxyprogesterone acetate (MPA) therapy. Patients were given a dose of 400–600 mg of MPA orally on a daily basis. They had histologically confirmed CAH or G1EA at presumed stage IA and wished to preserve fertility. Endometrial tissue sampling was carried out by dilation and curettage before and after the treatment and the pathologic response to MPA treatment was assessed. A total of 27 premenopausal patients received MPA therapy. The median follow-up time was 39.2 months (3.4–153.8 months). Complete response was achieved in 81.8 % (9/11) of CAH cases and 68.8 % (11/16) of G1EA. Although no recurrences were found in CAH patients, nine G1EA patients (81.8 %) eventually recurred and underwent total hysterectomy. Neither therapeutic death nor irreversible toxicities were observed during the follow-up periods. Five patients (4 CAH and 1 G1EA) became pregnant and had nine live births. The high efficacy of fertility-sparing treatment with MPA was shown demonstrated. MPA therapy can be considered acceptable for the purpose of enabling patients to preserve their fertility. However, the rate of recurrence was high in patients with G1EA. Even in responders, close follow-up is required and a total hysterectomy needs to be considered without delay. Patients should be aware of the risks and limitations of this conservative treatment.

Uterine adenomyoma is often overlooked, and cervical adenomyoma is extremely rare. Previous reports suggest that a uterine adenomyoma usually occurs in the uterine corpus but rarely in the uterine cervix. Approximately 20 reports of cervical adenomyoma have been published to date. However, cervical adenomyoma has been rarely investigated using magnetic resonance imaging. We encountered a large multicystic tumor in the uterine cervix of a 26-year-old woman that was difficult to diagnose preoperatively. On the basis of cytology, biopsy, and imaging findings, the cervical multicystic tumor measured approximately 13.0 cm. The patient underwent vaginal adenomyomectomy, and the tumor was completely resected. A histologic diagnosis of cervical adenomyoma was made because of proliferation of endocervical glands and the presence of rounded smooth muscle stroma. Awareness of this tumor in the uterine cervix is important for accurate diagnosis and treatment. Herein we present a rare case of a large cervical adenomyoma, with imaging studies, an image of the operation, histologic findings, and a literature review.

To investigate the monoclonality of hepatocellular carcinoma (HCC) and dysplastic nodule (DN) and the origin of multiple lesions, patterns of inactivation of X-linked human androgen receptor gene were studied. Fourteen of 15 patients (93%) were heterozygous in the size of the target, and were informative for clonal analysis. Monoclonal composition was demonstrated in all 17 HCCs and two DNs, whereas all non-cancerous hepatic tissues were polyclonal. Of four patients with more than two lesions of HCC or DN, two patients had two lesions with different patterns of X-chromosome inactivation, indicating that the two lesions were multicentric in origin.

Objective The aim of this study was to assess the tolerability, pharmacokinetic and pharmacodynamic properties of DX-9065a, a novel low-molecule specific factor Xa inhibitor in healthy male volunteers. Methods DX-9065a was intravenously administered to healthy male Japanese volunteers at doses of 0.625 to 30 mg. The drug concentrations in plasma and urine were measured and pharmacokinetic parameters were calculated. Coagulation time and bleeding time were also measured. Results No serious adverse event was observed during or after administration of DX-9065a. The pharmacokinetics of DX-9065a in human subjects after intravenous dosing was linear. The simulated plasma concentrations of DX-9065 were well in accordance with the observed values. Though prolongation of coagulation times was dependent on plasma concentration of DX-9065, bleeding time did not increase even at the highest plasma concentration of 1640 ng/mL. Conclusions DX-9065a had a good correlation between linear pharmacokinetics and pharmacodynamics after intravenous administration in humans. Clinical Pharmacology & Therapeutics (1999) 66, 258–264; doi

Simultaneous involvement of the endometrium and the ovary by carcinoma is a familiar problem in the routine practice of surgical pathology. Such cases may be considered either examples of a single primary carcinoma with metastasis or as synchronous primary neoplasms. The distinction between these two possibilities is made based on clinicopathologic observations, and therefore may not be definitive. In the present study, the authors used molecular techniques to analyze the clonal composition of five cases of concurrent adenocarcinomas of the endometrium and ovary that were clinicopathologically diagnosed as synchronous primary tumors. Patterns of X-chromosome inactivation, mutations in the K-ras gene, mutations or allelic loss of the p53 gene, or human papillomavirus detection were identical in both endometrial and ovarian lesions in three of the cases suggesting that those three cases represented single primary tumors with metastases. In both of the other two cases, the patterns of X-chromosome inactivation clearly demonstrated the presence of independent primary tumors. The application of molecular technology may play an important role for the differential diagnosis between synchronous primary carcinomas and a single carcinoma with metastasis.

The purpose of this study was to report on the safety and efficacy of gemcitabine used as salvage chemotherapy for ovarian cancer.From January 2002 to October 2011, 27 patients were treated with gemcitabine for platinum-resistant recurrent ovarian cancer. Gemcitabine (800 mg/m(2)) was given on days 1, 8, and 15 of every 28 days. The patients' medical records were retrospectively reviewed.All 27 patients had previously received paclitaxel/carboplatin doublet and their disease had become platinum-resistant. The median number of previous chemotherapy regimens was 2 (range 1-7). A total of 114 cycles of single-agent gemcitabine were administered, with a median of 3 (range 1-10). No complete responses were observed. Partial response (PR) was observed in five patients (18.5%). Eight patients demonstrated stable disease (SD). The median duration of response for 5 responders was 4 months (range 2-6 months). The median survival time was 15 months. Patients with PR or SD (n=13) had significantly better survival compared with the group with progressive disease (n=14) (p=0.03, by univariate analysis). In addition, multivariate Cox proportional hazards analysis revealed that responses to gemcitabine were a significant factor for survival (hazard ratio=0.08, 95% confidence interval=0.0138 to 0.5614, p=0.01). Cases with hematological toxicity included 10 patients (37.0%) with grade 3/4 neutropenia, 3 patients (11.1%) with grade 3 thrombocytopenia, and 3 patients (11.1%) with grade 3 anemia. Non-hematological toxicity was well-tolerated.Gemcitabine (800 mg/m(2)) used for recurrent ovarian cancer possesses a modest activity and a well-tolerated toxicity.

ObjectiveWe investigated the prognostic significance of multiple pelvic node metastases in cervical cancer patients who were treated with radical hysterectomy plus adjuvant chemoradiotherapy.MethodsWe retrospectively reviewed the medical records of 311 patients with International Federation of Gynecology and Obstetrics stage IB1-IIB cervical cancer who had been treated with radical hysterectomy plus adjuvant radiotherapy (RT) between January 1998 and December 2008. Of these, 119 received adjuvant RT and 192 received adjuvant concurrent chemoradiotherapy (CCRT) postoperatively. Multivariate analysis for progression-free survival (PFS) was performed using the Cox proportional hazards regression model to investigate the prognostic significance of pelvic node metastases in the 2 treatment groups. Survival was calculated using the Kaplan-Meier method and compared using the log-rank test.ResultsMultivariate analysis demonstrated pelvic node metastasis to be an independent prognostic factor for shorter PFS in both treatment groups. When the node-positive patients were analyzed according to the number of positive pelvic nodes, we found that the patients with multiple pelvic node metastases (≥3) displayed significantly shorter PFS than those with 1 or 2 pelvic node metastases in the RT group. In contrast, in the CCRT group, the PFS of the patients with multiple pelvic node metastases (≥3) was similar to that observed of the patients with 1 or 2 pelvic node metastases.ConclusionsThe presence of multiple pelvic node metastases was not an independent predictor of shorter PFS in the CCRT group.

Objective The aim of this study was to identify predictors of the response to paclitaxel-carboplatin chemotherapy (TC) in recurrent or patients with advanced cervical cancer. Methods The records of 61 consecutive women with recurrent or advanced cervical cancer who were treated with TC were retrospectively reviewed. Data regarding their primary disease, follow-up, recurrence, and the activity and toxicity of TC were collected. Multivariate analysis was performed using the Cox proportional hazards regression model to identify predictors of the response to TC. Survival was calculated using the Kaplan-Meier method and compared using the log-rank test. Results Overall, TC was well tolerated and displayed a response rate of 60.7% (19 complete response and 18 partial response). The median progression-free survival was 14 months for all patients and 20 months for the responders. Grade 3 to grade 4 toxicities were observed in 51 patients (83.6%). Multivariate analysis revealed that performance status, symptom status, and prior chemotherapy were independent prognostic predictors of a poor response. Patient survival was inversely correlated with the number of these prognostic factors. When the patients were divided into 2 prognostic groups (low risk: patients with no or one poor prognostic factor; and high-risk: patients with 2 or more poor prognostic factors), the patients in the high-risk group had a significantly shorter progression-free survival than those in the low-risk group (4 vs 16 months, log-rank; P Conclusions The combination of paclitaxel and carboplatin is effective in patients with recurrent or advanced cervical cancer. Our prognostic model composed of 3 clinical variables might enable physicians to identify patients who would not derive clinical benefit from TC and offer them the opportunity to receive other types of treatment.

To clarify the role of the p53 tumor suppressor gene in the development of human ovarian epithelial tumors and to study the association of p53 alterations with K-ras activation, a series of 70 common epithelial ovarian tumors from Japanese patients was studied. These included 31 serous adenocarcinomas, 12 mucinous adenocarcinomas, 5 mucinous tumors of borderline malignancy, 13 endometrioid adenocarcinomas, and 9 clear cell carcinomas. Allelic loss, recognized at the polymorphic site in codon 72 of the p53 gene, was detected in 14 of 36 (39%) informative cases by restriction fragment length polymorphism analysis and by single-strand conformation polymorphism (SSCP) analysis of polymerase chain reaction (PCR)-amplified DNA fragments. Mutations in the highly conserved regions of the p53 gene were detected by SSCP analysis of PCR-amplified fragments. Mutations were found in 22 of 70 (31%) ovarian tumors, including 1 of 5 mucinous tumors of borderline malignancy. Mutations were subsequently characterized by direct sequencing. Single missense base substitutions were detected in 13 ovarian carcinomas and in one case of mucinous tumor of borderline malignancy. Short (1-8 bp) deletions and insertions were found in 8 cases. Mutations in the p53 gene occurred more frequently in serous adenocarcinomas (14/31, 45%) than in all nonserous types of malignant epithelial tumors combined (7/34, 21%; P = 0.032). Point mutations in K-ras were identified by dot blot hybridization analysis of PCR-amplified fragments with mutation-specific oligonucleotides and by direct sequencing. The overall frequency of K-ras mutations was 19/70 (27%). K-ras mutations were found in 12 of 17 (71%) mucinous tumors (8/12 mucinous carcinomas [67%] and 4/5 mucinous tumors of borderline malignancy [80%]), and occurred more frequently than in serous carcinomas (4/31, 13%; P = 0.00009) or in all nonmucinous types of ovarian epithelial tumors combined (7/53, 13%; P = 0.00002). These data suggest that different combinations of oncogenes and/or tumor suppressor genes may be involved in the genesis and development of histologically distinct categories of common epithelial tumors of the human ovary.

To investigate the possibility of sexual transmission of human papillomavirus (HPV), 53 married couples were examined for the presence of HPV-16 and -18 DNAs in the uterine cervix and semen using the polymerase chain reaction method. Twenty-three of the 53 women and 12 of the 53 male partners were positive for HPV-16 DNA. No HPV-18 DNA was detected in samples from any of the partners. In 27 pairs, both partners were negative for HPV DNA in cervix or semen; in the remaining 26 pairs, at least 1 of the partners was HPV-16-positive. In 9 (35%) of these 26 pairs, both partners were infected. Furthermore, 9 (75%) of the 12 women with HPV-positive partners were HPV-positive, while 9 (39%) of the 23 men with HPV-positive female partners were HPV-positive. These findings suggest an increased risk of HPV transmission via sexual intercourse, thereby underscoring the importance of preventive care against HPV infection during intercourse.

A case-control study of 143 Japanese women with uterine endometrial cancer and 143 individually age-matched controls was conducted to assess the risk factors for endometrial cancers in Japan. Among the characteristics studied, the following factors were significantly greater in the cases than in the controls: nulliparity (odds ratio for parity 1-3 and > or = 4 versus nullipara are 0.40 and 0.02, respectively), obesity (odds ratio: 2.73), hypertension (odds ratio: 2.4), diabetes mellitus (odds ratio: 6.30), and a personal medical history of cancer (odds ratio: 3.06). The present study showed that Japanese women have the same risk factors for endometrial cancer as those reported in Western countries. The recent increase in the incidence of endometrial cancer in Japan may be largely attributed to the decrease in parity.

The aim of this study was to analyze the significance of dissection of unsuspicious para-aortic lymph nodes (PAN) in patients with advanced endometrial carcinomas with intra- or extra-abdominal metastasis.We conducted a retrospective comparison of the results of PAN dissection versus non-dissection for endometrial carcinomas with macroscopic metastatic lesions beyond the uterus (without significant swelling of the regional lymph nodes, including PAN), whose lesions were completely resected.Disease-free survival and overall survival did not exhibit a significant difference between the two groups. Multivariate Cox proportional hazards analysis demonstrated that PAN dissection was not an independent prognostic factor for survival. The frequency of PAN involvement at the first recurrence did not differ between the two groups.For advanced endometrial carcinomas with macroscopic metastatic lesions beyond the uterus, without significant swelling of regional lymph nodes, PAN dissection may be omitted without a significant adverse effect on prognosis and survival.

The aim of the study was to analyze the effectiveness of salvage chemotherapy for recurring ovarian carcinoma during or after consolidation chemotherapy.During the study period, 12 patients received salvage chemotherapy for recurrence during or after consolidation chemotherapy. These cases were retrospectively reviewed.The response rate for salvage chemotherapy was 67% and was significantly associated with treatment-free interval (TFI) after consolidation (p=0.038). Progression-free survival was also significantly related to TFI (p=0.032). Combination chemotherapy of cisplatin plus irinotecan was effective in all five cases with TFI≥6 months and in three out of seven cases with TFI6 months.Our study provides, for the first time, evidence that effectiveness of salvage chemotherapy for recurrent ovarian carcinoma occurring during or after consolidation chemotherapy can be predicted by TFI, and that combination chemotherapy of cisplatin plus irinotecan is potentially useful for these cases.

Psammocarcinoma is a serous peritoneal tumor arising from the ovary or the peritoneum and characterized by low-grade nuclear features, extensive psammoma bodies, and invasiveness. Only 62 cases have ever been documented, 30 primary peritoneal and 32 primary ovarian, most of which presented as small tumors. Adjuvant therapies, including chemotherapy and radiation, were performed in 12 of the primary peritoneal cases, without any clear evidence of benefit. We present a case of an unusually large primary peritoneal psammocarcinoma with unexpected outcome. The patient was a 38-year-old woman with a tumor of the peritoneum which adhered densely to the uterus and rectum and developed into the intra-abdominal cavity and retroperitoneal space. After adhesiolysis of the tumor and rectum, suboptimal surgical reduction left a 4 cm × 2 cm tumor segment. Postoperative chemotherapy, consisting of paclitaxel and carboplatin (TC) for 1 course, and cyclophosphamide and cisplatin (CP) for 5 courses, was conducted. The residual tumor responded completely to the chemotherapy and the patient is alive today, with no evidence of disease 15 months after the surgery. Our case implies that CP therapy is a potential regimen of postoperative remission-induction therapy for suboptimally resected primary peritoneal psammocarcinoma.

Recurrent or persistent clear cell carcinoma (CCC) of the ovary is particularly chemotherapy resistant. The purpose of this study was to review our extensive institutional experiences with recurrent or persistent CCC with the aim of finding a more effective chemotherapy regimen. The medical records of 67 patients treated for CCC of the ovary were retrospectively reviewed to select patients subsequently treated for recurrence or persistence of the disease. The review identified 20 patients treated for recurrent or persistent CCC. For these 20 patients, 9 chemotherapeutic regimens, with 125 cycles, were administered. Gemcitabine monotherapy showed the best response rate [1 partial response (20%) and 2 stable diseases out of 5 patients so treated]. A partial response was observed with a combination of docetaxel plus irinotecan in 1 of 11 patients (9%). Stable disease was observed in 1 of 9 cases on a paclitaxel/carboplatin doublet and in 1 case on a docetaxel/carboplatin doublet. The median overall survival time was 8 months (range, 2–52). One group of patients who received gemcitabine therapy showed significantly better survival (n = 5, median 18 months) compared with a group who did not (n = 15, median 7 months) (P = 0.0108, by univariate analysis). In addition, multivariate Cox proportional hazards analysis revealed that gemcitabine administration was a significant factor for survival (hazard ratio: 13.0, 95% CI: 1.4727–115.2255, P = 0.02). Although most chemotherapeutic regimens for recurrent or persistent CCC have little or no effect, gemcitabine showed modest activity and is the most effective agent we have tested to date.

The aim of this study was to determine if the disease-free interval after initial surgical resection has any useful prognostic value for recurrent endometrial carcinoma patients.Between 1998 and 2007, complete resection of endometrial carcinoma was achieved in 536 cases at the Departments of Obstetrics and Gynecology of the Osaka University and Osaka Rosai Hospitals of Osaka, Japan. Clinical characteristics of these cases were retrospectively reviewed.Recurrence was subsequently detected in 54 cases. Overall survival after recurrence in 27 patients with recurrences earlier than 12 months who received no postoperative therapy, radiation, and chemotherapy as an adjuvant therapy were significantly shorter than that of those with recurrences later than 12 months with similar treatments. Multivariate analysis demonstrated that the disease-free interval was an independent factor for prognosis.We demonstrate a significantly worse prognosis in cases with early versus late recurrence of resected endometrial carcinomas, irrespective of the type of adjuvant therapy.

The objective of this study was to identify features of preoperative computed tomography (CT) scans that can best predict outcomes of primary cytoreductive surgery in ovarian cancer patients.Preoperative CT scans of 98 patients were evaluated retrospectively. Multiple logistic regression analysis was used to develop two models.Although optimal surgical reduction was attempted in 98 patients, 12 had suboptimal results. Having tumor implants on the small or large bowel mesenteries (any size) or at other sites (cutoff index: ≥ 1 cm) was found to be significant (p0.001) for predicting a suboptimal cytoreduction outcome. Two predictive models were created using multiple logistic regression analysis; both consider diffuse peritoneal thickening (DPT), infrarenal para-aortic or pelvic lymph node involvement, a bowel encasement tumor (≥ 2 cm), and any tumor implants in the cul-de-sac as significant. Model 1 adds consideration to any tumors in the pelvic or retroperitoneum and has an accuracy of 90.8% for predicting a suboptimal surgery. Model 2 (accuracy of 93.9%) adds to the core of predictors the presence of tumor implants on the bowel mesenteries (≥ 2 cm), omental caking (≥ 2 cm), and ascites fluid.Using specific CT findings from patients with ovarian cancer, we have devised two predictive models that have an accuracy of greater than 90% for predicting whether cytoreductive surgery will completely remove all tumor tissue, which should greatly aid in the differential decision-making as to whether to attempt cytoreductive surgery first, or to advance directly to neoadjuvant chemotherapy.

TAP chemotherapy (paclitaxel, doxorubicin, and cisplatin) is effective for advanced and recurrent endometrial carcinoma, but has occasional severe toxicity. TEC chemotherapy (paclitaxel, epirubicin, and carboplatin) has been suggested to have less toxicity; however, the optimal dosage has yet to be determined.Phase I/II prospective study for TEC therapy was performed. A retrospective comparison of the prognosis between adjuvant TEC therapy and radiation for completely resected cases with risk factors was also performed.The recommended dose of TEC therapy was determined to be paclitaxel 150 mg/m(2), epirubicin 50 mg/m(2), and carboplatin AUC 4. A TEC regimen at this dose level was shown to be tolerable. The response rate and median overall survival were 74% and 37 months for those with advanced primary disease (Group B) and 50% and 26 months for recurrent tumors (Group C), respectively. A retrospective comparison showed that adjuvant TEC therapy for completely resected stage III cases improved their prognosis when compared to an adjuvant radiation therapy.TEC therapy was demonstrated to be a tolerable and effective treatment, not only as a remission-induction therapy for advanced and recurrent endometrial carcinomas but also as the adjuvant therapy.

Background/Aims: An intraoperative diagnosis in cases with primary and metastatic ovarian carcinomas is important for adequate treatment. The aim of the present study was to find a reliable method to discriminate primary from metastatic mucinous adenocarcinomas (MACs) of the ovary intraoperatively. Methods: Clinical features of all primary and metastatic mucinous ovarian carcinomas diagnosed from 1994 to 2008 at the Osaka University and Osaka Rosai Hospitals, Osaka, Japan, were reviewed retrospectively. Results: Among the 73 MACs, 51 (70%) and 22 cases (30%) were diagnosed as primary and metastatic ovarian carcinomas, respectively. The distributions of tumor size, patient age, and serum CA125 level were significantly different between primary and metastatic cases. Our algorithm that categorizes patients ≧50 years whose tumor size was Conclusions: A more reliable method to discriminate primary from metastatic MACs of the ovary by patient age and serum tumor markers was derived from our study population.

Clear cell carcinoma (CCC) of the ovary is known to be highly resistant to platinum-based chemotherapy. The purpose of our study was to identify a candidate protein that is associated with chemoresistance of CCC and to investigate the specific mechanism of chemoresistance conferred by the identified protein. Enhanced expression of Annexin A4 (Anx A4) was identified in ovarian CCC cells using 2-D differential gel electrophoresis (2D-DIGE) and mass spectrometry. Anx A4 levels were elevated in CCC cells compared with non-CCC cells as determined by real-time RT-PCR and Western blot analysis. Immunohistochemical analysis of Anx A4 was performed in 126 epithelial ovarian cancer tissue samples and demonstrated significantly elevated levels of Anx A4 protein levels in ovarian CCC tumors compared with ovarian serous and endometrioid tumors (p < 0.01). Anx A4-transfected ovarian non-CCC cells were more resistant to carboplatin (IC50 = 42 microM) compared with control cells (IC50 = 23 microM) as determined by modified MTT assay. Intracellular platinum levels were significantly lower in Anx A4-transfected cells compared with control cells after carboplatin treatment (p = 0.0020) and after an additional 360 min of carboplatin-free incubation (p = 0.0004), as measured by atomic absorption spectrophotometry. Expression of Anx A4 is elevated in ovarian CCC tumors and is associated with chemoresistance in cultured ovarian cancer cells. These results demonstrate that Anx A4 confers chemoresistance in ovarian cancer cells in part by enhancing drug efflux. Thus, Anx A4 may represent a novel therapeutic target of chemoresistance in patients with ovarian CCC.

Cervical intraepithelial neoplasia (CIN) has its highest incidence during women’s reproductive years. During 2 sequential 7-year periods, 1994 to 2000 and 2001 to 2007, 3695 and 3894 deliveries were performed, respectively, at Osaka University Hospital. CIN was detected in 21 cases (0.57%) during 1994–2000 and in 43 cases (1.1%) during 2001–2007. By comparison, cervical intraepithelial neoplasia—complicated pregnancies increased significantly in the latter period (P = .015 by Fisher exact test, Odds ratio = 1.95; 95% CI: 1.16–3.30). We observed CIN regression in 34 (76%) of 45 cases of vaginal delivery and in 6 (50%) of 12 cases of cesarean delivery, indicating that the outcome of an initially diagnosed CIN and the delivery routes appeared not to be significantly related. However, a different result was obtained when only those patients whose CIN lesions persisted until the delivery were analyzed. Among the 35 such cases in the vaginal delivery group, 24 cases (69%) regressed after the delivery; in 8 such cases from the cesarean delivery group, only 2 cases (25%) regressed afterward. Our study clearly shows that pregnancy complicated with CIN is increasing rapidly in Japan. We also find that there is a significantly more frequent postpartum regression of biopsy-proven CIN lesions following a vaginal delivery compared to cesarean section (P = .042 by Fisher exact test, Odds ratio = 6.55; 95% CI: 1.13–37.8).

This research was carried out to determine the degree of association between health related practices and chronic illness and to Identify their cumulative effects on physical health status among Koreans using data collected through a nationwide sample survey. The sample consisted of 5, 021 adults aged 20-59 selected through a stratified cluster random sampling method. The response rate was 99%. The survey was conducted from 30 October through 9 December 1989. Descriptive statistics and multiple logistic regression procedures were employed for analyses. This research corroborates studies carried out in Alameda County, California which demonstrated that desirable health related practices are positively related to physical health status. The relationships of these practices were indicated to be cumulative and independent.

In countries where antiretroviral therapy has been available or is being rapidly expanded, the World Health Organization (WHO) recommends surveillance for transmitted HIV drug resistance (HIVDR) by threshold surveillance methods using specimens from antenatal clinics or voluntary counselling and testing (VCT) sites. The aim of this study was to implement the HIVDR threshold survey in VCT sites in Vietnam, where HIV prevalence is high. Estimating transmitted resistance in the infected population will enable the appropriateness of current antiretroviral drug regimens to be assessed and will inform plans for future HIVDR surveillance.Consecutive blood specimens were collected from 70 newly diagnosed HIV-positive clients 18-24 years of age at two sites in Hanoi, Vietnam. Informed consent and serum specimens were obtained from each eligible client, with serum frozen at -70 degrees C until shipping to Thailand for resistance testing using the TruGene system.From February until August 2006, 559 clients were eligible to participate in this survey. Of the 535 clients (95.7%) who agreed to participate, 70 (13%) were HIV-positive and were included in the survey. Of the 70 specimens sent for genotyping, 52 consecutive samples were amplified, 49 of which could be genotyped. Only 1 of 49 genotyped specimens had mutations associated with drug resistance (L74V and Y181C) in the reverse transcriptase gene, indicating that the prevalence of transmitted HIVDR to all drugs and drug classes evaluated was5%.The prevalence of transmitted HIVDR was low in Hanoi as determined using threshold surveillance methods. The Ministry of Health plans to repeat this survey methodology in one more province and to confirm these findings by expanded HIVDR surveillance.

To better understand the molecular mechanisms of carcinogenesis induced in uterine endometrium by therapeutic anti-estrogenic Tamoxifen (TAM) exposure, 27 uterine tumors (4 benign endometrial polyps and 23 carcinomas) associated with TAM exposure were analyzed for the presence and spectrum of p53 and K-ras mutations. Although there was no significant difference between TAM-associated endometrial carcinomas and sporadic endometrial tumors in the frequency of these mutations, the spectrum of p53 mutations was characteristically unique to the TAM-associated tumors. The median duration of TAM exposure was significantly longer in patients with p53 mutations than those without p53 mutations (62 vs. 30 months, p=0.028). Our observation suggests that prolonged TAM exposure may directly inactivate the p53 gene by acting as a mutagen in a significant fraction of TAM-associated endometrial carcinomas.

Background: A pollen exposure chamber (OHIO Chamber) was built in central Tokyo, Japan, in order to study seasonal allergic rhinitis (SAR). Since satisfactory outcomes were obtained from the controlled pollen exposure at the chamber, we conducted preliminary studies in volunteers with SAR. Methods: Ten volunteers with SAR sensitive to Japanese cedar (JC) pollen were enrolled in this study. In order to investigate the intranasal and intraocular pollen number, volunteers were initially exposed to a low concentration of JC (2500 grains m 3 ) for at most 1 hour in this chamber. Before and after the exposure, nasal cavities and eyes were washed with 100 ml and 25 ml of saline, respectively. Nasal and eye washing solutions were collected and the number of JC pollen was counted. After 3 hours the volunteers were subsequently exposed to a moderate concentration of JC (4500 grains m3) for 2 hours. Subjective nasal and ocular symptoms were recorded and the amount of nasal secretion was measured during the allergen exposure periods. Results: During the initial exposure, all volunteers except one stayed in the chamber for 1 hour without any nasal or ocular symptoms. The number of pollen in the nose and eyes was 249.2 ± 120.9 and 13.6 ± 13.6 grains, respectively. During the subsequent 2-hour exposure to JC pollen, nasal and ocular symptoms developed gradually in a time dependent manner in all the volunteers except one. Conclusions: This is the first clinical study using Japanese cedar pollen under well-controlled conditions in the OHIO chamber in which the induction of allergic symptoms was observed. The OHIO chamber will be useful for studying allergic rhinitis in Japan.

Desmoid tumor is a locally aggressive, nonmetastasizing soft tissue tumor. Whether desmoid tumor is a truly neoplastic cellular proliferative process or, alternatively, an unchecked reactive process has been a subject of debate. In order to determine whether desmoid tumor is composed of a clonal cell population as opposed to being a polyclonal reactive process, analysis of patterns of X-chromosome inactivation was performed. Hematoxylin and eosin stained sections of paraffin-embedded, formalin-fixed tissues were microdissected to obtain both lesional and normal control samples, and the genomic DNAs were extracted by proteinase K digestion. Following treatment with methylation sensitive restriction endonuclease (Hha I or Hpa II), the genomic DNAs were amplified by polymerase chain reaction (PCR), using nested primers targeted to a highly polymorphic short tandem repeat (STR) of the human androgen receptor (HUMARA). In eight of 12 cases, PCR amplification of the genomic DNAs was successful, and all eight of the amplified cases were heterozygous in the size of the HUMARA target. The remaining cases could not be studied because of failure to amplify DNA. Following digestion with HhaI or Hpa II, uniform patterns of X-chromosome inactivation were found in all eight desmoid tumors, whereas normal control tissue remained heterozygous. These results confirm a clonal composition of the tumors. The demonstration of clonality in the tumors in all eight informative cases indicates that desmoid tumor is a true neoplastic process, not an unchecked polyclonal reactive process.

The possible association of human papillomavirus (HPV) with endometrial hyperplasia and endometrial adenocarcinoma was investigated. DNA from frozen tissues of 30 endometrioid carcinomas of Japanese patients was tested for HPV DNA by Southern blot hybridization analysis. Screening with HPV type 58 probe under low stringency conditions showed the presence of HPV DNA in two of 30 endometrioid carcinomas. High stringency hybridization identified HPV type 16 in the two positive specimens. The presence of HPV was further analyzed by polymerase chain reaction (PCR)-Southern blot analysis of DNA from archival tissue blocks of the initial 30 endometrioid carcinomas as well as an additional 17 endometrioid carcinomas and 13 atypical hyperplasias of the endometrium from Japan and 38 endometrioid carcinomas from the United States. Polymerase chain reaction amplification using type 16-specific HPV primers for a portion of the E6 open reading frame was positive in six of 47 (13%) endometrioid carcinomas from Japan, including two in which HPV 16 was not detected by Southern blot analysis and two of 38 (5%) endometrioid carcinomas from the United States. Polymerase chain reaction amplification using L1 consensus sequence primers was positive for HPV in two of 13 (15%) endometrial hyperplasias, 13 of 47 (28%) endometrioid carcinomas from Japan, and six of 38 (16%) endometrioid carcinomas from the United States. Slot blot hybridization identified HPV type 16 in seven of the L1 PCR products, including all but one specimen testing positive for HPV type, 16 using E6 type specific primers. In situ hybridization was positive for HPVs 16/18 in glandular epithelial tumor cells in six of the PCR-positive specimens. An additional specimen showed staining for HPVs 16/18 in acellular luminal debris in association with squamous metaplasia of the tumor, but staining was negative in the glandular cells of the tumor. Human papillomavirus was not detected by in situ hybridization in the remaining specimen, which was PCR positive for HPV 16. In situ hybridization was weakly positive for HPVs 31/33/35 in one specimen and was weakly positive for HPVs 6/11 in benign endometrial epithelial cells but not in tumor cells of another specimen that tested positive for HPV by L1 PCR. Two dimensional gel electrophoresis performed on two specimens showed that HPV DNAs were integrated into cellular DNA with no episomal coexistence. These findings suggest that HPV, especially HPV 16, may play an etiologic role in a fraction of endometrioid adenocarcinomas.

Background In the Asia-Pacific region, limited systematic assessment has been conducted on HIV service delivery models. Applying an analytical framework of the continuum of prevention and care, this study aimed to assess HIV service deliveries in six Asia and Pacific countries from the perspective of service availability, linking approaches and performance monitoring for maximizing HIV case detection and retention. Methods Each country formed a review team that provided published and unpublished information from the national HIV program. Four types of continuum were examined: (i) service linkages between key population outreach and HIV diagnosis (vertical-community continuum); (ii) chronic care provision across HIV diagnosis and treatment (chronological continuum); (iii) linkages between HIV and other health services (horizontal continuum); and (iv) comprehensive care sites coordinating care provision (hub and heart of continuum). Results Regarding the vertical-community continuum, all districts had voluntary counselling and testing (VCT) in all countries except for Myanmar and Vietnam. In these two countries, limited VCT availability was a constraint for referring key populations reached. All countries monitored HIV testing coverage among key populations. Concerning the chronological continuum, the proportion of districts/townships having antiretroviral treatment (ART) was less than 70% except in Thailand, posing a barrier for accessing pre-ART/ART care. Mechanisms for providing chronic care and monitoring retention were less developed for VCT/pre-ART process compared to ART process in all countries. On the horizontal continuum, the availability of HIV testing for tuberculosis patients and pregnant women was limited and there were sub-optimal linkages between tuberculosis, antenatal care and HIV services except for Cambodia and Thailand. These two countries indicated higher HIV testing coverage than other countries. Regarding hub and heart of continuum, all countries had comprehensive care sites with different degrees of community involvement. Conclusions The analytical framework was useful to identify similarities and considerable variations in service availability and linking approaches across the countries. The study findings would help each country critically adapt and adopt global recommendations on HIV service decentralization, linkages and integration. Especially, the findings would inform cross-fertilization among the countries and national HIV program reviews to determine county-specific measures for maximizing HIV case detection and retention.