Cost-effectiveness analysis of single-dose or 2-dose of bivalent, quadrivalent, or nonavalent HPV vaccine in a low/middle-income country setting.

OBJECTIVE: To compare the health impact and economic benefits among individuals who did not receive the human papillomavirus (HPV) vaccine to those who received a single dose, or 2 doses. The comparison was stratified by 4 types of vaccine in conjunction with primary HPV screening in a low/middle-income country setting. METHODS: A Markov model was employed to simulate HPV infection and cervical cancer in a cohort of 100,000 12-year-old girls free of HPV. The study scrutinized 9 strategies: 1 dose and 2 doses of 2vHPV (Cervarix®), 2vHPV (Cecolin®), 4vHPV (Gardasil®), 9vHPV vaccine (Gardasil9®), and no vaccination. The primary outcome measure was the quality-adjusted life year (QALY) of each strategy. Incremental cost-effectiveness ratios were estimated over a lifetime horizon, accompanied by sensitivity analyses conducted. RESULTS: All vaccination programs yielded 41,298-71,057 QALYs gained accompanied by cost savings of 14,914,186-19,821,655 USD compared to no vaccination. Administering 2 doses of 9vHPV vaccine emerged as the most cost-effective strategy, boasting 406 USD/QALY, within a lower willingness to pay threshold. Sensitivity analysis demonstrated an 80% probability of the cost-effectiveness of the 2 doses of 9vHPV vaccine regimen. Furthermore, uncertainty around the costs of vaccination and vaccine efficacy exerted the most substantial influence on the cost-effectiveness findings. CONCLUSION: Oping for 2 doses of 9vHPV vaccine in conjunction with a primary HPV screening represents the most cost-effective option for implementing a school-based HPV vaccination program targeting 12-year-old girls in Thailand. Such findings provide valuable insights for policymakers in the realm of cervical cancer prevention.

TIL expansion with high dose IL-2 or low dose IL-2 with anti-CD3/anti-CD28 stimulation provides different quality of TIL-expanded T cell clones.

Tumor infiltrating lymphocytes (TILs) are cells that are present inside the tumor environment, of which include T cells, B cells and natural killer (NK) cells. At present, TILs are used for immunotherapy in various cancers. Knowledge on adoptive transfer of TILs in ovarian cancer is still limited, especially regarding TIL expansion methods. Therefore, the aim of our study was to compare the quality of T cell clones between two expansion methods for ovarian cancer TILs. We show that TILs stimulated with the mitogenic stimulation method (low dose IL-2 with anti-human CD3/CD28) and the standard stimulation method (high dose IL-2 only) both increased total number of T cells. TCR repertoire analyses revealed different TCR repertoire patterns between TIL-expanded T cells that were stimulated with the standard stimulation method (high dose IL-2 only) and the mitogenic stimulation method (low dose IL-2 with anti-human CD3/CD28). Regardless, when TILs were expanded using the standard stimulation method (high dose IL-2 only), the predominant T cell receptor beta variable (TRBV) chains that were used in both TIL-expanded clones of the CD4+ and CD8+ subpopulations were similar. In addition, there were also TIL-expanded CD4+ and CD8+ T cell clones that were dominant in only one or the other subpopulations. These results reveal the bias in TIL quality after being stimulated with different protocols. Further studies are required to understand the selection of TIL expansion, in order for a more efficacy adoptive transfer treatment.

Evaluating efficacy and safety of the topical silicone gel containing onion extract in the treatment of post-cesarean surgical scars.

BACKGROUND: Cesarean section scars are post-surgical problems in women. Many active ingredients have been found to diminish scar formation. Clinical investigations on the onion extract have gained more attention due to its properties, such as improvement of scar appearance and texture. However, published studies evaluating the usefulness of the onion extract in the treatment of scars are controversial. METHODS: The three-month study period followed a prospective, randomized, and double-blinded design. Each enrolled subject's post-cesarean completely sealed wounds were divided into two halves along the closure axis. Each half was randomly assigned to the treatment with either silicone gel containing 5% onion extract or the silicone gel containing vitamin C. All subjects were respectively evaluated at the one, two, and three months of the treatment. RESULTS: After the three-month follow-up, there was a statistically significant difference in scar improvement between before and after treatment. None of statistically significant difference in the Patient and Observer Scar Assessment Scale (POSAS) and Vancouver Scar Scale (VSS) scores and melanin value was found between silicone gel containing 5% onion extract and the control silicone gel. However, the improvement of scar erythema by treatment with the silicone gel containing 5% onion extract was significantly greater than in the control group. No adverse effects were reported in either group.

Impacts of Blended Bombyx mori Silk Fibroin and Recombinant Spider Silk Fibroin Hydrogels on Cell Growth.

Binary-blended hydrogels fabricated from Bombyx mori silk fibroin (SF) and recombinant spider silk protein eADF4(C16) were developed and investigated concerning gelation and cellular interactions in vitro. With an increasing concentration of eADF4(C16), the gelation time of SF was shortened from typically one week to less than 48 h depending on the blending ratio. The biological tests with primary cells and two cell lines revealed that the cells cannot adhere and preferably formed cell aggregates on eADF4(C16) hydrogels, due to the polyanionic properties of eADF4(C16). Mixing SF in the blends ameliorated the cellular activities, as the proliferation of L929 fibroblasts and SaOS-2 osteoblast-like cells increased with an increase of SF content. The blended SF:eADF4(C16) hydrogels attained the advantages as well as overcame the limitations of each individual material, underlining the utilization of the hydrogels in several biomedical applications.

Neovaginal and Anal High-Risk Human Papillomavirus DNA Among Thai Transgender Women in Gender Health Clinics.

BACKGROUND: Although human papillomavirus (HPV)-related lesions in the neovagina of transgender women have been well documented, information on high-risk HPV (hrHPV) in the neovagina has been very limited. The objective of this study was to determine hrHPV DNA detection rate in the neovagina of transgender women. METHODS: Neovaginal and anal swab were collected in liquid-based cytology fluid from transgender women visiting Gender Health Clinic and Tangerine Community Health Clinic in Bangkok, Thailand. Samples were processed for hrHPV DNA (reported as subtypes 16 and 18 or the pooled result of subtypes 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 66) by automated real-time polymerase chain reaction and for neovaginal cytology according to the Bethesda system. Demographic data and sexual history were obtained, and physical examination was conducted. HIV status was obtained from existing medical records. RESULTS: Samples were collected from 57 transgender women (mean age, 30.4 years [interquartile range, 8 years]). From 35 of 57 valid neovaginal samples, 8 (20%) tested positive for hrHPV DNA. From 30 of 57 valid anal samples, 6 (19.4%) tested positive for hrHPV DNA. HIV status was known for 52 transgender women, 1 of which were HIV infected; neovaginal hrHPV was invalid in that patient. CONCLUSIONS: One of 5 transgender women visiting sexual health clinics in Bangkok was found to have hrHPV DNA in neovaginal and anal compartments. Studies are needed to look at incidence and persistence of hrHPV infection to inform anogenital precancerous and cancerous screening programs for transgender women.

The epidemiologic and economic impact of a quadrivalent human papillomavirus vaccine in Thailand.

BACKGROUND: The human papillomavirus (HPV) vaccine was introduced into Thailand's national immunization program in 2017 for 11-12 year old school girls. The objectives of this study were to examine the epidemiological consequences and cost-effectiveness of a routine quadrivalent HPV (4vHPV) vaccination and the routine 4vHPV vaccination plus 5-year catch-up vaccination by comparing with cervical cancer screening only (no vaccination) in Thailand. METHOD: A transmission dynamic model was used to assess the cost-effectiveness of the routine 4vHPV vaccination and the routine 4vHPV vaccination plus catch-up vaccination, compared with no vaccination (screening only) in Thai population. The vaccination coverage rate assumptions were 95% in 11-12-year-old girls for the routine vaccination and 70% in 13-24 year-old females for the 5-year catch-up vaccination. Vaccination costs, direct medical costs of HPV-related diseases, and the number of quality of life years (QALYs) gained were calculated for over a 100-year time horizon with discount rate of 3%. RESULT: The model indicated that the routine 4vHPV vaccination and the routine plus catch-up 4vHPV vaccination strategies could prevent approximately 434,130 and 472,502 cumulative cases of cervical cancer, 182,234 and 199,068 cumulative deaths from cervical cancer and 12,708,349 and 13,641,398 cumulative cases of HPV 6/11 related genital warts, respectively, when compared with no vaccination over 100 years. The estimated cost per QALY gained (ICER) when compared to no vaccination in Thailand was 8,370 THB/QALY for the routine vaccination and 9,650 THB/QALY for the routine with catch-up vaccination strategy. CONCLUSION: Considering the recommended threshold of 160,000 THB/QALY for Thailand, the implementation of the routine 4vHPV vaccination either alone or plus the catch-up vaccination was cost-effective as compared to the cervical cancer screening only.

Cost Effectiveness Analysis of Different Management Strategies between Best Supportive Care and Second-line Chemotherapy for Platinum-resistant or Refractory Ovarian Cancer.

BACKGROUND: There is no standard treatment for patients with platinum-resistant or refractory epithelial ovarian cancer. Single agent chemotherapies have evidence of more efficacy and less toxicity than combination therapy. Most are very expensive, with appreciable toxicity and minimal survival. Since it is difficult to make comparison between outcomes, economic analysis of single-agent chemotherapy regimens and best supportive care may help to make decisions about an appropriate management for the affected patients. OBJECTIVE: To evaluate the cost effectiveness of second-line chemotherapy compared with best supportive care for patients with platinum-resistant or refractory epithelial ovarian cancer. MATERIALS AND METHODS: A Markov model was used to estimate the effectiveness and total costs associated with treatments. The hypothetical patient population comprised women aged 55 with platinum-resistant or refractory epithelial ovarian cancer. Four types of alternative treatment options were evaluated: 1) gemcitabine followed by BSC; 2) pegylated liposomal doxorubicin (PLD) followed by BSC; 3) gemcitabine followed by topotecan; and 4) PLD followed by topotecan. Baseline comparator of alternative treatments was BSC. Time horizon of the analysis was 2 years. Health care provider perspective and 3% discount rate were used to determine the costs of medical treatment in this study. Quality-adjusted life-years (QALY) were used to measure the treatment effectiveness. Treatment effectiveness data were derived from the literature. Costs were calculated from unit cost treatment of epithelial ovarian cancer patients at various stages of disease in King Chulalongkorn Memorial Hospital (KCMH) in the year 2011. Parameter uncertainty was tested in probabilistic sensitivity analysis by using Monte Carlo simulation. One-way sensitivity analysis was used to explore each variable's impact on the uncertainty of the results. RESULTS: Approximated life expectancy of best supportive care was 0.182 years and its total cost was 26,862 Baht. All four alternative treatments increased life expectancy. Life expectancy of gemcitabine followed by BSC, PLD followed by BSC, gemcitabine followed by topotecan and PLD followed by topotecan was 0.510, 0.513, 0.566, and 0.570 years, respectively. The total cost of gemcitabine followed by BSC, PLD followed by BSC, gemcitabine followed by topotecan and PLD followed by topotecan was 113,000, 124,302, 139,788 and 151,135 Baht, respectively. PLD followed by topotecan had the highest expected quality-adjusted life-years but was the most expensive of all the above strategies. The incremental cost-effectiveness ratios (ICER) of gemcitabine followed by BSC, PLD followed by BSC, gemcitabine followed by topotecan and PLD followed by topotecan was 344,643, 385,322, 385,856, and 420,299 Baht, respectively. CONCLUSIONS: All of the second-line chemotherapy strategies showed certain benefits due to an increased life- year gained compared with best supportive care. Moreover, gemcitabine as second-line chemotherapy followed by best supportive care in progressive disease case was likely to be more effective strategy with less cost from health care provider perspective. Gemcitabine was the most cost-effective treatment among all four alternative treatments. ICER is only an economic factor. Treatment decisions should be based on the patient benefit.

Comparison of Perioperative and Oncologic Outcomes with Laparotomy, and Laparoscopic or Robotic Surgery for Women with Endometrial Cancer.

PURPOSE: To compare perioperative outcomes and oncologic outcomes in endometrial cancer patients treated with laparotomy, and laparoscopic or robotic surgery. MATERIALS AND METHODS: Endometrial cancer patients who underwent primary surgery from January 2011 to December 2014 were retrospectively reviewed. Perioperative outcomes, including estimated blood loss (EBL), operation time, number of lymph nodes retrieved, and intra and postoperative complications, were reviewed. Recovery time, disease free survival (DFS) and overall survival (OS) were compared. RESULTS: Of the total of 218 patients, 143 underwent laparotomy, 47 laparoscopy, and 28 robotic surgery. The laparotomy group had the highest EBL (300, 200, 200 ml, p<0.05) while the robotic group had the longest operative time (302 min) as compared with laparoscopy (180 min) and laparotomy (125 min) (p<0.05). Intra and postoperative complications were not different with any of the surgical approaches. No significant difference in number of lymph nodes retrieved was identified. The longest hospital stay was reported in the laparotomy group (four days) but there was no difference between the laparoscopy (three days) and robotic (three days) groups. Recovery was significantly faster in robotic group than laparotomy group (14 and 28 days, p=0.003). No significant difference in DFS and OS at 21 months of median follow up time was observed among the three groups. CONCLUSIONS: Minimally invasive surgery has more favorable outcomes, including lower blood loss, shorter hospital stay, and faster recovery time than laparotomy. It also has equivalent perioperative complications and short term oncologic outcomes. MIS is feasible as an alternative option to surgery of endometrial cancer.

Feasibility and safety of robotic surgery for gynecologic cancers.

BACKGROUND: To determine surgical outcomes, perioperative complications, and patient outcomes in gynecologic cancer patients undergoing robotic surgery. MATERIALS AND METHODS: Surgical outcomes, including docking time, total operative time, console time, estimated blood loss (EBL), conversion rate and perioperative complications were retrospectively reviewed in 30 gynecologic cancer patients undergoing robotic surgery. Patient outcomes included recovery time and patient satisfaction, as scored by a visual analogue scale (VAS) from 0-10. RESULTS: The operations included 24 hysterectomies with pelvic lymphadenectomy (PLD) and/or para-aortic lymphadenectomy, four radical hysterectomies with PLD, and two radical trachelectomies with PLD. Mean docking time was 12.8 ± 9.7 min, total operative time was 345.5 ± 85.0 min, and console time was 281.9 ± 78.6 min. These times were decreased in the second half of the cases. There was no conversion rate. Three intraoperative complications, including one external iliac artery injury, one bladder injury, and one massive bleeding requiring blood transfusion were reported. Postoperative complications occurred in eight patients, most were minor. Only one patient had port herniation that required reoperation. Mean hospital stay was 3.5 ± 1.7 days, and recovery time was 14.2 ± 8.1 days. Two-thirds of patients felt very satisfied and one-third felt satisfied; the mean satisfaction score was 9.4 +0.9. Two patients with stage III endometrial cancer developed isolated port site metastasis at five and 13 months postoperatively. CONCLUSIONS: Robotic surgery for gynecologic cancer appears to be feasible, with acceptable perioperative complication rate, fast recovery time and high patient satisfaction.

Is complete surgical staging necessary in clinically early-stage endometrial carcinoma?

The purpose of this study was to evaluate the incidence of pelvic/para-aortic node metastases and the other pathological characteristics from medical records of patients with endometrial carcinoma treated at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between 1996 and 2005. The records of 213 patients with endometrial carcinoma who had complete surgical staging were reviewed. A particular focus was on clinically early-stage disease. Clinical staging could be determined in 206 patients. Of the 206 patients, 182 (88.3%) presented with clinical stage I disease. However, only 142 (78%) of these patients were confirmed as surgical stage I and 22% were upstaged. Preoperative histologic grade was diagnosed inaccurately in 15.9% of patients and 7.7% were upgraded. Of patients with preoperative histologic grade 1, 33% had deep myometrial invasion, 8.2% had pelvic node metastasis, and 3.3% had para-aortic node metastasis. Even in clinical stage IaG1, pelvic node metastasis occurred in 5.6% and para-aortic node metastasis in 1.3%. It has been suggested that complete surgical staging may not be necessary in patients with low-risk endometrial carcinoma who have disease limited to the uterus without grade 3 or deep myometrial invasion. However, proper selection of such low-risk patients remains problematic. In situations where there is limited preoperative and intraoperative assessment of high-risk factors, particularly radiographic imaging and frozen section assessment, the role of complete surgical staging is beneficial.

Long term complications after radical hysterectomy with pelvic lymphadenectomy.

OBJECTIVE: To evaluate the incidence of long-term complications in stage IB and IIA cervical cancer patients undergoing radical hysterectomy with bilateral pelvic lymphadenectomy. MATERIAL AND METHOD: A retrospective review on 290 patients who were treated with primary type III radical hysterectomy with bilateral pelvic lymphadenectomy between January 1, 1997 and December 31, 2005. Long-term complications were classified in two categories, voiding dysfunction and complication from lymphadenectomy such as lymphocyst and lymphedema. RESULTS: Forty-two patients (14.5%) required urethral catheterization more than four weeks. Only four patients (1.4%) were diagnosed as neurogenic bladder and required permanent self-catheterization. Two hundred forty eight patients (85.5%) returned to normal voiding within 1 month postoperatively. The incidence of lymphocyst was 9.3%; however, almost of them were asymptomatic and resolved spontaneously within a few months. Only four patients (1.4%) had complicated lymphocyst and required hospitalization with intravenous antibiotic and drainage procedure. Six patients (2.1%) were diagnosed as lymphedema after exclusion of deep vein thrombosis and recurrent cervical carcinoma. Pelvic lymph node metastasis and postoperative adjuvant radiation were not significant risk factors for lymphocyst and lymphedema. CONCLUSION: Radical hysterectomy with lymphadenectomy is the treatment of choice in stage IB and IIA cervical cancer with excellent survival rate. However there are long-term complications such as voiding dysfunction, lymphocyst, and lymphedema. Although these complications are not life threatening, they can affect the quality of life.

Outcome of recurrent and persistent disease of malignant ovarian germ cell tumor: a retrospective analysis at King Chulalongkorn Memorial Hospital.

Malignant ovarian germ cell tumor has one of the most successful treatment outcomes in gynecological malignancy. More than 80% of the patients can be cured from this rare type of tumor However, patients with recurrent and persistent disease after primary treatment are still the problem of management. The present study has reviewed the treatment outcome of this cancer in King Chulalongkorn Memorial Hospital during the 12 years periodfrom 1993 to 2004. The overall cases of malignant ovarian germ cell tumor were 71 cases, 8 cases had recurrent disease after primary treatment and all cases received platinum-based chemotherapy for the salvage treatment. All patients in this group received long-term survival with median survival time of 87 months. In patients with persistent disease, 10 cases that resisted to first line adjuvant chemotherapy. Cisplatin and Etoposide regimen was applied as second line treatment, but none of these patients received long term response. The survival outcomes in these 2 groups are significantly different. The overall survival from the treatment of malignant ovarian germ cell tumor in King Chulalongkorn Memorial Hospital was 85.1%. In conclusion, the outcome of treatment in patients with recurrent disease after non-platinum chemotherapy is excellent. Salvage therapy in this group should contain platinum-based regimen. Patients whose disease persisted after platinum-containing regimen had a poor survival outcome.

Prevalence and prognostic significance of COX-2 expression in stage IB cervical cancer.

OBJECTIVES: To evaluate the prevalence of cyclooxygenase-2 (COX-2), correlation with various clinicopathologic factors and prognostic significance of COX-2 in stage IB cervical cancer patients. METHODS: 89 paraffin-embedded specimens of patients with stage IB cervical cancer underwent radical hysterectomy and pelvic lymphadenectomy at King Chulalongkorn Memorial Hospital during 1 January 1997-31 December 2002 and were stained with polyclonal goat antiserum against COX-2 using immunohistochemical method. Medical records were reviewed; clinicopathological variables were retrieved and used for analysis. RESULTS: The prevalence of positive COX-2 expression in stage IB cervical cancer in this study was 49.4%. Positive COX-2 expression in cervical adenocarcinoma was higher than squamous cell carcinoma (86.7% versus 40.6%, P < 0.05) and significantly expressed when lymph node metastasis was presented (100% versus 46.4%, P < 0.05). However, COX-2 expression was possibly associated with parametrial involvement (80% versus 47.6%, P > 0.05). There was no correlation between COX-2 expression and patient's age, tumor size, depth of stromal invasion and lymphovascular space invasion. Five-year disease free survival and 5-year overall survival in patients with positive COX-2 expression were 81% and 98% which were not differed from patients with negative COX-2 expression (92% and 95%, P > 0.05). CONCLUSIONS: Strong correlation was found in cervical adenocarcinoma and lymph node metastasis. However, COX-2 expression failed to demonstrate as a significant prognostic factor in stage IB cervical cancer.

Malignant ovarian germ cell tumor in King Chulalongkorn Memorial Hospital.

OBJECTIVES: To determine the frequency, characteristics, treatment and outcome of patients with malignant ovarian germ cell tumor (MOGCT) in King Chulalongkorn Memorial Hospital during the period January 1992 - December 2000. STUDY DESIGN: Retrospective descriptive study MATERIAL AND METHOD: All patients with malignant ovarian germ cell tumor in King Chulalongkorn Memorial Hospital during the period January 1992 - December 2000 were analyzed by the characteristics of patients, treatment and outcome. RESULTS: Sixty-six patients with MOGCT were demonstrated in that period with a mean age of 22.6 years old. Most of the patients were nulliparous and premenopausal status. Primary surgery was done in all patients. Forty-two patients (63.6%) received conservative surgery. Eight patients received no adjuvant treatment after surgery due to stage 1A dysgerminoma and immature teratoma stage I grade I. Fifty-six patients received chemotherapy for adjuvant treatment. VAC regimen was given in 27 cases (40.9%) and PVB regimen was given in 25 cases (37.9%). Salvage therapy in the patients with persistent and recurrent disease was treated in 9 patients, who received a platinum-base of regimen. Two-year survival was 88% with the median time to follow up 24 months. Overall five-year survival in the present study was 85%. CONCLUSION: MOGCT in King Chulalongkorn Memorial Hospital had clinical characteristics similar to other studies in malignant ovarian germ cell tumor Treatment by VAC regimen still has benefit in selected group.

Infected endometrioma in pregnancy masquerading as acute appendicitis.

BACKGROUND: A pregnancy complicated by ovarian endometrioma is rare. Other complications of ovarian endometrioma in pregnancy, i.e., rupture and infection are also rare. CASE: A 35-year-old woman, gravida 2, para 0-0-1-0, at 35 weeks' pregnancy, came to the hospital with a right abdominal pain. She also had a history of diarrhea. She had history of infertility and preexisting right endometrioma. The investigations revealed leukocytosis with neutrophils predominant. The preoperative diagnosis was acute appendicitis. Infected right ovarian endometrioma was demonstrated during exploratory laparotomy, opened and drainage of the right endometrioma and appendectomy were performed. The final diagnosis was infected ovarian endometrioma in pregnancy, later confirmed by a pathological report. CONCLUSION: Although complication of ovarian endometrioma such as infected endometrioma during pregnancy is rare, it should be included in the differential diagnosis of pelvic pain during pregnancy, especially in the patient who has history of ovarian endometrioma.