Background The situation of patients developing multiple primary cancers is becoming more frequent and graver. This study investigated the risks of developing second primary cancers that are related to first primary cancers, and the interval times of synchronous and metachronous multiple primary cancers. Patients and methods Retrospective data were retrieved from 109,054 patients aged ≥18 who were diagnosed with a first solid cancer and registered at Siriraj Cancer Center between 1991 and 2015. A two-month period between first- and second- primary cancers was used to differentiate metachronous and synchronous multiple primary cancers. The combinations of subsequent cancers and relative risks (RRs) of having multiple primary cancers versus having single primary cancer for the top-ten first and second primary cancers were examined. The RR was adjusted for age of the first primary cancer. A survival analysis of the time to second-primary-cancer development was performed. Results Multiple primary cancers were found in 1785 (1.63%) patients. Most (70.87%) second primary cancers occurred after 2 months of first breast, skin, colorectal, lung, head and neck, liver, male genital cancer–prostate, thyroid, and female genital cancer–non-uterine cancers, resulting in those cancers being classified as metachronous multiple primary cancer. After adjustment for age at first diagnosis, head and neck cancers had the highest metachronous association with second esophageal cancers (RR, 25.06; 95% CI, 13.41–50.77). Prostate cancer and second colorectal cancer also demonstrated a high metachronous association (RR, 2.00; 95% CI, 1.25–3.05). A strong synchronous association was found between uterine and ovarian cancers (RR, 27.77; 95% CI, 17.97–43.63). The median time from the first uterine cancer to second-cancer development was 55 days. Conclusions The top-ten most frequent multiple primary cancers were the following: breast; liver; head and neck; colorectal; male genital cancer–prostate; skin; female genital cancer–uterine; thyroid; lung; and female genital cancer–non-uterine. Second primary cancers showed specific associations that depended on the first primary cancer. Physicians should be cognizant of the most common combinations and the interval times of metachronous and synchronous multiple primary cancers.

Objective To evaluate the effect of depot medroxyprogesterone acetate (DMPA) in protecting against epithelial ovarian cancer (EOC) and to evaluate factors associated with the risk of EOC.Design A multicentre, case-control study.Setting Twelve hospitals located across Thailand.Population Three hundred and thirty patients with EOC ('cases') and 982 matched controls were recruited from the 12 hospitals. Cases were newly diagnosed patients with EOC, demonstrated pathologically. Controls were age-matched patients admitted to different wards in the same hospital.Methods Cases and controls were interviewed by trained interviewers using a standardised pre-tested questionnaire. The factors associated with EOC were evaluated using univariate and multivariate analyses.Main outcome measures The odds ratio (OR) and 95% confidence interval (95% CI) were calculated to assess the relationship between DMPA and EOC.Results The use of DMPA was found to be associated with a 39% reduction in the risk of EOC with an OR of 0.61 and a 95% CI of 0.44-0.85 (P = 0.002). A significant risk reduction (83%) was observed when the duration of DMPA use was >3 years (OR 0.17; 95% CI 0.07-0.39; P < 0.001). Other factors associated with a reduced risk of EOC were the use of combined oral contraceptive pills and breastfeeding. A factor associated with an increased risk of EOC was a family history of gynaecological cancer. ConclusionsThe results suggest that DMPA may have a protective effect against EOC. If this effect is real, then it represents an important non-contraceptive benefit of DMPA.

No abstract

The tumor microenvironment composed of a mixture of stromal cells and their secretions has a marked impact on cancer progression. In particular, soluble factors and metabolites contribute to malignancy through the dysregulation of autophagy in cancer cells. The present study investigated the effects of ovarian cancer-associated fibroblasts (OVCAFs) with their secretory substances on the autophagy and migration of ovarian cancer cells. The conditioned-medium (CM) of OVCAFs isolated from fresh human ovarian cancer tissues was analyzed for the levels of 27 common cytokines/chemokines using a cytokine array. Autophagy in cancer cells was assessed by determining the expression of the vacuolar form of LC3 by western blot analysis and immunofluorescence. Cancer cell migration was assessed by Transwell migration assay. Interleukin (IL)-8 was found to be the most highly upregulated cytokine among the cytokines/chemokines found in the OVCAF-CM. The role of IL-8 in ovarian cancer cell migration and its mechanistic link with autophagy was investigated. Recombinant human IL-8 (rhIL-8) stimulated the migration of SKOV3 and Kuramochi ovarian cancer cells, and concurrently downregulated basal autophagy, in concentration-dependent manner. Compared to the CM of control counterpart normal fibroblasts isolated from benign ovaries (OVNF-CM), the CM from 3 OVCAF isolates (namely, OVCAF-9, -20 and -43) exerted effects similar to rhIL-8 on both cancer cell lines. The pharmacological induction of autophagy with rapamycin or metformin attenuated the pro-migratory effects of IL-8. Neutralizing anti-IL-8 antibody counteracted the inhibitory effect of OVCAF-CM on basal autophagy. On the whole, the present study highlights the involvement of IL-8 released by CAFs in the ovarian tumor microenvironment in promoting cancer cell migration through the suppression of autophagy.

Background: To evaluate the rate of pathologic high-risk factors, intermediate-risk factors, and treatment outcomes in early-stage cervical cancer patients undergoing radical hysterectomy and pelvic lymphadenectomy (RHPL). Materials and Methods: Medical records of stage IA-IIA1 cervical cancer patients who underwent RHPL during the 2006 to 2012 time period and patient follow-up data until December 2013 were reviewed. Results: Of 331 patients, 52 women (15.7%) had pathologic high-risk factors and 59 women (17.8%) had intermediate-risk factors without high-risk factors. All studied patients had an initial complete response. At median follow-up time of 40.9 months (range 1-103.3 months) and mean follow-up time of 43.3±25.3 months, 37 women had disease recurrence and 4 women had died of disease. The most common site of recurrence was the pelvis (64.8%). Fiveyear and 10-year disease free survival rates were 96.1% and 91.5%, respectively. Five-year and 10-year overall survival rates were 100% and 99.4%, respectively. Independent factors related to recurrence were pelvic node metastasis (odds ratio [OR], 2.670; 95%CI, 1.001-7.119), and >1/3 cervical stromal invasion (OR, 3.763; 95%CI, 1.483-9.549). Conclusions: The rates of pathologic high-risk and intermediate-risk factors should be considered and disclosed when counseling patients regarding primary treatment by RHPL. Oncologic outcomes of primary surgical treatment for early-stage cervical carcinoma were found to be excellent.

No abstract

ObjectiveTo evaluate the recurrence rates and patterns of failure in patients with stage I endometrial carcinoma after surgical staging without adjuvant therapy.MethodsMedical records of 229 patients with stage I endometrial carcinoma, treated with surgery alone between 2002 and 2010 at Siriraj Hospital were retrospectively reviewed. The primary objective of this study was recurrence rates. The secondary objectives were patterns of failure, disease-free survival, overall survival, and prognostic factors related to outcomes.ResultsDuring median follow-up time of 53.3 months, 11 recurrences (4.8%) occurred with a median time to recurrence of 21.2 months (range, 7.7 to 77.8 months). Vaginal recurrence was the most common pattern of failure (8/11 patients, 72.7%). Other recurrences were pelvic, abdominal and multiple metastases. Factors that appeared to be prognostic factors on univariate analyses were age and having high intermediate risk (HIR) (Gynecologic Oncology Group [GOG] 99 criteria), none of which showed significance in multivariate analysis. The recurrence rates were higher in the patients with HIR criteria (22.2% vs. 4.1%, p=0.013) or patients with stage IB, grade 2 endometrioid carcinoma (9.4% vs. 4.3%, p=0.199). Five-year disease-free survival and 5-year overall survival were 93.9% (95% CI, 89.9 to 5.86) and 99.5% (95% CI, 97.0 to 99.9), respectively.ConclusionThe patients with low risk stage I endometrial carcinoma had excellent outcomes with surgery alone. Our study showed that no single factor was demonstrated to be an independent predictor for recurrence.

Cervical cancer is the most common female cancer in the developing countries. Treatments of bulky stage IB cervical cancer have been challenged as the local control is relatively poor compared to smaller stage I disease, whether treated by radical surgery or irradiation. The treatment options are definitive concurrent chemoradiation therapy or radical surgery with or without neoadjuvant or adjuvant therapy. The treatment decision is based on the patients' status and preferences, tumor characteristics, and experiences of clinician. This study will review and compare the treatment modalities and rationales of a combination of treatment including surgery, radiation therapy, and chemotherapy for bulky stage IB cervical carcinoma.