Comprehensive Clinicopathologic Analysis for Mismatch Repair Protein Expression in Unselected Endometrial Carcinoma Patients With an Emphasis on the Role of MLH1 Deficiency.

Screening for mismatch repair (MMR) deficiency in unselected patients with endometrial carcinoma (EC) and the clinicopathologic descriptions of ECs with MMR deficiency have been well demonstrated in Western populations, but studies on Asian populations are relatively scarce. In this study, we described the clinicopathologic features of ECs according to MMR status in unselected Taiwanese patients. We also conducted subgroup analysis of MMR-deficient (dMMR) cases according to the presence or absence of MLH1. Patients diagnosed with ECs between January 2017 and February 2020 at our institution were included. Immunohistochemistry analysis of MLH1, PMS2, MSH2, and MSH6 proteins on endometrial primary tumors and clinicopathologic variables were assessed retrospectively. A total of 231 EC patients were enrolled, of whom 50 (21.6%) had dMMR tumors. Of these 50 cases, 39 had tumors that lacked MLH1 expression and 11 were positive for MLH1. The overall dMMR group was significantly related to older age, parity, and high histologic grade compared with the MMR-proficient (pMMR) group. ECs with MLH1 deficiency were obviously associated with several poor pathologic features, including high histologic grade, lymph node metastasis, and lymphovascular space invasion. Moreover, we first reported that parity and the late age at menopause are strongly correlated with MLH1-related dMMR EC group compared with pMMR group. In conclusion, triaging EC patients into pMMR, MLH1-related dMMR and non-MLH1-related dMMR groups by immunohistochemistry analysis may help clinicians to predict disease behavior and guide further management. The strong association between parity and MLH1-related dMMR ECs warrants further investigation on the underlying mechanism.

Changes in the Prevalence of HBsAg and HBeAg: a Study of 8696 Parturients in a Well Vaccinated Area.

To elucidate the impact of a hepatitis B (HB) vaccination program on the prevalence of HB surface antigen (HBsAg) and HB envelope antigen (HBeAg) as well as the success rate of HBeAg clearance among parturients, we collected data on parturients who gave birth between 2000 and 2010, and recorded the HB status postpartum of those with positive HBeAg before birth. A total of 8696 parturients were enrolled, of whom 113 with prenatal positive HBeAg were invited back. The prevalence of HBsAg decreased over the study period, particularly in the vaccinated cohort, while there was no change in the prevalence of HBeAg. Foreign parturients had a higher HBeAg-positive rate and delayed HBeAg clearance, and those with a higher body mass index (>24 kg/m2) had earlier HBeAg clearance (51.9% vs. 23.9%, p = 0.005). Only 30% of the subjects who were positive for HBeAg before birth became negative 5 years after delivery. In conclusion, the downward trend in HB infection with more significance among vaccinated parturients reflects effective prevention and the impact of universal HB immunization. Nonetheless, aggressive follow-up is necessary for parturients who are persistently positive for HBeAg postpartum, as well as developing different public health policies for foreign parturients from endemic areas.

Difficulty in diagnosis and different prognoses between colorectal cancer with ovarian metastasis and advanced ovarian cancer: An empirical study of different surgical adoptions.

OBJECTIVE: To determine the clinical manifestations and optimal management of female patients with advanced colorectal cancer (CRC) metastasis in ovaries mimicking advanced ovarian malignancy. MATERIALS AND METHODS: A retrospective medical records review of female patients with primary CRC metastasis to ovaries, which were initially diagnosed as ovarian malignancy, and treated between 2001 and 2013. Clinical presentations, pathologic findings, and treatment outcomes were analyzed. RESULTS: In total, 19 cases were collected in the study through a hospital tumor registry. The mean age of the patients at the time of diagnosis was 45 years (range, 28-63 years). The most common symptoms were abdominal pain or increased abdominal girth (63%). None of them had rectal bleeding. The ratio of cancer antigen-125 to carcinoembryonic antigen was available in 13 out 19 patients (less than 25 in 76.9%). Barium enema or colonoscopic exam was only performed in 10 outpatients. None of them had a positive finding. All 19 patients went for surgery, all of them had ovarian metastasis but only eight of them had bilateral involvement, and 14 of them had carcinomatosis. All patients went for either optimal cytoreduction surgery or suboptimal cytoreduction surgery. The patients who received optimal cytoreduction surgery had a significant better progression-free and overall survival than those who did not. CONCLUSION: Clinical manifestations of primary CRC with ovarian metastasis may be confused with advanced ovarian cancer. Negative barium enema or colonoscopic exam cannot rule out the possibility of CRC. For patients with a cancer antigen-125 to carcinoembryonic antigen ratio less than 25, 76% are good reference of CRC metastasis to ovaries. Optimal cytoreduction surgery like that used for treating advanced ovarian cancer had a better prognosis than suboptimal cytoreduction colorectal cancer treatment.

Pretreatment Factors Associated with Recurrence for Patients with Cervical Cancer International Federation of Gynecology and Obstetrics Stage IB1 Disease.

BACKGROUND: Pretreatment prognostic information is lacking for patients with cervical cancer International Federation of Gynecology and Obstetrics (FIGO) stage IB1 disease. Thus, we attempted to identify a high-risk subgroup among them prior to treatment. METHODS: Cervical cancer FIGO stage IB1 patients who had received curative treatment with various modalities in our institute between January 2004 and December 2010 were enrolled. Pretreatment clinical parameters including age, squamous cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen, hemoglobin (Hb) level, platelet count, histological type, and treatment modality were analyzed for treatment outcomes. RESULTS: One hundred ninety-seven patients were included with a median follow-up of 66 months (range 6-119 months). In Cox regression analysis, only SCC histology (HR 0.457, 95% CI 0.241-0.967, p = 0.017) was an independent factor predicting better disease-free survival (DFS). Among SCC histology, patients with an Hb level less than 12 g/dl and a SCC-Ag level more than 3 ng/ml had worse treatment outcomes. The 5-year DFS rates were 89.2, 69.3, and 44.4% for the patients at low-risk (SCC, Hb >12 g/dl, SCC-Ag ≤3 ng/ml), intermediate-risk (non-SCC), and high-risk (SCC, Hb ≤12 g/dl, SCC-Ag >3 ng/ml), respectively (p < 0.001). CONCLUSION: Non-SCC and SCC histology with both anemia and high pretreatment SCC-Ag level were associated with recurrence. Further validation studies are warranted for clarification.

High immunohistochemical expression of TGF-ß1 predicts a poor prognosis in cervical cancer patients who harbor enriched endoglin microvessel density.

Endoglin, a coreceptor for transforming growth factor ß1 (TGF-ß1) in vascular endothelial cells, is highly upregulated in tumor vessels and therefore is a specific biomarker for angiogenesis. Some studies have suggested that assessment of tumor angiogenesis may predict cancer response to chemotherapy and radiotherapy. In this study, we attempted to analyze the immunohistochemical expression of endoglin and TGF-ß1 from 80 patients with different International Federation of Gynecology and Obstetrics (FIGO) stages of cervical cancer before they received concurrent chemoradiation and to investigate their prognostic significance. The median follow-up period was 86 months (range, 2-144 months). Endoglin staining was assessed by microvessel density (MVD), whereas TGF-ß1 expression was semiquantified as negative, weakly, or strongly staining. A receiver operating characteristic curve was established for endoglin MVD in predicting survival; the optimal cutoff value was 11.125. With a Cox regression analysis, we found that an advanced FIGO stage (hazard ratio 4.66; 95% confidence interval 2.10-10.32, P<0.001) and endoglin MVD more than 11.125 (hazard ratio 12.21; 95% confidence interval 3.62-41.16, P=<0.001) were independent factors to predict survival. Interestingly, a strong TGF-ß1 expression was significantly associated with poor survival only when the endoglin MVD value was higher than 10. Our study shows that evaluation of endoglin MVD by immunochemistry can be used as an independent prognostic marker for cervical cancer patients receiving concurrent chemoradiation. TGF-ß1 also had an impact on survival only when endoglin MVD was enriched, suggesting its involvement in tumor progression in the later stage of angiogenesis.

Disseminated peritoneal tuberculosis simulating advanced ovarian cancer: a retrospective study of 17 cases.

OBJECTIVES: The abdominopelvic cavity is one of the common sites for extrapulmonary tubercular infections. The rate of preoperative misdiagnoses between peritoneal tuberculosis (TB) and ovarian cancer is high because of overlapping nonspecific signs and symptoms. We attempted to analyze the experience within our hospital so as to establish the best means of discriminating between peritoneal TB and advanced ovarian cancer. METHODS: Seventeen patients diagnosed as having peritoneal TB between July 1986 and December 2008 at the Obstetrics and Gynecology Department of our hospital with the initial presentation simulating advanced ovarian cancer were retrospectively reviewed and evaluated. RESULTS: Patients' ages ranged from 24 years to 87 years (median, 38 years). Ten of 17 patients (60%) were younger than 40 years. All patients except one had elevated serum cancer antigen-125 levels with a mean of 358.8 U/mL (range, 12-733 U/mL). Computed tomographic (CT) scans showed ascites with mesenteric or omental stranding in all (100%), enlarged retroperitoneal lymph nodes in six (35.3%), and an adnexal mass in three (17.6%). Abdominal paracentesis was performed in seven cases, in which the findings revealed lymphocyte-dominant ascites without malignant cells. Surgical intervention by laparotomy was performed in 13 cases (76%) and by laparoscopy in three cases (18%), and a CT-guided peritoneal biopsy was performed in one case (6%). A frozen section was taken from 16 patients but not the patient who received a CT-guided peritoneal biopsy, and all revealed granulomatous inflammation. A final pathological examination confirmed a diagnosis of peritoneal TB. All patients responded to anti-TB treatment. CONCLUSIONS: In view of these data, a clinical diagnosis of peritoneal TB should be considered in a relatively young female with nonspecific symptoms of abdominal distension and wasting, as well as lymphocytic ascites without malignant cells. Laparoscopy or a minilaparotomy to obtain tissue samples for frozen-section analysis may be the most direct and least-invasive approach for a diagnosis, thus avoiding unnecessary extended surgery in these patients.

Mortality from breast, endometrial and ovarian cancers among grand multiparous women in Taiwan.

OBJECTIVE: This study was undertaken to examine whether there is a protective effect of grand multiparity on the risks of death from hormone-dependent cancers. METHODS: The study cohort consisted of 144 922 women with at least five children (grand multiparous (GM) women) in the Birth Register between 1 January 1978 and 31 December 1987. Standardised mortality ratios (SMRs) for cancers of the breast, endometrium and ovary were calculated by dividing the numbers of observed cancer deaths to the expected numbers of deaths based on the rates of national female population. RESULTS: Among the 144 922 GM women, a total of 394, 18 and 72 deaths were caused by cancers of the breast, endometrium and ovary, respectively. The SMRs among GM women were 0.73 (95% confidence intervals (CI) 0.66-0.80) for breast cancer, 0.54 (95% CI 0.29-0.79) for endometrial cancer and 0.64 (95% CI 0.49-0.79) for ovarian cancer. CONCLUSIONS: This study provides evidence that grand multiparity may confer a protective effect on the risk of death from cancers of the breast, endometrium and ovary.

Primary fallopian tube carcinoma: clinicopathological analysis of 12 cases.

OBJECTIVE: Primary fallopian tube carcinoma is one of the least common gynecological cancers and is difficult to diagnose preoperatively. We aimed to analyze the clinicopathological characteristics of this rare disease and to identify the prognostic factors predicting prognosis. MATERIALS AND METHODS: Twelve cases of primary fallopian tube carcinoma that had been diagnosed and treated in Kaohsiung Chang Gung Memorial Hospital between July 1986 and December 2005 were retrospectively reviewed. Factors, including age, gravidity, parity, stage, surgical intervention, pathological findings, relapse, and survival, were analyzed. RESULTS: The median age of the 12 cases was 54 years (range, 32-67 years), whereas the median follow-up time was 38 months. None of the 12 cases were diagnosed preoperatively. Preoperative diagnoses were adnexal mass of unknown nature in six (50%), tubo-ovarian abscess in three (25%), ovarian carcinoma in two (16.7%), and endometrioma in one (8.3%) cases. Two patients (16.7%) had experienced the typical symptom of watery vaginal discharge. Three patients (25%) were in Stage I, three (25%) in Stage II, four (33.3%) in Stage III, and two (16.7%) were unstaged. Nine patients had received postoperative platinum-based adjuvant chemotherapy. The 5-year disease-free survival rate was 64%. On evaluating the correlation between clinicopathological parameters and survival, only the Federation of Gynecology and Obstetrics stage (p=0.017) was a significant prognostic factor. CONCLUSION: Although preoperative diagnosis of fallopian tube carcinoma is difficult, still 16.7% of our patients experienced the typical symptom suggestive of tubal carcinoma. Prognostic factors associated with fallopian tube cancer were similar to those of epithelial ovarian cancer.

Parity, age at first birth, and risk of death from liver cancer: Evidence from a cohort in Taiwan.

BACKGROUND AND AIM: The present study was undertaken to examine whether there is an association between parity and age at first birth and risk of liver cancer. METHODS: The study cohort consisted of 1,292,462 women who had a first and singleton childbirth between 1 January 1978 and 31 December 1987. We tracked each woman from the time of their first childbirth to 31 December 2007, and their vital status was ascertained by linking records with the computerized mortality database. Cox proportional hazard regression models were used to estimate the relative risks (RR) of death from liver cancer associated with parity and age at first birth. RESULTS: There were 826 liver cancer deaths during 32,464,186.58 person-years of follow-up. The mortality rate of liver cancer was 2.54 cases per 100,000 person-years. The adjusted RR was 1.59 (95% confidence interval [CI] = 1.36-1.86) for women who gave birth between 26 and 30, 2.41 (95% CI = 1.81-3.20) for women who gave birth between 31 and 35, and 6.26 (95% CI = 4.27-9.19) for women who gave birth after 35 years of age, respectively, when compared with women who gave birth at less than 25 years of age. The adjusted RR was 0.72 (95% CI = 0.59-0.87) for women who had two to three children, and 0.63 (95% CI = 0.47-0.84) for women with four or more births, respectively, when compared with women who had given birth to only one child. CONCLUSIONS: The present study suggests that reproductive factors (parity and early age at first birth) may confer a protective effect on the risk of liver cancer.

Clinical characteristics of perforated pyometra and impending perforation: specific issues in gynecological emergency.

OBJECTIVE: To evaluate the clinical characteristics of pyometra and the differences between perforated pyometra and early-drained pyometra in order to prevent morbidity. MATERIAL AND METHODS: Retrospective study of 14 patients diagnosed between 1998 and 2008 with early-drainage pyometra and six patients with perforated pyometra were included. In addition, a review of the literature yielded another 30 perforated pyometra cases for comparison. RESULTS: Of 20 women with pyometra, the main presented symptoms at admission were abdominal pain (80%), fever (45%) and vaginal discharge (25%). The majority of organisms isolated were Bacteroides fragilis (seven cases), Streptococcus species (six cases) and Escherichia coli (five cases). Of the 36 cases with spontaneous uterine perforation to date, 35 cases (97%) had abdominal pain, 11 cases (31%) had fever, and 10 cases (27%) had vomiting. Hypoalbuminemia was found in seven patients (five cases in the perforation group and two cases in the drainage group). CONCLUSION: Early diagnosis of pyometra before perforation can avoid surgical exploration and decrease morbidity and mortality. Perforated pyometra should be considered as a differential diagnosis in women with pneumoperitoneum and fever. Hypoalbuminemia should be considered as a predisposing factor for pyometra perforation.

Synchronous presentation of uterine leiomyosarcoma and retroperitoneal liposarcoma: analysis by comparative genomic hybridization and review of the literature.

Multiple primary malignant neoplasms are not uncommon, whereas 2 different types of primary sarcomas simultaneously presenting in 1 individual is quite unusual. We encountered a patient presenting with a uterine sarcoma and another retroperitoneal mass at the same time. These 2 tumors showed distinct pathologic and immunohistochemical features. The diagnosis of a synchronous presentation of a uterine leiomyosarcoma and a retroperitoneal sclerosing well-differentiated liposarcoma was rendered. Further study by comparative genomic hybridization showed unrelated genomic alterations of these 2 tumors. Nevertheless, other common genetic alterations such as balanced translocations, point mutations, or epigenetic modifications could still exist because of the limitation of findings by comparative genomic hybridization. In conclusion, both metastasis and multiple primary tumors should always be taken into consideration in differential diagnosis while encountering synchronous sarcomas.

Angioleiomyoma originating from the ovary of an eleven-year-old premenarchal girl.

BACKGROUND: Angioleiomyoma (ALM) is a rare, benign neoplasm involving the peripheral soft tissues. ALM has not previously been described to originate from the ovary. We present a case herein of a premenarchal girl with a large ALM originating from the ovary. CASE: An 11-year-old girl underwent a laparotomy during the course of evaluation and treatment of a palpable, painless, abdominal mass. The mass was shown to have a strong blood flow by sonography. A solid mass left ovarian was identified and resected. The final pathologic report of the resected tumor was consistent with an ALM. CONCLUSION: To our knowledge, this is the first report of an ALM arising from the ovary. The treatment of choice for such an ovarian mass is surgical excision, which is usually a curative measure.

Management of relapsed/refractory epithelial ovarian cancer: current standards and novel approaches.

Approximately 60% to 70% of epithelial ovarian cancers are diagnosed at an advanced stage. Treatment of advanced disease involves cytoreductive surgery followed by systemic treatment with paclitaxel and platinum. Overall response rates are high, ranging from 70-80%; however, 70-80% of responders will relapse and require further systemic chemotherapy. Patients who experience disease relapse with platinum-free interval of less than 6 months are considered as platinum-refractory/resistant individuals. In this clinical setting, agents with non-cross-resistance to first-line therapy and favorable toxicity profiles are usually chosen. In the management of relapsed patients with platinum-free interval over 6 months, the generally accepted recommendation is retreatment with a platinum plus paclitaxel combination. In general, treatment of recurrent disease is palliative and is initiated with the goals of controlling disease-related symptoms, limiting treatment-related toxicity, maintaining or improving quality of life, delaying time to progression, and prolonging survival. A number of currently available and novel investigating agents in recurrent epithelial ovarian cancer will be reviewed in this context.

Value of preoperative serum CA125 in early-stage adenocarcinoma of the uterine cervix without pelvic lymph node metastasis.

OBJECTIVE: This investigation attempted to clarify the value of preoperative serum CA125 in predicting histopathological prognostic factors for early-stage cervical adenocarcinoma without lymph node metastasis. METHODS: This study initially surveyed 163 patients with clinical stage Ib or IIa cervical adenocarcinoma treated with radical hysterectomy and pelvic lymphadenectomy. Of the 163 patients, 116 had preoperative serum CA125 levels, and 14 had pelvic lymph node metastasis. The investigation group comprised 102 lymph node-negative patients. RESULTS: A cutoff value of 26 U/ml was obtained after the discriminant function analysis for identifying patients with positive lymph vascular space invasion (LVSI) or depth of stromal invasion > or =2/3 thickness. Multivariate analysis revealed that among the preoperative clinicopathological variables, including age, tumor size, parametrial invasion, and CA125 level, raised CA125 most significantly influenced the assessment of the LVSI (P = 0.040) and depth of cervical stromal invasion (P = 0.002). CONCLUSIONS: In early-stage cervical adenocarcinoma with negative pelvic lymph node metastasis, preoperative serum CA125 levels at the cutoff value of 26 U/ml impacted the determination of the poor histopathological prognostic factors.

High prevalence of genital human papillomavirus type 52 and 58 infection in women attending gynecologic practitioners in South Taiwan.

BACKGROUND: We attempted to determine the prevalence of genital human papillomavirus (HPV) infection in women attending gynecologic practitioners in South Taiwan. METHODS: The population included 4383 women aged 16-78 seeking HPV testing at primary gynecologic practitioners regardless of their cervical cytology results. HPV DNA was identified from cervical swabs using semi-nested polymerase chain reaction with MY11, MY09/HMB01, and MY11/bioGP6+ primers. Genotyping for high-risk HPV (HR-HPV) was done separately by a HR-HPV chip, which contained 13 type-specific oligonucleotides on a nylon membrane. RESULTS: The overall HPV prevalence was 19.3% (849/4383), 11.1% (488/4383) were confirmed as HR-HPV positive. Among the women with HR-HPV infection, HPV-16 was the most prevalent type (22.1%; 108/488), followed by HPV-52 (21.3%; 104/488), and HPV-58 (19.9%; 97/488). Multiple infections were detected in 73 women (15.0%; 73/488). For women with age 30 or younger, the overall HPV and HR-HPV prevalence were 32.0% and 20.7%, respectively, which were significantly higher than those of women age older than 30 (17.2% and 9.5%, P < 0.001). More multiple infections (22.1% vs. 12.4%) were also found in women with age 30 or younger (P = 0.021). However, the relative contribution of types to the overall HR-HPV positive among different age groups remains the same. CONCLUSIONS: Our results showed an HPV prevalence that is similar compared with worldwide levels. HPV prevalence and multiple infections rate were decreasing across the age groups. Unlike most previous studies, the relative high prevalence of HPV 52 and 58 among South Taiwan women has important implications in vaccine prophylaxis.

Therapeutic effect of topical applications of trichloroacetic acid for vaginal intraepithelial neoplasia after hysterectomy.

OBJECTIVE: We attempted to evaluate the therapeutic effect of trichloroacetic acid (TCA) for vaginal intraepithelial neoplasia (VaIN) after hysterectomy and to identify factors affecting persistence/recurrence. METHODS: Twenty-eight post-hysterectomy patients with various grades of VaIN were enrolled in this study between January 2001 and December 2003. They were managed with intravaginal 50% TCA once weekly for 1-4 weeks, and all patients were followed up every 3 months for at least 1 year. Assessments by Papanicolaou smear and colposcopy were performed, as was biopsy when indicated during the follow-up period. Cox regression analysis was used to identify independent factors predicting persistence/recurrence. RESULTS: In 20 of 28 patients (71.4%) VaIN went into remission. Treatment success was observed in all 11 patients with VaIN I, whereas only 9 out of 17 patients (53%) with VaIN II/III went into remission (P = 0.009). Severity of VaIN was the only significant independent predictor of persistence/recurrence (odds ratio = 3.5; 95% confidence interval = 1.1, 11.6; P = 0.038). The treatment was well tolerated with no major side effects. CONCLUSIONS: Based on our findings, 50% TCA was a potential agent with minimal side effects for low-grade VaIN. Further prospective controlled study is warranted to verify our statements. However, as for high-grade lesions, further investigation with different TCA concentration is compelling.

Acute diarrhea during pelvic irradiation: is small-bowel volume effect different in gynecologic patients with prior abdomen operation or not?

OBJECTIVE: To evaluate volume effect of small bowel for diarrhea during pelvic irradiation in gynecologic patients with or without prior abdomen operation. METHODS: From January 1996 through December 2003, 759 patients undergoing 4-field pelvic irradiation for cervical or uterine cancer were analyzed. Whole pelvic (WP), modified whole pelvic (MWP), or lower pelvic (LP) irradiation were delivered initially. According to contrast medium within small bowel in simulation films, we categorized the small-bowel volume of full dose related to WP fields as small-volume and large-volume groups. We recorded the severity of diarrhea until 39.6 Gy/22 fractions of pelvic irradiation. The actuarial rates of overall and moderate to severe diarrhea were compared among different groups. RESULTS: Significantly more large-volume distribution (85%) was noted in patients >60 years without prior operation (P < 0.001). Large-volume distribution was 53%, 65%, and 82% in post-operative patients with no diarrhea, mild diarrhea, and moderate to severe diarrhea (P = 0.002), respectively. The corresponding rate was 79%, 77%, and 80% in patients without prior abdomen operation (P = 0.869). In multivariate analysis, prior operation with LP fields (P = 0.005) and prior operation with small volume (P = 0.031) were significantly protective factors for overall diarrhea. The latter was also a protective factor for moderate to severe diarrhea (P = 0.026). Prior operation could diminish overall diarrhea in patients without simultaneous large-field (WP or MWP) and large-volume. Large volume was a significant factor of overall (P = 0.014) and moderate to severe (P = 0.004) diarrhea in large-field patients with operation. The volume effect did not exist in those patients without operation. CONCLUSION: Age and operation can change small-bowel distribution. Prior operation may attenuate diarrhea if irradiated volume of small bowel is small. There is a volume effect in post-operative rather than non-operative patients receiving large-field irradiation. More practical dose-volume evaluation of small bowel may be applied for volume effect in gynecologic patients without prior operation.