Practice guidelines for the early detection of cervical cancer in Korea: Korean Society of Gynecologic Oncology and the Korean Society for Cytopathology 2012 edition.

The consensus guideline development committee of Korean Society of Gynecologic Oncology was reconvened in March 2012. The committee consisted of 36 experts representing 12 university hospitals and professional organizations. The objective of this committee was to develop standardized guidelines for cervical cancer screening tests for Korean women and to distribute these guidelines to every clinician, eventually improving the quality of medical care. Since the establishment of the consensus guideline development committee, evidence-based guidelines have either been developed de novo considering specific Korean situations or by adaptation of preexisting consensus guidelines from other countries. Recommendations for cervical cancer screening tests, management of atypical squamous and glandular cells, and management of low-grade and high-grade squamous intraepithelial lesions were developed. Additionally, recommendations for human papillomavirus DNA testing and recommendations for adolescent and pregnant women with abnormal cervical screening test results were also included.

Clear cell carcinomas of the ovary: a multi-institutional study of 129 cases in Korea with prognostic significance of Emi1 and Galectin-3.

Accurate diagnosis of ovarian clear cell carcinoma (CCC) is important because of its poor prognosis with chemoresistance and a high recurrent rate. The clinicopathologic characteristics and prognostic significance of the cell cycle regulator [early mitotic inhibitor-1 (Emi1)] and galactoside-binding protein (Galectin-3) were evaluated. Among 155 CCCs from 18 hospitals in Korea between 1995 and 2006, 129 pure CCCs were selected with consensus using immunohistochemical stains for hepatocyte nuclear factor-1ß, Wilms' tumor protein, and estrogen receptor. The expressions of Emi1, Galectin-3, p53, and Ki-67 labeling index were analyzed with clinicopathologic parameters and the patient's survival. The mean age of the patients was 49.6 yr; the tumors were bilateral in 10.9%, and the average size was 12 cm. Adenofibromatous component was found in 7%, and endometriosis in 48.1% of the cases. Psammoma body was seen in 16.3%. Disease-free survival and overall survival rates were 78.3% and 79.1%, respectively. The International Federation of Obstetrics and Gynecology (FIGO) stage was the most important prognostic indicator. Emi1 expression (>5%) was seen in 23.3% of CCCs, and associated with high FIGO grades and poor overall survival (P<0.05). High Galectin-3 (≥80%) expression was seen in 59.7% of CCCs, and associated with FIGO stages III and IV, and high Ki-67 labeling index. High Ki-67 labeling index (≥50%) and p53 expression (≥50%) were seen in 27.1% and 18.6% of CCCs, respectively, but there was no clinicopathologic and prognostic significance. On the basis of the fact that the expression of Emi1 in CCC was correlated with a high histologic grade and worse overall survival, target therapy using inhibitors of Emi1 may be tried in the management of CCC patients with Emi1 expression.

Prognostic Significance of Substaging according to the Depth of Lamina Propria Invasion in Primary T1 Transitional Cell Carcinoma of the Bladder.

PURPOSE: To evaluate the prognostic significance of the depth of lamina propria invasion in primary T1 transitional cell carcinoma (TCC) of the bladder. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 183 patients with primary T1 TCC of the bladder who had undergone transurethral resection (TUR) at our institution. Substaging was defined according to the depth of lamina propria invasion as follows: T1a, superficial invasion of lamina propria; T1b, invasion into the muscularis mucosa (MM); T1c, invasion beyond the MM but not to the muscularis propria. The prognostic significance of various clinicopathological variables for recurrence and progression was analyzed. RESULTS: Of the 183 patients, substaging was T1a in 119, T1b in 57, and T1c in 7 patients. The recurrence rate was 32.8% for T1a and 40.6% for T1b/c, but there was no significant difference between the two groups. The progression rate was significantly different between the two groups: 5.8% in T1a and 21.9% in T1b/c (p=0.003). The cancer-specific mortality rate was also significantly different: 4.2% in T1a and 14.0% in T1b/c (p=0.036). In the univariate analysis, microscopic tumor architecture was the only significant prognostic factor for recurrence. In the univariate and multivariate analysis concerning progression, depth of lamina propria invasion and concomitant carcinoma in situ were significant prognostic factors. CONCLUSIONS: Substaging according to the depth of lamina propria invasion in primary T1 TCC of the bladder was an independent prognostic factor for progression. This suggests that substaging would be helpful for guiding decisions about adjuvant therapies and follow-up strategies.

Extensive systemic sarcoidosis with testicular involvement mimicking metastatic testicular cancer.

Sarcoidosis is an idiopathic, multisystem disease that rarely involves the genitourinary tract. Here we present an unusual case of testicular sarcoidosis with extensive lymphadenopathy that mimicked a metastatic testicular tumor. A 27-year-old male presented with a palpable right testicular mass accompanied by multiple palpable inguinal lymph nodes. The scrotal ultrasound showed a hypoechoic lesion at the inferior portion of the right testis. Extensive enlarged lymph nodes were noted in multiple areas on the abdominal computed tomography. Preoperative testicular tumor markers were within the normal range. Exploration of the right testis with a frozen section analysis of the right testicular mass and of a palpable right inguinal lymph node showed granulomatous inflammation. The testis was salvaged and the final pathological diagnosis was sarcoidosis. Treatment with high-dose corticosteroids resulted in complete resolution of the intratesticular mass and a significant decrease in the extent of the lymphadenopathy.

Sarcomatoid squamous cell carcinoma of the uterine cervix successfully treated by laparoscopic radical hysterectomy: a case report.

BACKGROUND: Sarcomatoid squamous cell carcinoma of the uterine cervix is a rare tumor with uncertain pathogenesis. The rarity of this neoplasm makes it difficult to diagnose and manage, and it seems to be an aggressive tumor with a short disease-free survival. To date, < 20 cases have been reported. We report the first case of sarcomatoid carcinoma successfully treated by laparoscopic radical hysterectomy. CASE: A 26-year-old woman presented with postcoital spotting. Gynecologic examination revealed an approximately 2.5-cm-diameter mass on the posterior lip of the cervix, and biopsy revealed a sarcomatoid carcinoma. After the baseline study for cervical cancer, the patient was found to have International Federation of Obstetricians and Gynecologists stage IB1 disease. The patient underwent laparoscopic radical hysterectomy with bilateral pelvic and paraaortic lymphadenectomy. Histopathologic examination showed no evidence of parametrial tumor extension or lymph node metastasis, and no adjuvant treatment was given. CONCLUSION: This report entails the first description of laparoscopic surgery for sarcomatoid carcinoma of the cervix. Despite short-term follow-up, it seems that early-stage disease could be successfully treated by laparoscopic radical hysterectomy.

Premenopausal early-stage endometrial carcinoma patients with low CA-125 levels and low tumor grade may undergo ovary-saving surgery.

OBJECTIVE: The purpose of this study was to determine the possible predicting factors of coexisting adnexal malignancies, and to evaluate the safety of ovary-saving surgery for early-stage endometrial carcinoma in premenopausal patients. METHODS: A retrospective review of 107 patients with endometrial carcinoma who underwent surgical treatment at our institution was conducted. All patients were younger than 50 years of age and premenopausal status. Statistical analysis was performed. RESULTS: Of the 107 patients, 78 patients had stage I to II disease and both preoperative CA-125 levels were measured and tumor grades evaluated. On multivariate analysis, preoperative CA-125 levels (p=0.018) and preoperative tumor grade (p=0.029) were independent predicting factors of adnexal diseases. The risk of coexisting ovarian malignancy was 1.8% in patients with preoperative CA-125 levels less than or equal to 34.5 U/ml and preoperative tumor grade 1 or 2. The risk increases to 20% for low CA-125 and grade 3, 13.3% for high CA-125 and grade 1 or 2, and 100% for high CA-125 and grade 3. Between patients who underwent unilateral salpingo-oophorectomy and those who underwent bilateral salpingo-oophorectomy, there was no statistically significant difference in terms of BMI, preoperative CA-125 levels, FIGO stage, histology, tumor grade, lymphadenectomy, and adjuvant treatment. CONCLUSION: Ovary-saving surgery for premenopausal, early-stage endometrial cancer patients may be considered as a treatment option in those with low preoperative CA-125 and low tumor grade.

A probable case of oral bisphosphonate-associated osteonecrosis of the jaw and recovery with parathyroid hormone treatment.

INTRODUCTION: Bisphosphonates are effective for treating osteoporosis, Paget's disease of bone, and malignancy-associated bone diseases. Bisphosphonate-associated osteonecrosis of the jaw (ONJ) is a rare but serious adverse effect of bisphosphonate therapy. Due to inhibitory actions on bone turnover, bisphosphonate therapy may result in the accumulation of microdamage. CASE SUMMARY: A 74-year-old Korean woman (height, 150 cm; weight, 51 kg) was referred to the Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, South Korea, for evaluation of pain and persistent abnormal exposure of jaw bone after extraction of teeth. She had been receiving weekly oral alendronate treatment for osteoporosis for ~5 years. The patient had the clinical features of bisphosphonate-associated osteonecrosis of the mandible, which was precipitated by teeth extraction ~14 months prior to the outpatient referral visit. At her clinical baseline visit, serum hormone concentrations and bone turnover markers were as follows: thyroid-stimulating hormone, 0.88 µIU/mL (reference range, 0.25-5.00 µIU/mL); 25-hydroxyvitamin D3, 20.9 (9.0-37.6) ng/mL; parathyroid hormone (PTH), 57 (11-62) pg/mL; serum osteocalcin, 8.7 (12.9-55.9) ng/mL; and urine N-telopeptide 21 (26-124) nM/mM creatinine. She had multiple systemic risk factors for ONJ, including older age, type 2 diabetes mellitus, and long duration of bisphosphonate therapy. There was no mandibular lesion improvement despite repeated surgical procedures performed within a 14-month period. Bisphosphonate therapy was discontinued and PTH therapy was started. After 2 months, exposed oral mucosa had healed. After 4 months of treatment, the pain had completely subsided, and after 6 months the patient's eating and drinking habits returned. The serum concentration of osteocalcin, a bone formation marker, which was initially suppressed (8.7 ng/mL), increased 174% (15.1 ng/mL) from baseline after 6 months of treatment with PTH. CONCLUSIONS: Here we report a probable case of oral bisphosphonate-associated ONJ featuring suppressed bone turnover. Treatment with the bone formation-stimulating agent PTH was beneficial.

5-fluorouracil, mitomycin-C, and polysaccharide-K adjuvant chemoimmunotherapy for locally advanced gastric cancer: the prognostic significance of frequent perineural invasion.

BACKGROUND/AIMS: Although adjuvant chemotherapy has demonstrated small but significant survival benefit in locally advanced gastric cancer in several meta-analyses, optimal chemotherapy regimen remains to be determined. METHODOLOGY: We retrospectively analyzed the survival of 207 gastric cancer patients (stage IB: 19, II: 65, IIIA: 58, IIIB: 28, IV: 37) who underwent 5-fluorouracil (5-FU), mitomycin-C (MMC), and polysaccharide-K (PSK) chemoimmunotherapy (CITX) after curative resection (FM group). The survival of FM group was compared with that of historical control cohort of 103 patients with almost identical stage distribution who received 5-FU and doxorubicin-based chemotherapy (FA group). RESULTS: Five-year disease-free survival and overall survival (OS) of FM group were 58.7% and 59.1%, respectively. Frequent perineural invasion was significantly associated with poor OS (p = 0.01) in multivariate analysis. There was no statistically significant difference in 5-year OS (59.1% vs. 56.2%, p = 0.637) between FM and FA groups. FM group showed superior 5-year OS (84.4% vs. 67.6%, p = 0.019) compared with FA group in stage IB or II patients without significant difference (p = 0.222) in stage IIIA to IV. CONCLUSIONS: 5-FU, MMC, and PSK CITX is as effective as 5-FU and doxorubicin-based chemotherapy. Moreover, frequent perineural invasion seems to be an important poor prognostic factor.

Three cases of xanthogranulomatous epididymitis caused by E. coli.

Xanthogranulomatous epididymitis is an uncommon but benign process, characterized by tissue destruction and the accumulation of abundant foamy macrophages mixed with lymphocytes and plasma cells. The pathogens generally found to cause xanthogranulomatous inflammation have been Proteus and E. coli. We identified such a pathogen by sequencing divergent regions of 16S rRNA, followed by pathogen-specific-PCR using alr, ipaH, ial, and iuc primer pairs in DNA microdissected from an H&E stained slide. We report here three cases of xanthogranulomatous epididymitis caused by E. coli.

Amniotic fluid embolism with isolated coagulopathy: a case report.

BACKGROUND: Amniotic fluid embolism is a life-threatening complication of pregnancy accompanied by a high mortality rate. The common clinical presentation is sudden onset of dyspnea, hypotension inappropriate to the volume of blood loss, and hypoxia, followed by cardiopulmonary arrest. Recently, cases of amniotic fluid embolism with isolated coagulopathy as an atypical presentation have been reported. CASE: A 27-year-old multigravida presented with continuous postpartum oozing after an uneventful vaginal delivery at 38 weeks of gestation. Laboratory evidence revealed disseminated intravascular coagulopathy. Despite good uterine contractions and massive blood component therapy, vaginal bleeding continued and finally led to emergency laparotomy. Histopathologic examination showed a deep cervical laceration in the endocervix, and multiple areas of amniotic fluid debris were demonstrated in the laceration site vasculature of the endocervix. After hysterectomy, the patient recovered fully, without sequelae. CONCLUSION: This case represents atypical symptoms and signs: clinical hemorrhage in the initial presentation rather than the classical pattern of cardiopulmonary collapse. In cases of suspected amniotic fluid embolism with an atypical presentation, a thorough histologic examination of the uterus, including the cervix, is critical to making the diagnosis of amniotic fluid embolism.

Immunohistochemical and clinicopathologic characteristics of invasive ductal carcinoma of breast with micropapillary carcinoma component.

CONTEXT: A micropapillary carcinoma (MC) component is generally considered to behave aggressively. Although several reports have described the prognostic significance of MC in breast carcinomas, immunohistochemical findings of MC, especially as compared to non-MC, are rarely described. OBJECTIVE: We compared clinicopathologic and immunohistochemical findings between 38 cases of invasive breast carcinoma with an MC component (IMC) and 217 cases of invasive breast carcinoma without an MC component (NIMC). DESIGN: We constructed a tissue microarray from 38 cases of IMC and performed immunohistochemical stainings for cytokeratin (CK) 7, CK20, estrogen receptor, progesterone receptor, p53, c-Erb-B2, CD34, CK5, epidermal growth factor receptor, and c-Kit in both MC and non-MC components. RESULTS: Cases with IMC were associated with greater tumor size, more frequent lymphovascular invasion, nodal metastases, greater mean numbers of positive lymph nodes, and higher stage than those with NIMC, but were not associated with poorer survival rates. On immunohistochemistry, only p53 reactivity was statistically different between MC and non-MC components in IMC cases. Estrogen receptor positivity tended to be lower in MC than non-MC, but the difference was not significant. Most of the MCs and non-MCs in IMC cases were positive for CK7, but none of them were positive for CK20, CK5, epidermal growth factor receptor, or c-Kit. CONCLUSIONS: Based on the frequent nodal metastases and association with higher stage found in IMC as compared with NIMC cases, as well as higher p53 positivity and lower frequency of estrogen receptor expression, MC could be considered an aggressive histologic type of breast carcinoma. In both MC and non-MC components in IMC cases, no basallike immunostaining pattern was detected.

Cyclooxygenase-2 and p53 expression as prognostic indicators in conventional renal cell carcinoma.

The aim of this study was to investigate the relationship of cyclooxygenase (COX)-2 and p53 expression with prognosis in patients with conventional renal cell carcinoma (RCC). Formalin-fixed, paraffin-embedded tissue sections of conventional RCC from 92 patients, who had undergone radical nephrectomy, were examined for COX-2 and p53 expression by immunohistochemistry and compared with clinicopathological variables. The COX-2 expression significantly correlated only with tumor size (p=0.049), whereas the p53 expression profoundly correlated with the TNM stage (p=0.024), M stage (p=0.001), and metastasis (synchronous or metachronous; p=0.004). The COX-2 overexpression did not significantly associate with p53 positivity (p=0.821). The survival rate of patients correlated with the p53 expression (p<0.0001) but not with the COX-2 expression (p=0.7506). Multivariate analyses indicated that tumor size, M stage, and p53 expression were independent prognostic factors for cancer-specific survival. The COX-2 expression was not an independent factor. These results show that the increased expression of p53 was associated with metastasis and a worse prognosis in conventional RCC, which suggests that p53 might have played an important role in the progression of conventional RCC. The increased expression of COX-2 was associated only with tumor size, but may not be an important prognostic factor in conventional RCC. No association was observed between COX-2 overexpression and p53 positivity in conventional RCC.

Renal cell carcinoma in South Korea: a multicenter study.

The incidence of renal cell carcinoma (RCC) in South Korea is steadily becoming similar to that in Western countries. This study summarizes the results of a 3-year multicenter survey of RCC in South Korea, conducted by the Korean Genitourinary Pathology Study Group. A total of 795 cases of RCC were collected from 20 institutes between 1995 and 1997, including 686 clear cell RCCs (86.3%), 58 papillary RCCS (7.30%), 49 chromphobe RCCs (6.16%), and 2 collecting duct RCCs (0.25%). At least 5 years of follow-up was available for 627 clear cell, 54 papillary, and 49 chromophobe RCCs. All subtypes presented most frequently with stage T3aN0M0 at the time of operation, and papillary RCCs demonstrated more frequent lymph node metastasis. Overall survival was not significantly related to the histological subtype (clear cell vs papillary, P = 0.8651; clear cell vs chromophobe, P = 0.0584; papillary vs chromophobe, P = 0.0743). For clear cell RCCs, statistically significant associations were found between overall survival and sex (P = 0.0153), multiplicity (P = 0.0461), necrosis (P = 0.0191), age, sarcomatoid change, TNM stage, nuclear grade, and modality of treatment (all P <0.0001). Overall survival was significantly associated with tumor size (P = 0.0307), nuclear grade (P = 0.0235), multiplicity, sarcomatoid change, and TNM stage (all P <0.0001) for papillary RCCs and with the presence of sarcomatoid change (P = 0.0281), nuclear grade (P = 0.0015), treatment modality (P = 0.0328), and TNM stage (P <0.0001) for chromophobe RCCs. Age (P = 0.0125), nodal stage (P = 0.0010), and treatment modality (P = 0.0001) were significant independent prognostic indicators for clear cell RCC on multivariate analysis. This is the first multicenter study of RCC in South Korea, demonstrating the general patterns and prognostic factors of Korean RCCs.

Sonographic findings of uterine polypoid adenomyomas.

Based on a retrospective analysis of 32 patients with polypoid adenomyomas of the uterus, the authors have identified 3 sonographic patterns: solid (pattern 1, 8 cases), solid with cystic areas (pattern 2, 22 cases), and predominantly cystic (pattern 3, 2 cases). Sonographic features include a heterogeneously isoechoic, polypoid, or pedunculated endometrial mass, with an ill-defined margin, hemorrhagic foci, posterior shadowing, and associated adenomyosis in the myometrium. Knowledge of these sonographic appearances may facilitate the diagnosis of polypoid adenomyoma and help differentiate it from other polypoid uterine tumors.

Primary malignant fibrous histiocytoma of the kidney.

Primary renal malignant fibrous histiocytoma is a rare tumor of the kidney. It is clinically and radiologically indistinguishable from a renal cell carcinoma. Even following radical surgery, the tumor shows a strong predilection for local recurrence and the prognosis is generally poor. We report on a 32-year-old man with malignant fibrous histiocytoma of the kidney who remained free of recurrence for 1 year after radical nephrectomy.

In vitro evidence of the role of COX-2 in attenuating gastric inflammation and promoting gastric carcinogenesis.

Although gastric adenocarcinoma is one of the most common malignancies in the world, little is known about its exact molecular processes in development and progression. Recent studies suggest that COX-2 is important in carcinogenesis of gastrointestinal cancers, and is especially involved in carcinogenesis in a mouse model of familial adenomatosis polyposis. To understand the role of COX-2 in gastric carcinogenesis and Helicobacter pylori-associated gastritis, we measured COX-2 expression in 170 human gastric carcinoma tissues byimmunohistochemical analysis and compared the expression of COX-2 in paired tissues obtained from normal-looking and cancer-bearing mucosa. Further evidence of the involvement of COX-2 in gastritis and gastric carcinogenesis was obtained by establishing stable cell lines overexpressing COX-2. After subcloning of COX-2 into pCB7 mammalian expression vector, two stable cell lines named MKN-28-COX-2 and MKN-45-COX-2 were generated by transfection of COX-2 cDNA. To understand the effect of COX-2 on gastritis, we performed an electrophoretic mobility shift assay of NF-kappaB (inflammation-associated transcription factor), and measured malondialdehyde levels and chemiluminescence activities in both mock-transfected MKN and MKN-COX-2 cells after stimulation of H. pylori (1 x 10(6) CFU/mL) and neutrophils (10(2) cells/mL). A marked attenuation of NF-kappaB bindings and generation of free radicals was observed in COX-2 overexpressed cells. Another set of experiments, including the growth inhibition by TGF-beta treatment, Matrigel invasion assay, and apoptosis assay, was done. COX-2 showed the advantage of the escape from the growth inhibition by TGF-beta through decreasing TGF-beta RII expression and increased cell invasiveness. In conclusion, COX-2 expression seems to be induced to attenuate the degree of atrophic gastritis, the initial event in gastric carcinogenesis, and promote gastric carcinogenesis.

Helicobacter pylori infection promotes gastric carcinogenesis in a mice model.

BACKGROUND AND AIM: Debate that Helicobacter pylori might play a causative role in gastric carcinogenesis still exists in spite of the World Health Organization's definition of H. pylori as a class I carcinogen. In order to define the exact role of H. pylori infection in gastric carcinogenesis, we established a mice model of H. pylori infection. METHODS: One hundred and forty-four female C57BL/6 mice were divided into nine groups according to N-methyl-N-nitrosourea (MNU) treatment and H. pylori infection. All mice were killed at the 50th or 80th week after treatment, and their histopathological changes were evaluated according to group. RESULTS: The incidence of gastric adenocarcinoma at the 50th week was 80% in mice treated with both MNU 240 microg/L and H. pylori infection, whereas the incidence was only 27% in mice treated with only MNU 240 microg/L. Although H. pylori caused marked expansion of the proliferative zone at the surface epithelium, H. pylori infection alone caused only chronic atrophic gastritis without any evidence of carcinomas until 80 weeks. The combination of MNU and H. pylori infection also resulted in a significantly higher incidence of gastric adenoma and adenocarcinoma. Significantly higher expressions of proliferating cell nuclear antigen were noted in the gastric mucosa infected with H. pylori compared to controls. CONCLUSIONS: These results clearly demonstrated the role of H. pylori infection, rather than direct carcinogens, in promoting gastric carcinogenesis in a mice model.