Intraperitoneal mitomycin C improves survival compared to cytoreductive surgery alone in an experimental model of high-grade pseudomyxoma peritonei.

Pseudomyxoma peritonei (PMP) is a rare cancer commonly originating from appendiceal neoplasms that presents with mucinous tumor spread in the peritoneal cavity. Patients with PMP are treated with curative intent by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The value of adding HIPEC to CRS has not been proven in randomized trials, and the objective of this study was to investigate the efficacy of intraperitoneal mitomycin C (MMC) and regional hyperthermia as components of this complex treatment. Xenograft tissue established from a patient with histologically high-grade PMP with signet ring cell differentiation was implanted intraperitoneally in 65 athymic nude male rats and the animals were stratified into three treatment groups; the cytoreductive surgery group (CRSG, CRS only), the normothermic group (NG, CRS and intraperitoneal chemotherapy perfusion (IPEC) with MMC at 35 ºC), and the hyperthermic group (HG, CRS and IPEC at 41 ºC). The main endpoints were survival and tumor weight at autopsy. Adequate imitation of the clinical setting and treatment approach was achieved. The median survival was 31 days in the CRSG, 60 days in NG and 67 days in HG. The median tumor weights at autopsy were 34 g in CRSG, 23 g NG and 20 g in HG. In conclusion, the addition of IPEC with MMC after CRS doubled the survival time and reduced tumor growth compared to CRS alone. Adding regional hyperthermia resulted in a modest improvement of treatment outcome.

Resection of biliary mucinous cystic neoplasms of the liver: a prospective cohort series of 13 consecutive patients.

BACKGROUND: Biliary mucinous cystic neoplasms (BMCNs) are uncommon neoplastic septated intrahepatic cysts which are often incorrectly diagnosed and have the potential for malignant transformation. OBJECTIVE: To assess the outcome of surgical resection of BMCNs. METHOD: A prospective liver surgery database was used to identify patients who underwent surgery at Groote Schuur Hospital Complex for BMCN from 1999 to 2015. Demographic variables including age and gender were documented as well as detailed preoperative imaging, location and size, operative treatment, extent of resection, histology, postoperative complications and outcome. RESULTS: Thirteen female patients (median age 45 years) had surgery. Eleven were diagnosed by imaging for symptoms. Two were jaundiced. One cyst was found during an elective cholecystectomy. Five cysts were located centrally in the liver. Before referral three cysts were treated with percutaneous drainage and two were treated with operative deroofing. Six patients had anatomical liver resections and seven patients had non anatomical liver resections of which two needed ablation of residual cyst wall. One patient needed a biliary-enteric reconstruction to treat a fistula. Median operative time was 183 minutes (range: 130-375). No invasive carcinoma was found. There was no operative mortality. One surgical site infection and one intra-abdominal collection were treated. Two patients developed recurrent BMCN after 24 months. CONCLUSION: BMCNs should be considered in middle aged women who have well encapsulated multilocular liver cysts. Treatment of large central BMCNs adjacent to vascular and biliary structures may require technically complex liver resections and are best managed in a specialised hepato-pancreatico-biliary unit.

Primary retroperitoneal mucinous cystadenocarcinoma (PRMCa): a systematic review of the literature and meta-analysis.

PURPOSE: Primary retroperitoneal mucinous cystadenocarcinoma (PRMCa) is a rare tumour. Prognosis and optimal management are not well established. In view of a case managed in our Centre, we performed a systematic review and meta-analysis. METHOD: Systematic review of medical electronic databases for published data (1950-12/10/2015). No RCTs identified. Individual patient data detracted from case reports and case series were analysed RESULTS: In total, 73 female and 5 male cases of PRMCa identified including our case. Median age at diagnosis was 42.0 years (range 18-86 years), with women being significantly younger than men at diagnosis (42.0 years versus 62.2 years, p = 0.005). A palpable abdominal mass and abdominal pain were the most common presentations in 42.9 and 23.8 % of cases, respectively. Twenty-six women were <38 years old. There were 16 women <38 years old that had surgical data reported, of which 14 underwent fertility-sparing surgery with excision of the mass. Adjuvant chemotherapy was given in 24.1 % (13/72) women. Follow-up ranged from 1 to 130 months with a median of 15 months. Of the 57 cases that had follow-up reported, recurrence occurred in 23 cases (40.4 %) within a median of 8 months from diagnosis. Median disease-free survival was 15 months (range 1-130 months). Of the women who recurred, 14 died of their disease giving 1, 2 and 5-year disease-specific survival rates of 85.9, 80.7 and 75.4 %, respectively. CONCLUSION: PRMCa are rare and potentially aggressive tumours that often occur in young women. Removal of the tumour, adequate staging and adjuvant chemotherapy needs to be considered.

Noninvasive intraductal papillary mucinous neoplasms and mucinous cystic neoplasms: recurrence rates and postoperative imaging follow-up.

BACKGROUND: Although surveillance guidelines for resected invasive mucinous neoplastic cysts are well-established, those for noninvasive cysts are not defined. We used our experience with resected noninvasive mucinous neoplastic cysts to define recurrence rates and the optimal frequency of postoperative imaging follow-up. METHODS: We reviewed the medical records of 134 patients with resected, pathologically confirmed noninvasive mucinous neoplasms between 2002 and 2012. Demographics, comorbidities, cyst characteristics, and recurrence were evaluated. Survival analysis was used to estimate the distribution of time to recurrence and regression models were used to investigate factors associated with recurrence. RESULTS: Eighty-seven patients with intraductal papillary mucinous neoplasms (IPMNs) were compared with 47 patients with mucinous cystic neoplasms (MCNs). Those with MCNs were more often females (P = .001), significantly younger (P = .001), more symptomatic (P = .009), and had cysts more often located in the tail (P < .001). Median follow-up was 42 months. Recurrence rates for IPMNs were 0%, 5%, and 10% versus 0% for MCNs respectively at postoperative years 1, 2, and 3 (P = .014). On multivariable analysis, size >3 cm (P = .027), higher grade dysplasia (P = .043), and positive resection margins (P < .001) were significantly associated with recurrence. CONCLUSION: Resected noninvasive IPMNs with moderate- or high-grade dysplasia and negative resection margins require imaging follow-up every 2 years, given the 16% overall recurrence rate. Although the follow-up interval for noninvasive, low-grade, dysplastic IPMNs with negative margins could be lengthened, all noninvasive IPMNs having positive margins require yearly follow-up at the minimum. Resected noninvasive MCNs--irrespective of grade and margin status--do not require surveillance, although the development of branch duct-IPMNs in the remnant pancreas can be investigated in the long term at the discretion of the provider.

Preoperative endoscopic ultrasound-guided fine needle aspiration does not impair survival of patients with resected pancreatic cancer.

OBJECTIVE: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) allows preoperative tissue confirmation of malignancy, but fear of tumour cell dissemination along the needle track has limited its use. We hypothesised that if tumour cell dissemination occurs with EUS-FNA, survival after complete resection would be impaired. We aimed to evaluate the association of preoperative EUS-FNA with long-term outcomes of patients with resected pancreatic cancer. DESIGN: Using the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified patients with locoregional pancreatic cancer who underwent curative intent surgery from 1998 to 2009. The patients who received EUS-FNA within the peridiagnostic period were included in the EUS-FNA group. Patients who did not receive EUS evaluation or who underwent EUS without FNA were included in the non-EUS-FNA group. Overall survival and pancreatic cancer-specific survival were compared after controlling for relevant covariates. RESULTS: A total of 2034 patients with pancreatic cancer were included (90% pancreatic adenocarcinoma). Of these, 498 (24%) patients were in EUS-FNA group. Patients with multiple comorbidities and more recent diagnosis were more likely to receive EUS-FNA. In multivariate analysis, after controlling for age, race, gender, tumour histology, tumour stage, tumour grade, tumour location, SEER site, year of diagnosis, undergoing percutaneous aspiration/biopsy, Charlson Comorbidity Index, radiation and chemotherapy, EUS-FNA was marginally associated with improved overall survival (HR 0.84, 95% CI 0.72 to 0.99), but did not affect cancer-specific survival (HR 0.87, 95% CI 0.74 to 1.03). CONCLUSIONS: Preoperative EUS-FNA was not associated with increased risk of mortality. These data suggest that EUS-FNA can be safely performed for the work-up of suspicious pancreatic lesions.

Association of pancreatic adenocarcinoma up-regulated factor expression in ovarian mucinous adenocarcinoma with poor prognosis.

Pancreatic adenocarcinoma up-regulated factor (PAUF) expression is elevated in both ovarian tumors and pancreatic adenocarcinoma. However, PAUF expression in ovarian tumors according to histologic subtype and grade has not been investigated. In this study, we examined various clinicopathologic features of 24 patients with mucinous cystadenoma (MCA), 36 with mucinous borderline tumors (MBTs), and 46 with mucinous adenocarcinomas (MACs) according to PAUF expression status assessed using immunohistochemistry. We found that MACs more frequently stained positive for PAUF than did MCAs and MBTs (P < 0.0001). Although there was no significant differences with respect to other clinicopathologic characteristics of MACs according to PAUF expression status, patients with PAUF-weakly positive and PAUF-strongly positive MACs tended to have a shorter overall survival (OS) than those with PAUF-negative MAC, determined using a Kaplan-Meier analysis (P = 0.1885). After adjusting for various clinicopathologic parameters, PAUF positivity of MACs was a significant predictive factor for disease-free survival (DFS) (negative vs. weakly positive: P = 0.045, hazard ratio [HR] = 57.406, 95% confidence interval [CI]: 1.090-3022.596; and negative vs. strongly positive: P = 0.034, HR = 97.890, 95% CI: 1.412-6785.925). In conclusion, PAUF was more frequently expressed in MAC than in its benign and borderline counterparts, and was associated with a poor OS and DFS in MAC patients. Therefore, we suggest that PAUF may be a practical biomarker for histopathological categorization and a prognostic marker for patients with an ovarian mucinous tumor.

Surgical resection and outcome of pancreatic cystic neoplasms in China: analysis of a 16-year experience from a single high-volume academic institution.

BACKGROUND: To investigate the clinicopathological features of surgically resected pancreatic cystic neoplasms (PCNs) at a single institution in China. METHODS: The medical charts of patients who operated in the Second Affiliated Hospital, Zhejiang University School of Medicine between 1 January 1997 and 30 June 2013, were pathologically shown to have PCNs. RESULTS: There was a reliable increase trend not just in the overall number of patients (3 to 75) but additionally in the number of incidentally diagnosed patients across the periods (33.3% to 48.0%). In 83 of 111 cases, preoperative diagnoses matched with pathology, whereas the remaining cases (16/28) were misdiagnosed as pancreatic cancer. The proportion of malignancy in mucin producing neoplasms was 24.3% (9 out of 37). Elevated serum carbohydrate antigen (CA19-9) or carcinoembryonic antigen (CEA) was independently associated with malignancy. The overall survival rate was 96.4%. CONCLUSIONS: The proportion of PCNs within this series differs with that revealed in Western countries. Appropriate preoperative differential diagnosing of PCNs remains challenging. It is strongly recommended that patients with elevated CA19-9 or CEA levels undergo surgical resection.

[Mucinous ovarian neoplasms. Prognostically mostly excellent, infrequently a wolf in sheep's clothing]. / Muzinöse Ovarialtumoren. Prognostisch meist exzellent, selten Wölfe im Schafspelz.

Mucinous ovarian neoplasms represent the second largest group of epithelial ovarian tumors after serous neoplasms, of which benign cystadenomas constitute more than 80 %. Mucinous cystadenomas and carcinomas cannot be distinguished by the clinical features or the mean age of onset of the disease. They typically occur unilaterally, are confined to the adnexae (FIGO stage I) and clinically present with non-specific abdominal symptoms or are diagnosed by chance. The mean age of disease onset is around 50 years old. The prognosis is excellent. Implants, peritoneal metastases and bilateral occurrence of ovarian mucinous neoplasms should lead to the suspicion of metastasis particularly from a gastrointestinal tumor. Neither microinvasion defined as a maximum extent of invasion of 5 mm, nor intraepithelial carcinoma characterized by high grade atypia without invasion, affect the prognosis of mucinous borderline tumors. Mucinous carcinomas typically show confluent glandular, expansile growth that leads to a labyrinth-like pattern. A destructive infiltrative or nodular growth pattern, however, should lead to the consideration of metastasis. Mural nodules that may reveal a spindle cell sarcomatous or anaplastic carcinomatous pattern occur infrequently in mucinous and do not affect the prognosis. Pax8 positivity is indicative of a primary ovarian neoplasm. In this case, however, mucinous tumors associated with teratomas may show the colonic immunoreaction pattern (CK7-/CK20+/CDX2+). The rare mucinous tumors with endocervical differentiation are now designated as seromucinous tumors and consist of two or more distinct cell types, are frequently associated with endometriosis and seem to show a molecular genetic relationship to endometrioid neoplasms.

Clinicopathological features and prognosis of mucin-producing bile duct tumor and mucinous cystic tumor of the liver: a multi-institutional study by the Japan Biliary Association.

BACKGROUND: The aim of this study was to determine the clinicopathological features and surgical outcomes of mucinous cystic neoplasm of the liver (MCN) and mucin-producing intraductal papillary neoplasm of the intrahepatic bile duct (M-IPNB). METHODS: We performed a multi-institutional, retrospective study of patients with MCN or M-IPNB pathologically defined by the presence or absence of an ovarian-like stroma. RESULTS: The M-IPNB and MCN were diagnosed in 119 and nine patients, respectively. MCN was observed in female patients, while M-IPNB produced symptoms of cholangitis. M-IPNBs were classed as low or intermediate grade in 53 cases, high grade in 23 and invasive carcinoma in 43. Fifty-one of the M-IPNBs were the pancreatobiliary type (PT), 33 were the intestinal type (IT), 23 were the oncocytic type (OT), and 12 were the gastric type (GT). The 1-, 5- and 10-year survival rates for the 105 patients with M-IPNB were 96%, 84% and 81%, respectively, while the 5-year survival rate for patients with MCN was 100%. OT and GT M-IPNB had better 10-year survival rates than PT and IT M-IPNB. CONCLUSIONS: Although MCN has different features from M-IPNB, both diseases have a good prognosis after resection. The cellular type of M-IPNB appears to predict outcome.

Examining the accuracy and clinical usefulness of intraoperative frozen section analysis in the management of pancreatic lesions.

BACKGROUND: Intraoperative frozen section analysis is often performed in the surgical management of pancreatic lesions. This test is used to obtain histologic diagnosis, to assess resectability because of unanticipated locoregional spread, and to ensure negative margins after resection. We sought to define the accuracy and clinical usefulness of intraoperative frozen section analysis in patients with pancreatic lesions and to determine the impact on long-term outcomes. METHODS: A retrospective database review was performed for all patients who underwent pancreatic resection at our institution from 2002 to 2011. Patient demographics, indications for frozen section analysis, final pathology, and long-term outcomes were analyzed. Five-year survival was compared using the Kaplan-Meier method. RESULTS: Sixty-eight patients were identified (mean age 65 ± 14 years, 52% female). Malignancy was identified on final pathology in 38 (56%) patients. Intraoperative frozen section analysis was performed in 59 (87%) patients. Frozen section analysis was performed for histologic diagnosis in 6 (10%) cases, to determine resectability in 15 (25%) cases, and to evaluate margin status in 58 (98%) cases. Frozen section analysis for histologic diagnosis was associated with a sensitivity of 80%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 50% with an overall accuracy of 83%. Frozen section analysis for the determination of resectability was associated with a sensitivity of 38%, specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 58% with an overall accuracy of 66%. Intraoperative frozen section analysis for the determination of the final margin status was associated with a sensitivity of 33%, specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 97% with an overall accuracy of 97%. There were no false-positive results on frozen section analysis. Errors on frozen section analysis interpretation did not negatively impact survival outcomes (mean survival = 2.2 years in those with concordant frozen section analysis vs 1.7 years in those with discordant frozen section analysis, P = .69). CONCLUSIONS: Although intraoperative frozen section analysis is helpful for ensuring negative final margins, its usefulness for obtaining histologic diagnosis and determining resectability is limited by low negative predictive potential. These results highlight the importance of preoperative staging and intraoperative surgical judgment for questionable resectable disease.

Prognostic significance of APE1 cytoplasmic localization in human epithelial ovarian cancer.

Cytoplasmic localization of apurinic/apyrimidinic endonuclease 1 (APE1) correlates with different tumorigenic processes and poor prognosis in several cancer types. However, rare investigation into the prognosis value of cytoplasmic localization of APE1 was provided in ovarian cancer. The present study examined for the first time the cytoplasmic localization of APE1 in epithelial ovarian cancer (EOC) by immunohistochemistry. The relationship between cytoplasmic localization of APE1 and clinicopathological parameters, as well as the correlation between cytoplasmic localization of APE1 and prognosis, was investigated. We found that cytoplasmic positivity was significantly higher in EOCs with low tumor differentiation (P = 0.002) and was significantly higher in advanced Federation International of Gynecology and Obstetrics (FIGO) stage (III + IV) patients compared to that in early FIGO stage (I + II) patients (40.7% vs. 11.8%; P = 0.002). No significant difference was observed in APE1 pattern referring to age, tumor size, family history, histological type, ascites, and lymphatic metastasis (P > 0.05). In addition, a lower survival rate was found in patients with cytoplasmic positive localization of APE1 compared to that in patients with cytoplasmic negative localization (P < 0.05). All these findings suggest that cytoplasmic localization of APE1 is associated with tumor progression and might be a valuable prognostic marker for EOC.

Prognostic impact of prechemotherapy serum levels of HER2, CA125, and HE4 in ovarian cancer patients.

OBJECTIVE: Human epididymis protein 4 (HE4) has attracted a lot of interest as a relatively novel biomarker for ovarian carcinoma. Research focus has been directed at HE4 as a diagnostic tool with potential for better triage of women with adnexal masses but the prognostic aspect of HE4 in ovarian cancer patients remains to be elucidated. The aim of the present study was to investigate the prognostic value of prechemotherapy serum HER2, cancer antigen 125 (CA125), and HE4 levels in ovarian cancer patients receiving standard combination chemotherapy. METHODS: Serum from 139 patients with newly diagnosed ovarian cancer was analyzed for HER2, CA125, and HE4 using enzyme-linked immunosorbent assay assays. Samples were collected just before first-line chemotherapy, and all patients were treated with carboplatin-paclitaxel combination chemotherapy. RESULTS: Increasing levels of serum HE4 (grouped into quartiles) was significantly associated with worse progression-free survival (PFS) (P < 10) and overall survival (P < 10). After adjustment in the Cox model, HE4 serum levels remained an independent prognostic parameter for PFS, with a hazard ratio of 1.77 (95% confidence interval, 1.03-3.04; P = 0.040) for patients with HE4 levels above the median compared with patients with HE4 levels below the median. The shorter PFS for patients with high levels of HE4 also translated into an independent significant difference in overall survival (hazard ratio, 3.17 [95% confidence interval, 1.41-7.10]; P = 0.005).Serum HER2 and CA125 levels did not demonstrate an independent prognostic value. CONCLUSIONS: High levels of serum HE4 is a strong and independent indicator of worse prognosis in epithelial ovarian cancer patients.

Immunohistochemical expression of epidermal growth factor receptor, E-cadherin, and matrix metalloproteinase-9 in ovarian epithelial cancer and relation to patient deaths.

Ovarian cancer is the most frequent cause of death from gynecologic cancer in the world. Current prognostic factors do not allow reliable prediction of response to chemotherapy and survival for individual ovarian cancer patients. Epidermal growth factor receptor (EGFR), E-cadherin, and matrix metalloproteinase (MMP)-9 are frequently studied in cancer; but their prognostic value in ovarian carcinoma remains unclear. In this study, we investigated the immunohistochemical expression of EGFR, E-cadherin, and MMP-9 in 120 cases of ovarian epithelial carcinoma; their relation to each other; their relation to histologic type, grade, and stage; and their relation to death rates after 3years of follow-up. Our results show that EGFR and MMP-9 were overexpressed extensively in high grades and advanced stages especially in nonserous carcinomas. E-cadherin was gradually lost in advanced cancers. There was a positive relation between the 3 antibodies and between them and the death rates. There is a strong relationship between EGFR and MMP-9, and this relation may occur by affecting E-cadherin. The present study provides a rationale for evaluating drugs that target these new pathways that may be promising in ovarian cancer treatment.

[Clinicopathologic features of 234 cases with borderline ovarian tumors].

OBJECTIVE: To determine the clinicopathologic characteristics and prognostic factors that may be used to predict the poor outcome of patients with borderline ovarian tumors. METHODS: All cases with borderline ovarian tumors treated in the West China Second University Hospital from January 2001 to June 2007 were analyzed retrospectively for clinicopathologic features, treatment parameters and outcome of treatment. Univariate and multivariate analyses were used to assess independent prognostic factors using the logistic regression model. RESULTS: The median age of 234 patients was 40.1 years with a range of 14 to 80 years. There were 101 (43.2%), 94 (40.2%), 19 (8.1%), 12 (5.1%), 8 (3.4%) cases of serous, mucinous, mixed, endometrioid and clear cell tumors, respectively. Out of 234 cases, 182 (77.8%) underwent laparotomy and 45 (19.2%) underwent laparoscopy. Seven women underwent laparoconversion. Fertility sparing surgery was performed on 119 cases (50.9%) and radical surgery was performed on 115 cases (49.1%). Totally 161 (68.8%) patients had stage I, 19 (8.1%) had stage II, 54 (23.1%) had stage III, and none had stage IV disease. Sixty-four women received postoperative chemotherapy. The median follow-up was 40 months with a range of 8 to 78 months. Recurrence was found in 26 cases (11.1%) during follow-up, and no tumor-related death was reported. The logistic regression model showed that surgery procedure (OR = 2.304, P = 0.024), cyst rupture (OR = 2.213, P = 0.038), stage (OR = 4.114, P < 0.01), microinvasion (OR = 2.291, P = 0.046) and peritoneal implants (OR = 2.101, P = 0.016) were the five independent prognostic factors affecting recurrence. CONCLUSIONS: Although patients with borderline ovarian tumors have an excellent prognosis, the risk of recurrence remains in some patients. Emphasis should be put on these patients with high risk factors and preventive strategies should be taken to prevent their progression.

Prognostic significance of extracellular matrix metalloproteinase inducer and matrix metalloproteinase 2 in epithelial ovarian cancer.

AIMS: We investigated the prognostic significance of extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase 2 (MMP-2) in epithelial ovarian cancer as well as their relation to hyaluronan (HA) expression. METHODS: The expression of EMMPRIN and MMP-2 was analyzed immunohistochemically in 295 primary epithelial ovarian cancer patients and 67 metastases. RESULTS: A low membranous EMMPRIN expression was detected more often in serous tumors than in other types (p < 0.0005) and it was associated with tumors of advanced stage (p = 0.012) or with a large primary residual (p = 0.011). A low expression of MMP-2 in cancer cells was associated with a high histologic grade (grade 3) of the tumor (p = 0.005) and endometrioid type of tumors (p < 0.0005). Stromal MMP-2 expression was significantly associated with strong stromal HA expression (p = 0.002, r = 0.187). In univariate analysis, 10-year disease-related (DRS) and recurrence-free survivals were significantly better when MMP-2 expression in cancer cells was high (p = 0.0057 and p = 0.0467, respectively). DRS was also better when membranous EMMPRIN expression was high (p = 0.013). In multivariate analysis, strong MMP-2 in cancer cells (RR = 1.48, CI = 1.07-2.04, p = 0.017) indicated favorable DRS. CONCLUSION: Our results show that EMMPRIN and MMP-2 in cancer cells are significant indicators of a favorable prognosis of epithelial ovarian cancer.

Expression of transmembrane carbonic anhydrases IX and XII in ovarian tumours.

AIMS: Carbonic anhydrase (CA) isozymes IX and XII have been suggested to play a role in oncogenic processes. The aim of the present study was to investigate CA IX and XII expression in patients with ovarian tumours. METHODS AND RESULTS: A series of ovarian tumours was immunostained for CA IX and XII and the results were correlated with histopathological and clinical parameters. Most cases of borderline mucinous cystadenomas, mucinous cystadenocarcinomas and serous cystadenocarcinomas were moderately or strongly positive for CA IX. In malignant tumours, the staining was most prominent in hypoxic regions. Expression of CA XII was detected in all tumour categories, although the mean staining intensity was weaker than for CA IX in all groups except for clear cell carcinomas. CONCLUSIONS: The wide expression of CA IX and XII in ovarian tumours suggests that these isozymes could represent potential targets in ovarian cancer therapy. The expression pattern of CA IX suggests that it could also serve as a useful histopathological marker protein for hypoxia in malignant ovarian tumours.

Expression of the chromatin remodeling factor Rsf-1 is upregulated in ovarian carcinoma effusions and predicts poor survival.

OBJECTIVE: We recently identified Rsf-1, a chromatin remodeling gene, as a potential oncogene that is frequently amplified and overexpressed in ovarian serous carcinoma. However, its clinical role in ovarian cancer effusions is not clear. In the present study, we assessed the clinical significance of Rsf-1 overexpression in ovarian carcinoma effusions. METHODS: Formalin-fixed paraffin-embedded sections from 168 effusions (134 peritoneal, 34 pleural) were analyzed for Rsf-1 expression using immunocytochemistry. Matched primary tumors (n=48) and solid metastases (n=73) from 48 patients were additionally studied. Rsf-1 expression in tumor cells in effusions was analyzed for possible association with clinicopathologic parameters and survival. RESULTS: Rsf-1 protein expression was found in carcinoma cells in 157/168 (93%) effusions. Of these, 70 (45%) stained weakly and 87 (55%) strongly. Specimens from patients diagnosed with FIGO stage IV disease had higher staining score (extent x intensity) compared with stage III tumors (P=0.008). Rsf-1 expression level was significantly lower in primary tumors and solid metastases (P<0.001 for extent, intensity and score). Univariate survival analysis for 59 patients with post-chemotherapy recurrence effusions demonstrated a significant association between higher Rsf-1 staining and shorter overall survival (OS; P=0.009 for staining extent and intensity, P=0.02 for staining score). FIGO stage was the only clinical parameter associated with OS in this group (P=0.032). In Cox analysis, Rsf-1 expression (P=0.022 for staining extent and intensity, P=0.045 for staining score) and FIGO stage (P=0.035) were independent predictors of shorter survival. CONCLUSIONS: Rsf-1 is frequently expressed and upregulated in ovarian carcinoma cells in effusions and is a novel prognostic marker for patients with post-chemotherapy recurrent disease. The above findings support a role of Rsf-1 in mediating disease progression and aggressive clinical behavior in this subset of ovarian carcinoma patients.

Is complete surgical staging necessary in patients with stage I mucinous epithelial ovarian tumors?

OBJECTIVE: To evaluate the impact on prognosis of complete surgical staging in patients with stage I mucinous epithelial ovarian tumors. METHODS: We retrospectively reviewed the medical records of all patients with stage I mucinous epithelial tumors apparently confined to ovaries treated in the Department of Obstetrics and Gynecology, Asan Medical Center, from 1990 through 2005. RESULTS: Of 264 patients treated during this time period, 62 (23.5%) had complete and 202 (76.5%) had incomplete initial surgical staging. No patient with clinically apparent stage I borderline tumor was upstaged, 5 of 85 patients with invasive mucinous cancer was upstaged due to positive peritoneal cytology and there was no upstaged patient owing to occult lymph node metastasis. No recurrence was observed in the completely staged and 2 (1.4%) in the incompletely staged group among the patients with borderline tumor developed relapse. Three (11.5%) recurrences in the completely staged and four (6.8%) in the incompletely staged group among the patients with invasive cancer were observed, and the difference was not statistically significant. We also observed no significant differences between two groups in progression-free survival and overall survival. CONCLUSION: Complete surgical staging could probably be omitted in patients with stage I mucinous epithelial tumors.

[Clinicopathological aspects of pancreatic cancer].

Using the nationwide database of the Japan Pancreas Society (JPS), the clinicopathological features of 23,284 cases (1981-2000) and 2,298 cases (2001-2002) with pancreatic neoplasms were compared. Intraductal papillary mucinous neoplasms and mucinous cystic neoplasms were increased in the registry. More detailed histological repertoires of endocrine tumors, intraductal tubular tumors and solid-pseudopapillary tumors were registered in the last two years. The numbers of serous cystadenocarcinomas and carcinomas in situ were decreased. The proportion of less differentiated adenocarcinoma was increased in the more advanced stages of the disease. In Stage IVa, the survival of the patients with papillary adenocarcinoma was not statistically different from that of patients with well or moderate tubular adenocarcinoma, though the difference was significant in earlier stages. The survival of the patients with poorly differentiated adenocarcinoma, adenosquamous carcinoma and undifferentiated carcinoma was miserable. Histological confirmation is critically important to prospect the outcome and to determine the treatment modality. Integration of the nationwide registry and pathological information will give new insights for the treatment of pancreatic cancer.

[Morphometrical and immunohistochemical criteria of prognosis in patients with serous and mucinous ovarian carcinoma]. / Morfometricheskie i immunogistokhimicheskie kriterii prognoza u bol'nykh seroznym i mutsinoznym rakom iaichnikov.

The aim of the study was to investigate the prognostic value of morphometrical features and expression of receptors to progesterone in malignant epithelial ovarian tumours. Surgical biopsy materials of 92 patients with serous and mucinous ovarian cancer were investigated. Tissues stained by hematoxilin and eosin were studied. Morphometry was performed with computer program Axio Vision 3.0. Immunohistochemical characteristics were evaluated with monoclonal progesterone antibodies. It was found that cytomorphometrical features vary in ovarian cancer with different histological structures and the level of differentiation of tumour, and can be used as prognostic factors. We revealed correlation between cytomorphometric factors (carcinoma cell area, total nuclear area, roundness of cell) and risk of recurrences and metastatic spread. In serous cancers presence of progesterone receptors is a favorable factor of prognosis and, as a rule, associates with a high degree of tumour differentiation. In this group of patients 3-year survival reached almost 100% indicating the efficiency of hormonotherapy and chemotherapy.