Inhibition of the phosphoinositide 3-kinase pathway for the treatment of patients with metastatic metaplastic breast cancer.

BACKGROUND: Mesenchymal/metaplastic breast cancers (MpBCs) are often triple-negative (TNBC), and chemo-refractory, and can harbor phosphoinositide 3-kinase (PI3kinase) alterations; thus, therapy with mTor inhibitors may demonstrate activity. PATIENTS AND METHODS: Patients with mesenchymal/MpBC treated with temsirolimus-based regimens were evaluated. Mutational analyses [polymerase chain reaction (PCR)-based DNA sequencing method, mass spectrometric detection (Sequenom MassARRAY), or next-generation sequencing] as well as loss of phosphatase and tensin homolog (PTEN) (immunohistochemistry) were performed (archived tissue when available). RESULTS: Twenty-three patients (one of whom was on two separate trials) were treated using temsirolimus-containing regimens: temsirolimus alone (n = 1 patient) or combined with the following: liposomal doxorubicin and bevacizumab (DAT, n = 18); liposomal doxorubicin (DT, n = 1); paclitaxel and bevacizumab (TAT, n = 2); paclitaxel (TT, n = 1); carboplatin and bevacizumab (CAT, n = 1). Response rate [complete response (CR) + partial response (PR)] was 25% across all regimens; 32% in the anthracycline-based regimens [DAT and DT (CR = 2, PR = 4; N = 19)]. An additional two patients achieved stable disease (SD) ≥6 months [total SD ≥6 months/CR/PR = 8 (33%)]. Molecular aberrations in the PI3K pathway were common: PIK3CA mutation = 6/15 (40%), PTEN mutation = 3/11 (27%), and PTEN loss = 2/11 (18%). A point mutation in the NF2 gene (K159fs*16; NF2 alterations can activate mTor) was found in one patient who attained CR (3+ years). Of the eight patients who achieved SD ≥6 months/CR/PR, all 4 patients with available tissue had a molecular aberration that activate the PIK3CA/Akt/mTOR axis: PIK3CA mutation = 2; PTEN loss = 1; NF2 aberration = 1. CONCLUSIONS: DAT has activity in MpBCs including complete CRs. Molecular aberrations that can activate the PI3 K/Akt/mTOR axis are common in MpBC.

High Expression of Cathepsin E in Tissues but Not Blood of Patients with Barrett's Esophagus and Adenocarcinoma.

BACKGROUND: Cathepsin E (CTSE), an aspartic proteinase, is differentially expressed in the metaplasia-dysplasia-neoplasia sequence of gastric and colon cancer. We evaluated CTSE in Barrett's esophagus (BE) and cancer because increased CTSE levels are linked to improved survival in several cancers, and other cathepsins are up-regulated in BE and esophageal adenocarcinoma (EAC). METHODS: A total of 273 pretreatment tissues from 199 patients were analyzed [31 normal squamous esophagus (NE), 29 BE intestinal metaplasia, 31 BE with dysplasia (BE/D), 108 EAC]. CTSE relative mRNA expression was measured by real-time polymerase chain reaction, and protein expression was measured by immunohistochemistry. CTSE serum levels were determined by enzyme-linked immunosorbent assay. RESULTS: Median CTSE mRNA expression levels were ≥1,000-fold higher in BE/intestinal metaplasia and BE/D compared to NE. CTSE levels were significantly lower in EAC compared to BE/intestinal metaplasia and BE/D, but significantly higher than NE levels. A similar expression pattern was present in immunohistochemistry, with absent staining in NE, intense staining in intestinal metaplasia and dysplasia, and less intense EAC staining. CTSE serum analysis did not discriminate patient groups. In a uni- and multivariable Cox proportional hazards model, CTSE expression was not significantly associated with survival in patients with EAC, although CTSE expression above the 25th percentile was associated with a 41 % relative risk reduction for death (hazard ratio 0.59, 95 % confidence interval 0.27-1.26, p = 0.17). CONCLUSIONS: CTSE mRNA expression is up-regulated more than any known gene in Barrett intestinal metaplasia and dysplasia tissues. Protein expression is similarly highly intense in intestinal metaplasia and dysplasia tissues.

Survival outcomes of metaplastic breast cancer patients: results from a US population-based analysis.

BACKGROUND: Metaplastic breast cancer (MBC) is a rare histologic subtype needing further characterization. The aim of our study was to compare MBC to infiltrating ductal carcinoma (IDC) of the breast and to identify demographic, clinicopathologic, treatment, and survival differences. METHODS: MBC and IDC patients were identified using the Surveillance, Epidemiology, and End Results (SEER) public-use data set. Disease-specific survival (DSS) differences were compared using the Kaplan-Meier method and log-rank tests. Univariate and multivariate Cox proportional hazard models were used to assess factors prognostic for DSS. To control for hormone receptor status, a subsequent planned analysis was completed for receptor-negative MBC and IDC. Lastly, a matched case-control analysis was conducted to minimize potential bias due to baseline demographic, clinical, and pathologic differences. RESULTS: The SEER data set included 1,011 MBC and 253,818 IDC patients diagnosed from 2001 to 2010. MBC patients had larger, higher grade tumors, had less frequent axillary nodal involvement, and were more likely to be treated with mastectomy. Five-year DSS rates were significantly worse for patients with MBC than for IDC patients (78 vs. 93 %, p < 0.0001) and for patients with receptor-negative MBC than receptor-negative IDC (77 vs. 85 %, p < 0.0001). The findings were confirmed on matched analysis. Prognostic factors identified on multivariate analyses included age, MBC histology, tumor grade, T stage, and axillary lymph node involvement. CONCLUSIONS: MBC patients have shorter DSS than IDC patients. Improved clinical and biological understanding of MBC may result in more effective therapy and better cancer outcomes.

Hormone receptor status does not affect prognosis in metaplastic breast cancer: a population-based analysis with comparison to infiltrating ductal and lobular carcinomas.

BACKGROUND: Metaplastic breast cancer is a rare histologic variant among breast cancers. We sought to investigate the impact of hormone receptor status in metaplastic breast cancer and compare outcomes with common histologic variants of breast cancer. METHODS: The study was performed utilizing the Surveillance, Epidemiology, and End Results database. A query was made for patients with metaplastic breast cancer from 2000 to 2010. A separate query identified all patients with infiltrating ductal (IDC) or lobular (ILC) carcinoma during the same period. Effect of hormone receptor status was evaluated using Cox regression analysis. Significance was assessed for p < 0.05. RESULTS: A total of 2,338 patients with metaplastic breast cancer were available for study. Most tumors were hormone receptor negative (79.0 %) and greater than or equal to grade 3 (82.9 %). For comparison, 382,667 and 44,813 patients with IDC and ILC, respectively, were obtained. Overall 5-year survival for metaplastic breast cancer was 62.2 % compared with 81.2 % for IDC (p < 0.001) and 80.2 % for ILC (p < 0.001). For metaplastic cases, no difference in 5-year survival was found between hormone-positive and hormone-negative tumors (65.7 vs. 63.5 %; p = 0.70). Multivariate analysis demonstrated metaplastic histology as an independent risk factor for cancer-related mortality both among hormone-positive (hazard ratio [HR] 2.4; 95 % confidence interval [CI] 1.8-3.0; p < 0.001) and hormone-negative (HR 1.7; 95 % CI 1.5-1.9; p < 0.001) breast cancers. CONCLUSION: Metaplastic breast cancer is an aggressive histologic variant that portends a poor prognosis compared with common breast cancer subtypes. Contrary to other breast cancers, hormone receptor positivity does not improve prognosis in metaplastic breast cancer.

Clinicopathological significance of claudin-4 in gastric carcinoma.

BACKGROUND: Aberrant expression of claudin proteins has been reported in a variety of cancers. Previous studies have demonstrated that overexpression of claudin may promote tumorigenesis and metastasis through increased invasion and survival of tumor cells. However, the prognostic significance of claudin-4 in gastric cancer remains unclear. METHODS: Immunohistochemistry was used to analyze the expression of claudin-4 in 329 clinical gastric cancer specimens and 44 normal stomach samples, 21 intestinal metaplasia samples, and 21 adjacent precursor lesions dysplasia samples. Statistical analysis methods were used to evaluate the relationship between claudin-4 expression and various clinicopathological parameters. Univariate and multivariate analyses were performed, respectively, to detect the independent predictors of survival. RESULTS: Claudin-4 expression was present in only 7(15.9%) normal gastric samples, but expression of claudin-4 in the intestinal metaplasia lesions and dysplasia lesions was 90.5% and 95.2%, respectively. The expression of claudin-4 was significantly associated with histological differentiation (P < 0.001) and tumor growth patterns (P < 0.001) but not associated with patient survival. However, intermediate type staining of claudin-4 exhibited a trend of correlation with patients' survival (P = 0.023). The five-year survival rate with low expression of claudin-4 in intermediate type (76.4%) was similar to expanding type (64.5%), while the high expression group (46.6%) was closer to infiltrative type (50.7%). CONCLUSIONS: The findings in this study demonstrate claudin-4 aberrant expression in gastric cancer and precursor lesions. The expression of claudin-4 could serve as a basis for identifying gastric cancer of the intermediate type.

Unique clinicopathological features of metaplastic breast carcinoma compared with invasive ductal carcinoma and poor prognostic indicators.

BACKGROUND: Metaplastic breast carcinoma is a rare aggressive malignant neoplasm. The purposes of this study are to review the pathologic features and clinical outcomes of metaplastic breast carcinoma compared to invasive ductal carcinoma and to evaluate the prognosis of metaplastic breast carcinoma. METHODS: The cases of 55 patients with metaplastic breast carcinoma presenting between 1991 and 2006 were analyzed and compared to the cases of 767 age-matched patients with invasive ductal carcinoma from the same time period. RESULTS: The group of patients with metaplastic breast carcinoma presented with a larger tumor size, lower lymph node involvement, higher percentage of triple-negative (estrogen receptor-, progesterone receptor- and human epidermal growth factor receptor-2-negative) cases, and Ki-67 over-expression compared with the group of patients with invasive ductal carcinoma and triple-negative invasive ductal carcinomas. Patients in the metaplastic breast carcinoma group tended to have more local (often chest wall) recurrences (P = 0.038) and distant (often lung) metastases (P = 0.001) than those in the invasive ductal carcinomas group. The prognosis of metaplastic breast carcinoma was poorer than that of invasive ductal carcinoma and triple-negative invasive ductal carcinomas; the 5-year overall survival rate was 54.5% in metaplastic breast carcinoma versus 85.1% in invasive ductal carcinoma, and 73.3% in triple-negative invasive ductal carcinomas (P <0.001). The 5-year disease-free survival rate was 45.5% in metaplastic breast carcinoma versus 71.2% in invasive ductal carcinoma, and 60.3% in triple-negative invasive ductal carcinomas (P <0.001). Multivariate analysis revealed tumor size larger than 5.0 cm, lymph node involvement and Ki-67≥14% were significantly related to 5-year overall survival (P = 0.010; P = 0.010; P = 0.035) and 5-year disease-free survival (P = 0.020; P = 0.018; P = 0.049). CONCLUSIONS: Metaplastic breast carcinoma shows a poorer prognosis than both invasive ductal carcinoma and triple-negative invasive ductal carcinomas. Tumor size larger than 5.0 cm, lymph node involvement and Ki-67 ≥14% indicate a poor prognosis in patients with metaplastic breast carcinoma.

May metaplastic breast carcinomas be actually basal-like carcinoma? Further evidence study with its ultrastructure and survival analysis.

Metaplastic breast carcinoma (MBC) encompasses a heterogeneous group of tumors. Based upon the microarray of MBCs, these tumors showed features of basal-like carcinoma and myoepithelial differentiation. However, MBCs entity still remained unclear. So we performed a systematic research to explicit metaplastic breast carcinomas further. A panel of ER, PR, HER-2, CK5/6, CK14, P63 and EGFR were prepared for detection of MBCs, and fluorescence in situ hybridization for HER-2 gene amplification and ultrastructure observation were also performed. Sensitiveness between CK5/6 and other antibodies in diagnosis was analysed, and survival analysis was also carried out. ER, PR and HER-2 were negative. CK5/6 (12/12), CK14 (9/12), EGFR (10/12) and P63 (8/12) were positive. FISH for HER-2 displayed no amplification (ratio values < 1.8). Ultrastructure showed tonofibrils, thin filament and dense body in the cytoplasm. Significant statistical differences were detected between groups (F = 8.080, P = 0.000) of score of CK5/6, CK14, P63 and EGFR. Significant statistical differences were also detected between age and lymph node involvement and survival (χ(2) = 10.835, P = 0.004). MBCs may be actually basal-like carcinomas. In the diagnosis of MBCs, CK5/6, CK14, P63 and EGFR may be effective and CK5/6 may be more sensitive than CK14 and P63. Survival of MBCs may be associated with age and lymph node involvement. However, given the limitations of our research accumulated cases, prospective clinicopathologic studies are needed to further elucidate MBCs.

Clinicopathologic study of 53 metaplastic breast carcinomas: their elements and prognostic implications.

Metaplastic carcinoma of the breast is a relatively rare cancer and includes various histologic types. In this cancer, metaplastic elements are heterogeneous and sometimes mixed. We investigated, by histopathologic means, these elements and clinical implications that could indicate the clinical course (including the prognosis). Fifty-three metaplastic breast carcinoma cases and their prognoses were investigated by initially examining the presence or absence of spindle-cell elements, and then the presence or absence of other elements. Spindle cells were classified as high or low grade. The number of spindle-cell-positive cases was 24 (45%) of 53. The 24 spindle-cell (+) cases were subdivided into 12 high-grade (HGsp) (distant metastatic rate per 100 person-years, 13.27) and 12 low-grade (LGsp) (0.00) patients. Spindle-cell (-) cases were subdivided into 22 pure squamous cell carcinomas (5.93) and 7 matrix-producing carcinomas (0.00). There were significant differences among the 4 groups with regard to the disease-free period (P = .0081, log-rank test). The distant metastatic risks in the HGsp and pure squamous cell carcinomas groups were significantly higher than that in the matrix-producing carcinoma + LGsp group (nonmetastatic groups) after controlling for the effects of tumor size and lymph node metastasis (P = .019 and P = .016, respectively, Poisson regression model). The presence of high-grade spindle cells was related to the prognosis, and some histologic subtypes may be important with respect to the prognosis. The presence of high-grade spindle cells in metaplastic breast carcinoma may indicate aggressive behavior.

Metaplastic carcinoma of the breast, an unusual disease with worse prognosis: the experience of the European Institute of Oncology and review of the literature.

BACKGROUND: Metaplastic carcinoma of the breast is a rare form of breast cancer and has an uncertain prognostic significance. The purpose of the present study was to compare the clinical course, and prognosis, between this type of tumor and poorly differentiated ductal carcinoma. PATIENTS AND METHODS: We analyzed 37 cases of metaplastic carcinoma of the breast treated at our institution (European Institute of Oncology in Milan, Italy) between 1997 and 2004, comparing them with 72 cases (control group) of poorly differentiated ductal carcinoma. All 109 patients had negative receptors and were G3 at final histology. The control cases were matched according to year of surgery, pT (pT1 vs. pT2/3/4), and pN (absent vs. present). RESULTS: Of the 37 patients, eleven died from disease progression, eight developed metastatic disease and two experienced local recurrence. In the control group (72 patients) we observed three deaths due to disease progression, 13 distant metastases, and two local recurrences. CONCLUSION: The overall survival in the metaplastic carcinoma group was significantly worse than in the control group. As regards to disease-free survival, there was no statistically significant difference between the two groups.

Metaplastic carcinoma of the breast: a retrospective review.

PURPOSE: Metaplastic carcinoma of the breast represents a rare and heterogeneous group of malignancies that accounts for less than 1% of all breast cancers. The purpose of this study is to better characterize the clinical management of this disease including the role of radiation therapy after surgery. We compared patients that have been treated with either modified radical mastectomy (MRM) or breast-conserving surgery (BCS). METHODS AND MATERIALS: We performed a retrospective review of 43 patients with metaplastic breast cancer who were evaluated in our regional radiation oncology department between 1987 and 2002. Twenty-one patients were treated with an MRM and 22 with BCS. Five patients from the MRM group received adjuvant radiation, as did 19 patients from the BCS group. Univariate and multivariate analysis of pathologic and treatment-related factors was performed. Local control, disease-free, and overall survival rates were calculated by the Kaplan-Meier method and compared for the two groups. RESULTS: Mean follow-up for all patients was 44.2 months. Mean tumor size was 3.4 cm. Four patients (9%) had positive estrogen receptors and 20 (25%) had positive nodes. The overall 5-year projected local recurrence-free (88% vs. 85%, p = 0.86), disease-free (55% vs. 84%, p = 0.13), and overall survivals (80% vs. 89%, p = 0.58) were not significantly different for both groups. The only tumor parameter significantly associated with overall survival was nodal status. CONCLUSION: Our study suggests that breast conservation appears to be a reasonable treatment option for women with metaplastic breast cancer, achieving equal survival to mastectomy. The use of adjuvant radiation seems essential for achieving high local control rates after conservation therapy. Further studies will be needed to determine the impact of chemotherapy on survival outcomes.

Multivariate independent prognostic factors in endometrial carcinoma: a clinicopathologic study in 181 patients: 10 years experience at the Department of Obstetrics and Gynecology of the Mainz University.

The aim of this study was to evaluate the biologic outcome of endometrial carcinomas as compared to clinical and pathologic parameters and to identify multivariate independent prognostic factors. Charts were abstracted from patients with endometrial carcinoma from 1985 to 1995. Data on clinicopathologic variables, adjuvant treatment, site of recurrence, and survival were collected. chi2 test was used to test association between variables. Kaplan-Maier method was used for survival analysis and Cox proportional hazards model for multiple regression analysis. Univariate analysis revealed that FIGO stage, tumor grade, depth of myometrial invasion, biochemical analysis of progesterone receptor status, age, additional diabetes mellitus, lymph node metastasis, and type of tumor were significantly associated with the overall-survival. For disease-free interval, FIGO stage, tumor grade, depth of myometrial invasion, biochemical analysis of progesterone receptor status, lymph node metastasis, and type of tumor were also significantly associated. Multivariate analysis revealed that FIGO stage, tumor grading, tumor type, depth of myometrial invasion, and biochemically measured progesterone receptor status were associated significantly with overall survival. A significant correlation as independent prognostic factors were also seen for recurrence free interval for FIGO stage, tumor grade, and biochemical progesterone receptor status. In multivariate statistical analysis we identified FIGO stage, tumor type, tumor grade, biochemical analysis of progesterone receptor status, and depth of myometrial invasion as independent prognostic factors for overall survival, and FIGO stage, biochemical analysis of progesterone receptor status, and tumor grade as independent prognostic factors for recurrence-free interval.

Argon beam plasma coagulation as therapy for high-grade dysplasia in Barrett's esophagus.

BACKGROUND & AIMS: Patients with high-grade dysplasia in Barrett's esophagus have a high chance of developing adenocarcinoma. Previously these patients have undergone resection, however, the management of patients unsuitable for surgical resection is unclear. We have studied the long-term outcome of patients who have undergone endoscopic Argon ablation for high-grade dysplasia in Barrett's. METHODS: Twenty-nine patients (median age, 64 yr; range, 43-85 yr) with high-grade dysplasia in Barrett's, who were unfit or had declined surgery, underwent Argon ablation and received follow-up evaluation over 7 years (mean follow-up, 37 mo; range, 7-78 mo). Treatment was stopped once there was no further histologic evidence of dysplasia. The patients then went on to receive a surveillance endoscopy at 3, 6, and 12 months after ablation, then annually thereafter. RESULTS: High-grade dysplasia responded to treatment in 25 patients (86%); 22 of these had complete regression to neosquamous esophageal mucosa. During follow-up evaluation, no patients died of esophageal adenocarcinoma. Four patients developed cancer, 3 of whom continue with ablation therapy. The fourth patient died of unrelated causes. A single esophageal perforation was the only significant adverse event attributable to therapy. No esophageal strictures occurred and patients returned to normal activity after 24 hours in the majority of cases. Patients who received Argon ablation showed no difference in survival to that of the general population. CONCLUSIONS: Argon beam ablation for high-grade dysplasia in Barrett's esophagus is an effective and safe treatment, especially in patients unfit for surgical resection.

CDX2 expression in the stomach with intestinal metaplasia and intestinal-type cancer: Prognostic implications.

CDX2, a transcriptional factor expressed in the intestine, is implicated in the development and maintenance of the intestinal mucosa. Recent studies have demonstrated that CDX2 is expressed in the intestinal metaplasia of the stomach and intestinal-type gastric cancer, while it is not expressed in the normal gastric mucosa. To investigate the role of CDX2 in gastric cancer, we determined CDX2 expression and cell proliferation rate in various types of gastric cancer tissues by immunostaining. Surgically dissected gastric cancer tissues were collected from 40 patients. Consistent with previous reports, CDX2 was expressed in most gastric mucosa samples with intestinal metaplasia (89%, 16/18), although it was not found in the adjacent normal mucosa. CDX2 expression was also detected in 64% (18/28) of intestinal-type gastric cancer cases, whereas it was not observed in the diffuse-type gastric cancer (0/12). Moreover, the CDX2-positive gastric cancer samples showed significantly lower index for Ki-67 immunostaining, indicating reduced cell proliferation rates than in the CDX2-negative samples. Importantly, multivariate analysis for the overall survival rate revealed that the CDX2-positive gastric cancer patients survived significantly longer than the CDX2-negative patients. Even among the intestinal-type gastric cancer cases, the CDX2-positive group showed a lower Ki-67 index and longer postoperative survival than the CDX2-negative group. These results collectively indicate that CDX2 expression in gastric cancer tissues can be a novel prognostic marker for patient survival.

Expression of the 27-kDa heat shock protein (HSP27) in gastric carcinomas and adjacent normal, metaplastic, and dysplastic gastric mucosa, and its prognostic significance.

PURPOSE: The investigation of heat shock protein 27 (HSP27) expression in gastric cancer and adjacent normal, metaplastic, and dysplastic gastric mucosa and its correlation with clinicopathological parameters and survival of patients. METHODS: Immunohistochemical methodology was performed on formalin-fixed paraffin-embedded sections by using a monoclonal anti-HSP27 antibody. HSP27 expression was screened and compared in 86 cases of gastric carcinoma and adjacent normal, metaplastic, and dysplastic gastric mucosa. RESULTS: In the normal mucosa, HSP27 was detected in 68 out of 86 cases (79%) and was more intense in the surface and upper two-thirds of gastric foveolae. In dysplastic gastric mucosa, HSP27 immunoreactivity was usually higher than that of the adjacent normal epithelium and was parallel to the severity of dysplasia. HSP27 expression was found in 54 out of 86 (62.7%) gastric carcinomas and was significantly related to more than six metastatic lymph nodes ( P =0.03). HSP27 expression was also higher in tumors of advanced stage and in those of female patients. HSP27 expression was associated with shorter overall survival in univariate analysis ( P =0.04), but this relationship was not retained in multivariate analysis. CONCLUSIONS: Our findings indicate that: i) HSP27 is commonly expressed in normal gastric epithelium where it seems to exert a protective role; and ii) HSP27 is involved in gastric carcinogenesis and its expression appears to be associated with parameters of unfavorable prognosis and shorter overall survival.

Adenocarcinoma, adenoacanthoma, and mixed adenosquamous carcinoma of the endometrium.

PURPOSE: To determine the frequency of endometrial adenocarcinoma (AC) with squamous cell differentiation and to compare the histopathologic and clinical characteristics of patients with adenoacanthoma (AA) and adenosquamous carcinoma (AS) to evaluate possible prognostic differences. MATERIALS AND METHODS: Two hundred forty patients with endometrial carcinoma (72.2% AC, 21.25% AA, 6.25% AS) treated at the Department of Gynecologic Oncology of Marmara University Hospital, between January 1986 and December 1997, were reviewed. The diagnoses of the diseases were made with fractional D&C, and the definitive therapy for all patients was carried out at the same hospital. Extrafascial hysterectomy + BSO with or without pelvic and para-aortic lymph node dissection, and omentectomy according to the FIGO staging and grading system were performed. RESULTS: AC and AS had median ages around 60 years with a similar percent distribution of postmenopausal patients (around 74%). AA had an earlier median age of 51 years which reflects an incidence of only 50% postmenopausal patients. There was a tendency for AA to be of low-grade malignancy (72%), 51% of AC were of low-grade, while only 20% of AS were low-grade tumors. There was no difference for any of the three pathological entities in survival by FIGO stages. Over 80% of the tumors were Stage I and about 10% were Stage II, with less than 10% in Stages III and IV. CONCLUSION: Considering the more modern and uniform approaches in therapy for these tumors, there seems to be no differences in prognosis for adenocarcinoma with or without squamous elements. The neoplasms AC, AA and AS should be regarded, and consequently approached, as any low-grade adenocarcinoma of the endometrium.

Postoperative radiotherapy in carcinoma of the cervix: treatment results and prognostic factors.

In order to assess the role of postoperative radiotherapy and prognostic factors, 126 patients who were treated with radiotherapy after surgery for clinical early-stage carcinoma of the cervix were reviewed. All patients received external pelvic radiotherapy and 37 patients were treated with additional vaginal cuff irradiation. The 5-year overall survival, disease-free survival and locoregional control rates were 71.1, 69.9 and 78.1%, respectively. The 5-year disease-free survival rates were 40% for grade 3 vs. 75.4% for grade 1 tumours (p = 0.05), 76.5% for pathological stage IB versus 54.1% for pathological stage IIA (p = 0.04), 36.6% for node-positive patients versus 82.5% for node-negative patients (p = 0.0017), 54% for full thickness cervical invasion versus 100% superficial cervical invasion (p = 0.01), 34.8% for positive margins versus 78.1 for negative margins (p < 0.0001). After a multivariate analysis, tumour grade (p = 0.026) and presence of positive margins (p = 0.006) were found to independently influence the outcome. Grade II and III complication rate was 5.5% in all patients. In conclusion, postoperative radiotherapy should be used in patients treated with simple hysterectomy as well as those treated with radical hysterectomy with unfavorable pathological findings.

[The prognostic aspects of the morphological signs of bladder cancer]. / Prognosticheskie aspekty morfologicheskikh priznakov raka mochevogo puzyria.

A clinico-morphological study of 150 bladder tumours showed significant dependence of bladder carcinoma prognosis on some morphological indices most important of which were the grade of malignancy, histological type and deepness of growth and spread along the lymphatic and blood vessels. Likewise, nuclear polymorphism and hyperchromasia, mitotic figure number, atypical mitosis have a direct connection with prognosis, but they are an integral part of malignancy grade determination and do not play an independent role. Nucleolar organizer zone may serve as an additional criterium of neoplasm biological activity, in particular, its role is important in differential diagnosis of bladder transitional cell carcinoma I and benign processes or transitional papilloma.

Splenectomy for patients with myelofibrosis with myeloid metaplasia: pretreatment variables and outcome prediction.

Since according to the early studies, the outcome after splenectomy in the individual patient with myelofibrosis with myeloid metaplasia (MMM) is unpredictable, we assessed retrospectively the pre-intervention characteristics that best predicted adverse events, hematological consequences, and survival in 71 splenectomized MMM patients. The findings indicate that the operative risk of splenectomy for both mortality (8.4%) and morbidity (39.3%) was unpredictable. New hemorrhagic or thrombotic complications occurred in 16.9% of surviving patients and were predicted by age < 50 years, a normal to high platelet count (> 200 x 10(9)/l) and huge splenomegaly (> 16 cm from the costal margin). Massive liver enlargement occurred in 24% of patients and has to be expected in patients splenectomized for transfusion-dependent anemia. Anemia improved substantially in 45% and 52% of patients at 3 months and at 1 year, respectively, and was predicted by severe anemia, low platelet count (< 100 x 10(9)/l) or normal to high white blood cell (WBC) count (> 4 x 10(9)/l). Survival from splenectomy was superior in patients < 45 years with WBC < 10 x 10(9)/l count. An unexpectedly high rate of blastic transformation was observed. It accounted for 42.8% of the deaths. The results suggest trials for prophylactic cytoreductive treatment in young patients and when platelet count is normal to increased. Further study is needed for elucidating the possible role played by splenectomy in inducing blastic transformation.