The Prediction Analysis of Microarray 50 (PAM50) Gene Expression Classifier Utilized in Indeterminate-Risk Breast Cancer Patients in Hungary: A Consecutive 5-Year Experience.

BACKGROUND: Breast cancer has been categorized into molecular subtypes using immunohistochemical staining (IHC) and fluorescence in situ hybridization (FISH) since the early 2000s. However, recent research suggests that gene expression testing, specifically Prosigna® Prediction Analysis of Microarray 50 (PAM50), provides more accurate classification methods. In this retrospective study, we compared the results of IHC/FISH and PAM50 testing. We also examined the impact of various PAM50 parameters on overall survival (OS) and progression-free survival (PFS). RESULTS: We analyzed 42 unilateral breast cancer samples, with 18 classified as luminal A, 10 as luminal B, 8 as Human epidermal growth factor receptor 2 (HER2)-positive, and 6 as basal-like using PAM50. Interestingly, 17 out of the 42 samples (40.47%) showed discordant results between histopathological assessment and the PAM50 classifier. While routine IHC/FISH resulted in classification differences for a quarter to a third of samples within each subtype, all basal-like tumors were misclassified. Hormone receptor-positive tumors (hazard rate: 8.7803; p = 0.0085) and patients who had higher 10-year recurrence risk scores (hazard rate: 1.0539; p = 0.0201) had shorter OS and PFS. CONCLUSIONS: Our study supports the existing understanding of molecular subtypes in breast cancer and emphasizes the overlap between clinical characteristics and molecular subtyping. These findings underscore the value of gene expression profiling, such as PAM50, in improving treatment decisions for breast cancer patients.

Isoform-Dependent Changes in Cytochrome P450-Mediated Drug Metabolism after Portal Vein Ligation in the Rat.

BACKGROUND: Surgical removal of complicated liver tumors may be realized in two stages via selective portal vein ligation, inducing the atrophy of portally ligated lobes and the compensatory hypertrophy of nonligated liver lobes. Unlike morphological changes, functional aspects such as hepatic cytochrome P450 (CYP)-mediated drug metabolism remain vaguely understood, despite its critical role in both drug biotransformation and hepatic functional analysis. Our goal was the multilevel characterization of hepatic CYP-mediated drug metabolism after portal vein ligation in the rat. METHODS: Male Wistar rats (n = 24, 210-230 g) were analyzed either untreated (controls; n = 4) or 24/48/72/168/336 h (n = 4 each) following portal vein ligation affecting approximately 80% of the liver parenchyma. Besides the weights of ligated and nonligated lobes, pentobarbital (30 mg/kg)-induced sleeping time, CYP1A(2), CYP 2B(1/2), CYP2C(6/11/13), CYP3A(1) enzyme activities, and corresponding isoform mRNA expressions, as well as CYP3A1 protein expression were determined by in vivo sleeping test, CYP isoform-selective assays, polymerase chain reaction, and immunohistochemistry, respectively. RESULTS: Portal vein ligation triggered atrophy in ligated lobes and hypertrophy nonligated lobes. Sleeping time was transiently elevated (p = 0.0451). After an initial rise, CYP1A, CYP2B, and CYP3A enzyme activities dropped until 72 h, followed by a potent increase only in the nonligated lobes, paralleled by an early (24-48 h) transcriptional activation only in nonligated lobes. CYP2C enzyme activities and mRNA levels were bilaterally rapidly decreased, showing a late reconvergence only in nonligated lobes. CYP3A1 immunohistochemistry indicated substantial differences in positivity in the early period. CONCLUSIONS: Beyond the atrophy-hypertrophy complex, portal vein ligation generated a transient suppression of global and regional drug metabolism, re-established by an adaptive, CYP isoform-dependent transcriptional response of the nonligated lobes.

[Laparoscopic colorectal resections -- experience based on 393 cases]. / Laparoscopos colorectalis resectiók -- 393 eset tapasztalatai.

Laparoscopic (LAP) colorectal surgery has become increasingly popular worldwide. Large comparative studies demonstrate the benefit of the method, but data about routine application are relatively moderate. This study presents the results of laparoscopic colorectal linterventions in a non-selected patient population, who were admitted to the 1st Department of Surgery, Semmelweis University between January 2004 and December 2011. 393 patients underwent LAP surgery. In 333 cases the malignant tumor indicated surgery. T3 tumor rate was 62.7%. Synchronous liver metastases were detected in 17 cases, three of them were single and operable, but 14 cases were multiplex and inoperable. Bowel was successfully resected in all cases. Complication rate was 9.9 percent. In-hospital mortality was 2.0%. Length of hospital stay of non-complicated cases was 6.7 days. In 9 cases single incision intervention was performed, with an average length of hospital stay of four days. Rate of sphincter preserving rectal resections were 87.2%. 59 (15.0%) patients underwent conversion from LAP to open surgery. Operating time decreased by time, but both OP time and conversion rate were tipically determinded by the surgeon's skill. LAP surgery was found to be useful for all kind colorectal diseases requiring elective resection. Application of LAP method requires organized training programs.

Inpatients and specialists' opinions about natural orifice translumenal endoscopic surgery.

In the last three years, investigations on natural orifice translumenal endoscopic surgery (NOTES) have entered the clinical experimental phase. Our aim was to carry out the first cross-sectional survey in Hungary about inpatients and specialists' opinions concerning natural orifice surgery. A total of 155 patients were included in the survey from two hospitals. Patients received a handout that described in detail the various available techniques for cholecystectomy, plus a 10-item questionnaire. Respondents had to choose between undergoing laparoscopic or NOTES cholecystectomy, indicate the acceptable complication rate, provide the reason for their choice, and select an ideal orifice. Specialists attending lectures on NOTES at two Hungarian congresses were given a separate questionnaire that was designed for physicians. We measured their perceptions about the need for the new method and about the unsolved issues it involved, their choice of entry site, their assessment of which type of specialist should perform NOTES operations, and the timeframe that would be needed for the widespread adoption of the method. With complication rates presumed to be equivalent to each other, 53% of inpatients chose a NOTES operation over laparoscopy for a cholecystectomy. Those who had prior endoscopy (p = 0.03), prior open surgery (p = 0.03), or who were male (p = 0.05) were more likely to opt for NOTES. The preferred approach was transvaginal (49%) for women, and transcolonic (66%) for men. Regarding the specialists, 37% would like to use NOTES in their practice and 49% would undergo a NOTES procedure; of these, 43% were unable to indicate the ideal orifice, 22% preferred the vagina, 20% the stomach, and 15% a hybrid approach. A total of 54% of surgeons believed that there is a real demand for NOTES, whereas 37% felt that it is an unnecessary innovation.