Pathologic assessment of response to chemotherapy in colorectal cancer liver metastases after hepatic resection: which method to use?

BACKGROUND: Patients with metastatic colorectal cancer receive chemotherapy prior liver resection more and more frequently. Histopathologic assessment methods of the resected specimen could evaluate the response to chemotherapy. In this study it is analyzed if these histopathologic changes are specific to preoperative chemotherapy and if these methods have correlation with survival. METHODS: Sixty three patients with available pathology slides, resected for colorectal cancer liver metastases were enrolled in this study. 46 patients (73%) received neoadjuvant chemotherapy. Five pathological evaluation methods were compared according to the literature: [1] residual tumor cell ratio, [2] tumor regression grade (TRG) scoring system, [3] modified tumor regression grade (mTRG) scoring system with the type of necrosis, [4] pattern of tumor regression and [5] the tumor thickness at the tumor-normal interface (TNI). RESULTS: Analyzing the pathological methods between the chemotherapy (CTX) and the non-chemotherapy group (NC), we found that that four evaluation methods showed significant and one showed strong correlation with the use of chemotherapy. (Residual tumor cell ratio: p = 0.08; TRG: p <0.01; mTRG: p = 0.03; pattern of tumor regression: p <0.01; TNI: p = 0.02). In the chemotherapy group none of the analyzed pathological methods showed significant correlation with progression free survival (PFS) or with overall survival (OS). Residual tumor cell ratio, TRG and the pattern of tumor cells showed positive but not significant correlation with OS and PFS and a slight difference in the group of patients with TNI <2 mm could be documented. CONCLUSIONS: Tumor regression grade (TRG) and tumor thickness at the tumor-normal interface (TNI) were the most useful methods for pathological response evaluation and these methods had some correlation with survival. According to these data, authors concluded, that a reproducible and well defined scoring system, based on different histopathological evaluation methods should be developed to predict more accurately the effect of neoadjuvant chemotherapy in CRCLM patients.

Massive hemoptysis complicating Behçet's syndrome: the importance of early pulmonary angiography and operation.

A 16-year-old patient with Behçet's syndrome had massive hemoptysis due to a ruptured aneurysm of a segmental artery of the left lung. Emergency left lower lobectomy was performed. The patient is well 12 months after operation. There have been no further episodes of hemoptysis.

Elevated serum tumor necrosis factor-alpha concentrations and bioactivity in Type 2 diabetics and patients with android type obesity.

The role of tumor necrosis factor-alpha in insulin resistance has been studied in 59 patients with Type 2 diabetes, 28 with android type obesity and 35 healthy lean controls. Immunoreactive concentrations and bioactivity of serum tumor necrosis factor-alpha have repeatedly been determined in 8 weeks intervals for 12 months, five times per patients, by using ELISA and L929 cell cytotoxicity bioassay. Significantly higher immunoreactive tumor necrosis factor-alpha concentrations and bioactivity have been found in both, the Type 2 diabetic and obese groups as compared to the healthy persons. Tumor necrosis factor-alpha concentrations and bioactivity have showed a significant positive linear correlation with the elevated basal serum C-peptide levels and body mass indexes in both groups of patients. According to these data the cytokine might play a role in insulin resistance in obesity as well in Type 2 diabetes.

Polymyalgia rheumatica and temporal arteritis in a married couple.

A husband suffering from temporal arteritis and his wife afflicted with polymyalgia rheumatica are reported. The possibility of the existence of an environmental factor rather than a genetic etiology is discussed.

Ochratoxin A content of human sera determined by a sensitive ELISA.

A sensitive, monoclonal antibody-based ELISA test was developed and used for quantitative determination of ochratoxin A (OA) in human sera. The measuring range of this test (without sample dilution) was 0.2-2.0 ng/mL, and the detection limit was 0.2 ng/mL. The OA concentrations of 355 sera samples varied from < 0.2 to 10 ng/mL OA, but 75% of the samples contained 0.2-1.0 ng/mL. This amount reflects a tolerable daily intake (TDI) value of toxin. However, in some cases (6.8%), more than 1.0 ng/mL OA was measured, which is probably a result of elevated intake of OA, which may even exceed the "virtually safe dose". Our data indicate that, like in many other countries, OA is present in food or feed products available in Hungary, and in order to save the health of consumers, their regular control is desirable.

Arteriovenous shunts in peripheral lymphedema: hemodynamic features and isotopic visualization.

The hemodynamic characteristics of peripheral lymphedema were studied in 28 patients with uni- or bilateral leg swelling. Leg blood flow was measured by venous isotope dilution (a technique for nutritive--capillary blood flow) and arteriovenous shunts were visualized by perfusion scintigraphy using radiolabelled macroaggregated albumin. Arteriovenous communications were uniformly detected in lymphedema, with a calculated "shunt flow" of 200 to 600 ml/min. Other features in the lymphedematous leg included an elevated limb blood flow rate and narrowed arteriovenous oxygen difference.

Multiple plasmocytomas of the liver and the spleen.

Imaging in a patient with multiple myeloma and Gaucher's disease showed space-occupying lesions in the liver and spleen. These were found to be plasmocytomas on histologic examination.

[Tumor necrosis factor-alpha; a possible pathogenic factor in obesity in insulin resistant and non-insulin-dependent diabetes mellitus?]. / Tumor necrosis faktor-alpha: az elhízás-inzulinrezisztencia-nem inzulindependens diabetes mellitus kapcsolat lehetséges patogenetikai faktora?

The role of tumor necrosis factor (TNF)-alpha in the development of insulin resistance has repeatedly been emphasized in the past few years. The present paper summarizes the data (including the authors' observations as well) focusing on the potential role of TNF-alpha in the pathogenesis of obesity and non-insulin-dependent diabetes mellitus: alteration of insulin receptor function, lipid metabolism, expression of sulphonylurea receptors, all of them suggested to be related to the TNF-alpha. The potential clinical relevances are shortly reviewed.

[Multiple endocrine adenomatosis IIB]. / Multiplex endokrin adenomatosis IIB.

The first Hungarian MEN IIB (multiplex endocrine neoplasia) syndrome is reported with the short summary of the literature about the pathogenesis and diagnosis of medullary thyroid carcinoma, presenting 80% in sporadic, 20% in hereditary form. The appearance of the patients alone (marfanoid stature, bulky lips, and ganglioneuromatosis of the tongue) may be almost enough for the presumption for the diagnosis of MEN IIB: For screening and preventing the clinical manifestation of the very aggressive medullary carcinoma in the relatives of the patient, the genetic screening is indispensable. The costs of the genetic screening and early treatment of the patients are much lower than the expenses of the traditional annual biochemical screening and the--delayed, often only supportive--treatment of the clinically manifested illness.

The comparison of thrombocytosis and platelet-lymphocyte ratio as potential prognostic markers in colorectal cancer.

The aim of the present study was to analyse the preoperative platelet count and the platelet-lymphocyte ratio (PLR) in patients with colorectal cancer (CRC) of different stages and with hepatic metastasis of CRC (mCRC) and to compare these factors as potential prognostic markers. Clinicopathological data of 10 years were collected retrospectively from 336 patients with CRC and 118 patients with mCRC. Both in the CRC and the mCRC group overall survival (OS) was significantly worse in patients who had elevated platelet count (hazard ratio [HR] = 2.2, p < 0.001 and HR = 2.9, p = 0.018, respectively). Multivariate analysis indicated that elevated platelet count was an independent prognostic factor of CRC (HR = 1.7, p = 0.035) and mCRC (HR = 3.1, p = 0.017). Disease-free survival (DFS) was significantly worse in patients with elevated platelet count in the CRC group (HR = 2.0, p = 0.011). In the multivariate analysis the PLR was not a prognostic factor in either of the two cohorts (HR = 0.92, p < 0.001 and HR = 0.89, p = 0.789, respectively). The platelet count is a valuable prognostic marker for the survival in patients both with CRC and mCRC while the PLR is not prognostic in either group.

Bevacizumab treatment before resection of colorectal liver metastases: safety, recovery of liver function, pathologic assessment.

Patients with metastatic colorectal cancer receive chemotherapy prior liver resection more and more frequently. This preoperative treatment has many effects which have to be analysed, like the safety of liver resection, toxicity, tissue regeneration, radiological and pathological response and survival data. The aim of the study was to evaluate the safety of bevacizumab containing preoperative chemotherapy and functional recovery of the liver after resection for colorectal liver metastases (CLM) and to analyse radiological and pathological data. Data of three groups of 120 consecutive patients-(1) CTX + BV: cytotoxic chemotherapy + bevacizumab, (2) CTX: cytotoxic chemotherapy, (3) NC: no treatment before liver resection-were analysed. Postoperative liver function and complications were compared, clinical, radiological and pathological data were evaluated. Between 01.12.2006 and 31.12.2010 41 resections was performed after chemotherapy + bevacizumab (CTX + BV) and 27 resections was performed after preoperative chemotherapy without bevacizumab (CTX). There were 60 hepatic resections in this period without neoadjuvant treatment (NC). 8 patients had repeated resections. The postoperative complication rate was 40 % but there was no statistical difference between the groups (P = 0.72). Only the type of resection was associated with a significantly higher complication rate (p = 0.03). The subgroup of patients, who received irinotecan had a higher complication rate in the CTX group than in the BV + CTX group (55 % vs 41 %). Preoperative administration of bevacizumab was associated with higher peak postoperative AST, ALT levels but did not affect functional recovery of the liver. The RECIST system was not able to predict the outcome after chemotherapy in every patient and in many cases this system overestimated the effect of chemotherapy. On histopathological examination the presence of necrosis was not associated with chemotherapy or pathological response. Use of chemotherapy before hepatic resection of CLM was not associated with a significant increase in complication rates. The functional recovery of the liver was not affected by the preoperative administration of chemotherapy. The use of combined neoadjuvant chemotherapy is safe before hepatic resection.