Immunohistochemical study of colorectal cancer liver metastases: the immune/inflammatory infiltrate.

Our study is focused on the investigation of the immune/inflammatory infiltrate in liver metastases secondary to colorectal cancer. Twenty cases of colorectal liver metastases have been studied, including eight with recurrent metastases occurred after a previous treatment by thermonecrosis (group 1) and 12 with primary metastases treated exclusively by surgery (group 2). The cases were investigated by routine histopathological exam and by immunohistochemistry, using CD3, CD20 and CD68 antibodies. The design of the study envisages a comparative qualitative and quantitative evaluation of the B- and T-lymphocytes and macrophages inside the tumor and at the interface between liver parenchyma and tumor. Student's t-test was used for all statistical comparisons. The qualitative exam revealed, for both groups, the presence of an important T-lymphocyte, and respectively B-lymphocyte cell population at the interface between the tumor and the liver parenchyma, the number of intratumoral cells being extremely reduced. The statistical analysis showed significant differences (p<0.05 for groups 1 and 2, T- and B-lymphocytes, intratumoral vs. peritumoral). However, the comparison of group 1 with group 2 revealed no statistically significant differences between the mean value of intratumoral and peritumoral T- and B-lymphocytes, respectively. The qualitative exam revealed the presence of a well represented macrophage cell population, with a heterogenous distribution from case to case. This finding was confirmed by numerical information, with a lack of a statistically significant difference between the mean number of macrophages quantified intra and peritumoral, for both study groups. However, statistically significant differences were noticed between intratumoral and peritumoral mean value, respectively, for group 1 vs. group 2 (p<0.05). T-lymphocytes are the most numerous, their peritumoral location being the landmark for the histoarchitecture of the immune/inflammatory infiltrate and conducting the immune response developed at the interface between the tumor and liver parenchyma. The quantitative assessment of the immune infiltrate shows similar features in surgically resected metastases and recurrent metastatic disease after thermonecrosis. On the contrary, the quantitative evaluation of the macrophage population indicates a functional association rather with the primary metastasis process than with the recurrent metastatic disorder.

[Parathyroid glands involvement in multiple endocrine neoplasia]. / Interesarea paratiroidelor in neoplaziile endocrine multiple.

UNLABELLED: Multiple endocrine neoplasias are syndromes characterized by the involvement of at least two endocrine glands. Parathyroid gland involvement is usually noted in Multiple Endocrine Neoplasia (MEN) type I and type II. Parathyroid glands tumor associated with endocrine pancreatic tumor, as well as pituitary tumors is the typical pattern of MEN I. The parathyroid gland is the most frequent abnormality in MEN I. CASES REPORTS: We presented five cases with MEN I and parathyroid glands involvement. In three cases with young ages (28-33 years old) and familial setting, the MEN I syndrome was "complete" (parathyroid adenoma, gastrinoma or insulinoma and pituitary adenoma--prolactinoma or GH-secreting tumors), and, in the other two cases, with 57 and 68 years old respectively, the MEN I syndrome was "incomplete" with parathyroid glands and pituitary gland involvement. The cases with gastrinomas were operated in emergency for complication of peptic ulcer (perforation associated with peritonitis and gastro-intestinal bleeding); then the pancreatic tumors were diagnosed and left pancreatectomy with spleen preservation and respectively, tumor resection have been performed. Hyperparathyrodism was then diagnosed and subtotal parathyroidectomy has been performed in both cases. Unfortunately one patients died due to severe endocrine disorder. During the necropsy, the pituitary adenoma has been diagnosed. The third case with "complete" MEN was a women of 33 years old, admitted for severe hypoglycemia. The imagistic and laboratory test diagnosed a tumor situated into the pancreatic body, and an parathyroid adenoma. The resection of pancreatic tumor associated with resection of the parathyroid adenoma, in the same time, were performed. The other two cases with "incomplete" MEN were older then the first patients, and were diagnosed with hyperparathyrodism and pituitary gland tumor. The resection of parathyroid gland adenoma has been performed in both cases, with uneventful postoperative course. The literature data was also discussed. CONCLUSIONS: The parathyroid glands involvement in MEN is common. There are two kinds of MEN associated with parathyroid gland involvement: the "complete" form, especially in young patients, with diffuse involvement of the parathyroid glands, and the subtotal parathyroidy is the best choice, and the "incomplete" form, especially in elderly, with the involvement of a single parathyroid gland; in this way, the resection of the adenoma associated with biopsy from the other parathyroid gland is the best approach. The presence of gastrinomas, complicate the disease prognosis and the surgical approach. The treatment of these patients is challenging and has to be done in multidisciplinary team.

Experimental COPD induced by solid combustible burn smoke in rats: a study of the emphysematous changes of the pulmonary parenchyma.

According to the GOLD 2006 definition, COPD is a preventable and treatable pathological situation characterized by the partially reversible airflow limitation determined by a variable proportion mixture of small airways disease (obliterative bronchiolitis) and parenchyma destruction (emphysema). A major impediment in the study of the COPD is represented by the fact the fundamental morphological changes that determine the major pulmonary dysfunction take place in the small, peripheral, airways, at the bronchiolo-alveolar attachments. That is why the experimental model of COPD developed progressively to the transgenic mouse. There are many experimental studies on the animal models that have obtained emphysema rapidly through intratraheal instillation of elastasis or bronchitis/bronchiolitis through intratraheal instillation of particles. It is accepted that the unnatural character of aggression, that does not permit the natural evolution of the inflammatory phenomenon, limits these models and tissue remodeling that take place in COPD patients. It is well known that cigarette smoking is a major cause of COPD. There have been reported some cases of COPD in never smoking patients exposed to air pollutants. We aimed to create an experimental model of COPD in rat through exposure to smoke resulted from solid combustibles burn for the same period and in the same conditions of cigarette smoke exposure and to compare the pulmonary morphological changes. Thirty Wistar rats were divided into three groups (n = 10): (1) the control group (C), (2) the cigarette smoke group (CS), and (3) the solid combustible smoke group (SCS). Apart from the control group, these were treated with solid combustibles smoke (SCS group) or cigarette smoke (CS group) for six months. Morphological and morphometry studies have been assessed. We have established a rat COPD model based on natural cigarette smoke exposure versus solid combustible burn resulted smoke, usable for a further approach in human non-smoker COPD investigation. Out procedures resulted in clear pulmonary morphological lesions that are characteristic for COPD. The achieved data support the idea that solid combustible burn resulted smoke determines emphysematous parenchyma lesions that are similar, but with an attenuated morphological appearance when comparing to the cigarette smoke exposure.

[Structural changes of tumor microenvironment in liver metastases of colorectal carcinoma]. / Modificari structurale de micromediu tumoral în metastazele hepatice ale carcinomului colorectal.

UNLABELLED: The immunohistochemistry represents a very effective tool for describing the biological phenomena that characterize the primary or secondary neoplastic development. By using a complex immuno-morphologic approach, our study aims to develop a characterization of the metastatic liver microenvironment, based on the following features: similarities and differences in the proliferation activity, particular aspects of vascularity and immune response, the cellular dialogue generated at the level of the parenchyma - neoplastic tissue interface, the structure of the associated stroma. MATERIAL AND METHODS: Ten cases of liver metastases have been studied, including five treated exclusively by surgery (group 1) and five with recurrent metastases occurred after a previous treatment by thermonecrosis (group 2). The cases were investigated by routine histopathological exam and by immunohistochemistry. The choice of the antibodies was motivated by the follow-up of the parameter classes presented below: (i) proliferation/apoptosis; (ii) structure; (iii) angiogenesis and lymphangiogenesis; (iv) immunological reactivity; (v) cytokines. RESULTS: The elements defining the histopathologic and immunohistochemical patterns allowed a comparative evaluation of the metastasis models considered for the two groups of studied cases. The analysis of proliferation / apoptosis parameters proved a high aggressiveness in tumor proliferation for both types of metastases. Recurrent metastases showed an increased angiogenesis and a moderate lymphangiogenesis, as well as a massive matrix reshaping. The evaluation of the inflammatory infiltrate suggested that the development of the liver metastases is not accompanied by significant immunologic rejection, but it rather induces the tissue remodeling at the invasion border level. The recurrence corresponds to a typical interval of 6 months or longer, and is associated with intense fibrogenesis, angiogenesis, and inconsistent inflammatory infiltrate. CONCLUSIONS: Therefore, the efficiency of the thermonecrosis procedure with water vapors seems to drastically depend on the complete necrosis of the target tumor, plus the adjacent cells of the parenchyma in a neighborhood of some millimeters. Moreover, the therapy must include anti-angiogenic resources as well as inflammation modulators, since the vascular supply and the leukocytic activity support the metastasis development.

[Liver resection for hepatocellular carcinoma in cirrhotic patients]. / Rezectia hepatica in carcinomul hepatocelular dezvoltat pe ciroza.

The incidence of hepatocellular carcinoma (HCC) in cirrhotic patients is increasing. Despite advances in imaging and laboratory screening which allow earlier diagnosis, the surgeon is all too often confronted with an HCC of advanced stage or arising in the setting of severe cirrhosis. Hepatic resection is still considered the treatment of choice for hepatocellular carcinoma in patients with liver cirrhosis. From 1998 to 2005, 6 patients (5 males, 1 female, age 52-70 years, mean age 64.1 years) with HCC associated severe, but well compensated liver cirrhosis (Child A-- 4 patients, Child B--2 patients) underwent 9 hepatic resection in our department. Mean tumor size was 56 mm (range 23-86 mm). Two of these lesions were in the left liver and four in the right lobe. Doppler ultrasonography was performed in all cases and CT in 3 cases to confirm the extension of the lesions. Laparoscopy was performed in 3 patients under CO2 pneumoperitoneum. The Pringle maneuver was not used. The transection of the liver parenchyma was obtained by the use of Ligasure and harmonic scalpel. Nine hepatic resections were performed: 7 segmentectomy and 2 non-anatomical resections. The resection margin was 1 cm. The mean operative time was 90 minutes (range 60-120). Mean blood loss was 250 ml and 2 patients required blood transfusion. One patient died on the tenth postoperative day from a severe respiratory distress syndrome and hepatic failure. Major morbidities occurred in three patients who developed moderate postoperative ascites, which resolved successfully with conservative treatment in two patients. Limited liver resection in cirrhotic patients with HCC is feasible with a low complication rate when careful selection criteria are followed (tumor size smaller than 8 cm, Child-Pugh A class and the good general conditions of the patients). Other medical and interventional treatments (chemoembolization, chemotherapy) can only slow the progress of HCC.

[Palliative therapy for malignant hepatic tumors with hyperthermia]. / Metode paleative de tratament al tumorilor hepatice maligne prin hipertermie.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with an annual occurrence of one million new cases. The incidence of liver metastasis is much higher than the incidence of HCC. Overall nearly 50% of the patients with colorectal adenocarcinoma will develop liver metastasis. Surgical resection remains the "gold standard" for resectable hepatic neoplasms, but only a minority of patients present with lesions which are potentially curable. In these nonresectable hepatic tumors palliative treatment using focal necrosis by hyperthermia (radiofrequency, microwave coagulation therapy, interstitial laser photocoagulation, thermo-ablation with hot water steam) appear as a valuable alternative. Best results are reported in the case of associations of thermo-necrosis with general or intraarterial chemotherapy. These methods of treatment can be performed by percutaneous, laparoscopic or open approach. Precise guidance of the focal necrosis can be realized using CT scan, IRM and intraoperative ultrasound exam and the results are evaluated by the same techniques. The key element in the management of the malignant tumors of the liver is the cooperation between surgeon, intensive care physician, oncologist and specialist in interventional radiology, to appreciate the indication of therapy. Further controlled trials are required to define the precise indications and long term results of these methods of treatment.

[ Etiopathogenesis of autoimmune thyroiditis]. / Etiopatogeneza tiroiditelor autoimune.

Human autoimmune thyroid diseases include both autoimmune hypothyroidism (thyroiditis) and autoimmune hyperthyroidism (Graves' disease). Either of the two feature profuse thyroidal infiltrates of CD4+ and CD8+ T-cells and a biased intrathyroidal T-cell-receptor repertoire. Despite strong epidemiologic evidence in favor of a genetic component in the etiology of autoimmune thyroiditis, few hereditary risk factors have been consistently identified, which include a well-characterized series of HLA genes. These may account for the progression from a harmless autoimmune response characterized solely by production of autoantibodies to thyroglobulin to pathogenic autoimmunity where injury occurs to the thyroid cells. We hereafter summarize the role of inherited risk factors along with that of environmental risk factors. It was suggested that iodine increase the autoantigenic potency of thyroglobulin, a major pathogenic antigen in the induction of autoimmune thyroiditis. The clinical entities included together as autoimmune thyroiditis is shortly reviewed, along with the presentation of the common pathogenetic pathways. Unique features of each member of the group are further emphasized.

[Male gender-- difficulty factor in cholecystectomies for cholelithiasis]. / Sexul masculin--factor de dificultate în colecistectomiile pentru colelitiaza.

Male gender has been recognized as a risk factor for an increased conversion rate of laparoscopic cholecystectomy and more severe disease in those with symptomatic cholelithiasis. The aim of this study was to determine the effect of male gender on the clinical presentation of symptomatic cholelithiasis, relation between male gender and acute cholecystectes, the operating time, the frequency of conversion and postoperative morbidity. The medical records of all patients with symptomatic cholelithiasis from 31 mars 1993 to 31 mars 2001 (4145 patients) were evaluated. These cases were divided into four groups: A--elective laparoscopic cholecystectomy group--patients with cholecystectes with elective laparoscopic cholecystectomy (3995 cases); B--patients with acute cholecystectes whose laparoscopic cholecystectomy was performed successfully (660 cases); C--acute conversion group converted to open surgery (240 cases); D--acute open group with elective open cholecystectomy. The study reveals that males suffer from a severe form of cholecystectes that raise difficulties when laparoscopic cholecystectomy is performed.