Colorectal Cancer: An Update on Treatment Options and Future Perspectives.

Throughout the years, colorectal cancer has steadily become a global health problem. While other types of cancers have seen a decline in cases because of screening and vaccination programs, colorectal cancer has risen become the third most diagnosed cancer worldwide and, more worryingly, the second leading cancer-related cause of death. The introduction of targeted therapy has been widely considered a major paradigm shift in the treatment of colorectal cancer, which agents such as bevacizumab and cetuximab quickly becoming mainstay options in the treatment of locally advanced or metastatic disease. However, this type of treatment has also shown its limitations, with limited or no benefit for a large portion of the patients. With more and more knowledge being gathered on the molecular mechanisms which govern the malignant phenotype presented by colorectal cancer, scientists are engaged in a continuous effort to develop new therapies based on these discoveries.

A Statistical Analysis of Risk Groups in Colorectal Cancer Patients.

Colorectal cancer (CRC) is considered a major global health concern due to an increasing number of new cases and cancer-related deaths each year, strong link to dietary habits prevalent in middle and high-income countries and limited therapeutic options especially in locally-advanced and metastatic settings. To counter this growing problem, the scientific community has strived to underpin the major molecular mechanisms behind the aggressive phenotype displayed by CRC and also develop new agents to selectively target and inhibit these core drivers. This evolution has allowed the separation of patients according to different risk groups in concordance with epidemiological parameters alongside novel biomarkers such as gene alterations, protein overexpression and aberrant signaling pathways. In this study we included 20 patients who underwent colonoscopy and were later received histopathologic confirmation of CRC. The statistical anamnestic data obtained from the patients (age, gender, home distribution, signs and symptoms) was corroborated with the results obtained from the histopathologic and immunohistochemical analysis of the samples obtained via colonoscopy. The average age was 63.8 years, the male: female ratio was 2.33 and the origin of 2/3 of the patients was urban and the most encountered symptoms were transit disorders (75%). In terms of colonoscopy results, the majority of tumors were found on the rectum (85%), 90% of tumors were adenocarcinomas, having a vegetant aspect in 60% of the cases and a moderate degree of differentiation in 50% of situations.

Hyponatremia - unfavourable prognostic factor in hepatic cirrhosis.

Hyponatremia is defined by a level of Na in serum below or equal to 136 mEq/L while in hepatic cirrhosis it is classically considered as relevant only at a level of Na below 130 mEq/L. Hyponatremia frequently occurs in patients with end-stage hepatic disease. The frequency and severity are variable but it has been estimated that it occurs with a frequency of 57% in hospitalized patients with cirrhosis and in those on waiting lists for hepatic transplants. Signs and symptoms of hyponatremia are related to dysfunctions of the central nervous system, due to migration of the water from intravascular space to the brain cells, resulting in the occurrence of cerebral edema. Therapeutic options in hyponatremia are limited and are based on restriction of water consumption, exclusion of diuretics and vaptans. Hepatic transplant remains the only definitive treatment for end-stage hepatic diseases in which hyponatremia has occurred.

Hepatorenal Syndrome: Diagnosis and Treatment - newsreel.

Hepatorenal syndrome (HRS) is defined as renal failure that occurs in the presence of severe acute or chronic liver disease in the absence of underlying renal pathology. Due to the functional nature of the disease and the absence of specific diagnostic markers, HRS diagnosis is determined based on positive criteria associated with excluding other causes of renal failure in patients with liver cirrhosis and ascites. Differentiation from other types of acute or chronic renal disease is extremely difficult and therapeutic options are limited, prophylactic behavior is most appropriate in patients with severe hepatic disease and risk factors for the installation of hepatorenal syndrome. Highlighting all precipitating factors of acute renal insufficiency and therapeutic modalities in order to minimize adverse events is an important step in improving the follow-up of the patients with liver cirrhosis. The prognosis is reserved especially for type 1 HRS. Liver transplantation is the best option for patients without contraindications. The therapies introduced in recent years, such as vasoconstrictor drugs or transjugular intrahepatic portosystemic shunt are effective methods in the renal function improvement.

Psychosocial issues in patients with chronic hepatitis B and C.

Psychosocial issues and the quality of life are important components at the patients diagnosed with chronic hepatitis B and C. In function of the severity of the infection with virus B or the patients who already have cirrhosis, the treatment and psychosocial education should be improved because they have bigger problems. The frequency of psychosocial disorders seems to be raised at the patients diagnosed with chronic hepatitis B. Factors as alcohol abuse and a low social support have a negatively impact above mental health of these patients. The prevalence rate of chronic hepatitis C infection at patients with severe mental illness can be nine times higher than in healthy population. Usually patients with chronic hepatitis B have a quality of life and a mental health better than patients with chronic hepatitis C. Patients with psychiatric affections (especially institutionalized people) have generally a higher risk of being infected with virus B in comparison with general population. Patients with chronic hepatitis B and C suggest a higher grade of stigmatization from society. Despite clinical challenges which treatment with interferon at patients with chronic hepatitis and comorbidities represents, recent studies indicate the fact that treatment can be administrated in safe conditions at patients with viral chronic hepatitis and psychiatric disorders.

Gastric eosinophilia--clinical and morphological correlations.

Eosinophils of the gastrointestinal tract are involved in the host immune response that occurs in the presence of the pathogens in the digestive lumen, taking part in maintaining the homeostasis of the gastrointestinal epithelium. Their involvement in inflammatory processes of chronic gastritis is less known. In our study, we identified the presence of eosinophils in chorion gastric mucosa (lamina propria) in over 34% of chronic gastritis. Eosinophils were more numerous in atrophic gastritis with intestinal metaplasia. More than 65% of chronic gastritis associated with Helicobacter pylori also had eosinophils in the gastric mucosa.

Immunohistochemical expression of EGF, c-erbB-2 and EGFR in intestinal variant of gastric adenocarcinomas.

In this study, we aimed to determine EGF, c-erbB-2 and EGFR expression in 25 specimens of intestinal gastric adenocarcinomas by standardized immunohistochemistry and to establish correlations with the major clinico-morphological parameters of these patients. We observed EGF reactivity in 22 (88%) cases, a c-erbB-2 protein expression in eight (32%) cases and an EGFR reactivity in 13 (46.42%) cases. The EGF expression was significantly correlated with the tumor degree of differentiation, but not with other investigated clinico-morphological parameters and nor with c-erbB-2 and EGFR1 expression. However, we noticed the existence of a dependence between c-erbB-2 and EGFR1 expression in the main tumor mass. Such immunoprofile suggests the possible intervention of autocrine and paracrine loops in the developing of intestinal variant of gastric adenocarcinomas.

Synchronous diagnosis of signet ring cell colon carcinoma and transitional carcinoma of the left distal ureter.

The presence of synchronous multiple primary carcinomas, although recognized, remains very uncommon. Their etiopathogeny is unclear. The wide spread of imaging techniques currently facilitates diagnosis of simultaneous tumors. We present the rare case of a signet ring cell colon carcinoma coexisting with a transitional cell carcinoma (TCC) of the ureter, which debuted with symptoms of intestinal obstruction in a 75-year-old male patient, with no prior relevant history. Computed tomography showed signs of a tumor mass on the transverse colon, as well as left hydronephrosis with a tumor in the lower third of the ureter, which prompted for immediate emergency surgery. After the appropriate surgical maneuvers, tissue collected from both tumors underwent usual histological preparation and Hematoxylin-Eosin staining, as well as multiple immunostaining with a complex panel of markers. The patient had a favorable postoperative course and during a six-month follow-up, we did not detect any signs of illness.

Immunohistochemical expression of TGF beta (TGF-ß), TGF beta receptor 1 (TGFBR1), and Ki67 in intestinal variant of gastric adenocarcinomas.

Although in the last decades the incidence of gastric cancer declined, at present it is ranked worldwide on the fourth place between all human cancer pathology. Also, it has an aggressive behavior, the majority of patients being diagnosed in advanced stages. One of the key factors to control survival improvement of those patients is to clarify the molecular mechanisms involved in initiation, progression, invasion, and metastasis of gastric cancer. We thus investigated the immunoreactivity for TGF-ß, TGFBR1, and Ki67 of 25 specimens of intestinal gastric adenocarcinomas, and compared this with the correspondent reactivity for three specimens of diffuse gastric carcinomas; in the end, we tried to establish a statistical correlation with major clinicomorphological parameters. As a result, we noticed that the highest reactivity was present in the diffuse type compared with the intestinal variant, in which the TGF-ß reactivity progressively increased along the normal epithelium-intestinal metaplasia-dysplasia-carcinoma sequence. Also, we found for intestinal variant that TGF-ß immunoreactivity correlated significantly with tumor degree of differentiation and proliferative activity measured based on Ki67 immunoreactivity. In conclusion, TGF-ß is implicated in the progression of intestinal type of gastric adenocarcinomas and its immunoreactivity assessment for these targets has a prognostic value.

Intestinal perforated malignant melanoma: diagnostic and therapeutic difficulties.

The intestinal malignant melanoma is a rare occurrence in the daily surgical practice, with difficult diagnosis (even on usual pathologic examination) and therapeutic attitude. Most of the lesions are secondary to a cutaneous primary melanoma, but there are cases in which the original site may not be discovered, and are considered as primitive intestinal melanomas. This paper presents the case of a 50 year old male patient, diagnosed and operated as emergency with acute abdomen caused by a tumoral perforation of the small bowel; several tumors, in different stages of local evolution, were discovered during laparotomy. A triple enterectomy with end-to-end entero-enteral anastomosis was performed, with uneventful postoperative recovery. The later postoperative evolution was marked by the occurrence of multiple subcutaneous recurrences and a bulky metastasis in the mediastinum; 18 month after the initial surgery, the patient died due to the melanoma recurrence. Diagnostic and therapeutic difficulties are discussed in this paper, related especially to the differential diagnosis of the origin of the intestinal lesion (a metastatic melanoma with unknown primary site or a primary malignant melanoma of the small bowel), since no other sites of origin were discovered after a thorough examination.

Chronic gastritis with intestinal metaplasia: clinico-statistical, histological and immunohistochemical study.

Chronic gastritis has a high incidence in adults, causing progressive destruction of glandular structures, favoring the development of gastric atrophy. The association of chronic gastritis with intestinal type metaplasia of gastric mucosa has a poor outcome as intestinal metaplasia is regarded as a precancerous lesion. Metaplasia is common in patients with Helicobacter pylori infection and also heavy smokers. The aim of our study was to evaluate the relationship between chronic gastritis and intestinal metaplasia. The study was conducted on a total of 1218 patients, aged between 5 and 90 years, who presented for dyspeptic disorders in the period 2007-2010 and were examined clinically and endoscopically. During the gastroscopic examination, fragments of gastric mucosa were collected for the histopathological study and for highlighting the H. pylori infection. For the histopathological study, the Hematoxylin-Eosin and PAS-Alcian Blue stains were performed, while for the immunohistochemical study the anti-TAG72 and anti-PCNA antibodies were used. A diagnosis of gastritis was established in 615 patients, representing approximately 50.5% of all cases. Most cases with gastritis were found in people of middle age. Gastritis was present in almost all age groups, from teenagers to the elders. Of the 615 cases of gastritis, urease test was positive in 353 patients, representing approximately 57.40% of all patients with gastritis. Histopathological examination identified the presence of intestinal metaplasia in 61.60% of patients with chronic gastritis, mostly complete metaplasia. PCNA immunohistochemistry revealed that cell proliferation processes are intensified in intestinal metaplasia. This study highlights the importance of chronic gastritis, intestinal metaplasia, and H. pylori infection in the etiopathogeny of gastric cancer.

The composite lymphoma: chronic lymphocytic leukemia--classic Hodgkin's lymphoma.

The composite lymphoma (CL) is defined by the presence in the same tissue or organ of two distinct histological aspects of non-Hodgkin's lymphoma (NHL), or NHL and Hodgkin's lymphoma (HL). The definition of the CL has evolved, requesting the identification of the immunophenotypic pattern and clonal distinct aspects for the two-lymphoproliferative lesions. We present a case of a 73-year-old farmer who presented with B-symptoms and multiple adenomegaly. The biopsy of a left cervical lymph node reveal a CL: a histological and immunophenotypic aspect of HL-mixed cellularity (CD15+, CD30+, CD20-) and a diffuse small cell infiltrate which meet the criteria for B-CLL (CD20+, CD23+, and CD5+). The lymphocytes in peripheral blood over 15 000/mm(3) and marrow infiltrate with small lymphocytes also sustain the B-CLL diagnosis. The relationship between the two lymphoproliferations is discussed reported to the case above, but also considering the literature data. In most of the cases the two proliferative processes are clonal related which means they have a commune lymphoid progenitor, pre-GC or early-GC with individual detachment and transit through GC (also, the afferent related processes). It is also possible that the two proliferations, which form the composite lesion to have different cellular origins, possibility sustained by the analysis of the IgH rearrangements and of the somatic mutations identified in the two clones. The EBV-role in HL-pathogeny is related to the way of salvage or/and initiation of a clonal process in a GC-cell which has major deletions in the variable part of IgH.

Correlations between gonadotropins level, vaginal cytology and menopause vessel-active phenomena.

INTRODUCTION: Vessel active phenomena from menopause as hot flushes have unknown cause but is demonstrated that the hormone substitution treatment has a very good efficiency in the disproof of the symptomatology. OBJECTIVES: To establish if there is a correlation between gonadotropins level, the presence of the vessel active manifestations and the atrophy of the vaginal epithelium in menopause. MATERIAL AND METHODS: The study design is cross-sectional, done on the 40 and 60-year-old women from the general population list of a family doctor. We studied the blood values of LH and FSH and the vagina cytology and the relations of these parameters with the presence of hot flushes and others vessel active phenomena in menopause. RESULTS: The group consists of 136 women aged between 40 and 60-year-old. Their blood tests prove: LH with normal levels in 79% of cases, FSH has high values in 85%, the vagina cytology marked out the epithelium atrophy in 76% of cases. DISCUSSION: The augmentation of the FSH values is associated with the presence of hot flashes. The ratio LH/FSH under 0.40 is strong associated with vessel active phenomena (p-value 0.000012). We could not establish a statistical correlation between the presence of the vessel active phenomena and vagina atrophy (p-value 0.098). CONCLUSIONS: Vessel active manifestations on the menopause have morphological substratum. The increase of FSH is statistic correlated to the vessel active disorders. It is possible that FRH be the trigger for the hypothalamic thermo detection.

The genotoxicity study of resveratrol in primary gastric adenocarcinoma cell cultures.

Gastric cancer is the second most common cause of cancer-related death in the world. Some studies indicate that polyphenolic compounds and antioxidants exert a protective action against gastric cancer. Among the polyphenolic compounds tested and proven effective against gastric cancer is resveratrol, a natural polyphenol present in red wines and various human food items. Resveratrol has been shown to suppress proliferation of a wide variety of tumor cells. We tested the genotoxic activity of resveratrol in primary cell cultures from gastric adenocarcinoma, obtained by mucosal biopsy at upper digestive endoscopy. The adenocarcinoma cells were analyzed for the presence of micronuclei at different concentrations of resveratrol at 48 hours and at 72 hours. The results showed that resveratrol induced micronuclei dose-dependently. The frequency of micronuclei increased progressively with the dose of resveratrol used, the high frequency is in the primary culture initiated from gastric adenocarcinoma: signet ring cell type. The high frequency of micronuclei is at 72 hours at the 20 microg/mL resveratrol and is decreased at low concentrations (5 microg/mL, 10 microg/mL resveratrol). This results show the genotoxic activity of resveratrol in adenocarcinoma gastric cell and the anticancer property of this substance.

Nonalcoholic fatty liver disease and metabolic syndrome: a concise review.

Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological entity increasingly recognized as a major health burden in developed countries. In the last decade, several studies have independently provided evidence for a strong association between NAFLD and each component of the metabolic syndrome, including central obesity, hyperglycemia, dyslipidemia, and hypertension. This article focuses on epidemiological, clinical, pathogenic and therapeutic aspects, which link these two syndromes.

The endoscopic and morphological forms of early gastric cancer.

The early gastric cancer is an endoscopic notion in which gastric cancer is strictly placed to mucosis and submucosis without extensive manifestations. It is the form with favorable prognosis and better survival at 5 and 10 years. Our study tries to systematize the debut forms of early gastric cancer and their association with the lesions with malignisation risk. We also try to evaluate the incidence of endoscopic and histopathologic forms of early gastric cancer found in an internal medicine division. Our study included 435 patients with gastric cancer endoscopic and histologic diagnosed. Statistically, 64.36% were men and 35.64% were women, the mean age 48 +/- 7 years. The endoscopic forms of early gastric cancer were type I: protruded in 19 cases, type II: superficially in eight cases, type III: excavated in six cases. Early gastric cancer is diagnosed with difficulty, it represents in 7.58% of the gastric cancer, being most frequently asymptomatic. The endoscopic forms frequently found in early gastric cancer in the population were type I: protruded and type IIa: superficially elevated. The histopathological examination is compulsory at this form of gastric cancer, while in advanced gastric cancer endoscopy is often sufficient for diagnosis. Analysing the histopathological results of cases diagnosed with early gastric cancer we found: 22 cases with intestinal type and 11 cases diffuse type. Microscopically, 15 were intramucosal and 18 had submucosal invasion. I and IIa lesions were predominantly located at the antrum and are histologically differentiated adenocarcinoma. Differentiated carcinoma frequently produces an elevated lesion and the border is well demarcated. There are frequent opportunities to detect gastric cancer in the early phase and the patient can expect a complete cure by the surgical operation or endoscopical mucosal resection.

Drug-induced hepatitis - morphological and ultrastructural aspects.

Frequency of drug-induced liver diseases is increasingly, more than 200 different drugs being incriminated in hepatic disorders. We performed a retrospective study on 65 cases of deaths due to drug intoxications and an experimental model of subacute hepatitis induced by acetaminophen. In our experimental model, we observed various histological lesions: granular degeneration, vascular congestion, lymphoplasmocyte infiltration, cytonecrosis. Histological criteria are not specifically, but very usefully, because based on these criteria we can suspect a drug etiology in hepatic disorders when any other cause is absent. Ultrastructural study of hepatocytes revealed some modifications, in addition to data provided by optical microscopy.

Microvolt T wave alternans (MTWA)--a new non-invasive predictor of sudden cardiac death.

Over 10 million people are at high risk of sudden cardiac death (SCD). In order to stratify the risk of SCD due to ventricular tachyarrhythmia, additional methods are required. In the past years, the development of implantable cardioverter/defibrillator (ICD) has become an effective therapeutic option for patients at high risk for SCD, albeit ICD is both expensive and invasive. The Microvolt T-Wave Alternans Test (MTWA, Cambridge Heart Inc.) is a non-invasive method with a stronger positive predictive value in the assessment of arrhythmic risk, when compared to invasive electrophysiological studies (EPS). MTWA has been proved at least an equivalent or even a more sensitive risk predictor of ventricular tachyarrhythmia and/or SCD. MTWA may be considered as a first-line screening test for patients with ventricular arrhythmia history, in order to discriminate the high risk / low risk subgroups, prior to invasive EPS and/or treatment.