TRP genes family expression in colorectal cancer.

UNLABELLED: Colorectal cancer (CRC) is the most common cancer of the gastrointestinal tract. Different factors are responsible for the development of CRC. Transient Receptor Potential (TRP) which is an important component of calcium channel is associated with several pathological conditions like cancer, neurodegenerative and cardiovascular diseases. Thirty members of the family of TRP ion channel in mammals have been determined till now. The aim of this study is to investigate TRPM, TRPV and TRPC gene expression levels in tumor tissues of CRC patients and to analyze the relationship of expression in tumor tissue of CRC with other known prognostic factors. MATERIAL AND METHODS: In this study, 93 CRC patients were included. The level of TRP gene expression in paraffin blocks of normal and cancerous colorectal tissue samples were studied at the level of mRNA with Real-time PCR. RESULTS: The mRNA expression level of TRPV3, TRPV4, TRPV5, TRPM4 and TRPC6 genes in 37 female and 56 male patients diagnosed with CRC was revealed lower in tumor tissue as compared to normal tissue (p < 0.05). No statistically significant differences of mRNA expression levels of other TRP genes were found. CONCLUSIONS: TRP gene family like TRPV3, TRPV4, TRPV5, TRPM4 and TRPC6 may be thought as potential genes contributing to tumorigenesis as their expression decreases in CRC as compared to normal tissues.

Gene expressions of TRP channels in glioblastoma multiforme and relation with survival.

Glioblastoma multiforme (GBM) is one of the most lethal forms of cancer in humans, with a median survival of 10 to 12 months. Glioblastoma is highly malignant since the cells are supported by a great number of blood vessels. Although new treatments have been developed by increasing knowledge of molecular nature of the disease, surgical operation remains the standard of care. The TRP (transient receptor potential) superfamily consists of cation-selective channels that have roles in sensory physiology such as thermo- and osmosensation and in several complex diseases such as cancer, cardiovascular, and neuronal diseases. The aim of this study was to investigate the expression levels of TRP channel genes in patients with glioblastoma multiforme and to evaluate the relationship between TRP gene expressions and survival of the patients. Thirty-three patients diagnosed with glioblastoma were enrolled to the study. The expression levels of 21 TRP genes were quantified by using qRT-PCR with dynamic array 48 × 48 chip (BioMark HD System, Fluidigm, South San Francisco, CA, USA). TRPC1, TRPC6, TRPM2, TRPM3, TRPM7, TRPM8, TRPV1, and TRPV2 were found significantly higher in glioblastoma patients. Moreover, there was a significant relationship between the overexpression of TRP genes and the survival of the patients. These results demonstrate for the first time that TRP channels contribute to the progression and survival of the glioblastoma patients.

Adrenomedullin expression does not correlate with survival in lung cancer.

It is suggested that adrenomedullin (AM) plays a role in lung carcinogenesis although, to confirm this suggestion, further clinical studies are needed to determine its relationship with prognosis in lung cancer. Archived 50 paraffin-embedded tumor samples of the lung were retrospectively evaluated for AM expression by immunohistochemistry and analyzed for a possible correlation with patient characteristics and survival. Quantitation of immunoreactivity was accomplished using an immunohistochemical scoring system. The pulmonary resection specimens contained 22 squamous cell carcinomas, 15 adenocarcinomas, and 13 small cell carcinomas. Non-small cell carcinomas of the lung were more likely to express AM than small cell carcinomas of the lung. Ninety-one percent of squamous cell carcinomas and 87% of adenocarcinomas expressed AM at a moderate to strong level and grade2-4 (30-100%), which were significantly higher from the non-neo-plastic lung tissue. Twenty-three percent of small cell carcinomas of lung expressed AM. Interestingly, AM immunoreactivity was essentially weak and grade 1 (<%30) in this group. AM expression is upregulated in non-small cell carcinomas of the lung, whereas it is downregulated in small cell carcinomas and non-neo-plastic lung tissues. AM expression did not show any correlation with the differentiation of the tumor, the stage of cancer, and the overall survival of patients. These results did not support the role of adrenomedullin as an independent survival factor for lung cancer. However, AM inhibition in conjunction with other anti-angiogenic agents may be useful in the prevention and treatment of malignancies.

Is post-Lipiodol CT better than i.v. contrast CT scan for early detection of HCC? A single liver transplant center experience.

Hepatocellular carcinoma is a highly vascular neoplasm usually arising from a cirrhotic liver. Delayed, noncontrast, computed tomography (CT) imaging after 7 to 14 days reveals an oil-based contrast agent to be concentrated in the tumor but not in normal hepatic parenchyma. The aim of this study was to retrospectively correlate the post Lipiodol CT scan findings with respect to tumor size in the explanted liver. We retrospectively reviewed adult patients who had undergone orthotopic liver transplantation between November 1995 and December 2004 and also had an hepatic arteriogram with Lipiodol injection as part of their pretransplant workup. We calculated sensitivity, specificity, false-negativity, false-positivity, and accuracy of the test, as well as positive and negative predictive values. Lipiodol CT exam had sensitivity of 1.0; specificity of 0.6 with a calculated positive predictive value of 0.89 and a negative predictive value of 1.0. Overall accuracy of Lipiodol CT scan test was found to be 0.91, which was superior to an intravenous contrast CT alone. In conclusion, because of the higher sensitivity and accuracy values, hepatic arterial Lipiodol injection can be considered during the pretransplantation workup of high-risk cirrhotic patients, since the current model for End-stage Liver Disease scoring system for hepatocellular carcinoma is built on the ultimate bulk of the tumor. Further multicenter, controlled, large-volume prospective studies are warranted to verify this observation.

A case representing coexistence of acute myeloblastic leukemia and dedifferentiated liposarcoma: the possible role of chemotherapy in triggering dedifferentiation.

Acute myelogenous leukemia (AML) is a hematological disorder that is characterized by an abnormal proliferation of immature myeloid cells. Dedifferentiated and well-differentiated liposarcomas are the two pathological subtypes of liposarcoma, based on the WHO classification. Transition from well-differentiated to dedifferentiated liposarcoma is a well-recognized phenomenon. Well-differentiated tumors are known to have low malignancy grade. However, when dedifferentiation occurs, the tumor acquires the aggressive features of a fully malignant lesion. This process largely is believed to progress in a time-dependant manner; however, time is not the only factor of importance. The potential roles of other factors in this transition are still unclear. To date, the coexistence of AML and liposarcoma has not been reported in the literature. In this paper, we report on a case of coexistence of AML and liposarcoma, and on the unusual behavior of a well-differentiated tumor after dedifferentiation occurs.

Histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto's disease) mimicking systemic lupus erythematosus: a review of two cases.

Kikuchi-Fujimoto's disease (KFD), or histiocytic necrotizing lymphadenitis, is a benign and self-limited lymphadenitis commonly found in young women. It often shares clinical features with systemic lupus erythematosus (SLE), such as arthralgias, fever and leukopenia. The etiology of KFD remains unknown and controversial. Clinical course is favorable, with spontaneous remission in less than four months in almost all cases. Herein, we present two cases. The former is a 53-year old woman presenting with cervical lymphadenopathy, arthralgia, pancytopenia and positive antinuclear antibody (ANA). Lymph node biopsy revealed histopathological features compatible with Kikuchi-Fujimoto histiocytic necrotizing lymphadenitis. The latter patient was a 20-year old woman presenting with left cervical lympadenopathy, a butterfly rash that was reminiscent of SLE, and a positive antinuclear antibody. Based upon clinical, histological and laboratory findings, the diagnosis of SLE was excluded. Careful attention should be paid to differentiating between KFD and SLE, because of their similar presentations, yet different clinical courses and therapeutic requirements.

The effect of total plasma exchange on fulminant hepatic failure.

Total plasma exchange (TPE) corrects coagulopathy in patients with liver disease and removes hepatotoxins/cytokines. This improvement is transient but can be used as a bridge until an organ is identified for liver transplantation (LTx) or the liver itself regenerates. Our aim was to retrospectively assess the efficacy of TPE in fulminant hepatic failure (FHF) and its impact on liver function tests. Between 1995-2001, 39 patients with FHF who had undergone TPE were reviewed. FHF was defined according to the O'Grady criteria based on the duration of encephalopathy as well as jaundice. TPE was performed using the Cobe Spectra TPE (Gambro) in Liver Intensive Care Unit, continued on a daily basis, until either adequate clinical response was achieved, the patient expired, or transplantation occurred. INR, PTT, Fibrinogen, ALT, AST, GGT, BUN, Ammonia, and Total Bilirubin were analyzed before and after TPE. Student's t-test and chi-square test and ANOVA were used for statistical analysis. Thirty-nine patients with FHF (31 females, 8 males with mean age of 32.3, range: 7-64) underwent TPE. Coagulopathy, hyperbilirubinemia, hyperammonemia were significantly improved (P < 0.05). Twenty-one patients survived (54%), 12 required LTx, and 18 patients (including one after LTx) expired. TPE was found to be significantly effective for correction of coagulopathy and improvement of liver tests. This intervention can be considered for temporary liver support until recovery or liver transplantation.

DNA analysis and DNA ploidy in gastric cancer and gastric precancerous lesions.

Gastric cancer (GCa) is still a common cause of cancer-related deaths worldwide, despite improved diagnostic and therapeutic implications. Hence, early diagnosis has critical importance. Flow cytometry reveals rapid and reproducible quantification of nuclear DNA content of disaggregated tissues and assessment of its significance in various malignant and precancerous lesions. A total of 121 patients with GCa, chronic atrophic gastritis (CAG), gastric polyps, intestinal metaplasia (IM) and gastric dysplasia and 36 healthy controls were enrolled in this study. Flow cytometric measurements of DNA ploidy, total S-phase, G2M-phase and proliferative indexes (PIs) were analysed on fresh gastric biopsy specimens obtained by gastroscopy. DNA aneuploidy was present in 43.75% of the GCas (p < 0.05). We found a DNA aneuploidy rate of 15.38% in CAG, 15.38% in IM and 25% in epithelial dysplasia. One of nine polyps had aneuploidy. None of the normal gastric mucosa samples showed aneuploidy. The controls had lower rates of total S-phase and PIs (p < 0.05). In conclusion, DNA flow cytometry may be offered as an objective diagnostic tool for early detection of malignant transformation in gastric lesions.

Liver transplantation for hepatitis B in the United States.

AIM: To evaluate the impact of hepatitis B virus (HBV) on US health care system, we reviewed the Organ Procurement and Transplantation (OPTN, formerly UNOS) HBV database. METHOD: We reviewed records of liver transplantations (LTx) performed in the United States listed for the diagnoses of HBV between 1993 and mid-October 2004. Both acute as well as chronic cases were included. Coinfection with hepatitis C virus was excluded from study. The specific states selected for review were chosen from those areas that are receiving large numbers of new immigrants from high HBV endemic areas (ie, Texas, Pennsylvania, California, New York, and Florida). One-, 3-, and 5-year patient survival rates for both cadaveric and living related donors were analyzed. Survival rates were obtained from OPTN database as Kaplan-Meyer survival test. RESULTS: Between 1993 and mid-October 2004, 53,312 LTx had been performed nationwide. Of these, 2314 (4.34%) were performed for the diagnosis of HBV; 1816 cases (78%) were due to chronic HBV infection (45 of them were living donor LTx) and 498 cases (22%) were due to HBV-induced acute liver failure (seven of them were living donor LTx). Three- and 5-year survival rates of chronic HBV-related LTx patients were better than acute HBV-related and overall LTx patients. CONCLUSION: HBV is generally considered to have a minor health significance by many community gastroenterologists. With growing immigration from overseas, it may eventually have a higher impact on LTx. Therefore, it is crucial to further educate gastroenterologists and primary care physicians caring for this specific group of patients.

The impact of total plasma exchange on early allograft dysfunction.

INTRODUCTION: Early allograft dysfunction (EAD) is a rare but serious complication encountered among patients undergoing liver transplant surgery. Total plasma exchange (TPE) in EAD has been suggested, but its role is still considered investigational. We retrospectively assessed the efficacy of TPE in EAD and its impact on other parameters of liver function. MATERIALS AND METHODS: Between 1995 and 2001, 25 orthotopic liver transplant recipients developed EAD, which was defined as early postoperative prothrombin time (PT) >17 seconds, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >2500 IU/L, and/or the presence of hepatic encephalopathy, and development of renal failure. Daily TPE was performed using the Cobe Spectra TPE (Gambro) for 4 hours until an adequate clinical response, the patient underwent retransplantation, or the patient died. International normalizing ratio (INR), partial thromboplastin time (PTT), fibrinogen, ALT, AST, gamma-glutanyl transpeptidase (GGT), blood urea nitrogen (BUN), ammonia, and total bilirubin were analyzed before and after TPE. Student t and chi-square tests were used for statistical analysis. RESULTS: Twenty-five patients with EAD included 13 females, 12 males of mean age 42.3 years (range, 1-63 years). Coagulopathy and hyperbilirubinemia significantly improved with TPE. Nineteen patients (76%) survived and 2 required retransplantation. Mean number of TPE sessions was 4.3. CONCLUSION: TPE was effective to correct coagulopathy and improve liver function. These results suggest the benefit of potential temporary liver support until recovery or retransplantation, in the absence of sepsis or multi-system organ failure.

SV40 in human thyroid nodules.

BACKGROUND: Simian virus 40 (SV40) has been a model experimental system for the study of cell transformation and tumorigenesis for many years. The study of SV40 in humans has aroused interest in the related BK virus (BKV) and JC virus (JCV) and their role in human disease. OBJECTIVES: SV40 has been found in a variety of human samples, both malignant and normal. Many independent studies have suggested that SV40 plays a role for some cancers. However, in most cases the role of SV40 remains unclear. STUDY DESIGN: The subject of this study consisted of 99 patients with thyroid nodules. Both thyroid nodule and normal thyroid tissue were taken from each patient to test whether they contained SV40 sequences. RESULTS: We detected SV40 sequences by polymerase chain reaction (PCR) in four of 99 thyroid nodules. Two of them were papillary thyroid carcinomas and the others were benign thyroid nodules. No SV40 was detected in 99 of normal thyroid tissues of the same patients. DNA sequence analysis, performed in four positive samples, confirmed that PCR products belong to the SV40 T antigen (Tag) region. CONCLUSION: The possible role of SV40 in the development of thyroid nodules and the spread of SV40 by horizontal infection in the human population are discussed.

The prevalence of hepatitis G virus in cancer patients.

Hepatitis G virus (HGV) is transfusion-transmissible and has a global distribution. However, its frequency and clinical impact have not been well established in extrahepatic cancer patients. In this study, we determined the prevalence of HGV RNA positivity, and its relationship with history of transfusion, amount of transfusion, age and sex in patients with hematological and solid malignancies in Southeastern Turkey. Sixty-one patients (35 males and 26 females) followed up for various malignancies and 60 healthy subjects were included in the study. HGV RNA was investigated by the reverse transcription polymerase chain reaction. HGV RNA was detected in none of the patients with cancer (0%) and only one person (1.6%) in the control group. There was no difference between the groups. This observation indicates that the prevalence of HGV is very low in cancer patients and healthy people in our geographical area. In addition, the role of HGV in the pathogenesis of extrahepatic malignancies seems insignificant.

Hemobilia.

BACKGROUND: Laparoscopic procedures are safe and effective treatment methods in experienced hands. However, complications have been reported for laparoscopic procedures. One of the complications of laparoscopic cholecystectomy is vascular injuries. Hepatic and cystic artery injuries may occur alone or in association with bile duct injury. Bleeding from arterial injury may be seen during operation or in the late postoperative period. One of the most significant pathologies leading to this rare phenomenon is hemobilia. METHODS: We present a case of a 62-year-old woman who underwent routine laparoscopic cholecystectomy for cholelithiasis at another hospital. She presented 6 months later with the clinical feature of upper gastrointestinal bleeding. RESULTS: There was a 42 x 40 x 11 mm anechoic lesion and an echoic pattern compatible with a metallic object was found in the subhepatic region using abdominal ultrasonography. In the endoscopic examination, fresh blood was found in the stomach. The source of hemorrhage could not be identified. Bulbus duodeni was normal but a fresh clot on the papilla of Vateri was seen on gastroduodenoscopic examination. Laparotomy was performed and the provisional diagnosis of hemobilia was reached. The injured hepatic artery and pseudoaneurysmatic structure were repaired. CONCLUSION: Hemobilia is a late complication of laparoscopic cholecystectomy. We believe that it is important to take into consideration that bile duct injuries may be accompanied by arterial pathology.

Early multimodal therapy in adult Wilms' tumor: case report.

Wilms' tumor occurs rarely in adults, especially after the third decade. In adults, the prognosis of Wilms' tumor is worse than in children. In this case report, we present a 48-year old patient who relapsed with advanced stage shortly after primary surgery. A definitive treatment plan has not been established because of the rarity of this tumor in adults. After surgical removal, multimodal therapy should be begun immediately for long-lasting, complete remission.

The prevalence of TT virus in cancer patients.

Transfusion-transmitted virus (TTV) is a recently discovered transfusion-transmissible DNA virus. Its frequency and clinical impact has not been established in cancer patients in Turkey. In this study, we determined the prevalence of TTV DNA positivity, and its relationship with history of transfusion, amount of transfusion, age and sex in patients with hematological and solid malignancies. Sixty-one patients (35 male and 26 female) followed up for various malignancies and 45 healthy subjects were included in the study. ITV DNA was assayed by the polymerase chain reaction (PCR). TTV DNA was detected in 18 of 61 patients (29.5%) and in 5 of 45 control subjects (11.1%). In cancer patients, the prevalence of TTV DNA positivity was higher to comparison with control group. In addition, the prevalence of TTV DNA positivity was significantly higher in 22 patients who had a history of blood transfusion in the last 6 months than 39 patients who had no current or past history of transfusion (40.9% vs 23.0% respectively). These results suggest that the prevalence of TTV DNA is high and the parenteral route is an important mode of transmission for TTV in cancer patients. In addition, the high prevalence and persistence of TTV in cancer patients with parenteral risk exposure could be related to the immunodeficiency due to cancer and high viral loads by parenteral route.

Neoadjuvant chemotherapy in ovarian cancer.

Patients with advanced ovarian cancer have a chance of less than 50% after radical debulking surgery. In spite of the currently more effective combination chemotherapy agents that have become available as adjuvant therapy in the last decade, the prognosis of patients with residual tumor mass larger than 1 cm in diameter following surgery is still poor. Neoadjuvant or primary chemotherapy has been suggested as an alternative approach to primary laparotomy of the bulky ovarian cancer. The advantages and available data on neoadjuvant chemotherapy are discussed in this review.

The effect of continuous ambulatory peritoneal dialysis on serum CA-125 levels.

Malignant and non-malignant serosal fluids were found to be associated with high serum levels of CA-125, suggesting that the presence of fluid in the serosal cavities may stimulate its release. In this study, we investigated the relationship between serum CA-125 levels and peritoneal irritation during continuous ambulatory peritoneal dialysis (CAPD). We performed a clinical study in 24 stable patients (15 amenstrual females and 9 males), aged 46 +/- 14 years on CAPD. The control group consisted of 32 healthy volunteers (20 females, 12 males) aged 44 +/- 12 years. CA-125 levels were determined prior to the CAPD dwell (without dialysate in abdomen) and during the CAPD dwell (dialysate in abdomen 4 hours after). As a result, serum CA-125 levels were found to be 14.86 +/- 5.98 U/ml and 15.23 +/- 6.05 U/ml respectively, whereas it was 8.32 +/- 5.54 U/ml in the control group. Serum CA-125 levels were found to be significantly elevated in CAPD patients when compared with healthy volunteers. However, serum CA-125 levels detected prior to and after CAPD did not differ between the groups. Interestingly, all of the patients in our study group were detected to have normal serum CA-125 levels (< 35 U/ml). We concluded that CAPD-induced abdominal artificial ascites did not affect serum levels of CA-125. Moreover, short and non-inflammatory mechanical pressures in the CAPD procedure do not have any effect on serum CA-125 levels.

Superior vena cava syndrome caused by chemotherapy-induced fibrosis.

We report a case of a 51-year old man with small cell lung cancer who developed superior vena cava syndrome due to obstruction of the superior vena cava at the junction of the brachiocephalic vein by a fibrotic band, 2 months after completing six cycles of chemotherapy with cisplatin and etoposid. Superior vena cava syndrome caused by chemotherapy-induced pulmonary fibrosis should be kept in mind during follow-up.

Plasma lipid peroxidation products and antioxidant enzyme activities in patients with type 2 diabetes mellitus.

Diabetes is associated with a significant increase in thiobarbituric acid reactive substances (TBARS) which are considered as an index of endogenous lipid peroxidation. The human body has a complex antioxidant defense system that prevents the initiation of free radical chain reactions. We measured plasma TBARS levels, superoxide dismutase (SOD) and catalase (CAT) activities and compared their relation to the metabolic control of diabetes and diabetic microangiopathy. Sixty-four patients (19 men), aged 52.35+/-9.31 years with type 2 diabetes mellitus were included in the study. Thirty-six healthy subjects (12 men), aged 51.02+/-7.01 years formed the control group. TBARS levels and SOD activity were elevated in the diabetic group when compared with the control group ( p<0.001 and p<0.00001, respectively). However CAT activity was significantly decreased in the diabetic group when compared with the control group ( p<0.00001). Patients with diabetic nephropathy and retinopathy, but not neuropathy, had elevated TBARS levels but there was no statistically significant difference when compared with diabetic patients without microangiopathy ( p>0.05). There was a positive correlation between plasma TBARS levels and SOD activity (r=0.770, p=0.0001) and a negative correlation between plasma TBARS levels and CAT activity (r=0.482, p=0.0001). There was also a negative correlation between SOD and CAT activities (r=-0.609, p=0.0001). We found significantly elevated TBARS levels in diabetic patients. We did not observe any correlation between TBARS levels and blood glucose and HbA(1c) levels. Elevated TBARS levels and SOD activity and decreased CAT activity may be due to a compensation mechanism of the body.