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Abstract Background Over-expression of HER2 in a subset of breast cancers (HER2+) is associated with high histological grade and aggressive clinical course. Despite these distinctive features, the differences in response of HER2+ patients to both adjuvant cytotoxic chemotherapy and targeted therapy (e.g. trastuzumab) suggests that unrecognized biologic and clinical diversity is confounding treatment strategies. Furthermore, the small but established risk of cardiac morbidity with trastuzumab therapy compels efforts towards the identification of biomarkers that might help stratify patients. Methods A single institution tissue array cohort assembled at the Clearview Cancer Institute of Huntsville (CCIH) was screened by immunohistochemistry staining using a large number of novel and commercially available antibodies to identify those with a univariate association with clinical outcome in HER2+ patients. Staining with antibody directed at TRMT2A was found to be strongly associated with outcome in HER2+ patients. This association with outcome was tested in two independent validation cohorts; an existing staining dataset derived from tissue assembled at the Cleveland Clinic Foundation (CCF), and in a new retrospective study performed by staining archived paraffin blocks available at the Roswell Park Cancer Institute (RPCI). Results TRMT2A staining showed a strong correlation with likelihood of recurrence at five years in 67 HER2+ patients from the CCIH discovery cohort (HR 7.0; 95% CI 2.4 to 20.1, p < 0.0004). This association with outcome was confirmed using 75 HER2+ patients from the CCF cohort (HR 3.6; 95% CI 1.3 to 10.2, p < 0.02) and 64 patients from the RPCI cohort (HR 3.4; 95% CI 1.3-8.9, p < 0.02). In bivariable analysis the association with outcome was independent of grade, tumor size, nodal status and the administration of conventional adjuvant chemotherapy in the CCIH and RPCI cohorts. Conclusions Studies from three independent single institution cohorts support TRMT2A protein expression as a biomarker of increased risk of recurrence in HER2+ breast cancer patients. These results suggest that TRMT2A expression should be further studied in the clinical trial setting to explore its predictive power for response to adjuvant cytotoxic chemotherapy in combination with HER2 targeted therapy.

Hereditary hemochromatosis (HH) is an autosomal recessive disorder of iron metabolism characterized by increased iron absorption and tissue deposition. Three loss-of-function mutations in the hemochromatosis gene (HFE), namely, C282Y (c.845G>A), H63D (c.187C>G), and S65C (c.193A>T), account for the vast majority of HH cases. These mutations cause alterations in HFE membrane expression, structure, and/or activity, leading to dysregulation of iron absorption. It is well established that the phenotypic expression of HFE mutations varies markedly. Herein, we describe a 64-year-old Caucasian woman with a reported history of hemochromatosis. The father of the patient had died of complications due to iron overload. Testing of HFE codon C282Y, H63D, and S65C mutations showed heterozygous C282Y. The patient had significantly elevated transferrin saturation (TS) and serum ferritin (SF) levels. Her liver function test results showed elevated alanine transaminase (ALT) and aspartate aminotransferase (AST) levels. The patient has been treated with regular phlebotomy to prevent the clinical manifestations of hemochromatosis. [ABSTRACT FROM AUTHOR]

Background: Over-expression of HER2 in a subset of breast cancers (HER2+) is associated with high histological grade and aggressive clinical course. Despite these distinctive features, the differences in response of HER2+ patients to both adjuvant cytotoxic chemotherapy and targeted therapy (e.g. trastuzumab) suggests that unrecognized biologic and clinical diversity is confounding treatment strategies. Furthermore, the small but established risk of cardiac morbidity with trastuzumab therapy compels efforts towards the identification of biomarkers that might help stratify patients. Methods: A single institution tissue array cohort assembled at the Clearview Cancer Institute of Huntsville (CCIH) was screened by immunohistochemistry staining using a large number of novel and commercially available antibodies to identify those with a univariate association with clinical outcome in HER2+ patients. Staining with antibody directed at TRMT2A was found to be strongly associated with outcome in HER2+ patients. This association with outcome was tested in two independent validation cohorts; an existing staining dataset derived from tissue assembled at the Cleveland Clinic Foundation (CCF), and in a new retrospective study performed by staining archived paraffin blocks available at the Roswell Park Cancer Institute (RPCI). Results: TRMT2A staining showed a strong correlation with likelihood of recurrence at five years in 67 HER2+ patients from the CCIH discovery cohort (HR 7.0; 95% CI 2.4 to 20.1, p < 0.0004). This association with outcome was confirmed using 75 HER2+ patients from the CCF cohort (HR 3.6; 95% CI 1.3 to 10.2, p < 0.02) and 64 patients from the RPCI cohort (HR 3.4; 95% CI 1.3-8.9, p < 0.02). In bivariable analysis the association with outcome was independent of grade, tumor size, nodal status and the administration of conventional adjuvant chemotherapy in the CCIH and RPCI cohorts. Conclusions: Studies from three independent single institution cohorts support TRMT2A protein expression as a biomarker of increased risk of recurrence in HER2+ breast cancer patients. These results suggest that TRMT2A expression should be further studied in the clinical trial setting to explore its predictive power for response to adjuvant cytotoxic chemotherapy in combination with HER2 targeted therapy. [ABSTRACT FROM AUTHOR]

First-line platinum-based chemotherapy combinations are considered standard-of-care in locally advanced and metastatic urothelial cancer. However, long-term outcomes, including disease-specific and overall survival, remain poor. In addition, a number of patients with advanced urothelial carcinoma have co-existing medical issues that preclude the use of conventional chemotherapy. Improvements in our understanding over the molecular mechanisms of urothelial cancer have led to first-generation clinical trials evaluating novel agents targeting molecular pathways that may be relevant, at least in sub-populations. Emerging information regarding outcome with agents targeting novel molecular targets in advanced urothelial cancer is discussed in this review., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Introduction: First-line platinum-based combinations are active in locally advanced and metastatic urothelial carcinoma; however, long-term outcomes including disease-specific and overall survival remain suboptimal. In addition, approximately 40 - 50% of patients with advanced urothelial carcinoma have coexisting medical issues that preclude the use of cisplatin-based therapy. Improvements in our understanding of the molecular mechanisms of urothelial tumorigenesis have led to first-generation clinical trials evaluating novel agents targeting molecular pathways. These are particularly relevant in regard to subpopulations. Novel trial designs warrant consideration to accelerate accrual., Areas Covered: In this review, novel molecular targets for the therapy of urothelial carcinoma, as well as recently completed and ongoing clinical trials utilizing novel targeted agents, are discussed. A Medline search with key words, abstracts reported at national conferences on urothelial carcinoma and NCI clinical trial identifiers was used for this review., Expert Opinion: Improved understanding of molecular biology has identified a number of new molecular targets, but there is a seeming absence of one dominant molecular driver for urothelial cancer. An adaptive and biomarker-derived strategy may be warranted. Clinical trials utilizing targeted agents are ongoing and results are awaited.

Objective: The aim of this study was to evaluate the sonographic features of stents and the flow parameters of the visceral arteries after stent implantation., Methods: Since 1996, 34 stenoses of the visceral arteries (2 mesenteric, 4 celiac trunk, and 28 renal arteries) in 28 patients have been treated with metallic stent implantation in the Department of Radiology of Szeged Medical University. All these patients were regularly followed sonographically. For the diagnosis of restenosis, previously published criteria were used., Results: All the mesenteric and celiac stents could be visualized, but none of the renal stents were clearly seen sonographically. The flow parameters could be established in all cases. Sonographic examination revealed 1 occlusion, 2 restenoses, and 1 stent displacement. All these abnormalities were confirmed by other imaging modalities., Conclusions: Sonography is a useful tool in the follow-up of patients after visceral artery stenting. Despite the fact that none of the renal artery stents were visualized directly, the flow parameters could be evaluated, and the pathologic changes were found.

The authors report on a rare case of malignant hemangiopericytoma. A 56-year old female patient had developed a painless node on her left gluteal region 20 years ago. Years later, the resistance became tender and was subsequently surgically removed. On histology, the lesion was identified as malignant hemangiopericytoma. After a symptom-free period of 8 years distant pulmonary metastases arose, which were removed by surgery again. Shortly afterwards the patient manifested with further metastasis involving the lung again, as well as the abdomen, the skin and the breast, leading to the patient's death 2 years later. The authors review the literature, clinical course, diagnostic possibilities, prognosis and therapeutic options of malignant hemangiopericytomas. Special attention is drawn to the unexceptionally long clinical course at this particular malignancy, as well as to the late occurrence of metastases and their unusual breast localisation.

The authors report a total of 62 middle and low third rectal cancer cases operated on by total mesorectal excision by the method of Heald. The oncological basis of this procedure is the horizontal regional metastatization of rectal cancer. The total mesorectal excision facilitates, the low anterior resections and preservation of sphincter with an ultra-low colorectal, or coloanal anastomosis using the double stapling technique. In the authors' experience, the "UltraCision" cutting-coagulating device permits an atraumatic, bloodless and oncologically correct dissection. Using the double stapling technique, we succeeded in 60% of our middle- and low-third rectal cancer patients to perform a sphincter preserving low anterior resection. In 9 (28%) of the low third rectal cancer patients, preservation of the sphincter was possible with oncologically correct anterior resection and an ultra-low colo-anal anastomosis. Three anastomotic insufficiencies occurred, two of them healed on lotion-suction drainage, and one on the application of transient protective ileostomy. The literature data suggest a lower local recurrency rate after radical rectal cancer surgery, if total mesorectal excision is performed.

The laparoscopic cardiomyotomy with anterior fundoplication (Heller-Dor procedure) is accepted for treatment of esophageal achalasia. The crucial point of the procedure is proper myotomy and avoid perforation of the esophagus. Hook cautery is widely accepted to dissect the oesophageal muscle. We'd like to demonstrate our experiences with a new device--Ultrasonically Activated Harmonic Scalpel-, witch was used at our operation for achalasia to make the cardiomyotomy. Between December 1993 and December 1996, 11 patients with esophageal achalasia underwent laparoscopic Heller's operation with Dor's antireflux procedures. In one patient we applied the Ultrasonically Activated Harmonic Scalpel (HS) to make the cardiomyotomy. The use of HS and results were evaluated. Application of the Harmonic Scalpel is effective for cardiomyotomy. It can be used more safe than electrocoagulation, because it cause less thermic lesion. It's easy to use at laparoscopic way. A perforation of the esophagus didn't occur. There was no intra-, or postoperative complications. After the operation the patient is free of complains. After our first operation, we have found, that Ultrasonically Activated Scalpel can be applied with safe and good results for the cardiomyotomy at laparoscopic operations for esophageal achalasia.

The essential of laparoscopic Nissen fundoplication is creating a loose and tension free wrap requiring mobilisation of the gastric fundus. Division of the short gastric vessels (SGV) is a standard component of that procedure which requires considerable part of the operation time, and despite of a careful dissection sometimes significant blood loss can be occurred. The Ultracision Harmonic Scalpel (HS) makes the process quicker safer and can cause less intraoperative complication. This study compares our original method of vessel control (at 10 cases, Group 1), to the Ultracision Harmonic Scalpel (at 10 cases, Group 2) Times for SGV division, estimated blood loss and intraoperative and postoperative complications were evaluated. In the favour for Group 2 a significant reduction was reached in the time required for division of SGV to mobilize the fundus. As the most common postoperative complication, the dysphagia concerns we found significant difference in the two groups and dysphagia was mild at Group 2. Application of HS provide safer, easier and faster division of SGV resulting significant savings of time and less prone to thermic trauma and recommended at LNF operations to avoid potential intra- and postoperative complications.

The treatment of two operated solid splenic cysts has been reported by authors. Laparoscopic cyst fenestration has been demonstrated to be a useful alternative method to open surgery. The aim of the authors was to analyse the use of Ultracision Harmonic Scalpel in two spleen preserving procedures. Cysts were located in the superior and the anterior-inferior pole of the spleen. Cyst wall not covered by spleen tissues was removed, drain was left in the abdomen. In the demonstrating spleen cyst operation the advantages of HS instrument was the clean operating field, correct coagulation of cyst wall, short hospital stay. Authors believe that this new technology will make it easier and more desirable for surgeons to fenestrate symptomatic spleen cysts.

The method of laparoscopic repair of hiatal hernia is accepted in surgery. Usually associated with Nissen fundoplication which is the most commonly performed antireflux operation. Within a ten-year period authors have done 90 antireflux operations, 52 was laparoscopic procedures. (30 operations for GERD, 10 for hiatal hernia, 12 for the combination of both.) A patient was submitted to operation with large hiatal hernia. He was treated laparoscopic way with success and good results. The Ultracision Harmonic Scalpel instrument helped their operation in many ways, and provided correct bloodless preparation of cardiac region. The authors demonstrate our procedure and the use of the Harmonic Scalpel. Their patient were completely pleased with the results after discharge, they are still under regular control.

Between February 1991 and July 1991, 74 laparoscopic cholecystectomies were performed. The number of all cholecystectomies during this period was 168. Two surgeons performed the operations. Stone in the common bile duct, old age, acute cholecystitis, severe obesity and heart rhythm disorders were regarded as contraindications. The duration of the operation was 45-210 min. (mean 127 min). The intervention was diverted to open cholecystectomy in 2 instances (2.7%). Early postoperative complications were observed in 2 cases (2.7%): biliary discharge and bleeding. Reoperation was necessary in one patient (1.3%) because of bleeding. There was no operative mortality. The mean duration of hospitalization was 5.6 days, and the mean postoperative period was 2.7 days. It is considered that, laporoscopic cholecystectomy can be carried out only by specialists in both bile surgery and laparoscopic techniques, provided that all the personal and technical conditions necessary for traditional cholecystectomies are at hand. Both medically and economically, the laparoscopic cholecystectomy results attain or even exceed those of the traditional open technique.