Results of isolated limb perfusion for metastasized malignant melanoma.

BACKGROUND AND OBJECTIVES: Locoregional metastases are typical biological manifestations of advanced malignant melanomas. Treatment with hyperthermic isolated limb perfusion (HILP) should be considered in affected patients. In the present study, we have analyzed the results of HILPs performed in our department. PATIENTS AND METHODS: Eighty patients with locoregional metastases of the extremities received HILP at the Department of Surgery between January 2007 and December 2016. The mean follow-up was 38 months. RESULTS: The study included 50 men and 30 women (mean age: 63 years). The median time between melanoma diagnosis and HILP was 25 months (range: 1-219 months). HILP was performed in curative (n = 45) and palliative (n = 35) intention. Seventy-five patients received a drug combination of melphalan/dactinomycin and five patients received a drug combination of melphalan/tumor necrosis factor-alpha. Remission rates were determined in 72 of 80 patients (90%) as follows: partial response n = 28, complete response n = 25, no response n = 19. Of the 25 patients with complete response, 13 patients developed a new tumor manifestation during follow-up (locoregional recurrences n = 4; distant metastases n = 3; both n = 6). The median overall survival rate was 33 months. Tumor stage influenced the survival rate significantly (p = 0.001). Patients with complete response showed a significantly better overall survival than patients with partial or no response (p = 0.016). CONCLUSION: HILP is an effective therapeutic option in patients with locoregional metastases. This procedure carries a certain risk of side effects and adverse events but overall results in good response rates. Therefore, HILP should be offered to selected patients based on an individual discussion, considering their health status and oncological prognosis.

Computed Tomography-Guided Percutaneous Gastrostomy/Jejunostomy for Feeding and Decompression.

BACKGROUND: An effective method for long-term enteral feeding or stomach decompression is the use of a percutaneous gastrostomy (PEG) or sometimes jejunostomy (PEJ). Under certain circumstances (eg, inadequate transillumination), endoscopic placement of PEG/PEJ tubes is impossible. In these cases, computed tomography (CT)-guided PEG/PEJ may represent an alternative technique. In this study, we evaluate indications, results, and complications of CT-guided PEG/PEJ. MATERIALS AND METHODS: A total of 102 consecutive referred patients were enrolled in the study. Patients came to the endoscopy unit of our department to undergo a CT-guided PEG/PEJ for long-term intragastric/intrajejunal feeding (n = 57) or decompression (n = 45). The majority (n = 98) received a pull-through PEG/PEJ with simultaneous gastroscopy/jejunoscopy. Dose length product and the effective dose for every patient were calculated. RESULTS: PEG/PEJ tube placement was successful in 87.3% (89 of 102). Feeding PEG/PEJ tube placement was successfully completed in 91.2% (52 of 57); decompressive PEG/PEJ tube placement was likewise successfully completed in 82.2% (37 of 45). No procedure-related mortality was observed. Minor complications (eg, tube dysfunction, local bleeding, minimal leakage, local skin infection) were observed in 13 patients. The complication rate was similar between the feeding and decompression groups ( P = .9). CONCLUSIONS: CT-guided PEG/PEJ is a feasible and safe method with a low procedure-related morbidity rate for patients where endoscopic placement via transillumination is not successful. Thus, the procedure is an attractive alternative to surgical tube placement. Long-term complications, mainly tube disturbances, can be treated easily.

High post surgical opioid requirements in Crohn's disease are not due to a general change in pain sensitivity.

Crohn's disease (CD) is a painful inflammatory bowel disease with complex multigenic inheritance. Suggested on the basis of a few isolated reports CD patients require significantly higher post operative opioid doses than patients undergoing comparable severe abdominal surgery. Crohn's disease therefore may be a suitable model for the identification of novel pain susceptibility genes. In order to confirm this observation and to elucidate the underlying molecular mechanisms, we investigated if higher opioid needs of CD patients are due to a general change in pain sensitivity. Quantitative sensory testing (QST) was applied to a subgroup of patients and polymorphisms in the mu-opioid receptor (OPRM1) and catechol-O-methyltransferase (COMT) were investigated. Significantly increased post operative opioid requirements in CD patients were confirmed and QST assessment demonstrates that CD patients do not display increased pain sensitivity in terms of lowered thresholds to thermal and mechanical stimuli. The data also suggest that common variants in OPRM1 and specific 'high pain sensitivity'COMT haplotypes may not be the cause of high opioid needs. The results indicate that a more complex pathway is involved in the greater post operative opioid demand in CD. Therefore the presence of other, as yet unknown, genes could modulate opioid requirements in CD patients.

Celiac trunk compression syndrome requiring surgery in 3 adolescent patients.

BACKGROUND/METHODS: Celiac trunk compression syndrome is a rare cause of recurrent, nonspecific upper abdominal pain. In this article, we present 3 cases of celiac trunk compression syndrome in 15- and 16-year-old adolescents who were treated surgically in our clinic and discuss our findings with existing literature. RESULTS: All 3 adolescents complained about unspecific upper gastrointestinal pain. The performance of digital subtraction angiography and, accordingly, magnetic resonance angiography showed, respectively, a stenosis and an occlusion of the celiac artery. In all cases, a decompression of the celiac trunk as well as a resection of the celiac plexus in the region near the outlet of the trunk was performed. Patients have been surveyed between 12 and 18 months postoperatively. In all cases, the gastrointestinal symptoms have completely disappeared. DISCUSSION: Celiac artery compression syndrome is understood to consist of symptoms of recurrent pain, caused by a neurovascular narrowing of the aortic hiatus and celiac trunk. The surgical approach of choice is sharp transection of the median arcuate ligament, along with complete resection of the nerve fibers of the celiac plexus with or without performance of revascularisation. In summary, celiac trunk compression syndrome is a rare cause of recurrent epigastric pain that should be not be ignored completely as a differential diagnosis.

Common denominator genes that distinguish colorectal carcinoma from normal mucosa.

PURPOSE: Microarray technology has been used by a growing number of investigators and several studies have been published that list hundreds of genes differentially expressed by colorectal carcinoma (CRC) and normal mucosa (MC). On the basis of our own and other investigators' microarray data, our goal was to identify a common denominator gene cluster distinguishing CRC from MC. METHODS: Thirty GeneChips (HG-U133A, Affymetrix) were hybridized, 20 with RNA of CRC stages I-IV (UICC) and 10 with MC. Expression signals showing at least a 4-fold difference between CRC and MC (p<0.01) were identified as differentially expressed. In addition, in our integrative data analysis approach only those genes whose expression was altered simultaneously in at least 2 of 5 recently published studies were subjected to an unsupervised hierarchical cluster analysis. RESULTS: We detected 168 up- and 283 down-regulated genes in CRC relative to MC. Twenty-three genes were filtered from the five articles reviewed. An unsupervised hierarchical cluster analysis of these 23 genes confirmed the high specificity of these genes to differentiate between CRC and MC in our microarray data. CONCLUSIONS: Colorectal cancer and mucosa could be clearly separated by 23 genes selected for being differentially expressed more than once in a recent literature review. These genes represent a common denominator gene cluster that can be used to distinguish colorectal MC from CRC.

Tissue preparation for gene expression profiling of colorectal carcinoma: three alternatives to laser microdissection with preamplification.

Colorectal-carcinoma specimens are heterogeneous and include areas of nonmalignant mucosal and connective tissue. For those study designs in which laser microdissection and RNA preamplification are impracticable, the optimal yield of genuine cancer RNA is a key factor in gene-expression analysis. In this study we compared alternative methods of tissue purification. Three contiguous 0.5-cm(3) samples taken from an advanced primary adenocarcinoma of the sigmoid colon were processed immediately after surgery with the use of the following methods: (1) cryotomy after manual dissection (CMD), (2) microscopically assisted manual dissection (MAMD), and (3) tumor-cell isolation with the use of Ber-EP4 antibodies and Dynabeads (Dynal Biotech GmbH, Hamburg, Germany; technique abbreviated as DB). We generated gene-expression profiles with the use of GeneChip technology (Affymetrix, Santa Clara, Calif) and recorded preparation times, costs, and RNA quantity and quality. CMD took 60 minutes, MAMD 180 minutes, and DB 90 minutes to isolate 22, 8, and 23 microg of RNA, respectively. Expenses for materials amounted to 41, 23, and 91 US dollars for CMD, MAMD, and DB, respectively. The 3'/5' ratio, as determined with the GeneChips, for GAPDH/beta-actin was 1.01:1.03 for CMD, 1.13:1.28 for MAMD, 1.43:1.68 for DB, K-ras, APC, smad 2, transforming growth factor-beta, and p53 were marked as present in all cases, with the exception of APC, which was graded as marginal on DB. The correlation values of gene-expression profiles were 91% (CMD/DB), 93% (CMD/MAMD), and 97% (DB/MAMD). All 3 methods provided enough RNA, of sufficient quality, for gene-expression microarray analysis in colorectal carcinoma. Cross-methodologic analyses of array data should not be performed uncritically.