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Werner Hohenberger

Publications and source records attributed to Werner Hohenberger.

At least 37 records · Page 2Linked to original sources
PubMed2005

Genetic testing for germline mutations of the APC gene in patients with apparently sporadic desmoid tumors but a family history of colorectal carcinoma.

PURPOSE: Desmoid tumors, also known as aggressive fibromatosis, occur with an incidence of 10 to 15 percent in patients affected by familial adenomatous polyposis, an autosomal inherited disease caused by germline mutations in the APC gene. However, sporadic forms with no hereditary background exist. The aim of this study was to find out whether there are APC germline mutations in apparently sporadic desmoid tumor patients without clinical or familial signs of familial adenomatous polyposis but with a family history of colorectal carcinoma in at least one family member. METHODS: Genomic DNA and mRNA were isolated from peripheral blood leukocytes of index patients of eight nonrelated families. Mutation screening was performed using reverse transcriptase polymerase chain reaction-based protein truncation test for APC exons 1-14. The large APC exon 15 was scrutinized by the protein truncation test of four overlapping genomic fragments. Additionally, genomic DNA from five desmoid tumors was analyzed for loss of heterozygosity at D5S346 close to the APC locus. RESULTS: No translational stop mutations typical for familial adenomatous polyposis could be found in the APC gene in any of the analyzed blood samples from the desmoid tumor patients. Additionally, no loss of heterozygosity at D5S346 was found in four of five desmoids; one tumor was not informative. CONCLUSIONS: These results may suggest that patients with sporadic desmoids and no clinical signs of familial adenomatous polyposis detected on careful examination, esophagogastroduodenoscopy, and complete colonoscopy do not need to be tested routinely for germline mutations of the APC gene. However, as large studies dealing with this problem are absent, it might be more time and cost effective to perform an APC mutational analysis instead.

Adenomatous Polyposis Coli↗
PubMed2005

Laparoscopic total colectomy for slow-transit constipation.

INTRODUCTION: Total colectomy is the preferred surgical option in proven slow-transit constipation. With advances in technology and instrumentation, laparoscopic total colectomy has become feasible. METHODS: After a mechanical bowel preparation, the patient is placed in a modified lithotomy position and pneumoperitoneum is established. Using a subumbilical 12-mm trocar the camera is inserted. Two further 12-mm and 5-mm trocars, each, are used for access to the peritoneal cavity. In an approach from medial to lateral, ileocolic, middle colic vessels and the inferior mesenteric artery are divided. Medial mobilization is completed before the sigmoid is freed up laterally. The lateral mobilization continues orally to the descending, transverse, and ascending colon with the omentum being separated from the transverse colon completely. The mesorectum is divided using the harmonic scalpel, and the upper rectum is transected with either one or two passes of the endoscopic linear cutting stapler. The colon is exteriorized through a 5-cm Pfannenstiel incision. The terminal ileum is transected extracorporeally. After pneumoperitoneum has been reestablished, the ileorectal anastomosis is performed laparoscopically using a double-stapling technique. RESULTS: The video reports about a 56-year-old lady who had been suffering from chronic constipation since childhood and had become dependent on laxatives. A dolichocolon had been found in barium enema. A prolonged colonic passage was proven in an x-ray transit study. There were no intraoperative or postoperative complications. After surgery, first bowel movements occurred on the second day and the patient was discharged from the hospital on the sixth postoperative day. CONCLUSIONS: Laparoscopic total colectomy is a safe, feasible operation for slow transit constipation. With fast recovery and short length of stay it may become an attractive surgical approach.

Anastomosis, Surgical↗
PubMed2005

Tumor site predicts outcome after radiochemotherapy in squamous-cell carcinoma of the anal region: long-term results of 101 patients.

PURPOSE: This study was designed to assess the long-term results following radiochemotherapy in patients with anal squamous-cell carcinoma and to evaluate the impact of tumor location on response, survival, and colostomy-free survival. PATIENTS AND METHODS: Between 1985 and 2001, a total of 101 patients with anal carcinoma were registered for curative treatment, of whom 77 had involvement of the anal canal alone, 10 cases had extension into the perianal skin, and 14 patients had pure anal margin tumors. Small tumors of the anal margin were not included since they were treated by surgical excision only. Among the 101 patients were 74 women and 27 men with a median age of 62 (range, 26-84) years. T categories (International Union against Cancer) were T1 (15), T2 (36), T3 (34), and T4 (16). Seventy-one patients had no evidence of nodal disease, whereas 30 presented with involved regional nodes. Radiation treatment was directed to the primary tumor region and to the inguinal, perirectal, and internal iliac nodes using a three-field to four-field box technique with 10MV photons up to a total dose of 5040 cGy. Lesions greater than 5 cm received an additional boost by interstitial or external radiation depending on circumferential extension of the residual tumor. All patients were scheduled for simultaneous chemotherapy with two cycles of 5-fluorouracil at a dose of 1000 mg/m (2)/day as 120 hours of continuous intravenous infusion on Days 1 to 5 and 29 to 33 and mitomycin C at 10 mg/m (2)/day on Days 1 and 29. Median follow-up time was was 7.5 (range, 1-16) years. RESULTS: Overall survival and colostomy-free survival rates for patients with anal canal cancer were 75 percent and 87 percent at five years, respectively. Patients with anal margin cancer had a less favorable outcome with five-year-overall and colostomy-free survival rates of 54 percent and 69 percent, respectively. After correction for imbalance between anal canal and anal margin tumors, i.e., exclusion of T1 tumors of the anal canal, difference in overall survival remained significant (73 percent vs. 54 percent, P = 0.01). Following multivariate analysis, tumor location (anal canal vs. anal margin, P = 0.02), age (P = 0.003), and dose intensity of chemotherapy (< or =75 percent vs. >75 percent, P = 0.03) remained independent significant factors for overall survival. Initial tumor response at six weeks (P = 0.03) was predictive for colostomy-free survival. CONCLUSIONS: With colostomy-free survival rates around 85 percent, long-term treatment results for anal canal carcinoma have reached a satisfactory level. However, patients with larger lesions of the perianal skin are at high risk for locoregional recurrence and possible treatment intensification in this subgroup seems desirable.

Adult↗
PubMed2005

Laparoscopic resection rectopexy for rectal prolapse.

INTRODUCTION: The laparoscopic approach in suture rectopexy with sigmoid resection is appealing as surgery is mainly confined to the pelvis. METHODS: The procedure is performed in modified lithotomy position using five trocars. In the case reported, the inferior mesenteric artery is divided distally to the left colic artery branch. The sigmoid colon is mobilized medially and may be mobilized laterally up to the descending colon, depending on the extent of resection. The splenic flexure remains in place. The rectum is mobilized from the presacral fascia down to the pelvic floor, sparing the hypogastric nerves. The rectum is transected in its upper third and the colonic stump pulled outside after enlarging the left lower abdominal incision to a length of 5 cm. The colorectal anastomosis is established intracorporeally in a double-stapling technique. Three 2-0 braided nonabsorbable sutures are placed to attach the right lateral stalks of the rectum to the presacral fascia. Proctoscopic examination has to ensure that there is no luminal compromise or air leakage. RESULTS: The videotape reports about a 37-year-old male patient with a rectal prolapse of 8 cm in length. First symptoms had occurred in childhood. He reported about temporary constipation and repeated rectal bleeding. During surgery, an elongated sigmoid was found. Laparoscopic sigmoid resection and suture rectopexy were carried out. There were no intraoperative or postoperative complications. The patient was discharged from the hospital on the sixth postoperative day. CONCLUSION: Laparoscopic resection rectopexy is safely feasible as a minimally-invasive treatment option for rectal prolapse.

Adult↗
PubMed2005

Successful treatment of hepatitis C reinfection with interferon-alpha2b and ribavirin after liver transplantation.

INTRODUCTION: Recurrence of hepatitis C virus (HCV) infection after orthotopic liver transplantation (OLT) is a virtually universal occurrence, and a significant proportion of patients develop chronic hepatitis and cirrhosis. The aim of this study was to evaluate the safety and efficacy of interferon (IFN)-alpha2b plus ribavirin (RIBA) in the treatment of recurrent HCV after OLT over the long term. MATERIAL AND METHODS: Fifteen patients with recurrent HCV infection (positive serum HCV RNA, elevated serum aminotransferases, histological activity) were started on IFN-alpha2b (3-6 million units administered subcutaneously three times a week) plus RIBA (800-1200 mg/day) 18+/-5 months after OLT. HCV RNA was determined 1, 3, 6, 9, 12 and 18 months after initiation of treatment. Liver biopsy was performed before and after therapy. The patients were followed up for a mean of 33+/-5 months. RESULTS: Thirteen patients (87%) were treated for at least 6 months and nine patients (60%) for 12 months. After 3 months, 11 patients (73%) were free from HCV RNA (<50 copies/ml); the virological end-of-treatment response was 67%. Five patients (33%) remained HCV RNA-negative 6 months posttreatment (sustained response (SR)). During the follow-up period, four patients (27%) died of liver failure, recurrent HCV after virological response, or HCC. The histological activity index improved significantly for both inflammatory activity and fibrosis, from 8.8 to 4.7 and from 7.3 to 4.8, respectively. In none of the patients were signs of rejection observed. CONCLUSION: Combination therapy with IFN and RIBA in transplanted patients with chronic hepatitis C is an effective treatment that results in a high virological SR rate. It is well tolerated and leads to an improvement in histological outcome.

Adult↗
PubMed2004

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.

Carcinoma↗
PubMed2004

Alterations in the tissue inhibitor of metalloproteinase-3 (TIMP-3) are found frequently in human colorectal tumours displaying either microsatellite stability (MSS) or instability (MSI).

Methylation of promoter regions and frameshift mutations in microsatellites of the coding sequence (CDS) of genes are frequently associated with loss of expression in microsatellite instable (MSI) colorectal carcinoma. In a panel of 40 MSI and 24 microsatellite stable (MSS) colorectal tumours as well as six cultured colorectal carcinoma cell lines hypermethylation of the TIMP3-promoter was found in 28% of MSI and 25% of MSS tumours, respectively. Additionally, three MSI tumours and one cell line displayed instability of a C7-repeat located in the CDS of the TIMP-3 gene. TIMP-3 fulfils all important criteria for being a target gene in the mutator pathway. Thus, TIMP-3 might be a factor of general importance for colorectal carcinogenesis.

Animals↗
PubMed2004

Effects of portal vein arterialization on regeneration and morphology in liver transplantation: investigations using the rat model.

BACKGROUND: Portal vein arterialization (PVA) has been proposed as a technical variant in liver transplantation in the case of non-recanalizable thrombosis. The present study investigates the effects of the arterialized portal vein on the function, morphology, and regenerative behavior of the liver. METHODS: Different PVA techniques, including orthotopic liver transplantation, were used in a rat model. Portal blood flow was measured using a ultrasonic flowmeter. The regeneration capacity was determined on the basis of the increase of liver weight and the proliferating cell nuclear antigen index. The amount of hydroxyproline and the transcript levels of procollagen I were measured to determine the degree of fibrosis. The extracellular matrix was visualized with Picro-Sirius staining. RESULTS: The measurements obtained with an ultrasonic probe revealed a significant increase in portal blood flow after PVA. The regeneration capacity in the groups after PVA with no flow reduction was comparable to that of the control. Liver transplantation and PVA with no flow reduction was followed by a significant increase (four- to sixfold) in the amount of hydroxyproline and the level of the mRNA for procollagen I. In the Picro-Sirius staining, periportal and perivascular fibrosis with incipient formation of septa was seen. After reduction of the portal blood flow, these effects were significantly less pronounced. CONCLUSIONS: These operative techniques represent an excellent small animal model for studying the mechanism of liver regeneration and the genesis of fibrosis in liver and vessel tissue. The presenting findings indicate that the negative effects of "overarterialization" may be largely avoided by reducing portal blood flow. This implies that permanent PVA in clinical liver transplantation should be performed only in conjunction with a down-regulation of portal flow.

Alanine Transaminase↗
PubMed2004

Preoperative versus postoperative chemoradiotherapy for rectal cancer.

BACKGROUND: Postoperative chemoradiotherapy is the recommended standard therapy for patients with locally advanced rectal cancer. In recent years, encouraging results with preoperative radiotherapy have been reported. We compared preoperative chemoradiotherapy with postoperative chemoradiotherapy for locally advanced rectal cancer. METHODS: We randomly assigned patients with clinical stage T3 or T4 or node-positive disease to receive either preoperative or postoperative chemoradiotherapy. The preoperative treatment consisted of 5040 cGy delivered in fractions of 180 cGy per day, five days per week, and fluorouracil, given in a 120-hour continuous intravenous infusion at a dose of 1000 mg per square meter of body-surface area per day during the first and fifth weeks of radiotherapy. Surgery was performed six weeks after the completion of chemoradiotherapy. One month after surgery, four five-day cycles of fluorouracil (500 mg per square meter per day) were given. Chemoradiotherapy was identical in the postoperative-treatment group, except for the delivery of a boost of 540 cGy. The primary end point was overall survival. RESULTS: Four hundred twenty-one patients were randomly assigned to receive preoperative chemoradiotherapy and 402 patients to receive postoperative chemoradiotherapy. The overall five-year survival rates were 76 percent and 74 percent, respectively (P=0.80). The five-year cumulative incidence of local relapse was 6 percent for patients assigned to preoperative chemoradiotherapy and 13 percent in the postoperative-treatment group (P=0.006). Grade 3 or 4 acute toxic effects occurred in 27 percent of the patients in the preoperative-treatment group, as compared with 40 percent of the patients in the postoperative-treatment group (P=0.001); the corresponding rates of long-term toxic effects were 14 percent and 24 percent, respectively (P=0.01). CONCLUSIONS: Preoperative chemoradiotherapy, as compared with postoperative chemoradiotherapy, improved local control and was associated with reduced toxicity but did not improve overall survival.

Adult↗
PubMed2004

The impact of surgery and mild hyperthermia on tumor response and angioneogenesis of malignant melanoma in a rat perfusion model.

BACKGROUND: The aim of this experimental study was to determine the effect of mild hyperthermia on tumor response and angioneogenesis in an isolated limb perfusion model with a human melanoma xenograft. METHODS: A human melanoma xenograft was implanted into the hindlimbs of 30 athymic nude rats. The animals were randomized into five groups: group I: control, group II: sham group, group III: external hyperthermia with a tissue temperature of 41.5 degrees C for 30 minutes without ILP, group IV: normothermic ILP (tissue temperature 37 degrees C for 30 minutes, group V: hyperthermic ILP (tissue temperature 41.5 degrees C for 30 minutes). Tumor response was evaluated by tumor size determination and immunohistochemical analysis 6 weeks postoperatively. Tissue sections were investigated for expression of CD34 and basic fibroblast growth factor (bFGF). RESULTS: Average tumor volumes of the controls (I) increased from 105 mm3 to 1388 mm3. In the sham operated group (II) tumor volumes were significantly larger than in group I. Tumor volumes in group IV were significantly smaller than in group I and lowest in group V. There were no significant differences in size between group I and group III after six weeks. In group III and IV each, 5 animals showed tumor progression and one had a partial tumor response. In group V only 2 animals showed tumor progression. Immunhistochemical analysis of the tissue sections demonstrated that angioneogenesis was more pronounced in group II than in group I and less pronounced in group IV and V compared with group I. CONCLUSIONS: Our results suggest that even a surgical manipulation such as a skin incision promotes tumor growth, probably by induction of growth factors like bFGF. External hyperthermia of 41.5 degrees C tissue temperature for 30 minutes only has no impact on tumor growth and angioneogenesis in vivo.

Animals↗
PubMed2004

Circulation and homing of melanoma-reactive T cells to both cutaneous and visceral metastases after vaccination with monocyte-derived dendritic cells.

Anticancer immune therapies aim at the induction of tumor-specific T cells, which ultimately should kill tumor cells. The effector cells should, therefore, not only exert cytotoxic activity but also home to and infiltrate the tumor site. Hence, monitoring of immune modulating therapies should not be restricted to the circulating pool of peripheral blood mononuclear cells (PBMC) but also include tumor-infiltrating lymphocytes (TIL), as well as the correlation of these findings to the clinical course. We report here on the longitudinal immunologic workup of a melanoma patient who developed remarkably potent ex vivo detectable antimelanoma cytotoxic T-cell (CTL) responses after vaccinations with autologous peptide-pulsed dendritic cells. Such potent CTL responses to multiple tumor antigens have, to the best of our knowledge, not been described previously in melanoma patients, neither spontaneously nor after any therapy. This patient first experienced a transient response to therapy but finally succumbed to disease progression and died. Progression was associated with the decline of the numbers of tumor-reactive T cells in circulation and at skin metastases in addition to the loss of MHC class I antigens. The immunologic analysis revealed that fully functional tumor-specific T cells were present in the peripheral blood of this patient during the phase of a relatively stable disease, and in situ tetramer staining demonstrated that these cells were also accumulated at cutaneous and visceral tumor sites. Furthermore, comparative clonotype mapping of PBMC and TIL depicted an overlapping TCR repertoire usage among these 2 compartments. Since strong CTL responses as observed in this patient are the goal of cancer vaccination but are so far only rarely observed, the thorough analysis of patients exhibiting either exceptional clinical and/or immunologic responses appears critical to understanding how vaccine therapies work and can be further improved.

Aged↗
PubMed2004

Primary signet-ring cell carcinoma of the colorectum.

BACKGROUND: Objective of the study was to investigate particular clinicopathological features of colorectal signet-ring cell carcinoma. METHODS: The data of 34 patients with primary colorectal signet-ring cell carcinoma were compared with those of 4,458 consecutive patients with primary non-signet-ring cell colorectal adenocarcinoma between 1978 and 1999. For outcome analysis patients, after curative resection of signet-ring cell cancer, were matched for age, gender, tumour site and stage with patients suffering from poorly differentiated non-signet-ring cell colorectal adenocarcinoma. RESULTS: Signet-ring cell carcinoma patients were significantly younger than patients with non-signet-ring cell colorectal adenocarcinoma (median age 60 years vs 64 years, P=0.033). The most common tumour sites were the rectum (47%) and the right hemicolon (29%). They presented with significantly more advanced tumour stages and a significantly higher frequency of distant metastases (44% vs 21%, P=0.002). The rate of curative resections was significantly lower (35% vs 79%, P<0.001). However, the prognosis after curative resection of signet-ring cell cancer was as poor as in poorly differentiated non-signet-ring cell colorectal adenocarcinoma of the same stage (5-year survival rate 46% vs 57%, p=0.935). CONCLUSIONS: Colorectal signet-ring cell carcinoma is characterized by diagnosis in more advanced tumour stages resulting in lower rates of curative resection. Prognosis is as poor as in non-signet-ring cell colorectal cancer of low differentiation in the same stage.

Adult↗
PubMed2004

Improved prediction of recurrence after curative resection of colon carcinoma using tree-based risk stratification.

BACKGROUND: Patients who are at high risk of recurrence after undergoing curative (R0) resection for colon carcinoma may benefit most from adjuvant treatment and from intensive follow-up for early detection and treatment of recurrence. However, in light of new clinical evidence, there is a need for continuous improvement in the calculation of the risk of recurrence. METHODS: Six hundred forty-one patients with R0-resected colon carcinoma who underwent surgery between January 1, 1984 and December 31, 1996 were recruited from the Erlangen Registry of Colorectal Carcinoma. The study end point was time until first locoregional or distant recurrence. The factors analyzed were: age, gender, site in colon, International Union Against Cancer (UICC) pathologic tumor classification (pT), UICC pathologic lymph node classification, histologic tumor type, malignancy grade, lymphatic invasion, venous invasion, number of examined lymph nodes, number of lymph node metastases, emergency presentation, intraoperative tumor cell spillage, surgeon, and time period. The resulting prognostic tree was evaluated by means of an independent sample using a measure of predictive accuracy based on the Brier score for censored data. Predictive accuracy was compared with several proposed stage groupings. RESULTS: The prognostic tree contained the following variables: pT, the number of lymph node metastases, venous invasion, and emergency presentation. Predictive accuracy based on the validation sample was 0.230 (95% confidence interval [95% CI], 0.227-0.233) for the prognostic tree and 0.212 (95% CI, 0.209-0.215) for the UICC TNM sixth edition stage grouping. CONCLUSIONS: The prognostic tree showed superior predictive accuracy when it was validated using an independent sample. It is interpreted easily and may be applied under clinical circumstances. Provided that their classification system can be validated successfully in other centers, the authors propose using the prognostic tree as a starting point for studies of adjuvant treatment and follow-up strategies.

Adenocarcinoma↗
PubMed2004

Liver transplantation for hepatocellular carcinoma: a single European centre experience.

BACKGROUND: With respect to deficient donor grafts and the risk of tumour recurrence, indication for orthotopic liver transplantation (OLT) is still controversial. OLT offers the only chance for both the tumour and the underlying liver disease to be eliminated in patients with hepatocellular carcinoma (HCC) and cirrhosis. The aim of this study was to assess survival and related factors of recurrence. PATIENTS AND METHODS: This retrospective study analyses data from 45 patients with HCC (UICC stage I/II, n=16; III, n=13; IV, n=12) treated with OLT between 1992 and 2002 in our centre. There were 39 primary tumours and two recurrent ones after previous surgical resection. Four perioperative deaths were excluded from analysis. RESULTS: Mean follow-up was 50.4 months. Five-year rates after OLT were 64% for overall survival, 78% for disease-specific survival, 73% for recurrence-free survival, and 22% for tumour recurrence. No tumour recurrence has been observed so far in patients with tumours of UICC stage I/II. None of the patient characteristics had a significant impact on survival, while tumour stage was significantly correlated with freedom from recurrence. CONCLUSION: Our results demonstrate that the risk of recurrent HCC in liver transplanted patients is low for small and solitary tumours with no vascular invasion (UICC I/II). Even in advanced tumour stages (UICC III/IV), there is a real chance of cure or at least a survival benefit in selected patients.

Carcinoma, Hepatocellular↗
PubMed2004

Prognostic significance of microsatellite instability in curatively resected adenocarcinoma of the small intestine.

Adenocarcinoma of the small intestine (ACSI) is a rare condition with few studies addressing follow-up and prognosis. Tumors of 35 patients with curative resection of an ACSI were retrospectively analyzed by immunohistochemistry: p53, hMLH1, hMSH2 and hMSH6 and microsatellite instability (MSI): BAT-26, BAX, TGF-beta RII. With a median follow up of 6.1 years, the median cancer-specific survival (CSS) was 36.2 months. Patients who were highly instable (MSI-H) (n=10) had a CSS of 49.6 months in contrast to patients with stable tumors (23.2 months) (P=0.010). Additionally, a low tumor stage according to UICC and MSI-H were shown to be independent factors (P=0.005 and P<0.001) for an increased survival in multivariate analysis. Therefore, it is suggested that analysis of the MSI status might prove useful in discerning prognosis within cancers of the same stage.

Adenocarcinoma↗
PubMed2004

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.

Adenocarcinoma↗
PubMed2004

Evaluation of in vivo endoscopic autofluorescence spectroscopy in gastric cancer.

BACKGROUND: The aim of this study was to evaluate light-induced autofluorescence spectroscopy for the in vivo diagnosis of gastric cancer. METHODS: A total of 344 endogenous fluorescence spectra were obtained from normal (164) and cancerous gastric mucosa (180) in 15 patients with pure adenocarcinoma and in 16 patients with gastric cancer containing signet-ring cells. A special light source capable of delivering either white or violet-blue light for the excitation of tissue autofluorescence via the endoscope was used. Endogenous fluorescence spectra emitted by the tissue were collected with a fiberoptic probe and analyzed with a spectrograph. RESULTS: Gastric adenocarcinoma exhibits specific changes in the emitted fluorescence spectra as compared with normal gastric mucosa. By algorithmic classification of the spectra, a sensitivity of 84%, specificity of 87%, a likelihood ratio for a positive test of 6.5 and for a negative test of 0.18 were obtained for the diagnosis of pure adenocarcinoma of the stomach. However, gastric cancer with signet-ring cells exhibits great variation in emitted autofluorescence spectra as compared with normal mucosa. The sensitivity for the diagnosis of all carcinomas containing signet-ring cells was 55%, specificity 85%, the likelihood ratio for a positive test was 3.7 and for a negative test, 0.53. The diagnostic value decreases with increasing numbers of signet-ring cells and tumor grade. CONCLUSIONS: Light-induced autofluorescence spectroscopy is a new and promising bio-optical technique for the endoscopic in vivo diagnosis of gastric adenocarcinoma. The poor diagnostic accuracy for signet-ring cell carcinoma may be explained by the diffuse and frequent submucosal growth of this tumor and the presence of collagen fibers.

Adenocarcinoma↗