Different survival outcomes after curative R0-resection for Eastern Asian and European gastric cancer: Results from a propensity score matched analysis comparing a Korean and a German specialized center.

Several retrospective analyses on patients who underwent gastric cancer (GC) surgery revealed different survival outcomes between Eastern (Korean, Japanese) and Western (USA, Europe) countries due to potential ethnical and biological differences. This study investigates treatment outcomes between specialized institution for GC in Korea and Germany.The prospectively documented databases of the Gastric Cancer Center of the National Cancer Center, Korea (NCCK) and the Department of Surgery of the Technische Universitaet Muenchen (TUM), Germany were screened for patients who underwent primary surgical resection for GC between 2002 and 2008. Baseline characteristics were compared using χ testing, and 2 cohorts were matched using a propensity score matching (PSM) method. Patients' survival was estimated using Kaplan-Meier method, and multivariable Cox proportional hazard model was used for comparison.Three thousand seven hundred ninety-five patients were included in the final analysis, 3542 from Korea and 253 from Germany. Baseline characteristics revealed statistically significant differences for age, tumor location, pT stage, grading, lymphatic vessel infiltration (LVI), comorbidities, number of dissected lymph nodes (LN), postoperative complications, lymph-node ratio stage, and application of adjuvant chemotherapy. After PSM, 171 patients in TUM were matched to NCCK patients, and baseline characteristics for both cohorts were well balanced. Patients in Korea had significantly longer survival than those in Germany both before and after PSM. When the analysis was performed for each UICC stage separately, same trend was found over all UICC stages before PSM. However, significant difference in survival was observed only for UICC I after PSM.This analysis demonstrates different survival outcomes after surgical treatment of GC on different continents in specialized centers after balancing of baseline characteristics by PSM.

Long-term outcome of 2920 patients with cancers of the esophagus and esophagogastric junction: evaluation of the New Union Internationale Contre le Cancer/American Joint Cancer Committee staging system.

OBJECTIVE: We analyzed the long-term outcome of patients operated for esophageal cancer and evaluated the new seventh edition of the tumor-node-metastasis classification for cancers of the esophagus. BACKGROUND: Retrospective analysis and new classification. METHODS: Data of a single-center cohort of 2920 patients operated for cancers of the esophagus according to the seventh edition are presented. Statistical methods to evaluate survival and the prognostic performance of the staging systems included Kaplan-Meier analyses and time-dependent receiver-operating-characteristic-analysis. RESULTS: Union Internationale Contre le Cancer stage, R-status, histologic tumor type and age were identified as independent prognostic factors for cancers of the esophagus. Grade and tumor site, additional parameters in the new American Joint Cancer Committee prognostic groupings, were not significantly correlated with survival. Esophageal adenocarcinoma showed a significantly better long-term prognosis after resection than squamous cell carcinoma (P < 0.0001). The new number-dependent N-classification proved superior to the former site-dependent classification with significantly decreasing prognosis with the increasing number of lymph node metastases (P < 0.001). The new subclassification of T1 tumors also revealed significant differences in prognosis between pT1a and pT1b patients (P < 0.001). However, the multiple new Union Internationale Contre le Cancer and American Joint Cancer Committee subgroupings did not prove distinctive for survival between stages IIA and IIB, between IIIA and IIIB, and between IIIC and IV. CONCLUSION: The new seventh edition of the tumor-node-metastasis classification improved the predictive ability for cancers of the esophagus; however, stage groups could be condensed to a clinically relevant number. Differences in patient characteristics, pathogenesis, and especially survival clearly identify adenocarcinomas and squamous cell carcinoma of the esophagus as 2 separate tumor entities requiring differentiated therapeutic concepts.

Results of a multimodal therapy in patients with stage IV Barrett's adenocarcinoma.

BACKGROUND: Locally advanced and metastatic Barrett's carcinomas account for the majority of this tumor entity at the time of diagnosis. Many studies have shown that a multimodal therapy concept consisting of neoadjuvant chemotherapy followed by resection can result in improved long-term survival in patients responding to chemotherapy. The benefit of a multimodal therapy concept in patients with stage IV disease remains unclear. METHODS: A total of 178 patients with Barrett's carcinoma who underwent multimodal therapy with resection of the tumor were reviewed. The pathological staging and the clinical course of patients with metastatic disease, who were treated equally, were compared to patients with locally advanced tumors. RESULTS: As expected, postoperative pathological staging showed that patients with metastatic disease have a more advanced T- and N-status. Moreover, the histopathological response according to Becker showed a chemoresistence in 84% of cases with metastatic disease, whereas 54% of patients with locally advanced carcinomas had a good response rate. Overall survival was poor, with 9 months in the metastatic group. CONCLUSIONS: This is the first study to compare the outcome of a modern multimodal therapy concept in patients with metastatic Barrett's carcinoma in comparison to patients with the locally advanced form of the disease. There are profound differences in the two groups with regard to survival time and response rates. Because of the poor outcome to date, multimodal therapy with resection of the tumor in stage IV disease cannot be recommended.

Pancreatic resection for metastatic renal cell carcinoma: a single center experience and review of the literature.

Renal cell carcinoma (RCC) is one of the few tumour types metastatic to the pancreas. In order to evaluate the outcome following resection of pancreatic metastases of RCC a retrospective review of surgical patients was performed. The initial histopathological staging, disease-free interval, surgical outcome and survival were evaluated. The median interval between nephrectomy and pancreatic resection was 9 years. Six out of the ten patients preoperatively presented with severe complaints caused by the pancreatic metastasis, such as pain, chronic pancreatitis, jaundice and gastrointestinal bleeding. Severe postoperative complications only occurred in two patients, who presented in a deteriorated condition preoperatively. The median follow-up was 56 months, in 3 patients more than 5 years. Although the spontaneous course of RCC metastases can be favourable, the complete resection of pancreatic metastases for patients in good physical condition is suggested if possible. Moreover, good palliation of symptoms in patients with long-term survival can be achieved.

Multicentric Adenocarcinomas in a Long-Segment of Barrett's Esophagus.

This report describes a complicated course of a 58-year-old patient with multicentric Barrett's carcinoma within a long-segment of Barrett metaplasia. After abdominal-thoracic resection of the cancer, with incomplete removal of the long-segment metaplastic lesion, invasive carcinoma was diagnosed in the remnant Barrett's segment. Endoscopic mucosal resection was done, but Barrett's mucosa was left in situ again. Recurrent tumor growth was diagnosed only few months later. Finally, transthoracic complete resection on the remnant Barrett's segment was performed. Thus, our case demonstrates impressively the appearance of multicentric adenocarcinomas in Barrett's esophagus and underlines the necessity of resection of the complete Barrett mucosa.

Sentinel lymph node biopsy in colon cancer: a prospective multicenter trial.

INTRODUCTION: The clinical impact of sentinel lymph node biopsy (SLNB) in colon cancer is still controversial. The purpose of this prospective multicenter trial was to evaluate its clinical value to predict the nodal status and identify factors that influence these results. METHODS: Colon cancer patients without prior colorectal surgery or irradiation were eligible. The sentinel lymph node (SLN) was identified intraoperatively by subserosal blue dye injection around the tumor. The SLN underwent step sections and immunohistochemistry (IHC), if classified free of metastases after routine hematoxylin and eosin examination. RESULTS: At least one SLN (median, n = 2) was identified in 268 of 315 enrolled patients (detection rate, 85%). Center experience, lymphovascular invasion, body mass index (BMI), and learning curve were positively associated with the detection rate. The false-negative rate to identify pN+ patients by SLNB was 46% (38 of 82). BMI showed a significant association to the false-negative rate (P < 0.0001), the number of tumor-involved lymph nodes was inversely associated. If only slim patients (BMI < or =24) were investigated in experienced centers (>22 patients enrolled), the sensitivity increased to 88% (14 of 16). Moreover, 21% (30 of 141) of the patients, classified as pN0 by routine histopathology, revealed micrometastases or isolated tumor cells (MM/ITC) in the SLN. CONCLUSIONS: The contribution of SLNB to conventional nodal staging of colon cancer patients is still unspecified. Technical problems have to be resolved before a definite conclusion can be drawn in this regard. However, SLNB identifies about one fourth of stage II patients to reveal MM/ITC in lymph nodes. Further studies must clarify the clinical impact of these findings in terms of prognosis and the indication of adjuvant therapy.

Gastric duplication cyst: a rare endosonographic finding in an adult.

Cystic lesions located in the gastric wall are a rare finding in endosonography of the gastrointestinal tract. Compared to all forms of benign and malignant tumours of the stomach, gastric duplication cysts are an uncommon anomaly--especially in adults. We report on a 59-year-old woman suffering from intermittent abdominal pain, weight loss and nausea. A gastric duplication cyst was identified by endoscopic ultrasound (EUS), but malignancy was excluded by EUS and fine-needle aspiration histology. Because of continuously increasing abdominal complaints, surgery was performed with partial resection of the gastric corpus and splenectomy. Gross anatomy and histology showed a gastric cyst measuring 150 mm in maximum diameter with no evidence of malignancy or inflammation. Following surgery, the patient's condition recovered fully.

Gene expression profiles of different clinical stages of colorectal carcinoma: toward a molecular genetic understanding of tumor progression.

BACKGROUND AND AIMS: Colorectal cancer is one of the leading causes of cancer deaths in the Western world. A better understanding of the development and progression of colorectal carcinoma is needed to define novel targets and strategies for treatment. PATIENTS/METHODS: Gene expression profiles were determined for primary tumors of 10 locally restricted (T3N0M0), 8 lymphatically metastasized (T3N+M0), 7 systemically metastasized (T3N+M1) colorectal carcinomas, and 6 specimens of normal colorectal tissue by histology-guided oligonucleotide microarray analysis. RESULTS: A total of 1,995 genes were differently regulated in primary tumors of colorectal carcinoma compared with normal colorectal tissue. Besides common features of dedifferentiation and different expression of genes involved in cell division, cell adhesion, angiogenesis, signal transduction and metabolism we observed a deregulation of genes with an as yet unclear function. We identified 126 genes that were subsequently up- and 204 genes down-regulated during tumor progression. Furthermore, we found a cluster of five genes exclusively up-regulated in primary tumors of systemically metastasized colorectal carcinomas. A comparison of locally restricted (T3N0M0) and systemically metastasized (T3N+M1) primary tumors showed 50 deregulated genes with a massive down-regulation of immune-modulatory genes in primary tumors of systemically metastasized carcinomas. Primary tumors of lymphatically (T3N+M0) and systemically metastasized (T3N+M1) carcinomas differed in the expression of 19 genes. CONCLUSION: These results provide an additional step toward the identification of crucial genes for the progression of colorectal cancer and the identification of novel treatment targets or strategies.

Telomere length and human telomerase reverse transcriptase expression as markers for progression and prognosis of colorectal carcinoma.

PURPOSE: Maintenance of telomeres through reactivation of telomerase is a prerequisite for tumors to preserve their ability to proliferate. The purpose of this study was to evaluate telomere length and human telomerase reverse transcriptase (hTERT) expression as markers for progression and prognosis of colorectal carcinoma. PATIENTS AND METHODS: Telomere length and hTERT expression were analyzed in matched cancer and adjacent noncancer mucosa samples from 57 patients with R0-resected colorectal carcinoma. The median follow-up time was 76 months. RESULTS: Telomere length and hTERT expression correlated significantly in cancer tissues and adjacent mucosa samples (r = 0.52, P <.001; and r = 0.54, P <.001, respectively). Overall, cancer tissue had shorter telomeres than adjacent mucosa (P <.001). Only in noncancer tissue did telomere length decrease with age (r = 0.36; P <.01). Telomere length in cancer tissue was significantly correlated with tumor stage (P <.01), with longer telomeres in advanced tumors. Patients with ratios of telomere length in cancer to noncancer tissue greater than 0.90 had a significantly poorer overall survival compared with patients with smaller telomere length ratios (P <.002). In multivariate analysis, the telomere length ratio proved to be of independent prognostic value (P <.03). CONCLUSION: Telomeres in colorectal carcinoma tissue were significantly shorter compared with adjacent normal mucosa as an indication for extensive cell proliferation. The correlation with tumor stage and patient survival suggest that hTERT-mediated telomere stabilization may be critical for progression and prognosis of colorectal carcinoma.

Prognostic evaluation and review of immunohistochemically detected disseminated tumor cells in peritumoral lymph nodes of patients with pN0 colorectal cancer.

BACKGROUND: The value of immunohistochemical detection of disseminated tumor cells in histopathologically tumor-free lymph nodes (pN0) of patients with colorectal cancer is still of uncertain prognostic value. We therefore evaluated the immunohistochemical detection rates and their prognostic value comparing three different monoclonal antibodies. METHODS: A total of 170 lymph nodes of 85 patients with curatively resected colorectal carcinoma at UICC stage I or II were evaluated for disseminated tumor cells. Frozen sections of each lymph node were immunohistochemically stained using three antibodies directed against CEA, CK20, and Ber-EP4. The detection rates were compared with histopathological tumor parameters and with the patient's survival. The median follow-up time was 86 months. RESULTS: CEA-, CK20-, and Ber-EP4-positive disseminated tumor cells were identified microscopically in lymph nodes of 23 patients (27%), 24 patients (28%), and 23 patients (27%), respectively. In 18 patients (21%) disseminated tumor cells were found in consecutive sections and stained positive for all three monoclonal antibodies. The lymph nodes of 10 of 18 patients (56%), which developed tumor recurrence, contained CEA- and CK20-positive disseminated tumor cells. Ber-EP4-positive cells were present in lymph nodes of 9 of 18 patients (50%) with tumor recurrence. The 5-year overall survival of the 23 patients with CEA-positive disseminated tumor cells was 72% compared to 91% of the patients without immunohistochemical evidence of tumor cells (p<0.01). While the identification of CK20-positive tumor cells was also correlated significantly with a worse overall patient survival (p<0.01), the application of Ber-EP4 failed to reach significance (p=0.057). Multivariate analysis identified the tumor site (colon versus rectal cancer) (p<0.006) and the presence of CEA-positive disseminated tumor cells (p<0.03) as independent prognostic factors. CONCLUSION: In colorectal carcinoma, the immunohistochemical detection of disseminated tumor cells in histopathologically pN0 peritumoral lymph nodes allows the identification of a subgroup with a significantly worse prognosis. Nevertheless, the prognostic value of immunohistochemically detected disseminated tumor cells remains controversial due to the nonuniform data in the literature.

Detection of circulating tumor cells in blood using an optimized density gradient centrifugation.

The aim of the study was to compare the new density gradient centrifugation system OncoQuick with the standard density gradient centrifugation system Ficoll for improved tumor cell enrichment in blood of tumor patients. Evaluation of OncoQuick and Ficoll density gradient centrifugation was performed by flow-cytometry and immunocytochemistry using 10 ml unspiked and tumor cell-spiked blood samples of tumor-free probands. From 10 ml blood, OncoQuick density gradient centrifugation separated a cell fraction which consisted of a mean cell number of 9.5x10(4) mononuclear cells compared to 1.8x10(7) cells by Ficoll. Density gradient centrifugation of tumor cell-spiked blood samples with OncoQuick and Ficoll led to similar tumor cell recovery rates, between 70% and 90% for both methods. The improved depletion of mononuclear blood cells by OncoQuick simplified further immunocytochemical evaluation of the enriched cell fraction, which could be spun onto 1-2 glass slides by cytocentrifugation. In comparison, the mononuclear cells separated by Ficoll had to be spun onto more than 50 glass slides for complete immunocytochemical evaluation. Consequently, tumor cell density on each cytospin was higher after OncoQuick preparation compared to Ficoll. Density gradient centrifugation with OncoQuick results in higher relative tumor cell enrichment than Ficoll density gradient centrifugation. This simplifies further immunocytochemical tumor cell detection and is a promising tool for the detection of circulating tumor cells in blood of tumor patients.

Telomere length and hTERT expression in patients with colorectal carcinoma.

The stabilization of telomere length by telomerase activation is an important step in carcinogenesis. Quantification of the catalytic telomerase subunit hTERT (human Telomerase Reverse Transcriptase) is a new indirect measure for telomerase. Telomere length and hTERT expression in cancer tissue and corresponding normal mucosa of 57 patients with completely resected colorectal carcinoma (UICC stage I-IV, R0) were determined for correlation with histopathological parameters and survival. Telomere lengths were measured using Southern Blot and hTERT-encoding mRNA was quantified by real-time RT-PCR. Telomere length and hTERT expression were significantly correlated in normal mucosa and cancer tissue (p<0.001). Telomere length and hTERT expression decreased with ageing only in normal mucosa. Cancer tissue had significantly shorter telomeres (p<0.001) and significantly lower hTERT expression levels (p<0.001) than corresponding normal mucosa. UICC stage I tumors showed significantly shorter telomeres than UICC stage II-IV tumors (p<0.002). Telomere length and hTERT expression were significantly correlated with overall survival. Telomere length and hTERT expression play an important role in ageing and carcinogenesis. Both parameters were identified as prognostic factors in patients with colorectal carcinoma.

Prognostic potential of the telomerase subunit human telomerase reverse transcriptase in tumor tissue and nontumorous mucosa from patients with colorectal carcinoma.

BACKGROUND: The stabilization of telomere lengths by telomerase activation is an important step in carcinogenesis and cell immortalization. Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of this enzyme. The objective of this study was to evaluate the use of real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis for the quantification of hTERT in tumor and nontumorous tissue samples. METHODS: Matched samples of tumor and adjacent nontumorous mucosa samples from 57 patients with completely resected colorectal carcinoma (International Union Against Cancer Stage I-IV) who underwent complete resection (R0) were quantified for hTERT mRNA expression using real-time RT-PCR. The expression levels were correlated with histopathologic findings and with survival. The median follow-up was 76 months. RESULTS: hTERT mRNA was expressed in all tumor samples and in all samples of adjacent mucosa. In 12 patients (21%), there was higher hTERT expression in tumor samples compared with nontumorous samples. Compared with tumor samples, the expression of hTERT in samples of nontumorous mucosa decreased with age (P = 0.06). hTERT mRNA expression in both tumor tissue and adjacent mucosa was correlated significantly with the histologic grade of colorectal carcinoma (P < 0.04 and P < 0.05, respectively). Patients with hTERT expression in tumor tissue in relation to the adjacent mucosa of > 0.57 had a significantly poorer overall survival compared with patients with lower hTERT ratios (P < 0.02). In addition to the established prognostic factor lymphatic vessel invasion, the hTERT ratio proved to be of independent prognostic value (P < 0.05). CONCLUSIONS: The prognostic potential of hTERT in patients with colorectal carcinoma and the correlation of hTERT with tumor grade underlines the role of hTERT as a molecular marker for biologic tumor staging.