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To study the role of loss of heterozygosity (LOH) in serum microsatellite DNA of patients with gastrointestinal stromal tumors (GIST).In GIST, tumor markers from peripheral blood are missing.Seventy-eight patients (59 GIST, 13 leiomyomas, 2 leiomyosarcomas, and 4 schwannomas) underwent resection at our institute between 1985 and 2006. Thirty-three preoperative sera (26 GIST and 7 non-GIST) and 62 postoperative sera (47 GIST and 15 non-GIST) were available and tested for alterations in 12 representative microsatellite loci on chromosomes 22, 17, 13, 9, and 3, using fluorescence-based automated capillary electrophoresis by ABI Prism. Survival was calculated with Kaplan-Meier plots.Seventeen out of 26 GIST patients had a positive preoperative serum LOH score (or =2 LOH, sensitivity 65.4%), and 6 out of 7 non-GIST patients had a negative score (or =1 LOH, specificity 85.7%, P=0.030, Fisher exact test). Serum LOH in GIST were strongly correlated with Fletcher risk groups (P=0.016, chi test). All metastasized GIST (7/7) showedor =2 LOH preoperatively. Postoperative sensitivity and specificity of LOH analysis for prediction of relapse in 47 GIST was 75.0% and 64.1%, respectively. After a median observation time of 51.3 months (95% confidence interval, 39.4-61.4), LOH in serum significantly predicted overall survival (P=0.007, log-rank test).LOH serum analysis in GIST may play a role as a noninvasive, differential diagnostic, prognostic, and monitoring marker in the clinical routine.

SummaryThe increasing use of primary tumors as surrogate markers for prognosis and therapeutic decisions neglects evolutionary aspects of cancer progression. To address this problem, we studied the precursor cells of metastases directly for the identification of prognostic and therapeutic markers and prospectively analyzed single disseminated cancer cells from lymph nodes and bone marrow of 107 consecutive esophageal cancer patients. Whole-genome screening revealed that primary tumors and lymphatically and hematogenously disseminated cancer cells diverged for most genetic aberrations. However, we identified chromosome 17q12–21, the region comprising HER2, as the most frequent gain in disseminated tumor cells that were isolated from both ectopic sites. Survival analysis demonstrated that HER2 gain in a single disseminated tumor cell but not in primary tumors conferred high risk for early death.

To investigate the importance of lymph node yield (LNY) and the ratio of afflicted lymph nodes in esophageal carcinoma patients.Between 1992 and 2004, 368 patients with esophageal carcinoma underwent surgery. Esophagectomy with curative intent was performed in 255 patients. Subtotal esophagectomy was performed either by thoracoabdominal (104 patients, 40.8%) or by transhiatal approach (151 patients, 59.2%).According to the LNY, patients were grouped into 3 groups. Twenty-six patients hador =5, 96 had 6 to 18, and 113 hador =19 dissected lymph nodes. In patients with nodal involvement (pN1), no significant overall survival differences were identified when stratifying subgroups according to the LNY. However, LNY had striking prognostic relevance in pN0 patients. The median overall survival was 23 (or =5 LN), 36 (6-18 LN), and 88 months (or =19). Even for patients with tripled LNY than the proposed minimum by the International Union Against Cancer (UICC) (18 LN), the rate of patients with detected lymph node metastases was only 46%, compared with 61% for patients with a LNY ofor =19 (P = 0.002). In pN1 patients classified according to the ratio of afflicted lymph nodes, median overall survival was 27 months in patients with a ratio11%, compared with 15 and 13 months in patients with a ratio of 11% to 33% and33%, respectively (P0.001). Multivariate Cox regression modeling identified ratio as the strongest independent prognostic factor for overall survival in pN1 and the LNY in pN0 patients.The minimal regional LNY of 6 lymph nodes as recommended by the UICC for esophageal carcinoma is far too low to appropriately stage the disease. The LNY and the ratio should be reflected in the next version of the UICC classification.

Background: To assess in-hospital complication rates and survival duration after en bloc vascular resection (VR) for infiltration of pancreatic malignancies in major vessels. Methods: Between 1994 and 2005, 585 patients underwent potentially curative pancreatic resection without adjuvant chemotherapy. Four hundred forty-nine patients (77%) underwent standard oncologic resection (VR−), whereas 136 (23%) received VR (VR+). For calculation of in-hospital morbidity and mortality rates, all 136 patients who underwent VR were considered. In contrast, for survival analysis, only pancreatic adenocarcinoma patients (n = 100) were included. Results: One hundred twenty-eight VR+ patients underwent portal or superior mesenteric vein resection and 13 hepatic artery (HA) or superior mesenteric artery (SMA) resection. In 5 patients, synchronous VR addressing both the mesenterico-portal axis and either the HA or SMA was performed. In-hospital morbidity and mortality rates of VR− patients (39.7%/4.0%) nearly equaled that of VR+ patients (40.3%/3.7%). From the 100 patients with pancreatic adenocarcinoma, histopathology confirmed “true” vascular invasion in 77 patients. Twenty-three patients had peritumoral inflammation, mimicking tumor invasion. Median survival was 15 months (11.2–18.8) in patients with histopathologic proven vascular invasion and 16 months (14.0–17.9) in those without (P = 0.86). Two-year survival probabilities were 36% (without) versus 34% (with vascular invasion; P = 0.9). Among VR+ patients with histopathologically evidenced vascular invasion, 19 survived longer than 30 months, and 6 were still alive 5 years after surgery. Multivariate modeling identified nodal involvement (N1) and poor grading (G3) as the only predictors of decreased survival. Evidence of vascular invasion had no adverse impact on survival. Conclusion: Postoperative morbidity and mortality rates after en bloc VR are comparable with “standard” pancreatectomy procedures. Median survival of 15 months in patients with vascular invasion is superior to that of patients who undergo palliative therapy and nearly equals that of patients who are not in need for VR.

Short tandem repeat (STR) polymorphisms in exon 4 of esophageal cancer related gene 2 (ECRG2) are a prognostic marker for squamous cell carcinoma (SCC) of the esophagus. The aim of the present study was to correlate these STRs with clinical outcome of the similar tumor type oral squamous cell carcinoma (OSCC). DNA of 81 patients that underwent complete surgical resection of OSCC was analyzed for STRs TCA3/TCA3, TCA3/TCA4 and TCA4/TCA4 in exon 4 of ECRG2 by PCR, capillary electrophoresis and DNA sequencing. ECRG2 STR TCA3/TCA3 were found in 45 (56%), TCA3/TCA4 in 33 (41%) and TCA4/TCA4 in 3 (3%) patients. TCA3/TCA3 was significantly associated with reduced relapse-free survival of OSCC, compared with TCA3/TCA4 and TCA4/TCA4 genotypes (P

L1 is a cell adhesion molecule expressed at the invasive front of colorectal tumors with an important role in metastasis. The aim of the present study was to determine L1 protein expression in a large cohort of colorectal cancer patients and its impact on early metastatic spread and survival. A total of 375 patients that underwent surgical treatment for colorectal cancer were chosen retrospectively. A tissue microarray was constructed of 576 tissue samples from these patients and analyzed by immunohistochemistry with a monoclonal antibody against human L1 (UJ127). Lymph node and bone marrow micrometastasis were assessed with monoclonal antibodies Ber-EP4 and pancytokeratin A45-B/B3, respectively. Associations between L1 expression and lymph node, bone marrow micrometastasis and survival were investigated with Fisher's, log-rank test and Cox multivariate analysis. All statistical tests were two-sided. L1 was detected in a subset of 48 (13%) of 375 patients examined. Analysis of L1 expression and survival revealed a significantly worse outcome for L1-positive patients by log-rank test (P

Neuroblastoma is the most common solid tumor in childhood with unconventional clinical behavior. L1, a neuronal cell adhesion molecule, is associated with poor survival in malignant adult tumors. The aim of the current study was to determine expression of L1 in pediatric neuroblastoma. L1 expression was assessed on a tissue microarray with 66 surgically resected neuroblastoma samples by immunohistochemistry with a monoclonal antibody and peroxidase method. Additionally, mRNA expression was analyzed by reverse transcriptase–polymerase chain reaction with L1-specific primers. Data were correlated survival data by log rank test and Cox regression multivariate analysis. L1 was detected in 57 (86%) of 66 neuroblastomas, whereas 9 (14%) were L1 negative. Median survival of all children was 72 months. Analysis with Kaplan-Meier method revealed a surprising and contrary finding to adult tumor entities: an association of L1 positivity with better event-free and overall survival (P

Background and study aims Endoscopic ultrasonography (EUS) is generally established as the most sensitive diagnostic tool for the assessment of locoregional tumor stage in esophageal carcinoma. It therefore has a crucial impact on the decision whether patients should undergo surgery as primary treatment or should receive neoadjuvant therapy. This study retrospectively evaluates the accuracy of EUS in tumor and nodal staging of prospectively evaluated patients with esophageal carcinoma in relation to tumor type, tumor grading, tumor site, and the influence of dilation. Patients and methods All 214 patients included in the study underwent surgery without neoadjuvant therapy and had tumor-free resection margins with no evidence of distant metastasis. EUS investigations were done at our Department of Interdisciplinary Endoscopy. EUS results were compared with the pathological findings. Results EUS correctly identified T status in 141 patients (65.9 %). The sensitivity and specificity in relation to T status were 68.1 % and 98.2 % respectively for T1, 40.9 % and 83.4 % for T2, 84.3 % and 64.6 % for T3, and 14.3 % and 98.8 % for T4. The overall diagnostic accuracy of EUS in relation to N status was 64.5 % (n = 138); sensitivity and specificity for the diagnosis of N1 were 93.8 % and 20 %, respectively. Sixty-eight (80 %) of 85 pN0-staged tumors were overstaged as uN1. Dilation had a significant influence on the accuracy of EUS staging in advanced tumors ( P = 0.02), whereas tumor grading impacted on EUS staging in early tumors ( P = 0.01). Tumor site and tumor type did not show any influence. Conclusions Endosonographic staging of esophageal carcinoma is still unsatisfactory. An improvement in staging accuracy may be achieved by adding fine-needle aspiration biopsy (FNA) to EUS, because FNA improves N-stage accuracy, but it has no bearing on T-stage accuracy.

To evaluate surgical strategies for neuroendocrine pancreatic tumors (NEPT) in the light of the new WHO classification from 2004 and to draw conclusions for future surgical concepts.: The extent of surgical resection in primary and recurrent NEPT is unclear.Between 1987 and 2004, 62 patients with sporadic NEPT were treated at our institution and sections from biopsy and resection specimen were histopathologically reclassified. Clinical presentation, surgery, metastases, and pattern of recurrence were related to survival.Fifteen well-differentiated tumors (WDT, 24%), 39 low-grade carcinomas (LGC, 63%), and 8 high-grade carcinomas (HGC, 13%) were identified. Median observation time was 30.5 months; 48 of 62 patients (78%) were surgically resected, and in 45 patients R0/R1 status was achieved. Overall 2- and 5-year survival in the latter group was 80% and 64%, respectively. Retrospective WHO classification revealed that organ-preserving segmental resections had been performed in 10 LGC and 1 HGC. These patients showed equal outcome as radically resected counterparts (n = 19). Liver and other organ metastases were present in 19 of 62 patients (31%), and resection was accomplished in 7 of 19 patients, which conferred better overall survival (P = 0.026, log-rank test); 21 of 45 R0/R1-resected patients (47%) suffered from recurrence, and reoperation was accomplished in 9 patients, which resulted in better overall survival (P = 0.066).Organ-preserving resections offer sufficient local control in LGC; therefore, radical resections do not seem to be justified. On the other hand, radical resection is indicated even in metastasized patients or in case of loco-regional recurrence. The silent and slow course of the disease facilitates long-term surgical control.

Midkine (MK), a heparin-binding growth factor, has an important role in cancer progression. The outcome of patients with gastrointestinal stromal tumors (GISTs) is correlated with tumor size and mitotic count. The aim of this study was to determine MK expression in GISTs. Midkine was detected in 31 (55%) of 57 surgically resected GISTs by immunohistochemistry with a rabbit antibody against MK and peroxidase method. A significant worse outcome of MK-positive patients was found (P

Common surgical policy in neuroendocrine pancreatic tumors (NEPT) should be reviewed after the appearance of the new WHO classification of 2004. A correct preoperative assessment is of paramount im

Background Adenocarcinoma of the esophago-gastric junction (EGJ) potentially spreads to abdominal and mediastinal lymph nodes. Methods Eighty-five patients with type I and II EGJ cancer underwent curative esophagectomy or esophago-gastrectomy and radical abdominal and mediastinal lymphadenectomy. Microinvolvement was detected with the mAb Ber-Ep4 in all histopathologically free lymph nodes. Results In type I tumors (n = 40), lower mediastinal lymph nodes were positive in 24% and among type II tumors (n = 45) in 10% of patients. Ber-Ep4+ cells in apparently free lymph nodes were found in 49% of patients. On inclusion of Ber-Ep4+ nodes, positive mediastinal lymph node staging was rising to 40 and 33% in type I and II patients, respectively. After a median observation time of 27.1 months, 37 of 85 patients (43.5%) had died of tumor disease. Kaplan–Meier analysis revealed a significant impact of nodal microinvolvement on disease-specific survival for type I and type II tumors (P = 0.016 and P

Purpose The appropriate surgery for curable squamous cell cancer (SCC) of the esophagus is discussed controversially. Patients and Methods Transthoracic esophagectomy (TTE) with radical en-bloc-lymphadenectomy was performed in 79/120 patients (66%). Due to severe comorbidity, 41/120 patients (34%) underwent less traumatizing transhiatal esophagectomy. Lymph nodes were stained using mAb BER-Ep4. Results pN0 status was found in 54 patients (45%) and pN1 status in 66 patients (55%). In the pN0 subgroup, 30 out of 54 patients (55.6%) had occult tumor cells in lymph nodes detected with BER-Ep4. pN1 patients had additional BER-Ep4 positive cells in histopathologically negative lymph nodes in 41 out of 66 patients (59.2%). Median disease-specific survival was 31.4 and 16.8 months for the transthoracic and transhiatal groups, respectively (P = 0.129). pN0 patients lived longer after transthoracic resection (P = 0.0349), and in the subgroup without lymph node micrometastases this effect was even stronger (P = 0.025). In contrast, in pN0 patients with nodal microinvolvement, TTE did not entail a survival benefit when compared with the transhiatal group (P = 0.333). Conclusion TTE results in improved outcome in the absence of lymph node micrometastases. Poor survival in patients with lymphatic micro-dissemination indicates systemic disease and the need for adjuvant treatment. J. Surg. Oncol. 2006;93:541–549. © 2006 Wiley-Liss, Inc.

BACKGROUND The chemokine and bone marrow-homing receptor CXCR4 has been implicated in metastatic dissemination of various cancers. We investigated CXCR4 expression in esophageal cancer specimens and its association with survival, lymph node microinvolvement, and bone marrow micrometastasis. METHODS We analyzed frozen tumor specimens from 136 patients with completely resected esophageal cancer for CXCR4 expression by immunohistochemistry. Lymph node microinvolvement and bone marrow micrometastasis were assessed by immunohistochemistry with monoclonal antibodies Ber-EP4 (against epithelial cell adhesion molecule) and pancytokeratin A45-B/B3 (against several cytokeratins), respectively. Associations between CXCR4 expression and clinicopathologic features, including tumor stage, histologic grade, lymph node metastasis and microinvolvement, bone marrow micrometastasis, and survival, were investigated with Fisher's test, log-rank test, and Cox multivariable analysis. All statistical tests were two-sided. RESULTS CXCR4 protein was expressed in 75 (55%) of 136 esophageal tumors examined. CXCR4 expression was statistically significantly associated with reduced median overall and disease-specific survival, compared with CXCR4 nonexpression (P < .001; log-rank test). The median overall survival of patients with CXCR4-positive tumors was 20 months and with CXCR4-negative tumors, 76 months (difference = 56 months, 95% confidence interval [CI] = 4 to 108 months; P < .001). The median disease-specific survival of patients with CXCR4-positive tumors was 25 months and with CXCR4-negative tumors was 97 months (difference = 72 months, 95% CI = 34 to 110 months; P < .001). CXCR4 expression was statistically significantly associated with increased lymph node microinvolvement (P < .001) and with increased bone marrow micrometastasis (P < .001). In multivariable analysis, CXCR4 expression, compared with its nonexpression, was identified as the independent variable that was most strongly associated with reduced disease-specific survival (relative risk [RR] of death = 2.03, 95% CI = 1.20 to 3.41; P = .008) and overall survival (RR of death = 2.18, 95% CI = 1.33 to 3.59; P = .002). CONCLUSION CXCR4 expression was associated with poor clinical outcome in esophageal cancer patients. CXCR4 may have a role in early metastatic spread because its expression was associated with micrometastases to both the lymph nodes and bone marrow. Thus, CXCR4 should be explored further as a target for adjuvant therapy for micrometastatic disease.

Background: The aim of this study was to assess the prognostc significance of nodal microinvolvement as well as the mode of spread in the early phase of lymphatic metastasis in patients with node-negative pancreatic ductal adenocarcinoma. Methods: Lymph nodes from 48 node-negative patients with R 0 resected pancreatic ductal adenocarcinoma were sampled from 3 different compartments: 1) distal hepatoduodenal ligament, 2) superior-anterior compartment, and 3) posterior-inferior. Tissue sections of 148 lymph nodes classified as tumor free by routine histopathology were examined, using a sensitive immunohistochemical assay with the antiepithelial monoclonal antibody Ber-EP4 for tumor cell detection. With regard to histopathologic tumor staging and grading, 26 (54.2%) of the patients were staged as pT 1 /pT 2 , 22 (45.8%) as pT3/pT4, while 31 (64.6%) as G 1 /G 2 and 17 (35.4%) patients as G 3 . Of the 148 tumor free lymph nodes, 56 contained Ber-EP4-positive tumor cells. These 56 lymph nodes were from 28 of the 4 8 patients. The multivariate Cox regression analysis revealed the independent prognostic impact of nodal microinvolvement on relapse-free and overall survival. Analysis by compartment, from which the lymph nodes were collected, revealed that overall survival time (P = 0.006) and time to local recurrence (P = 0.015) depend on the presence of nodal microinvolvement in the superior-anterior compartment. Conclusions: The influence of occult tumor cell dissemination n lymph nodes of patients with histologically proven pancreatic duct al adenocarcinoma supports the need for further tumor staging through immunohistochemistry. This could be a helpful tool in proper selection of patients for adjuvant chemotherapy.

Pulmonal und mediastinal vergroserte Lymphknoten bei bekannten malignen Grunderkrankungen sind immer hochverdachtig auf eine lymphogene Metastasierung. Dies gilt insbesondere dann, wenn schon in regionaren Lymphknotenstationen Tumorresiduen isoliert werden konnten. Dass trotz modernster praoperativer Diagnostik uberraschende Befunde zutage kommen, zeigt der vorliegende Fall eines jungen Mannes mit einem nichtseminomatosen Hodenkarzinom, bei dem sich eine bihilare Lymphknotenschwellung nicht als Rezidiv, sondern als ein simultane Sarkoidose herausstellte.

We describe the development of an aggressive orthotopic metastatic model of esophageal cancer, which is visualized in real time with combined magnetic resonance imaging (MRI) and fluorescence imaging. The aim of the study was to describe the development of a novel model of metastatic tumor disease of esophageal carcinoma and use this model to evaluate fluorescence and MRI in early detection of local and metastatic disease. The human esophageal adenocarcinoma cell line PT1590 was stably transfected with green fluorescent protein (GFP). Nude mice were orthotopically implanted with PT1590-GFP cells. Orthotopic tumor growth as well as metastatic spread was examined by fluorescence imaging and high-resolution MRI at defined intervals after orthotopic implantation. Highly aggressive novel fluorescent cell lines were isolated from metastatic tissues and put into culture. After implantation of these cells, 100% of the animals developed orthotopic primary tumors. In 83% of animals, metastatic spread to liver, lung and lymph nodes was observed. Primary tumor growth could be visualized with fluorescence imaging and with MRI with high correlation between the 2 methods. Fluorescence imaging allows fast, sensitive, and economical imaging of the primary and metastatic tumor without anesthesia. With MRI, anatomical structures are visualized more precisely and tumors can be more accurately localized to specific organs. This model should prove highly useful to understand esophageal carcinoma and to identify novel therapeutics for this treatment-resistant disease.

Background Patients with gastrointestinal stromal tumors (GIST) harbor increased levels of circulating tumor DNA in their peripheral blood. In the current study, the aim was to investigate whether the frequency of loss of heterozygosity (LOH) on cell-free DNA in blood may reflect tumor stage and recurrent disease of these patients. Materials and Methods Serum DNA and follow-up samples of 92 patients suffering from recurrent GIST were analyzed by a PCR-based fluorescence microsatellite analysis using a panel of 12 polymorphic markers. The data were correlated with established risk factors, and patients were followed-up over 4 y. Results Microsatellite analysis demonstrated a positive LOH score on cell-free DNA of 30/92 patients. A significant correlation with recurrence in CT imaging showed that a positive LOH score (n ≥ 2) was detected in 58% (11/19) of patients with recurrent disease (P = 0.030, χ2 test), but only in 25% of patients were clinically free of recurrence. No prognostic significance of a positive LOH score was observed after a median observation time of 48 mo. Conclusion Our findings show that LOH on circulating serum DNA correlates with the tumor status and is a frequent event in GIST patients with recurrent disease.

Esophageal adenocarcinoma is currently the most rapidly increasing cancer in Western populations. L1 (CD171), a neural cell adhesion molecule, has an essential function in tumor progression and has been shown to be expressed in the proliferating cells of the intestinal crypts in mice. The aim of the current study was to determine L1 expression in esophageal cancer and to evaluate whether L1 could serve as a potential marker and therapeutic target for this tumor type.L1 expression was assessed on a tissue microarray with 257 surgically resected esophageal cancer samples by immunohistochemistry with a monoclonal antibody (Clone UJ127). L1 expression was correlated with clinicopathological data.L1 was detected in 22 (9%) of 257 esophageal cases, whereas 235 (91%) were L1 negative. Nineteen (86%) of the 22 L1-positive cases were adenocarcinoma. Cross table analysis showed a significant association between L1 expression and adenocarcinoma subtype (p0.001), but not squamous cell carcinoma.L1 expression in a subgroup of esophageal cancer is specifically prevalent in adenocarcinoma. Data suggest L1 as a potential target for biological therapy in L1-positive esophageal adenocarcinoma patients.

Inflammatory cytokines have been shown to mediate organ damage by their action on vascular endothelia and leukocytes, in part by upregulating the expression of adhesion molecules, which in turn convey transmigration of leukocytes into tissue. The upregulation and activation of vascular cell adhesion molecules on the endothelial cells avail firm leukocyte adhesion to the vascular endothelium and enhance their transmigration and consecutive tissue injury. The aim of this study was to evaluate the expression of vascular adhesion molecules CD 31 (PECAM-1), CD 106 (VCAM-1), CD 62E (E-Selectin) and CD 62P (P-Selectin) in the pancreas and distant organs of pigs suffering from acute necrotizing pancreatitis (AP). AP was induced in 13 pigs by a combination of intravenous cerulein and intraductal glycodeoxycholic acid. For immunostaining of vascular adhesion molecules slides of porcine pancreas, lung, kidney and liver tissue were stained with monoclonal antibodies (Ab) against PECAM-1-1, VCAM-1 E- and P- SELECTIN. The endothelial cell expression of CD 31 (PECAM-1), CD 106 (VCAM), CD 62E (E-Selectin) and CD 62P (P-SELECTIN) in severe porcine pancreatitis is detectable and upregulation is partly significantly.

Aims: Gastrointestinal stromal tumours (GISTs) display genetic alterations on chromosome 22. GTn repeat (GTn) length polymorphism in the promoter of haeme oxygenase-1 gene (HMOX-1) is located on chromosome 22 and associated with malignant growth. The aim was to investigate the role of HMOX-1 promoter polymorphism in GIST patients. Methods and results: Tumour and corresponding healthy tissue DNA of 44 patients who underwent surgical resection of GIST were analysed by polymerase chain reaction, capillary electrophoresis and DNA sequencing. GTn polymorphism was classified into short (S) and long (L) allele. There was no difference detected in GTn genotype between tumour and healthy tissue DNA. Short GTn allele (SGTn) was significantly associated with metastatic disease, higher tumour recurrence rates and high risk GIST (consensus criteria 2001). Furthermore, SGTn allele carriers had significantly shorter disease-free and overall survival (log rank test, P

Purpose: Recurrence of a gastrointestinal stromal tumor (GIST) may require multimodal therapy and the role of repeated surgery in this concept is unclear. Patients and Methods: A consecutive series of GIST patients treated by surgery, imatinib therapy or both was retrospectively reviewed, and long-term survival was studied by Kaplan-Meier analysis. Results: Institutional primary surgeries before 1999 necessitated reclassification of the histopathological sections and 58/78 patients were classified as having true GIST. In primary surgeries, liver metastases were observed in GIST (6/58) but not in sarcoma/schwannoma patients (0/20), and exulceration of the primary tumor did not correlate with adverse outcome. Additionally, 86 patients were seen on an outpatient basis or were treated for recurrence at our institution, thus a total of 144 GIST patients were seen at our institution between 1994 and 2007 for either primary or secondary tumor manifestation. After 2003, 19/144 GISTs recurred and were treated by targeted therapy with imatinib. The patients showed better overall survival than historic controls. Imatinib therapy enhanced re-resectability due to tumor downsizing, and re-resection (n = 16) improved survival significantly (p = 0.046, log-rank test). Conclusion: A multimodal approach including targeted therapy and repeated surgery in the long-term management of recurrent GIST improves survival.

To assess the prognostic significance of nodal microinvolvement in patients with carcinoma of the papilla of Vater. From 1993 to 2003 at the University Clinic Hamburg, 777 patients were operated upon pancreatic and periampullary carcinomas. The vast majority of patients were operated upon pancreatic ductal adenocarcinoma (n = 566, 73%), followed by carcinomas of the papilla of Vater (n = 112, 14%), pancreatic neuroendocrine carcinomas (n = 39, 5%), intraductal papillary mucinous neoplasms (n = 33, 4%), and distal bile duct carcinomas (n = 27, 3%). Fresh-frozen tissue sections from 169 lymph nodes (LNs) classified as tumor free by routine histopathology from 57 patients with R0 resected carcinoma of the papilla of Vater who had been spared from adjuvant chemotherapy were immunohistochemically (IHC) examined, using a sensitive IHC assay with the anti-epithelial monoclonal antibody Ber-EP4 for tumor cell detection. With regard to histopathology, 39 (63%) of the patients were staged as pT1/pT2, 21 (37%) as pT3/pT4, 30 (53%) as pN0, while 38 (67%) as G1/G2. Of the 169 “tumor-free” LNs, 91 LNs (53.8%) contained Ber-EP4-positive tumor cells. These 91 LNs were from 40 (70%) patients. The mean overall survival in patients without nodal microinvolvement of 35.8 months (median—not yet reached) was significantly longer than that in patients with nodal microinvolvement (mean 16.6; median 13; p = 0.019). Multivariate Cox regression analysis for overall survival revealed that grading was the most significant independent prognostic factor (p = 0.001), followed by nodal microinvolvement (p = 0.013). The influence of occult tumor cell dissemination in LNs of patients with histologically proven carcinoma of the papilla of Vater supports the need for further tumor staging through immunohistochemistry.

Esophageal cancer is one of the most frequent cancers worldwide and is associated with poor outcome. Besides clinicopathological data, few prognostic molecular markers exist. Esophageal-cancer-related gene1 (ECRG1) short tandem repeats are associated with higher risk for developing esophageal squamous cell carcinoma. The aim of the present study was to evaluate the impact of DNA polymorphisms in the coding region of ECRG1 in esophageal carcinoma. Genomic DNA of 107 patients with esophageal cancer that underwent complete surgical resection between 1997 and 2005 was extracted. DNA was analyzed for ECRG1 polymorphisms Arg290Arg, Arg290Gln, and Gln290Gln by PCR and gel electrophoresis. Polymorphisms were correlated with survival data by the Kaplan–Meier method, multivariate Cox regression analysis, and odds ratio were determined. For all variables, cross tables were generated, followed by calculation of the p value by using the chi-square test/Fisher-exact test. Follow-up data of 102 patients with esophageal cancer were available after complete surgical resection for a median follow-up time of 24.3 months. Polymorphism Arg290Arg was found in 47 patients (46.1%), Arg290Gln in 48 patients (47.0%), and Gln290Gln in seven cases (6.9%). Arg290Arg polymorphism was significantly associated with reduced overall survival (p = 0.01) and tumor-free survival (p = 0.01) by the log-rank test. Multivariate regression analysis by Cox revealed polymorphism Arg290Arg to be a significant prognostic factor for survival (p = 0.012). Polymorphism Arg290Arg in ECRG1 is associated with poor clinical outcome after complete surgical resection in patients with esophageal cancer.

To date, the survival benefit of redo surgery in locally recurrent rectal adenocarcinoma remains unclear. In an institutional study, operations for recurrence were retrospectively analyzed. Survival was calculated using the Kaplan–Meier plot and Cox regression analysis. A total of 72 patients with local recurrence were explored or resected. In 38 patients, there was synchronous distant organ recurrence. Forty-five of 72 were re-resected and in 37 of 45 cases, R0 situations were achieved. In 11 of 38 metastasized patients, both local and distant organ recurrence were successfully removed. For obtaining tumor control, resections of inner genitals, bladder, and sacral bone were necessary in 10, 4, and 11 patients, respectively. Survival was better for patients re-resected with a median overall survival of 54.9 months, as compared with 31.1 months among non-resected patients (p = 0.0047, log-rank test). Subgroup analysis revealed that a benefit of re-resection was observed to a lesser extent in synchronous local and in distant disease. Cox analysis showed that initial Dukes stage and complete resections of local recurrences were independently determining prognosis (relative risk 1.762 and 0.689, p = 0.008 and p = 0.002, respectively). Radical surgery for local recurrence can improve survival if complete tumor clearance is achieved, and concomitant distant tumor load should not principally preclude re-resection.

The clinical distinction between cancer and chronic pancreatitis is difficult in patients with pancreatic masses. To test whether detection of aberrant serum DNA could assist in this important differential diagnosis, we tested a panel of 12 microsatellitemarkers from chromosomes 17p, 17q, 13q, 9p, 5q, and 2p in the blood of 35 pancreatic cancer patients, 22 patients with chronic pancreatitis, and 20 healthy individuals. An average of 2.8 loss of heterozygosity (LOH) was found in 32 of 35 cancer patients of whom 30 (86%) had 2 or more LOH. LOH was also found in 7 of 22 pancreatitis patients but all these patients had only 1 LOH. No LOH was detected in healthy donors of comparable age. These data suggest that LOH analysis may be a substantial help for diagnosing pancreatic masses. An extension of the panel, perhaps in combination with a better selection of markers may further improve this assay.

Although mortality after pancreatic surgery in most high-volume centers has decreased to less than 3%,1–3 morbidity still remains considerably high, ranging from 18% to 52%.4–9 The most frequent causes for morbidity are anastomotic insufficiencies (pancreatic, biliary, gastric/duodenal, and enteral), pancreatic fistulas, and delayed gastric emptying. Postpancreatectomy hemorrhage (PPH) is a less frequent, however, in some patients, devastating complication. Since both its pathophysiologic and clinical features may differ considerably, it is difficult to establish diagnostic and therapeutic algorithms for adequate management of PPH: 1) time of onset (early PPH occurring within 24 to 48 hours postoperatively versus delayed PPH after several days to weeks); 2) severity [(a) mild, (b) moderate, (c) severest, ie, life-threatening]; 3) intraluminal or extraluminal manifestation; 4) underlying disease (pancreatic carcinoma vs. chronic pancreatitis); 5) kind of index operation; and 6) a possible association to erosive vascular pathologies due to pancreatic fistula are factors that are important for estimating the prognosis of PPH. A customized risk analysis should precede individual decision-making. The armory of diagnostic and therapeutic means ranges from observant monitoring and fluid replacement, interventional procedures, ie, endoscopy and radiology, to surgical relaparotomy. Early bleeding within the immediate postoperative period is unlikely due to vascular erosions but rather a result of simple technical failures. In case of PPH in the abdominal cavity, no doubt exists that immediate relaparotomy is indicated. However, in case of early bleeding in the gastrointestinal tract, endoscopy may also be an option for interventionally treating bleeding sites located at the gastrojejunostomy or, if accessible, at the enteroenteric anastomosis. Because of the life-threatening potential of PPH, standardized rules with respect to its management are urgently needed. So far, in clinical routine, the decision about how to handle PPH is often arbitrary and is usually based on institutional or even individual experiences. The aim of the presented evaluation was therefore to “dissect” the heterogeneous causes of PPH. Onset of manifestations, clinical features, courses, and success rates of nonsurgical options, ie, interventional radiology and endoscopy, and surgical procedures for treatment of PPH were analyzed. Based on a 15-year institutional experience, we sought, in particular, to classify different bleeding types and suggest a diagnostic and therapeutic algorithm that may help to allocate patients to a customized therapy (Fig. 1). FIGURE 1. Suggested algorithm for treatment of early (A) and delayed (B) postpancreatectomy hemorrhage after major pancreatic surgery.

Loss of heterozygosity (LOH) may be a valuable tool for detection of malignant proceedings. The aim of our study was to investigate LOH in the serum of patients with adenocarcinoma of the distal oesophagus and the cardia for diagnostic and prognostic utility.Matched tumour and serum samples from 46 surgically treated patients with oesophageal adenocarcinoma and cardia carcinoma divided in two groups were analysed. Twelve markers were examined with a PCR-based microsatellite analysis.A similar high frequency of LOH (range from 77% to 96%) was detected in the tumour and serum of both groups, whereas no LOH was detected in 20 healthy individuals. However, no significant correlation between LOH incidence and clinicopathological characteristics and survival was found.The results indicate that DNA alterations in tumours of the oesophagus and cardia are uniform. The high frequency of LOH in tumour patients underlines the utility of this molecular approach as a diagnostic tool.

Short tandem repeat (STR) polymorphisms in exon 4 of the Kazal-type esophageal cancer related gene (ECRG2) have been reported to be associated with esophageal carcinoma. Kazal-type genes are associated with cancer and pancreatic disease. The aim of the present study was to examine whether ECRG2 STR polymorphisms are associated with pancreatic carcinoma and chronic pancreatitis.A total of 209 surgically treated patients were analyzed, 92 with pancreatic adenocarcinoma and 117 with chronic pancreatitis. We retrospectively analyzed genomic DNA from peripheral blood leukocytes for STR TCA3/TCA3, TCA3/TCA4 and TCA4/TCA4 in the noncoding region of exon 4 of ECRG2. Associations between STRs and survival of cancer patients were investigated using log-rank test.ECRG2 STR of highest incidence was TCA3/TCA3 [47 (51%) in pancreatic carcinoma; 59 (50%) in pancreatitis patients], followed by the TCA3/TCA4 [37 (40%); 54 (46%)] and TCA4/TCA4 [8 (9%); 4 (4%)] genotypes. No correlation in frequency of STRs comparing chronic pancreatitis and pancreatic cancer was determined using the Chi-squared test (p = 0.23). STR polymorphisms were not significantly associated with reduced tumor-specific or overall survival (p0.05; log-rank test).The data show that ECRG2 STR polymorphism TCA3/TCA3 in exon 4 is the most prevalent polymorphism found in pancreatic adenocarcinoma and chronic pancreatitis detected in peripheral blood. None of the polymorphisms was associated with poor clinical outcome in pancreatic cancer patients.

Purpose: Angiogenesis and lymphangiogenesis are important steps in tumor growth and dissemination and are of prognostic importance in solid tumors. The determination of microvessel density (MVD) by immunohistology is subject to considerable variability between different laboratories and observers. We compared MVD determination by immunohistology and quantitative real-time PCR and correlated the results with clinical variables. Experimental Design: The expression of endothelial antigens vascular endothelial cadherin (CD144), P1H12 (CD146), tie-2, and VEGFR-2, and lymphatic endothelial markers VEGFR-3, Prox, and LYVE was assessed by quantitative PCR (qPCR) in primary surgical samples. The expression of angiogenetic growth factors VEGF-A, VEGF-C, VEGF-D, angiopoietin-1, and angiopoietin-2 was quantified by PCR and correlated with MVD and clinical variables. Results: The expression of endothelial antigens vascular endothelial cadherin (CD144), P1H12 (CD146), tie-2, and VEGFR-2 correlated with each other in 54 samples of primary esophageal cancer (P < 0.0001 for all comparisons). MVD determined immunohistologically by CD31 staining in a subgroup of 35 patients correlated significantly with the qPCR method. The expression of angiogenetic growth factors VEGF-A, VEGF-C, VEGF-D, angiopoietin-1, and angiopoietin-2 was significantly associated with MVD (P < 0.0001 for all comparisons). Analysis of the expression of lymphendothelial markers VEGFR-3, Prox, and LYVE revealed concordant results, indicating that quantification of lymphendothelial cells is possible by qPCR. The presence of lymph node metastasis on surgical specimens was significantly correlated with MVD (P < 0.003), VEGFR-2 (P < 0.048), and VEGF-C (P < 0.042) expression. Conclusions: These results indicate that quantification of MVD by qPCR in surgical samples of esophageal carcinoma yields similar results with immunohistology. Interestingly, the extent of angiogenesis and lymphangiogenesis was not related in individual tumor samples. Lymph node metastases could be predicted by MVD and VEGF-C expression.

HER-2 is the target for antibody based treatment of breast cancer (Herceptin). In order to evaluate the potential role of such a treatment in esophageal cancers, HER-2 amplification and overexpression was investigated in primary and metastatic cancers of the esophagus. A tissue microarray was constructed from 255 primary esophageal cancers (110 adenocarcinomas and 145 squamous cell carcinomas), 89 nodal and 33 distant metastases. Slides were analyzed by immunohistochemistry (HercepTest; DAKO) and fluorescence in situ hybridization (FISH; PathVysion; Vysis-Abbott) for HER-2 amplification and overexpression. Amplification was seen in 16/110 (15%) adenocarcinomas and in 7/145 (5%) squamous cell carcinomas. There was a strong association between HER-2 amplification and overexpression, especially in adenocarcinomas (P

Loss of heterozygosity (LOH) in tumors has been described to have prognostic impact. HoxllLl gene, located on chromosome 2, has a role in proliferation of neuronal myenteric Cajal cells being the progenitor cells of GISTs. The aim was to examine the frequency and prognostic value of allelic loss of Hoxl 1L1 gene locus in GISTs. Tumor and control DNA of 72 GIST patients was extracted after microdissection from tissue sections. Patients underwent surgery between 1992 and 2003 and were histopathologically reclassified. Microsatellite marker D2S286 on chromosomes 2 near Hoxl 1L1 gene locus was used for detection of LOH by PCR and capillary electrophoresis. Survival was calculated by Kaplan-Meier plots. LOH was found in 7 (10%) of 72 GISTs. Fifty-four (75%) cases did not show LOH. Eleven (15%) were homozygous and consequently non-informative. Survival analysis (n=59) revealed a significantly worse tumor-specific and relapse-free survival for GIST patients with LOH in the tumor by univariate analysis (p

Purpose: In gastrointestinal stromal tumors (GIST), loss of heterozygosity (LOH) on chromosome 22 and its presumptive biological function has been described. The prognostic value of these and other DNA regions for patient survival remains unclear.Experimental Design: Sixty patients who underwent surgery at our institution between 1992 and 2003 for GIST were histopathologically reclassified by immunohistochemistry and the GIST consensus group criteria 2001. Twenty-one microsatellite loci on chromosomes 3, 9, 13, 17, 18, and 22 were screened for alterations in tumor and healthy DNA. Survival was calculated by Kaplan-Meier plots.Results: Eleven (18.3%) of 60 patients showed metastases at presentation. Thirteen (21.7%) of 60 were high-risk GISTs. LOH was found in all tumors. Twenty-eight (46.7%) of 60 showed more than two LOH in 21 microsatellite marker sites. The frequency of single marker LOH varied from 1.7% to 28.3% among tumors. Frequent LOH was found on chromosomes 22 and 17. The correlation of LOH positivity and the consensus scoring was significant (P = 0.005, χ2 test). After a median observation time of 33.3 months (95% confidence interval, 23.9-42.6), overall survival was best for patients with tumors of very low, low, and intermediate risks with only 6 of 36 death events, whereas 14 of 24 high-risk and metastasized patients had died (P < 0.001, log-rank test). Likewise, LOH significantly predicted survival (P = 0.013) and the effect was particularly detrimental for LOH on chromosome 17 (P < 0.001).Conclusions: LOH is a useful phenomenon for the prognosis of GIST. Rather than chromosome 22 markers, chromosome 17 markers independently predict survival.

Background: The role of sentinel lymph nodes in colorectal cancer remains unclear. Methods: Cryosections from central para-aortic mesenterial lymph nodes were stained using mAb BER-Ep4. Overall survival and distant recurrence were calculated using Kaplan-Meier plots. Results: All patients (n = 48) were free of distant metastases and curatively resected (R0). 23 pN0, 13 pN1 and 12 pN2 stages were found. 21/48 patients (44%) showed BER-Ep4+ cells in their central lymph nodes (7/23 pN0, 8/13 pN1, 6/12 pN2). In 6/23 pN0 patients, BER-Ep4+ cells were also found in locoregional nodes (p = 0.03, Fisher’s exact test). pN status predicted overall survival (p = 0.006, Kaplan-Meier curve, log-rank test). An impact was exerted by central mesenteric BER-Ep4+ cells on overall survival (p = 0.009 in pN0 patients, p = 0.07 for all pN) and distant recurrence-free survival (p = 0.001 in pN0 patients, p = 0.007 for all pN). Multivariate analysis showed an independent prognostic effect on overall survival in pN0 patients (p = 0.022). Conclusion: Central lymph nodes are sentinels of disease not amenable to extended lymphadenectomy and might identify patients at risk of distant organ recurrence.

AIM: Microcirculatory dysfunction and free oxygen radicals are important factors in the pathogenesis of severe acute pancreatitis. Additional oxygen delivery might enhance lipid peroxidation but may also improve pancreatic microcirculation. This study assesses the effect of free cellular bovine hemoglobin on the formation of oxygen radicals and microcirculation in a rodent model of severe acute pancreatitis. METHODS: Fifteen minutes after induction of acute pancreatitis Wistar rats received either 0.8 mL bovine hemoglobin (HBOC-200), hydroxyethyl starch (HES) or 2.4 mL of normal saline to ensure normovolemic substitution. After 6 h of examination the pancreas was excised and rapidly processed for indirect measurement of lipid peroxidation products malondialdehyde (MDA) and reduced glutathione (GSH) in pancreatic tissue. RESULTS: The single application of HBOC-200 improved pancreatic microcirculation and reduced histopathological tissue damage significantly. Tissue concentration of MDA did not differ between the groups. Also no differences in GSH levels were detected. CONCLUSION: Though the single application of HBOC-200 and HES improve pancreatic microcirculation, no differences in lipid peroxidation products were detected. The beneficial effect of additional oxygen supply (HBOC-200) does not lead to enhanced lipid peroxidation.

Background Short tandem repeat (STR) polymorphisms in exon 4 of the esophageal cancer-related gene 2 ( ECRG2 ) are a risk marker for esophageal carcinoma. The aim of the present study was to correlate these STRs with clinical outcome. Methods Genomic DNA of 86 patients who underwent complete surgical resection was analyzed for STRs TCA 3 /TCA 3 , TCA 3 /TCA 4 , and TCA 4 /TCA 4 in exon 4 of ECRG2 by polymerase chain reaction and DNA sequencing. Results ECRG2 STR TCA 3 /TCA 3 and TCA 3 /TCA 4 were found in 40 (47%) patients, respectively, and TCA 4 /TCA 4 in 6 (7%) cases. TCA 3 /TCA 3 genotype was significantly associated with reduced survival ( P 3 /TCA 3 STR was the strongest prognostic factor determined by multivariate Cox regression analysis. Conclusions Genetically fixed STR polymorphism TCA 3 /TCA 3 in exon 4 of ECRG2 is associated with poor clinical outcome in surgically treated esophageal cancer patients and might be a potential prognostic marker. The usefulness of these genetic markers to predict responsiveness toward neoadjuvant treatment of esophageal cancer patients would be of high clinical interest and should be examined in future studies.

Pancreatic adenocarcinoma is a tumor with fatal outcome. Cell adhesion molecules, such as L1 (CD171), have an essential function in tumor progression. L1 has been shown to be specifically expressed in poorly differentiated neuroendocrine carcinomas of the pancreas. The aim of this study was to determine the expression of L1 in pancreatic adenocarcinomas to evaluate whether L1 might differentiate between pancreatic carcinomas of neuroendocrine and ductal origin.L1 expression was retrospectively analyzed in 111 cases of pancreatic adenocarcinomas by immunohistochemistry on paraffin sections of primary tumors. Staining was performed by the peroxidase technique with monoclonal antibody against human L1. All tumors were classified according to the most recent TNM classification.The focal expression of L1 was detected in 2 (2%) out of 111 pancreatic carcinomas only, the remaining 109 (98%) being L1-negative. No expression was found in acinar or ductal cells of normal pancreatic tissue.Our data suggest that L1 is expressed in few cases of pancreatic ductal adenocarcinoma. Since L1 was previously found to be expressed specifically in neuroendocrine pancreatic carcinomas, its absence in unclear pancreatic masses might hint at a ductal origin for a malignant pancreatic tumor.

The treatment strategy for mesenchymal tumors of the gastrointestinal tract is based upon typing of the tumor. Especially differential diagnosis of gastrointestinal stromal tumors (GISTs) to leiomyomas is crucial for determining radicality of surgery. L1 cell adhesion molecule (CD171) plays an essential role in tumor progression. The aim of this study was to determine expression of L1 in GISTs, smooth muscle tumors, desmoid-type fibromatosis and peripheral nerve sheath tumors (PNSTs). We retrospectively analyzed a total of 129 surgically resected primary tumors or metastases of 72 GISTs, 29 smooth muscle tumors, seven PNSTs and 21 desmoid-type fibromatosis by immunohistochemistry for c-kit, CD34, smooth muscle actin, desmin, vimentin, S-100 and L1 expression. L1 expression was detected in 53 (74%) of 72 GISTs but in none of 29 smooth muscle tumors or 21 desmoid-type fibromatosis (P

AIM: To determine the expression of L1 in pancreatic neuroendocrine tumor and to correlate it with WHO classification of this tumor. METHODS: We retrospectively analyzed L1 expression in 63 cases of pancreatic neuroendocrine tumor by immunohistochemistry on paraffin sections of primary tumors or metastases. Staining was performed by peroxidase technique with monoclonal antibody UJ127.11 against human L1. All tumors were classified according to WHO classification as well-differentiated neuroendocrine tumors and carcinomas or poorly-differentiated neuroendocrine carcinomas. RESULTS: L1 was detected in 5 (7.9%) of 63 pancreatic neuroendocrine tumors. Four (44.4%) of 9 poorly-differentiated carcinomas expressed L1. In contrast, only 1 (1.9%) of 54 well-differentiated tumors or carcinomas was positive for L1. No expression was found in Langerhans islet cells of normal pancreatic tissue. Cross table analysis showed a significant association between L1 expression and classification of neuroendocrine tumors of the pancreas (P

Background: The chemokine and bone marrow homing receptor CXCR4 has been implicated in metastatic dissemination in different tumor types. In this study we investigated CXCR4 expression in esophageal cancer and the association with survival, lymph node and bone marrow micrometastasis. Methods: We retrospectively analyzed frozen tumor samples of 136 patients with completely resected esophageal cancer for CXCR4 expression by immunohistochemistry. Lymph node micrometastasis was determined by staining with mAb Ber-EP4, bone marrow micrometastasis by using pancyto-keratin mAb A45-B/B3. CXCR4 expression was correlated with these results and other clinicopathological features. Results: CXCR4 expression was found in 75 out of 136 (55%) esophageal tumors. Patients with positive immunostaining of CXCR4 had a significantly shorter overall and tumor-specific survival than patients without (p = 0.002; log-rank test). Further, CXCR4 expression significantly correlated with lymph node as well as bone marrow micrometastasis. Multivariate analysis identified CXCR4 expression as an independent prognostic factor (p = 0.001). Conclusion: CXCR4 expression is associated with a significantly worse outcome in esophageal cancer patients. Our results implicate a role for CXCR4 in systemic spread since expression correlates with lymph node and bone marrow micrometastasis and it could be a potential target for immunotherapy.

e15640 Background: The objective of this study was to investigate whether limited resection of the oesophagogastric junction can be successfully used in the treatment of the patients with early oesophageal carcinomas. Methods: A total of 111 patients with early oesophageal cancer (57 adenocarcinomas, 54 squamous cell carcinomas) had surgical resection with systematic lymphadenectomy (41 thoracoabdominal-TA, 52 transhiatal-TH and 18 with limited resection of the oesophagogastric junction- LROGJ). Results: In all patients, regardless from the surgical procedure, a complete resection (R0) was achieved. The median lymph node yield was significantly higher (p=0.0001) in TA patients (24 LN), compared with TH (14LN) and LROGJ (16LN). The median in hospital and ICU stay were shorter in patients with the LROGJ (12 and 2 days, respectively) compared with the TA (24 and 8 days) and TH patients (23 and 4 days). None of the 43 patients with high grade intraepithelial neoplasia (HGIEN) or oesophageal carcinoma limited to the mucosa had lymphatic spread, as compared with 15 of 68 (22.1%) with affection of the submucosa. Although lymph node metastases were usually limited to locoregional lymph node stations, two patients had metastases in distant lymph nodes (pM1a) The infiltration of the submucosa was accompanied with significant worsening of the overall survival (pT1a vs. pT1b; p=0.002). Multifocal neoplasia was detected in three patients with SCC HGIEN (30%) but not in AC HGIEN! Nine out of 44 (20.4%) patients with early SCC had multifocal neoplasia, compared to 6 out of 53 (11.3%) patients in AC (p=0.322). The sensitivity of the preoperative tumour dept staging (endoscopic ultra sound - EUS; and CT) was astonishing low (only 50% for cT1b), as was the specificity (66.7% for cT1a and only 87.5% for cT1b). On multivariate analysis, only histological tumor type (AC) was independent predictor of survival. Conclusions: Considering the limitations and pitfalls of endoscopic and classical resectional procedures, the quest for alternative and “patient tailored” treatment in patients with early oesophageal carcinoma carries on. A valuable alternative can be the limited resection of the oesophago-gastric junction under sparing of the healthy oesophagus and stomach. No significant financial relationships to disclose.