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Background: Postoperative pancreatic fistula (POPF) is a major cause of morbidity after pancreaticoduodenectomy. There is no consensus on the best technique to protect the pancreato-enteric anastomosis and reduce the rate of POPF. This study investigated the feasibility and efficiency of external suction drainage of the pancreatic duct to improve the healing of pancreaticogastrostomy.Methods: Between July 2019 and June 2021, 21 consecutive patients undergoing elective pancreaticoduodenectomy were included. In all patients we performed a pancreaticogastrostomy and inserted a negative pressure drainage into the pancreatic duct. The length and diameter of the pancreatic duct were measured and the texture of the pancreas was evaluated. The daily secretion volume and the lipase value via pancreatic duct drainage were documented. The occurrence of POPF was evaluated.Results: None of the patients had drainage-related complications. In 4 patients we registered a dislocation of the drainage from the pancreas duct into the stomach. 17/21 Patients showed no signs of POPF. A biochemical leak was measured in one patient. Furthermore, 2 patients had a POPF grade B. In one patient, POPF grade C required reoperation and resection of the remnant pancreas. All 4 cases of POPF met the risk criteria soft pancreas, high volume and high lipase value in the duct drainage.Conclusion: The insertion of the pancreatic duct drainage was feasible and caused no drainage-related morbidity. POPF-rate was moderate in the risk population of soft pancreas and small duct.

Loss of the coxsackie and adenovirus receptor (CAR) has previously been observed in gastric cancer. The role of CAR in gastric cancer pathobiology, however, is unclear. We therefore analysed CAR in 196 R(0)-resected gastric adenocarcinomas and non-cancerous gastric mucosa samples using immunohistochemistry and immunofluorescence. Coxsackie and adenovirus receptor was found at the surface and foveolar epithelium of all non-neoplastic gastric mucosa samples (n=175), whereas only 56% of gastric cancer specimens showed CAR positivity (P0.0001). Loss of CAR correlated significantly with decreased differentiation, increased infiltrative depths, presence of distant metastases, and was also associated with reduced carcinoma-specific survival. To clarify whether CAR impacts the tumorbiologic properties of gastric cancer, we subsequently determined the role of CAR in proliferation, migration, and invasion of gastric cancer cell lines by application of specific CAR siRNA or ectopic expression of a human full-length CAR cDNA. These experiments showed that RNAi-mediated CAR knock down resulted in increased proliferation, migration, and invasion of gastric cancer cell lines, whereas enforced ectopic CAR expression led to opposite effects. We conclude that the association of reduced presence of CAR in more severe disease states, together with our findings in gastric cancer cell lines, suggests that CAR functionally contributes to gastric cancer pathogenesis, showing features of a tumour suppressor.

Sentinel lymph node biopsy (SLNB) in colorectal cancer (CRC) is a controversial issue. Different detection techniques, various protocols for the histopathological work-up of the SLN and a greatly differing experience between the investigators make the comparison of the available studies problematic. Nevertheless, it is clear, that the successful clinical application of SLNB in breast cancer and melanoma cannot simply be transferred into colorectal cancer treatment. In this paper we try to define the current status of clinical application of this technique in CRC by means of a literature review and our own experience. Moreover, the background and the potential clinical implications of additionally small tumor deposits in the SLN (so-called "upstaging") is critically reviewed. Summarizing the results, it is clear, that the value of SLNB in CRC is still unclear. If current techniques are to be applied outside a study protocol and no patient selection is performed the correct identification of macrometastases needs further investigation. Although still under debate, there is otherwise growing evidence, that -at least if RT-PCR-techniques are used- the detection of small tumor deposits in the SLN may be of prognostic and therefore clinical value. Future studies should focus on two subjects: First, alternative detection techniques and careful patient selection may clarify, if an improvement of the sensitivity to detect macrometastases is feasible. Second, large prospective trials using a standardized histopathological lymph node assessment should compare SLN and Non-SLN for its incidence to bear small tumor deposits. If SLNB proves to be sensitive, the prognostic and predictive value of these additional findings should be clarified.

Although 15-25% of patients with anal cancer present with superficial inguinal lymph node metastases but the routine application of groin irradiation is controversial because of serious side effects. Inguinal sentinel lymph node biopsy (SLNB) can be used to select patients appropriately for inguinal radiation. The study evaluates the efficiency and clinical impact of SLNB.Forty patients with anal cancer underwent 1 ml Tc(99m)-Nanocolloid injection in four sites around the tumour. Patients with inguinal radio colloid enrichment were selected for sentinel lymph node biopsy (SLNB). Lymph node status was examined by haematoxylin and eosin (HE) as well as immunohistochemistry-staining. All SLN-positive patients were scheduled for inguinal radiation; SLN-negative patients with T1 and early T2 tumours were not scheduled for inguinal radiation.SLN were detected in 36/40 patients. Three common patterns of lymphatic drainage were observed: mesenterial, iliacal and inguinal. Twenty patients with inguinal SLN underwent SLN-biopsy. 6/20 patients were SLN-positive. In 10/20 patients SLNB altered the therapy plan--four patients with T1-tumours and positive SLN had additional groin irradiation, whereas 6 patients with small T2-tumors and tumour-free inguinal SLN did not undergo inguinal irradiation.Inguinal sentinel node biopsy in anal cancer is efficient and could assist in the decision for inguinal radiation. The validity and safety of the proposed therapeutic algorithm has to be proven by a larger, prospective study.

Sentinel lymph node biopsy (SLNB) in gastrointestinal-(GI)-tract cancer is not yet of clinical relevance. Nevertheless, the results in the upper GI-tract promise to be helpful to individualize the indication for surgical therapy. SLNB in colon cancer still fails to show high validity to predict the nodal status, but may be helpful to clarify the prognostic role of micrometastases/isolated tumor cells. In anal cancer SLNB is able to guide the indication for groin irradiation.

Isolated tumor cells as a consequence of minimal residual disease are often not detectable by routine diagnostic procedures. However, before or after surgery, isolated tumor cells in lymph nodes, the peritoneal cavity, blood, or bone marrow can frequently be identified by immunohistochemical or molecular methods. Failure to reveal the presence of such cells results in under-staging of tumor patients and may constitute the source of unexpected tumor recurrence after radical surgery. These facts emphasize the importance of isolated tumor cells at least as a surrogate marker. The frequency of appearance of isolated tumor cells in different organ systems also depends on the type of primary tumor. Developments in modern detection methods have led to increasing sensitivity but at the expense of specificity. Isolated tumor cells demonstrate remarkable heterogeneity with respect to proliferative potential and tumorigenicity. This characteristic is also reflected by a striking variability in the expression of various genes conditioning the aforementioned biological behavior. Unfortunately there is also remarkable heterogeneity in methods used for sampling and processing patient material as well as for the enrichment and detection of isolated tumor cells. Despite the ongoing controversies concerning detection methods and biological significance of isolated tumor cells, several clinical trials providing data supporting the prognostic relevance of minimal residual disease should also be considered for gastrointestinal carcinoma. In future this finding should be integrated in the planning of trials in surgical oncology, and "minimal residual disease" should receive stronger attention as a stratification criterion in such clinical studies.

Epithelial cells in the bone marrow of patients with gastric cancer suggest tumor dissemination; however, their prognostic implications are controversial. We prospectively evaluated the correlation of bone marrow findings, recurrence rate, and disease-free survival after long-term follow-up.Bone marrow were aspirated from both iliac crests and stained with monoclonal cytokeratin (CK)-18 antibody in 209 patients before their initial operation. Patients were followed up for a median of 56 months.Overall, 39 (19%) of 209 patients and 15 (14%) of 109 R0-resected patients had CK-positive cells. CK-positive patients had more local, regional, and distant recurrence than CK-negative patients (P.05). We found a significantly shorter disease-free survival (P.05) in the patients with2 CK-positive cells per 2 x 10(6) bone marrow cells (mean, 35 months) than in patients withor=2 CK-positive cells per 2 x 10(6 )bone marrow cells (mean, 70 months) or in patients with no CK-positive cells (mean, 86 months). Multivariate analysis confirmed that2 CK-positive cells per 2 x 10(6) bone marrow cells was an independent prognostic factor for tumor-related death (P.05).Not only the mere presence of CK-positive epithelial cells in bone marrow, but also the cell number, correlates with prognosis. Our findings suggest that classifying CK-positive bone marrow cells in these patients will facilitate future studies.

Purpose Vascular endothelial growth factor (VEGF)-D and its homolog VEGF-C influence lymphangiogenesis through activation of VEGF receptor 3 (VEGFR-3), and have been implicated in lymphatic tumor spread. Nodal dissemination of gastric adenocarcinomas critically determines clinical outcome and therapeutic options of affected patients. Therefore, we analyzed expression and prognostic significance of VEGF-D along with VEGF-C, and VEGFR-3 in gastric adenocarcinomas. Materials and Methods VEGF-C, VEGF-D, and VEGFR-3 were analyzed in 91 R0-resected primary gastric adenocarcinomas, corresponding noncancerous gastric mucosa, and lymph node metastases employing immunohistochemistry and/or in situ hybridization. Blood and lymph vessel densities were assessed after staining with CD31 and LYVE-1–specific antibodies. Results VEGF-D and VEGF-C were detected in 67.0% and 50.5% of gastric cancers, respectively. Healthy gastric mucosa was negative for VEGF-C and in 12.5% positive for VEGF-D. Presence of VEGF-D (P = .005) or VEGF-C (P = .006) was correlated with lymphatic metastases and decreased survival (VEGF-D, P < .05; VEGF-C, P < .05). VEGFR-3 was correlated with reduced carcinoma-specific survival (P < .05), and Cox multivariate regression analysis qualified VEGF-D and VEGFR-3, but not VEGF-C, as independent prognostic parameters. In lymph node–positive gastric cancers, presence of VEGF-D/VEGFR-3 was associated with poor survival, whereas absence of VEGF-D/VEGFR-3 defined a subgroup of patients with clearly favorable prognosis. Conclusion VEGF-D and VEGFR-3 are novel independent prognostic marker molecules aiding to identify patients with poor prognosis after curative resection of gastric adenocarcinomas. Combined analysis of the VEGF-C/VEGF-D/VEGFR-3 system can be useful to identify patients with unfavorable clinical outcome and thereby may help to refine therapeutic decisions in gastric cancer.

Routine determination of the nodal status in colon cancer is strongly dependent on the individual quality and technique of histopathological assessment and surgical lymph node dissection. We evaluated whether sentinel lymph node biopsy (SLNB) could contribute to an improvement in staging. At least one SLN (median n=2) was detected (detection rate 84%) in each of 38 of 45 patients with primary colon cancer. Ten of these 38 were found to have lymph node metastases by HE staining (26%), six of them in the SLN. Nine of the 28 patients that were initially nodal-negative by HE revealed one micrometastasis and eight cases of isolated tumor cells by immunohistochemical (IHC) staining (32% upstaging response). Including the IHC-positive cases, 19 of the 38 patients were nodal-positive (50%), 15 of them with tumor-infiltrated SLN (overall sensitivity of SLNB 79%). Using the dye method, SLNB is clinically practicable and leads in the majority of the patients to the detection of SLN. The selective, intensified histopathological assessment of SLN identifies small tumor cell deposits in a relevant percentage of patients with little and clinically practicable effort.

We evaluated the feasibility of the sentinel lymph node technique to refine staging and potentially individualize therapy for anal cancer. Seventeen patients with cancer of the anal canal underwent peritumoral injection of 99mTc-colloid, followed 17 hours later by lymphoscintigraphy. A selective lymph node biopsy (SLNB) was attempted in 12 of 13 cases with scintigraphically detected SLNs. Lymph node metastases were present in 5 of 12 cases (42%); in 2 of these 5 cases, micrometastases were detected only by immunohistochemical staining. Hence, SLNB refines the diagnostic workup for anal cancer and provides an accurate basis for individualized therapy.

Background Oesophageal anastomotic leakage is associated with considerable morbidity and mortality. The aim of the present study was to assess the feasibility of using temporary self-expanding plastic stents to treat postoperative oesophageal leaks. Methods Patients with anastomotic leakage after abdominothoracic oesophagectomy treated by endoscopic insertion of self-expanding plastic stents between 2001 and 2007 were studied. Clinical outcomes were analysed, including healing of the leak, morbidity and mortality. Results Stents were inserted successfully in all 22 patients without procedure-related complications. Ten patients also required computed tomography-guided drainage because surgical drains had been removed. Non-ventilated patients received oral nutrition a mean of 4 days after stent placement. Combined treatment with stenting and drainage resulted in resolution of the leak in 21 of 22 patients. The mean healing time (time to stent removal) was 23 days. Stent migration occurred in five of 22 patients, but endoscopic reintervention with placement of a new stent was successful in all patients. Repeat thoracotomy with intraoperative stent placement was necessary in one patient with an oesophagocolonic anastomosis. One patient died in hospital. Conclusion In combination with effective drainage, self-expanding plastic stents are an option for the treatment of oesophageal anastomotic leaks, and may reduce leak-related morbidity and mortality.

Vascular endothelial growth factors VEGF-A, VEGF-C and VEGF-D are considered to be potentially angiogenetic and lymphangiogenetic. "Minimal residual disease" is responsible for cancer progression and recurrence. In this study, we investigated the relation between expressions of VEGF-A, VEGF-C and VEGF-D in gastric cancer tissue and the presence of tumour cells in bone marrow.A total of 50 resected primary gastric adenocarcinomas, 44 non-cancerous gastric mucosa and 36 lymph node metastases were analyzed by immunohistochemistry for VEGF-A, VEGF-C and VEGF-D. The specimens used were drawn from a previous study cohort, where the presence of ITC in bone marrow was confirmed with immunohistochemical assay with cytokeratin (CK)-18.The levels of expression of VEGF-A, VEGF-C and VEGF-D were highest in tumour (p0.001), and the level in lymph node metastases was significantly higher (p0.01) than in mucosa. The expression of VEGF-A was correlated significantly with venous tumour invasion (p0.05) and the presence of tumour cells in bone marrow (p0.05). Tumours expressing high levels of VEGF-D showed significantly advanced stages of tumour infiltration (p0.05) and lymph node metastasis (p0.01).VEGF-A is a significant marker for the presence of tumour cells in the bone marrow of gastric cancer patients. Our results confirm VEGF-D as a predictor for the lymphatic spread of tumour cells. Therefore, the route of metastatic spread of gastric cancer could be determined, at least in part, by the profile of VEGF family members expressed in the primary tumour of gastric cancer patients.

Background Gastric cancer frequently spreads to the peritoneal cavity. Whether laparoscopy is useful in planning therapy remains controversial. The aim of this study was to investigate the value of laparoscopy and to develop a therapeutic algorithm. Methods Six hundred and sixty consecutive patients with gastric cancer were included in this prospective observational study. The sensitivity of abdominal ultrasonography, computed tomography (CT) and laparoscopy for detecting peritoneal carcinomatosis was compared. The lesions were biopsied and classified as P1, P2 or P3 according to the recommendations of the Japanese Research Society for Gastric Cancer. Prognosis was determined according to the stage of peritoneal carcinomatosis and therapeutic procedure adopted. Results One hundred and ten (16·7 per cent) of 660 patients presented with synchronous peritoneal carcinomatosis. The sensitivity for detecting peritoneal carcinomatosis was 85 per cent for laparoscopy compared with 19 per cent for ultrasonography and 28 per cent for CT. Patients with P3 disease did not benefit from additional surgery compared with chemotherapy alone. Those with P1 carcinomatosis had improved survival rates after complete resection followed by chemotherapy. Conclusion Laparoscopy improves the detection and classification of peritoneal carcinomatosis, and offers patients with gastric cancer a more individualized and effective therapy.

The clinical impact of sentinel lymph node biopsy (SLNB) in gastric cancer is controversial. We performed a prospective trial to compare different methods: radiocolloid method (RM), dye method (DM), and both methods simultaneously (dual method, or DUM) for reliability and therapeutic consequences. RM and DM were applied in 35 gastric cancer patients. After endoscopic peritumoral injection of 99mTc-colloid and Patent Blue V, the positions of all blue sentinel lymph nodes (SLNs) were recorded, and the SLNs microscopically examined by hematoxylin and eosin, step sections, and immunohistochemistry. RM, DM, and DUM identified the SLNs in 34 (97%) of 35 patients. The sensitivity for the prediction of positive lymph node status for RM was 22 (92%) of 24, for DM 16 (66%) of 24, and for DUM 22 (92%) of 24. In 7 of 17 (RM), 5 of 15 (DM), and 7 of 17 (DUM) patients classified as N0 by routine hematoxylin and eosin staining, micrometastases or isolated tumor cells were found in the SLN (upstaging) after focused examination. If only a limited lymph node dissection of the SLN basins would have been performed in patients, residual lymph node metastases were left in 9 of 24 (RM), in 7 of 34 (DM), and in 5 of 24 (DUM) of patients with node-positive disease. Use of RM was superior. DUM did not further increase the sensitivity. A limited lymph node dissection—i.e., lymphatic basin in patients with SLN-positive disease—is associated with a high risk of residual metastases. Patients with negative SLNs may be selected for a limited surgical procedure if they meet certain criteria.

About 20% to 30% of colon cancer patients classified as node negative by routine hematoxylin-eosin (HE) staining are found to have micrometastases (MM) or isolated tumor cells (ITC) in sentinel lymph nodes (SLNs) if analyzed by step sections and immunohistochemistry (IHC). Whether SLNs are in this respect representative for all lymph nodes was addressed in this study. SLNs were identified using the intraoperative blue dye detection technique. If all lymph nodes (SLNs and non-SLNs) of a patient were negative by routine HE staining, they were step-sectioned and analyzed by IHC using pancytokeratin antibodies. We identified at least one SLN in 47 of the 55 patients (85%) and examined a median of 26 lymph nodes per patient (range 10-59). By routine HE staining, 14 of the 47 patients showed lymph node metastases (30%); the remaining 33 were classified as node-negative. In this group (33 patients), 1011 lymph nodes were analyzed by step sections and IHC: 14 of 70 SLNs. (20%) but only 37 of 941 non-SLNs (4%) had MM/ITC (p0.001). Furthermore, 13 of the 33 HE-negative patients were found to have MM/ITC (39%). In 11 of the 13 patients, MM/ITC were identified in both SLNs and non-SLNs in 1 patient in the SLN only, and in 1 patient in a non-SLN only (sensitivity for the identification of MM/ITC: 92%; negative predictive value: 95%). The SLN biopsy is a valid tool to detect, as well as exclude, the presence of MM/ITC in colon cancer patients. Our results may be of prognostic relevance and influence patient stratification for adjuvant therapy trials.

Aims The extent of lymph node dissection in gastric cancer remains controversial. The Maruyama computer model and the sentinel lymph node biopsy (SLNB) are compared for their value to predict the nodal status and lead to stage-adapted surgery. Methods Thirty four patients with stage I–IV gastric cancer underwent both staging procedures. For SLNB, 15 patients underwent endoscopic, peri-tumoural injection of 99m Tc-colloid, and 19 patients were injected of Patent blue V ® . All ‘hot’ or blue sentinel lymph nodes (SLNs) were separately excised and histopathologically assessed. If the SLN was negative after routine staining by H&E, it was processed completely and reanalysed after immunohistochemistry. Results At least, one SLN was detected by means of SLNB in 33/34 of the patients. The sensitivity to identify a positive nodal status was 22/33 and the specificity/positive predictive value was 10/10 and 22/22. Additional micrometastases or isolated tumour cells in the SLN led to ‘upstaging’ of 5/15, initially classified as nodal negative by H&E-staining. Using the Maruyama computer model, a sensitivity of 22/23 for the correct prediction of the lymph node involvement was associated with a specificity of 2/10 and a positive predictive value of 22/30. Conclusions The clinical impact of the Maruyama computer model is limited due to low specificity and a low positive predictive value, rendering the method less useful as an indicator for individualised surgery.

Background The value of sentinel node biopsy in visceral cancers is uncertain. We evaluated the feasibility and utility of radiocolloid lymphatic mapping and selective lymph node sampling in patients with rectal cancer. Methods Forty-eight patients with rectal cancer were investigated. Thirty-seven patients had already undergone preoperative radiochemotherapy for locally advanced tumors. Eleven patients underwent primary surgery. An endoscopic injection of 1 mL technetium 99m–sulfur-colloid into the peritumoral submucosa was performed 15 to 17 hours before surgery. Ex vivo identification of the nuclide-enriched “sentinel lymph nodes” (SLNs) was performed using a hand-held γ-probe. The selected SLNs were then carefully and systematically examined using serial sections and immunohistochemistry. Results One or more SLNs were found in 46 of the 48 patients. The SLN detection rate was 96%. Sixteen of the 48 patients had lymph node metastases (35%). In 7 of the 16 patients, the SLNs correctly represented the nodal status. In 9 of the 16 patients, the SLN was tumor-free whereas non-SLN harbored metastases. This result represents a sensitivity of only 44%, and a false-negative rate of 56%. Further analysis showed that the method correctly predicted the nodal status only in the small subgroup of 5 patients with early cancer without preoperative radiation. In 4 patients, juxtaregional lymph nodes were excised on the basis of intraoperative radiocolloid detection, leading to upward staging in 1 patient. Conclusions Sentinel lymph node biopsy using the radiocolloid technique with ex vivo lymph node identification shows a relatively high detection rate; however, the sensitivity in patients with locally advanced/irradiated rectal cancer is low. Nevertheless, the detection of juxtaregional metastases can improve staging in some patients. Further studies should focus on patients with early rectal cancers where the data were more promising.

Aberrant glycosylation of membrane components due to specific alterations of glycosyltransferase activity is a common feature of carcinoma cells and is usually associated with invasion and metastasis. In a prospective study, the enzyme activity of the sialyltransferases ST6GAL-I and ST3GAL-III was studied in gastric cancer and normal mucosa in 55 patients by a radiometric assay. Cellular localization of sialyltransferase ST6GAL-I mRNA expression was studied by in situ hybridization. Sialyltransferase ST6GAL-I mRNA expression was mainly localized to epithelial cells. ST6GAL-I enzyme activity was enhanced within the tumor tissue. Significant correlations were found between the presence of signet ring cells and enhanced ST6GAL-I activity in the tumor tissue (p = 0.047) or in the mucosa (p = 0.024), and between signet ring cells and ST3GAL-III activity in the mucosa (p < 0.001). Multivariate Cox analysis demonstrated that only lymph node metastases (p = 0.044) had a significant influence on tumor-related survival. ST3GAL-III and ST6GAL-I activity showed no independent prognostic relevance in multivariate analysis, but high levels of ST3GAL-III and ST6GAL-I in the tumor tissue correlated with secondary local tumor recurrence (p = 0.005; p = 0.012). Interestingly, also the nonmalignant and uninvolved mucosa of tumor patients was altered on the molecular level and in some cases showed enhanced sialyltransferase levels indicative of the alteration of glycosylation very early during tumorigenesis.

Background: The extent of standard lymph node dissection (D1, D2, or D3) in gastric cancer patients is still controversial. Several prospective European trials attained contradictory results. A generally increased body mass index (BMI) of the European patients was assumed to be one of the major causes for postoperative morbidity. Methods: We evaluated the effect of BMI on the quality of routine D2 lymph node dissection and on postoperative morbidity in patients with gastric cancer who underwent a potentially curative total gastrectomy. A total of 199 consecutive gastric cancer patients who underwent a total gastrectomy and a routine D2 lymph node dissection between 1992 and 2001 were included in the study. According to BMI, they were assigned to three groups: group A, with BMI 30 kg/m2 (obesity). Parameters such as complete histopathological staging, intraoperative blood loss, length of operation, and surgical and nonsurgical morbidity were recorded and correlated within the different groups. Results: No significant differences were found with regard to the number of examined lymph nodes, blood loss, length of operation, surgical complications, or length of stay in the intensive care unit. Conclusions:In contrast to comparable Japanese studies, our analysis reveals that even for overweight patients, a standard D2 lymph node dissection is justified without significantly increased morbidity.

Die axillare Lymphknotendissektion stellt ein Standardverfahren in der chirurgischen Behandlung des primaren Mammakarzinoms dar. Sie ist gleichsam Staging und Therapie. Bei negativem Lymphknotenstatus ist dies jedoch eine Ubertherapie und rechtfertigt nicht die mit dem Eingriff in 10-30% verbundene Morbiditat. Durch Farbstoff- oder Nucleidmarkierung kann der im Hinblick auf eine mogliche lymphogene Metastasierung relevante Lymphknoten (SN) detektiert werden. Durch gezielte Exploration und histologische Untersuchung kann mit einer 97%igen Vorhersagegenauigkeit eine Aussage uber den axillaren Lymphknotenbefall getroffen werden. Bei Patienten mit nicht tumorbefallenem SN ware damit vom Prinzip her die Moglichkeit gegeben, auf eine konventionelle Axilladissektion zu verzichten. Inwieweit dies generell indiziert ist bzw. welche zusatzlichen Kriterien beachtet werden mussen, wird derzeit in prospektiven Studien untersucht.

The aim of this study was to develop a technique for three-dimensional endoscopic ultrasound of the esophagus based on standard ultrasonic images.Endoscopic ultrasound was performed in five esophageal cancer patients using a high-resolution miniprobe (360 degrees, 12.5 MHz). For acquisition of three-dimensional data sets, the miniprobe was attached to a stepping motor that enabled ECG-triggered withdrawal of the transducer. Three-dimensional images were reconstructed from serial transverse sections on a PC-based 3D work station.Twelve volume scans were obtained in five patients with esophageal cancer. The system enabled the acquisition of accurate three-dimensional ultrasound data within 30-50 s. Computed image processing allowed us to display the data in transverse, longitudinal, and oblique sections, or as a 3D reconstruction. Three-dimensional imaging provided accurate visualization of the tumor and surrounding structures in all cases. The tumor stage was determined correctly in four of five patients. Longitudinal scan planes and 3D views improved the assessment of longitudinal tumor infiltration and the spatial relation of the tumor to relevant mediastinal structures.This study shows that three-dimensional endoscopic ultrasound of the esophagus is technically feasible. The technique allows the assessment of local tumor spread in previously unattainable scan planes and 3D views. This promising preliminary experience should encourage further exploration of this method.

With a 5-year survival rate of more than 90%, early stage gastric carcinoma has a far better prognosis than the more advanced stages. However, this survival advantage is currently achieved at the cost of subtotal or total gastrectomy. It is, thus, understandable that physicians are searching for ways to reach the same result by limited approaches. With this goal in mind, several endoscopic and laparoscopic procedures have been developed. For example, endoscopic mucosa resection is increasingly employed, especially in early cancers of limited extension [1]. Also, total or partial gastrectomies with limited lymphadenectomy (D0 or D1) are performed by minimal access surgery [2, 3]. Profound experience with these methods is a prerogative for their successful application. However, the indication for limited surgery depends on tumor localization and lymphatic involvement, too. The article by Skoropad et al. [4] in this issue of O NKOLOGIE confirms the well-known fact that nodal involvement impairs the prognosis of early gastric cancer, even after radical surgery. As a consequence, a limited approach is especially questionable in the presence of nodal metastases. The probability of lymphatic involvement in early gastric carcinoma is approximately 10‐12%. It is lower (4%) in mucosal carcinomas and much higher (up to 23%) in submucosal tumors. Metastases are not confined to the D1 compartment but can also be found in the D2 compartment [5]. Therefore, an exact lymphatic staging is a prerequisite for limited surgery in early gastric cancer. Three possible approaches exist: 1. Prediction of lymphatic state on the basis of the characteristics of the primary tumor. These comprise size, appearance (elevated, depressed, ulcerated etc.), histological differentiation (Lauren classification), and depth of invasion (mucosa/submucosa). Currently, molecular markers (e.g. VEGF) in biopsy specimens are tested as predictors for nodal involvement. However, results are still contradictory. Gene chip analyses of tumor tissues will eventually give more conclusive data in the future.

4510 Background: Combined pre- and postoperative chemotherapy improves overall survival in operable gastric cancer, although postoperative treatment is not feasible in half of the patients. We conducted a randomized phase III trial with thorough attention to preoperative staging and to the extent of surgical resection to assess the value of neoadjuvant chemotherapy (CTx). Methods: Patients with locally advanced adenocarcinoma of the stomach and cardia were randomized between primary surgery or two 48-day cycles of weekly folinic acid 500 mg/m2/2h, 5-FU 2,000 mg/m2/24h plus biweekly cisplatin 50 mg/m2/1h followed by surgery. The study was designed to detect an improvement in median survival from 17 months with surgery to 24 months with CTx plus surgery (HR=0.708, power of 80%, type I error of 4% to allow for an interim analysis). It was planned to randomize 360 patients in order to observe the 262 deaths required for the final analysis. Results: From 7/99 to 2/04, 144 patients were randomized (72:72) with comparable baseline characteristics. Median follow-up is 4.4 years. Based on 67 deaths, overall survival between the two arms did not differ (HR=0.84; 95% CI: 0.52 to 1.35; p=0.466). Median survival exceeded 36 months in both arms. Due to low accrual, this trial was stopped early. The unexpected long median survival in the surgery arm would have made the primary objective difficult to reach anyway. Based on 77 events, difference in time to progression was borderline significant (HR=0.66; 95% CI, 0.42–1.03; p=0.065). Response rate to CTx was 35.2% (95% CI: 23.7%-45.7%). The R0-resection rate was 81.9 % after CTx as compared to 66.7% with surgery alone (P=0.036). There were no major differences in intra- or postoperative complications. Conclusions: This prematurely closed trial showed a significantly increased rate of R0 resections after CTx although it could not demonstrate a survival benefit. The outcome after a radical surgical procedure alone with extended lymphadenectomy was better than expected. No significant financial relationships to disclose.