Gastric cancer: which patients benefit from systematic lymphadenectomy?

AIMS: The purpose of this study was to evaluate the value of systematic lymphadenectomy (SLA) in curative resected gastric cancer patients with respect to long-term survival, peri-operative morbidity and mortality. METHODS: We reviewed our prospectively gathered database of 309 resected gastric cancer patients and analysed the outcome of 185 R0-resected patients (60%) with respect to peri-operative morbidity, mortality and long-term survival by comparing 81 patients resected with SLA (D2-group) versus 104 patients resected without SLA (D1-group). RESULTS: Overall 5-year survival rates of R0-resected patients (n = 173; exclusion of peri-operative mortality) amounted to 49% and did not differ significantly between D2- and D1-groups (53% vs 47%); P=0.344). Nevertheless, subgroups of patients taking a benefit from SLA could be defined. Gastric cancer patients without LN metastases (pTx pN0; n=78) and patients with LN metastases only in perigastric lymph nodes (pTx pN1; n=34) showed a significantly better long-term prognosis when SLA was performed (84% vs 51%; P=0.001). Regarding peri-operative morbidity (38% vs 39%) and mortality (6% in each case) we could not find any differences between the D2- and D1-groups. CONCLUSIONS: We conclude that SLA is able to improve long-term survival for some tumour stages. Therefore SLA should be recommended as a standard procedure in all gastric cancer patients resected with curative intention.

Characterization of two newly established cell lines derived from squamous cell carcinomas of the oesophagus.

This study describes characteristics of two newly established cell lines (OSC-1 and OSC-2), derived from two oesophageal squamous cell carcinomas. Morphologically, OSC-1 cells and OSC-2 cells grew in epithelial cobblestone patterns with cells piling up to 4 cells. Ultrastructurally, both cell lines showed formation of desmosomes; however, tonofilaments were only formed by OSC-2 cells. Immunohistochemical investigations revealed coexpression of vimentin and cytokeratin in OSC-1 cells and OSC-2 cells. A cytokeratin subtype typical for mature squamous epithelia (cytokeratin 13) was expressed only in OSC-2 cells. OSC-1 cells showed tumour formation in nude mice, whereas OSC-2 cells did not. Cytogenetic analysis revealed that OSC-1 cells had a hyperdiploid karyotype and OSC-2 cells had a near-triploid karyotype. In both cell lines, the formation of multicellular spheroids could be induced. In conclusion, in comparison with OSC-2 cells the OSC-1 cells were characterized by a poorer degree of differentiation and by a more aggressive growth behaviour in vivo.

[Early stomach carcinoma--pathologic-anatomic findings and prognosis]. / Das Magenfrühcarcinom--Pathologisch-anatomische Befunde und Prognose.

BACKGROUND: The therapy for early gastric cancer (endoscopy, gastric resection, D1/2 dissection) is controversial. MATERIALS AND METHODS: In a retrospective study (4/86-12/95) we analyzed the prognosis of 57 early gastric cancer patients with respect to pathological findings and surgical therapy. RESULTS: The R0 resection rate was 100%. In 7% multifocal tumor growth was seen. The 5-year survival rate was 70%. LN-metastases were found in 12% of all cases, more often in pT1b than in pT1 a tumors (17 vs 9%) and more often in large carcinomas than in small carcinomas (> 1000 mm2: 27%; < 300 mm2: 0%). Long-term survival was significantly better in pN0 patients than in patients with LN metastasis (P = 0.020). CONCLUSION: Prognosis of early gastric cancer after curative resection is good.

[Adenocarcinoma of the esophagogastric junction: prognostic factors and results of primary surgery]. / Ergebnisse der primär chirurgischen Therapie beim Adenokarzinom des ösophagogastralen Ubergangs.

INTRODUCTION: The incidence of adenocarcinoma of the esophagogastric junction (AEG) is increasing worldwide, and classification systems and resection procedures are being controversially discussed. METHODS AND PATIENTS: We report on 225 AEG patients undergoing primary resection in our unit (1986-2000) with a special focus on perioperative morbidity, mortality, and long-term prognosis under consideration of the AEG type (Siewert classification) and operative procedure performed (subtotal esophagectomy with proximal gastric resection in AEG I, total gastrectomy with distal esophageal resection in AEG II and AEG III). RESULTS: Types I, II, and III carcinomas were found in 32%, 42%, and 26% of the patients, respectively, with R(0) resections in 65%, 69%, and 51% ( P=0.039). The overall 5-year survival rates were 29%, 31%, and 14% ( P=0.068), respectively; in R(0)-resected patients, they were 40%, 41%, and 27% ( P=0.771). In univariate analysis, the TNM classification ( P<0.001), R classification ( P<0.001), and tumor stage ( P<0.001) were relevant prognostic factors. In multivariate analysis, only the R classification ( P=0.003), LN ratio ( P=0.012), and N stage ( P=0.027) were independent prognostic factors. In 35 of 177 patients resected with curative intent, R(0) resections could not be achieved, mainly because of residual tumor in the circumferential plane (22/35=63%). Only in 37% of cases (13/35) was the R(1) situation due to exclusive positive oral or aboral resection margins. Therefore, in only 7% of all patients resected with curative intent (13/177) did the question arise of whether the R(1) resection could have been avoided by a different surgical approach. Surgical, pulmonary, and cardiac complications were found in 33%, 26%, and 10%, respectively. The mortality within 30 days was 4%. CONCLUSIONS: Failure of R(0) resection in patients treated with curative intent is mostly caused by residual tumor in the circumferential plane. Therefore, different surgical approaches with varying oral and aboral resection margins are of minor importance for reducing the frequency of R(1) resections. Downstaging of tumors by neoadjuvant treatment may increase the R(0) resection rate.

[Endoscopic ultrasound in routine clinical practice for staging adenocarcinomas of the stomach and distal esophagus]. / Endosonographie in der klinischen Routine beim Adenokarzinom des distalen Osophagus und Magens. Eine ernüchternde Bilanz.

PROBLEM: Endoscopic ultrasound (EUS) is an important diagnostic tool for determining the best therapeutic strategy (primary resection, neoadjuvant therapy or palliation only) to offer esophageal or gastric cancer patients. PATIENTS AND METHODS: In the present study (1992-2001),we evaluated the accuracy of EUS in adenocarcinomas of the distal esophagus and stomach and compared our results with pathologists findings as the gold standard. RESULTS: Of the 222 patients studied, the precise examination of 11% EUS was not completely possible due to severe tumor stenosis. The accuracy of EUS with respect to T, N+/- and TN+/- amounted to 51%, 65% and 34% in 131 patients with adenocarcinomas of the esophageal gastric junction and to 50%, 66% and 37% in 91 patients with adenocarcinomas located in the fundus, corpus or antrum of the stomach respectively. With respect to T-stage, the overstaging of tumors was more common than understaging, especially in pT2b-carcinomas. The subgroup analysis of the 131 EGJ adenocarcinoma patients showed that the results obtained by EUS were slightly better in type I (distal esophageal cancer) than in type II and III cardia carcinomas (proximal gastric cancer).When comparing two observation periods (1992-1996 and 1997-2001), the accuracy of endoscopic ultrasound staging was very similar in both periods for T-category (51% vs 49%) and N-category (63% vs 64%) as well as for combined TN-staging (36% vs 35%) respectively. CONCLUSIONS: In clinical routine examinations of adenocarcinomas of the stomach and the distal esophagus, the accuracy of EUS is not as good as the excellent results in the past--mostly obtained under study conditions--may suggest.

Multivisceral surgery in advanced gastric carcinoma.

From April 1986 to June 1994 a total of 284 patients with gastric carcinoma were admitted to the authors' department. Mainly advanced tumour stages were seen: stage I = = 23%, II = 13%, III = 22% and IV = 42%. In 256 tumour resections (resection rate = 90%) multivisceral surgery (mvs) was necessary in 146 patients (mvs = 57%). Long-term survival of stage IV gastric cancer patients cannot be prolonged by mvs, and RD-resection can be achieved in few patients (9/120 = 7.5% in stage IV). Perioperative morbidity, postoperative complications and the mean postoperative hospital stay were increased after extensive surgery. Major complications were anastomotic leakage, local infections and pulmonary diseases. Even when resection seems to be an acceptable palliation for stage IV gastric cancer patients, mvs in only justified where RD-resection seems achievable.

[Utilization of multimodal therapy concepts in stomach carcinoma in Germany]. / Anwendungspraxis multimodaler Therapiekonzepte beim Magenkarzinom in Deutschland.

INTRODUCTION: In view of disappointing results after surgery alone multimodal therapeutic regimes are used to improve long-term prognosis in locally advanced gastric carcinomas. In presence of many reports about encouraging results ("down staging", improved R0-resection rates) but simultaneously missing evidence of efficiency of neoadjuvant therapies in respect to long-term survival (large randomized multicenter trials do not exist until today) and the herewith related uncertainties, we started an inquiry among many surgical units with the intention to evaluate the clinical practice of multimodal treatment for gastric cancer patients in Germany today. METHODS: In a questionnaire (3/99) we asked among 97 surgical units (41 university hospitals, 56 big community hospitals) in Germany for the management of gastric cancer patients with special interest to practice and state of adjuvant and neoadjuvant therapeutic strategies. Further we analyzed all resected gastric cancer patients (1986-1995) without neoadjuvant treatment in advanced stage of disease (pT3/4NxMx; stage III/IV (UICC'92) in respect to R0-resection rate and long-term prognosis (Kaplan-Meier). RESULTS: Overall feedback amounted to 78% (76/97) and was higher in university hospitals (90%) than in big community hospitals (70%). Today, neoadjuvant therapies are of more interest than adjuvant therapeutic regimes. But also neoadjuvant therapy is only used in 32% as a rule (in 16% with, in 16% without study conditions). 25% of all surgical units do not employ any neoadjuvant therapy in locally advanced gastric cancer until today. In all other surgical units neoadjuvant treatment is performed more individually and sporadically (43%) only in some patients. Neoadjuvant therapies are practiced by haematooncologists in 50%, gastroenterologists in 32% and surgeons in 27%. The predominant neoadjuvant therapeutic strategy is chemotherapy alone (84%). Many surgical units in Germany are interested to participate in a multicenter trial with more interest in neoadjuvant than adjuvant therapy. 185 of 309 resected gastric cancer patients (60%) were classified as stage IIIa, stage IIIb or stage IV patients. R0-resection rate of these advanced gastric cancer patients amounted to 37%; only 24% of them survived 5 years or more. CONCLUSIONS: Considering the missing evidence that multimodal therapies are able to prolong long-term survival in advanced gastric cancer patients, its use without study conditions is questionable. Conclusions, taken from data of clinical trials regarding carcinomas of the esophagus and esophagealgastric junction, are inconsistent in respect to long-term prognosis and results are not transferable to gastric carcinomas. A prospective randomized multicenter trial in advanced gastric cancer patients is of great importance. Following our data, in Germany a high readiness to participate in the forthcoming EORTC-study is present.

[The site and extent of arteriosclerosis. Comparative planimetric studies of the left descending coronary artery, internal carotid artery, superficial femoral artery and abdominal aorta in 104 cadavers]. / Lokalisation und Ausdehnung der Arteriosklerose. Vergleichende planimetrische Untersuchungen an der linken absteigenden Kranzarterie, den Aa. carotides internae, den Aa. femorales superficiales und der Bauchaorta von 102 Verstorbenen.

BACKGROUND: Arteriosclerosis is generally considered to be a generalized disease, involving different vascular regions to approximately the same extent. PATIENTS AND METHODS: In order to assess the extent of ateriosclerosis quantitatively, all arteriosclerotic lesions and additionally the complicated (calcified, ulcerated, thrombosed) arteriosclerotic lesions of the abdominal aorta, the superficial femoral arteries, the left descending coronary artery and the internal carotid arteries were measured by planimetry in 102 autopsies (64 male, 38 female; mean age: 62 +/- 16 years). RESULTS: Arteriosclerosis increased with age. The overall extent of arteriosclerotic lesions of each artery was classified to one of the following 4 degrees of intimal involvement (0-25, 26-50, 51-75%, 76-100%). When comparing the 4 different vascular regions of each patient we found maximal deviations by 1 degree in 34%, by 2 degrees in 41% and by 3 degrees in 20%. In only 5% of the patients studied were all arteriosclerotic lesions of the same degree. In order to analyze the complicated plaques 7 degrees were used (intimal involvement: 0, 1-10, 11-20, 21-30, 31-40, 41-50% and > 50%). In 14 patients we found no complicated plaques. The remaining 88 showed complicated lesions in at least 1 vascular region. Deviations by 1 degree were found in 22%, by 2 degrees in 32%, and by 3 or more degrees in 46%. In the paired arteries (carotid, femoral) there were no significant differences comparing the mean values of the extent of arteriosclerotic lesions on the right and left side. In many cases, however, remarkable intraindividual differences occurred. Patients with main risk factors usually had more pronounced arteriosclerotic lesions than those without. In patients who died from coronary artery disease the extent of arteriosclerotic lesions was also usually larger in the other vascular regions as compared to those patients who died from other reasons. Comparing postmortem and intravital extent of arteriosclerotic lesions some peculiarities of postmortem specimens should be considered. CONCLUSIONS: A uniform involvement of all vascular regions by arteriosclerosis occurs only rarely. Considerable intraindividual differences are the rule and a severe, generalized uniform affection is an exception. This, however, does not exclude in patients with severe arteriosclerosis of one region that a larger involvement of other vascular regions may also occur, as this was found for patients with severe arteriosclerosis in coronary arteries. Regarding the extent of arteriosclerosis there are artery- and additional localization-specific features.

[Prognostic factors in curative resection of stomach carcinoma. A uni- and multivariate analysis]. / Prognostische Faktoren beim kurativ resezierten Magenkarzinom. Eine uni- und multivariate Analyse.

The TNM system, including tumor infiltration (T category), lymph node infiltration (N category) and metastasis (M category), is a well-established system of prognostic factors. To evaluate the prognostic importance of patient characteristics and tumor parameters 5 clinical and 13 pathological factors were analyzed. Data on 200 consecutive patients with histologically verified stomach cancer were prospectively recorded using a standardized form. In the subgroup with curative resection (R0, n = 108) a uni- and multivariate analysis was performed with respect to 5-year survival. In the univariate analysis statistical significance was demonstrated for the following factors: tumor size, tumor localization, T category, N category, number of infiltrated lymph nodes infiltrated, lymph node compartments, tumor stage, lymph node ratio: infiltrated/inspected. Multivariate analysis, taking into consideration the interaction between prognostic factors, revealed only two factors as statistically significant: number of infiltrated lymph nodes and tumor size. Our results and those in the literature indicate that the infiltration of lymph nodes is the most relevant prognostic factor. In addition to the TNM system the number of infiltrated lymph nodes seems to be of prognostic importance.