[Primary gastric lymphoma]. / Primäre Magenlymphome.

Primary gastric lymphoma derives from a secondary MALT system developing after a reaction of the immune system, e.g. following chronic gastritis induced by Helicobacter pylori. Morphologically, follicular hyperplasia is found in the gastric mucosa. The pathoetiologic model confirms the transformation of a malignant lymphoma from low grade to high grade by demonstrating increasing autonomous proliferation and, finally, uncontrolled dissemination. Modern diagnostic tools are essential for staging and planning an adequate therapeutic strategy. At present, the therapeutic strategies regarding primary lymphoma are under discussion. Nevertheless, the consensus of international medical and surgical associations still recommends surgical therapy with curative intention for low-grade malignant lymphomas staged I 2-II 2. In cases of high-grade malignant lymphoma, conservative therapy is supposed to be similarly successful. The recent success of noninvasive therapeutic concepts seems to justify the application of triple eradication medication in case of Hp infection as well as radio- and chemotherapy in low- and high-grade malignant lymphomas. However, in cases of nonremission or therapy-associated complications such as uncontrollable bleeding or tumor perforation, surgery is the only therapeutic option. Regarding the oncological aspects of lymphoma growth, surgery should then be performed in order to achieve R0 resection.

[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.

Laser-induced interstitial thermotherapy of liver metastases in an interventional 0.5 Tesla MRI system: technique and first clinical experiences.

Laser-induced interstitial thermotherapy (LITT) surveyed by magnetic resonance imaging (MRI) has been shown to be effective in various applications. The laser treatment of colorectal liver metastases usually requires a separate device (e.g., ultrasound or CT) to position the laser applicator. In this study, we used an interventional 0.5 T MRI system, allowing both the navigation to the target tissue and on-line thermometry. Laser irradiation was performed using a near-infrared laser source combined with a cooled laser light guide. We treated 20 patients exhibiting a total of 58 colorectal liver metastases. Clinically relevant complications did not occur. No residual tumor was observed after laser irradiation in all metastases with a diameter below 2 cm. Metastases with a mean diameter between 2 and 3 cm demonstrated total necrosis in 71%, while in larger tumors this proportion decreased to 46% (diameter, 3-4 cm) and 30% (diameter, >4 cm), respectively. We conclude that LITT, guided by the employed interventional MRI system, is feasible and safe. The results suggest a more aggressive treatment, especially for larger metastases. J. Magn. Reson. Imaging 2001;13:729-737.

Primary gastric B-cell lymphoma: results of a prospective multicenter study. The German-Austrian Gastrointestinal Lymphoma Study Group.

BACKGROUND & AIMS: Appropriate management of primary gastric lymphoma is controversial. This prospective, multicenter study aimed to evaluate the accuracy of endoscopic biopsy diagnosis and clinical staging procedures and assess a treatment strategy based on Helicobacter pylori status and tumor stage and grade. METHODS: Of 266 patients with primary gastric B-cell lymphoma, 236 with stages EI (n = 151) or EII (n = 85) were included in an intention-to-treat analysis. Patients with H. pylori-positive stage EI low-grade lymphoma underwent eradication therapy. Nonresponders and patients with stage EII low-grade lymphoma underwent gastric surgery. Depending on the residual tumor status and predefined risk factors, patients received either radiotherapy or no further treatment. Patients with high-grade lymphoma underwent surgery and chemotherapy at stages EI/EII, complemented by radiation in case of incomplete resection. RESULTS: Endoscopic-bioptic typing and grading and clinical staging were accurate to 73% and 70%, respectively, based on the histopathology of resected specimens. The overall 2-year survival rates for low-grade lymphoma did not differ in the risk-adjusted treatment groups, ranging from 89% to 96%. In high-grade lymphoma, patients with complete resection or microscopic tumor residuals had significantly better survival rates (88% for EI and 83% for EII) than those with macroscopic tumor residues (53%; P < 0.001). CONCLUSIONS: There is a considerable need for improvement in clinical diagnostic and staging procedures, especially with a view toward nonsurgical treatment. With the exception of eradication therapy in H. pylori-positive low-grade lymphoma of stage EI and the subgroup of locally advanced high-grade lymphoma, resection remains the treatment of choice. However, because there is an increasing trend toward stomach-conserving therapy, a randomized trial comparing cure of disease and quality of life with surgical and conservative treatment is needed.

Helicobacter pylori in the upper gastrointestinal tract: medical or surgical treatment of gastric lymphoma?

The treatment of primary gastric lymphoma is controversial. The role of surgery has come to be questioned with increasing knowledge about the pathogenesis of gastric lymphoma and with new therapeutic approaches such as eradication of Helicobacter pylori. We review published clinical trials of primary gastric lymphoma, including preliminary results of our own prospective multicenter trial. The results of 7 trials of H. pylori eradication and 12 prospective therapeutic trials trial are discussed. On basis of these data it is concluded that surgery with intention of R0 resection is the treatment of choice in stages EI2 and EII1 of low-grade lymphoma. In high-grade lymphomas it is still unclear whether surgery or its primary combination with radio- or chemotherapy should be preferred. The eradication of H. pylori is a promising therapeutic approach for localized low-grade mucosa-associated lymphoid tissue lymphoma. A randomized trial is needed to clarify whether medical or surgical management of localized gastric lymphoma or a combination of two is the best treatment modality.

[Principles of surgical management of stromal tumor]. / Prinzipien des chirurgischen Vorgehens beim Stromatumor.

Gastrointestinal stromal tumors (GIST) have been regarded as rare tumor manifestations of the mesenchymal tissue fraction of the intestinal building principle; however, this tumor is now established as an independent tumor entity owing to independent immunohistochemical and ultrastructural characteristics. In spite of increasing awareness of their biological behavior and their molecular-biological basis, evaluating the grade of many of these tumors remains open, not only on a preoperative but also on a postoperative basis. Thus, how radical the surgical procedure must be is not standardized, as it is in carcinoma surgery. The literature available today is not sufficient to make a valid analytical assumption possible because of small numbers of cases and the heterogeneity of clinical and pathological variables. Therefore, recommendations concerning oncological-surgical radicality have at this time an empirical character. Owing to the rarity of the tumor, this will probably not change in the near future. Adjuvant therapeutical treatment of relevant effectiveness does not exist. Therefore, the radicalness of the operation is organ-specific, tumor-specific and based on tumor-biological criteria.

Simple data from history and physical examination help to exclude bowel obstruction and to avoid radiographic studies in patients with acute abdominal pain.

OBJECTIVE: To assess the value of plain abdominal radiographs and of data from the medical history and physical examination in the diagnosis of acute abdominal pain in general and of bowel obstruction in particular. DESIGN: Prospective study. SETTING: 4 university and 2 community hospitals, Germany. SUBJECTS: 1254 patients with acute abdominal pain lasting less than 7 days, and with no history of abdominal injury including surgery. INTERVENTIONS: Standardised and structured medical history and physical examination, study of results of plain abdominal radiographs. MAIN OUTCOME MEASURES: Positive predictive value and sensitivity of clinical variables and abdominal film with respect to the diagnosis at discharge. RESULTS: 48 patients (3.8%) had bowel obstruction. 704 patients (56.1%) had plain abdominal films taken at the time of initial presentation. 111 studies (15.8%) showed important findings leading to diagnosis or immediate treatment, 455 (64.7%) showed unimportant or no findings. In 138 (19.6%) results of films were not reported. 16 of 45 single variables were of help in diagnosing bowel obstruction. The six with the highest sensitivity were distended abdomen, increased bowel sounds, history of constipation, previous abdominal surgery, age over 50, and vomiting. If only patients presenting with any two of these symptoms had had radiographs taken, 300 (42.6%) could have been avoided without loss in diagnostic accuracy. CONCLUSION: A considerable number of plain abdominal films taken for patients with acute abdominal pain could be avoided by focusing on clinical variables relevant to the diagnosis of bowel obstruction.

[Stage-adapted radical principles in gastric carcinoma]. / Stadienadaptierte Radikalitätsprinzipien beim Magenkarzinom.

The aim of any surgical approach to gastric carcinoma should be a complete resection with no residual tumor left behind, that is, a R0-resection according to UICC. Complete tumor resection in this respect refers to the primary tumor as well as to the lymphatic drainage and requires an adequate safety margin. The indications for surgical therapy of gastric cancer and the choice of procedure should consequently be guided by the tumor stage. This requires accurate preoperative staging, which can today be achieved with endoscopic ultrasonography and surgical laparoscopy. Gastric carcinoma stage IA (mucosa carcinoma) can be cured by local excision. In patients with tumor Stages IB (submucosa carcinoma), II, and IIIA, lymph node metastases are common. Based on the available data, this group of patients benefits from radical resection and D2 lymph node dissection. The overall 5-year survival rate of 50% for the large number of patients undergoing gastric resection for cancer seems to demonstrate convincingly the value of extended lymphadenectomy. In patients with advanced gastric carcinoma, that is, tumor stages IIIB and IV, a complete tumor removal usually can not be achieved by surgical dissection. Neoadjuvant therapeutic modalities should consequently be assessed in these patients. Based on tumor location and growth pattern, a total gastrectomy is the procedure of choice in patients with middle and proximal third gastric cancer. A subtotal gastrectomy may be performed in patients with tumors of the distal third and "Laurens intestinal type" growth pattern. The distal site of the main lesion must be investigated carefully to ensure that incidental concomitant lesions are not overlooked. Depending on the individual tumor situation, the gastrectomy can be extended toward varying portions of the distal esophagus or the pancreas, preserving splenectomy and resection of the retroperitoneal lymph nodes. The high incidence of locoregional recurrences and distant metastases after curative surgery for gastric cancer calls for improved locoregional control and systemic adjuvant treatment.

[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.

[Current therapeutic strategy in primary intestinal non-Hodgkin's lymphoma]. / Aktuelle therapeutische Strategie des primären Intestinalen Non-Hodgkin-Lymphoms.

Of all surgical interventions of intestinal non-Hodgkin's lymphomas 58% (15 or 26 patients) are performed in an emergency situation. In 42% of cases, examination by ultrasonography, endosonography, intestinoscopy. Sellink's enema, thoracic, abdominal/pelvic CT and bone marrow puncture could determine the stage preoperatively. This could also be done by examining the regional and juxtaregional lymph nodes or performing a liver biopsy intraoperatively. Crucial for the therapy is in all cases the adequate staging even in emergency situations. Only special knowledge of the intestinal non-Hodgkin's lymphoma can lead to the necessary stage-adapted multimodal therapy--operation/irradiation/chemotherapy.

[Perspectives of virtual control of visceral surgery interventions in open MRI]. / Perspektiven der virtuellen Kontrolle viszeralchirurgischer Eingriffe im offenen MRT.

Since July 1997 we have operated on 23 patients with different visceral surgical diagnoses in an open-configured Magnetic Resonance System (MRI). Among them we found 7 patients with benign soft tissue tumors, 5 patients with anal fistulas, 1 patient with an abscess on the pelvic wall, 1 patient with a rectocele, 1 patient with an inoperable, restrictive oesophageal carcinoma, and 8 patients with metastatic lesions in the liver. In the last 8 patients we performed MRI-guided laser-induced interstitial thermotherapy, in one patient in an open development. We did not face any postoperative complications. The median duration of the intervention was 2 hours, pre- and postscans included. Our experiences show that it is possible to carry out visceral surgical interventions in the open-configured MRI. The main indications we see now are anal fistulas, soft tissue tumors and MRI-guided laser-induced interstitial thermotherapy of liver metastases.

[Therapy planning and surgical indications for Crohn-associated anal fistulas]. / Therapieplanung und Operationsindikation Crohn-assoziierter Analfisteln.

A prospective study conducted from April 1988 to April 1998 in 83 patients with anal fistulas associated Crohn's diseases registers and evaluates data regarding the type of fistula, the planned therapy, the operative procedure, and the therapy itself. The choice of the operation time with special regard to the type of fistula and the presence of proctitis as well as the interdisciplinary management in cooperation with the gastroenterologist and the strict observance of the operative procedure for the different types of fistulas enable individually defined surgical treatment of anal fistulas associated with Crohn's disease. It is important that the primary intervention be performed by a surgeon who is experienced in classifying the different types of fistulas because of the recurrence rate of 23% and the required interval between the first and final surgical intervention and so that patients are well informed.

[Perioperative therapy of HIV infections]. / Perioperative Therapie bei HIV-Infektionen.

A meta-analysis of the literature demonstrates high operation complication rates in HIV-positive patients. Own experience connected with a general hospital in San Francisco, University of California, indicates that such an analysis provides the surgeon with the possibility of optimizing the treatment of HIV-positive patients in the perioperative phase.

Expression of Bax, a pro-apoptotic member of the Bcl-2 family, in esophageal squamous cell carcinoma.

Samples of normal esophageal squamous epithelium (n = 10), severe squamous cell dysplasia (n = 22), carcinoma in situ (n = 15), invasive squamous cell carcinoma (n = 172), lymph-node metastasis (n = 21) and 2 permanent esophageal squamous cell carcinoma cell lines were analyzed immunohistochemically for Bax expression using a polyclonal anti-Bax antibody. Immunostaining was evaluated according to a score system (0-8 points) based on the percentage of positive tumor cells and the relative immunostaining intensity. Cytoplasmatic staining for Bax protein was found uniformly in all cell layers of the normal esophageal squamous epithelium. In contrast, a gradual loss of immunoreactivity for Bax was found in a fraction of pre-neoplastic and neoplastic lesions. Upon comparison of the amount of Bax expression between the different types of lesion, however, no significant differences were found between severe squamous cell dysplasias, carcinomas in situ, invasive carcinomas and lymph-node metastases. In both esophageal carcinoma cell lines, immunoreactivity for Bax was found and confirmed by means of Northern blot analysis. In invasive carcinomas, Bax immunoreactivity was inversely correlated with Bcl-2 expression (p = 0.0243) and decreased continuously with decreasing tumor differentiation (p = 0.0011). No correlation was found between Bax expression and the following parameters: depth of invasion, nodal status and tumor size. Bax expression had no influence on the post-operative survival of esophageal cancer patients.

Basaloid squamous cell carcinoma of the esophagus: diagnosis and prognosis.

BACKGROUND: Basaloid squamous cell carcinoma (BSCC) is a recently recognized, poorly differentiated variant of squamous cell carcinoma (SCC), which is located predominantly in the upper aerodigestive tract. METHODS: In this study, clinical and pathologic parameters of 17 BSCCs and 133 typical SCCs of the esophagus that underwent potentially curative resection (no distant metastases, no residual tumor) were compared. In addition, light microscopic, electron microscopic, and immunohistochemical features of BSCC were investigated, to determine whether this type of carcinoma could be differentiated from other poorly differentiated carcinomas of the esophagus. RESULTS: Light microscopic study showed that BSCC was composed of relatively small tumor cells, arranged in solid lobules with abundant comedo-type necrosis. BSCC was almost invariably accompanied by areas of concomitant typical SCC, foci of squamous cell differentiation, and/or severe squamous cell dysplasia or carcinoma in situ of the adjacent mucosa. Ultrastructurally, BSCC inconsistently showed features of squamous cell differentiation. Immunohistochemically, BSCC displayed poor reactivity for antibodies against wide-range cytokeratins and cytokeratin subtypes that are typical of squamous cell epithelia (cytokeratin 13 and cytokeratin 14). Infrequently, expression of Leu7, smooth muscle actin, and S-100 protein was found. In comparison with typical SCC, the characteristic features of BSCC were older patient age, higher proliferative activity (MIB-1 labelling index), and higher apoptotic indices. No differences were found with regard to pT classification, pN classification, tumor size, blood vessel invasion, lymphatic vessel invasion, neural invasion, or patient gender. Moreover, no differences in overall survival rates were found. CONCLUSIONS: BSCC is a distinct histopathologic variant of SCC, characterized by a poor degree of differentiation and high proliferative activity. However, after potentially curative resection, the prognosis of patients with BSCC of the esophagus does not differ from that of patients with typical SCC.

[Roentgen imaging in acute abdominal pain is dispensable]. / Röntgennativaufnahmen bei akuten Bauchschmerzen sind vermeidbar.

Plain abdominal X-ray films are overused in patients with acute abdominal pain. Focusing on medical history and physical examination helps to reduce the number of plain films used and saves costs.

Prognostic significance of urokinase-type plasminogen activator expression in squamous cell carcinomas of the esophagus.

In the present study, urokinase-type plasminogen activator (uPA) expression in 150 potentially curatively resected SCCs of the esophagus was analyzed immunohistochemically by means of a murine monoclonal antibody (American Diagnostica, Greenwich, CT) and correlated with survival. Altogether, 122 of the 150 tumors (81.3%) expressed different levels of uPA. Among the 122 uPA-positive tumors, 104 (85.2%) showed a weak staining intensity, and 18 (14.8%) showed a strong staining intensity. Among the uPA-positive tumors, 29 (23. 8%) tumors showed a uPA immunoreactivity in 6-25% of all tumor cells, 30 (24.6%) showed a uPA immunoreactivity in 26-50% of all tumor cells, 41 (33.6%) showed a uPA immunoreactivity in 51-75% of all tumor cells, and 22 (18.0%) showed a uPA immunoreactivity in 76-100% of all tumor cells. No significant correlation could be shown between the different patterns of uPA expression and various clinicopathological parameters, such as pT category, pN category, tumor size, histological grade, blood vessel invasion, lymphatic vessel invasion, and inflammatory response. Concerning the overall postoperative survival, no significant differences between uPA-positive and uPA-negative tumors could be verified. This also held true when different cut points in the percentage of uPA-positive tumor cells were used. In contrast, the intensity of uPA staining provided significant prognostic information in that patients with strongly uPA-positive tumors had a poorer outcome than patients with weakly uPA-positive or uPA-negative tumors. Moreover, as shown by stepwise multivariate Cox regression analysis, the intensity of uPA expression was an independent prognostic factor.

The prognostic significance of epidermal growth factor receptor expression in squamous cell carcinomas of the oesophagus.

EGFR expression in 150 potentially curative resected squamous cell carcinomas of the oesophagus was analyzed immunohistochemically and correlated with survival. Altogether, 124 of 150 (82.7%) tumours expressed different levels of EGFR. The percentage of tumour cells expressing EGFR varied greatly between the different tumours (median: 70%). 62 (50.0%) tumours showed weak and intense staining, respectively. Regarding the staining pattern 19 (15.3%) tumours showed exclusively membraneous immunoreactivity, 27 (21.8%) an exclusively cytoplasmic immunoreactivity and 78 (62.9%) a mixed staining pattern. No significant correlation however could be found between EGFR expression and various clinicopathologic parameters such as pT category, pN category, tumour size, histologic grade and blood vessel invasion. In univariate survival analysis, no correlation between EGFR expression and postoperative survival time was observed. In a forward multivariate Cox regression analysis only the parameters lymphatic-vessel invasion (p = 0.001), pT category (p = 0.0034) and pN category (p = 0.0256), but not the EGFR expression, could be verified as independent prognostic variables. In conclusion, the evaluation of the EGFR expression does not provide prognostic information for patients who underwent potentially curative resection for SCC of the oesophagus.

[MALT-lymphoma--surgical therapy]. / MALT-Lymphome--chirurgische Therapie.

To perform laparotomy in each histological sub-type of a primary gastric lymphoma with the intention of a total resection seems to be rather aggressive and should be seen with respect to other effective treatment modalities. But for curative treatment total gastrectomy with systematic lymphadenectomy or sampling respectively seem to be necessary. Classification is changing and there is an uncertainty about nature and dissemination of the tumor and even an uncertainty with respect to diagnosis. Basic informations become available only by standardized operative procedures. Multi-modal therapy planning is based on this knowledge but it has to hold up to clinical investigation such as the German multi-center trial. Preliminary data show an overall total resection rate of 88%.

bcl-2 expression and prognosis in squamous-cell carcinomas of the esophagus.

The bcl-2 proto-oncogene is a known inhibitor of apoptosis and may be an important regulator of tumor growth. In the present study, bcl-2-protein expression was investigated by immunohistochemistry and correlated with prognosis in a series of 150 potentially curatively resected squamous-cell carcinomas of the esophagus. For comparison, bcl-2-protein expression was analyzed in normal esophageal mucosa, severe squamous dysplasias and carcinomas in situ. bcl-2 immunoreactivity was found in 40 out of 150 invasive squamous-cell carcinomas; the remaining carcinomas were completely negative. bcl-2-protein expression was found more frequently among poorly differentiated than among well-differentiated tumors (p < 0.0001). No correlation was found between bcl-2-protein expression and the parameters tumor size, depth of invasion and nodal status. Moreover, bcl-2-protein expression had no significant influence on overall survival. Whereas in normal mucosa bcl-2 immunoreactivity was restricted to the basal-cell layer, in 9 out of 15 severe squamous dysplasias and in 7 out of 14 carcinomas in situ bcl-2 staining was detected in all epithelial layers. Thus, bcl-2-protein is frequently expressed in invasive squamous-cell carcinomas of the esophagus and in precursor lesions of esophageal cancer, but has no significant impact on the outcome of esophageal cancer.