Isolated tumor cells are frequently detectable in the peritoneal cavity of gastric and colorectal cancer patients and serve as a new prognostic marker.

OBJECTIVE: To evaluate the prognostic significance of isolated tumor cells detected by a panel of various monoclonal antibodies. SUMMARY BACKGROUND DATA: Previously, we showed by using immunocytology that cancer cells are frequently found in bone marrow and peritoneal cavity samples of gastrointestinal cancer patients. METHODS: Findings in bone marrow and peritoneal cavity samples were compared and correlated with the 4-year survival rate of 84 gastric and 109 colorectal patients with cancer. RESULTS: Although positive results in the bone marrow showed little prognostic significance, the peritoneal cavity results correlated with the 4-year survival rate (gastric cancer: p = 0.0038; colorectal cancer: p = 0.0079). Additionally, in subgroups of patients with early (gastric cancer: p = 0.02, colorectal cancer: p = 0.48) and advanced (gastric cancer: p = 0.02, colorectal cancer: p < 0.0001) tumor stages, a correlation of immunocytologic findings and the survival rate was seen. CONCLUSIONS: The detection of minimal residual disease in the peritoneal cavity serves as a new prognostic marker.

[Prospects]. / Ausblick.

With the warning that the future is always different than you imagine, the following considerations were discussed: currents issues; institutionalisation of commission of programms; standing order for the congress; publication of proceedings; increased engagement in the scientific forum and modern surgery; more interdisciplinary participation and involving surgical practitioners in the congress; a close cooperation with the German Society of the Profession; supporting and protecting innovation; cooperation with the Society of Public Health; regular public relations work; overcoming political naivety; discussions on "one-week surgery" with the participation of related groups; traditional surgical societies; and upholding the sovereignty and necessity of a larger unity of surgery.

[Limits of geriatric surgery--where are they, can they be defined?]. / Grenzen der Alterschirurgie--wo liegen sie, lassen sie sich definieren?

Ageing is not a disease; it does not necessarily imply physical and intellectual deterioration. If the possibilities of an adequate training are not exploited the aged person finds himself in a "state of regression". Only the elderly person himself can assess his welfare. His quality of life is not to be objectively judged by others. The elderly person wants to live and to die; he does not fear death but an agonizing death. The limit of surgical treatment is when a patient capable of making his own decision refrains from doing so and the surgeon is certain that there is not even a remote chance of survival. The determination of scientific and clinical limits may be very difficult. This is a question of deliberation, not of ethics.

Is radical surgery in locally advanced gallbladder carcinoma justified?

OBJECTIVES: Advanced gallbladder carcinoma is associated with a dismal long term prognosis. The aim of the present study was to evaluate the effectiveness of radical surgery in advanced stages of gallbladder carcinoma. METHODS: The course of 66 patients operated for advanced gallbladder carcinoma was evaluated in a retrospective study; 14% of patients had stage II, 29% had stage III, and 57% had stage IV tumors. Twelve patients underwent cholecystectomy (CHE) and lymphadenectomy of the hepatoduodenal ligament (LA); 17 patients underwent cholecystectomy combined with segment IV/V liver resection (CHE+LR) and LA; and 10 patients underwent right extended hemihepatectomy (EHH). Complete tumor resection (R0) was achieved in six patients with CHE and LA, in 14 patients with CHE combined with segment IV/V LR and LA, and in all patients with right EHH. Resections with microscopic residual tumor (R1) were performed in nine patients. Mean follow-up was 15.4 months (range 3-90 months). RESULTS: The perioperative mortality rate was 1.5%, and the morbidity rate was 20%. In R0 resections, mean survival was 23.3, 25.0, and 26.3 months for the patients who underwent CHE and LA, CHE combined with segment IV/V LR and LA, and right EHH, respectively. After 24 months, 46.4% of the patients with R0 resection were still alive compared with none of the patients with residual tumor. In the patients with R0 resection, no difference in survival was detected when node-negative status (pN0) was compared with positive locoregional lymph nodes (pN1a), whereas the degree of dedifferentiation (G2/G3) influenced survival. CONCLUSIONS: If complete resection is achieved, radical surgical procedures, including segment IV/V liver resection and extended right hepatectomy, significantly improve survival rates with an acceptable morbidity and mortality rate.

[Immunocytologic detection of disseminated tumor cells in the peritoneal cavity and bone marrow in patients with pancreatic carcinoma]. / Immuncytologischer Nachweis disseminierter Tumorzellen in der Bauchhöhle und im Knochenmark von Pankreascarcinom-Patienten.

Despite radical surgical treatment, the prognosis of patients with pancreatic cancer is poor. The success of surgical treatment is often limited due to local recurrence and especially the development of metastases and peritoneal carcinosis by cells which have been seeded already at the time of operation. Immunocytological methods enabled the detection of disseminated cancer cells before their clinical manifestation as demonstrated by this study. Lavage samples from the peritoneal cavity and bone marrow samples from 34 patients with an adenocarcinoma of the pancreas were investigated with a panel of six different monoclonal antibodies against tumor-associated antigens (CEA, CA-19-9, 17-1A, C-54-0, Ra96) and cytokeratin, respectively. Additionally, 43 patients with benign diseases were investigated as a control group. By this method, micrometastases were detected either in the bone marrow or the peritoneal cavity in 76% of pancreatic cancer patients. The occurrence of stained cells in the peritoneal cavity and bone marrow samples correlated with the tumor stage and showed even in early stages (I and II) a detection rate of 43% (bone marrow) and 33% (peritoneal cavity), respectively. No unspecific reactions were found in the control group. The 1-year follow-up shows a significant correlation between tumor cell detection and the survival (p = 0.03). Our study demonstrates that in most patients pancreatic cancer is a disseminated disease at time of diagnosis. It underlines the need for adjuvant postoperative therapy concepts.

Immunocytological detection of micrometastatic cells: comparative evaluation of findings in the peritoneal cavity and the bone marrow of gastric, colorectal and pancreatic cancer patients.

The prognosis of digestive cancers is poor mainly due to intraperitoneal relapse by cells which may have already been seeded at the time of surgery. Using immunocytology we investigated the peritoneal cavity and, as a comparison, the bone marrow of 147 patients with gastric, colorectal and pancreatic cancer for micrometastatic cells. Cytological samples from peritoneal cavity lavages and bone marrow aspirates were analyzed using monoclonal antibodies (MAbs) against tumor-associated antigens (TAA) (CEA, CA-19-9, 17-1-A, C-54-0, Ra96) and compared to a MAb staining cytokeratins (KL-1). Patients with benign diseases served as controls. Intraperitoneal micrometastatic cells were detected in 27% of colorectal, 43% of gastric and 58% of pancreatic cancer patients. In the bone marrow, the corresponding data were 29% for colorectal, 25% for gastric and 58% for pancreatic cancer patients. Combined evaluation of both compartments increased the detection rate significantly (colorectal cancer: 40%, gastric cancer: 52%, pancreatic cancer: 72%). No unwarranted reactions were found in the control group. Combining 3 antibodies (CA-19-9, Ra96, C-54-0) enabled good detection for peritoneal cavity samples. In the bone marrow, the use of 2 antibodies (KL-1 and CA-19-9) detected 94% of all positive samples, whereas KL-1 and CA-19-9 stained approx. 70% of all positive samples in each case. The occurrence of stained cells in the peritoneal cavity correlated with classical prognostic factors (TNM classification).

Specific detection of carcinoembryonic antigen-expressing tumor cells in bone marrow aspirates by polymerase chain reaction.

PURPOSE: To establish a sensitive assay for the specific detection of carcinoembryonic antigen (CEA)-expressing tumor cells in the bone marrow of patients with colorectal cancer and other CEA-positive carcinomas. PATIENTS AND METHODS: A CEA-specific nested reverse transcriptase (RT) polymerase chain reaction (PCR) assay was developed and optimized using limiting dilutions of a CEA-positive cancer cell line mixed with normal bone marrow cell specimens. The optimized test was then used to examine bone marrow samples obtained from 15 patients with abdominal carcinomas (colorectal, n = 10; pancreatic, n = 3; gastric, n = 2) and six patients with breast cancer. Specificity was assessed by examination of 56 negative controls (malignant hematologic disease, n = 28; nonmalignant disease conditions, n = 5; healthy bone marrow donors, n = 8; normal peripheral-blood samples, n = 15). For 11 patients with abdominal carcinomas, immunostaining evaluations were performed using an anti-CEA and an anticytokeratin antibody, and the results compared with the nested PCR assay. RESULTS: In the sensitivity calibration system, single CEA-expressing tumor cells were detected in 2 to 5 x 10(7) normal bone marrow cells. All 56 control samples failed to amplify. This demonstrates that mRNAs coding for highly homologous CEA-related antigens expressed by various lineages of blood cells do not interfere. Bone marrow samples from 10 of 15 patients with abdominal cancers and four of six breast cancer patients scored positive, indicating micrometastatic bone disease. Four of 11 samples from the gastrointestinal cancer patients were found to be positive by the PCR method, but were negative with the immunocytology method. CONCLUSION: Since approximately 30% of the colorectal carcinoma patients that score negative in immunocytology staining of bone marrow samples have been reported to relapse, earlier diagnosis of the presence of malignant cells is needed. Our result that samples scoring positive in the described CEA-specific PCR test remained negative by two immunostaining methods suggests a higher sensitivity. We conclude that PCR amplification of CEA mRNA may lead to an earlier diagnosis of micrometastatic bone disease in patients with CEA-expressing carcinomas.

Pulverisation of calcified and non-calcified gall bladder stones: extracorporeal shock wave lithotripsy used alone.

Using a modified electromagnetic lithotripter (Siemens), extracorporeal shock wave lithotripsy (ESWL) was performed in 260 patients with gall bladder stones. Exclusion criteria for treatment were a non-functioning gall bladder, subcostal gall bladder location, and multiple stones occupying more than three quarters of the gall bladder volume. Stone pulverisation was the end point of ESWL. The number of shock wave discharges and sessions was not limited. Pulverisation was achieved in 250 patients (96.1%) after a median of three ESWL sessions (range 1-21). The number of sessions required depended upon stone composition and burden. More than three sessions were required in 60.2% of patients with calcified stones compared with 35.9% of patients with non-calcified stones (p < 0.001). 65.8% of patients with stones measuring more than 30 mm in total diameter required more than three sessions compared with 42.9% of patients with a stone burden less than 30 mm (p < 0.01). At 18-24 (8-12) months follow up, stone clearance was achieved in 94.3% (80.4%) of patients with non-calcified stones, compared with 89.5% (76.8%) in patients with calcified stones and in 75% (71.4%) of patients with a total stone diameter more than 30 mm compared with 95.7% (80.4%) for patients with a total stone diameter less than 30 mm (p < 0.05). ESWL related complications (gross haematuria) occurred in three patients. Thirty six (13.8%) patients experienced biliary colic; four had cholecystectomy, and five endoscopic papillotomy because of common bile duct obstruction. Stone recurrence was seen in 5.3% of patients over a follow up period of up to two years (median 16.6 months).

[Angioarchitecture of the ulna and radius and their practical relevance]. / Angioarchitektur von Ulna und Radius und ihre praktische Relevanz.

The periosteal and endosteal blood supply of the human ulna and radius was investigated by anatomical dissection. The main artery concerned is the anterior interosseous artery. It supplies the diaphysis of ulna and radius; its branches feed the distal one-fourths of both the ulna and the radius. The proximal one-fourth of the ulna is supplied by the ulnar artery, the ulnar recurrent artery and the recurrent interosseous artery. Periosteal branches of the common interosseous artery, the ulnar artery and the recurrent interosseous artery supply the proximal one-fourth of the radius. In both bones the main branch of the nutrient artery has an ascending course. The anterior interosseous artery, as the main artery of the periosteal and endosteal supply of the human ulna and radius, is important in transplantation and reconstruction, especially with a view to reducing the rate of pseudarthrosis. When osteosynthesis is planned so-called LC-DC plates should be chosen to preserve the periosteal branches. When a vascularized bone graft is taken from the forearm the vascularization of the remaining bones has to be considered. The vascularity of this area allows various options in grafting.

[Resection of liver metastases of colorectal cancers. Results and prognostic factors]. / Resektion von Lebermetastasen colorectaler Carcinome. Ergebnisse und prognostische Faktoren.

Between 1985 and 1991 268 liver resections were performed at the Department of Surgery of the University of Hamburg. 89 patients underwent liver resections because of colo-rectal secondaries. 82 patients could be followed for more than 1 year postoperatively. Their courses were analysed regarding the prognostic factors: age, sex, localisation of the primary tumor, size, number and localisation of metastases and radicality (R0-R1-R2-stage of resection). The results showed, that a significant prognostic influence regarding the long-term-survival rate could only be observed in patients, in which a R0-resection with a tumor-free margin of more than 1 cm was performed. In these patients the cumulative 5-year survival rate was 37% with a median survival time of 39 months. In patients with a tumor-free margin < 1 cm (R0b) the long-term prognosis did not differ significantly from cases with R1 or R2 resections (under 10%).

Detection of colorectal carcinomas by intraoperative RIS in addition to preoperative RIS: surgical and immunohistochemical findings.

The immunoscintigraphic detection of tumour foci less than 1 cm in diameter fails even with single photon emission tomography (SPET) owing to low contrast against background activity. In an attempt to improve detection of macroscopically invisible tumour spread, intraoperative scintimetry (IOSM) with a hand-held gamma-probe was performed in addition to SPET 24-30 and 41-48 h after injection of the technetium-99m carcinoembryonic antigen (CEA MoA) on 12 patients with colorectal carcinoma and 3 patients with different neoplastic and inflammatory diseases. Tumour specimens were measured in vitro in a gamma well counter. For comparison, the presence and amount of CEA in the tumour cells were evaluated immunohistochemically. After modification, the gamma-probe originally designed for iodine-131 was 20 times more sensitive; activities of 99mTc located close to the collimator hole were measured with absolute sensitivity of 100 cps = 2.5 kBq 99mTc. The unfavourably high background activity affected both the in vitro and in vivo analysis: SPET results had been considered positive in 8 of 15 cases. In vitro tumour/non-tumour (t/nt) ratios greater than 2.0 were found in 4 cases. In vivo IOSM resulted in t/nt ratios greater than 2.0 in only 3 patients. In most cases, there was no coincidence of elevated t/nt ratios from the different methods. A correlation was derived between positive immunoscintimetric in vitro findings and immunohistochemically proven interstitial localization of CEA in tumor cells. In conclusion, the measurement technique of IOSM seems adequate, but clinical success will depend on a more specific enrichment of MoA in tumour tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

[Conservative surgery--introduction]. / Schonendes Operieren--Einführung.

To choose a careful operative technique is to choose an advantageous cost/benefit ratio in terms of natural and human science. The results are comparable with those of other techniques, but there is an additional advantage in terms of quality of life.