[R1 resection for gastric carcinoma]. / R1-Resektion beim Magenkarzinom.

The results reported in the literature in the context of an R1 situation for a resected gastric carcinoma are not uniform. An R1 situation worsens the prognosis for the long-term survival of patients. This is significant especially for low T stages and lymph node metastasis with 0-≤3 lymph node metastases. In higher tumor stages with extensive lymph node metastases, the survival difference between R0 and R1 resections is lower and frequently no longer significant. The frequency of R1 resection is approximately 5% (range 1.8-9%) and for adenocarcinoma of the esophagogastric junction (AEG tumors)> 10%. The data are mainly related to the oral and aboral resection line but there are only a few specifications on the circumferential margin. The risk of an infiltrated resection line increases with the size of the tumor (>5 cm), T3+4 and pN2/pN3 stages. Poorly differentiated signet ring cell or mucinous adenocarcinomas and carcinomas of the Bormann type 3+4 also lead to an increased R1 rate. In order to achieve an R0 resection, an intraoperative frozen section is the standard approach. Immediate reoperation should be performed in the case of tumor infiltration. If an R1 resection is detected only in the definitive histology, surgical re-excision to achieve an R0 resection is the standard approach in publications. Nevertheless, a reoperation is rare. Only 1 study showed 122 patients with 100% re-operations, which were successfully performed in 50 patients (41% R0). For the R0 group, median survival was extended from 18 months to 23 months. There are only sporadic literature data and no evidence for postoperative additive treatment (chemotherapy, radiotherapy and radiochemotherapy).

[Palliative chemotherapy for colorectal cancer--current state, significance, trends]. / Palliative Chemotherapie beim kolorektalen Karzinom--Stand, Wertigkeit, Tendenzen.

BACKGROUND: There are a number of effective substances available for palliative treatment of colorectal cancer, contributing to a considerable extension of the median survival time either purely medically or by increasing the chance of secondary resectability through improved effectiveness of the administered drugs. PATIENTS / MATERIAL: Defining treatment depending on predominant patient characteristics remains crucial for any therapeutic success. This requires interdisciplinary co-ordination within tumour boards. METHODS: In aggressive tumours a therapeutic approach inducing high response rates is favoured, usually including a triple or quadruple combination incl. antibodies. In cases of slow tumour progress and limited patient profile, a sequence of chemotherapy is chosen. Implementing and integrating locally ablative modes of therapy into the treatment strategy can increase the effectiveness additionally. In a best case scenario additional systemic side effects can be avoided resulting in a not insignificant benefit in quality of life. RESULTS: Further genotyping beyond the K-RAS state is necessary to make predictive and prognostic statements concerning the drugs applied and to avoid ineffectiveness. CONCLUSION: Considerable progress has been achieved in the medical therapy for metastasised colorectal cancer. The targeted application of already available as well as recently developed substances requires further evaluation by appropriate studies.

Gemcitabine, oxaliplatin and 5-FU in advanced bile duct and gallbladder carcinoma: two parallel, multicentre phase-II trials.

BACKGROUND: Gemcitabine, oxaliplatin and 5-fluorouracil (5-FU) are active in biliary tract cancer and have a potentially synergistic mode of action and non-overlapping toxicity. The objective of these trials was to determine response, survival and toxicity separately in patients with bile duct cancer (BDC) and gallbladder cancer (GBC) treated with gemcitabine/oxaliplatin/5-FU chemotherapy. METHODS: Eligible patients with histologically proven, advanced or metastatic BDC (n=37) or GBC (n=35) were treated with gemcitabine (900 mg m(-2) over 30 min), oxaliplatin (65 mg m(-2)) and 5-FU (1500 mg m(-2) over 24 h) on days 1 and 8 of a 21-day cycle. Tumour response was the primary outcome measure. RESULTS: Response rates were 19% (95% CI: 6-32%) and 23% (95% CI: 9-37%) for BDC and GBC, respectively. Median survivals were 10.0 months (95% CI: 8.6-12.4) and 9.9 months (95% CI: 7.5-12.2) for BDC and GBC, respectively, and 1- and 2-year survival rates were 40 and 23% in BDC and 34 and 6% in GBC (intention-to-treat analysis). Major grade III and IV adverse events were neutropenia, thrombocytopenia, elevated bilirubin and anorexia. CONCLUSION: Triple-drug chemotherapy achieves comparable results for response and survival to previously reported regimens, but with more toxicity.

An 11-year retrospective study of totally implanted central venous access ports: complications and patient satisfaction.

AIMS: We wanted to assess the factors that predict complications and patient satisfaction of totally implanted central venous access ports (TIAP). METHODS: We reviewed 550 patients with breast or gynaecological malignancies who had initial port placement for chemotherapy between 1995 and 2006. We retrospectively assessed all TIAP complications, port duration and follow-up care until the TIAPs were removed (or the last known recorded documentation) or until the death of the patient. TIAP-related patient satisfaction was also assessed via a questionnaire-based survey of 356 patients. RESULTS: 561 TIAPs were placed in 550 cancer patients (11 patients received 2 TIAPs during the study period); the median time of port duration was 22.5 months. There were 104 complications in this group. Of these, 81 occurred during chemotherapy treatment that lasted a median time of 182 days. Removal secondary to complication was observed in 48 cases. TIAPs placed on the left chest side, through the subclavian vein or with the catheter tip localized in the peripheral part of superior vena cava demonstrated the highest incidence of complications. Patients with a BMI >28.75 had an increased risk for developing complications. Our follow-up questionnaire revealed a 93% patient satisfaction rate with the TIAP. CONCLUSIONS: Patients with left-sided ports, catheter tips lying in the upper part of the superior vena cava and implantation via the subclavian vein are at a higher risk for TIAP-associated complications. Being excessively overweight was assessed as another risk factor for developing complications. TIAPs are highly accepted and further recommended by patients.

A multicentre phase II study of docetaxel plus cisplatin for the treatment of advanced gastric cancer.

BACKGROUND: The optimum regimen for advanced gastric cancer requires definition. This multicentre phase II study evaluated docetaxel-cisplatin combination in advanced gastric cancer. METHODS: Chemotherapy-naive patients with locally advanced or metastatic disease received docetaxel plus cisplatin (75/75 mg/m(2)) every 21 days for up to 9 cycles. Endpoints included tumour response, time to progression, overall survival and toxicity. RESULTS: Of 113 patients recruited, 88 were completely evaluable. The median age was 58 years, and most patients had metastatic disease. The overall response rate was 29.6%. Five patients (5.7%) achieved a complete response and 21 patients (23.9%) had a partial response. Tumour control, including stable disease, was achieved in 57 patients (64.8%). The median time to progression and median overall survival time was 4.8 and 8.7 months, respectively. The major toxicity was haematological: 37.5% of patients experienced grade 3-4 neutropenia, whereas febrile neutropenia was observed in only 2% of patients. CONCLUSION: Docetaxel-cisplatin was active with a predictable and manageable toxicity profile.

[Endoscopic treatment of mediastinal anastomotic leaks]. / Endoskopische Therapieoptionen bei mediastinaler Anastomoseninsuffizienz.

BACKGROUND: Surgery, as well as conservative treatment, in patients with clinically apparent intrathoracic anastomotic leaks are often associated with poor results and carry a high morbidity and mortality. This report describes our results with the endoscopic treatment of intrathoracic anastomotic leakages. PATIENTS: 27 consecutive patients presenting with clinically apparent intrathoracic anastomotic leak, caused by resection of an epiphrenic diverticulum (n=1), esophagectomy for esophageal cancer (n=19), limited resection for carcinoma of the gastroesophageal junction (n=1) or gastrectomy for gastric cancer (n=6) were endoscopically treated. The extent of the dehiscences ranged from about 10-70%. After endoscopic lavage and debridement of the leakage (mean duration: 16,8 days) the leaks were closed with fibrin clue (n=9) or endoclips (n=2) in cases of smaller leaks or by stent placement (n=11), stent placement after unsuccessful fibrin clue injections (n=3) or stent placement and endoclipping (n=1) in patients with a large leakage. Simultaneously the periesophageal mediastinum was drained by chest drains. RESULTS: 25 of 27 patients were successfully treated endoscopically. Under endoscopic treatment one patient died due to septic multiorgan failure. Another patient developed a refractory, persistent leak. Procedure related complications (stent migration, anastomotic stenosis) were obtained in 6 patients. CONCLUSION: An endoscopic approach is successful and safe to treat symptomatic intrathoracic anastomotic leaks smaller than 70% of the circumference. An endoscopic lavage and debridement of the leak, prior to leak closure, seems to be helpful to reduce mediastinal and pleural inflammation. In patients with smaller leaks (<30%) fibrin clue injections and endoclipping is recommended. Patients with a dehiscence from 30-70% of the circumference profit from stent placement.

[Multimodal treatment of colon cancer?]. / Multimodale Therapie beim Kolonkarzinom?

Surgical therapy is still the basis of therapy of patients with colon carcinoma. Multimodal therapeutical concepts are presently applied as a therapeutical standard in the adjuvant therapy and increasingly in the systemic therapy of patients with primarily inoperable metastases of the liver to reach a secondary operability. Interdisciplinary multimodal therapeutical concepts are even accepted within the therapy of metastasized colon carcinomas. There are still unanswered questions regarding sequences of palliative systemic therapies and their combinations with local ablative methods.

Multicenter phase-I/II study using a combination of gemcitabine and docetaxel in metastasized and unresectable, locally advanced pancreatic carcinoma.

AIMS: To assess the maximum tolerability of a combined therapy regimen of gemcitabine and docetaxel, and to evaluate tumour response rate, survival time and tolerability in patients receiving these agents for advanced pancreatic carcinoma. PATIENTS AND METHODS: Patients (n=68) with pancreatic carcinoma (advanced and/or unresectable tumour growth or histopathologically diagnosed metastases) were enrolled in a multicenter phase-I (n=25) and phase-II study (n=43). Treatment during phase II of the study was continued until either complete tumour remission (CR), tumour progression, indicated clinically or by means of radiological imaging, or until unacceptable toxicity occurred. RESULTS: Phase I: the tolerability maximum of the combined agents was established at gemcitabine 1000 mg/m(2) and docetaxel 35 mg/m(2) with tolerable adverse events. Phase II: a total of 139 chemotherapy cycles were completed (mean, 3.2; range, 1-10). While CR was achieved in three of 43 patients (7%), in five further cases, partial remission (PR) was documented, amounting to an overall response rate (OR) of 18.6%. Eighteen patients showed stable disease (41.9%), whereas in 17 of 43 subjects (39.5%), primary tumour progression was detected. The median survival time was 9.0 months; the 1-year survival rate was 13.9% (six of 43 patients). These results were associated with a side-effect profile of moderate severity and acceptable quality of life (QOL). CONCLUSION: The combination of gemcitabine and docetaxel for chemotherapy in unresectable pancreatic carcinoma was well tolerated. Survival time and 1-year survival rate proved promising and the regimen appears suitable for further evaluation in a prospective phase-III study setting.

[Oncologic surgical procedures in ambulatory and brief inpatient surgery]. / Chirurgisch-onkologische Therapiemassnahmen in der ambulanten und kurzzeitstationären Chirurgie.

The number of surgical interventions in an outpatient clinic setting has continuously increased. An important advantage of such approach is the low infection rate. From an economic point of view, this setting leads to lower costs and, subsequently, lower charges to the health insurance companies according to the today's contracts. However, an essential prediction for surgical interventions in an outpatient clinic setting is that there is no increased risk compared with interventions of hospitalized patients. Taking this in consideration, we conclude that the very specific onco-surgical interventions can only be executed in a hospital setting because of their risk profile and the characteristics of tumor patients.

[Value of cytokeratin and Ca 19-9 antigen in immunohistological detection of disseminated tumor cells in lymph nodes in pancreas carcinoma]. / Stellenwert von Cytokeratin- und CA19-9-Antigen im immunhistologischen Nachweis disseminierter Tumorzellen in Lymphknoten beim Pankreascarcinom.

INTRODUCTION: Based on the fact that pancreatic carcinoma is still associated with poor outcome, the aim of the study was to determine frequency of early tumor cell dissemination using immunohistology in lymph nodes classified as tumor-free by conventional histopathology. METHODS: Fifteen patients with ductal pancreatic carcinoma and 10 patients with carcinoma of the papilla of Vater underwent radical tumor resection (resection status R0, tumor staging pTxpN0M0). In total, 229 lymph nodes classified as tumor-free by histopathology were investigated for disseminated tumor cells using antibodies against cytokeratin and CA19-9. As control, 81 lymph nodes obtained from patients with chronic pancreatitis were analyzed. RESULTS: In 55 of 229 lymph nodes (26.3%), cytokeratin-positive, disseminated tumor cells were detected. Cytokeratin-positive cells were found in at least one resected lymph node of each patient with ductal carcinoma of the pancreatic head (100%), whereas in patients with carcinoma of the papilla of Vater, no disseminated tumor cells were detected using the antibody against cytokeratin. Similarly, there was no detection of tumor cells (false-positive) in patients with chronic pancreatitis. In contrast, CA19-9 antigen was detectable in resected lymph nodes of each of the 25 carcinoma patients (pancreatic carcinoma and carcinoma of the papilla of Vater). Interestingly, 52 of 81 lymph nodes (64.2%) from the control group (chronic pancreatitis) were false-positive. CONCLUSION: Detection of disseminated tumor cells in lymph nodes using an antibody against cytokeratin is specific and suitable while use of an antibody against CA19-9 is not recommendable because of the high rate of false-positive results. The results may indicate that ductal pancreatic carcinoma generates early dissemination of tumor cells into lymph nodes. This may be one explanation for the poor outcome of this carcinoma compared with that of the carcinoma of the papilla of Vater (14 versus 48 months P < 0.05).

Can a coated Dacron vascular graft maintain a heparin-induced thrombocytopenia type II?

In the course of reconstruction of peripheral arterial occlusion processes, two gelatin-coated Dacron grafts and one collagen-coated Dacron patch were implanted in a 52-year-old male patient. Eight days following low-dose heparinization (5 days prior to surgery, 3 days postoperatively) with unfractionated heparin, with no clinical symptoms present, a dramatic isolated thrombocyte depression occurred, from 212 Gpt/l prior to surgery to 14 Gpt/l on postoperative day 3. Laboratory tests verified an HIT type II [heparin-induced platelet aggregation assay (HIPAA) and ELISA]. Despite immediate discontinuation of heparin and commencement of an anticoagulant therapy with Revasc and Refludan, an 8-week thrombocyte depression occurred which was eliminated only temporarily by administration of gammaglobulin. The specific antibody tests turned out positive for more than 5 months. Having ruled out other causes of thrombocytopenia, we assume that the case presented was either due to an interaction not elucidated to date or triggered by the grafts (gelatin/collagen/Dacron). The manufacturers of the grafts have disputed a heparinoid action.

Diagnostic workup before laparoscopic cholecystectomy--which diagnostic tools should be used?

BACKGROUND/AIMS: A prerequisite for successful laparoscopic cholecystectomy is the exclusion of potential risks such as cholangiolithiasis, anatomical malformations or diseases of the stomach. As there is no general agreement regarding the appropriate preoperative diagnostic workup, we compared different diagnostic methods as to their value in detecting unknown accompanying diseases and complications. METHODOLOGY: Between 9/90 and 8/93, we performed 850 laparoscopic cholecystectomies. The first 700 were included in this study. A prospective comparison was carried out of the diagnostic accuracy of history, physical examination, laboratory tests, upper gastrointestinal endoscopy or barium meal, i.v. cholangiography and abdominal ultrasound. RESULTS: Measurement of the diameter of the common bile duct was found to be a good noninvasive method for diagnosing common bile duct stones (sensitivity 80%, specificity 99%). In combination with the history and the laboratory tests the sensitivity could be improved to 99%. The sensitivity of i.v. cholangiography in detecting common bile duct stones was 80%, the specificity 99.3%. 646/700 patients underwent preoperative endoscopy/barium meal. In 53 (8.2%) patients pathological findings were found, but only in 4 cases (0.6%) they influenced the indication for laparoscopic cholecystectomy. In 1 patient an advanced gastric cancer was diagnosed 6 months after laparoscopic cholecystectomy, the preoperative barium meal did not show any pathological findings. CONCLUSIONS: The results show that routine ultrasonography in combination with history and laboratory tests prior to laparoscopic cholecystectomy can be recommended for detecting common bile duct stones. In patients with 1 or more pathologic finding endoscopic retrograde cholangiopancreatography should be performed preoperatively. A gastroscopy should be done in patients with nonspecific upper abdominal pain, history of peptic ulcer disease and persisting pain after laparoscopic cholecystectomy.

Combination chemotherapy with docetaxel and cisplatin for locally advanced and metastatic gastric cancer.

BACKGROUND: Poor treatment results obtained with palliative chemotherapy for advanced gastric cancer indicate the need for new effective and well-tolerated regimens. PATIENTS AND METHODS: Forty-three patients with locally advanced or metastatic gastric cancer were enrolled in a phase II study to evaluate the efficacy and safety of combination chemotherapy with doxetacel 75 mg/m2 and cisplatin 75 mg/m2 given every three weeks. RESULTS: Thirty-nine patients were evaluable for response. Four achieved a complete response and twelve a partial response, for an overall response rate of 37.2% (16 of 43 patients; 95% confidence interval (CI): 22.98-53.72). Median time to progression was 6.1 months and median overall survival 10.4 months. Forty-two percent of all patients were still alive at one year and twelve percent at two years. The major toxicity was leukopenia which reached grade 3-4 in 18.6% (n = 8) of the patients. However, no febrile neutropenia occurred. Non-haematological toxicities were usually mild to moderate. Grade 3 toxicities included diarrhea (9% of the patients), nausea and vomiting (7%), and alopecia (7%). Severe ototoxicity with or without peripheral neuropathy developed after completion of chemotherapy in two patients. CONCLUSIONS: These results suggest that the combination of docetaxel and cisplatin has moderate toxicity and is an effective regimen for the treatment of advanced gastric cancer, both with regard to response rate and survival.

Sequential coil embolization of bilateral internal iliac artery aneurysms prior to endovascular abdominal aortic aneurysm repair.

PURPOSE: To report the endovascular repair of concomitant aneurysms of the abdominal aorta and both internal iliac arteries. CASE REPORT: A 72-year-old man with a 5.5-cm abdominal aortic aneurysm (AAA) extending to the right common iliac artery also presented with separate aneurysms of both internal iliac arteries. The patient refused conventional surgery, so an endovascular strategy was devised. Initially, the iliac aneurysms were sequentially coil embolized, allowing several weeks to elapse between the embolization sessions to encourage collateral development. A bifurcated Talent endograft was inserted successfully 8 months after the initial intervention; no evidence of endoleaks or mesenteric ischemia has been seen over a 1-year follow-up. CONCLUSIONS: This case illustrates the feasibility of inducing collateralization prior to endovascular AAA repair that would jeopardize internal iliac artery circulation bilaterally. Sequential embolization of the internal iliac arteries over several months initiates this response, paving the way for eventual endovascular repair of the primary aortic aneurysm.

[Aneurysm development and late rupture of retrogradely perfused iliac arteries]. / Aneurysmaentwicklung und Spätruptur von retrograd perfundierten Iliakalarterien.

We report the course of 2 patients with ruptured aneurysms of the iliac artery admitted in hemorrhagic shock which were treated successfully. These 2 cases demonstrate that a rupture of a retrogradely perfused aneurysm as a late complication of aortobifemoral bypass grafting is possible even after 10 years. Wether these aneurysms are causally connected with the peripheral run-off remains unclear. In our opinion, these 2 examples underline the importance of long-term follow up after resection of abdominal aortic aneurysms with femoral end to side bypass anastomoses. The goal is the early detection and therapy of metachronous iliac aneurysms before rupture.

[Single intervention for treatment of Salmonella typhimurium-induced symptomatic abdominal aortic aneurysm with spondylitis]. / Die einzeitige Behandlung eines durch Salmonella typhimurium induzierten symptomatischen Bauchaortenaneurymas mit Spondylitis.

Simultaneous treatment of Salmonella typhimurium-induced symptomatic abdominal aortic aneurysm with associated spondylitis. Bacterially infected aneurysms associated with local spondylitis, while representing a potentially fatal clinical picture, are an operative challenge for vascular surgeons and orthopaedic surgeons alike. In this context, the concurrent occurrence of an infection with Salmonella typhimurium as a causative agent is a rare observation. The case report gives an outline of the simultaneous vascular and orthopaedic surgical procedure. The subrenal mycotic aneurysm was removed in a first step. The continuity of the aorta was restored centrally through an autogenic aortic graft with caudal anastomosis to a dacron vascular prosthetic tube. Initially, the latter was chosen of excessive length so as to facilitate the orthopaedic surgeon's approach. Upon completion of stabilising surgery of the vertebral column, the dacron tube was reduced in length as necessary and the surgical area was enclosed with an omentum majus plastic mesh. No complications were noted during the 18-month follow-up period.

[Outcome of treatment of iatrogenic vascular lesions]. / Ergebnisse der Behandlung iatrogener Gefässläsionen.

The incidence and etiology of iatrogen vascular injuries have changed during the last years due to the fact that many vascular procedures, including invasive catheter procedures, minimally invasive interventions and osteosynthetic operations are more frequently performed. 66 patients who were treated between 1993 and 1997 were retrospectively analysed. The most common cause of surgical repair were lesions after catheter procedures (n = 47; 71.2%) followed by various other causes (traumatology n = 6, orthopedics n = 5, gynecology n = 4, general surgery n = 4). In patients with complicated catheterizations and need for acute vascular-surgical repair, the limb could only be preserved in 12 of 21 cases (57.1%). Vascular lesions on account of other operative specialities finally required an amputation in 3 patients. One patient in this group died. Besides the seriousness of injury one main reason for an unfavourable outcome was a delayed diagnosis with subsequent exceeding of the ischemic tolerance in 18 patients (27.3%). Some rare and serious complications are especially discussed.