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Hans Lippert

Publications and source records attributed to Hans Lippert.

11 recordsLinked to original sources
PubMed2003

Combined endoscopic and open inguinal dissection for malignant melanoma.

BACKGROUND: Positive sentinel node biopsy or clinically/radiologically demonstrable lymph node metastases in patients with malignant melanoma establishes the indication for inguinal dissection. Currently the deep (pelvic) part of the dissection is the subject of lively discussion. For the past 3 years we have been carrying out all pelvic lymph node dissections using an endoscopic extraperitoneal approach in combination with conventional superficial inguinal dissection. METHODS: In analogy to endoscopic extraperitoneal hernia repair we open the extraperitoneal space with the aid of a dissection balloon and then perform a complete dissection of the para-iliac and obturator lymph nodes. The superficial part of inguinal dissection is then carried out in the conventional manner. RESULTS: Among a total of 31 consecutive dissections performed on 30 malignant melanoma patients between April 1999 and June 2002 neither intraoperative nor postoperative complications of the endoscopic part of the dissection were observed. CONCLUSIONS: While enabling better local tumor control as a result of the complete dissection, this modification entailing the use of endoscopic pelvic dissection also appreciably reduces the extent of operative trauma without compromising oncological radicalness or increasing morbidity. We recommend this approach to all surgeons with experience with endoscopic extraperitoneal procedures for use in patients requiring inguinal dissection.

Adult↗
PubMed2003

Ethical and regulatory issues arising from proteomic research and technology.

Over the last two decades, medical research has begun to make extensive use of products of human origin in therapeutics, oncology, and most recently, in genetic diseases. This has raised many ethical issues involving patient rights, including issues of consent. Besides informed consent, researchers should address several topics when designing studies using human tissues. Reward for the patient should be kept minimal. Sample transfer should be organized along non-profit lines, at least in Europe. Sampling procedures should be at no risk for human volunteers, and at minimal risk for patients. Biosafety aspects should be addressed, in particular when international collaborations are intended or when collaboration is existing between academia and industry. Regulations on importation and exportation of human tissues should be observed. Data acquisition and storage should be addressed in accordance with national data protection regulations, in particular when using computerized databases. If follow-up information is to be taken, the authorization for such information should be requested. The right for patient's information (or for no information) on the research results should also be addressed. The issues of validation and patenting should be also solved, usually by informing the patient that he/she will have no commercial rights on potential research results. The patient should be told if the samples are transferred to another research laboratory or private company. Samples and related data should be destroyed on request at any time point during the course of the study. If possible, traceability of the donor should be ensured.

Ethics, Research↗
PubMed2003

Differences in loss of p16INK4 protein expression by promoter methylation between left- and right-sided primary colorectal carcinomas.

The p16INK4 gene, encoding a cyclin-dependent kinase inhibitor, is frequently methylated in colorectal cancer, and a side-specific methylation frequency was suggested. To clarify the frequency of real loss of tumor suppressor function dependent on anatomical localization, we investigated 43 primary colorectal carcinomas by determining aberrant promoter methylation using methylation-specific PCR. In addition, we evaluated the p16INK4 protein expression immunohistochemically. P16INK4 methylation was found in 18 of 43 (41.9%) cases. Fourteen of 43 cases (32.6%) were negative for p16INK4 protein, whereas 10 of these 14 cases showed methylation of the promoter region of the p16INK4 gene. Methylation of the promoter region was significantly correlated with loss of p16INK4 protein (p<0.01). P16INK4 tumor suppressor inactivation was significantly correlated with proximal location (p=0.031 for methylation and p=0.028 for immunostaining). The groups characterized by tumors with and without aberrant promoter methylation or loss of p16INK4 immunostaining showed no significant difference in either Dukes' stage and grade or age and gender. This is further evidence that p16INK4 methylation causes gene silencing. Loss of p16INK4 tumor suppressor function in colorectal tumors was associated with proximal location in the gut.

Aged↗
PubMed2002

Early postoperative results of surgery for rectal carcinoma as a function of the distance of the tumor from the anal verge: results of a multicenter prospective evaluation.

BACKGROUND: The problems associated with rectal surgery are frequently discussed with no reference being made to the distance of the tumor from the anal verge. This study examined the effect of the location of the tumor on early postoperative results. PATIENTS AND METHODS: This was a multicenter study involving 75 German hospitals and 3756 patients, of whom 1463 had rectal carcinoma. On the basis of the location of the tumor (distance from the anal verge), four groups were distinguished: <4, 4-7.9, 8-11.9, and 12-16 cm. RESULTS: Resection and abdominoperineal resection rates and the incidence of postoperative complications depended on the location of the tumor. Significantly higher resection rates and fewer specific complications, and a significant reduction in overall postoperative morbidity were found with tumor locations more than 8 cm from the anal verge. The highest anastomotic leak rate was observed with anastomoses less than 7 cm from the anal verge. The logistic regression showed that the distance of the tumor from the anal verge is an independent variable for the development of an anastomotic leak. CONCLUSIONS: Early results are greatly affected by the location of the rectal carcinoma. This applies to both abdominoperineal resection rates and specific postoperative complications, such as anastomotic leak rate and operation morbidity in general.

Adult↗
PubMed2002

Intraoperative and early postoperative chemotherapy into the abdominal cavity using gemcitabine may prevent postoperative occurence of peritoneal carcinomatosis.

BACKGROUND AND OBJECTIVES: Malignant tumors of various abdominal organs are blamed to be the cause of death in approximately 40% of cases per year in Western Europe. At the time of death, about half of them show peritoneal carcinomatosis which is considered an unfavorable prognostic factor. In case of peritoneal carcinomatosis, there is no curative treatment available for any of the tumors in the abdominal cavity. The aim of this experimental study was to evaluate the preventive potential of intra-operative or early postoperative local administration of gemcitabine into the abdominal cavity against peritoneal carcinomatosis. METHODS: Peritoneal carcinomatosis was induced in male WAG rats (n = 18) by transfer of 5 x 10(6) cells of the adenocarcinoma cell line CC-531 via minilaparotomy carried out in all rats under general anesthesia. Thirty days after cell transfer, rats were sacrificed and peritoneal carcinomatosis was confirmed using histologic investigation in specimens obtained from the peritoneal site. Extension of this carcinomatosis was quantified by (i) counting tumor nodes per square centimeter (mean of several counts) and (ii) determining tumor weight (weight of the greater omentum plus the resected mesentery). Rats were subdivided into three groups (n = 6 per group): group 1 (controls); group 2, simultaneously with tumor cell transfer 24 mg/kg of gemcitabine were administered into the abdominal cavity; group 3, postoperative intraperitoneal irrigation with 24 mg/kg of gemcitabine was achieved via a previously implanted port-a-cath on days(d) 15, 21, and 27. RESULTS: On the 30th postoperative day, all six animals of the control group showed extensive tumor growth at the peritoneum and greater omentum, indicating carcinomatosis. In contrast, none of the rats of group 2 revealed any traces of intraperitoneal tumor growth. While all rats of group 3 demonstrated intraperitoneal tumor growth, but early postoperative treatment with gemcitabine, however, resulted in a significant reduction of the number of tumor nodes and tumor weight in comparison with group 1 (controls). CONCLUSIONS: Immediate, i.e., simultaneous intraoperative application of a cytostatic agent such as gemcitabine into the abdominal cavity may completely prevent the generation of peritoneal carcinomatosis from occuring tumor cells, whereas early postoperative locoregional chemotherapy into the abdominal cavity can only reduce the severity of the peritoneal carcinomatosis.

Adenocarcinoma↗
PubMed2002

Impact of age on the short-term postoperative outcome of patients undergoing surgery for colorectal carcinoma.

BACKGROUND: Patient age has a decisive impact on the short-term postoperative results in surgery for carcinoma. PATIENTS AND METHODS: This prospective multicenter study involved 75 German hospitals and 3756 patients undergoing treatment in 1999: 1447 aged under 65 years, 1847 aged 65-79 years, and 458 aged over 80 years. RESULTS: In the oldest patient group, there was a significantly higher proportion of extensive, localized tumors (UICC stage II: 25.9%, 28.4%, and 36.1%, respectively) and significant differences were found among the three groups in operation rates (98.8%, 98.6%, and 96.5%), resection rate (94.2%, 93.2%, and 83.9%), general postoperative complications (21.5%, 28.6%, and 41.2%), morbidity (36.5%, 42.6%, and 50.0%) and mortality (2.7%, 6.6%, and 11.8%). CONCLUSION: In the elderly, locally advanced tumors, but not metastasizing tumors, are to be expected. The increase in postoperative morbidity and mortality rates with increasing age was due to the increase in general postoperative complications. Surgery for colorectal carcinoma in patients of advanced age is not associated with any increase in intraoperative or specific postoperative complications.

Adenocarcinoma↗
PubMed2002

Value of a protective stoma in low anterior resections for rectal cancer.

INTRODUCTION: Anastomotic leakage is a major problem in colorectal surgery and in particular in operations for low rectal cancer. The present study investigates the question whether a protective stoma can reduce the (clinical and radiologic) anastomotic leakage rate and/or the rate of leakage requiring surgery. METHODS: The investigation took the form of a prospective multicenter study involving 75 German hospitals and was performed between January 1, 1999, and December 31, 1999. A comparison was made of the postoperative results of procedures performed with and those performed without a protective stoma in patients undergoing low anterior rectal resection. In addition, logistic regression using the target criteria, overall anastomotic leakage and anastomotic leakage requiring surgery, was applied. RESULTS: Among the 3,695 operations performed for carcinoma of the rectum or colon, 482 were low anterior resections. In 334 patients (69.3 percent) no protective stoma was constructed, whereas 148 (30.7 percent) received such protection. Age, American Society of Anesthesiologists physical status, and body mass index were identical in both groups. In the group receiving a protective stoma, however, neoadjuvant radiochemotherapy was more common, the tumors were lower-and thus the total mesorectal excision rate higher, the intraoperative complication rate was higher, and the duration of the operation was longer. The differences were all significant. The major criterion (overall anastomotic leakage rate) was identical in the two groups, but the rate of leakage requiring surgery was significantly lower in patients receiving a protective stoma (p = 0.028). The logistic regression revealed that use of a protective stoma is a predictor of protection against anastomotic leakage requiring surgery. The distance of the tumor from the anal verge and the duration of the operation are further predictors. CONCLUSION: The particular benefit of a covering stoma is reduction in the rate of leaks requiring surgery and thus in the severe consequences of an anastomotic leakage.

Adult↗
PubMed2002

Soluble thrombomodulin plasma levels are an early indication of a lethal course in human acute pancreatitis.

BACKGROUND: The potential to predict severe disease and lethality by using plasma soluble thrombomodulin (sTM) and C-reactive protein (CRP) levels in 73 patients with acute pancreatitis was analyzed in a prospective 5-year investigation performed at a single institution. METHODS: According to the Atlanta criteria, pancreatitis was classified as mild in 23 patients and as severe in 50 patients. Blood was collected on days 1, 3, 5, 7, 10, 14, 21, and 28 after the onset of pain and analyzed for sTM and CRP. RESULTS: During the period between days 3 and 10 of acute pancreatitis when most of the admissions occurred, sTM levels at a cutoff of 75 ng/mL on day 3 (sensitivity, 100%; specificity, 77%; positive predictive value, 38%; negative predictive value, 100%) and 71 ng/mL on day 10 (sensitivity, 100%; specificity, 77%; positive predictive value, 41%; negative predictive value, 100%) were predictive of a lethal outcome. With sTM levels, it was not possible to differentiate patients with mild pancreatitis from those with severe pancreatitis (Atlanta classification). In contrast, CRP levels at a cutoff of 113 mg/L on day 3 differentiated severe from mild courses with a diagnostic sensitivity of 84%, a specificity of 60%, a positive predictive value of 78%, and a negative predictive value of 69%. CRP levels at a cutoff of 122 mg/L on day 10 differentiated mild from severe courses (nonsurvivors) with a diagnostic sensitivity of 72%, a specificity of 72%, a positive predictive value of 86%, and a negative predictive value of 53%. In contrast, differentiation of mild forms of acute pancreatitis from severe pancreatitis (survivors) on day 10 was not possible. CONCLUSIONS: CRP is a valuable marker of disease severity in acute pancreatitis especially in the first period of pancreatitis, whereas sTM identifies early those patients with the most severe courses and a high risk of dying (negative predictive value, 100%). Determination of sTM in addition to CRP offers the opportunity of identifying early those patients who require intensive care most urgently. Of course, further investigations of sTM in acute pancreatitis are indicated to confirm our results.

Acute Disease↗
PubMed2002

Trypsin activity is not involved in premature, intrapancreatic trypsinogen activation.

A premature and intracellular activation of digestive zymogens is thought to be responsible for the onset of pancreatitis. Because trypsin has a critical role in initiating the activation cascade of digestive enzymes in the gut, it has been assumed that trypsin also initiates intracellular zymogen activation in the pancreas. We have tested this hypothesis in isolated acini and lobules from rat pancreas. Intracellular trypsinogen activation was induced by supramaximal secretagogue stimulation and measured using either specific trypsin substrates or immunoreactivity of the trypsinogen activation peptide (TAP). To prevent a trypsin-induced trypsinogen activation, we used the cell-permeant, highly specific, and reversible inhibitor Nalpha-(2-naphthylsulfonyl)-3-amidinophenylalanine-carboxymethylpiperazide (S124), and to prevent cathepsin-induced trypsinogen activation, we used the cysteine protease inhibitor E-64d. Incubation of acini or lobules in the presence of S124 completely prevented the generation of trypsin activity in response to supramaximal caerulein but had no effect whatsoever on the generation of TAP. Conversely, when trypsin activity was recovered at the end of the experiment by either washout of S124 from acini or extensive dilution of lobule homogenates, it was up to 400% higher than after caerulein alone and corresponded, in molar terms, to the generation of TAP. Both trypsin activity and TAP release were inhibited in parallel by E-64d. We conclude that caerulein-induced trypsinogen activation in the pancreas is caused by an E-64d-inhibitable mechanism such as cathepsin-induced trypsinogen activation, and neither involves nor requires intracellular trypsin activity. Specific trypsin inhibition, on the other hand, prevents 80% of trypsin inactivation or autodegradation in the pancreas.

Acute Disease↗
PubMed2002

Tumor cell dissemination during laparoscopy: prevention and therapeutic opportunities.

Port-site recurrences (PSRs) are abdominal wall recurrences that occur in the subcutaneous tissue within a trocar site after cancer laparoscopy and are not associated with peritoneal carcinomatosis. In order to develop PSRs, viable tumor cells must be liberated from the primary tumor, be transported to a wound, and find there a favorable environment for growth. The short clinical delay in the occurrence of PSRs and their size suggest massive cell seeding into the abdominal wall. Traumatic handling of the tumor, slipping of trocars, liquid projection, as well as poor extraction techniques can all cause implantation of malignant cells into the subcutaneous tissue. Such contact can also occur postoperatively if the trocar channels remain open. Some histologies (e.g. gallbladder adenocarcinoma), the presence of ascites and advanced tumor stage are risk factors for PSRs. Further conditions--including the use of gas--might also play a limited role. The first preventive measure is the correct indication for a laparoscopic approach. Several techniques have been demonstrated to prevent PSRs in the animal model: (a) fixation of trocars to the abdominal wall; (b) prevention of leakage; (c) careful specimen handling; (d) reducing trauma to the abdominal wall; (e) specimen isolation before extraction from the abdominal cavity; (f) trocar-site irrigation with a cytotoxic solution, and (g) closure of peritoneum. Further innovative therapies are currently under investigation. In the clinical setting, correct indication, surgical expertise and application of prophylactic measures seem to be the best way to prevent the occurrence of PSRs.

Abdominal Wall↗