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W Hohenberger

Publications and source records attributed to W Hohenberger.

At least 145 records · Page 8Linked to original sources
PubMed1999

Laparoscopic-assisted colon anastomosis using the Valtrac ring: an animal study.

PURPOSE: For deep colon anastomoses in laparoscopic surgery, the mainstay is the circular stapler. Theoretically, however, such anastomoses can also be constructed with the aid of the Valtrac ring. The aim of the present study was to investigate the feasibility of this approach. METHODS: In this approved animal study nine pigs weighing 15 to 20 kg were operated on under general anesthesia. After intracorporeal preparation, the colon was divided at the level of the entry to the pelvis. To fix the proximal half of the Valtrac ring, the proximal limb of the colon was exteriorized via a minilaparotomy. After replacing this part of the colon--now bearing the Valtrac ring--in the abdominal cavity and reestablishment of pneumoperitoneum, the ring was fixed to the applicator inserted transanally into the abdominal cavity. After placement of the distal half of the ring in the rectal limb and extracorporeal knotting of the pursestring suture previously placed with the aid of the laparoscopic pursestring clamp, the two halves of the Valtrac ring were reliably closed with the help of the applicator. RESULTS: Eight of nine animals survived. One animal died on the fourth postoperative day as a result of an anastomotic insufficiency. At follow-up examination in the fifth postoperative week, none of the surviving eight animals showed any signs of prior anastomotic insufficiency. CONCLUSION: This animal study has shown that using the newly developed applicator system, the Valtrac ring can be just as readily employed as the circular stapler for creation of a colonic anastomosis below the level of the promontorium.

Anastomosis, Surgical↗
PubMed1999

[Neoadjuvant radiochemotherapy in soft tissue sarcomas. Optimization of local functional tumor control].

BACKGROUND: Adequate local control rates > 90% and acceptable functional results are the paramount goals in the treatment of soft-tissue sarcoma. Purpose of this paper is to evaluate response, long-term control, functional outcome and toxicity following neoadjuvant radiochemotherapy (RCT) in advanced and recurrent soft tissue sarcoma. PATIENTS AND METHODS: Between 1992 and 1998, a total of 23 patients in whom primary curative limb and function sparing surgery seemed impossible entered the study. Sixteen patients had primary and 7 patients recurrent sarcoma. The stages according to AJCC/UICC 1997 were as follows: rIA (2), rIIA (5) IIA (4), IIB (2), III (7), IV (3). RCT consisted of an accelerated split-course radiation (1.5 to 1.6 Gy twice daily, median total dose 60 Gy, range 60 to 64 Gy, break of 1 week after 30 Gy) with concomitant chemotherapy using adriamycin (50 mg/m2/d on days 2 and 30) and ifosfamide (1.5 g/m2/d on days 1 to 5, 29 to 33). Median follow-up was 26 months (range 2 to 92 months). RESULTS: Twenty-two patients underwent surgery with a curative (R0) resection being achieved in 20/22 (91%) patients and gross residual (R2) tumor or unclear tumor margins (RX) in 1 patient, respectively. Effective tumor-downstaging was documented in 4/22 (18%) patients (ypT0: 3 patients, ypT1: 1 patient). Long-term local tumor control after R0/RX resection remained 100%. Without prognostic impact on tumor response and local control have been the variables primary vs. recurrent tumor, grading, stage and gender. Delayed wound healing was only noted in 1/22 (5%) patients. Four patients developed distant metastases. Overall-, NED- and distant-metastases-free survival rates were 83%, 64% and 68%, respectively, at 3 years. Grade 3/4 neutropenia (WHO) was seen after 21/46 (46%) cycles of chemotherapy with 1 patient dying of septicemia. The functional results were good to excellent in 18/22 (82%) patients. CONCLUSION: Accelerated split-course radiation with 60 to 64 Gy and concurrent chemotherapy using adriamycin/ifosfamide is a safe and effective treatment for soft tissue sarcoma. This regimen may be considered in all cases with recurrent and advanced disease not amenable to primary curative or limb sparing surgery.

Adult↗
PubMed1999

[Locally recurrent and metastatic malignant melanoma. Long-term results and prognostic factors after percutaneous radiotherapy].

PURPOSE: Radiotherapy (RT) is used as last resort for patients with advanced cutaneous malignant melanoma (MM). Herein our 20-year clinical experience is presented analyzing different endpoints and prognostic factors in patients with locally advanced, recurrent or metastatic MM. PATIENTS AND METHODS: From 1977 to 1995, 2,917 consecutive patients were entered in the MM registry of our university hospital. RT was indicated in 121 patients (56 females, 65 males) for palliation in locally advanced recurrent and metastatic MM stages UICC IIB to IV. At the time of RT initiation, 11 patients had primary or recurrent lesions which were either not eligible for surgery or had residual disease (R2) after resection of a primary or recurrent MM lesion (UICC IIB); 57 patients had lymph node (n = 33) or in-transit metastases (n = 24) (UICC III), and 53 had distant organ metastases (7 M1a, 46 M1b) (UICC IV). The time from first diagnosis to on-study RT averaged overall 19 months (median: 18; range: 3 to 186 months). In 77 patients conventional RT and in 44 patients hypofractionted RT was applied with 2 to 6 Gy fractions up to a mean total RT dose of 45 (median: 48; range: 20 to 66) Gy. RESULTS: At 3 months follow-up, complete response (CR) was achieved in 7 (64%), overall response (CR + PR) in all (100%) UICC IIB patients, in 25 (44%) and 44 (77%) of 57 UICC III patients, and in 9 (17%) and 26 (49%) of 53 UICC IV patients. Tumor progression during RT occurred in 25 (21%) patients. Patients with CR survived longer (median: 40 months) than those without CR (median 10 months) (p < 0.01). At the time of evaluation and last FU (December 31, 1996), 26 patients were still alive: 6 (55%) stage UICC IIB, 17 (30%) stage UICC III, and 3 (6%) stage UICC IV patients (p < 0.01). Univariate analysis revealed following prognostic factors for CR and long-term survival: UICC stage (p < 0.001), primary location in the head and neck, total RT dose > 40 Gy (all p < 0.05), while age, gender and primary histological subtype had no impact. In multivariate analysis, UICC stage was the only independent favorable prognostic factor for achievement of CR and long-term survival (p < 0.001). CONCLUSION: External RT provides effective palliation in advanced UICC stages. The UICC staging system is a good predictor of initial and long-term tumor response in metastatic MM. Prospective randomized trials using RT with or without adjuvant therapy for advanced MM are justified.

Adult↗
PubMed1999

[Long term results following radiation therapy of locally recurrent and metastatic malignant melanoma].

The 20-year radiotherapy (RT) experience in patients with locally advanced, recurrent or metastatic malignant melanoma (MM) is analyzed with respect to different endpoints and prognostic factors. From 1977 to 1995, 2917 consecutive patients were entered in our MM registry. RT was indicated in 121 patients (56 females, 65 males) for palliation in advanced MM stages. The histology of the primary lesion was nodular in 51, superficial spreading in 35, acral-lentiginous in 8 and lentigo maligna in 4 patients); 22 were missing or could not be reclassified. Eleven patients had primary or recurrent lesions which were ineligible for surgery or had residual disease (R2) after resection of a primary or recurrent lesion (UICC IIB); 57 patients had lymph node (33) or in-transit metastases (24) (UICC III), 53 had distant organ metastases (7 M1a; 46 M1b) (UICC IV). Time from first diagnosis to on-study RT averaged 19 (median: 18; range: 3-186) months. In most cases conventional RT was applied (2-6 Gy single fractions) up to a mean total RT dose of 45 (median: 48; range: 20-66) Gy. At 3 months follow-up (FU), complete response (CR) was achieved in 7 (64%) and overall response (CR+PR) in all (100%) UICC IIB patients, in 25 (44%)/44 (77%) of 57 UICC III patients, and in 9 (17%)/26 (49%) of 53 UICC IV patients. Progression during RT occurred in 25 (21%) patients. Patients with CR survived longer (median: 40 months) than those without CR (median: 10 months) (p<0. 01). At last FU, 26 patients were alive: 6 (55%) UICC IIB, 17 (30%) UICC III, and 3 (6%) UICC IV patients (p<0.01). In univariate analysis following favorable prognostic factors for CR and long-term survival were identified: low UICC stage (p<0.001), primary site head and neck and total dose >40 Gy (all p<0).

Adult↗
PubMed1999

Pharmacokinetics of melphalan in isolated limb perfusion.

The pharmacokinetics of melphalan was studied by sampling of tissue and plasma in 72 rats that underwent isolated hyperthermic limb perfusion under different conditions. A miniaturized extracorporeal circulation system for small animals was used for perfusion of the rat hindlimb. Melphalan levels (L-phenylalanine mustard, L-PAM) were determined by high-performance liquid chromatography (HPLC). The temperature of the perfusate plasma and tissue, pH, administration method, and flow rate were modified and compared with regard to their influence on pharmacokinetic parameters. The highest tissue penetration of melphalan was observed under the following conditions: (a) pH range of the perfusate plasma between 7.3 and 7.7 (physiological environment), (b) temperature range of the perfusate from 40 degrees to 41.5 degrees C (destruction of cellular carrier systems at higher temperatures and increased inactivation by hydrolysis of melphalan above 41.5 degrees C), (c) application of melphalan as a single dose into the reservoir of the extracorporeal circuit (optimal tissue penetration), and (d) reduced perfusate flow (prolonged contact time between perfusate and tissue).

Algorithms↗
PubMed1999

Laparoscopic resection of sigmoid diverticulitis. Results of a multicenter study. Laparoscopic Colorectal Surgery Study Group.

BACKGROUND: In the large bowel, resection of the sigmoid colon is the most commonly performed laparoscopic intervention because large bowel lesions often are located in this part of the bowel and the procedure technically is the most favorable one. A number of publications involving case series or the results of highly experienced individual surgeons already have confirmed the feasibility of laparoscopic resection in cases of diverticulitis. The aim of the present prospective multicentric investigation was to check the results obtained by a large number of surgeons performing laparoscopic resection of the sigmoid colon for diverticulitis in various stages of severity. RESULTS: Between January 8, 1995 and January 1, 1998, the Laparoscopic Colorectal Surgery Study Group recruited 1,118 patients to the prospective multicenter study. Diverticulitis of the sigmoid colon, which accounted for 304 cases, was the most common indication for laparoscopic intervention. In most of these patients undergoing laparoscopic surgery (81.9%), the diverticulitis manifested as acute phlegmonous peridiverticulitis, recurrent attacks of inflammation, or stenosis. Complicated forms of diverticulitis in Hinchey stages I to IV and late complications of chronic diverticular disease with fistula formation and bleeding accounted for only 18.1% of the cases. For the overall group, the conversion rate was 7.2%. Patients with less severe diverticulitis (i.e., those presenting with peridiverticulitis, stenosis, or recurrent attacks of inflammation) had a conversion rate of 4.8% and the rate for complicated cases was 18.2%. Regarding laparoscopically completed interventions, 3 of 282 patients died (1.1%). In the group of patients with peridiverticulitis, stenosis, or recurrent attacks of inflammation the overall complication rate was 14.8%. The group with perforated diverticulitis in Hinchey stages I to IV or those with fistula and bleeding, the corresponding rate was 28.9%, and after conversion it was 31.8%. CONCLUSIONS: Laparoscopic colorectal interventions in sigmoid diverticulitis are, for the most part, carried out as elective procedures for peridiverticulitis, stenosis, or recurrent attacks of inflammation. The conversion, complication, and mortality rates associated with these interventions are acceptable. Laparoscopic procedures in Hinchey stages I to IV sigmoid diverticulitis and in the presence of fistula and bleeding are more likely to be associated with complications, and should be carried out only by highly experienced laparoscopic surgeons.

Diverticulitis, Colonic↗
PubMed1999

Laparoscopic colorectal anastomosis: risk of postoperative leakage. Results of a multicenter study. Laparoscopic Colorectal Surgery Study Group (LCSSG).

BACKGROUND: We report on a prospective observational multicenter study of more than 1,000 consecutive patients undergoing laparoscopic colorectal procedures. The aim of the current study was to investigate the safety of laparoscopic colorectal surgery as reflected by the anastomotic insufficiency rates in the various sections of the bowel, and to compare these rates with those of open colorectal surgery. METHODS: The study was begun on August 1, 1995. Twenty-four centers in Germany, Austria, and Switzerland participated in this prospective multicenter study. All patients undergoing laparoscopic colorectal surgery were included in the study. No selection criteria were applied, which means that every operation begun as a laparoscopic procedure was included. Data on patient demographics, surgical indications, surgical course, and patient outcome were recorded prospectively in a computer database. All data were rendered anonymous. RESULTS: Between August 1995 and February 1998, the 24 participating centers treated 1,143 patients (male/female ratio, 1:1.36; mean age, 60.7 years). In all, 626 operations were performed for benign indications and 517 for cancer. Most procedures involved the sigmoid colon and rectum (80.9%). An anastomosis was performed in 83% of the operations. Most of the anastomoses were laparoscopically assisted using the stapling technique. We observed an overall leakage rate of 4.25% (colon 2.9%; rectum 12.7%), and surgical reintervention was required in 1% of the cases. The rate of conversion to open surgery was 5.6%. Intraoperative complications occurred in 5.9%, and reoperation was necessary in 4.1% of the cases. The overall morbidity rate was 22.3%, and the 30-day mortality rate was 1.57%. CONCLUSIONS: The feasibility and safety of the laparoscopic colorectal approach is demonstrated clearly. The current study shows that the laparoscopic or laparoscopically assisted approach to colorectal surgery is not associated with a higher risk of anastomotic leaks. Morbidity and mortality rates with this method approximate those seen with conventional colorectal surgery.

Adult↗
PubMed1999

Percutaneous endoscopic gastrostomy/jejunostomy (PEG/PEJ) for decompression in the upper gastrointestinal tract. Initial experience with palliative treatment of gastrointestinal obstruction in terminally ill patients with advanced carcinomas.

BACKGROUND: Signs of gastrointestinal obstruction, with intractable vomiting and an inability to take oral food, are common symptoms in terminally ill cancer patients with advanced primary tumors or peritoneal carcinomatosis. The application of percutaneous endoscopic gastrostomy or jejunostomy (PEG/PEJ) instead of the usual nasoenteral tube is a simple method of achieving permanent decompression in the upper gastrointestinal tract. The goals of this study, in addition to establishing indications and outcome, were to identify specific aspects of tube placement and to determine the incidence of complications. METHOD: Over a period of 3 years, a total of 24 consecutive patients (mean age, 64 years; range, 37-83 years) underwent either a PEG (17/71%) or a PEJ (seven/29%). RESULTS: In all patients, PEG/PEJ obviated the need for the nasoenteral tube. A total of 22 patients (92%) were enabled to take liquids orally, and 20 (83%) were discharged to home care. With the exception of a single spontaneous dislodgement of the PEG tube, no major complications were observed. CONCLUSION: We believe that PEG/PEJ represents an effective, minimally invasive, and cost-effective method for gastrointestinal decompression in patients with advanced incurable cancer.

Abdominal Neoplasms↗
PubMed1999

Immunocytology improves prognostic impact of peritoneal tumour cell detection compared to conventional cytology in gastric cancer.

AIMS: Studies on the value of peritoneal tumour cell dissemination for prognosis in gastric cancer using various methods to detect tumour cells have produced conflicting conclusions. We studied the incidence and prognostic relevance of microscopic intraperitoneal tumour cell dissemination in gastric cancer, comparing conventional and immunocytological detection. METHODS: Peritoneal wash-outs of 111 consecutive gastric patients without overt peritoneal carcinomatosis, including 75 curatively resected patients, were studied. Sixty patients with benign disorders served as controls. 100 ml of warm NaCl 0.9% was instilled intraoperatively and 20 ml was reaspirated. The specimens were stained peri-operatively with H&E. In the last 47 patients (30 of whom were curatively resected) additional immunostaining with the HEA-125 antibody was performed. The results of cytology were correlated with the TNM categories and with post-operative follow-up. RESULTS: Of the patients, 42.3% and 48.9% were positive when conventional and immunocytological staining were employed, respectively. Conventional cytology was significantly associated with the pT and M categories. Immunocytology was significantly associated with the pT, pN and M caterogies. In four of 30 curatively resected patients (13.3%), the results of conventional and immunocytology were different. Three patients with positive immunocytology but negative conventional cytology died during follow-up (median follow-up 45.3 months), whereas one patient with positive conventional but negative immunocytology is still alive. In an univariate analysis 4 years post-surgery, positive immunocytology was significantly associated with an unfavourable prognosis in patients with curatively resected gastric cancer. While only 28.6% (six of 21) of the patients with negative immunocytology had died, this proportion increased to 77.8% (seven of nine) with positive immunocytology (P=0.018). The mean survival of negative vs positive patients amounted to 1205+/-91 vs 772+/-147 days (P=0.007). In contrast, in conventional cytology we found no significantly different survival time between negative and positive patients. CONCLUSIONS: Immunocytology seems to be superior to conventional cytology and should be preferred.

Case-Control Studies↗
PubMed1999

Organ-preserving surgery for multicentric carcinoma of the pancreas.

Multicentric ductal carcinoma of the pancreas is usually treated by total pancreatectomy if surgically resectable. We present a case of metachrone, multicentric ductal carcinoma of the pancreas which was treated using an organ-preserving method. The reasons for doing so and the oncological and functional outcomes are discussed.

Adenocarcinoma↗
PubMed1999

Association of low preoperative serum albumin concentrations and the acute phase response.

OBJECTIVE: To investigate the incidence of a preoperative acute phase response and its association with low albumin concentrations. DESIGN: Prospective open study. SETTING: Teaching hospital, Germany. SUBJECTS: 225 patients who were to undergo major abdominal operations, and who had no acute infections. INTERVENTIONS: Measurements of serum concentrations of albumin, C-reactive protein (CRP), alpha-1 antitrypsin, and interleukin-6 (IL-6). RESULTS: Abnormal concentrations of acute phase proteins (indicating an acute phase response) were detected in 43 of 225 patients (19%). The mean (SD) albumin concentration in these patients (35[5]g/L) was lower than that of patients who did not mount an acute phase response preoperatively (40[5]g/L). High concentrations of CRP (> or =60mg/L) were associated with low albumin concentrations (33[5]g/L); high alpha-1 antitrypsin concentrations (> or =4.0g/L) were associated with low albumin concentrations (34[6]g/L); and high IL-6 concentrations (> or =4pg/ml) were associated with low albumin concentrations (37[6]g/L) compared with a mean(SD) albumin concentration of 40(5)g/L in patients who had no evidence of an acute phase response. CONCLUSION: A metabolic response to disease referred to as an acute phase response may explain low preoperative albumin concentrations. This association interferes with the association of low preoperative albumin concentrations and malnutrition. It is a new aspect of preoperative risk evaluation and may indicate a potential for prevention.

Acute-Phase Proteins↗
PubMed1999

Tumour necrosis factor-alpha and interleukin-10 production in septic patients and the regulatory effect of plasma.

OBJECTIVE: To investigate the capacity of patients' whole blood to produce proinflammatory and antiinflammatory cytokines in severe sepsis and to relate abnormalities to the effect of the patients' plasma on cytokine production in healthy donor blood. DESIGN: Open, prospective clinical study. SETTING: Teaching hospital, Germany. PATIENTS: Ten patients in the surgical intensive care unit with shock and a systemic inflammatory response syndrome (SIRS), a mean APACHE II score of 27, and dysfunction of at least two organ systems at the time of investigation, resulting in 70% mortality. MAIN OUTCOME MEASURES: Tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) concentrations. RESULTS: TNF-alpha and IL-10 production of the whole blood in response to lipopolysaccharide (LPS) was reduced from 2000 pg/ml to 90 pg/ml and from 9163 pg/ml to 622 pg/ml, respectively (p < 0.01). When the plasma of these septic patients was added to the whole blood cells of healthy donors TNF-alpha production decreased by 38% to 1238 pg/ml (p < 0.01) and IL-10 production by 36% to 5857 pg/ml (p = 0.03). CONCLUSION: The effect of plasma from septic patients on the cytokine production in healthy donor blood cells paralleled the decreased production of proinflammatory TNF-alpha and antiinflammatory IL-10 in the whole blood of septic patients. Efforts to modulate cytokine production in septic patients therefore need to take account of the signals from the plasma as well as the functional capacity of the cells.

APACHE↗
PubMed1999

Secretion of IL-6, monocyte chemoattractant protein-1, macrophage inflammatory protein-1alpha, and TNFalpha by cultured intact human peritoneum.

The peritoneum is an important site of host defence. The mesothelial cells, lining the peritoneum, and the fibroblasts found in the layers below are potent sources of a variety of mediators. Furthermore, granulocytes, mast cells, and macrophages, either resident or attracted by inflammatory processes, are interspersed within the tissue. We investigated the production of mediators by samples of fresh human peritoneum. The method described here has the advantage that the cellular composition of the human peritoneum remains intact. Samples of peritoneum were excised at the beginning of elective abdominal operations in infection-free patients. The tissue was placed across the wells of a microtitre plate, fixed in place by the plate cover and incubated with culture medium with or without lipopolysaccharide (LPS) for up to 5 h. The accumulation of IL-6, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha) and TNFalpha in culture supernatants was measured by ELISA. Production of MCP-1 and IL-6 occurred spontaneously during incubation and was enhanced by as much as 4-fold in the presence of different concentrations of LPS (0. 5-500 ng/ml) in a dose-dependent manner. MIP-1alpha and TNFalpha were detected in culture supernatants of LPS-stimulated samples with concentrations about 8 times as high as those of samples cultured with no such stimulus. The addition of IL-1beta resulted in an increase in the release of IL-6 and MCP-1, similar to that observed with LPS stimulation, but failed to increase the production of TNFalpha. MIP-1alpha production was only marginally enhanced by IL-1beta. In conclusion, our experimental system is suitable for the investigation of chemokine and cytokine production by the human peritoneum, with the aim of assessing aspects of local immunocompetence.

Cell Survival↗
PubMed1999

Long-term survival after extended surgical resection of melanoma metastasis and immunotherapy.

A patient with a huge melanoma metastasis to the left adrenal gland was treated by multivisceral surgical resection. Progression of disease could be controlled by systemic immunotherapy resulting in long-term survival. In selected cases, above all with late manifestation of distant melanoma metastases, even major surgical resection of such lesions can be worthwhile.

Adrenal Gland Neoplasms↗
PubMed1999

[Production of chemokines by the human peritoneum].

AIM OF THE STUDY: Peritonitis is characterised by a continued infiltration of the peritoneal cavity with leukocytes, attracted by chemotactic mediators. The aim of this study was to demonstrate the capacity of the human peritoneum to secrete chemokines and to show a therapeutic option by impairing the proinflammatory function of the peritoneum. METHODS: Peritoneum was obtained from 12 consenting patients undergoing abdominal surgery for noninflammatory diseases. After opening the peritoneal cavity a piece of the parietal peritoneum was excised and subsequently incubated with lipopolysaccharide (LPS, 50 ng/ml) +/- interleukin-10 (IL-10, 100 U/ml) for five hours in vitro. The culture supernatants were assayed for concentrations of interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1) and monocyte inflammatory protein-1 alpha (MIP-1 alpha) by using the ELISA. RESULTS: The cultured peritoneum secreted MCP-1 (mean (SEM): 3416 (659) pg/ml) and IL-8 (2946 (894) pg/ml). The presence of LPS resulted in a fourfold enhancement of this secretion (MCP-1: 13563 (1613), IL-8: 9854 (1305) pg/ml) and led to the production of MIP-1 alpha (1476 (240) pg/ml). The LPS-stimulated production of all of these chemokines was significantly diminished by the presence of IL-10. CONCLUSION: The reaction of the peritoneum to LPS indicates its proinflammatory function in the context of peritonitis caused by gram-negative bacteria. This inflammatory reaction might be diminished by application of IL-10.

Chemokine CCL2↗
PubMed1999

A proven de novo germline mutation in HNPCC.

Hereditary non-polyposis colon cancer (HNPCC) is a heterogeneous group of tumour predisposition syndromes caused by germline mutations in at least four different mismatch repair genes. HNPCC patients are prone to the development of carcinomas of the intestinal tract and other specific sites. Identification of presumptive HNPCC patients is primarily based on a positive family history of colorectal cancer in at least two generations. In the course of mutation screening of the MLH1 and MSH2 genes in patients manifesting a carcinoma of the HNPCC tumour spectrum before the age of 45 years, we identified a germline MSH2 344delA frameshift mutation in a male proband. This index patient, at the age of 25 years, initially developed a large rectal adenoma that was removed by polypectomy. Ten years later he was operated on for an invasive right sided colon carcinoma in the caecum (International Union Against Cancer (UICC) stage III). The mother and father, aged 61 and 66 years, respectively, were healthy and had no family history of colorectal cancer. Subsequent molecular analyses excluded the germinal MSH2 344delA alteration identified in their son and at the same time paternity was confirmed with a set of informative polymorphic markers. Thus, the genetic alteration identified in our patient definitely represented a de novo germline mutation in one of the major HNPCC genes. This case report of a patient with colorectal cancer at a relatively young age with no family history is intended to encourage mutation screening of the MSH2 and MLH1 genes in similar cases to find out whether this group of patients contains an increased proportion of de novo mutations in mismatch repair genes.

Adaptor Proteins, Signal Transducing↗