[Liver surgery: technical and conceptional changeover].
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Carcinoma, Hepatocellular↗
Biomedical subjects
C Herfarth
Publications and source records attributed to C Herfarth.
[Tumor related prognostic factors--established and hypothetical aspects].
The prognostic assessment of cancer patients is of special importance clinically and scientifically. Prognostic factors are divided into three groups: patient-, treatment- and tumor-related factors. Only a minority of those factors, for example the UICC TNM classification, have been proven by multivariate studies to be of prognostic significance and have an impact on patient management, even then only as prognostic groups. The individual prognosis of a specific patient, which would allow an individualized therapy, cannot yet be adequately assessed. New prognostic factors may result in improved prognostic predictions; currently it is unclear whether this will be accomplished by molecular prognostic parameters assessed on the basis of the primary tumor or rather by the detection of disseminated cancer cells. Of major importance are well-designed clinical studies, in order to prove the clinical benefit of an individualized patient management.
Biomarkers, Tumor↗
["High pouch output" syndrome. Role of mineralocorticoid diagnosis after restorative proctocolectomy].
UNLABELLED: The two-phase restorative proctocolectomy is the treatment of choice for surgical therapy of the familial adenomatous polyposis (FAP) and also for the ulcerative colitis (UC). Besides the well-known complications the entire removal of the colorectum leads to an impairment of fluid and electrolyte resorption. PATIENTS AND METHODS: Over a time period of two years we observed 320 proctocolectomized patients with ileal pouch-anal anastomosis (IPAA). All patients with high pouch output but without organic malfunction were identified. The organic reasons were excluded with the help of pouchoscopy, radiography or MR imaging. We evaluated routine parameters, the kidney function, the electrolyte changes, the acid-base balance and the urine pH, as well as the hormonal changes of the suprarenal glands. We identified seven patients with 'high pouch output' out of 320 patients observed. The control group consisted of 14 proctocolectomized patients without hints of complications in the endoscopic, radiographic and routine laboratory diagnostics. RESULTS: Neither group showed any significant differences in the analysis of the routine parameters. A significant drop of the urine sodium concentration of 40.5 +/- 18.7 mmol/l (control group 98 +/- 43.4 mmol/l) was observed in the group with 'high pouch output'. In this group the plasma aldosterone values were strongly increased with an average of 42.6 +/- 28.9 ng/dl (control group 13.2 +/- 6.8 ng/dl) as well as the plasma 18-hydroxycorticosterone with an average of 153.7 +/- 121.1 ng/dl (control group 153.7 +/- 121.1 ng/dl). Neither group of patients showed increased activity of free corticosterone and free cortisol. Only free 11-desoxycorticosterone was elevated in the group with 'high pouch output'. CONCLUSION: Our results prove that the mineralocorticoid adrenal activity plays a central role in order to preserve the volume and electrolyte homeostasis. The low frequency of 'high-pouch-output'-complications in realms of the restorative proctocolectomy proves the excellent compensation of the removal of the colon mucosa. Plasma aldosterone seems to be a diagnostic marker encapsulating the reabsorption problems of intestinal salt and volume losses after proctocolectomy.
18-Hydroxycorticosterone↗
[Extreme challenges in hepatobiliary surgery].
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Biliary Tract Neoplasms↗
Adenocarcinoma in the ileal pouch: late risk of cancer after restorative proctocolectomy.
Restorative proctocolectomy and ileal pouch-anal anastomosis is the surgical treatment of choice for patients with ulcerative colitis. As a long-term complication of this procedure, chronic pouchitis impairs the outcome in a number of patients. Aneuploidia and dysplasia have been observed after long-lasting inflammation of ileal mucosa. The question arises whether chronic inflammation of ileal mucosa predisposes to malignant transformation similar to the situation in the chronically inflamed colon. Cancer of the ileal mucosa has been reported in patients with Brooke's ileostomy and in patients with Kock pouch but not as yet in those with an ileoanal pouch. We report a patient with carcinoma in an ileoanal pouch originating from terminal ileal mucosa who had been suffering from pancolitis with long-term backwash ileitis before, and from chronic pouchitis after, restorative proctocolectomy. This case demonstrates the importance of regular follow-up with pouchoscopy and random biopsies in all patients with long-standing inflammation of the ileal mucosa.
Adenocarcinoma↗
Duodenal adenomatosis in familial adenomatous polyposis coli. A review of the literature and results from the Heidelberg Polyposis Register.
Familial adenomatous polyposis coli (FAP) is an autosomal dominant genetic disorder caused by mutations of the APC gene on the long arm of chromosome 5. While multiple colorectal adenomas usually developing in early adolescence represent the most conspicuous phenotypic feature, the disease represents a generalized hyperproliferative disorder with various extracolonic manifestations. Duodenal cancer and desmoids are the leading causes of death in FAP patients after prophylactic colectomy. The prevalence of duodenal adenomatosis among FAP patients varies from 50% to greater than 90%, while only few patients (3-5%) develop duodenal cancer. Periampullary adenomas seem to carry a high risk of malignant transformation. The sensitivity of endoscopic procedures for early detection of severely dysplastic or malignant duodenal lesions is low, and the prognosis of duodenal cancer is poor. Thus the question arises whether it is possible to define a subgroup of high-risk patients for duodenal malignancy, and whether severe duodenal adenomatosis should lead to an aggressive prophylactic surgical approach. This contribution discusses the current literature and presents the experience of the Heidelberg Polyposis Register based on gastroduodenoscopy findings in 231 FAP patients. In 135 cases (58.4%) macroscopic duodenal adenomas were observed. The majority of patients displayed numerous lesions throughout the duodenum, while adenomas were restricted to the periampullary region in ten. Four patients suffered from duodenal cancer. Twenty-two required an endoscopic or operative intervention. Five were treated by laparotomy and duodenotomy, while ampullary excision was indicated in six cases. Eight patients underwent partial pancreaticoduodenectomy for severe duodenal adenomatosis.
Adenoma↗
Serum tenascin-C is an indicator of inflammatory bowel disease activity.
Tenascin-C is a multifunctional matrix protein that is induced in inflammation and neoplasia. In the colonic mucosa of ulcerative colitis patients tenascin-C indicates tissue repair, and mucosal concentrations are correlated with local disease activity. We prospectively examined the relationship between serum concentrations of tenascin-C parameters of disease activity in surgically treated patients with ulcerative colitis and patients with inflammatory bowel disease (IBD). Perioperative serum concentrations were quantified by ELISA in 58 patients admitted for restorative proctocolectomy; controls were 37 patients with familial adenomatous polyposis receiving the same treatment. We also measured tenascin-C serum levels in 47 patients with ulcerative colitis and Crohn's disease who were receiving nonsurgical treatment. Preoperative serum tenascin-C levels were significantly higher in ulcerative colitis patients than in controls (17.2 +/- 14.6 microg/ml vs. 3.2 +/- 1.7 microg/ml) and were significantly correlated with clinical and histological parameters of disease activity; levels decreased significantly after restorative proctocolectomy. Serum tenascin-C levels were also correlated with the course of disease activity in conservatively treated IBD patients. Tenascin-C is thus not disease-specific. However, it does indicate the activity of IBD and may reflect the degree of tissue remodeling. The tenascin-C levels therefore offers a novel serum parameter for assessing disease activity and monitoring therapy in patients with IBD.
Adolescent↗
Systemic vs local administration of delta-aminolevulinic acid for laparoscopic fluorescence diagnosis of malignant intra-abdominal tumors. Experimental study.
BACKGROUND: Administration of delta-aminolevulinic acid (ALA) either systemically or locally results in tumor-specific accumulation of protoporphyrin IX (PpIX). When excited with light at a defined wavelength and viewed with the appropriate filter cells containing PpIX, have a characteristic red fluorescence. We evaluated both locally (intraperitoneally [i.p.]) and systemically (intravenously [i.v.]) administered ALA to compare its effectiveness for laparoscopic fluorescent visualization of intraperitoneal tumors. METHODS: Peritoneal carcinosis was induced in rats using colon carcinoma cells (CC531). Photosensitization was achieved either by intravenous (i.v. group) or intraperitoneal (i.p. group) application of ALA solution. Staging laparoscopy was performed in both groups, first using conventional white light and subsequently using blue light (380-440 nm) to excite PpIX-induced fluorescence. RESULTS: Conventional white light laparoscopy showed 142 visible intraperitoneal tumor foci in the i.p. group and 116 such foci in the i.v. group. In the i.p. group, all tumors (100%) also were fluorescence positive, whereas in the i.v. group only 32 of the tumors (28%) showed the typical red fluorescence. In the i.p. group, 30 additional tumors were detected by fluorescence excitation (21%), as compared with eight additional tumors in the i.v. group (7%). CONCLUSIONS: Fluorescence laparoscopy after local (i.p.) photosensitization with ALA is a more reliable and effective method than systemic (i.v.) photosensitization for the detection of small or occult i.p. tumors.
Aminolevulinic Acid↗
Backwash ileitis is strongly associated with colorectal carcinoma in ulcerative colitis.
BACKGROUND & AIMS: Commonly accepted risk factors for colorectal carcinoma (CRC) in ulcerative colitis are duration and extent of disease. By identifying still unknown risk factors, surveillance strategies may be improved further. We investigated whether backwash ileitis is also a factor associated with CRC in ulcerative colitis. METHODS: Five hundred ninety consecutive patients with ulcerative colitis who received restorative proctocolectomy were classified into 3 groups: (1) pancolitis with backwash ileitis, (2) pancolitis without backwash ileitis, and (3) left-sided colitis. The association with CRC was analyzed in these 3 groups of patients. As further risk factors, we investigated disease duration, dysplasia, primary sclerosing cholangitis, age at diagnosis of disease, disease activity, and gender. Univariate and multivariate logistic regression were used for analysis. RESULTS: CRC was diagnosed in 11.2% of all patients. CRC was found in 29.0% of 107 patients in group 1, compared with 9.0% of 369 patients in group 2, and in 1.8% of 114 patients in group 3 (P < 0.001). Cancer patients in group 1 showed significantly more multiple tumor growth (45.2%) than patients in group 2 (24.2%) and group 3 (0%) (P = 0.041). Estimating the relative risk for CRC in the multivariate analysis, patients in group 1 showed a significantly higher odds ratio than patients in groups 2 and 3 (odds ratio: 19.36 vs. 9.58 vs. 1; P < 0.001). High-grade dysplasia, low-grade dysplasia, disease duration of more than 10 years, and disease duration of less than 10 years in patients older than 45 years were further factors with significantly increased risk (odds ratios: 21.69, 6.36, 3.63, 4.37), but primary sclerosing cholangitis was not (P = 0.080). However, primary sclerosing cholangitis was strongly associated with backwash ileitis. CONCLUSIONS: There is a strong association of backwash ileitis with CRC in patients with ulcerative colitis who undergo proctocolectomy. The predictive value of backwash ileitis for CRC and premalignant dysplasia in patients with ulcerative colitis should be investigated in future studies based on colonoscopic surveillance.
Adolescent↗
One- or two-stage procedure for restorative proctocolectomy: rationale for a surgical strategy in ulcerative colitis.
OBJECTIVE: To analyze the results of different strategies for restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) in ulcerative colitis. SUMMARY BACKGROUND DATA: No commonly accepted criteria exist for choosing between the one-stage or the two-stage procedure (with or without temporary diverting ileostomy) for IPAA. The authors analyzed the outcome of patients principally suitable for either of the two alternative surgical strategies. METHODS: A matched-pair control study was performed, comparing surgical details and the early and late outcome of the one-stage (study group, n = 57) versus the two-stage procedure (control group, n = 114), for IPAA. RESULTS: No differences were found between the study group and the control group regarding the matching criteria gender, median age at IPAA, systemic corticoid medication, or activity of colitis. Comparing the patients who underwent a one-stage procedure with those who underwent a two-stage procedure, the proportion of patients without complications was significantly higher (P =.0042) and the frequency of late complications was significantly lower (P =.0022) in patients who underwent the one-stage procedure. The percentage of patients with anastomotic strictures was significantly higher in the control group than in the study group (P =.0022). No significant difference was found between the two groups regarding early complications, pouch-related septic complications, pouchitis, median duration of surgery for IPAA, median blood loss, need for transfusion, or median hospital stay. CONCLUSIONS: In patients with ulcerative colitis in whom there is a choice between a one-stage procedure or a two-stage procedure with a defunctioning ileostomy, the one-stage procedure is clearly superior. This finding is of great clinical relevance both for the subjective interests of the patient and from an economic point of view.
Adult↗
Endothelin-1 and big-endothelin concentrations are elevated in liver graft tissue during cold storage and reperfusion.
Endothelin (ET) and its precursor big-ET were synchronously analyzed by RIA in liver biopsies and systemic plasma during porcine orthotopic liver transplantation (OLT) before graft harvesting (phase A), after cold storage (phase B), and early (phase C) and late reperfusion (phase D). Tissue and plasma concentrations were correlated with length of survival and reperfusion. Increased tissue ET/big-ET levels were already detected during phase B (ET: 46 +/- 20; big-ET: 245 +/- 119 pg/mg cytosolic protein) and remained elevated in phase C (ET: 49 +/- 16; big-ET: 306 +/- 144 pg/mg) compared to baseline (ET: 32 +/- 13; big-ET: 185 +/- 164 pg/mg; p < 0.05). In phase D, a rapid concentration decline was detected (ET: 36 +/- 26; big-ET: 163 +/- 138 pg/mg). Systemic ET levels were elevated in phase B (3.4 +/- 3.0 pg/ml), C, (2.8 +/- 1.2 pg/ml) and D (2.6 +/- 2.0 pg/ml), compared to baseline (1.7 +/- 1.1 pg/ml; p < 0.05). ET/big-ET kinetics in liver tissue and systemic plasma showed analogous characteristics. Intrahepatic ET accumulation during storage and early reperfusion could be of relevance for harvest-related disturbances of hepatic microcirculation.
Animals↗
Intraoperative fluorescence visualization of the parathyroid gland in rats.
Bilateral neck exploration is the standard procedure of primary hyperparathyroidism. Preoperative localization is not mandatory. Intraoperative visualization methods help to avoid unsuccessful explorations and to reduce morbidity rates. In our study, the application of 5-Aminolevulinic acid (5-ALA), a precursor in the heme biosynthesis pathway, led to Protoporphyrin IX (PpIX) accumulation within the parathyroid gland (PTG). PpIX, a metabolite of 5-ALA, causes red fluorescence (635 nm) when stimulated by light of a defined wavelength. Largely invisible under conventional illumination, all PTGs were fluorescence positive and detectable after PpIX targeting and blue light excitation (380-440 nm). Point spectrometry to measure fluorescence intensities, showed a fluorescence ratio between PTG and surrounding thyroid gland tissue of 5.7:1 (p < 0.001). Fluorescence guided PTG biopsies showed no false positive findings in histology. 5-ALA induced PpIX fluorescence to detect PTGs suggests to be a highly sensitive intraoperative visualization method. Hence, the performance of minimally invasive video-assisted parathyroidectomy will be facilitated by this innovative technique.
Aminolevulinic Acid↗
Development of an international net-based medical information system for advanced surgical education.
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Computer-Assisted Instruction↗
[Surgery and molecular biology: new insight or stray path?].
Surgery has the optimal possibility for theoretical-clinical transfer of molecular biological knowledge. On the basis of the existing research emphasis on clinical molecular biology at the Department of Surgery, University of Heidelberg, this is shown by the example of colorectal cancer: Establishment of a large clinical register for hereditary colorect cancer, use of molecular biological methods to improve phenotype/genotype correlations, definition of risk groups, decision on surgical therapeutical concepts for hereditary cancers and considerations on the creation of problem-orientated centers for hereditary cancer. A further example for the application of molecular methods is the detection of minimal residual disease or tumor cells in the different compartments (blood, lymph nodes, bone marrow and peritoneum) in order to achieve a better risk evaluation exceeding the standard pathohistological stage definition. The goal is an individualized or more focused therapy for each patient. Transfer of research from the basic sciences into the clinical setting, integrated into the daily clinical work, is possible in a so-called tandem model.
Adenomatous Polyposis Coli↗
[Progress in oncological visceral surgery: colon carcinoma].
The main progress in surgical oncology regarding colonic cancer has been made by standardizing the mode of resection: En block resection of the tumor-bearing colon segment together with the draining lymph nodes, including the lymph nodes at the origin of the respective main vessel, is mandatory. Minimal invasive surgery is an option for resection, however, results of ongoing multicenter trials have to clarify the situation. Adjuvant therapy is used for patients in stage III, who are not included in studies. Since quality of surgery has a major influence on prognosis, this factor also needs to be taken into account when judging the impact of adjuvant therapy. New chemotherapeutic agents have been proven to be valid for palliative and probably also for adjuvant treatment. Prophylactic surgery is routine for patients with ulcerative colitis and FAP, the benefit for patients with HNPCC has to be further evaluated. New knowledge on the individual prognosis might optimize treatment; most probably this will be accomplished by detection of minimal residual disease. The impact of the sentinel node concept in colon cancer is unclear. New progress will be possible by an approach adapted to the individual problem together with accumulating and linking experience and knowledge.
Chemotherapy, Adjuvant↗
Changes in glucocorticoid and mineralocorticoid hormone levels due to compensation for ileostomy losses.
BACKGROUND: The Ileo-Pouch-Anal-Anastomosis (IPAA) is the standard restorative procedure for Ulcerative Colitis and Familial Adenomatous Polyposis (FAP). IPAA may lead to considerable losses of fluids, especially in association with a protective loop ileostomy. AIM: The aim of this study was to investigate adrenal mechanisms in the regulation of volume homeostasis immediately after IPAA and protective ileostomy. METHODS: For that purpose, 20 patients out of our patient population with elective IPAA with ileostomy participated in this study between 1993 and 1997. In all patients, routine laboratory tests and gluco- and minealocorticoid hormone measurements were performed preoperatively and 10 days after operation. RESULTS: These blood analyses indicated functional hyperaldosteronism immediately after IPAA. Significantly elevated levels of Aldosterone (36.4 +/- 25.1 ng/dl) and 18-OH-Corticosterone ( 173 +/- 11.3 ng/dl) were found. Among hormones with glucocorticoid effects, blood levels of Cortisol (10.4 +/- 4.8 microg/dl) were significantly elevated, while 11-Desoxycortiosterone (13.9 +/- 8.4 ng/dl) and Corticosterone (0.8 +/- 0.6 microg/dl) were not significantly elevated. Serum electrolytes remained unchanged. CONCLUSIONS: Our results indicate that hormones with mineralocorticoid effects play a predominant role in the compensation of ileostomy losses after IPAA.
Adaptation, Physiological↗
Thiol-mediated redox regulation of intestinal lamina propria T lymphocytes.
Intestinal lamina propria T lymphocytes (LP-Ts) have a markedly low proliferative potential both in vivo and in vitro. Here, we have identified that the capacity of antigen-presenting cells to release cysteine upon receptor-ligand interactions represents a critical parameter for proliferation of LP-Ts. The availability of cysteine is limiting for the intracellular production of glutathione, which in turn is essential for cell cycle progression. When cysteine is provided either directly or by addition of the reducing agent 2-mercaptoethanol to cystine-containing culture medium, proliferation of LP-T is fully restored. Importantly, coculture with peripheral blood monocytes that easily take up cystine, reduce cystine, and secrete cysteine also restores reactivity of LP-Ts to T cell receptor/CD3 stimulation. In marked contrast, lamina propria macrophages lack this capacity to elaborate cysteine, and thereby secure physiological unresponsiveness to antigen exposure in the intestinal microenvironment. The well-documented local recruitment of blood monocytes in inflammatory bowel disease (IBD) may thus represent an important parameter underlying hyperresponsiveness of T cells, an essential component of the pathogenesis of IBD.
Antigen-Presenting Cells↗
The impact of 3-dimensional reconstructions on operation planning in liver surgery.
BACKGROUND: Operation planning in liver surgery depends on the precise understanding of the 3-dimensional (D) relation of the tumor to the intrahepatic vascular trees. To our knowledge, the impact of anatomical 3-D reconstructions on precision in operation planning has not yet been studied. HYPOTHESIS: Three-dimensional reconstruction leads to an improvement of the ability to localize the tumor and an increased precision in operation planning in liver surgery. DESIGN: We developed a new interactive computer-based quantitative 3-D operation planning system for liver surgery, which is being introduced to the clinical routine. To evaluate whether 3-D reconstruction leads to improved operation planning, we conducted a clinical trial. The data sets of 7 virtual patients were presented to a total of 81 surgeons in different levels of training. The tumors had to be assigned to a liver segment and subsequently drawn together with the operation proposal into a given liver model. The precision of the assignment to a liver segment according to Couinaud classification and the operation proposal were measured quantitatively for each surgeon and stratified concerning 2-D and different types of 3-D presentations. RESULTS: The ability of correct tumor assignment to a liver segment was significantly correlated to the level of training (P<.05). Compared with 2-D computed tomography scans, 3-D reconstruction leads to a significant increase of precision in tumor localization by 37%. The target area of the resection proposal was improved by up to 31%. CONCLUSION: Three-dimensional reconstruction leads to a significant improvement of tumor localization ability and to an increased precision of operation planning in liver surgery.
Computer Simulation↗