Josef Stern

Risk factors for ileoanal J pouch-related septic complications in ulcerative colitis and familial adenomatous polyposis

ObjectiveTo analyze the association between pre- and perioperative factors and pouch-related septic complications (PRSC) in ulcerative colitis (UC) and in familial adenomatous polyposis (FAP) after ileal pouch–anal anastomosis (IPAA). Summary Background DataFor patients with UC and FAP, IPAA is the surgical therapy of choice, but in some patients the outcome is compromised by PRSC. MethodsA total of 706 consecutive patients (494 UC, 212 FAP) were assessed in a study aimed at identifying subgroups of patients who were at high risk for PRSC. The rate of PRSC was analyzed as a time-dependent function (Kaplan-Meier estimation). Patients with UC and FAP were stratified separately according to associated factors (age, sex, surgeon’s experience, temporary ileostomy, colectomy before IPAA, anastomotic tension, and several factors specific for UC). ResultsIn all, 131 (19.2%) patients had PRSC (23.4% UC, 9.4% FAP). In patients with UC, the estimated 1-year PRSC rate was 15.6% and the estimated 3-year PRSC rate was 24.2%. In patients with FAP, the estimated 1-year and 3-year PRSC rates were 9.2%. The difference between the estimated rates of PRSC was significant (P < .001). In the univariate analysis, patients with UC younger than 50 years, with severe proctitis, with preoperative hemoglobin levels less than 10 g/L, or receiving corticoid medication had a significantly higher risk for PRSC (P = .039, P = .037, P = .047, P = .003, respectively). Multivariate analysis showed that patients with UC receiving a systemic prednisolone-equivalent corticoid medication of more than 40 mg/day had a significantly greater risk of developing pouch-related complications than patients with UC receiving 1 to 40 mg/day and patients with UC who were not receiving corticoid medication (RR: 3.78, 2.25, 1, respectively, P < .001). Patients with FAP proved to have a significantly higher risk for PRSC in the univariate and multivariate analyses if anastomotic tension had occurred (RR 3.60, P = .0086). ConclusionsPouch-related septic complications occur as late complications and should therefore be considered in regular, specific long-term follow-up examinations. The authors identified significant risk factors for PRSC specific to patients with UC and FAP; these must be considered for each individual surgical strategy.

Indications for and results of surgical therapy for male gynecomastia

BACKGROUND The objective of our study was to analyze factors determining diagnostic versus cosmetic indication and postoperative results in the treatment of gynecomastia. PATIENTS AND METHODS Data from 100 patients and 141 breasts were analyzed retrospectively, and reevaluated by questionnaire (n = 81) and clinical examination (n = 33). Except for 2 patients, all underwent subcutaneous mastectomy through various incisions. RESULTS Diagnostic surgery was exclusively performed in unilateral, nodular gynecomastia being preferentially of grade I. Higher grade, bilateral gynecomastia led mainly to cosmetic surgery. Minor complications (skin retraction, hypertrophic scars, hypesthesia, skin redundancy) occurred in 53% of patients and significantly more often in grade III or II gynecomastia. Each incision was preferentially associated with specific sequelae. However, 86% of patients were satisfied with surgical results. CONCLUSIONS Laterality, consistency, grade, and age at onset of symptoms determine surgical indication. Despite the high number of sequelae due to preoperative grade and selected incision, most patients are satisfied with postoperative results.

Laparoscopic Fluorescence Diagnosis for Intraabdominal Fluorescence Targeting of Peritoneal Carcinosis: Experimental Studies

ObjectiveTo assess 5-aminolevulinic acid (ALA)-induced protoporphyrin IX accumulation and fluorescence in peritoneal colon carcinoma metastases and its benefits for laparoscopic fluorescence diagnosis. Summary Background DataOccult, macroscopically nonvisible peritoneal micrometastases can be missed in laparoscopy or open surgery. Laparoscopic fluorescence diagnosis allows detection of these lesions after intraperitoneal lavage with ALA and subsequent fluorescence induction by blue-light excitation. MethodsA disseminated peritoneal carcinosis was induced by laparoscopic implantation of colon carcinoma cells (CC531) in the peritoneum of 55 WAG/Rij rats. After 12 days of tumor growth the animals were randomized into 11 groups with different photosensitization parameters. Peritoneal lavage was performed either with 1.5% or 3.0% ALA solution, except for one control group. Photosensitization times were 0.5, 1, 2, 4, or 8 hours. Spectrometry was performed using an optical multichannel analyser. ALA and protoporphyrin IX serum levels were measured by high-performance liquid chromatography to determine systemic load. ResultsProtoporphyrin IX tumor accumulation and fluorescence peaked 2 to 4 hours after ALA application in both main groups, 1.5% and 3.0% ALA. Tumor detection rate was most effective in the 1.5% ALA group. Compared with conventional white-light laparoscopy alone, blue-light excitation detected 35% additional intraabdominal tumor foci. ConclusionsLaparoscopic fluorescence diagnosis can increase the sensitivity and specificity of diagnostic staging laparoscopy. It allows determination of the extent of peritoneal carcinosis. Improved preoperative assessment helps to avoid unnecessary laparotomies and radical resections.

Improving diagnostic staging laparoscopy using intraperitoneal lavage of δ-aminolevulinic acid (ALA) for laparoscopic fluorescence diagnosis

BACKGROUND Lymph node metastases and peritoneal carcinosis, occurring as a result of gastrointestinal cancer, reduce the likelihood that conventional therapy will be adequate to remove the cancer. Although diagnostic techniques have greatly improved, it is not always possible to diagnose the entire extent of the metastases. Often, peritoneal micrometastases are not visible and may be missed during laparoscopic or open surgery. METHODS Peritoneal carcinosis was induced in WAG-Rij rats (n = 6), by laparoscopically implanting 1,2-dimethylhydrazine-induced colon carcinoma tumor cells (CC531, 5 x 10(5)) at multiple sites within the peritoneal cavity. After 12 days of tumor growth, the animals were given delta-aminolevulinic acid (ALA) (5 mL, 3% solution in 0.17 mol/L NaHCO3) by peritoneal lavage. The tumors were visualized laparoscopically using both white and blue light (D-light, Karl Storz, Tuttlingen, Germany). Fluorescence was detected by using a modified CCD camera and a special observation filter incorporated into the laparoscope. RESULTS Peritoneal carcinoma foci ranging in size from 0.05 to 2.0 cm were clearly visible laparoscopically with conventional white light (n = 142). After blue light excitation, all 142 tumors identified with white light were also identified by fluorescence. There were an additional 30 tumors that could only be identified by blue light-induced fluorescence and were histologically confirmed to be derived from colon carcinoma tumor cells. CONCLUSIONS Peritoneal colonic carcinoma foci were detected laparoscopically after intraperitoneal lavage with delta-aminolevulinic acid (ALA) and excitation with blue light. These experiments demonstrate that fluorescence laparoscopy is an important technique for the staging of gastrointestinal cancer, including colorectal cancer, because of the enhanced ability to detect small cancerous foci.

PRA- UND POSTOPERATIVE LEBENSQUALITAT VON PATIENTEN MIT COLITIS ULCEROSA UND FAMILIARER ADENOMATOSER POLYPOSIS BEI ILEOANALER POUCHOPERATION

Summary. After ileal pouch-anal anastomosis in patients with ulcerative colitis (UC) and familial adenomatous polyposis (FAP), in addition to postoperative morbidity and functional outcome quality of life is a relevant factor for assessment of the operations success. Between 1982 and 1997 restorative proctocolectomy was performed in 602 patients (UC: n = 424; FAP: n = 178) at the Department of Surgery, University of Heidelberg. The assessment of pre- and postoperative quality of life was done through a prospective study (before restorative proctocolectomy, before and 1 year after closure of ileostomy). This study (UC: n = 27; FAP: n = 7) revealed a poor preoperative quality of life in patients with ulcerative colitis. Proctocolectomy is the decisive factor for the improvement of quality of life in the surgical treatment in UC. Quality of life could not be further significantly improved by ileostomy closure. Before proctocolectomy, FAP patients showed a quality of life, activity and function similar to that of healthy controls. In FAP patients proctocolectomy led to a significant loss of quality of life. This loss could only partly be regained by ileostomy closure. Quality of life and activity comparable to that of healthy controls can be achieved in UC patients by restorative proctocolectomy.Zusammenfassung. Die Lebensqualität stellt nach ileoanaler Pouchoperation bei Patienten mit Colitis ulcerosa (CU) und familiärer adenomatöser Polyposis (FAP), neben postoperativer Morbidität und funktionellen Parametern, eine relevante Größe zur Beurteilung des Operationserfolges dar. In den Jahren 1982 bis 1997 wurden an der Chirurgischen Universitätsklinik Heidelberg 602 Patienten (CU: n = 424; FAP: n = 178) mit einer Proktocolektomie und kontinenzerhaltenden ileoanalen Pouchanlage versorgt. Bei 27 CU- und 7 FAP-Patienten führten wir eine prospektive Verlaufsbe-obachtung zur prä- und postoperativen Lebensqualität – vor restaurativer Proktocolektomie, vor Ileostomarückverlagerung, ein Jahr nach Ileostomarückverlagerung – durch. CU-Patienten zeigten präoperativ eine sehr schlechte Lebensqualität. Der entscheidende therapeutische Schritt war die Proktocolektomie. Durch die Rückverlagerung der protektiven Ileostomie konnte die Lebensqualität nicht mehr signifikant gesteigert werden. FAP-Patienten besaßen vor Proktocolektomie eine gute Lebensqualität, Aktivität und Funktion, entsprechend der einer gesunden Kontrollgruppe. Durch die Proktocolektomie zeigten sie deutliche Verluste. Diese wurden durch Ileostomarückverlagerung teilweise wieder ausgeglichen. Wichtigstes Ergebnis ist, daß bei CU- und FAP-Patienten durch die restaurative Proktocolektomie eine gute Lebensqualität und Aktivität, vergleichbar einer gesunden Kontrollgruppe, erreicht werden kann.

LEBENSQUALITAT IM LANGZEITVERLAUF NACH KONTINENZERHALTENDER PROKTOCOLEKTOMIE WEGEN COLITIS ULCEROSA UND FAMILIARER ADENOMATOSER POLYPOSIS

Summary. After ileal pouch-anal anastomosis in patients with ulcerative colitis (UC) and familial adenomatous polyposis (FAP), quality of life is a relevant factor for the assessment of the operations success, in addition to postoperative morbidity and functional outcome. Between 1982 and 1995 restorative proctocolectomy was performed in 453 patients (UC: n = 332; FAP: n = 121) at the Department of Surgery, University of Heidelberg. We studied postoperative quality of life through a longterm follow-up study (median follow-up time 43.2 months). This study 1 year or more following ileostomy closure of persons who had undergone J-pouch anastomosis (n = 243 total; UC n = 185, FAP n = 58) revealed that at the time of follow-up, the underlying disease (UC versus FAP) and successfully treated complications are without influence on the quality of life. The patients age (P < 0.01) and the presence of unsuccessfully treated complications (P < 0.0001) showed a significant influence on the quality of life. There was a distinct relation between the functional index and the quality of life index (coefficient of correlation r = –0.714). However, quality of life, comparable to that of healthy controls, can be achieved with UC and FAP patients by restorative proctocolectomy only if postoperative complications can be avoided or are successfully treated.Zusammenfassung. Nach ileoanaler Pouchoperation wegen Colitis ulcerosa (CU) oder familiärer adenomatöser Polyposis (FAP) stellt die Lebensqualität, neben postoperativer Morbidität und funktionellen Parametern, eine relevante Größe zur Beurteilung des Operationserfolges dar. In den Jahren 1982 bis 1995 wurden an der Chirurgischen Universitätsklinik Heidelberg 453 Patienten (CU: n = 332; FAP: n = 121) mit einer Proktocolektomie und kontinenzerhaltenden ileoanalen Pouchanlage versorgt. An diesem Krankengut führten wir eine Langzeitnachbeobachtung zur postoperativen Lebensqualität (mediane Nachbeobachtungszeit 43,2 Monate) durch. Im Langzeitverlauf (mindestens 1 Jahr nach Ileostomarückverlagerung; J-Pouch: n = 243, davon CU: n = 185, FAP: n = 58) waren Nachbeobachtungszeit, Grunderkrankung (CU vs. FAP) und beherrschte Komplikationen ohne Einfluß auf die Lebensqualität. Den stärksten Einfluß auf die Lebensqualität hatten das Patientenalter (p < 0,01) und aktuelle, nicht beherrschte Komplikationen (p < 0,0001). Es zeigte sich ein deutlicher Zusammenhang zwischen Funktionsindex und Lebensqualitätsindex (Korrelationskoeffizient r = –0,714). Nach Proktocolektomie und J-Pouch können Lebensqualitätswerte vergleichbar einer gesunden Kontrollgruppe erreicht werden. Entscheidend ist die Vermeidung und Beherrschung von postoperativen Komplikationen.

Local 5-aminolevulinic acid application for laser light–induced fluorescence diagnosis of early staged colon cancer in rats

5‐Aminolevulinic acid (ALA) increases the intracellular accumulation of endogenous protoporphyrin IX in colon cancer. Protoporphyrin IX itself is a potential photosensitizer that can be used for laser light‐induced fluorescence diagnosis. The aim of this study was to detect cancer in the rat colon before macroscopic visibility.

Changes in Intestinal Transit Time after Proctocolectomy Assessed by the Lactulose Breath Test

After proctocolectomy with ileal pouch-anal anastomosis (IPAA) patients have increased stool frequency and intermittently use antidiarrheal medication. In addition to other factors, gastrointestinal transit time (MTT) could influence stool frequency. The aim of this study was to investigate how MTT changes after IPAA and to study whether MTT has an influence on daily stool frequency. In a prospective trial MTT was investigated with the lactulose breath test in 12 patients undergoing surgery for chronic ulcerative colitis (CUC) or familial adenomatous polyposis coli (FAPC) at different stages: before proctocolectomy, after IPAA with loop ileostomy, and 3 months and 1 year after ileostomy closure. MTT was also measured in 12 patients with IPAA, 12 patients with subtotal colectomy and ileorectal anastomosis (IRA), and 8 patients with conventional proctocolectomy and Brooke ileostomy (CPC) several years after surgery. Twelve healthy volunteers served as controls. Before IPAA, MTT was prolonged in CUC versus FAPC and controls. After restoration of gut continuity MTT was markedly accelerated. After 1 year MTT was slowed again, though values before proctocolectomy and those in controls were not reached. Several years after surgery MTT was significantly prolonged in IPAA and IRA versus controls. In CPC, MTT could not be determined by lactulose breath test. Stool frequency showed an inverse correlation to MTT in IPAA. In conclusion, this study shows that orocecal and oropouch transit are accelerated in the early postoperative period after (procto)colectomy but prolonged in the long-term course. Adaptation of the small bowel takes longer than 1 year. Impairment of stool frequency may be partly due to this adaptation.

Photodynamische Therapie im Gastrointestinaltrakt Möglichkeiten und Grenzen

ZusammenfassungDie photodynamische Therapie (PDT) zeichnet sich durch die weitgehend selektive Anreicherung eines photoaktiven Stoffs, dem Photosensitizer, in malignen und präkanzerösen Tumorzellen aus. Durch Licht einer spezifischen Wellenlänge erfolgt die Aktivierung des Photosensitizers und daraus resultierend die Zerstörung der Tumorzelle. Die PDT gastrointestinaler Tumoren wird sowohl unter kurativer als auch unter palliativer Zielsetzung klinisch erprobt. Sie wird in beiden Fällen entweder als alleinige oder als Teil einer multimodalen Therapie eingesetzt. Anhand der aktuellen Fachliteratur wurden der gegenwärtige Status und die klinische Bedeutung der PDT zur kurativen bzw. palliativen Behandlung gastrointestinaler Neoplasien bestimmt. Die PDT in kurativer Absicht empfiehlt sich ausschließlich in selektierten Fällen zur alleinigen Behandlung von Frühkarzinomen und kleinen Tumoren. Die additive Anwendung nach vorausgegangener Tumorverkleinerung (z. B. operativ, thermische Ablation etc.) scheint ebenfalls günstige Ergebnisse zu liefern. Besonders für Patienten, für die Kontraindikationen für einen operativen Eingriff bestehen bzw. die ein operatives Vorgehen ablehnen, bietet sich die PDT im Vergleich zu etablierten therapeutischen Ansätzen als eine viel versprechende Alternative an. Im Vergleich zu den konventionellen Therapieformen zeigt die palliative PDT weit fortgeschrittener gastrointestinaler Tumoren in Pilotstudien einige Überlebensvorteile. Ob als alleinige oder adjuvante, kurative oder palliative Behandlungsform, die PDT besitzt durch ihren minimalinvasiven Charakter ein effektives aussichtsreiches therapeutisches Potenzial. Jedoch bedarf es weiterer standardisierter klinischer Studien, um den Stellenwert der PDT in der Onkologie zu bestimmen.AbstractBackground. Photodynamic therapy (PDT) is characterized by the extensive selective accumulation of a photoactive agent, the photosensitizer, in malignant or precancerous tumour cells. The photoactive compound is activated by light beam of a specific wavelength and causes cell death. A significant proportion of patients with gastrointestinal malignancies cannot undergo curative treatment, as either the cancer is too advanced or the patients general constitution is too poor to allow invasive strategies. In such cases, PDT has already proven to be a promising therapeutic modality for selected dysplasias and malignancies in the gastrointestinal tract. Material and methods. A retrospective review of the literature was performed in order to determine the experience gained with PDT and to assess its clinical value in the curative and palliative management of gastrointestinal neoplasms. Results. PDT seems to be an adequate treatment for selected forms of early cancer and small lesions of the GI tract or for small residual areas after the tumour has been debulked by other techniques (e. g. limited surgical resection, thermal ablation). Especially for patients who refuse or are ineligible for conventional surgery, PDT offers promising results compared to currently accepted clinical approaches. Conclusions. As a primary or adjuvant mode for either curative or palliative treatment of gastrointestinal neoplasms, PDT is a potentially effective, minimally invasive therapeutic modality. However, further clinical assessment by means of comparative, standardized studies is essential to the definition of its role in oncology.

Selective gastrointestinal uptake of ALA and its benefits for laserlight-induced fluorescence diagnostics (LIFD) and photodynamic therapy (PDT)

LIFD and PDT are based on the selective uptake of photosensitizers resp. the selective metabolism of their precursors in malignant tissue. Excitation with laserlight results in fluorescence or phototoxic reactions which can be used for the detection or destruction of colorectal carcinoma and dysplasia. General photosensibilization resulting in an increased photosensitivity of the whole body represents the main side and necessitates avoidance of daylight for days up to weeks. Local application of (delta) - aminolevulinic acid (ALA) may reduce systemic uptake. Rats with DMH induced colorectal cancer were photosensitized for LIFD by oral, intravenous or local application of ALA. Urine concentrations of ALA and porphobilinogen (PBG) representing systemic photosensibilization were determined by two-column chromatography. Local colon application of ALA not only increases the quality of LIFD of colorectal cancer, it also provokes three times lower concentrations of PBG in comparison to oral or intravenous administration and reduces in consequence general photosensibilization.