Hiatoplasty for Intrathoracic Gastric Migration Associated with One Anastomosis Gastric Bypass (OAGB).

PURPOSE: The standard of surgical correction of post-bariatric intrathoracic gastric migration (ITGM) is hiatal hernia repair, but little is known about its efficacy in patients with one anastomosis gastric bypass (OAGB). We present our experience. METHODS: This retrospective cohort study includes all patients with OAGB who had undergone hiatal hernia repair from 2014 to 2019. The primary outcome was recurrence of ITGM as diagnosed by computed tomography and gastroscopy. RESULTS: A total of 63 patients underwent hiatal hernia repair 2-54 months (median 13) after primary OAGB (40 patients) or concurrent with revisional OAGB after prior sleeve gastrectomy (23 patients). ITGM recurred in 48% of patients with hiatal repair after primary OAGB and in 91% of patients with concomitant hiatal repair. Recurrences were diagnosed after a median interval of 9 and 8.5 months, respectively. Thirty-six patients (57% of total number) required a revision, and a re-recurrence of ITGM was detected in 15 patients. The Cox regression analysis of all hiatal repairs showed that two variables significantly influenced the likelihood of ITGM recurrence: the length of the migrated pouch (hazard ratio 1.32; p = 0.016) and the type of repair. Combining hiatoplasty with ligamentum teres augmentation (LTA) and conversion to Roux-en-Y gastric bypass (RYGB) lowered the probability of ITGM recurrence (compared with stand-alone hiatoplasty; hazard ratio 0.21, p = 0.029). CONCLUSION: The outcome of hiatal repair in patients with OAGB is unsatisfactory. Stand-alone hiatoplasty is particularly ineffective. The combination of hiatoplasty with LTA and conversion to RYGB improves the early results, but the long-term durability needs to be tested.

[LSD score. A new classification system for peristomal skin lesions]. / LSD-Score. Ein neues Klassifikationssystem für peristomale Hautläsionen.

BACKGROUND: Peristomal skin lesions are frequent complications of ostomy; however, there is no generally accepted nomenclature and classification system. OBJECTIVE: An interdisciplinary German expert panel (GESS) composed of ten members, developed an innovative semiquantitative classification system for peristomal skin lesions for further stratification of ostomy therapy. This score is based on criteria which can be assessed by stomal therapists and treating physicians. RESULTS: The new peristomal skin lesion score grades three categories: lesion (L), status of ostomy (S) and disease (D). The L category describes the integrity of the skin as normal (L0), lesion with sustained integrity of skin (L1), integrity destroyed (L2) and local infection (L3). The S category rates the complexity of ostomy therapy as normal (S0), increased (S1) and high but not sufficiently effective (S2). The additional letters for categorization O. R. P. H. E. US describe anatomical pathologies of the stoma itself: ostomy stenosis (O), retraction (R), prolapse (P), hernia (H), edema (E) and unfavorable site (US). A systemic disorder is either absent (D0), irrelevant (D1) or relevant (D2). The LSD score is the basis for a management algorithm. CONCLUSION: The LSD score is comprehensive, standardized and holistic. Its straightforward use by health professionals can improve the consistency of the description of skin lesions and enhance the quality of ostomy therapy.

[Specific complications of minimally invasive surgery]. / Die spezifischen Komplikationsrisiken der minimal-invasiven Chirurgie.

Minimally invasive surgery (MIS) is fundamentally different from open surgery regarding positioning of the patient, access routes and instrumentation. Each of these aspects is associated with its own specific morbidity, such as positioning-related complications, trocar-induced lesions, hypercapnia-associated phenomena and thermal damage. The growing experience of surgeons and technological progress have increased patient safety to a maximum and have resulted in an impressive spread of MIS in the various fields of surgery including the most common, such as cholecystectomy and hernia repair and special fields, such as bariatric, thoracic and oncological surgery. This narrative review summarizes the current knowledge on the inherent complications of MIS.

[Stenosis and ulceration after bariatric surgery]. / Stenosen und Ulzerationen nach bariatrischen Eingriffen.

INTRODUCTION: The increasing number of morbidly obese patients leads to a rising number of bariatric procedures in Germany. The operative techniques are highly standardized but such a standardization is lacking for the management of postoperative complications such as stenosis and ulceration after Roux-en-Y gastric bypass (RYGB) surgery and sleeve gastrectomy (SG). METHODS: The current literature is reviewed and a complication management is developed and presented in this article. RESULTS AND CONCLUSION: Postoperative stenoses occure with a frequency of 0.1-3.9% after SG and 3-27% after RYGB. Stenosis is secondary to inadequate surgical technique or microinsufficiency. Ulcers can be due to reaction to foreign body, local ischemia, peptic lesion, fistula and microinsufficiency. CONCLUSION: Endoscopic interventions are successful in most cases for stenosis after RYGB and for short stenoses after SG. After SG long stenoses require redo surgery and conversion to RYGB. Ulcers can be managed by medication with the exception of perforation and hemorrhage, which require emergency laparoscopy.

[Abdominothoracic esophageal resection according to Ivor Lewis with intrathoracic anastomosis : standardized totally minimally invasive technique]. / Abdominothorakale Ösophagusresektion nach Ivor-Lewis mit intrathorakaler Anastomose : Standardisierte total-minimalinvasive Technik.

BACKGROUND: The clinical and scientific interest in minimally invasive techniques for esophagectomy (MIE) are increasing; however, the intrathoracic esophagogastric anastomosis remains a surgical challenge and lacks standardization. Surgeons either transpose the anastomosis to the cervical region or perform hybrid thoracotomy for stapler access. AIM: This article reports technical details and early experiences with a completely laparoscopic-thoracoscopic approach for Ivor Lewis esophagectomy without additional thoracotomy. MATERIAL AND METHODS: The extent of radical dissection follows clinical guidelines. Laparoscopy is performed with the patient in a beach chair position and thoracoscopy in a left lateral decubitus position using single lung ventilation. The anvil of the circular stapler is placed transorally into the esophageal stump. The specimen and gastric conduit are exteriorized through a subcostal rectus muscle split incision. The stapler body is placed into the gastric conduit and both are advanced through the abdominal mini-incision transhiatally into the right thoracic cavity, where the anastomosis is constructed. Data were collected prospectively and analyzed retrospectively. RESULTS: A total of 23 non-selected consecutive patients (mean age 69 years, range 46-80 years) with adenocarcinoma (n = 19) or squamous cell carcinoma (n = 4) were surgically treated between June 2010 and July 2013. Neoadjuvant therapy was performed in 15 patients resulting in 10 partial and 4 complete remissions. There were no technical complications and no conversions. Mean operative time was 305 min (range 220-441 min). The median lymph node count was 16 (range 4-42). An R0 resection was achieved in 91 % of patients and 3 anastomotic leaks occurred which were successfully managed endoscopically. There were no postoperative deaths. CONCLUSION: The intrathoracic esophagogastric anastomosis during minimally invasive Ivor Lewis esophagectomy can be constructed in a standardized fashion without an additional thoracotomy. Reduction of surgical morbidity remains the highest priority.

[Natural orifice transluminal endoscopic surgery in Germany: Data from the German NOTES registry]. / "Natural orifice transluminal endoscopic surgery" in Deutschland : Daten aus dem deutschen NOTES-Register.

BACKGROUND: The German NOTES registry (GNR) was initiated by the German Society for General and Visceral Surgery (DGAV) as a treatment and outcome database for natural orifice transluminal endoscopic surgery (NOTES). AIM: The aim of this study was the descriptive analysis of all GNR data collected over a 5-year period since its start in 2008 with more than 3000 interventions. MATERIAL AND METHODS: The GNR is an online database with voluntary participation available to all German-speaking clinics. Demographic data, therapy details, complications and data on the postoperative course of patients are recorded. All cases in the GNR between March 2008 and November 2013 were included in the analysis. RESULTS: From a total of 3150 data sets 2992 (95 %) were valid and suited for the analysis. Hybrid transvaginal cholecystectomy was the most frequently used procedure (88.7 %), followed by hybrid transvaginal/transgastric appendectomy (6.1 %) and hybrid transvaginal/transrectal colon procedures (5.1 %). Intraoperative complications occurred in 1.6 %, postoperative complications in 3.7 % and conversions were reported in 1.5 %. Intraoperative bladder injuries and postoperative urinary tract infections were identified as method-specific complications of transvaginal procedures. Bowel injuries occurred as a rare (0.2 %) but potentially serious complication of transvaginal operations. CONCLUSION: The German surgical community ensures a safe and responsible introduction of the new NOTES operation techniques with its active participation in the GNR. Despite an overall low complication rate, the high number of procedures in the GNR permitted the identification of method-specific complications. This knowledge can be used to further increase the safety of NOTES in practice.

Systematic review and evidence based recommendations for the use of negative pressure wound therapy in the open abdomen.

INTRODUCTION: Negative Pressure Wound Therapy (NPWT) is widely used in the management of the open abdomen despite uncertainty regarding several aspects of usage. An expert panel was convened to develop evidence-based recommendations describing the use of NPWT in the open abdomen. METHODS: A systematic review was carried out to investigate the efficacy of a range of Temporary Abdominal Closure methods including variants of NPWT. Evidence-based recommendations were developed by an International Expert Panel and graded according to the quality of supporting evidence. RESULTS: Pooled results, in non-septic patients showed a 72% fascial closure rate following use of commercial NPWT kits in the open abdomen. This increased to 82% by the addition of a 'dynamic' closure method. Slightly lower rates were showed with use of Wittmann Patch (68%) and home-made NPWT (vac-pack) (58%). Patients with septic complications achieved a lower rate of fascial closure than non-septic patients but NPWT with dynamic closure remained the best option to achieve fascial closure. Mortality rates were consistent and seemed to be related to the underlying medical condition rather than being influenced by the choice of dressing, Treatment goals for open abdomen were defined prior to developing eleven specific evidence-based recommendations suitable for different stages and grades of open abdomen. DISCUSSION AND CONCLUSION: The most efficient temporary abdominal closure techniques are NPWT kits with or without a dynamic closure procedure. Evidence-based recommendations will help to tailor its use in a complex treatment pathway for the individual patient.

[Correction of parastomal hernia using meshes]. / Korrektur der parastomalen Hernie mit Netz.

The incidence of parastomal hernia in ileal conduit urinary diversion ranges from 4% to 16%. Surgical correction is necessary in about one third of cases and different techniques of surgical reconstruction have been described. Primary fascial repair has a high recurrence rate of 46-100% whereas stoma translocation is associated with complication rates of up to 88%. The use of alloplastic material (usually polypropylene meshes) has reduced the recurrence rate by up to 100% for primary fascial repair and 71% for stoma translocation down to 33%.Composite meshes consist of two layers, a polypropylene layer and an expanded polytetrafluoroethylene (ePTFE) layer. The former is placed against the abdominal wall for permanent reinforcement by ingrowing connective tissue and the ePTFE layer is placed against the abdominal organs preventing adhesions with the bowel. The intraperitoneal placement of such composite meshes is a standardized, simplified, gentle and controllable surgical procedure. This article reports experiences with the surgical correction of parastomal hernias in ileal conduits using composite meshes.

Evidence-based recommendations for the use of negative pressure wound therapy in chronic wounds: steps towards an international consensus.

AIM: Negative Pressure Wound Therapy (NPWT) has become widely adopted over the last 15 years and over 1000 peer-reviewed publications are available describing its use. Despite this, there remains uncertainty regarding several aspects of usage. In order to respond to this gap a global expert panel was convened to develop evidence-based recommendations describing the use of NPWT. In this communication the results of the study of evidence in chronic wounds including pressure ulcers, diabetic foot ulcers (DFU), venous leg ulcers (VLU), and ischaemic lower limb wounds are reported. METHODS: Evidence-based recommendations were obtained by a systematic review of the literature, grading of evidence, drafting of the recommendations by a global expert panel followed by a formal consultative consensus development program in which 422 independent healthcare professionals were able to agree or disagree with the recommendations. The criteria for agreement were set at 80% agreement. Evidence and recommendations were graded according to the SIGN (Scottish Intercollegiate Guidelines Network) classification system. RESULTS: The primary treatment goal of NPWT in most chronic wounds is to achieve wound closure (either by secondary intention or preparing the wound for surgical closure). Secondary goals commonly include: to reduce wound dimensions, and to improve the quality of the wound bed. Thirteen evidence based recommendations were developed in total to address these treatment goals; 4 for pressure ulcers, 4 for DFU, 3 for ischaemic lower limb wounds and 2 for VLU. CONCLUSION: The present evidence base is strongest for the use of NPWT in non-ischaemic DFU and weakest in VLU. The development of evidence-based recommendations for NPWT with direct validation from a large group of practicing clinicians offers a broader basis for consensus than work by an expert panel alone.

Evidence-based recommendations for negative pressure wound therapy: treatment variables (pressure levels, wound filler and contact layer)--steps towards an international consensus.

Negative pressure wound therapy (NPWT) is becoming a commonplace treatment in many clinical settings. New devices and dressings are being introduced. Despite widespread adoption, there remains uncertainty regarding several aspects of NPWT use. To respond to these gaps, a global expert panel was convened to develop evidence-based recommendations describing the use of NPWT. In a previous communication, we have reviewed the evidence base for the use of NPWT within trauma and reconstructive surgery. In this communication, we present results of the assessment of evidence relating to the different NPWT treatment variables: different wound fillers (principally foam and gauze); when to use a wound contact layer; different pressure settings; and the impact of NPWT on bacterial bioburden. Evidence-based recommendations were obtained by a systematic review of the literature, grading of evidence and drafting of the recommendations by a global expert panel. Evidence and recommendations were graded according to the Scottish Intercollegiate Guidelines Network (SIGN) classification system. In general, there is relatively weak evidence on which to base recommendations for any one NPWT treatment variable over another. Overall, 14 recommendations were developed: five for the choice of wound filler and wound contact layer, four for choice of pressure setting and five for use of NPWT in infected wounds. With respect to bioburden, evidence suggests that reduction of bacteria in wounds is not a major mode of action of NPWT.

Evidence-based recommendations for the use of Negative Pressure Wound Therapy in traumatic wounds and reconstructive surgery: steps towards an international consensus.

Negative pressure wound therapy (NPWT) has become widely adopted over the last 15 years and over 1000 peer reviewed publications are available describing its use. Despite this, there remains uncertainty regarding several aspects of usage. In order to respond to this gap a global expert panel was convened to develop evidence-based recommendations describing the use of NPWT. In this paper the results of the study of evidence in traumatic wounds (including soft tissue defects, open fractures and burns) and reconstructive procedures (including flaps and grafts) are reported. Evidence-based recommendations were obtained by a systematic review of the literature, grading of evidence, drafting of the recommendations by a global expert panel, followed by a formal consultative consensus development program in which 422 independent healthcare professionals were able to agree or disagree with the recommendations. The criteria for agreement were set at 80% approval. Evidence and recommendations were graded according to the SIGN (Scottish Intercollegiate Guidelines Network) classification system. Twelve recommendations were developed in total; 4 for soft tissue trauma and open fracture injuries, 1 for burn injuries, 3 for flaps and 4 for skin grafts. The present evidence base is strongest for the use of NPWT on skin grafts and weakest as a primary treatment for burns. In the consultative process, 11/12 of the proposed recommendations reached the 80% agreement threshold. The development of evidence-based recommendations for NPWT with direct validation from a large group of practicing clinicians offers a broader basis for consensus than work by an expert panel alone.

Expression and function of endothelial Ca(2+)-activated K(+) channels in human mesenteric artery: A single-cell reverse transcriptase-polymerase chain reaction and electrophysiological study in situ.

Ca(2+)-activated K(+) (K(Ca)) channels have been suggested to play a role in the control of endothelial functions such as regulation of vascular tone and cell proliferation. We established a method for single-cell reverse transcriptase-polymerase chain reaction analysis in combination with the patch-clamp technique to characterize K(Ca) channel expression and function in single endothelial cells (ECs) within the endothelial monolayer of intact human mesenteric arteries (MAs) and in disease states. We tested whether endothelial K(Ca) channel expression and function are altered in MAs obtained from patients with colonic adenocarcinoma (CA) compared with those in MAs from non-cancer patients with inactive diverticulitis. Expression of the intermediate-conductance K(Ca) channel (hIK1) was detected in non-cancer and CA patients. In whole-cell patch-clamp measurements, only ECs expressing hIK1 exhibited corresponding K(Ca) currents, whereas respective K(Ca) currents were missing in hIK1-negative ECs. This heterogeneity of hIK1 expression patterns is indicative of a specialized subset of ECs within the endothelial monolayer. In CA patients, compared with non-cancer patients, a 2.5-fold increase in hIK1-expressing ECs per MA was observed (P:<0.05). However, K(Ca) current densities in hIK1-expressing ECs of both groups were similar. In addition to hIK1, expression of the large-conductance K(Ca) channel (hSlo) was detected in single ECs from CA patients. The increased K(Ca) channel expression in CA patients resulted in a 2. 7-fold increase of bradykinin-induced endothelial hyperpolarization compared with controls (P:<0.05). This increased expression and function of K(Ca) channels might indicate an altered functional state of the endothelium in cancer patients and could play a role in tumor angiogenesis.

[Radiotherapeutic strategies in the multimodal therapy of resectable and nonresectable pancreatic carcinoma]. / Strahlentherapeutische Strategien in der multimodalen Therapie des resektablen und nicht resektablen Pankreaskarzinoms.

BACKGROUND: The prognosis of patients with adenocarcinoma of the pancreas remains poor. Only patients with small tumors and complete resection have a curative chance. The value of combined radio-chemotherapy adjuvant or even palliative in case of unresectable tumors is controversial due to the short median survival times of all patients ranging from 8 to 15 months. Within the last years, significant new treatment modalities were introduced into the multimodality approach. Even the intraoperative boost therapy (IORT) with fast electrons remains still controversial. MATERIAL AND METHODS: Since the publication of the results of the historic GITSG study, in the US postoperative adjuvant radio-chemotherapy with 5-FU remains the treatment of choice. Successor studies of the ESPAC and the EORTC have been closed or are recruiting patients, the results are still pending. Neoadjuvant treatment modalities were investigated within the last 3 years, mostly in case of primary operable but also in unresectable tumors. Using 3-D-treatment planning, the total dose of radiotherapy was increased from 40 up to 45 to 50 Gy. In centers with great experience, an IORT was added to these combined modalities. More modern chemotherapeutic agents like gemcitabine or the taxanes are under investigation, using combined radio-chemotherapy in phase-II protocols in patients with unresectable tumors. RESULTS: In case of both, adjuvant or neoadjuvant radio-chemotherapy following or before pancreaticoduodenectomy, median survival times range from 15 to 25 months. The neoadjuvant radio-chemotherapy seems to reduce the rate of positive surgical margins and the rate of patients with positive lymph nodes. For the moment, there is no proven survival advantage or increase of local control (about 80% in both cases) for patients treated with neoadjuvant radio-chemotherapy compared with adjuvant radio-chemotherapy. However, about 25% of the patients don't receive adjuvant therapy due to the perioperative morbidity. Because prolongation of survival with adjuvant therapy is only 5 to 10 months, in Europe adjuvant radio-chemotherapy is not accepted as the treatment standard. Combined radio-chemotherapy in patients with unresectable tumors results in significant improvement of survival. 5-FU continuous infusion with 250 mg/m2 seems to be the treatment of choice. IORT is effective in achieving long-term local control and an effective pain palliation. More modern chemotherapeutic agents seem to be effective in vitro as radio-sensitizers. In first reported results, the MTD was not found. Toxicity seems not to be increased with single radiotherapy doses of 1.8 to 2 Gy. However, higher single doses should not be used. CONCLUSIONS: Due to the worse prognosis of patients with adenocarcinoma of the pancreas, new combined treatment modalities as adjuvant and neoadjuvant radio-chemotherapy, particularly with more modern chemotherapeutic agents, for patients with resectable and unresectable tumors are under investigation. For some reasons, the neoadjuvant setting seems to be better. However, these results are not proven by prospective randomized clinical trials. Therefore, these trials are necessary to define the treatment of choice in these patients. IORT is a helpful tool to improve local control. However, these aggressive multimodality approaches are only indicated in a minority of patients. In patients with unresectable tumors and good condition, combined radio-chemotherapy remains the treatment of choice.

The insertion of the lesser and greater gastric omenta and its significance for the T classification of gastric carcinomas (UICC).

The problem of T classification of proximal gastric carcinomas is becoming increasingly important due to a rise in the incidence of these tumors. The aim of this study was to examine the gastric insertion of the lesser and greater omenta and its role in the T classification of gastric carcinomas. The stomach and greater and lesser omenta were removed from 76 fixed cadavers and 12 measurements each were done in defined localizations. The lesser omentum extended to the gastric wall in 98% of the cases. This junction as well as the omental thickness and thus the retroperitoneal part are especially pronounced in the cardiac region. According to the current UICC classification, even advanced tumors extending into the gastric wall can be classified T2 as long as they do not penetrate the visceral peritoneum. This results in "understaging" and a seemingly poorer prognosis for cardiac carcinomas. Our study results support the recommendation of Hermanek and Wittekind [5] to subdivide the T2 stage of gastric carcinomas on the basis of infiltration depth.

Co-expression of renin-angiotensin system genes in human adipose tissue.

OBJECTIVE: The renin-angiotensin system plays a central role in blood pressure regulation, both by affecting renal function and by modulating vascular tone and structure. Recent studies in rodents demonstrated the existence of several components of this system in adipose tissue. The activity of the renin-angiotensin system appears to be regulated by food intake, suggesting that it may be involved in obesity-associated hypertension. Few data are available on the presence of renin-angiotensin system components in human adipose tissue. MATERIALS AND METHODS: In order to explore the expression of renin-angiotensin system genes in human adipose tissue and adipocytes, total RNA was isolated from whole adipose tissue (subcutaneous and omental) or cultured adipocytes (mammary) and subjected to reverse-transcriptase polymerase chain reaction with primers specific for human angiotensinogen, renin, renin-binding protein, angiotensin converting enzyme, chymase and type 1 and type 2 angiotensin receptors. RESULTS: Angiotensinogen, angiotensin converting enzyme and type 1 angiotensin receptor genes were widely expressed, both in human adipose tissue and in cultured human adipocytes. Furthermore, we found expression of the chymase and renin-binding protein genes in these samples. CONCLUSIONS: Our findings suggest the presence of a local renin -angiotensin system in human adipose tissue, with adipocytes being an important part of this system, and prompt speculation that this local renin-angiotensin system may be involved in obesity-related disorders, including hypertension and the metabolic syndrome.

Manometric analysis of anal sphincter damage after ileal pouch-anal anastomosis.

A constant reduction in anal sphincter pressure follows an ileoanal pouch procedure for ulcerative colitis and familiar adenomatous polyposis. We analyzed whether this reduction is more likely due to neurogenic damage or to direct sphincter trauma. Three-dimensional vector volume manometry was performed in 75 patients prior to the ileoanal pouch procedure and 3 months thereafter. Resting pressure was significantly reduced from 83.5 +/- 24.4 to 58.1 +/- 18.0 mmHg and squeezing pressure from 204.7 +/- 63.3 to 173.4 +/- 50.6 mmHg. Moreover, significant vector volume reductions were recorded postoperatively, and the asymmetry index increased significantly (resting: 11.5 +/- 4.1% to 18.4 +/- 7.4%; squeezing: 9.6 +/- 3.1 to 13.0 +/- 6.7%). Functional anal sphincter length at the high-pressure zone remained unchanged. Thus, there was no local damage to proximal or distal anal sphincter segments, which suggests that the postoperative impairment of sphincter function is secondary to neurogenic rather than morphological damage.

[Cavernous hemangioma of the rectum--a rare differential per anal hemorrhage diagnosis]. / Kavernöses Hämangiom des Rektums--eine seltene Differentialdiagnose der peranalen Blutung.

A 19-year-old woman suffered from recurrent peranal hemorrhage. Over a period of five years she was treated under the suspicion of ulcerative colitis. After a sigmoid resection with a colostomy, proctectomy with an end colostomy followed due to recurrent intractable peranal hemorrhage. Histology of the specimen showed surprisingly a hemangioma of the rectum. Thereafter reconstruction was performed by colopouchanal anastomosis. Afterwards the patient was free of disease and had a good stool-continence. Stool-frequency was twice daily. The second case consisted in a 27-year-old woman who underwent emergency sigmoidectomy due to massive peranal hemorrhage. Here as well diagnosis was a hemangioma of the sigmoid. One year after the first operation the patient had a recurrence of peranal bleeding again due to rectal hemangioma. Since endoscopy and endosonography confirmed a rectal hemangioma a rectal exstirpation with a colopouchanal reconstruction was performed successfully. The reviewed literature shows including the two presented cases a total of 81 cases with rectal hemangiomas. Because of the good results concerning function and morbidity the therapy of choice is rectal exstirpation with colopouchanal reconstruction.

Altered tight junction structure contributes to the impaired epithelial barrier function in ulcerative colitis.

BACKGROUND & AIMS: Mechanisms of diarrhea in ulcerative colitis (UC) are still unknown. Functional and structural characterization of epithelial barrier and transport properties in ulcerative colitis (UC) was performed. METHODS: Inflamed sigmoid colon epithelium from UC patients was studied by alternating current impedance analysis to determine the pure epithelial resistance as a measure of intestinal barrier function. Tight junction (TJ) structure was investigated by freeze-fracture electron microscopy. RESULTS: Although total wall resistance was reduced in UC by 50%, impedance analysis uncovered a much more pronounced barrier defect. Epithelial resistance decreased from 95 +/- 5 to 20 +/- 3 omega3. cm2, which in conventional analysis is masked by an increase in subepithelial resistance from 14 +/- 1 to 36 +/- 3 omega3. cm2 caused by inflammation. This was paralleled by a change in epithelial cell TJ structure in UC. Strand count decreased from 6.94 +/- 0.25 to 4.76 +/- 0.47 at the surface and from 7.26 +/- 0.31 to 5.46 +/- 0.37 in the crypts. CONCLUSIONS: The inflamed colonic mucosa in UC has an impaired barrier function that is much more pronounced than previously assumed. An altered TJ structure contributes to this barrier defect which, because of increased back leak, can reduce net ion transport. Thus, a leak-flux mechanism contributes to the diarrhea in UC.

The prognostic significance of tumor vascularization in patients with localized colorectal cancer.

Angiogenesis is essential for tumor growth and metastasis, and vascular density is known as an independent prognostic factor in several tumor entities. We studied the prognostic relevance of vascular density in colorectal cancer, examining 146 patients treated surgically for cure. Tumor sections were immunostained with JC70, an endothelial cell marker. Microvessel quantification used light microscopy. The slides were scanned at a low magnification, and individual microvessel counts were made on a x200 field in the area of the most dense neovascularization. Vascular density was found to be 75+/-27/visual field and to be independent of age, sex, pT and pN categories, tumor recurrence, and overall survival. Overall survival in the subgroup of patients with tumor recurrence was significantly shorter with tumors of greater vessel density (>75) than in those of less vessel density (<75). Multivariate analysis showed microvessel count to be an independent prognostic factor for the overall survival rate of patients with tumor recurrence; among these patients there was also a significant difference in the relapse-free survival rates between the hypovascular and the hypervascular groups. Our findings suggest that the microvessel density of the primary tumor determines the speed of tumor recurrence after metastatic disease has been triggered by other, unknown mechanisms. Although tumor vascularization can be linked to the aggressiveness of colorectal cancer, it has no value as a new prognostic marker in clinical practice.

Pouchitis: pathophysiology and treatment.

Pouchitis is a potential complication after proctocolectomy and restorative ileoanal anastomosis. It is more frequent in UC than in familial polyposis. Little is known about the etiopathology of pouchitis. Risk factors include the presence of extraintestinal manifestations, primary sclerosing cholangitis, cessation of smoking, and previous course of disease. A host of pathophysiological pathways have been identified as potential mechanisms of pouchitis, which include inflammatory mediators, adhesion molecules, oxygen radical species, p-ANCA, and short-chain fatty acids. The microflora in the pouch may also be an important factor in causing inflammation. The risk of developing cancer in cases of pouchitis has not been established as clearly as in those of UC. Particular attention should be paid to patients who have remaining anorectal mucosa after pouch construction. Experience in the treatment of chronic relapsing and chronic refractory pouchitis is limited. The continuation of conventional anti-inflammatory treatment is successful only in a small percentage of patients. New biological response-modifying therapies which target novel immunoregulatory molecules in IBD will also have impact on the systemic and topical treatment of pouchitis.