Mismatch repair deficiency, chemotherapy and survival for resectable gastric cancer: an observational study from the German staR cohort and a meta-analysis.

PURPOSE: In a post hoc analysis of the MAGIC trial, patients with curatively resected gastric cancer (GC) and mismatch repair (MMR) deficiency (MMRd) had better median overall survival (OS) when treated with surgery alone but worse median OS when treated with additional chemotherapy. Further data are required to corroborate these findings. METHODS: Between April 2013 and December 2018, 458 patients with curatively resected GC, including cancers of the esophagogastric junction Siewert type II and III, were identified in the German centers of the staR consortium. Tumor sections were assessed for expression of MLH1, MSH2, MSH6 and PMS2 by immunohistochemistry. The association between MMR status and survival was assessed. Similar studies published up to January 2021 were then identified in a MEDLINE search for a meta-analysis. RESULTS: MMR-status and survival data were available for 223 patients (median age 66 years, 62.8% male), 23 patients were MMRd (10.3%). After matching for baseline clinical characteristics, median OS was not reached in any subgroup. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd and MMRp had a HR of 0.67 (95% CI 0.13-3.37, P = 0.63) and 1.44 (95% CI 0.66-3.13, P = 0.36), respectively. The meta-analysis included pooled data from 385 patients. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd had an improved OS with a HR of 0.36 (95% CI 0.14-0.91, P = 0.03), whereas those with MMRp had a HR of 1.18 (95% CI 0.89-1.58, P = 0.26). CONCLUSION: Our data support a positive prognostic effect for MMRd in GC patients treated with surgery only and a differentially negative prognostic effect in patients treated with perioperative chemotherapy. MMR status determined by preoperative biopsies may be used as a predictive biomarker to select patients for perioperative chemotherapy in curatively resectable GC.

[Safety of resection of symptomatic and asymptomatic Meckel's diverticulum and literature review]. / Das Meckel-Divertikel: Sicherheit der Resektion symptomatischer und asymptomatischer Befunde und Literaturübersicht.

BACKGROUND: Meckel's diverticulum (MD) is the most common diverticulum of the small bowel and an important finding in surgical practice. The aim of this study was to assess the safety of the resection of symptomatic and asymptomatic MD concerning postoperative complications. As MD are relatively rare, an overview of the literature is given. PATIENTS AND METHODS: All patients with MD at the department at general surgery of the Charité - Campus Benjamin Franklin between 1996 and 2010 were assessed. An analysis for symptomatic and incidental MD was performed for incidence, indication, intraoperative findings, histology and postoperative outcome. RESULTS: An MD was intraoperatively found in 71 of 29 682 patients (0.2 %). Of these, a symptomatic MD occurred in 26 patients (37 %). A symptomatic MD was causal in 6 of 7 patients with gastrointestinal bleeding (GIB, p = 0.005). All symptomatic MD and 30 (67 %) asymptomatic MD were resected. Ectopic gastric mucosa was found significantly more frequently in patients with symptomatic MD (p = 0.001). Patients with asymptomatic MD and resection had less complications as a trend (p = 0.057). CONCLUSION: Ectopic mucosa is more frequent in symptomatic MD, especially in bleeding MD. MD should always be considered in GIB of unknown origin. Resection of incidental MD can be recommended in patients without contraindications such as peritonitis, cancer, ascites or immunosuppression.

Locally recurrent colorectal cancer: results of surgical therapy.

PURPOSE: Up to 20 % of colorectal cancer patients develop recurrent disease despite standardized surgical techniques and multimodal treatment strategies. Radical resection is the central component of curative therapy in these cases. The aim of this study was to evaluate treatment results in patients with locoregionally recurrent colorectal cancer. METHODS: From January 1995 to December 2007, surgery was performed for recurrent colorectal cancer in 82 patients who had undergone curative (R0) resection of their primary tumor. Assessment included patient, tumor and treatment characteristics, postoperative complications, and time without re-recurrence; recurrence-free and overall survival rates were calculated according to the Kaplan-Meier method. RESULTS: Resection was performed in 60 of the 82 patients (73 %), repeat R0 resection in 52 % (31/60). Patients had a postoperative morbidity of 39 % (31/82), a relaparotomy rate of 13 % (11/82), and a lethality of 7 % (6/82). Forty-eight percent of all surgically-treated patients received a permanent stoma. Re-recurrence was seen in 52 % (16/31). R0 resection was associated with a 5-year survival rate of 35 % (11/31). CONCLUSIONS: Extensive reinterventions often enable repeat R0 resection. Despite relevant morbidity, the lethality appears to be acceptable. Decisive for the prognosis is re-recurrence.

Management and results of complications after anterior resection with colonic pouch reconstruction for rectal cancer.

AIM: Colonic J-pouch reconstruction is widely carried out during low anterior resection. The aim of this observational study was to describe the complications and evaluate the results of adverse event management. METHOD: A total of 128 patients underwent an elective anterior resection with colorectal or coloanal J-pouch reconstruction for primary rectal cancer between January 1997 and December 2008. RESULTS: The overall mortality was 1.6%. Three (2.3%) patients developed pouch necrosis, one of whom died. The rate of anastomotic leakage was 11.7%. Other major complications included intra-abdominal abscess (3.1%), haemorrhage (0.8%) and abdominal dihiscence (0.8%). In all cases of anastomotic leakage, the pouch was salvaged, with 80% of patients undergoing surgical revision with relaparotomy and transanal suture. Patients with pouch necrosis underwent relaparotomy with removal of the pouch and a terminal colostomy. In all cases of intra-abdominal abscess without anastomotic leakage, radiologically controlled percutaneous drainage was carried out. CONCLUSION: Anal function can usually be saved after anastomotic leakage by salvage surgery without increase in mortality.

Do the cardiovascular risk profile and the degree of arterial wall calcification influence the performance of MDCT angiography of lower extremity arteries?

OBJECTIVES: To retrospectively assess the influence of arterial wall calcifications on the accuracy of run-off computed tomographic angiography (CTA) and to analyse whether cardiovascular risk factors are predictors of compromising calcifications. METHODS: In 200 consecutive patients who underwent run-off CTA, calcifications were assessed in pelvic, thigh and calf arteries using a four-point scale. Fifty-nine patients with digital subtraction angiography (DSA) were assessed by both techniques to estimate a threshold of compromising calcifications, defined as a decrease of sensitivity, specificity, PPV or NPV below the lower 95% confidence interval of overall results. Regression analysis was performed to investigate a potential relationship between compromising calcifications and presence of cardiovascular risk factors, advanced patient age and severe peripheral arterial disease (PAD). RESULTS: The highest Ca(++)-score was chosen as the cut-off for the regression analysis, as a relevant decrease of specificity (0.91; overall: 0.95) above the knee and of sensitivity (0.66; overall: 0.83), specificity (0.65; overall: 0.93), positive predictive value (PPV) and negative predictive value (NPV) below the knee was observed. In the pelvic and thigh arteries, severe PAD (Fontaine Stage >or=III) showed the highest odds ratio for compromising calcifications (2.9), followed by diabetes mellitus (2.4), renal failure (2.1) and smoking (1.7). In the calf, renal failure (12.2) and diabetes mellitus (3.3) were the strongest predictors. CONCLUSIONS: Patients with diabetes and renal failure should be considered as candidates for alternative vessel imaging in order to avoid inconclusive examination results.

The vasculitis in IBD is associated with the degree of inflammation.

The role of vasculitis in the pathogenesis of IBD remains unclear. The aim of this study was to evaluate the detection rate of vasculitis in patients with IBD, its location in the intestinal wall layers and whether it occurs dependent of the degree of inflammation. Immunohistological staining with the endothelial cell marker CD31 and the pan-T cell marker CD3 was performed in 56 colonic specimens of Crohn's disease, in 43 of ulcerative colitis, and in 5 of colon cancer. Quantification of the degree of inflammation was done using a histological colitis score. There was no sign of vasculitis in the healthy intestinal wall layers. In Crohn's disease, specimens with minor inflammatory activity (score 0-2) disclosed no vasculitis. Vasculitis was observed in 82% of the specimens with an inflammatory degree of 3 and in 100% with an inflammatory degree of 4. Vasculitis was detected in all intestinal wall layers altered by inflammation. A direct association between vasculitis and granulomas was observed in only 5% of the specimens with an inflammatory degree of 4. All ulcerative colitis specimens evidenced an inflammatory degree between 2 and 4. No vasculitis was found in specimens with an inflammatory degree of 2, but in 57% with an inflammatory degree of 3 and in 100% with an inflammatory degree of 4. Vasculitis is only detectable in the mucous membrane changed by inflammation. Thus, the vasculitis in IBD is exclusively observed in the intestinal wall layers altered by inflammation. The extent of vasculitis depends on the degree of inflammation. An association between vasculitis and granuloma in Crohn's disease is seen in 5% of the cases.

[Is hepatic portal venous gas the writing on the wall?]. / Hepato-portomesenteriale Lufteinschlüsse - ein Menetekel?

BACKGROUND: Hepatic portal venous gas, which may occur in conjunction with severe intra-abdominal infections, is associated with a high mortality rate and is considered as an alarm signal. HISTORY: CT diagnostics revealed hepatic portal venous gas in a 65-year-old patient with advanced perforated sigmoid diverticulitis. This phenomenon was also observed in a 75-year-old patient in association with an upside-down stomach incarceration. Both patients underwent emergency surgery and survived this life-threatening disease. CONCLUSION: Since hepatic portal gas is usually caused by severe intra-abdominal diseases with a high mortality rate, this warning sign should, at the latest, result in urgent laparotomy, if the indication has not already been established for other reasons.

[An unusual case of upper GI bleeding: esophageal cancer metastasis at a percutaneous endoscopic gastrostomy site--case report and review of the literature]. / Ungewöhnlicher Fall einer akuten oberen gastrointestinalen Blutung: PEG-Implantationsmetastase eines Osophaguskarzinoms--Fallbericht und Literaturübersicht.

We present the case of a patient with an esophageal squamous cell carcinoma, who was treated primarily by radiotherapy. Due to dysphagia, the patient received a percutaneous endoscopic gastrostomy (PEG) without any sign of tumour at that time. Five months later the patient presented with an upper GI bleeding from a gastric ulcer, which histologically turned out to be a metastasis of the previously diagnosed squamous cell carcinoma. So-called "implantation metastases" at the percutaneous endoscopic gastrostomy site are rare and most of the cases have been described in patients with head and neck tumours. Moreover, the presentation as an upper GI bleed is very uncommon and needs the attention of both endoscopists as well as gastrointestinal oncologists. Clinicopathological features of this case with a brief review of the literature are presented.

[Results of multivisceral resection of primary colorectal cancer]. / Ergebnisse der multiviszeralen Resektion des primären kolorektalen Karzinoms.

BACKGROUND: In about 10 % of all patients with colorectal cancer, the primary invention already discloses adhesions or infiltration of adjacent organs. En bloc resection of the tumor-bearing bowel segment with adjacent organs is done to give patients a chance for curation, since intraoperative differentiation is not possible. The aim of this study is characterization of the patient population as well as evaluation of the morbidity and mortality associated with this type of extensive intervention. METHOD: Between 1/95 and 6/04, we analyzed all patients with progressive primary colorectal cancer, who underwent multivisceral surgery with en bloc resection of at least one other organ. The target parameters were tumor characteristics as well as postoperative morbidity and mortality. RESULTS: A total of 1 001 patients with colorectal cancer underwent surgery. 101 patients (10 %) required multivisceral resection. In 17 % the indication was exigent. About 70 % of the interventions involved the colon. Tumor perforation was seen in 17 % of patients with colon cancer and 16 % with rectal cancer. Resection of the inner genitals was most frequent in both colon and rectal cancer (26 and 84 %) followed by small bowel resection (21 %) and partial bladder resection (19 %). Other organs play a secondary role in rectal cancer while partial bladder resection (20 %) and abdominal wall resection (14 %) is observed more frequently in colon cancer. Resection of parenchymatous organs (kidney, suprarenal gland, spleen, pancreas, liver) and others like the stomach is quite rare in colon cancer. Actual tumor infiltration (T4 situation) was observed in 51 % of patients with colon cancer and in 64 % of those with rectal cancer. Local R0 resection (97 vs. 96 %) was successfully performed in nearly all colon and rectal cancer patients. The surgical major complication rate was 9 % in colon cancer and 19 % in rectal cancer. The mortality rate was 4 %. CONCLUSION: Multivisceral en-bloc resection enables local R0 resection in the majority of cases with primary colorectal cancer. Despite sometimes extensive surgery, this type of procedure is associated with an acceptable morbidity and mortality. Since long-term survival is comparable to that in the T category (T3 or T4), multivisceral en-bloc resection is not only justified but also absolutely required in interventions with curative intention.

[16-row multidetector CT angiography of the aortoiliac system and lower extremity arteries: contrast enhancement and image quality using a standarized examination protocol]. / Becken-Bein-CT-Angiographie mit der 16-Zeilen-Multislice-Technik: Kontrastmittel-Enhancement und Bildqualität unter Einsatz eines standardisierten Untersuchungsprotokolls.

PURPOSE: To assess the degree of enhancement and image quality of 16-slice multidetector CT angiography (MDCTA) of pelvic and lower limb arteries with a monophasic contrast medium injection protocol. MATERIALS AND METHODS: Fifty patients underwent a CT angiography of the pelvic and lower limb arteries using the following parameters: collimation 16 x 1.5 mm, rotation time 0.5 s, table feed 40 mm/sec, slice thickness 2 mm, reconstruction interval 1.2 mm, 100 ml Iomeprol 400 + 60 ml normal saline, flow rate 4 ml/s, bolus tracking (threshold of 250 DeltaHU in aorta). Arterial enhancement was measured in all arterial segments. Maximum intensity projections (MIP) together with axial images were reviewed by two radiologists (consensus). If the results were inconclusive for stenosis, additional curved multiplanar reformations (MPR) were performed. RESULTS: The mean arterial enhancement values were aorta: 314 +/- 69, pelvis: 342 +/- 105, thigh: 347 +/- 139, calf: 231 +/- 109 DeltaHU. The image quality was judged as excellent in 346 (77.6 %), adequate in 76 (17 %), and inadequate in 24 (5.4 %, all but one in calf and foot) of 446 arterial territories. An override of the contrast bolus below the knee occurred in 2 patients rendering the calf arteries nondiagnostic. Venous enhancement occurred in 13 patients but this compromised the diagnostic assessment in only one case. Additional MPRs were required accurately to assess stenoses in 22 of 200 arterial levels in 16 patients with marked arterial calcifications. CONCLUSION: 16-slice MDCTA with a monophasic contrast bolus of Iomeprol 400 provided good arterial enhancement and diagnostic image quality in 94.6 % of the depicted arterial segments. The majority (67 %) of nondiagnostic segments were below the ankle. MPRs were required in patients with marked calcification for accurate assessment of stenosis.

[Emergency management of thoracic trauma]. / Die Notfallversorgung des Thoraxtraumas.

Thoracic injuries are a major cause of mortality during the "golden hour" of trauma. Many patients with chest trauma die after reaching the hospital. Less than 10% of all blunt thoracic injuries require a thoracotomy, and many potentially life-threatening conditions can be relieved by simple procedures, such as chest tube insertion.Thus, many cases of traumatic deaths due to chest injury may be prevented by prompt diagnosis and a standardized therapeutic approach in the emergency room. A high index of suspicion for lethal injury patterns, based on the mechanism of trauma and the clinical presentation, is a crucial prerequisite for an adequate initial assessment and management of patients with chest trauma. The worldwide implementation of standardized diagnostic and therapeutic guidelines, such as the "Advanced Trauma Life Support" (ATLS) protocol, has led to a significant reduction of early deaths attributed to thoracic injuries.

[Transluminal retrieval of intravasal foreign bodies. Incidence, clinical signs, diagnostics and interventional therapy of catheter embolization]. / Transluminale Bergung intravasaler Fremdkörper. Inzidenz, Klinik, Diagnostik und interventionelle Therapie der Katheterembolie.

Patients with central venous lines or implanted Hickman catheters and port systems, suffer catheter embolization in 0.1-2.8% of the cases due to material fatigue or medical malpractice. In a 58-year-old vascular surgery patient, a central venous line catheter fragment was successfully retrieved from the pulmonary artery using a snare catheter via a transfemoral approach. From this case, we discuss the incidence, clinical aspects, diagnosis and interventional therapy of catheter embolization.

[Diagnostics and surgical therapy of enteric intussusception in adults illustrated by three cases]. / Dünndarminvagination beim Erwachsenen. Diagnostik und chirurgische Therapie anhand von 3 Fallbeispielen.

The diagnosis of enteric intussusception is rare in adults but not in children. The clinical picture often takes an insidious course. Acute abdomen may also be caused by enteric intussusception. We report on three patients with enteric intussusception and acute abdomen. In two cases, a CT led to the diagnosis of invagination of the small intestine. In one patient, invagination of the terminal ileum was detected during coloscopy. All patients were submitted to limited segment resection and end-to-end anastomosis. In all three cases, the invagination was caused by benign pathological changes. Enteric intussusception in adults always requires surgery. In more than 95% of the cases, pathological findings are obtained intraoperatively, which are benign in the small intestine in 85-95% of the cases.

Tumour necrosis factor alpha and nuclear factor kappaB inhibit transcription of human TFF3 encoding a gastrointestinal healing peptide.

BACKGROUND: and aims: Tumour necrosis factor alpha (TNF-alpha) induction of nuclear factor kappaB (NFkappaB) activation plays a major role in the pathogenesis of inflammatory bowel disease (IBD). Trefoil factor family peptides TFF1, TFF2, and TFF3 exert protective, curative, and tumour suppressive functions in the gastrointestinal tract. In this study, we investigated effects of the TNF-alpha/NFkappaB regulatory pathway by TNF-alpha on expression of TFFs. METHODS: After TNF-alpha stimulation, expression of TFF genes was analysed by quantitative real time polymerase chain reaction and by reporter gene assays in the gastrointestinal tumour cell lines HT-29 and KATO III. Additionally, NFkappaB subunits and a constitutive repressive form of inhibitory factor kappaB (IkappaB) were transiently coexpressed. In vivo, morphological changes and expression of TFF3, mucins, and NFkappaB were monitored by immunohistochemistry in a rat model of 2,4,6-trinitrobenzene sulphonic acid induced colitis. RESULTS: TNF-alpha stimulation evoked up to 10-fold reduction of TFF3 expression in the colon tumour cell line HT-29. Downregulation of reporter gene transcription of TFF3 was observed with both TNF-alpha and NFkappaB, and was reversible by IkappaB. In vivo, the increase in epithelial expression of NFkappaB coincided with reduced TFF3 expression during the acute phase of experimental colitis. CONCLUSIONS: Downregulation of intestinal trefoil factor TFF3 is caused by repression of transcription through TNF-alpha and NFkappaB activation in vitro. In IBD, perpetual activation of NFkappaB activity may contribute to ulceration and decreased wound healing through reduced TFF3.

Persistent left superior vena cava: a reason for pseudodisplacement of a port catheter.

Port catheters have been increasingly used in recent years. Using one case as an example, we demonstrate how an anatomic variation can easily become a pitfall when inserting a central venous catheter, port catheter, pacemaker or Swan-Ganz catheter. We report a case of persistent left superior vena cava, the most common variation in the thoracic venous system. Since these procedures are increasingly being performed, surgeons, anesthesiologists and radiologists should be aware of the possible anatomic variations.

[Radical resection of colorectal carcinoma in the oldest old]. / Radikale Resektion des kolorektalen Karzinoms bei Hochbetagten.

INTRODUCTION: The percentage of old people with colorectal cancer is steadily increasing in Western industrialized countries. Since there are only a few reports on the extent of surgery, it is unclear whether radical lymphadenectomy can also be safely performed as a standard operation in this age group. METHODS: In a prospective study, we analyzed all patients who were > or = 80 years of age at the time of surgery and who were submitted to surgery between 1/95 and 12/00 due to a colorectal carcinoma. Target parameters were postoperative morbidity and mortality. RESULTS: Fifty-seven of 665 patients (8.6%) were > or = 80 years of age. The median age was 85 years (range: 80-92). The gender ratio was 1:1.6 (G:E). Palliative surgery was performed in 19 of 57 patients. The remaining 38 patients underwent curative radical lymphadenectomy; 32 were elective and 6 emergency procedures. Mean ASA scores were 2.1 +/- 0.3 and 2.5 +/- 0.6. The following operations were performed: 13 right-sided and 15 left-sided hemicolectomies, 5 rectal resections, 3 rectal extirpations and 2 Hartmann's procedures. Two anastomotic insufficiencies (6%) had a complication-free course after revision. The rate of major surgical complications was 11%, that of internal complications 16%. Three patients (8%) died, one after an elective procedure and two after emergency laparotomy. One of the latter was an 89-year-old woman who refused to undergo a revision due to bleeding after Hartmann's procedure. Pneumonia and myocardial infarction were the cause of death in the other two patients. CONCLUSION: Radical resection can be safely performed even at an advanced age. Since age-corrected survival is comparable to that of younger patients, surgery should be performed in the elderly under elective conditions according to oncological criteria.

Changes of colonic mucosal microcirculation and histology in two colitis models: an experimental study using intravital microscopy and a new histological scoring system.

This study investigated capillary blood flow (CBF) and pathomorphological alterations in the mucosa of different bowel segments at different times after disease onset in rats with colitis induced by either trinitrobenzensulfonic acid (TNBS) or mitomycin-C. CBF was determined by intravital microscopy using fluorescein-labeled erythrocytes. The histological degree of inflammation was assessed by a new scoring system. Severe acute histological changes were found in the distal colon 24 hr after induction of TNBS colitis (score: 8.9+/-1.0). CBF was increased (2.9+/-0.05 vs. 2.6+/-0.04 nl/min in healthy controls). The histological alterations persisted until day 3 (8.5+/-0.9) when CBF significantly decreased (1.8+/-0.05 nl/min). After 15 days, moderate acute inflammation was still detectable histologically (5.4+/-1.3), but CBF had returned to normal values. In mitomycin-C colitis, changes developed mainly in the proximal colon: After three days, there was mild inflammation (2.8+/-1.2) with normal CBF (2.5+/-0.1 nl/min). After seven days, the inflammation had increased (4.8+/-1.1), while CBF had decreased (1.5+/-0.06 nl/min). These changes persisted for six weeks (5.3+/-0.7; 1.2+/-0.05 nl/min). These data suggest that disturbed colonic microcirculation may play an important role in the pathogenesis of inflammatory bowel disease regardless of the histopathomorphological alterations.

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.

Does glutamine reduce bacterial translocation? A study in two animal models with impaired gut barrier.

Failure of intestinal barrier function and subsequent translocation of bacteria from the gut are believed to play a decisive role in the development of systemic septic complications, for example, following major trauma or major abdominal surgery. This study evaluated: (a) the effect of glutamine on colonic microcirculation and electrophysiological parameters reflecting gut barrier function, (b) the translocation of live bacteria to extraintestinal organs, and (c) disease outcome in two animal models with impaired gut barrier function. Severe acute pancreatitis or colitis was induced in rats randomized for therapy with or without glutamine (0.5 g/kg daily). After 48 h one animal group was prepared for intravital microscopy of colonic capillary blood flow and electrophysiological measurement of gut permeability; another was killed after 96 h for histological and microbiological examination. In animals with pancreatitis, glutamine (Gln) supplementation significantly improved gut permeability, i.e., Gln increased colonic transmucosal resistance from 67+/-7 to 92+/-3 Omega/cm(2) and decreased mannitol flux through the epithelium by 53%. Capillary blood flow in the colonic mucosa was improved by 25%. The prevalence of pancreatic infections was reduced from 86% in animals on standard parenteral nutrition to 33% in animals given the Gln-enriched diet (P<0.05); mortality decreased by 32%. In colitis, Gln had no significant effect on these parameters except for improving colonic capillary blood flow in colon segments not adjacent to the major injury site. Glutamine supplementation improves colonic capillary blood flow, stabilizes gut permeability, and reduces secondary pancreatic infections and mortality in severe rodent pancreatitis, but it is not helpful in colitis. This confirms previous reports that glutamine stabilizes gut barrier function only in certain diseases. Our experimental data strongly suggest that acute pancreatitis (rather than colitis) is one of the diseases with gut barrier dysfunction in which glutamine substitution may be helpful to reduce bacterial translocation and should therefore be tested in a controlled clinical trial.

Does microcirculation play a role in the pathogenesis of inflammatory bowel diseases? Answers from intravital microscopic studies in animal models.

The potential role of intestinal microcirculation for the development of inflammatory bowel diseases (IBD) has not been systematically investigated, mainly because of methodological problems. Using a well-established rodent model of IBD and intravital microscopy, the present study investigated whether (and when) gut microcirculation is disturbed in IBD, and whether microcirculatory disorders contribute to histological and functional alterations in the development of IBD. Colitis was induced by rectal injection of trinitrobenzene sulfonic acid. After 1, 3, and 15 days rats were laparotomized for intravital microscopic determination of mucosal colonic blood flow. In a second series it was examined whether enhancing colonic capillary blood flow by hemodilution therapy stabilizes colonic wall resistance and other electrophysiological parameters of gut permeability. Additional measurements involved hemodynamic monitoring and histological examinations. Colonic capillary blood flow was significantly decreased 3 days after colitis induction (1.8 +/- 0.05 vs. 2.6 +/- 0.04 nl/min in healthy control animals) when histology revealed signs of acute inflammation, and normal values after 15 days (2.4 +/- 0.06 nl/min) when chronic histological changes were evident. Hemodilution therapy enhanced colonic capillary blood flow in the initial stage (2.1 +/- 0.02 vs. 1.6 +/- 0.02 nl/min in saline-treated animals with trinitrobenzene sulfonic acid colitis) and improved gut resistance and electronic chloride secretion (73 +/- 15 vs. 33 +/- 8 microA cm2). Histological alterations were not significantly attenuated. Impaired colonic capillary blood flow in the initial stage of experimental colitis and improved mucosal microcirculation with stabilized gut permeability suggests that the early microcirculatory disturbances precede chronic histological changes and influence functional alterations in the course of the disease. Research should be continued in this field because important mechanisms in the pathogenesis of IBD and potentially therapeutic (vasoactive) substances may otherwise be overlooked.