Endoscopic full-thickness resection using an over-the-scope device for treatment of recurrent / residual colorectal neoplasia: a single-center case series.

BACKGROUND: Endoscopic mucosal resection (EMR) in piecemeal technique is the treatment standard for larger flat or sessile colorectal lesions. The method is burdened by a high recurrence rate mostly presenting as difficult to resect lesions. In these situations, endoscopic full thickness resection (EFTR) with an over-the-scope device offers the option of complete resection despite scar formation. METHODS: We conducted a retrospective case review of 30 consecutive EFTR interventions on small (< 20 mm), difficult to resect recurrent / residual colorectal neoplastic lesions treated by EFTR. RESULTS: EFTR was technically feasible in 28/30 (93,3%) of the cases with an R0 resection in 24/30 (80%) and a median procedure time (marking to full thickness resection) of 34,5 min (11-120). After the first 15 procedures, the per-protocol rate increased from 13/15 to 15/15 and the R0 resection rate increased from 9/15 (69,2%) to 15/15 (100,0%; p < 0.01). One patient suffered from a delayed perforation the day after the procedure and needed emergency surgery (3,6%). Minor bleeding occurred in 3/28 patients (10,7%) and post-interventional fever in one patient (3,6%). The 30-day mortality rate was 0%. CONCLUSIONS: EFTR with an over-the-scope device is a useful method for endoscopic resection of difficult to treat recurrent or residual colorectal neoplasia after previous endoscopic therapy. High R0 resection rates were observed after a relatively short learning curve. The complication rate in this series seems acceptable given the complexity of the resected lesions.

Implementation of endoscopic submucosal dissection for early upper gastrointestinal tract cancer after primary experience in colorectal endoscopic submucosal dissection.

Background Current guidelines recommend endoscopic submucosal dissection (ESD) as a treatment option for early cancers of the upper gastrointestinal tract with absent or minimal risk of lymph node metastasis. However, due to the low prevalence of these entities, it is difficult to achieve a competence level for ESD of upper gastrointestinal tract cancers in the Western World. Here, we present single-center data on the implementation of upper gastrointestinal ESD after previous experience with 89 colorectal ESD cases. Methods Retrospective case series of 39 consecutive patients with early cancers of the esophagus (n = 13) or cardia and stomach (n = 26) treated with ESD over a 4-year period. Results ESD was technically feasible in all cases with en bloc, R0, and curative resection rates of 100 %, 76.9 %, and 71.8 %, respectively, and a mean procedure time of 100 minutes (30 - 360 minutes). After an initial 20 procedures, the R0 and curative resection rates increased from 65.0 % to 89.5 %, and from 60.0 % to 84.2 %, respectively. Complications were observed in four patients (10.3 %): three perforations, one case of delayed bleeding, and one esophageal stricture. No case required emergency surgery; the 30-day mortality rate was 0 %. Conclusion In this modest case series from Europe, we observed an effectiveness and complication rate for ESD for early esophageal and gastric cancer that are comparable to other series from Europe but also to more abundant data from Asia. The results indicate that even small numbers of upper gastrointestinal cancers can be managed adequately in centers with expertise in colorectal ESD.

Full-thickness resection with an over-the-scope device: possible translocation of adenoma tissue in a case of an incomplete resection at the appendix.

Background and study aims Clip-assisted endoscopic full-thickness resection has great potential for treatment of difficult-to-resect colorectal neoplasia. Here, we report on endoscopic full-thickness resection at the appendiceal orifice with the appendix in situ requiring emergency surgery due to acute appendicitis. Final histopathology showed appendicitis and residual serrated adenoma within the appendiceal stump, but unexpectedly, also a displaced adenoma fragment at the serosal surface of the cecum. Given the transmural placement of the clip prior to snare resection, translocation of neoplastic tissue to the extra luminal site in cases of incomplete adenoma/carcinoma resection could be a concern.

Endoscopic submucosal dissection for flat or sessile colorectal neoplasia > 20 mm: A European single-center series of 182 cases.

BACKGROUND AND STUDY AIMS: Colorectal endoscopic submucosal dissection (ESD) is an attractive method for en bloc resection of larger flat neoplastic lesions. Experience with this method is limited in the Western World. PATIENTS AND METHODS: A total of 182 consecutive flat or sessile colorectal lesions (cecum n = 43; right-sided colon n = 65; left-sided colon n = 11, rectum: n = 63) with a size > 20 mm (mean 41.0 ±â€Š17.4 mm) were resected in 178 patients. The data were recorded prospectively. RESULTS: ESD was technically feasible in 85.2 % of patients with a mean procedure time of 127.5 min (±â€Š99.8) min and a complication rate of 11.5 % (microperforation 9.3 %, delayed bleeding 2.7 %, no case of emergency surgery, 30-day mortality rate 0 %). For 155 successfully completed procedures the en bloc and R0 resection rates were 88.4 and 62.6 %. Efficacy was better for smaller lesions (20 mm to 49 mm; n = 131) than for larger lesions (50 mm to 140 mm; n = 51) with R0 rates of 70.8 vs. 40.5 % (P < 0.001) and procedure times of 92.7 ±â€Š62.4 minutes vs. 217.0 ±â€Š120.9 minutes (P < 0,001). CONCLUSIONS: This series confirms the efficacy of ESD for en bloc resection of colorectal lesions > 20 mm. RESULTS are satisfactory for lesions up to 50 mm. ESD for larger lesions was associated with low R0 resection rates and very long procedure times. The clinical consequences of microperforations were minor and do not argue against the spread of ESD in the West. Meeting presentations: The data were presented in part at DDW 2014, Chicago IL, USA (Gastrointest Endosc 2014; 79: AB536).

Endoscopic mucosal resection of colorectal adenomas > 20 mm: Risk factors for recurrence.

AIM: To evaluate risk factors for local recurrence after endoscopic mucosal resection of colorectal adenomas > 20 mm. METHODS: Retrospective data analysis of 216 endoscopic mucosal resections for colorectal adenomas > 20 mm in 179 patients (40.3% female; median age 68 years; range 35-91 years). All patients had at least 1 follow-up endoscopy with a minimum control interval of 2 mo (mean follow-up 6 mo/2.0-43.4 mo). Possible factors associated with local recurrence were analyzed by univariate and multivariate analysis. RESULTS: Median size of the lesions was 30 mm (20-70 mm), 69.0% were localized in the right-sided (cecum, ascending and transverse) colon. Most of the lesions (85.6%) showed a non-pedunculated morphology and the majority of resections was in piecemeal technique (78.7%). Histology showed carcinoma or high-grade intraepithelial neoplasia in 51/216 (23.6%) lesions including 4 low risk carcinomas (pT1a, L0, V0, R0 - G1/G2). Histologically proven recurrence was observed in 33/216 patients (15.3%). Patient age > 65 years, polyp size > 30 mm, non-pedunculated morphology, localization in the right-sided colon, piecemeal resection and tubular-villous histology were found as associated factors in univariate analysis. On multivariate analysis, only localization in the right-sided colon (HR = 6.842/95%CI: 1.540-30.394; P = 0.011), tubular-villous histology (HR = 3.713/95%CI: 1.617-8.528; P = 0.002) and polyp size > 30 mm (HR = 2.563/95%CI: 1.179-5.570; P = 0.017) were significantly associated risk factors for adenoma recurrence. CONCLUSION: Meticulous endoscopic follow-up is warranted after endoscopic mucosal resection of adenomas localized in the right-sided colon larger than > 30 mm, with tubular-villous histology.

Endoscopic Submucosal Dissection (ESD) in Colorectal Tumors.

BACKGROUND: Endoscopic submucosal dissection (ESD) - initially developed for the treatment of early gastric cancer in Japan - is an attractive option for en bloc resection of larger sessile or flat colorectal neoplasia. METHODS: A review of the current literature on colorectal ESD was carried out. RESULTS: In contrast to conventional endoscopic mucosal resection (EMR), ESD for larger colorectal neoplasia yields high en bloc resection rates and very low recurrence rates. The frequency of delayed bleeding is similar for EMR and ESD. Higher perforation rates during ESD are mostly due to microperforations identified and treated during the intervention, and are therefore of minor clinical relevance. A major disadvantage of ESD is the necessity for high-level endoscopic skills and long procedure times. ESD also has the potential to replace laparoscopic surgery or transanal endoscopic microsurgery mainly due to its lower complication rates. CONCLUSION: ESD for the resection of larger flat or sessile colorectal lesions has potential advantages over conventional EMR or minimally invasive surgery. Due to the low incidence of early gastric cancer, experience with ESD will remain limited in Western countries. The spread of colorectal ESD will depend on adequate training opportunities and also on modifications yielding a reduction in procedure time.

Selective downregulation of retinoic acid-inducible gene I within the intestinal epithelial compartment in Crohn's disease.

BACKGROUND: A defective innate immune response may contribute to the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). Employing a global gene expression analysis, this study was aimed at identifying specifically regulated genes within the epithelial compartment in inflammatory bowel disease (IBD). METHODS: The epithelial fraction of human ileal mucosa samples from surgical specimens was obtained by laser microdissection. Gene expression was examined by global expression profiling (n = 18, Affymetrix), quantitative reverse-transcription polymerase chain reaction (RT-PCR) (n = 35), immunoblot analysis (n = 9), and immunohistochemistry (n = 25). RESULTS: Global expression profiling revealed a pronounced downregulation of the retinoic acid-inducible gene I (RIG-I) within the epithelial layer of the ileum in patients with CD but not with UC. The downregulation of RIG-I was confirmed by quantitative RT-PCR, immunoblot analysis, and immunohistochemistry. CONCLUSIONS: Epithelial downregulation of RIG-I, a known pattern recognition receptor for viral components, might contribute to alterations of the innate mucosal immune response, particularly in CD.

A prominent role for mucosal cystine/cysteine metabolism in intestinal immunoregulation.

BACKGROUND & AIMS: T-cell receptor reactivity of intestinal lamina propria T cells (LP-T) critically depends on the capacity of local accessory cells to secrete cysteine. For T cells, cysteine is the limiting precursor for glutathione synthesis, a prerequisite for antigen-dependent proliferation. We aimed to determine the role of the redoxactive microenvironment for hyporeactivity of LP-T in normal human gut vs hyperreactivity of LP-T in inflammatory bowel disease. METHODS: Parameters relevant to cysteine production, determined as acid-soluble thiol, by intestinal lamina propria macrophages (LP-MO) vs peripheral blood monocytes were investigated (L-[(35)S]cystine uptake via system x(c)(-), messenger RNA, and protein expression of the cystine transporter subunit xCT). Glutathione levels in LP-T and peripheral blood T cells were analyzed both spectrophotometrically and by immunofluorescent staining in situ and in vitro. RESULTS: LP-MO from normal gut, unlike peripheral blood monocytes, are unable to take up cystine, which is due to a deficient expression of the transporter xCT in situ and in vitro. As a consequence, LP-MO do not secrete cysteine. The glutathione content in LP-T from normal gut is <50% of that in autologous peripheral blood T cells. In contrast, in inflammatory bowel disease, CD14(+)CD68(+) LP-MO express xCT and secrete substantial amounts of cysteine upon stimulation, which results in high glutathione levels and full T-cell receptor reactivity in LP-T. CONCLUSIONS: The antioxidative microenvironment of LP-T in inflammatory bowel disease and the prooxidative microenvironment in normal gut explain the differential T-cell receptor reactivities.

Management of a rare case of fulminant hemobilia due to arteriobiliary fistula following total pancreatectomy.

Hemobilia is a rare cause of acute upper gastrointestinal bleeding and is often associated with a history of hepatic or biliary tract injury, tumor growth, hepatic artery aneurysm, cholecystitis, or hepatic abscess. We report a case of a 76-year-old patient with massive hemobilia due to intrahepatic bleeding from the segment 8 hepatic artery without evidence of a true aneurysm, abscess, or metastatic disease 4 weeks following pylorus-preserving total pancreatectomy for pancreatic cancer. Gastroduodenoscopy suggested hemorrhage from the duodenojejunostomy but failed to achieve hemostasis, and the patient underwent exploratory laparotomy. It was realized intraoperatively that the bleeding originated from the intrahepatic biliary tract. Bleeding was controlled by blocking the right hepatic bile duct with a Fogarty catheter and subsequent transarterial embolization. Computed tomography did not reveal any local liver or vascular pathology. Retrospectively, the cause of delayed profuse hemobilia was most likely a traumatic intrahepatic pseudoaneurysm following endoscopic bile duct stenting 3 weeks before the pancreatectomy. The reported case is exceptional and of particular interest because of the absence of a typical history or cause of hemobilia, preoperative misleading diagnostic results in an altered anatomic situation, and the operative management to achieve bleeding control in this emergency setting.

Low intestinal glutamine level and low glutaminase activity in Crohn's disease: a rational for glutamine supplementation?

Intestinal glutamine utilization is integral to mucosal regeneration. We analyzed the systemic and intestinal glutamine status in Crohn's disease (CD) and evaluated the therapeutic effect of glutamine supplementation in an animal model of ileitis. In CD, glutamine concentrations were decreased systemically and in noninflamed and inflamed ileal/colonic mucosa. Mucosal glutaminase activities were depressed in the ileum independent of inflammation but were not different from controls in the colon. In experimental ileitis, oral glutamine feeding prevented macroscopic inflammation, enhanced ileal and colonic glutaminase activities above controls, and normalized the intestinal glutathione redox status. However, glutamine supplementation enhanced myeloperoxidase activity along the gastrointestinal tract and potentiated lipid peroxidation in the colon. In conclusion, glutamine metabolism is impaired in CD. In experimental ileitis, glutamine supplementation prevents inflammatory tissue damage. In the colon, however, which does not use glutamine as its principal energy source, immune enhancement of inflammatory cells by glutamine increases oxidative tissue injury.

Carcinoid of the ampulla of Vater.

Endocrine neoplasms only rarely occur at the ampulla of Vater, comprising mostly carcinoids and malignant carcinoids, as well as few cases of poorly differentiated endocrine carcinomas (small cell carcinomas). Only 105 cases are reported in the literature, most as single case reports. For many years, the neoplasms of the disseminated neuroendocrine cell system of the gastrointestinal tract have been subsumed as 'carcinoids'. Instead, in the latest World Health Organization (WHO) classification published in 2000, it is recommended to distinguish between (i) well-differentiated endocrine tumors (carcinoids); (ii) well-differentiated endocrine carcinomas (malignant carcinoids); and (iii) poorly differentiated endocrine carcinomas (small cell carcinomas). Patients with carcinoid tumors of the ampulla of Vater are very often free of clinical and laboratory findings that belong to the carcinoid syndrome. Approximately 26% of all patients with carcinoid tumor reported in the literature had neurofibromatosis. Besides endoscopic retrograde cholangiopancreatography, endosonography, computed tomography or magnetic resonance imaging may complete the staging approach of this tumor. The Kausch-Whipple procedure or pylorus-preserving pancreaticoduodenectomy is considered the treatment of choice for ampullary, well-differentiated carcinoids >2.0 cm and for ampullary neuroendocrine carcinomas. However, it should be considered that long-term survival of patients with ampullary carcinoids is also reported after local tumor excision (5-year survival rate of 90%). The dilemma is that the differentiation of neuroendocrine tumors cannot be assessed intraoperatively in most cases. Therefore, considering that the 5-year survival rate in patients with neuroendocrine carcinomas of the ampulla of Vater is very low without radical resection, neuroendocrine tumors of the ampulla of Vater without definite histological differentiation should undergo extended surgery.

Intrapulmonal dislocation of a totally implantable venous access device.

BACKGROUND: Totally implantable venous access devices are widely used for infusion of chemotherapy or parenteral nutrition. Device associated complications include technical operative problems, infections, paravasal infusions and catheter or punction chamber dislocation. CASE PRESENTATION: We present the case of a 49-year-old patient with the rare complication of a intrapulmonal catheter dislocation of a totally implantable venous access system. Treosulfane for chemotherapy of metastatic breast cancer was infused via the catheter causing instant coughing and dyspnoea which lead to the diagnosis of catheter dislocation. The intrapulmonal part of the catheter was removed under thoracoscopic control without further complications. CONCLUSION: Intrapulmonal catheter dislocation is a rare complication of a totally implantable venous access device which can not be avoided by any prophylactic measures. Therefore, the infusion system should be tested before each use and each new symptom, even when not obviously related to the catheter should be carefully documented and evaluated by expert physicians to avoid severe catheter-associated complications.

Potential role of thioredoxin in immune responses in intestinal lamina propria T lymphocytes.

Thioredoxin (TRX) is a ubiquitous oxidoreductase with strong co-cytokine, chemoattractant and anti-apoptotic activities. TRX expression was found to be particularly elevated in the intestinal mucosa, where its physiologic function is entirely unknown. Here, we demonstrate a high level of TRX expression in lamina propria T cells (LP-T) as opposed to autologous peripheral blood T lymphocytes (PB-T). Addition of recombinant human TRX (rhTRX) to PB-T enhances TRX gene expression. This autoregulation involves the calcineurin signaling pathway, as rhTRX antagonizes the cyclosporine A (CsA)- and tacrolimus-mediated suppression of TRX gene expression. Similarly, rhTRX reverses the suppression of IL-2 mRNA production by CsA and enhances cytokine production preferentially in prestimulated cells. The differential TRX expression in LP-T versus PB-T may thus contribute to the high-level, CsA-resistant IL-2 production characteristic for CD2-stimulated LP-T. Inversely, inactivation of TRX in LP-T through inhibition of TRX reductase abolishes cytokine gene expression. TRX may play a key role in the specialized intestinal microenvironment in amplifying immediate immune responses of LP-T whenever appropriate costimulation of LP-T is provided.

Inflammatory response after abdominal surgery.

Surgical manipulation of the gut elicits an inflammatory cascade within the intestinal muscularis that contributes to postoperative bowel dysmotility. A range of cytokines is sequentially released into the peritoneal fluid following abdominal surgery, their concentrations reflecting the magnitude of surgical trauma. The overproduction of inflammatory mediators might have detrimental effects on organ function and contribute to the enhanced risk of anastomotic leakage in the presence of sepsis. Specific cellular immune functions such as the microbicidal activity of peritoneal phagocytes are depressed after elective surgery, imposing a risk of infectious complications. Laparoscopic surgery decreases the local and systemic production of cytokines and acute-phase reactants, and better preserves peritoneal immunity compared with open surgery. As concluded from animal studies, the gas used for the pneumoperitoneum may possess substantial immunomodulatory activity.

Cytokine/chemokine messenger-RNA expression profiles in ulcerative colitis and Crohn's disease.

To define mediator profiles in inflamed and noninflamed areas in inflammatory bowel disease (IBD) we analyzed the expression of 35 messenger-RNAs (mRNAs) encoding cytokines, chemokines, and some related molecules in transmural gut tissues (n=138) from patients with ulcerative colitis (UC), Crohn's disease (CD), and inflammatory and normal controls by real-time quantitative reverse transcription polymerase chain reaction. Using sample collectives with a comparable degree of inflammation, most parameters investigated showed similarly increased mRNA expression levels in both active UC and CD. This included proinflammatory cytokines, but also interferon (IFN) gamma and several IFN-gamma inducible chemokines. Only macrophage inflammatory protein (MIP)-2alpha mRNA was expressed at higher levels in inflamed UC vs. CD. IH revealed that MIP-2alpha protein was produced mainly by intestinal epithelial cells. Importantly, in histologically noninflamed/inactive IBD samples mRNAs for several mediators were significantly enhanced, accompanied by elevated levels of migration-inhibition factor related protein (MRP) 14 transcripts. CD14 positive macrophages were found especially in noninflamed/inactive UC, many of which coexpressed the RFD-7 antigen. Our results indicate a substantial overlap in cytokine/chemokine mRNA expression in UC and CD. Elevated mediator expression is evident in noninflamed/inactive areas in both diseases. Local recruitment of MRP-14 positive leukocytes might contribute to this phenomenon. In inactive UC a phenotypically altered population of macrophages expressing CD14 might play an additional role.