Implementation of hyperspectral imaging in a trauma resuscitation room: a randomized controlled trial.

BACKGROUND: Hyperspectral imaging (HSI) is a novel imaging technology with the ability to assess microcirculatory impairment. We aimed to assess feasibility of performing HSI, a noninvasive, contactless method to assess microcirculatory alterations, during trauma resuscitation care. METHODS: This randomized controlled clinical trial was conducted in a dedicated trauma resuscitation room of a level one trauma center. We included adult patients who were admitted to the trauma resuscitation room. Patients were allocated in a 1:1 ratio to the HSI group (intervention) or control group. In addition to the standard of care, patients in the intervention group had two hyperspectral recordings (HSR) of their hand palm taken. Primary outcomes were the treatment duration of the primary survey (until end of ABCDE-evaluation, ultrasound and evaluation by the trauma team) and the total resuscitation room care (until transport to definitive care) as well as the ability to perform measurements from all HSR. Secondary outcomes were analyses from the intervention group compared to HSI measurements of 26 healthy volunteers including an analysis based on the ISS (Injury severity score) (< 16 vs. ≥ 16). Care givers, and those assessing the outcomes were blinded to group assignment. RESULTS: Our final analysis included 51 patients, with 25 and 26 allocated to the control and intervention group, respectively. There was a statistically significant shorter median duration of the primary survey in the control group (03:22 min [Q1-Q3 03:00-03:51]) compared to the intervention group (03:59 min [Q1-Q3 03:29-04:35]) with a difference of -37 s (95% CI -66 to -12). Total resuscitation room care was longer in the control group, but without significance: 60 s (95% CI -60 to 180). From 52 HSI, we were able to perform hyperspectral measurements on all images, with significant differences between injured patients and healthy volunteers. CONCLUSION: HSI proved to be feasible during resuscitation room care and can provide valuable information on the microcirculatory state. Trial registration DRKS DRKS00024047- www.drks.de . Registered on 13th April 2021.

Prolyl Hydroxylase Inhibition Mitigates Pouchitis.

BACKGROUND: Pouchitis is the most common long-term complication after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) or familial adenomatous polyposis (FAP), which can eventually progress to pouch failure, necessitating permanent stoma construction. Hypoxia-inducible transcription factor prolyl hydroxylase-containing enzymes (PHD1, PHD2, and PHD3) are molecular oxygen sensors that control adaptive gene expression through hypoxia-inducible factor (HIF). Emerging evidence supports PHDs as being therapeutic targets in intestinal inflammation. However, pharmacological inhibition of PHDs has not been validated as a treatment strategy in pouchitis. METHODS: PHD1-3 mRNA and protein expression were analyzed in mucosal pouch and prepouch ileal patient biopsies. After establishment of a preclinical IPAA model in rats, the impact of the pan-PHD small-molecule inhibitor dimethyloxalylglycine (DMOG) on dextran sulfate sodium (DSS)-induced pouchitis was studied. Clinical and molecular parameters were investigated. RESULTS: PHD1, but not PHD2 or PHD3, was overexpressed in pouchitis in biopsies of patients with IPAA for UC but not FAP. In addition, PHD1 expression correlated with disease activity. DMOG treatment profoundly mitigated DSS-induced pouchitis in a rodent IPAA model. Mechanistically, DMOG restored intestinal epithelial barrier function by induction of tight junction proteins zona occludens-1 and claudin-1 and alleviation of intestinal epithelial cell apoptosis, thus attenuating pouch inflammation. CONCLUSIONS: Together, these results establish a strong therapeutic rationale for targeting PHD1 with small-molecule inhibitors in pouchitis after IPAA for UC.

Prognosis of Ulcerative Colitis-Associated Colorectal Carcinoma Compared to Sporadic Colorectal Carcinoma: A Matched Pair Analysis.

BACKGROUND: Ulcerative colitis (UC) patients have an increased risk of developing colorectal carcinoma (CRC). In contrast to clinical and pathogenetic differences, little is known about how prognosis compares between these patients and those with sporadic CRC. The aim of this study was to compare their characteristics and prognosis and identify independent risk factors for patients with UC-associated CRC. METHODS: A total of 126 patients who underwent surgery in our department (1984-2010) for UC-associated (n = 63) or sporadic (n = 63) CRC were included in this analysis. Patients were matched according to sex, tumor location, and disease stage. Clinical parameters and overall, recurrence-free, and disease-specific survival were compared. In subgroup analyses, clinical parameters of UC patients were correlated with survival. RESULTS: Median follow-up was 129 months in the UC group and 99 months in the sporadic CRC group. UC patients were significantly younger and had more multifocal, high-grade, and mucinous carcinomas. Five-year overall survival rate for UC-associated and sporadic CRC was similar (65.7 vs. 63.2%, p = 0.98). Recurrence-free survival for International Union Against Cancer (UICC) stage II disease was superior in the sporadic CRC group (p = 0.039). In a subgroup analysis of UC patients, a shorter duration of UC (p = 0.045) and male sex (p = 0.005) were associated with a worse prognosis. CONCLUSIONS: Despite multiple clinical and histopathologic differences between UC-associated and sporadic CRC patients, overall survival and disease-specific survival are similar. In a subgroup analysis of UC patients with CRC, female sex was associated with a significantly better prognosis. This finding implies that estrogens may play a protective role in UC-associated CRC carcinogenesis.

Anti-angiogenic activity of VXM01, an oral T-cell vaccine against VEGF receptor 2, in patients with advanced pancreatic cancer: A randomized, placebo-controlled, phase 1 trial.

VEGFR-2 is expressed on tumor vasculature and a target for anti-angiogenic intervention. VXM01 is a first in kind orally applied tumor vaccine based on live, attenuated Salmonella bacteria carrying an expression plasmid, encoding VEGFR-2. We here studied the safety, tolerability, T effector (Teff), T regulatory (Treg) and humoral responses to VEGFR2 and anti-angiogenic effects in advanced pancreatic cancer patients in a randomized, dose escalation phase I clinical trial. Results of the first 3 mo observation period are reported. Locally advanced or metastatic, pancreatic cancer patients were enrolled. In five escalating dose groups, 30 patients received VXM01 and 15 placebo on days 1, 3, 5, and 7. Treatment was well tolerated at all dose levels. No dose-limiting toxicities were observed. Salmonella excretion and salmonella-specific humoral immune responses occurred in the two highest dose groups. VEGFR2 specific Teff, but not Treg responses were overall increased in vaccinated patients. We furthermore observed a significant reduction of tumor perfusion after 38 d in vaccinated patients together with increased levels of serum biomarkers indicative of anti-angiogenic activity, VEGF-A, and collagen IV. Vaccine specific Teff responses significantly correlated with reductions of tumor perfusion and high levels of preexisting VEGFR2-specific Teff while those showing no antiangiogenic activity had low levels of preexisting VEGFR2 specific Teff, showed a transient early increase of VEGFR2-specific Treg and reduced levels of VEGFR2-specific Teff at later time points - pointing to the possibility that early anti-angiogenic activity might be based at least in part on specific reactivation of preexisting memory T cells.

Standardization of a human organ culture model of intestinal inflammation and its application for drug testing.

Targeting early molecular events in intestinal inflammation may represent a useful therapeutic strategy for maintaining remission in inflammatory bowel disease. Recently, we established an intestinal organ culture model (LEL model), which allows to study the initiation of an intestinal inflammatory response in human tissue. In this model, EDTA-mediated depletion of epithelial cells of colonic mucosa results in an instantaneous inflammatory response in resident lamina propria cells, which shows features of intestinal inflammation in vivo. Furthermore, activated immune cells emigrate from the lamina propria onto the luminal side of the basement membrane. Here, we standardize the LEL model and explore its suitability for drug testing. To this end, human mucosal punches of defined surface area were prepared, depleted of epithelial cells, and cultured at an optimized ratio of medium volume/punch area. The intra-assay variability of measurements of inflammatory parameters ranged from 13% for cell migration to 19% for secretion and 30% for tissue gene expression, respectively, of the inflammatory mediators IL-8 and IL-6. Importantly, known suppressive effects of dexamethasone, a drug employed for the treatment of inflammatory bowel diseases, on leucocyte migration, IL8, IL6, and TNF-α production as well as CD86 surface expression by myeloid cells were observed in this model. In conclusion, the present results suggest that the LEL model may represent a useful human experimental system not only for studying initial activation mechanisms in intestinal inflammation but also for evaluating drug compounds for the treatment of mucosal inflammation.

Residual rectal mucosa after stapled vs. handsewn ileal J-pouch-anal anastomosis in patients with familial adenomatous polyposis coli (FAP)--a critical issue.

INTRODUCTION: Restorative proctocolectomy has become the standard surgical procedure for familial adenomatous polyposis (FAP) patients. The use of stapler devices has initiated a controversial discussion concerning the ileal pouch-anal reconstruction. Some authors advocate a handsewn anastomosis after transanal mucosectomy. A double-stapled anastomosis leads to better functional results but seems to bear a higher risk of residual rectal mucosa with dysplasia and adenomas. The present study systematically analyses the rate of residual rectal mucosa after restorative proctocolectomy and handsewn vs. stapled anastomosis. PATIENTS AND METHODS: One hundred FAP patients after restorative proctocolectomy undergoing regular follow-up at our outpatient clinic were included in the study. Proctoscopy with standardised biopsy sampling was performed. RESULTS: Of the 100 patients, 50 had undergone a stapled and 50 a handsewn anastomosis. Median follow-up was 146.1 months (handsewn) vs. 44.8 months (stapled) (P < 0.0001). Eighty-seven patients received a proctoscopy with standardised biopsy sampling. Thirteen patients had been diagnosed with residual rectal mucosa before. Sixty-three patients (63 %) showed remaining rectal mucosa (42 (66.6 %) stapler, 21 (33.3 %) handsewn, P < 0.0001). Patients after stapled anastomosis had higher rates of circular rectal mucosa seams, while small mucosa islets predominated in the handsewn group. The rate of rectal adenomas was significantly higher in the stapler group (21 vs. 10, P = 0.02). CONCLUSION: Rectal mucosa, especially wide mucosa seams, as well as rectal adenomas are found significantly more often after a stapled than after a handsewn anastomosis. As the follow-up interval in the stapler group was significantly shorter, the impact of these findings may still be underestimated.

Survival after renal cell carcinoma metastasis to the thyroid: single center experience and systematic review of the literature.

BACKGROUND: Renal cell carcinoma can metastasize to uncommon sites, for example, the thyroid gland where metastases are rarely found. To determine the patient survival and the time between cancer diagnosis and thyroid metastasis, we analyzed a large patient cohort from our hospital records and performed a systematic review. PATIENTS AND METHODS: Patients diagnosed between 1978 and 2007 with thyroid metastases from renal cell carcinoma were retrospectively identified from the hospital database. A systematic literature search was performed for publications describing at least three cases of thyroid metastasis from renal cell carcinoma. Case data from the identified studies were collected and used to determine the survival data. RESULTS: We identified 34 patients (19 females) from our hospital records with a mean age of 67 years (range, 33-79) when thyroid metastasis was diagnosed. Median time to primary metastasis after resection of renal cell carcinoma was 6.5 years (range, 0-25) with a single case of synchronous metastasis. Median survival after primary metastasis was 4.7 years (95% confidence interval [CI]: 1.8-7.6). The systematic review included 32 studies with 285 patients. Case data could be extracted for 202 patients. Median time to thyroid metastasis (without synchronous cases) was 8.8 years (95% CI: 7.5-10.1). Median actuarial survival after thyroid metastasis was 3.4 years (95% CI: 2.2-4.6). Total thyroidectomy was not associated with a better survival compared to partial thyroidectomies. CONCLUSIONS: Time to thyroid metastasis of renal cell carcinoma can be very long, and survival after thyroidectomy is favorable compared to metastasis to other sites.

Initiation of an inflammatory response in resident intestinal lamina propria cells -use of a human organ culture model.

Resident human lamina propria immune cells serve as powerful effectors in host defense. Molecular events associated with the initiation of an intestinal inflammatory response in these cells are largely unknown. Here, we aimed to characterize phenotypic and functional changes induced in these cells at the onset of intestinal inflammation using a human intestinal organ culture model. In this model, healthy human colonic mucosa was depleted of epithelial cells by EDTA treatment. Following loss of the epithelial layer, expression of the inflammatory mediators IL1B, IL6, IL8, IL23A, TNFA, CXCL2, and the surface receptors CD14, TLR2, CD86, CD54 was rapidly induced in resident lamina propria cells in situ as determined by qRT-PCR and immunohistology. Gene microarray analysis of lamina propria cells obtained by laser-capture microdissection provided an overview of global changes in gene expression occurring during the initiation of an intestinal inflammatory response in these cells. Bioinformatic analysis gave insight into signalling pathways mediating this inflammatory response. Furthermore, comparison with published microarray datasets of inflamed mucosa in vivo (ulcerative colitis) revealed a significant overlap of differentially regulated genes underlining the in vivo relevance of the organ culture model. Furthermore, genes never been previously associated with intestinal inflammation were identified using this model. The organ culture model characterized may be useful to study molecular mechanisms underlying the initiation of an intestinal inflammatory response in normal mucosa as well as potential alterations of this response in inflammatory bowel disease.

Allogeneic blood transfusion does not affect outcome after curative resection for advanced cholangiocarcinoma.

PURPOSE: To assess the impact of perioperative blood transfusion on overall and disease-free survival in patients undergoing curative resection for cholangiocarcinoma. METHODS: In a single-center study, 128 patients undergoing curative resection for cholangiocarcinoma between 2001 and 2010 were assessed. The median follow-up period was 19 months. Transfused and nontransfused patients were compared by Cox regression and propensity score analyses. RESULTS: Overall, 38 patients (29.7 %) received blood transfusions. The patient characteristics were highly biased with respect to receiving transfusions (propensity score 0.69 ± 0.22 vs. 0.11 ± 0.16, p < 0.001). In the unadjusted analysis, blood transfusion was associated with a 105 % increased risk of mortality [hazard ratio (HR) 2.05, 95 % CI 1.19-3.51, p = 0.010]. In the multivariate (HR 1.14, 95 % CI 0.52-2.48, p = 0.745) and the propensity score-adjusted Cox regression (HR 1.02, 95 % CI 0.39-2.62, p = 0.974), blood transfusion had no influence on overall survival. Similarly, in the propensity score-adjusted Cox regression (HR 0.62, 95 % CI 0.24-1.58, p = 0.295), no relevant effect of blood transfusion on disease-free survival was observed. CONCLUSIONS: To our knowledge, this is the first propensity score-based analysis providing compelling evidence that the worse oncological outcome after curative resection for advanced cholangiocarcinoma in patients receiving perioperative blood transfusions is caused by the clinical circumstances requiring the transfusions, not by the blood transfusions themselves.

Laparoscopic versus conventional ileoanal pouch procedure in patients undergoing elective restorative proctocolectomy (LapConPouch Trial)-a randomized controlled trial.

PURPOSE: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the standard surgical procedure for ulcerative colitis (UC) and familial adenomatous polyposis (FAP). While minimal invasive techniques have been applied increasingly, clear evidence of superiority for laparoscopic pouch procedures is not yet available. The aim of the LapConPouch Trial was to compare the effectiveness of laparoscopic (LAP) versus conventional (CON) ileoanal pouch procedure in patients undergoing elective restorative proctocolectomy. METHODS: The trial was designed as a single-centre, pre-operatively randomized, controlled trial using a two-group parallel superiority design. Eligible for participation were patients scheduled for restorative proctocolectomy either for FAP or for UC. Patients and outcome assessors were blinded to group assignment. The primary endpoint was defined as the amount of blood loss. Statistical analyses were explorative since the trial had to be stopped prematurely. RESULTS: A total of 42 patients (21 LAP (50.0 %); 21 CON (50.0 %)) were randomized. The trial had to be stopped prematurely due to insufficient patient recruitment. There was no difference in the amount of blood loss between both groups: LAP 261.5 ± 195.4 ml, CON 228.1 ± 119.5 ml. Secondary endpoints differ in both groups. Laparoscopic surgery was superior regarding the length of skin incision; in contrast, the conventional approach was superior in duration of operation. There were no discrepancies in length of hospital stay, postoperative pain, bowel function, and quality of life between both approaches. The conversion rate from LAP to CON approach was 23.8 %. CONCLUSION: There was no difference with respect to blood loss between the LAP and the CON group. The LAP approach is feasible for restorative proctocolectomy, and IPAA seems at least as safe as CON surgery. The most obvious advantage of the minimal invasive technique is the improved cosmesis.

Renal tumors and second primary pancreatic tumors: a relationship with clinical impact?

BACKGROUND: The occurrence of synchronous or metachronous renal cell carcinoma and pancreatic tumors has been described only in a few cases in the scientific literature. The study of double primary cancers is important because it might provide understanding of a shared genetic basis of different solid tumors and to detect patients at risk for secondary malignancy. METHODS: In a combined analysis of patient registries from University Departments of Urology and Visceral Surgery, 1178 patients with pancreatic tumors and 518 patients with renal cell carcinoma treated between 2001 and 2008 were evaluated, RESULTS: Overall 16 patients with renal cancer and synchronous (n = 6) or metachronous (n = 10) primary pancreatic tumors were detected. The median survival of all patients was 12.6 months, for the patients with synchronous resections 25.7 months and for the patients with metachronous resections 12.2 months, respectively. CONCLUSIONS: The association between these two etiologies of malignancy demands more detailed epidemiological and molecular investigation. Clinical outcomes would support a resection as a recommended clinically valid option.

Double-blind, placebo-controlled first in human study to investigate an oral vaccine aimed to elicit an immune reaction against the VEGF-Receptor 2 in patients with stage IV and locally advanced pancreatic cancer.

BACKGROUND: The investigational oral DNA vaccine VXM01 targets the vascular endothelial growth factor receptor 2 (VEGFR-2) and uses Salmonella typhi Ty21a as a vector. The immune reaction elicited by VXM01 is expected to disrupt the tumor neovasculature and, consequently, inhibit tumor growth. VXM01 potentially combines the advantages of anti-angiogenic therapy and active immunotherapy. METHODS/DESIGN: This phase I trial examines the safety, tolerability, and immunological and clinical responses to VXM01. The randomized, placebo-controlled, double blind dose-escalation study includes up to 45 patients with locally advanced and stage IV pancreatic cancer. The patients will receive four doses of VXM01 or placebo in addition to gemcitabine as standard of care. Doses from 106 cfu up to 1010 cfu of VXM01 will be evaluated in the study. An independent data safety monitoring board (DSMB) will be involved in the dose-escalation decisions. In addition to safety as primary endpoint, the VXM01-specific immune reaction, as well as clinical response parameters will be evaluated. DISCUSSION: The results of this study shall provide the first data regarding the safety and immunogenicity of the oral anti-VEGFR-2 vaccine VXM01 in cancer patients. They will also define the recommended dose for phase II and provide the basis for further clinical evaluation, which may also include additional cancer indications. TRIAL REGISTRATION: EudraCT No.: 2011-000222-29, NCT01486329, ISRCTN68809279.

Quality of life ten and more years after restorative proctocolectomy for patients with familial adenomatous polyposis coli.

PURPOSE: Few studies on long-term quality of life after restorative proctocolectomy and ileal pouch-anal anastomosis have been published. Most of them survey a mixed patient population of familial adenomatous polyposis and ulcerative colitis. The present study analyzes long-term results more than 10 years after ileal pouch-anal anastomosis for patients with familial adenomatous polyposis, exclusively. METHODS: One hundred thirty-five patients who underwent ileal pouch-anal anastomosis more than 10 years ago were identified from the prospective familial adenomatous polyposis registry at Heidelberg University hospital. They received the German version of the health-specific Short Form 36 Health Survey and the disease-specific Gastrointestinal Quality of Life Index by mail. To assess the impact of disease-specific factors, 10 questions asking for ability to work, current medication, pouchitis, and extracolonic manifestations of familial adenomatous polyposis were added to the Gastrointestinal Quality of Life Index questionnaire. RESULTS: Among 84 patients who answered the questionnaires the median follow-up was 13.4 years (range, 10.3-23.8 y).The results of the Short Form 36 Health Survey were comparable to a German normative population in all dimensions, whereas the overall score for the Gastrointestinal Quality of Life Index was significantly reduced compared with healthy individuals (111.8 vs 120.8, P = .0014). Carcinoma at the time of ileal pouch-anal anastomosis, desmoid tumors, or duodenal adenomas had no significant influence on quality of life. More than 7 bowel movements during the daytime were found to reduce quality of life significantly (103.5 vs 115, P = .0127). More than 2 defecations per night diminished the score further (101 vs 125, P < .0001). Patients younger than 40 years at the time of ileal pouch-anal anastomosis had significantly better results than older patients (120 vs 109.5, P = .0076). CONCLUSION: Ileal pouch-anal anastomosis is a safe surgical procedure with a high quality of life comparable to that of a normative population after long-term follow-up of patients with familial adenomatous polyposis.

Long-term outcome 10 years or more after restorative proctocolectomy and ileal pouch-anal anastomosis in patients with ulcerative colitis.

PURPOSE: The aim of this study was to assess quality of life (QOL) in a long-term follow-up of patients with ulcerative colitis (UC) 10 years and more after ileal pouch-anal anastomosis (IPAA) to correlate these results with pouch function and to assess the long-term pouch failure rate. METHODS: In a unicentric study, 294 consecutive patients after IPAA between 1988 and 1996 were identified from a prospective database. QOL was evaluated according to the validated Gastrointestinal Quality of Life Index (GIQLI). RESULTS: Overall median follow-up was 11.5 years. Thirty-seven patients experienced pouch failure (12.6%). The rates of ileal pouch success after 5, 10 and 15 years were 92.3%, 88.7% and 84.5%. According to the GIQLI, patients with a functioning pouch achieved a mean score of 107.8, reflecting a decrease of QOL of 10.8% compared to a healthy population. There were significant negative correlations between QOL and an age of >50 years (p < 0.05), pouchitis, perianal inflammation and increased stool frequency (p < 0.0001). CONCLUSIONS: QOL and functional results of patients with UC 10 years or more after IPAA were acceptable; however, those were reduced when compared to a healthy population. Pouch failure rate still increases up to 15.5% 15 years after IPAA. This result represents an important issue in providing patients with comprehensive preoperative information.

Quality of life after restorative proctocolectomy for ulcerative colitis: preoperative status and long-term results.

BACKGROUND: Restorative proctocolectomy has become the surgical procedure of choice in patients with ulcerative colitis. Only smaller studies have compared postoperative to preoperative quality of life (QoL). METHODS: Patients with ulcerative colitis who had undergone restorative proctocolectomy at least 5 years before and who had filled out a disease-specific validated questionnaire (Gastrointestinal Quality of Life Index, GIQLI) prior to surgery (n = 128) were included into this follow-up study. Factors potentially influencing QoL at the time of operation were investigated with regard to pre- and postoperative QoL in univariate and multivariate analysis. RESULTS: A total of 105 patients responded (82%). QoL at least 5 years after colectomy was significantly improved compared to the preoperative situation (109 versus 75). This improvement was evident in all 5 dimensions (P < 0.0001). The Colitis Activity Index (CAI) (P < 0.00001), a shorter duration of the disease (P < 0.05), and a 3-staged procedure (<0.001) were negatively correlated with preoperative QoL, whereas neoplasia (P < 0.001) was positively correlated. Colectomy was the reason for most of the increase in QoL. Ileostomy closure resulted in a further improvement in 3 of 5 dimensions but not in overall QoL. Uni- and multivariate analysis of the difference in QoL before and 5 years after colectomy revealed CAI, the type of operation (both P < 0.001), and neoplasia as significant factors (P < 0.05). CONCLUSIONS: The patients in the worst clinical situation profit the most from restorative proctocolectomy.

Differential expression of toll-like receptor 3 and 5 in ileal pouch mucosa of ulcerative colitis patients.

BACKGROUND AND AIMS: The pathogenesis of pouchitis, major complication after restorative proctocolectomy, and ileal J pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC) is still unclear. Changes in intraluminal bacterial colonization and correlated changes of pouch mucosa are thought to play an important role. Toll-like receptors (TLRs) as part of the innate immune system are capable of recognizing bacterial antigens. Their activation can lead to secretion of proinflammatory mediators. In this study, TLR2, 3, 4, and 5 expression profiles in the pouch mucosa of patients with UC and IPAA were analyzed and correlated with pouchitis. MATERIALS AND METHODS: Clinical symptoms, endoscopy, and histology were assessed in 35 patients using the Heidelberg Pouchitis Activity Score to classify patients as either having pouchitis or not. TLR mRNA expression in normal ileal mucosa and pouch mucosa was investigated by performing semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). The results of RT-PCR were associated with the pouchitis score. RESULTS: In the analysis of all patients, TLR3 expression was decreased significantly whereas TLR5 expression was increased significantly in pouch mucosa compared to normal ileal mucosa (p-values 0.0076 and 0.016, respectively). A more detailed analysis upon dividing the patients into patients with and without pouchitis showed decreased TLR3 expression in the pouch mucosa only of patients without pouchitis (p-value=0.0067). TLR5 expression was increased in the pouch mucosa only of patients with pouchitis (p-value=0.023). No differences in TLR2 and 4 expression were found in either group. CONCLUSION: Differential expression of TLR3 and 5 suggests bacterial involvement in the pathogenesis of pouchitis in patients with UC.

Perioperative outcome in sarcoma surgery.

INTRODUCTION: Soft tissue sarcomas (STS) are rare tumors accounting for less than 1% of all malignancies. Although disease-specific surgical management is increasingly important, only few data are available for STS. Here, we analyze a single institution setting focusing on perioperative surgical and clinical parameters. METHODS: Prospectively gathered data of all adult patients undergoing surgery for STS including gastrointestinal stroma tumors (GIST) between October 2001 and October 2004. Patients undergoing only biopsy or ambulatory surgery were excluded. Statistical analysis was performed using SAS(R) software and patient's data from a computerized sarcoma registry. RESULTS: 159 patients with a median age of 60.2 years underwent a total of 179 operations. Three major sites of occurrence were notified: the visceral cavity (VIS) (36.3%), the retroperitoneum (RET) (31.3%), and the extremities (EXT) (27.4%). GIST (53.9%) were the most common type in the VIS, liposarcoma (62.5%) in the RET, and either liposarcoma (30.6%) or malignant fibrous histiocytoma (28.6%) in the EXT. Recurrence was treated in more than half of the patients with RET STS, and in almost one third of the EXT lesions, while primary occurrence dominated in the VIS. Median operation times in the VIS, RET, and EXT were 210, 240, and 120 min, respectively. Blood loss was 300, 500, and 50 ml for VIS, RET, and EXT operations. Morbidity was 26.2, 30.4, and 34.7% in VIS, RET, and EXT operations, respectively (reoperation rates were 9.4, 5.4, and 14.3%). Mortality was 1.5, 8.9, and 2.0% for VIS, RET, and EXT. Length of hospital stay in the groups was comparable. CONCLUSION: STS surgery of a single surgical unit contains predominantly VIS, RET, and EXT tumors. The STS subtype varies with location, as does length of operation, blood loss, morbidity, mortality, and reoperation rate. These data are helpful for planning the perioperative management of adult patients with STS and can be used for prognostic analyses.

Clinical results of surgery for retroperitoneal sarcoma with major blood vessel involvement.

PURPOSE: The study was conducted to evaluate the clinical results of resection for retroperitoneal soft tissue sarcoma (STS) with vascular involvement. METHODS: The study group consisted of consecutive patients (mean age, 52 years) who underwent surgery for retroperitoneal STS with vascular involvement. The procedures were performed between 1988 and 2004. Vessel involvement by STS was classified as type I, artery and vein; type II, only artery; type III, only vein; and type IV, neither artery nor vein (excluded from the analysis). Patient data were prospectively gathered in a computerized database and retrospectively analyzed. RESULTS: Of 141 patients with retroperitoneal STS, 25 (17.7%) underwent surgery for tumors with vascular involvement. The most common vascular involvement pattern was vein only (type III) at 64%. Arterial and vein (type I) and arterial only (type II) involvement were observed in 16% and 20% of the cases, respectively. STS originating from the vessel wall (primary vessel involvement) was seen in eight patients, and 17 patients had secondary vascular involvement. Resection and vascular repair were done in 22 patients (no vascular repair in three patients due to ligation of the external iliac vein in one patient, and debulking procedures in two). All patients with arterial involvement (type I and II) had arterial reconstruction consisting of aortic replacement (Dacron, n = 3; and expanded polytetrafluoroethylene [ePTFE], n = 2), iliac repair (Dacron, n = 3), and truncal reimplantation (n = 1). The inferior vena cava (6 ePTFE tube grafts, 3 ePTFE patches, 2 venoplasties), iliac vein (1 ePTFE bypass, 1 Dacron bypass, 1 venous patch), and superior mesenteric vein (1 anastomosis, 1 Dacron bypass) were restored in 80% of the patients (n = 16) with either arterial and venous or only venous involvement (type I and type III setting). Morbidity was 36% (hemorrhage, others), and mortality was 4%. At a median follow-up of 19.3 months (interquartile range, 12.8 to 49.9 months) the arterial patency rate was 88.9%, and the venous patency rate was 93.8% (primary and secondary). Thrombosis developed in one arterial and venous (type I) iliac reconstruction due to a perforated sigmoid diverticulitis 12 months after surgery. The local control rate was 82.4%. The 2-year and 5-year survival rates were 90% and 66.7% after complete resection with tumor-free resection margins (n = 10 patients, median survival not reached at latest follow-up). The median survival was 21 months in patients with complete resection but positive resection margins (n = 7) and 8 months in patients with incomplete tumor clearance (n = 8, persistent local disease or metastasis). CONCLUSIONS: Patency rates and an acceptable surgical risk underline the value of en bloc resection of retroperitoneal STS together with involvement of blood vessels. The oncologic outcome is positive, especially after complete resection with tumor-free resection margins. A classification of vascular involvement can be used to plan resection and vascular replacement as well as to compare results among reports in a standardized fashion.

Ruptured angiosarcoma of the liver treated by emergency catheter-directed embolization.

Angiosarcoma is a rare primary malignant neoplasm of the liver with a poor prognosis. Here, we report a case of a patient with a ruptured hepatic angiosarcoma which was treated by emergency catheter-directed embolization, followed by left-sided hemihepatectomy.

Malignant vascular tumors: clinical presentation, surgical therapy, and long-term prognosis.

BACKGROUND: The aim of this study was to analyze the presentation of, surgery for, and prognosis of malignant vascular tumors (MVTs). METHODS: This was an observational single-center study. Patients who underwent operation for MVTs between 1988 and 2004 were included. Data were gathered prospectively in a computerized registry. RESULTS: Of 568 adult patients with soft tissue malignancies, 43 (7.6%) were treated for MVTs. Twenty-four men and 19 women (median age, 55.3 years) were referred for 30 primary tumors and 13 recurrences. Symptoms were observed in 90.7% of the cases (swelling [37.2%], pain [34.9%], extrusion [11.6%], hemorrhage [7%], weight loss [4.7%], loss of energy [4.7%], impaired function [4.7%], and others [30.2%]). Tumors were located in the extremities (n = 16), trunk (n = 3), abdomen (n = 15), retroperitoneum (n = 7), and thyroid gland (n = 2). Twenty-two (51.2%) angiosarcomas, nine (20.9%) malignant hemangiopericytomas, eight (18.6%) malignant epithelioid hemangioendotheliomas, and four (9.3%) lymphangiosarcomas were seen. The median overall survival after surgery was 21.4 months, with 2-, 5-, and 10-year overall survival rates of 41.5%, 38.3%, and 18.8%, respectively. MVTs of the extremities and trunk and localized disease indicated a better prognosis than abdominal or retroperitoneal MVTs (univariate and multivariate analyses: P = .0122 and P = .0287) and metastasized stages (univariate and multivariate analyses: P = .0187 and P = .0287). CONCLUSIONS: A considerable number of patients with soft tissue malignancies undergo surgery for MVT. Various symptoms and a multilocular occurrence are typical. The course of MVTs is aggressive. Tumor site and stage are important prognostic factors. Surgery is potentially curative, especially for localized disease of the extremities and trunk.