Is there a weekend effect in emergency surgery for colorectal carcinoma? Analysis from the German StuDoQ registry.

BACKGROUND: Higher postoperative mortality has been observed among patients who received emergency colorectal surgery on the weekend compared to during the week. The aim of this study was to determine whether the weekday of emergency surgery affects the 30-day mortality and postoperative course in emergency colorectal surgery. METHODS: Prospectively acquired data from the 2010-2017 German StuDoQ|Colorectal surgery registries were analysed. Differences in 30-day mortality, transfer and length of stay (MTL30) (primary endpoints), postoperative complications, length of stay and pathological results of resected specimens (secondary endpoints) were assessed. Multivariable analysis was performed to identify independent risk factors for postoperative outcome. RESULTS: In total, 1,174 patients were included in the analysis. Major postoperative complications and the need for reoperation were observed more frequently for emergency colorectal surgery performed during the week compared to the weekend (23.01 vs. 15.28%, p = 0.036 and 17.96% vs. 11.11%, p = 0.040, respectively). In contrast, patients who received emergency surgery on the weekend presented with significantly higher UICC tumour stages (UICC III 44.06 vs. 34.15%, p = 0.020) compared to patients with emergency colorectal surgery on a weekday. Emergency surgery performed during the week was an independent risk factor for the development of severe postoperative complications (OR 1.69 [1.04-2.74], p = 0.033) and need for reoperation (OR 1.79 [1.02-3.05], p = 0.041) in the multivariable analysis. CONCLUSION: Emergency surgery for colorectal carcinoma in Germany is performed with equal postoperative MTL30 and mortality throughout the entire week. However, emergency surgery during the week seems to be associated with a higher rate of severe postoperative complications and reoperation.

Does Concurrent Cholestasis Alter the Prognostic Value of Preoperatively Elevated CA19-9 Serum Levels in Patients with Pancreatic Head Adenocarcinoma?

BACKGROUND: Pancreatic adenocarcinoma (PDAC) patients with preoperative carbohydrate antigen 19-9 (CA19-9) serum levels higher than 500 U/ml are classified as biologically borderline resectable (BR-B). To date, the impact of cholestasis on preoperative CA19-9 serum levels in these patients has remained unquantified. METHODS: Data on 3079 oncologic pancreatic resections due to PDAC that were prospectively acquired by the German Study, Documentation and Quality (StuDoQ) registry were analyzed in relation to preoperative CA19-9 and bilirubin serum values. Preoperative CA19-9 values were adjusted according to the results of a multivariable linear regression analysis of pathologic parameters, bilirubin, and CA19-9 values. RESULTS: Of 1703 PDAC patients with tumor located in the pancreatic head, 420 (24.5 %) presented with a preoperative CA19-9 level higher than 500 U/ml. Although receiver operating characteristics (ROC) analysis failed to determine exact CA19-9 cut-off values for prognostic indicators (R and N status), the T, N, and G status; the UICC stage; and the number of simultaneous vein resections increased with the level of preoperative CA19-9, independently of concurrent cholestasis. After adjustment of preoperative CA19-9 values, 18.5 % of patients initially staged as BR-B showed CA19-9 values below 500 U/ml. However, the postoperative pathologic results for these patients did not change compared with the patients who had CA19-9 levels higher than 500 U/ml after bilirubin adjustment. CONCLUSIONS: In this multicenter dataset of PDAC patients, elevation of preoperative CA19-9 correlated with well-defined prognostic pathologic parameters. Bilirubin adjustment of CA19-9 is feasible but does not affect the prognostic value of CA19-9 in jaundiced patients.

Successful surgical closure of infected abdominal wounds following preconditioning with negative pressure wound therapy.

PURPOSE: Traditionally, previous wound infection was considered a contraindication to secondary skin closure; however, several case reports describe successful secondary wound closure of wounds "preconditioned" with negative pressure wound therapy (NPWT). Although this has been increasingly applied in daily practice, a systematic analysis of its feasibility has not been published thus far. The aim of this study was to evaluate secondary skin closure in previously infected abdominal wounds following treatment with NPWT. METHODS: Single-center retrospective analysis of patients with infected abdominal wounds treated with NPWT followed by either secondary skin closure referenced to a group receiving open wound therapy. Endpoints were wound closure rate, wound complications (such as recurrent infection or hernia), and perioperative data (such as duration of NPWT or hospitalization parameters). RESULTS: One hundred ninety-eight patients during 2013-2016 received a secondary skin closure after NPWT and were analyzed and referenced to 67 patients in the same period with open wound treatment after NPWT. No significant difference in BMI, chronic immunosuppressive medication, or tobacco use was found between both groups. The mean duration of hospital stay was 30 days with a comparable duration in both patient groups (29 versus 33 days, p = 0.35). Interestingly, only 7.7% of patients after secondary skin closure developed recurrent surgical site infection and in over 80% of patients were discharged with closed wounds requiring only minimal outpatient wound care. CONCLUSION: Surgical skin closure following NPWT of infected abdominal wounds is a good and safe alternative to open wound treatment. It prevents lengthy outpatient wound therapy and is expected to result in a higher quality of life for patients and reduce health care costs.

Prognostic impact of additive chemotherapy after curative resection of metachronous colorectal liver metastasis: a single-centre retrospective study.

BACKGROUND: A prognostic benefit of additive chemotherapy in patients following resection of metachronous colorectal liver metastases (CRLM) remains controversial. Therefore, the goal of this retrospective study was to investigate the impact of perioperative chemotherapy on disease-free survival (DFS) and overall survival (OS) of patients after curative resection of metachronous CRLM. METHODS: In a retrospective single-centre study, patients after curative resection of metachronous CRLM were included and analysed for DFS and OS with regard to the administration of additive chemotherapy. The Kaplan-Meier method was applied to compare DFS and OS while Cox regression models were used to identify independent prognostic variables. RESULTS: Thirty-four of 75 patients were treated with additive 5-FU based chemotherapy. OS was significantly prolonged in this patient subgroup (62 vs 57 months; p = 0.032). Additive chemotherapy significantly improved 10-year survival rates (42% vs 0%, p = 0.023), but not 5-year survival (58% vs 42%, p = 0.24). Multivariate analysis identified additive chemotherapy (p = 0.016, HR 0.44, 95% CI 0.23-0.86), more than five CRLM (p = 0.026, HR 2.46, 95% CI 1.16-10.32) and disease recurrence (0.009, HR 2.70, 95% CI 1.29-5.65) as independent risk factors for OS. CONCLUSION: Additive chemotherapy significantly prolonged OS and 10-year survival in patients after curative resection of metachronous CRLM. Randomized clinical trials are needed in the future to identify optimal chemotherapy regimens for those patients.

Preoperative Liver Function Guiding HCC Resection in Normal and Cirrhotic Liver.

BACKGROUND: Liver resection is the most effective available therapy for patients with hepatocellular carcinoma (HCC). The accurate selection of patients for surgery requires determination of technical resectability and the risk of recurrence, as well as assessment of liver function and functional reserve to avoid postoperative liver failure. Previous studies have underlined the effectiveness and reliability of the LiMAx® test to evaluate liver function preoperatively. Nevertheless, data concerning HCC evaluation are lacking. METHODS: From 2014 to 2019, 92 patients with HCC underwent additional assessment of liver function using the LiMAx test prior to decision for or against liver resection. Preoperative LiMAx results were compared between cirrhotic and noncirrhotic liver. The clinical decision for surgery was evaluated applying the various liver function parameters available. RESULTS: Forty-six patients underwent liver resection. The LiMAx results were higher in resected patients (388 vs. 322 µg/kg/h; p = 0.004). LiMAx values were an independent risk factor for the presence of liver cirrhosis in multivariate analysis. In 17 patients, surgical treatment was cancelled due to major impairment of liver function. Only 4 out of 46 resected patients presented with post-hepatectomy liver failure (PHLF) grade ≥B. Histologic assessment revealed liver cirrhosis in 10 resected patients without PHLF. CONCLUSION: Preoperative determination of liver function by the LiMAx test enables effective and safe patient selection for HCC resection in both cirrhotic and noncirrhotic liver.

Impact of Borderline Resectability in Pancreatic Head Cancer on Patient Survival: Biology Matters According to the New International Consensus Criteria.

BACKGROUND: International consensus criteria (ICC) have redefined borderline resectability for pancreatic ductal adenocarcinoma (PDAC) according to three dimensions: anatomical (BR-A), biological (BR-B), and conditional (BR-C). The present definition acknowledges that resectability is not just about the anatomic relationship between the tumour and vessels but that biological and conditional dimensions also are important. METHODS: Patients' tumours were retrospectively defined borderline resectable according to ICC. The study cohort was grouped into either BR-A or BR-B and compared with patients considered primarily resectable (R). Differences in postoperative complications, pathological reports, overall (OS), and disease-free survival were assessed. RESULTS: A total of 345 patients underwent resection for PDAC. By applying ICC in routine preoperative assessment, 30 patients were classified as stage BR-A and 62 patients as stage BR-B. In total, 253 patients were considered R. The cohort did not contain BR-C patients. No differences in postoperative complications were detected. Median OS was significantly shorter in BR-A (15 months) and BR-B (12 months) compared with R (20 months) patients (BR-A vs. R: p = 0.09 and BR-B vs. R: p < 0.001). CA19-9, as the determining factor of BR-B patients, turned out to be an independent prognostic risk factor for OS. CONCLUSIONS: Preoperative staging defining surgical resectability in PDAC according to ICC is crucial for patient survival. Patients with PDAC BR-B should be considered for multimodal neoadjuvant therapy even if considered anatomically resectable.

The Effect of Day of the Week on Morbidity and Mortality From Colorectal and Pancreatic Surgery.

BACKGROUND: A number of studies have revealed higher postoperative mortality after operations that were performed toward the end of the week. It is not yet known whether a day-of-the-week effect exists after visceral surgical procedures for cancer in Germany. METHODS: Data on resections of carcinomas of the colon, rectum (2010-2017), and head of the pancreas (2014-2017) (n = 19 703) that had been prospectively acquired by the Study, Documentation, and Quality Center of the German Society for General and Visceral Surgery were analyzed in relation to the day of the week on which the operation was performed. The primary endpoint was postoperative 30-day mortality; the secondary endpoints were complications, length of hospital stay, and MTL30 (a combined outcome criterion that is positive if the patient has died, is still in the hospital, or has been transferred to another acute care hospital 30 days after the index procedure). RESULTS: Resections of colon carcinomas that were performed on Mondays were associated with more advanced tumor stages (T4: 18.4% vs. 15.7%, p <0.001), higher 30-day mortality (3.5% vs. 2.3%, p = 0.004), and a more frequently positive MTL30 (10.5% vs. 8.5%, p = 0.004). Among patients who underwent pancreatic head resections, those whose procedures were on Tuesday had higher mortality (6.2% vs. 3.8%; p = 0.021). Among those who underwent surgery for rectal carcinoma, the day of the week on which the procedure was performed had no effect on postoperative morality. Multivariate analysis revealed that the independent risk factors for postoperative mortality were colonic resection on a Monday (odds ratio [OR]: 1.45; 95% confidence interval [1.11; 1.92], p = 0.008) and pancreatic head resection on a Tuesday (OR: 1.88 [1.18; 2.91], p = 0.006). CONCLUSION: Elective surgery for carcinoma of the colon or pancreatic head is associated with slightly higher mortality if per - formed toward the beginning of the week. On the other hand, the day of the week has no effect on the outcome of surgery for rectal carcinoma.

Pathological complete response due to a prolonged time interval between preoperative chemoradiation and surgery in locally advanced rectal cancer: analysis from the German StuDoQ|Rectalcarcinoma registry.

BACKGROUND: Preoperative chemoradiotherapy is the recommended standard of care for patients with local advanced rectal cancer. However, it remains unclear, whether a prolonged time interval to surgery results in an increased perioperative morbidity, reduced TME quality or better pathological response. Aim of this study was to determine the time interval for best pathological response and perioperative outcome compared to current recommended interval of 6 to 8 weeks. METHODS: This is a retrospective analysis of the German StuDoQ|Rectalcarcinoma registry. Patients were grouped for the time intervals of "less than 6 weeks", "6 to 8 weeks", "8 to 10 weeks" and "more than 10 weeks". Primary endpoint was pathological response, secondary endpoint TME quality and complications according to Clavien-Dindo classification. RESULTS: Due to our inclusion criteria (preoperative chemoradiation, surgery in curative intention, M0), 1.809 of 9.560 patients were suitable for analysis. We observed a trend for increased rates of pathological complete response (pCR: ypT0ypN0) and pathological good response (pGR: ypT0-1ypN0) for groups with a prolonged time interval which was not significant. Ultimately, it led to a steady state of pCR (16.5%) and pGR (22.6%) in "8 to 10" and "more than 10" weeks. We were not able to observe any differences between the subgroups in perioperative morbidity, proportion of rectal extirpation (for cancer of the lower third) or difference in TME quality. CONCLUSION: A prolonged time interval between neoadjuvant chemoradiation can be performed, as the rate of pCR seems to be increased without influencing perioperative morbidity.

Prognostic impact of simultaneous venous resections during surgery for resectable pancreatic cancer.

BACKGROUND: The aim of this study was to evaluate the prognostic impact of simultaneous venous resection during pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PDAC) that was preoperatively staged resectable according to NCCN guidelines. METHODS: A retrospective analysis of 153 patients who underwent PD for PDAC was performed. Patients were divided into standard PD and PD with simultaneous vein resection (PDVR). Groups were compared to each other in terms of postoperative morbidity and mortality, disease free (DFS) and overall survival (OS). RESULTS: 114 patients received PD while 39 patients received PDVR. No differences in terms of postoperative morbidity and mortality between both groups were detected. Patients in the VR group presented with a significantly shorter OS in the median (13 vs. 21 months, P = 0.011). In subgroup analysis, resection status did not influence OS in the PDVR group (R0 13 vs. R1 12 months, P = 0.471) but in the PD group (R0 23 vs. R1 14 months, P = 0.043). PDVR was a risk factor of OS in univariate but not multivariable analysis. CONCLUSION: PDVR for PDAC preoperatively staged resectable resulted in significantly shorter OS regardless of resection status. Patients who require PDVR should be considered for adjuvant chemotherapy in addition to other oncological indications.

The local immune phenotype influences prognosis in patients with nodal-positive rectal cancer after neoadjuvant chemoradiation.

INDROCUTION: The local immune contexture in patients with locally advanced rectal cancer (LARC) has important prognostic value after neoadjuvant chemoradiation and surgical resection. In this study, we examined the prognostic role of Indoleamine-2,3-Dioxygenase (IDO1) and infiltrating cytotoxic T lymphocytes (CD8+) according to the nodal stage of LARC patients. MASTERIAL AND METHODS: Expression of IDO1 and CD8 was evaluated through immunohistochemistry in 106 archival tumour tissue samples from patients following neoadjuvant chemoradiation and radical resection. The average infiltration of IDO1+ and CD8+ cells was calculated and expressed as total scores as previously described. Kaplan-Meier curves were used to describe overall and disease-free survival. RESULTS: In nodal-positive tumours (N+), IDO-positivity was associated with a reduced disease-free survival (DFS) (p = 0.063) and CD8-positivity with an impaired OS (p = 0.024). Patients with a N+ LARC and a high total IDO1 score showed a clear advantage regarding five-year disease-free survival rates compared with patients with a low total IDO1 score (N+ 5y-DFS IDO1 high: 66.7% vs IDO low: 19%). We also detected better 5-years-OS rates in N+ LARC with a high total CD8 score (N+ 5y-OS CD8 high: 83.3% vs CD8 low: 32.3%). These survival benefits were not evident in patients with N-tumours. CONCLUSION: Analysis of the local CD8 and IDO1 expression influences prognosis in nodal-positive LARC patients after multimodal therapy and may be a helpful tool in specifying individual adjuvant treatment strategies according to different immune profiles.

Suprapubic bladder drainage and epidural catheters following abdominal surgery-A risk for urinary tract infections?

BACKGROUND: Epidural catheters are state of the art for postoperative analgesic in abdominal surgery. Due to neurolysis it can lead to postoperative urinary tract retention (POUR), which leads to prolonged bladder catheterization, which has an increased risk for urinary tract infections (UTI). Our aim was to identify the current perioperative management of urinary catheters and, second, to identify the optimal time of suprapubic bladder catheter removal in regard to the removal of the epidural catheter. METHODS: We sent a questionnaire to 102 German hospitals and analyzed the 83 received answers to evaluate the current handling of bladder drainage and epidural catheters. Then, we conducted a retrospective study including 501 patients, who received an epidural and suprapubic catheter after abdominal surgery at the University Hospital Würzburg. We divided the patients into three groups according to the point in time of suprapubic bladder drainage removal in regard to the removal of the epidural catheter and analyzed the onset of a UTI. RESULTS: Our survey showed that in almost all hospitals (98.8%), patients received an epidural catheter and a bladder drainage after abdominal surgery. The point in time of urinary catheter removal was equally distributed between before, simultaneously and after the removal of the epidural catheter (respectively: ~28-29%). The retrospective study showed a catheter-associated UTI in 6.7%. Women were affected significantly more often than men (10,7% versus 2,5%, p<0.001). There was a non-significant trend to more UTIs when the suprapubic catheter was removed after the epidural catheter (before: 5.7%, after: 8.4%). CONCLUSION: The point in time of suprapubic bladder drainage removal in relation to the removal of the epidural catheter does not seem to correlate with the rate of UTIs. The current handling in Germany is inhomogeneous, so further studies to standardize treatment are recommended.

Prognostic value of tumour-infiltrating CD8+ lymphocytes in rectal cancer after neoadjuvant chemoradiation: is indoleamine-2,3-dioxygenase (IDO1) a friend or foe?

The prognostic value of the local immune phenotype in patients with colorectal cancer has been extensively studied. Neoadjuvant radiotherapy and/or chemotherapy may potentially influence these immune responses. In this study, we examined the prognostic role of indoleamine-2,3-Dioxygenase (IDO1) and infiltrating cytotoxic T lymphocytes (CD8+) in locally advanced rectal carcinomas after neoadjuvant treatment. Expression of IDO1 and CD8 was evaluated by immunohistochemistry in 106 archival tumour tissue samples from patients following neoadjuvant chemoradiation and radical resection. The average infiltration of IDO1+ and CD8+ cells was calculated along the tumour invasive front, in the tumour centre and within the neoplastic cells and expressed as total scores. Of the tumour specimens evaluable for immunohistochemistry, 100% showed CD8+ lymphocyte infiltration and 93.4% stained positive for IDO1. Total IDO1 score positively correlated with total CD8 score for all three subsites (p = 0.002, Kendall-tau-b 0.357). A high total CD8 score was positively correlated with lower ypUICC-stages (p = 0.047) and lower ypT-categories (p = 0.032). Total IDO1 expression showed a clear trend towards a lower risk of recurrence (p = 0.078). A high total IDO1 score was an independent prognostic marker for prolonged disease-free survival (HR 0.38, p = 0.046) and a high total CD8 score for favourable overall survival (HR 0.16, p = 0.029). Analysis of the local CD8 and IDO1 expression profile may be a helpful tool in predicting prognosis for patients with locally advanced rectal cancer following neoadjuvant chemoradiation.

Perioperative management of anticoagulant therapy.

About 10% of patients taking a chronic, oral anticoagulant therapy require an invasive procedure that can be associated with an increased risk for peri-interventional or perioperative bleeding. Depending on the risk for thromboembolism and the risk for bleeding, the physician has to decide whether the anticoagulant therapy should be interrupted or continued. Patient characteristics such as age, renal function and drug interactions must be considered. The perioperative handling of the oral anticoagulant therapy differs according to the periprocedural bleeding risk. Patients requiring a procedure with a minor risk for bleeding do not need to pause their anticoagulant therapy. For procedures with an increased risk for perioperative bleeding, the anticoagulant therapy should be adequately paused. For patients on a coumarin derivative with a high risk for a thromboembolic event, a perioperative bridging therapy with a low molecular weight heparin is recommended. Due to an increased risk for perioperative bleeding in patients on a bridging therapy, it is not recommended in patients with a low risk for thromboembolism. For patients taking a non-vitamin K oral anticoagulant, a bridging therapy is not recommended due to the fast onset and offset of the medication.

Comparison of conventional access routes for right hemicolectomy in colon cancer-data from the DGAV StuDoQ registry.

BACKGROUND: Access for right hemicolectomy can be gained by median or transverse incision laparotomy. It is not known whether these routes differ with regard to short-term postoperative outcomes. METHODS: Patients in the DGAV StuDoQ|ColonCancer registry who underwent open oncological right hemicolectomy by median (n = 2389) or transverse laparotomy (n = 1311) were compared regarding Clavien-Dindo classification (CDC) complications (primary endpoint) as well as specific postoperative complications, operation time, length of stay, and MTL30 status (secondary endpoints). RESULTS: A total of 3700 StuDoQ registry patients underwent open oncological right hemicolectomy by median (n = 2389) or transverse laparotomy (n = 1311) without additional interventions. The median and transverse access routes did not differ regarding CDC complication rates (CDC > =3a: 13.1% vs. 12.6%; p = 0.90). However, univariate and multivariate analyses showed that operation times (OR 0.71, 95% CI 0.62-0.81; p < 0.001), length of stay (OR 0.69, 95% CI 0.6-079; p < 0.001), and MTL30 (OR 0.7, 95% CI 0.61-0.81, p < 0.001) were significantly reduced in the transverse laparotomy group. CONCLUSIONS: For oncological right hemicolectomy, open transverse upper abdominal laparotomy appears to be superior to median laparotomy in short-term course.

Pharmacodynamics of Oxaliplatin-Derived Platinum Compounds During Hyperthermic Intraperitoneal Chemotherapy (HIPEC): An Emerging Aspect Supporting the Rational Design of Treatment Protocols.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) is used to treat peritoneal surface malignancies with application of cytostatic drugs such as oxaliplatin (OX) after cytoreductive surgery. Despite its increased use, evidence for optimal drug dosage, and notably duration of HIPEC, is scarce. METHODS: In this study, OX distribution was comprehensively assessed in nine patients during HIPEC (300 mg OX/m2 body surface area in Physioneal solution for 30 min). Oxaliplatin and its derivatives were measured in peritoneal perfusates over time by liquid chromatography coupled with mass spectrometry (LC-MS), and the resulting total platinum concentration in tissue was analyzed by atomic absorption spectrometry. Additionally, a novel impedance-based real-time cytotoxicity assay was used to evaluate the bioactivity of perfusates ex vivo. RESULTS: Compared with amounts of OX expected in peritoneal perfusates by calculation, only 10-15% of the parent drug could be detected by LC-MS during HIPEC. Notably, the study additionally detected platinum compounds consistent with OX transformation, accounting for a further fraction of the applied drug. The cytotoxic properties of perfusates remained unchanged during HIPEC, with only a slight but significant attenuation evidenced after 30 min. CONCLUSIONS: The bioactivity of peritoneal perfusates ex vivo is a useful parameter for evaluating the actual cytotoxic potential of OX and its derivatives used in HIPEC over time, overcoming important limitations and disadvantages associated with respective drug monitoring only. Ex vivo cytotoxicity assays may be a promising tool to aid guiding future standardization and harmonization of HIPEC protocols based on drug-mediated effects.

Simvastatin reduces tumor cell adhesion to human peritoneal mesothelial cells by decreased expression of VCAM-1 and ß1 integrin.

Peritoneal carcinomatosis describes cancer metastasis onto the surface of the peritoneum. It is frequently caused by ovarian and colorectal cancer. Once a tumor has penetrated the peritoneum, cancer cells disseminate into the abdominal cavity. Additionally, surgery can account for the spread of free tumor cells. Their subsequent adhesion to mesothelial cells (HMCs) initiates peritoneal carcinomatosis. Therefore, this study analyzed the effect of simvastatin on tumor cell adherence. HMCs were isolated from human greater omentum. Fluorescence-labeled tumor cells (SKOV-3, OvCar-29, OAW42, FraWü; ovarian/HT29; colorectal) were incubated on confluent mesothelial monolayers with 10 µM simvastatin for 48 h. Adhesion was quantified using a fluorescence reader. Expression of the adhesion molecules VCAM-1, ICAM-1 and ß1 integrin chain under the influence of simvastatin 0.1-100 µM for 24-72 h was analyzed using flow cytometry. Simvastatin significantly reduced the adhesion of all ovarian cancer cells and HT29 to HMCs (P≤0.001). Concomitantly simvastatin decreased the expression of VCAM-1 on HMCs. ICAM-1 and ß1 integrin chain expression on ovarian cancer cells was also clearly reduced. By contrast, the expression of the analyzed adhesion molecules on HT29 cells remained unchanged. Simvastatin clearly inhibits tumor cell adhesion to HMCs. In the case of ovarian cancer cell lines it appears to be mediated by decreased expression of both VCAM-1 on HMCs and the integrin α4ß1 on tumor cells. As an example of adhesion molecule down-regulating drugs, simvastatin may provide a novel therapeutic approach to the prevention of peritoneal carcinomatosis.

Increased pretransplantation plasma kynurenine levels do not protect from but predict acute kidney allograft rejection.

Indoleamine 2,3-dioxygenase (IDO), an enzyme expressed in many cell types, catalyses degradation of tryptophan (Trp) to kynurenine (Kyn) and may exert immunosuppressive functions, mediated mainly by kynurenines. Therefore, increased Kyn concentrations would be expected to protect allografts from rejection. We conducted this study to examine whether Kyn has predictive value for kidney graft outcome. End-stage renal disease patients (n = 210) demonstrated an increased Kyn/Trp ratio compared with healthy controls (n = 30). Both Kyn and Trp levels were significantly higher in patients who subsequently developed acute rejection than in patients who did not (p < 0.001 and p < 0.001, respectively). Furthermore, pretransplantation Kyn and Trp plasma concentrations were significantly different in patients who went on to develop acute rejection (high values) or acute tubular necrosis (low values) (p = 0.007 and p = 0.021, respectively). After transplantation Kyn levels decreased. Approximately 3 days before biopsy-confirmed rejection, Kyn was significantly increased in patients with rejection compared with those without rejection (p < 0.001). Contrary to expectation, high Kyn plasma levels before transplantation were not predictive of low rejection risk. Although informative in overall terms, at the present stage, Kyn levels do not allow the concise risk differentiation of individual patients.