A Simple Classification of Pancreatic Duct Size and Texture Predicts Postoperative Pancreatic Fistula: A classification of the International Study Group of Pancreatic Surgery.

OBJECTIVE: The aim of this study was to develop a classification system for pancreas-associated risk factors in pancreatoduodenectomy (PD). SUMMARY BACKGROUND DATA: Postoperative pancreatic fistula (POPF) is the most relevant PD-associated complication. A simple standardized surgical reporting system based on pancreas-associated risk factors is lacking. METHODS: A systematic literature search was conducted to identify studies investigating clinically relevant (CR) POPF (CR-POPF) and pancreas-associated risk factors after PD. A meta-analysis of CR-POPF rate for texture of the pancreas (soft vs not-soft) and main pancreatic duct (MPD) diameter was performed using the Mantel-Haenszel method. Based on the results, the International Study Group of Pancreatic Surgery (ISGPS) proposes the following classification: A, not-soft (hard) texture and MPD >3 mm; B, not-soft (hard) texture and MPD ≤3 mm; C, soft texture and MPD >3 mm; D, soft texture and MPD ≤3 mm. The classification was evaluated in a multi-institutional, international cohort. RESULTS: Of the 2917 articles identified, 108 studies were included in the analyses. Soft pancreatic texture was significantly associated with the development of CR-POPF [odds ratio (OR) 4.24, 95% confidence interval (CI) 3.67-4.89, P < 0.01) following PD. Similarly, MPD diameter ≤3 mm significantly increased CR-POPF risk compared with >3 mm diameter MPDs (OR 3.66, 95% CI 2.62-5.12, P < 0.01). The proposed 4-stage system was confirmed in an independent cohort of 5533 patients with CR-POPF rates of 3.5%, 6.2%, 16.6%, and 23.2% for type A-D, respectively ( P < 0.001). CONCLUSION: For future pancreatic surgical outcomes studies, the ISGPS recommends reporting these risk factors according to the proposed classification system for better comparability of results.

Neoadjuvant Chemotherapy in Pancreatic Cancer: An Appraisal of the Current High-Level Evidence.

At the time of diagnosis, only about 20% of patients with pancreatic ductal adenocarcinoma (PDAC) have resectable disease. PDAC treatment necessitates a multidisciplinary approach, and adjuvant chemotherapy after upfront resection is an established means of preventing recurrence. Neoadjuvant chemotherapy (NAT), originally introduced to downstage tumor size, is nowadays more frequently used for selection of patients with favorable tumor biology and to control potential micrometastases. While NAT is routinely applied in locally advanced (LA) PDAC, there is increasing evidence demonstrating benefits of NAT in borderline resectable (BR) PDAC. The concept of NAT has recently been tested in resectable PDAC, but to date NAT has been restricted to clinical trials, as the data are limited and no clear benefits have yet been shown in this patient group. This review summarizes the current evidence for NAT in resectable, BR, and LA PDAC, with a focus on high-level evidence and randomized controlled trials.

4/5 Gastrectomy in Patients Undergoing Pancreaticoduodenectomy Reduces Delayed Gastric Emptying.

BACKGROUND: Delayed gastric emptying (DGE) is a frequent complication after pancreaticoduodenectomy (PD), impairing oral food intake and reducing the quality of life. The aim of this study was to investigate the effect of 4/5 gastrectomy on DGE after PD. MATERIALS AND METHODS: Patients undergoing pylorus-preserving PD (ppPD) were compared with PD with 4/5 subtotal gastrectomy, including resection of the gastric fundus (SGPD). The primary endpoint was DGE, according to the International Study Group of Pancreatic Surgery definition. Secondary outcomes included time to solid food intake, time to first flatus, postoperative morbidity, and body weight change 6- and 12-wk after surgery. RESULTS: Sixty patients underwent either ppPD (n = 32) or SGPD (n = 28). Patient characteristics were well balanced between the groups. DGE occurred in 47% after ppPD and 18% after SGPD (P = 0.027). Compared with ppPD, time to solid food intake and time to first flatus were significantly shorter after SGPD (8 d [interquartile range 5-12] versus 5 d [4-6]; P = 0.003 and 5 d [4-7] versus 3 d [2-5]; P = 0.001, respectively). Major postoperative morbidity and hospital stay was similar between the groups. Weight loss at 6 wk was less pronounced after ppPD (-4.8% [-6.3 to -2.7] versus -7.5% [-8.9 to -5.9]; P = 0.013), however, comparable after 3 and 6 mo (ppPD -7.6% [-8.5 to -4.8] versus SGPD -8.4% [-17.3 to -5.2]; P = 0.334 and ppPD -6.0% [-14.5 to 6.0] versus SGPD -9.5% [-11.8 to -7.0], P = 0.414, respectively). CONCLUSIONS: Compared with pylorus preservation, 4/5 gastrectomy significantly reduced the frequency of DGE and led to a faster gastrointestinal passage after PD. However, the benefits of a reduced DGE rate and a faster gastrointestinal passage should be carefully balanced against an increased weight loss after 4/5 gastrectomy in the early postoperative phase.

Spondylodiscitis after minimally invasive recto- and colpo-sacropexy: Report of a case and systematic review of the literature.

BACKGROUND: Rectopexy and colpopexy are established surgical techniques to treat pelvic organ prolapse. Spondylodiscitis (SD) after rectopexy and colpopexy represents a rare infectious complication with severe consequences. We presented a case of SD after rectopexy and performed a systematic review. METHODS: A systematic literature search was performed to identify case reports or case series reporting on SD after rectopexy or colpopexy. The main outcomes measures were time from initial surgery to SD, presenting symptoms, occurrence of mesh erosion or fistula formation and type of treatment. RESULTS:XS: Forty-one females with a median age of 59 (54-66) years were diagnosed with SD after a median of 76 (30-165) days after initial surgery. Most common presenting symptoms were back pain (n = 35), fever (n = 20), pain radiation in the legs (n = 9) and vaginal discharge (n = 6). A mesh erosion (n = 8) or fistula formation (n = 7) was detected in a minority of cases. The treatment of SD consisted of conservative treatment with antibiotics alone in 29%, whereas 66% of the patients had to undergo additional surgical treatment. If a revision surgery was necessary, more than one intervention was performed in 40%. Mesh and tack excision was performed in most cases (n = 21), whereas a neurosurgical intervention was necessary in 10 patients. CONCLUSION: Although a rare complication, surgeons performing rectopexy and colpopexy must be aware of the potential risk of SD Careful suture or tack placement into the anterior longitudinal ligament at the level of the promontory while avoiding the disc space is of paramount importance. Prompt diagnosis and multidisciplinary management are the cornerstones of a successful treatment.

Posterior enucleation of the pancreatic head: an alternative route of access for parenchyma-sparing pancreatic resection.

BACKGROUND: Enucleation has become an alternative treatment in benign or low-malignant cystic tumors, including intraductal papillary mucinous neoplasms (IPMN). For enucleation to be a safe alternative to the standard procedures, there must be good access to the resection area. In this report, we present such a route for dorsally situated IPMNs. METHODS: The head of the pancreas was exposed by an extended Kocher maneuver to the left lateral edge of the aorta. Stay sutures were placed along the second part of the duodenum to allow maximal rotation of the pancreatic head to the left, which exposed the posterior aspect of the pancreatic head. The cystic lesion was then enucleated followed by a protective pancreaticojejunostomy on the resection cavity. RESULTS: Two consecutive patients with IPMNs of the dorsal pancreatic head successfully underwent dorsal enucleation. The postoperative course was uneventful in the first patient, while the course of the second patient was complicated by a clinically relevant pancreatic fistula, delayed gastric emptying, and hospital discharge on day 35. CONCLUSION: This study shows the feasibility of a dorsal approach to the pancreatic head for enucleation as well as reconstruction by means of posterior Roux-en-Y pancreaticojejunostomy. In very selected cases in specialized centers, cystic lesions in the posterior aspect of the pancreatic head will become amenable to enucleation with preservation of pancreatic functionality. However, more research is needed to clarify postoperative outcomes of this approach.

Transpapillary endopancreatic surgery: decompression of duct system and comparison of greenlight laser with monopolar electrosurgical device in ex vivo and in vivo animal models.

BACKGROUND: Endopancreatic surgery (EPS) is an experimental minimally invasive technique for resection of pancreatic tissue from inside the pancreatic duct, accessed via the duodenum and papilla. It is proposed as an alternative to duodenum-preserving pancreatic head resection in benign diseases such as chronic pancreatitis (CP). This study evaluated the use of EPS for resection of pancreatic duct stenoses. Moreover, greenlight laser (GLL) and monopolar electrosurgical device (MES) were compared as resection tools for EPS. METHODS: The suitability of EPS for resection of stenoses was evaluated in ex vivo bovine pancreas (n = 8). Artificially created stenoses in the pancreatic head were accessed via the duodenal papilla and resected from inside the organ with MES through a rigid endoscope. Furthermore, standardized pancreatic resections were performed in an in vivo porcine model using either GLL (n = 18) or MES (n = 18) to compare blood loss, operating time, and complications. Thermal damage to the surrounding tissue was assessed using a standardized histological classification. RESULTS: Stenosis resection by EPS was feasible in 8/8 bovine pancreases, with a procedure time of 17 (12-24) min. No perforation of the organ occurred. Resection by GLL was associated with reduced blood loss [median 1.7 (interquartile range 0.6-2.6) ml vs. 5.1 (3.8-13.2) ml; p < 0.01] and shorter operating time [109 (81-127) s vs. 390 (337-555) s; p < 0.01] compared with MES. The zone of thermal tissue damage was more extensive when using GLL than with MES [4.12 (3.48-4.89) mm vs. 1.33 (1.09-1.48) mm; p < 0.01]. CONCLUSION: Transduodenal-transpapillary EPS can be used to resect stenoses and decompress the pancreatic duct system. Both GLL and MES are feasible resection methods for EPS. However, GLL showed better hemostatic characteristics than MES in an in vivo porcine model. Safety measures such as temperature control and image-guided navigation should be employed to monitor the resection and tissue heating.

Transduodenal-transpapillary endopancreatic surgery with a rigid resectoscope: experiments on ex vivo, in vivo animal models and human cadavers.

BACKGROUND: Surgery for chronic pancreatitis is afflicted with high morbidity. A novel transduodenal-transpapillary endopancreatic resection (EPR) may provide a less invasive alternative approach. MATERIALS AND METHODS: After laparoscopic duodenotomy the papilla was dilated and accessed with a rigid resectoscope. A resection of pancreatic head tissue was performed from inside the organ. First, the feasibility and resection volume were assessed in bovine pancreas. Bleeding and intraoperative complications were evaluated in an acute in vivo pig model. Finally, the total laparoscopic approach was tested in human cadavers. RESULTS: EPR was feasible in 6/6 bovine and 5/6 porcine pancreases; in one case the papilla could not be located. The resected surface accounted for 30 (23-39)% of the total pancreatic surface and the resection volume was 14.2 (9-25) cm3. In vivo blood loss was minimal [10 (5-20) ml]. The operating time for EPR was 84 (75-110) min in all cadavers. CONCLUSION: The EPR technique is feasible and provides a resection comparable with duodenum-preserving pancreatic head resection (DPPHR). Given the reduced surgical trauma, EPR may emerge as a minimally invasive alternative to DPPHR.

Role of proteomics to differentiate between benign and potentially malignant pancreatic cysts.

Pancreatic cystic neoplasms represent 10-15% of primary cystic masses of the pancreas. While pancreatic cysts are detected with an increasing frequency due to the use of advanced imaging modalities in clinical practice, the diagnosis of pancreatic cystic neoplasms remains unsatisfactory because available diagnostic techniques proved not sensitive enough so far. This study was designed to characterize the proteomic pattern of pancreatic cyst fluids obtained from various cystic lesions. Cyst fluids were collected by direct puncture during open surgery to avoid any possible contamination from other tissues. CEA, CA-19-9, and amylase concentrations were measured using specific immunoassays. After immunodepletion and fractionation by SDS-PAGE, proteins were digested and analyzed by LC-MS/MS. Specific histological lesions were found to be associated with distinct protein patterns. Interestingly, some of these proteins have been proposed as biomarkers of pancreatic cancer. Immunoblots allowed for verifying the differential expression in specific cyst fluids of two selected proteins, olfactomedin-4 and mucin-18. Finally, immunohistochemistry was performed to correlate these data with the expression pattern of olfactomedin-4 and mucin-18 in pancreatic cyst tissues. Results from this study indicate that proteomic analysis of cyst fluid could provide reliable candidates for developing new biomarkers for the preoperative management of malignant and premalignant pancreatic cysts.

Advances in circular stapling techniques for gastric bypass: the circular stapler introducer.

BACKGROUND: Modern laparoscopic bariatric surgery relies strongly on stapling devices and the perfection of the anastomotic technique is at the core of the patient's safety. METHODS: Circular stapler anastomosis is a common technique for performing gastro-jejunostomy in gastric bypass surgery. In obese patients, transabdominal circular stapler introduction can be challenging and associated with morbidity. To overcome these technical obstacles, we have developed a new device, circular stapler introducer (CSI) to assist both the abdominal wall passage of the circular staplers and its introduction into the jejunum. RESULTS: The CSI facilitates the insertion of the circular stapler not only into the abdomen but also into the jejunum enhancing safety and swiftness of laparoscopic Roux-en-Y gastric bypass. CONCLUSIONS: Our innovative CSI device facilitates this part of the operation significantly and makes the performance of bariatric surgery more convenient.

Circular stapler introducer: a novel device to facilitate stapled colorectal anastomosis.

OBJECTIVES: A circular stapler introducer was developed to protect the head of the circular stapler and enable atraumatic introduction and advancement of the circular stapler without interfering with the application and safety of an anastomosis. METHODS: In a Phase I prospective study, we tested the feasibility and safety of the novel circular stapler introducer device in 60 consecutive patients undergoing left-sided colorectal resections. RESULTS: The median distance of the anastomoses from the anal verge was 12 cm (7-20, n = 60). Total morbidity was 15 percent. No mortality was observed. Handling of the circular stapler introducer was considered nonproblematic by all surgeons who participated in the study. No interference of the circular stapler introducer with the circular stapling devices used was encountered. The advancement of the stapler into the end of the colorectal stump was always possible with the aid of the circular stapler introducer. CONCLUSIONS: Use of the circular stapler introducer facilitates the double-stapling technique of colorectal anastomosis. The circular stapler introducer has great potential and should be tested in larger studies.

Severe recurrent hypoglycemia after gastric bypass surgery.

BACKGROUND: Bariatric surgery is, at present, the most effective method to achieve major, long-term weight loss in severely obese patients. Recently, severe recurrent symptomatic hyperinsulinemic hypoglycemia was described as a consequence of gastric bypass surgery (GBS) in a small series of patients with severe obesity. Pancreatic nesidioblastosis, a hyperplasia of islet cells, was postulated to be the cause, and subtotal or total pancreatectomy was the suggested treatment. METHODS: We observed that severe, disabling hypoglycemia after GBS occurred only in patients with loss of restriction. Whether restoration of gastric restriction might treat severe, recurrent hypoglycemia after GBS is unknown. RESULTS: Therefore, gastric restriction was restored by surgical placement of a silastic ring (n = 8, first two patients with additional distal pancreatectomy) or an adjustable gastric band (n = 4) around the pouch in 12 consecutive patients presenting with severe hypoglycemia (blood glucose below 2.2 mM). At follow-up after restoration of gastric restriction (median follow-up 7 months, range 5 to 19 months), 11 patients demonstrated no hypoglycemic episodes, while one had recurrence of hypoglycemia and underwent distal pancreatectomy. Procedural mortality was 0% and morbidity 8.3%. CONCLUSION: Patients suffering from severe recurrent hypoglycemia after GBS can be treated, in most cases, just by restoration of gastric restriction. Distal pancreatectomy should be considered a second-line treatment.

Acceptance of neoadjuvant short-term radiotherapy: a survey under surgeons and radiotherapists.

BACKGROUND AND AIMS: Since introduction of total mesorectal excision (TME) the prognosis of rectal cancer patients has improved significantly. Debate exists regarding the optimal mode of multimodal treatment. The aim of this survey was to determine the preferred multimodal treatment and the significance and acceptance of short-term radiotherapy (5 x 5 Gy) in Germany. METHODS: In August 2003, a questionnaire was sent to the heads of all 1,275 surgical and 157 radiotherapy departments in Germany. RESULTS: Four hundred ninety-three of 1,275 surgical (39%) and 89 of 157 radiotherapeutic questionnaires (56%) were returned. The majority of the answering surgeons and radiotherapists performed adjuvant (89 and 100%), followed by neoadjuvant (61 and 94%) and short-term radiotherapy (5 x 5 Gy) (16 and 17%). Other questions of the survey dealt with indications for each treatment modality, the initiation of treatment, and reasons for objection to short term radiotherapy. CONCLUSION: Short-tem radiotherapy played a minor role in the treatment of rectal cancer patients in 2003 and was mainly initiated by surgeons (approximately 70%). However, 74% of the answering surgeons and 42% of the answering radiotherapists not performing short-term radiotherapy in 2003 were open minded towards the introduction of this treatment modality.

High frequencies of functional tumor-reactive T cells in bone marrow and blood of pancreatic cancer patients.

Pancreatic cancer is characterized by aggressive growth and treatment resistance. New approaches include immunotherapeutic strategies but the type and extent of spontaneous immune responses against tumor antigens remains unclear. A dominance of TH2 cytokines in patients' sera reported previously suggests systemic tumor-induced immunosuppression, potentially inhibiting the induction of tumor-reactive T cells. We characterized the localization, frequencies, and functional potential of spontaneously induced memory T cells specific for individual tumor antigens or the tumor-associated antigen mucin-1 in the peripheral blood and bone marrow of 41 pancreatic cancer patients. We found high numbers of tumor-reactive T cells in all bone marrow samples and in 50% of the blood samples. These cells secreted the TH1 cytokine IFN-gamma rather than TH2 cytokines upon stimulation with tumor antigens. Although consistently induced during pancreatic cancer, T cells specific for pancreatic antigens were not detected during chronic pancreatitis, suggesting that their evaluation may be of diagnostic use in both diseases. Freshly isolated T cells from cancer patients recognized autologous tumor cells and rejected them in vitro and in a xenotransplant model in vivo, suggesting their therapeutic potential. Thus, tumor antigen-specific T cell responses occur regularly during pancreatic cancer disease and lead to enrichment of tumor cell-reactive memory T cells in the bone marrow. The bone marrow can therefore be considered an important organ for antitumor immune responses in pancreatic cancer.

Balloon Dilatation of the Minor Duodenal Papilla Up to 4 mm is Safe in a Porcine Model.

OBJECTIVES: Balloon dilatation of the minor duodenal papilla is a treatment option for symptomatic pancreas divisum. The histologic effects of balloon dilatation have not yet been evaluated. The aim of this study is to investigate the tolerated extent of dilatation of the minor papilla. MATERIALS AND METHODS: A dilatation of the minor papilla was performed in freshly explanted pancreas of pigs using biliary balloon dilatators. Three organs were not dilated (control group), in each 8 organs a dilatation of 4, 6, and 8 mm, respectively, was performed. Tissue damage was assessed by microscopic evaluation. Ductal wall disruption and perforation as well as a semiquantitative inflammation score was described and compared. RESULTS: Ductal wall disruption was increased by dilatation of 6 (5/8; P=0.019) and 8 mm (6/8; P=0.006) compared with 4 mm (1/8). Median inflammation score was 0 (0 to 0), 1 (0 to 2), and 1 (0 to 2) for dilatation of 4, 6, and 8 mm, respectively (4 vs. 6 mm, P=0.007; 4 vs. 8 mm, P=0.026). No perforation occurred in the 4 (0/8) and 6 mm (0/8) group, 1 perforation occurred in the 8 mm group (1/8). CONCLUSIONS: A dilatation of up to 4 mm seems to be safe. However, dilatation of the minor papilla from 4 mm onwards is increasingly associated with tissue damage. These findings should be considered in endoscopic procedures dilating the minor duodenal papilla.

Case-matched study of lesser versus greater curvature approach in laparoscopic Warshaw pancreatectomy.

BACKGROUND: In laparoscopic distal pancreatectomy (LapDP), the pancreas is accessed in a greater curvature approach (GCA). The lesser curvature approach (LCA) has been proposed in underweight patients. The study investigated the feasibility of LCA irrespective of the body mass index (BMI). METHODS: This retrospective study included consecutive patients scheduled to undergo LapDP with the LCA. A matched cohort (1:1) underwent GCA. Spleen preservation was performed using the Warshaw technique. Splenic perfusion was intraoperatively assessed by indocyanine green (ICG) angiography. RESULTS: The LCA with LapDP was successful in 12/15 patients. In 2 cases, LCA had to be converted to GCA and in 1 patient to open surgery. The cohorts were well matched in sex (P = 1.0), age (P = .67), indication (P = 1.0), and median BMI (23.4 kg/m2 vs 24.8 kg/m2, P = .41). Splenic preservation was achieved in 14/15 patients with LCA and 4/15 patients with GCA (P = .33). In all LCA cases, ICG angiography indicated sufficient spleen perfusion. The groups had similar morbidity (P = 1.0) and hospital stay (P = .74). CONCLUSIONS: LCA was feasible in 80% irrespective of BMI and provided an excellent field of exposure. ICG angiography was feasible in the Warshaw technique. Its reliability should be evaluated in prospective studies.

Short- versus long-term complementary nutritional support via needle catheter jejunostomy after pancreaticoduodenectomy: Study protocol of a randomized controlled trial.

INTRODUCTION: Pancreatic resection is the only curative treatment for pancreatic cancer. Due to tumor cachexia most patients present with a weight loss at the time of diagnosis. Postoperatively the weight loss is often intensified. Tumor cachexia has an influence on the post-operative morbidity and mortality and on the overall survival. Complementary nutrition has a benefit on the mentioned issues. Needle catheter jejunostomy (NCJ) offers a well-tolerated and safe way for additional nutrition therapy. Until today, the optimal length of postoperative supplementary nutrition has not been evaluated. METHODS AND ANALYSIS: The study is designed as a randomized controlled trial to compare the effect of complementary nutritional support until discharge and until 8-weeks after discharge for patients after pancreaticoduodenectomy (PD). The primary endpoint is the comprehensive complications index assessed 12 weeks postoperatively. The grading of the complications will be performed by a blinded assessor. The secondary endpoints are: quality of life, a nutritional assessment and the assessment of the effect on adjuvant therapies and 5-year survival. Follow-up visits are planned 1-, 3-, 6-, 12- and 60 month postoperatively. A total sample size of 140 patients was determined for the analysis of the primary endpoint. The confirmatory analysis will be performed based on the intention-to-treat principle. ETHICS AND DISSEMINATION: The ethics committee of the University of Bern reviewed and approved this study on 22.08.2016 (KEK BE 322/14). The trial was registered in the German Clinical Trial Register (DRKS00010237) on 25.08 2016. The present trial is the first study comparing short- and long-term complementary nutritional support after PD in randomized controlled study. The results will allow a postoperative nutritional therapy after PD based on high quality data. The results will be presented at relevant surgical conferences and written publications of the short-term results and long-term oncologic results are planned within surgical journals.

Expression of cytokeratin-20 in pancreatic cancer: an indicator of poor outcome after R0 resection.

BACKGROUND: After complete removal of the neoplasm (R0 resection), approximately 80% of pancreatic cancer patients will die of the disease within 5 years. The expression panel of cytokeratins (CK) is linked closely with cell differentiation. The aim of the study was to investigate the expression of CK-20 in pancreatic cancer tissue and to correlate CK-20 expression with survival in R0-resected pancreatic cancer patients. METHODS: Tissue samples of 63 patients with pancreatic cancer were subjected to CK-20 reverse-transcription polymerase chain reaction. Thirty-four of 63 patients underwent R0 resection and were followed-up for survival statistics. From these 34 patients, 26 (76%) neoplasms were CK-20 positive and 8 (24%) samples were CK-20 negative. The mean follow-up period for the entire group was 17 months (range, 4-36 mo), the follow-up period in censored patients was 23 months (range, 10-36 mo). RESULTS: In the R0-resected group, 3 of 8 (38%) patients with CK-20-negative neoplasms, and 16 of 26 (62%) patients with CK-20-positive neoplasms (P = .15) died of recurrent disease. The median survival time of patients with CK-20-positive neoplasms was 13 months (range, 4-36), the median survival in R0-resected patients with CK-20-negative neoplasm was 26 months (range, 13-35; P = .06). The survival difference observed in patients with CK-20-negative neoplasms could not be attributed to intergroup variations in tumor stage or tumor grade. CONCLUSIONS: A majority of primary ductal pancreatic adenocarcinomas express CK-20. This seems to be associated with poorer survival in R0-resected patients. Our data suggest that ductal pancreatic adenocarcinomas negative for CK-20 constitute a subgroup of patients showing a more favorable disease outcome. The expression of CK-20 in resected pancreatic cancer may be of interest as a prognostic parameter.

Expression of the drug transporters MDR1/ABCB1, MRP1/ABCC1, MRP2/ABCC2, BCRP/ABCG2, and PXR in peripheral blood mononuclear cells and their relationship with the expression in intestine and liver.

ATP binding cassette (ABC)-transporters like P-glycoprotein (multidrug resistance (MDR)1/ABCB1), the multidrug resistance associated proteins 1 and 2 (MRP1/ABCC1 and MRP2/ABCC2), and the breast cancer resistance protein (BCRP/ABCG2) have a large impact on the pharmacokinetics of numerous drugs and may also modulate the effectiveness of drug therapy. Prediction of a patient's susceptibility to xenobiotics and individualization of drug therapy would become possible, if a simple test were available for an easy screening of transporter expression. This study quantified the mRNA expression of the four ABC-transporters and of the pregnane X receptor (PXR), a key regulator in drug metabolism and efflux, in peripheral blood mononuclear cells (PBMCs), and corresponding liver or small intestine samples of humans by real-time reverse transcription-polymerase chain reaction (RT-PCR). The results obtained prove the absence of a correlation between the expression of four major ABC-transporters in PBMCs and in the intestine or liver. For all transporters (except MRP1/ABCC1 in the intestine), mRNA amount of the ABC-transporters was positively correlated with PXR expression in PBMCs and intestine. In conclusion, the study suggests that basal expression levels of the transporters are directly influenced by PXR expression in liver and PBMCs and demonstrates that PBMCs do not qualify as surrogate tissue for the expression of the four ABC-transporters in small intestine and liver. However, the transporter status in PBMCs remains important for drugs, whose primary site of therapeutic action is the lymphocyte and which are known substrates of the transporters.