Improved survival after retrieval of 12 or more regional lymph nodes in appendiceal cancer.

BACKGROUND: To evaluate the role of regional lymph node (RLN) retrieval on stage migration, overall (OS), and cancer-specific survival (CSS) in appendiceal cancer. METHODS: Between 2004 and 2012, 1046 patients with primary stage I-III carcinoma of the appendix were identified in the Surveillance, Epidemiology and End Results database. The impact of the number of RLN removed on OS and CSS was assessed using joinpoint regression, Cox regression, and propensity score methods. RESULTS: The rate of node-positive cancer increased with the number of retrieved RLN from 10.5% in patients with one RLN removed to 30.6% in patients with 10 RLNs removed. This leveling off at 10 RLN was confirmed by joinpoint regression analysis (p = 0.023). Despite the finding that retrieval of 10 RLN should be sufficient for appendiceal cancer, for the survival analysis the somewhat higher cutoff of 12 RLN was applied, since this cutoff is recommended by the guidelines for colorectal cancer. Retrieval of 12 or more RLN was beneficial compared to less than 12 RLN retrieved for OS (HR = 0.60, p < 0.001) and CSS (HR = 0.67, p = 0.020) in multivariable analysis, as well as in propensity score matched analysis (OS: HR = 0.58, p = 0.001, CSS: HR = 0.61, p = 0.005). CONCLUSION: The rate of node-positive cancer increased with the number of retrieved RLN up to about 10 RLN (95%CI: 3.6-16.3, p = 0.023). Over 10 retrieved RLN, the node-positive cancer rate no longer increased. This correlates with the recommended number of 12 RLN to be retrieved in colorectal cancer, but differs from the guideline for neuroendocrine tumors.

Survival after resection of appendiceal carcinoma by hemicolectomy and less radical than hemicolectomy: a population-based propensity score matched analysis.

AIM: The operative treatment for non-metastatic appendiceal carcinoma is controversial despite the recommendation of right hemicolectomy (RH) by many researchers. The aim of this population-based study was to compare outcomes after RH and less radical resection than right hemicolectomy (LRH). METHOD: A total of 1144 patients who underwent resection with additional lymphadenectomy of Stages I-III appendiceal carcinoma from 2004 to 2012 were identified in the Surveillance, Epidemiology and End Results database. Overall survival (OS) and cancer-specific survival (CSS) after RH and LRH were assessed by unadjusted and risk-adjusted Cox regression analysis and by propensity score matched analysis. RESULTS: A total of 855 (74.7%) patients underwent RH and 289 (25.3%) underwent LRH. In an unadjusted analysis, survival after LRH and RH did not differ in OS [hazard ratio (HR) 0.95, 95% CI 0.71-1.26, P = 0.707] and CSS (HR 0.95, 95% CI 0.69-1.32, P = 0.762). The 5-year OS and CSS in patients who underwent RH were 71.6% (95% CI 67.8-75.6%) and 76.4% (95% CI 72.8-80.3) compared with 73.8% (95% CI 67.9-80.2) and 78.7% (95% CI 73.2-84.7) in patients with LRH, respectively. No relevant difference in survival between LRH and RH could be observed in a multivariable analysis (OS, HR 0.90, 95% CI 0.65-1.25, P = 0.493; CSS, HR 0.87, 95% CI 0.60-1.26, P = 0.420) and after propensity score adjusted analysis (OS, HR 0.87, 95% CI 0.62-1.22, P = 0.442; CSS, HR 0.97, 95% CI 0.67-1.40, P = 0.883). CONCLUSIONS: In this retrospective analysis, survival after RH for non-metastatic appendiceal carcinoma was not statistically significantly superior to LRH. Hence, LRH with lymphadenectomy might be sufficient for treatment of non-metastatic appendiceal carcinoma.

Staging of pancreatic cancer based on the number of positive lymph nodes.

BACKGROUND: The International Study Group on Pancreatic Surgery has stated that at least 12 lymph nodes should be evaluated for staging of pancreatic cancer. The aim of this population-based study was to evaluate whether the number of positive lymph nodes refines staging. METHODS: Patients who underwent pancreatectomy for stage I-II pancreatic cancer between 2004 and 2012 were identified from the Surveillance, Epidemiology, and End Results database. The predictive value of the number of positive lymph nodes for survival was assessed by generalized receiver operating characteristic (ROC) curve analysis and propensity score-adjusted Cox regression analysis. RESULTS: Some 5036 patients were included, with a median of 18 (i.q.r. 15-24) lymph nodes examined. Positive lymph nodes were found in 3555 patients (70·6 per cent). The median duration of follow-up was 15 (i.q.r. 8-28) months. ROC curve analysis revealed that two positive lymph nodes best discriminated overall survival. Patients with one or two positive lymph nodes (pN1a) and those with three or more positive lymph nodes (pN1b) had an increased risk of overall mortality compared with patients who were node-negative (pN0): hazard ratio (HR) 1·47 (95 per cent c.i. 1·33 to 1·64) and HR 2·01 (1·82 to 2·22) respectively. These findings were confirmed by propensity score-adjusted Cox regression analysis. The 5-year overall survival rates were 39·8 (95 per cent c.i. 36·5 to 43·3) per cent for patients with pN0, 21·0 (18·6 to 23·6) per cent for those with pN1a and 11·4 (9·9 to 13·3) per cent for patients with pN1b disease. CONCLUSION: The number of positive lymph nodes in the resection specimen is a prognostic factor in patients with pancreatic cancer.

Isolated tumor cells in stage I & II colon cancer patients are associated with significantly worse disease-free and overall survival.

BACKGROUND: Lymph node (LN) involvement represents the strongest prognostic factor in colon cancer patients. The objective of this prospective study was to assess the prognostic impact of isolated tumor cells (ITC, defined as cell deposits ≤ 0.2 mm) in loco-regional LN of stage I & II colon cancer patients. METHODS: Seventy-four stage I & II colon cancer patients were prospectively enrolled in the present study. LN at high risk of harboring ITC were identified via an in vivo sentinel lymph node procedure and analyzed with multilevel sectioning, conventional H&E and immunohistochemical CK-19 staining. The impact of ITC on survival was assessed using Cox regression analyses. RESULTS: Median follow-up was 4.6 years. ITC were detected in locoregional lymph nodes of 23 patients (31.1%). The presence of ITC was associated with a significantly worse disease-free survival (hazard ratio = 4.73, p = 0.005). Similarly, ITC were associated with significantly worse overall survival (hazard ratio = 3.50, p = 0.043). CONCLUSIONS: This study provides compelling evidence that ITC in stage I & II colon cancer patients are associated with significantly worse disease-free and overall survival. Based on these data, the presence of ITC should be classified as a high risk factor in stage I & II colon cancer patients who might benefit from adjuvant chemotherapy.

Meta-analysis of the predictive value of C-reactive protein for infectious complications in abdominal surgery.

BACKGROUND: The aim of this analysis was to assess the predictive value of C-reactive protein (CRP) for the early detection of postoperative infectious complications after a variety of abdominal operations. METHODS: A meta-analysis of seven cohort studies from a single institution was performed. Laparoscopic gastric bypass and colectomies, as well as open resections of cancer of the colon, rectum, pancreas, stomach and oesophagus, were included. The predictive value of CRP was assessed by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. RESULTS: Of 1986 patients, 577 (29·1 (95 per cent c.i. 27·1 to 31·3) per cent) had at least one postoperative infectious complication. Patients undergoing laparoscopic gastric bypass (383 patients) or colectomy (285), and those having open gastric (97) or colorectal (934) resections were combined in a meta-analysis. Patients who had resection for cancer of the oesophagus (41) or pancreas (246) were analysed separately owing to heterogeneity. CRP levels 4 days after surgery had the highest diagnostic accuracy (AUC 0·76, 95 per cent c.i. 0·73 to 0·78). Sensitivity and specificity were 68·5 (60·6 to 75·5) and 71·6 (66·6 to 76·0) per cent respectively. Positive and negative predictive values were 50·4 (46·0 to 54·8) and 84·3 (80·8 to 87·3) per cent. The threshold CRP varied according to the procedure performed. CONCLUSION: The negative predictive value of serum CRP concentration on day 4 after surgery facilitates reliable exclusion of postoperative infectious complications.

Randomized clinical trial on the effect of coffee on postoperative ileus following elective colectomy.

BACKGROUND: Postoperative ileus is a common problem after abdominal surgery. It was postulated that coffee intake would decrease postoperative ileus after colectomy. METHODS: This was a multicentre parallel open-label randomized trial. Patients with malignant or benign disease undergoing elective open or laparoscopic colectomy were assigned randomly before surgery to receive either coffee or water after the procedure (100 ml three times daily). The primary endpoint was time to first bowel movement; secondary endpoints were time to first flatus, time to tolerance of solid food, length of hospital stay and perioperative morbidity. RESULTS: A total of 80 patients were randomized, 40 to each group. One patient in the water arm was excluded owing to a change in surgical procedure. Patient characteristics were similar in both groups. In intention-to-treat analysis, the time to the first bowel movement was significantly shorter in the coffee arm than in the water arm (mean(s.d.) 60·4(21·3) versus 74·0(21·6) h; P = 0·006). The time to tolerance of solid food (49·2(21·3) versus 55·8(30·0) h; P = 0·276) and time to first flatus (40·6(16·1) versus 46·4(20·1) h; P = 0·214) showed a similar trend, but the differences were not significant. Length of hospital stay (10·8(4·4) versus 11·3(4·5) days; P = 0·497) and morbidity (8 of 40 versus 10 of 39 patients; P = 0·550) were comparable in the two groups. CONCLUSION: Coffee consumption after colectomy was safe and was associated with a reduced time to first bowel action.

Long-term in vitro culture of hamster pancreatic ß-cells and induction of adenocarcinoma by treatment with N-nitrosobis(2-oxopropyl)amine.

OBJECTIVES: Earlier studies indicated that hamster pancreatic ductal adenocarcinoma not only derives from ductal/ductular structures but also from cells within the islet. So far unidentified cells within the islet are responsive to the carcinogenic effect of N-nitrosobis (2-oxopropyl) amine (BOP) forming poorly differentiated ductal adenocarcinoma. However, studies indicated a major role of ß-cells during carcinogenesis. To find out, if ß-cells are the primary target cells of BOP and if they are capable to form ductal adenocarcinoma after malignant transformation, we established a long-term culture of undifferentiated cells deriving from isolated ß-cells and treated them with BOP. METHODS: Langerhans' islets from pancreata of Syrian golden hamsters were isolated and dispersed into single cells by dispase digestion. Cells were labeled with a highly specific ß-cell surface antibody (K14D10) and these K14D10+ cells were extracted from the suspension by paramagnetic Dynabeads. Cells were cultured in vitro and treated with BOP. Untreated cells served as control. RESULTS: K14D10+ cells formed a monolayer and produced insulin over a period of 28 days in culture. However, with time in culture they became undifferentiated with a higher proliferation rate and after about 60 days in culture BOP treated cells showed anchorage independent growth. These cells autotransplanted s.c. formed a well-differentiated ductal adenocarcinoma. CONCLUSIONS: Pancreatic ß-cells are the primary target of BOP without necessarily being embedded in the compound of the Langerhans' islet. With time in culture, they give rise to undifferentiated cells and after malignant transformation they are able to form ductal adenocarcinoma.

Elevated preoperative CEA is associated with worse survival in stage I-III rectal cancer patients.

BACKGROUND: The objective of this investigation was to assess whether preoperative carcinoembryonic antigen (CEA) level is an independent predictor of overall survival in rectal cancer patients. METHODS: All patients (n=504) undergoing a resection for stage I-III rectal cancer at the Kantonsspital St Gallen were included into a database between 1991 and 2008. The impact of preoperative CEA level on overall survival was assessed using risk-adjusted Cox proportional hazard regression models and propensity score methods. RESULTS: In risk-adjusted Cox proportional hazard regression analyses, preoperative CEA level (hazard ratio (HR): 1.98, 95% confidence interval (CI): 1.36-2.90, P<0.001), distance from anal verge (<5 cm: HR: 1.93, 95% CI: 1.11-3.37; P=0.039), older age (HR: 1.07, 95% CI: 1.05-1.09; P<0.001), lower body mass index (HR: 0.94, 95% CI: 0.89-0.98; P=0.006), advanced tumour stage (stage II HR: 1.41, 95% CI: 0.85-2.32; stage III HR: 2.08, 95% CI: 1.31-3.31; P=0.004), R 1 resection (HR: 5.65, 95% CI: 1.59-20.1; P=0.005) and chronic kidney disease (HR: 2.28, 95% CI: 1.03-5.04; P=0.049) were all predictors for poor overall survival. CONCLUSION: This is one of the first investigations based on a large cohort of exclusively rectal cancer patients demonstrating that preoperative CEA level is a strong predictor of decreased overall survival. Preoperative CEA should be used as a prognostic factor in the preoperative assessment of rectal cancer patients.

The role of an interdisciplinary transplant team on living donation kidney transplantation program.

During the last decades, the disparity between the organ supply and the demand for kidney transplantation in Europe has led to consider living donors as a more acceptable option. In the last 7 years, we have established an interdisciplinary supporting transplant team to increase the rate of living donation. After 2001, the new interdisciplinary transplant team consisted of a transplant surgeon, a nephrologist, a pediatrician, a radiologist, a psychologist, a transplant coordinator, and a transplant nurse. We performed a prospective analysis to examine the effect of implementing this team on our living donation program. Demographic data, the annual number of procedures, the duration of waiting, and the cold ischemia time were evaluated among brain-dead and living donors. From January 2002 until December 2008, the number of patients who were annually on the waiting list increased 42% (from 377 to 536 patients). Consequently, the number of the total kidney transplants increased from 81 to 120 with an annual median of 98 cases. By implementing the interdisciplinary transplant team, a significant increase of living kidney donors was observed: from 18 to 42 cases; median = 27). In the last 7 years, a total number of 796 kidney transplants have been performed: 567 from brain-dead and 229 from living donors. In 2001, the waiting list times for recipients who received grafts from brain-dead versus living donors were 1356 versus 615 days respectively. Compared with 2008, the duration on the waiting list decreased significantly for patients receiving a living donor graft, whereas there was a slight increase for the patients in the brain-dead group: brain death versus living donors: 1407 versus 305 days. The interdisciplinary approach has also reduced the cold ischemia time for the living donor recipients: 3 hours and 42 minutes in 2001 versus 2 hours and 50 minutes in 2008. During the last years, by implementing an interdisciplinary transplant team, supporting living donor procedures has produce a gradual increase in the number of kidney transplants from living donors with a remarkable decrease in waiting and cold ischemia times, the latter presumably influencing graft quality.

A single center experience of combined liver kidney transplantation.

With advancements in the operative techniques, patient survival following liver transplantation (LTx) has increased substantially. This has led to the acceleration of pre-existing kidney disease because of immunosuppressive nephrotoxicity making additional kidney transplantation (KTx) inevitable. On the other hand, in a growing number of patients on the waiting list to receive liver, long waiting time has resulted in adverse effect of decompensated liver on the kidney function. During the last two decades, the transplant community has considered combined liver kidney transplantation (CLKTx) to overcome this problem. The aim of our study is to present an overview of our experience as well as a review of the literature in CLKTx and to discuss the controversy in this regard. All performed CLKTx (n = 22) at our institution as well as all available reported case series focusing on CLKTx are extracted. The references of the manuscripts were cross-checked to implement further articles into the review. The analyzed parameters include demographic data, indication for LTx and KTx, duration on the waiting list, Model for End-Stage Liver Disease (MELD) score, Child-Turcotte-Pugh (CTP) score, immunosuppressive regimen, post-transplant complications, graft and patient survival, and cause of death. From 1988 to 2009, a total of 22 CLKTx were performed at our institution. The median age of the patients at the time of CLKTx was 44.8 (range: 4.5-58.3 yr). The indications for LTx were liver cirrhosis, hyperoxaluria type 1, polycystic liver disease, primary or secondary sclerosing cholangitis, malignant hepatic epithelioid hemangioendothelioma, cystinosis, and congenital biliary fibrosis. The KTx indications were end-stage renal disease of various causes, hyperoxaluria type 1, polycystic kidney disease, and cystinosis. The mean follow-up duration for CLKTx patients were 4.6 +/- 3.5 yr (range: 0.5-12 yr). Overall, the most important encountered complications were sepsis (n = 8), liver failure leading to retransplantation (n = 4), liver rejection (n = 3), and kidney rejection (n = 1). The overall patient survival rate was 80%. Review of the literature showed that from 1984 to 2008, 3536 CLKTx cases were reported. The main indications for CLKTx were oxalosis of both organs, liver cirrhosis and chronic renal failure, polycystic liver and kidney disease, and liver cirrhosis along with hepatorenal syndrome (HRS). The most common encountered complications following CLKTx were infection, bleeding, biliary complications, retransplantation of the liver, acute hepatic artery thrombosis, and retransplantation of the kidney. From the available data regarding the need for post-operative dialysis (n = 673), a total of 175 recipients (26%) required hemodialysis. During the follow-up period, 154 episodes of liver rejection (4.3%) and 113 episodes of kidney rejection (3.2%) occurred. The cumulative 1, 2, 3, and 5 yr survival of both organs were 78.2%, 74.4%, 62.4%, and 60.9%, respectively. Additionally, the cumulative 1, 2, 3, and 5 yr patient survival were 84.9%, 52.8%, 45.4%, and 42.6%, respectively. The total number of reported deaths was 181 of 2808 cases (6.4%), from them the cause of death in 99 (55%) cases was sepsis. It can be concluded that there is still no definitive evidence of better graft and patient survival in CLKTx recipients when compared with LTx alone because of the complexity of the exact definition of irreversible kidney function in LTx candidates. Additionally, CLKTx is better to be performed earlier than isolated LTx and KTx leading to the avoidance of deterioration of clinical status, high rate of graft loss, and mortality. Shorter graft ischemia time and more effective immunosuppressive regimens can reduce the incidence of graft malfunctioning in CLKTx patients. Providing a model to reliably determine the need for CLKTx seems necessary. Such a model can be shaped based upon new and precise markers of renal function, and modification of MELD system.

Functional outcome after restorative proctocolectomy in pigs: comparing a novel transverse ileal pouch to the J-pouch and straight ileoanal anastomosis.

BACKGROUND: Restorative proctocolectomy followed by an ileoanal J-pouch procedure is the therapy of choice for patients with familial adenomatous polyposis and ulcerative colitis. After low anterior rectal resection, the authors have reported on a novel, less complex pouch configuration, a transverse coloplasty pouch. The aim of the present work was to apply this new design to the ileal pouch construction, to evaluate feasibility, and to measure functional results in comparison with the J-pouch and the straight ileoanal anastomosis using the pig as an animal model. METHODS: Twenty-three pigs underwent restorative proctocolectomy followed by reconstruction with straight ileoanal anastomosis (IAA; n = 5), J-pouch (n = 7), and a transverse ileal pouch (TIP; n = 11). Pigs were followed for 6 days postoperatively. Peristaltic function was assessed by manometry proximal to the pouch, in the reservoir, and at the level of the ileoanal anastomosis. Functional outcome was monitored by semiquantitative assessment of the general condition of the animals, postoperative feeding habits, and stool frequency and consistency. A Fourier analysis was performed in order to compare peristalsis in the ileal reservoirs. The reservoir volume was measured in situ by triple contrast computed tomography scan with 3D reconstruction. RESULTS: Seventeen animals survived for 1 week. There was no difference in the general condition or the feeding habits of the groups. A significant number of pigs with the TIP pouch (7/10) had semisolid or formed stools as opposed to liquid stools after J-pouch (6/6) and IAA (4/5; p = 0.01). TIP animals had a lower stool frequency (3.2 +/- 1.14 per day) on day 6 after the operation than pigs with J-pouch, 5.33 +/- 1,03, and IAA, 4.6 +/- 1.82 (p = 0.0036). The in situ volume of the pouches did not differ significantly. The Fourier analysis demonstrated a disruption of peristalsis by the J-pouch and the TIP reconstruction but not after IAA. CONCLUSION: The function of ileoanal reservoirs after proctocolectomy may result from the disruption of properistaltic waves after pouch formation. The mechanism of peristalsis disruption is independent of the in situ volume of the pouch.

[Differentiated therapy for intraductal papillary mucinous neoplasms]. / Differenzierte Therapie der intraduktalen papillären muzinösen Neoplasie.

Intraductal papillary mucinous neoplasms (IPMN) of the pancreas are of increasing interest in the field of pancreatic surgery ever since their first description as an individual pancreatic tumor entity in 1982. The decision for surgical or conservative management is based on the adenoma-carcinoma sequence and the differentiation into main-duct or branch-duct IPMN. Invasive IPMN forms (carcinoma in situ and invasive carcinoma) and in particular noninvasive IPMNs (adenoma and borderline tumors) reveal significantly better survival rates than ductal adenocarcinoma of the pancreas.

In vivo accuracy assessment of a needle-based navigation system for CT-guided radiofrequency ablation of the liver.

Computed tomography (CT)-guided percutaneous radiofrequency ablation (RFA) has become a commonly used procedure in the treatment of liver tumors. One of the main challenges related to the method is the exact placement of the instrument within the lesion. To address this issue, a system was developed for computer-assisted needle placement which uses a set of fiducial needles to compensate for organ motion in real time. The purpose of this study was to assess the accuracy of the system in vivo. Two medical experts with experience in CT-guided interventions and two nonexperts used the navigation system to perform 32 needle insertions into contrasted agar nodules injected into the livers of two ventilated swine. Skin-to-target path planning and real-time needle guidance were based on preinterventional 1 mm CT data slices. The lesions were hit in 97% of all trials with a mean user error of 2.4 +/- 2.1 mm, a mean target registration error (TRE) of 2.1 +/- 1.1 mm, and a mean overall targeting error of 3.7 +/- 2.3 mm. The nonexperts achieved significantly better results than the experts with an overall error of 2.8 +/- 1.4 mm (n=16) compared to 4.5 +/- 2.7 mm (n=16). The mean time for performing four needle insertions based on one preinterventional planning CT was 57 +/- 19 min with a mean setup time of 27 min, which includes the steps fiducial insertion (24 +/- 15 min), planning CT acquisition (1 +/- 0 min), and registration (2 +/- 1 min). The mean time for path planning and targeting was 5 +/- 4 and 2 +/- 1 min, respectively. Apart from the fiducial insertion step, experts and nonexperts performed comparably fast. It is concluded that the system allows for accurate needle placement into hepatic tumors based on one planning CT and could thus enable considerable improvement to the clinical treatment standard for RFA procedures and other CT-guided interventions in the liver. To support clinical application of the method, optimization of individual system modules to reduce intervention time is proposed.

Precision targeting of liver lesions with a needle-based soft tissue navigation system.

In this study, we assessed the targeting precision of a previously reported needle-based soft tissue navigation system. For this purpose, we implanted 10 2-ml agar nodules into three pig livers as tumor models, and two of the authors used the navigation system to target the center of gravity of each nodule. In order to obtain a realistic setting, we mounted the livers onto a respiratory liver motion simulator that models the human body. For each targeting procedure, we simulated the liver biopsy workflow, consisting of four steps: preparation, trajectory planning, registration, and navigation. The lesions were successfully hit in all 20 trials. The final distance between the applicator tip and the center of gravity of the lesion was determined from control computed tomography (CT) scans and was 3.5 +/- 1.1 mm on average. Robust targeting precision of this order of magnitude would significantly improve the clinical treatment standard for various CT-guided minimally invasive interventions in the liver.

Thymoglobulin and ischemia reperfusion injury in kidney and liver transplantation.

Since the beginning of organ transplantation, graft preservation has been one of the most important concerns. Ischemia reperfusion injury (IRI), which plays an important role in the quality and function of the graft, is a major cause for increased length of hospitalization and decreased long term graft survival. Among numerous attempts which have been made to minimize graft damage associated with IRI, the use of Thymoglobulin (TG) seems to offer potential benefits. TG is a polyclonal antibody which blocks multiple antigens related to IRI, in addition to its better known T cell depleting effects. This review will focus on the use of TG in preventing IRI in kidney transplantation (KTx) and liver transplantation (LTx). Different studies in experimental and clinical transplantation have shown that TG protects renal and liver grafts from IRI. Improvement in early graft function and decreased delayed graft function (DGF) rates are some of the clinical benefits of TG. Additionally, it is used in patients with hepatorenal syndrome to support the recovery of kidney function after LTx, by allowing reduced exposure to nephrotoxic calcineurin inhibitors as well as improving liver graft function by minimizing IRI. TG can reduce acute rejection rates in kidney and liver transplant recipients, decrease the length of hospital stay, and hence reduce transplantation costs. TG can play an important role in expanding the donor pool in both KTx and LTx by improving long-term graft and patient survival rates which increases the possibility of using marginal donors. Although controversial, the development of post-transplant lymphoproliferative disorder is a potential side effect of TG. No single optimal immunosuppressive regimen has given consistent results in decreasing the graft damage following IRI; however, TG usage in KTx and LTx appears to have some benefits in reducing IRI.

C-reactive protein as early predictor for infectious postoperative complications in rectal surgery.

BACKGROUND: This study evaluated the role of the acute phase C-reactive protein (CRP) in the postoperative course of a large series of rectal resections on the basis of a prospective database. Main focus of this study was the early identification of complications. MATERIALS AND METHODS: Three hundred eighty-three rectal resections with primary anastomosis for rectal cancer were screened for infectious postoperative complications. Forty-eight complicated cases were identified and matched with 48 patients with an uneventful postoperative course. RESULTS: In the postoperative setting, CRP peaked on postoperative day (POD) 2 with a median serum CRP of 140 mg/l and gradually declined thereafter in uncomplicated cases. In complicated cases, CRP elevation generally persisted after POD 2, whereas white blood cells and body temperature were within normal range in the early postoperative period. A cutoff CRP value of 140 mg/dl on PODs 3 and 4 resulted in predictive values of 85.7 and 90.5% (adjusted to the prevalence: 37.6 and 50.3%), sensitivities of 80.0 and 54.3%, and specificities of 81.0 and 92.3% for a complicated postoperative course (P<0.001), respectively. CONCLUSION: Persistent CRP elevation and elevation of serum CRP above 140 mg/dl on PODs 3-4 are predictive of infectious postoperative complications and should prompt intense clinical search for an inflammatory process, especially for an anastomotic leak if pneumonia and wound infection are unlikely or excluded.

Creation and establishment of a respiratory liver motion simulator for liver interventions.

Image-guided surgery and navigation have resulted from convergent developments in radiology, teletransmission, and computer science and are well-established procedures in the surgical routine in orthopedic, neurosurgery, and head-and-neck surgery. In abdominal surgery, however, these tools have gained little attraction so far. The inability to transfer the methodology from orthopedic or neurosurgery is mainly a result of intraoperative organ movement and shifting. To practice and establish navigated interventions in the liver, a custom-designed respiratory liver motion simulator was built which models the human torso and is easy to recreate. To simulate breathing motion, an explanted porcine or human liver is mounted to the diaphragm model of the simulator, and a lung ventilator causes a periodic movement of the liver along the craniocaudal axis. Additionally, the liver can be connected to a circulating pump device which simulates hepatic perfusion and provides real surgical options to establish navigated interventions and simulate management of possible complications. Respiratory motion caused by the simulator was evaluated with an optical tracking system and it was shown that in vitro movement and deformation of a liver mounted to the device are similar to the liver movements in human or porcine bodies. Based on the tests, it is concluded that the novel respiratory liver motion simulator is suitable for in vitro evaluation of navigated systems and interventional and surgical procedures.

The role and value of sirolimus administration in kidney and liver transplantation.

Enormous advancements in visceral transplantation have led to significant improvements in the quality of life of patients. However, despite these developments, the average graft half-life after transplantation has remained almost unchanged and chronic rejection is still considered a major problem. In this regard, more concerns have shifted to factors influencing long-term graft survival, patient survival, and quality of life. To achieve this goal, detrimental effects of immunosuppressive (IS) agents, which have deleterious influence on the quality of life and/or patient survival, should be reduced. In the course of recent years, the transplant community has worked on reducing these side effects by developing new ISs, employing new combination regimens, or finding and adjusting optimal dosages and blood level concentrations. Among the IS agents, the antifungal, antitumoral and IS activity of mammalian target of rapamycin (mTOR) inhibitors without nephrotoxicity, have received special attention regarding this new class of IS. Sirolimus (SRL), as the first member of mTOR inhibitors, has been utilized in many clinical trials with respect to its benefit-risk assessment. In our review, the clinical evolution of SRL, as well as the evidence-based clinical benefits of SRL in kidney and liver transplantation (KTx, LTx), are summarized. Various studies of SRL in KTx and LTx have shown that combination therapy with SRL will enrich the variety of IS modalities. It also can be regarded as a safe base therapy to which other necessary drugs can be added. In addition to the enhanced acute rejection prophylaxis, and in contrast to the calcineurin inhibitors (CNI) and steroids, this drug solely does not have common side effects such as nephrotoxicity, neurotoxicity, diabetes mellitus and hypertension. Moreover, this agent might diminish vasculopathic processes that mediate chronic allograft nephropathy (CAN). Therefore, by reducing the likelihood of CAN it can decrease the rate of long-term organ failure. One possibly desirable characteristic of SRL is its antiproliferative effect, which could provoke antitumoral or antiatherogenic activity following transplantation. Despite all promising impacts of SRL in organ transplantation, there are some concerns regarding the adverse effects of this drug, for instance dyslipidemia, pneumonitis and wound healing problems. However, the majority of these side effects can be reduced or ceased by careful dose adjustments and correct timing of use. In conclusion, after a decade of both in vivo and in vitro studies on SRL, it can be advocated that SRL is a promising, potent and effective IS agent as it reduces the rate of acute rejection episodes in de novo transplants. It could improve the quality of life, graft and patient survival rate, and achieve excellent outcomes with few adverse effects when wisely used in combination with other immunosuppressants.

Immunosuppressive standards in simultaneous kidney-pancreas transplantation.

Simultaneous pancreas-kidney transplantation is an established procedure for patients with type I diabetes and end-stage renal disease. Continuous advances in the operation techniques with consequent reduction of perioperative morbidity and mortality and the introduction of modern immunosuppressive agents improved not only patients but also graft survival and significantly decreased rejection episodes of both kidney and pancreas grafts. Availability of a variety of new immunosuppressants in the clinical routine and increasing experience of the transplant specialists allowed further developments of therapeutic schemes with application of induction and maintenance immunosuppressive protocols. In this article, we summarize the current status of immunosuppressive regimens in simultaneous pancreas and kidney transplantation.

How to increase inflow in liver transplantation.

Liver transplantation (LTx) has become the treatment of choice for selected cases of benign and malignant liver disease. Despite becoming increasingly safer in recent years this procedure still incurs several serious postoperative complications. The most significant surgical complications are related to surgical technique, particularly the reconstruction and/or anastomosis of the hepatic artery. Arterial hypoperfusion may lead to graft failure, sepsis, or ischemic biliary lesions. In this review we focus on the Achilles' heel of LTx: the hepatic artery. We provide transplant surgeons with an overview of the technical options that are available to increase arterial inflow and subsequently improve patient outcome. We exemplify some of the discussed techniques using a liver transplant case with an eventful postoperative course because of arterial complications.