Chemotherapy versus chemoradiotherapy in borderline resectable and locally advanced pancreatic adenocarcinoma.

The role of radiotherapy in borderline resectable (BRPC) and locally advanced pancreatic carcinoma (LAPC) remains controversial. In our study, we retrospectively evaluated 48 patients with BRPC (14; 29.2%) and LAPC (34; 70. 8%) who underwent 6-8 cycles of induction mFOLFIRINOX chemotherapy alone (23; 47.9%) or 4-6 cycles of mFOLFIRINOX followed by hypofractionated radiotherapy (up to the total dose of 39.9 Gy in 15 fractions) (25; 52.1%). Survival parameters were evaluated using the Gehan-Breslow-Wilcoxon Test and compared by using the long-rank test. The addition of radiotherapy was not associated with better survival (16.9 months for chemotherapy only versus 15.9 months for the combined therapy; p=0.486), as well as for both subgroups (13.5 months vs. 18.3 months; p=0.679) and (20.7 months vs. 13.8 months; p=0.425) for BRPC and LAPC, respectively. A higher resection rate was seen in the BRPC group compared to the LAPC group (43% vs. 17.6%, respectively). Our study revealed a significantly higher rate of lung metastases in patients after the combination therapy compared to those treated by chemotherapy only (19% vs. 0%, respectively; p=0.045). Such a borderline result, however, prevents us from drawing clear conclusions about whether this is an artifact caused by the low number of patients or whether radiotherapy leads to a selection of stem cells with a predilection to the generalization to the lungs.

Benchmarks in colorectal surgery: multinational study to define quality thresholds in high and low anterior resection.

BACKGROUND: Benchmark comparisons in surgery allow identification of gaps in the quality of care provided. The aim of this study was to determine quality thresholds for high (HAR) and low (LAR) anterior resections in colorectal cancer surgery by applying the concept of benchmarking. METHODS: This 5-year multinational retrospective study included patients who underwent anterior resection for cancer in 19 high-volume centres on five continents. Benchmarks were defined for 11 relevant postoperative variables at discharge, 3 months, and 6 months (for LAR). Benchmarks were calculated for two separate cohorts: patients without (ideal) and those with (non-ideal) outcome-relevant co-morbidities. Benchmark cut-offs were defined as the 75th percentile of each centre's median value. RESULTS: A total of 3903 patients who underwent HAR and 3726 who had LAR for cancer were analysed. After 3 months' follow-up, the mortality benchmark in HAR for ideal and non-ideal patients was 0.0 versus 3.0 per cent, and in LAR it was 0.0 versus 2.2 per cent. Benchmark results for anastomotic leakage were 5.0 versus 6.9 per cent for HAR, and 13.6 versus 11.8 per cent for LAR. The overall morbidity benchmark in HAR was a Comprehensive Complication Index (CCI®) score of 8.6 versus 14.7, and that for LAR was CCI® score 11.9 versus 18.3. CONCLUSION: Regular comparison of individual-surgeon or -unit outcome data against benchmark thresholds may identify gaps in care quality that can improve patient outcome.

A comparison of surgical approaches in the treatment of grade C postoperative pancreatic fistula: A retrospective study.

Background: Postoperative pancreatic fistula is one of the most dreaded complications following pancreatic resections with Grade C the most severe. Several possible types of surgical intervention are available but to date, none of them have clearly shown superiority. This study aims to compare different surgical approaches. Methods: A retrospective analysis of patients who underwent revision surgery for postoperative pancreatic fistula between 2008 and 2020 was performed. Three surgical approaches were compared: open drainage; a disconnection of the pancreaticojejunostomy; and salvage total pancreatectomy. The data of nine monitored parameters were collected. Selected parameters were statistically analyzed and compared. Results: A total of 54 patients were included. Eighteen patients underwent open drainage, 28 had disconnections of the pancreaticojejunostomy and eight had salvage total pancreatectomy. Statistically significant differences were observed in the time of Intensive Care Unit stay, the number of surgical interventions, 90-day mortality, the number of administered blood transfers and treatment costs. Open drainage showed to be superior in each category. The difference in long-term survival also slightly favored simple drainage. Conclusion: Open drainage procedure showed to be superior to other types of interventions in most of the monitored parameters. Disconnection of the pancreaticojejunostomy and a salvage total pancreatectomy had similar results, which correlated with the surgical burden of these interventions.

Echinococcus multilocularis: Diagnostic problem in a liver core biopsy.

Echinococcus multilocularis causes an aggressive form of hydatidosis whose histomorphological picture is generally not well recognized. We report a case of 39-year-old women presenting with poorly circumscribed nodules in the right hepatic lobe. Owing to the clinical suspicion of focal nodular hyperplasia and hepatocellular adenoma, a core biopsy was performed. The histological findings of necrotic fibrous tissue infiltrated by narrow epithelial cords and small cysts containing cytokeratin positive material were in concordance with the diagnosis of cholangiocarcinoma. Subsequent examination of the surgically resected necrotic nodules with a vital tissue at the periphery corresponded to a reparative fibrosis accompanied by a striking ductular proliferation. Serological and molecular genetic work-up led to the diagnosis of Echinococcus multilocularis. The aim of this report is to point out the unusual histological features of the solid foci of alveolar hydatidosis, which consisted of necrotic fibrous tissue with ductular reaction. Such findings in a core biopsy may simulate regressively altered carcinoma.

Increasing incidence of tuberculosis diagnosed by surgery: a single centre analysis in low-incidence country.

OBJECTIVE: The aim of this study was to assess the incidence of thoracic tuberculosis (TB) in patients who underwent surgery for indeterminate lung nodules, mass and pleural effusions. METHODS: A monocentric retrospective study was carried out from 2012 to 2018 in a high-volume thoracic surgery centre. All patients with finding of thoracic TB within surgery and/or confirmed post-surgery were studied. Demography, origin, TB related symptoms, immunosuppression, type of surgery, and complication of surgery were analyzed. RESULTS: During the seven-year period TB was diagnosed in 71 cases, 58% were men. The mean age was 50 years. 21% of the cases had family history of TB or were successfully treated for TB in the past. 14% of patients had prior history of treatment for malignancy. Five patients (7%) received immunosuppressive therapy. The indication for surgery was indeterminate lung nodules and mass in 55 patients (77.5%) and indeterminate recurrent or persistent pleural effusions in 21 patients (22.5%). In five patients (7%) a lung carcinoma and a concomitant TB infection was detected. 63 of the cases (88.7%) had positive real-time PCR TBC test. Direct microscopic detection of Mycobacterium tuberculosis detected TB in five cases (7%). The microbiological diagnosis by culture was achieved in 19 patients (26.8%). Two patients (2.8%) were diagnosed with multidrug-resistant TB. Surgical procedure complications occurred in nine cases (12.7%). CONCLUSIONS: Although the overall incidence of TB in the Czech Republic is low and constantly continues to decrease, the number of TB detected by surgical procedures is increasing. Surgery still remains an important tool in diagnostics of nonobvious cases of TB, especially in patients with a potential risk of malignancy.

Calprotectin and Calgranulin C as Biomarkers of Pancreatic Tumors: Baseline Levels and Level Changes after Surgery.

Pancreatic tumors and their surgical resection are associated with significant morbidity and mortality, and the biomarkers currently used for these conditions have limited sensitivity and specificity. Because calprotectin and calgranulin C serum levels have been demonstrated to be potential biomarkers of certain cancers and complications of major surgery, the levels of both proteins were tested in the current study in patients with benign and malignant pancreatic tumors that were surgically removed. The baseline serum levels and kinetics of calprotectin and calgranulin C during the 7-day postoperative period were evaluated with immunoassays in 98 adult patients who underwent pancreatic surgery. The baseline serum levels of calprotectin and calgranulin C in patients with malignant (n = 84) and benign tumors (n = 14) were significantly higher (p < 0.01) when compared to those in the healthy controls (n = 26). The serum levels of both proteins were also significantly (p < 0.05) higher in patients with benign tumors than in those with malignant tumors. After surgery, the serum levels of calprotectin and calgranulin C were significantly (p < 0.01) higher than their baseline values, and this elevation persisted throughout the seven days of the follow-up period. Interestingly, starting on day 1 of the postoperative period, the serum levels of both proteins were significantly (p < 0.05) higher in the 37 patients who developed postoperative pancreatic fistulas (POPFs) than in the patients who had uneventful recoveries (n = 61). Moreover, the serum levels of calprotectin and calgranulin C demonstrated a significant predictive value for the development of POPF; the predictive values of these two proteins were better than those of the serum level of C-reactive protein and the white blood cell count. Taken together, the results of this study suggest that calprotectin and calgranulin C serum levels are potential biomarkers for pancreatic tumors, surgical injury to the pancreatic tissue and the development of POPFs.

Significance of postoperative follow-up of patients with metastatic colorectal cancer using circulating tumor DNA.

BACKGROUND: One of the most notable applications for circulating tumor DNA (ctDNA) detection in peripheral blood of patients with metastatic colorectal cancer (mCRC) is a long-term postoperative follow-up. Sometimes referred to as a "liquid (re)biopsy" it is a minimally invasive procedure and can be performed repeatedly at relatively short intervals (months or even weeks). The presence of the disease and the actual extent of the tumor burden (tumor mass) within the patient's body can be monitored. This is of particular importance, especially when evaluating radicality of surgical treatment as well as for early detection of disease progression or recurrence. AIM: To confirm the radicality of surgery using ctDNA and compare available methods for detection of recurrence in metastatic colorectal cancer. METHODS: A total of 47 patients with detected ctDNA and indications for resection of mCRC were enrolled in the multicenter study involving three surgical centers. Standard postoperative follow-ups using imaging techniques and the determination of tumor markers were supplemented by ctDNA sampling. In addition to the baseline ctDNA testing prior to surgery, a postoperative observation was conducted by evaluating ctDNA presence up to a week after surgery and subsequently at approximately three-month intervals. The presence of ctDNA was correlated with radicality of surgical treatment and the actual clinical status of the patient. RESULTS: Among the monitored patients, the R0 (curative) resection correlated with postoperative ctDNA negativity in 26 out of 28 cases of surgical procedures (26/28, 93%). In the remaining cases of R0 surgeries that displayed ctDNA, both patients were diagnosed with a recurrence of the disease after 6 months. In 7 patients who underwent an R1 resection, 4 ctDNA positivities (4/7, 57%) were detected after surgery and associated with the confirmation of early disease recurrence (after 3 to 7 months). All 15 patients (15/15, 100%) undergoing R2 resection remained constantly ctDNA positive during the entire follow-up period. In 22 cases of recurrence, ctDNA positivity was detected 22 times (22/22, 100%) compared to 16 positives (16/22, 73%) by imaging methods and 15 cases (15/22, 68%) of elevated tumor markers. CONCLUSION: ctDNA detection in patients with mCRC is a viable tool for early detection of disease recurrence as well as for confirmation of the radicality of surgical treatment.

Toward a Consensus on Centralization in Surgery.

OBJECTIVES: To critically assess centralization policies for highly specialized surgeries in Europe and North America and propose recommendations. BACKGROUND/METHODS: Most countries are increasingly forced to maintain quality medicine at a reasonable cost. An all-inclusive perspective, including health care providers, payers, society as a whole and patients, has ubiquitously failed, arguably for different reasons in environments. This special article follows 3 aims: first, analyze health care policies for centralization in different countries, second, analyze how centralization strategies affect patient outcome and other aspects such as medical education and cost, and third, propose recommendations for centralization, which could apply across continents. RESULTS: Conflicting interests have led many countries to compromise for a health care system based on factors beyond best patient-oriented care. Centralization has been a common strategy, but modalities vary greatly among countries with no consensus on the minimal requirement for the number of procedures per center or per surgeon. Most national policies are either partially or not implemented. Data overwhelmingly indicate that concentration of complex care or procedures in specialized centers have positive impacts on quality of care and cost. Countries requiring lower threshold numbers for centralization, however, may cause inappropriate expansion of indications, as hospitals struggle to fulfill the criteria. Centralization requires adjustments in training and credentialing of general and specialized surgeons, and patient education. CONCLUSION/RECOMMENDATIONS: There is an obvious need in most areas for effective centralization. Unrestrained, purely "market driven" approaches are deleterious to patients and society. Centralization should not be based solely on minimal number of procedures, but rather on the multidisciplinary treatment of complex diseases including well-trained specialists available around the clock. Audited prospective database with monitoring of quality of care and cost are mandatory.

Gastric duplication cyst communicating to accessory pancreatic lobe: A case report and review of the literature.

BACKGROUND: The combination of a gastric duplication cyst and duplicated part of the pancreas is an extremely rare developmental defect. The incidence in the population, or the clinical impact thereof, has not been uncovered. Symptoms are unspecific. Surgery is the treatment of choice. Timely diagnostics are of utmost importance, albeit they might be challenging at times. Being so rare, case reports are currently the only relevant source of information about the condition. Therefore each published finding is of a clinical impact. CASE SUMMARY: Our work describes the case of a 22 year-old patient, who developed idiopathic acute pancreatitis. A computed tomography scan discovered liquid collection between the antrum of the stomach and the head of the pancreas. Initially, the collection was thought to be a pancreatic pseudocyst. Endoscopic ultrasound-guided transgastric drainage showed to have only a temporary therapeutic effect. Magnetic resonance cholangiopancreatography showed an accessory pancreatic lobe with a separate duct system. The accessory pancreatic lobe exited the body of the pancreas and was in contact with the cystic collection. The patient was indicated for surgical resection. Within the surgery, an en bloc resection of the accessory pancreatic lobe was performed with the antrum of the stomach containing the gastric duplication cyst. No complications were observed in the surgery or thereafter. In the five months follow-up period, the patient was completely symptom free. Histopathological findings confirmed the gastric duplication cyst communicating to accessory pancreatic lobe. CONCLUSION: This developmental defect is extremely rare. It can cause recurrent acute pancreatitis. Diagnostics are challenging. Surgery is treatment of choice.

Echinococcosis mimicking liver malignancy: A case report.

INTRODUCTION: Human Alveolar Echinococcosis - Alveolar Hydatid disease (AE) is an omitted zoonotic infection presenting with focal liver lesions. Cause of AE is a larval stage of Echinococcus multilocularis tapeworms. CASE PRESENTATION: In this report an extraordinary case of a 38 year-old female examined due to 2 liver tumors and 2 pulmonary nodules is described. The patient underwent pulmonary and liver surgery for suspected advanced cholangiocellular carcinoma and surprisingly AE was found. DISCUSSION: Distinguishing intrahepatic AE from other focal liver lesion can be complicated and in many cases is diagnosed incorrectly as intrahepatic cholangiocarcinoma or other liver malignancy. CONCLUSION: AE is a rare but potentially fatal parasitic infection primarily affecting liver, although it can metastasise to lung, brain and other organs. The diagnosis and treatment can be difficult and clinical misinterpretation as malignancy is not rare. The principal treatment of AE is surgery accompanied with chemotherapy.

A new experimental model of calculous cholecystitis suitable for the evaluation and training of minimally invasive approaches to cholecystectomy.

BACKGROUND: Novel, less invasive approaches such as single-incision laparoscopic cholecystectomy or natural orifice transluminal endoscopic surgery require preclinical evaluation and training. Therefore, there is a need for an experimental model closely mimicking the clinical situation. The aim of our study was to create an experimental model of calculous cholecystitis in a large laboratory animal and test its feasibility for the evaluation of different techniques of cholecystectomy. METHODS: In 11 laboratory pigs, gallstones were placed inside the gallbladder laparoscopically. Levels of inflammatory markers-leucocytes (WBC), C-reactive protein (CRP) and interleukin 6 (IL-6)-were monitored on the postoperative days (POD) 1, 2, 3, 7 and 30. Abdominal ultrasound was performed 2 and 4 weeks after the operation. Four weeks after the lithiasis induction, laparoscopic cholecystectomy was performed. The control group consisted of ten healthy animals in which a cholecystectomy was performed. The pigs were monitored for 30 days after surgery. All removed gallbladders were assessed histologically. RESULTS: The induction of lithiasis took 42 (35-52) min with no morbidity and mortality. The values of WBC, CRP and IL-6 increased significantly (vs. baseline) on POD 1, 2 and 3 (p < 0.05) and then normalised. Ultrasonography confirmed the presence of chronic calculous cholecystitis in all cases after 4 weeks. Laparoscopic cholecystectomy was significantly longer in animals with lithiasis, 63 (42-91) versus 46 (31-62) min (p = 0.018). Perioperative gallbladder wall perforation was significantly more frequent in the model group (8/11 vs. 1/10; p = 0.04). In contrast to healthy animals, all gallbladders with stones showed histological signs of chronic inflammation. CONCLUSIONS: A new animal model of calculous cholecystitis was created. Laparoscopic cholecystectomy was more technically difficult compared to operating on a healthy gallbladder. This model may be a suitable tool for effective preclinical training and also for the evaluation of different techniques of cholecystectomy.

[Pancreatic cancer - current effective diagnostic and therapeutic approach]. / Karcinom pankreatu - soucasný efektivní diagnosticko-terapeutický postup.

UNLABELLED: Pancreatic cancer is solid malignant, chemoresistant tumour with unfavourable prognosis. Radical resection with adjuvant chemotherapy is only potential curable therapeutic modality enabling to prolong survival of 20 % patients. Borderline conception contents active approach to primary non-resectable patients to reach resectability by neoadjuvant chemo(radio)therapy. Palliative and symptomatic therapy is indicated in about 70 % patients.In the case of suspicious of pancreatic cancer, patient should be referral to specialized centre. Effective diagnostic therapeutic approach only guarantees optimal quality of life of these patients. KEY WORDS: pancreatic cancer - diagnosis and therapy, multidisciplinary approach, quality of life.

TERT gene harbors multiple variants associated with pancreatic cancer susceptibility.

A small number of common susceptibility loci have been identified for pancreatic cancer, one of which is marked by rs401681 in the TERT-CLPTM1L gene region on chromosome 5p15.33. Because this region is characterized by low linkage disequilibrium, we sought to identify whether additional single nucleotide polymorphisms (SNPs) could be related to pancreatic cancer risk, independently of rs401681. We performed an in-depth analysis of genetic variability of the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC) genes, in 5,550 subjects with pancreatic cancer and 7,585 controls from the PANcreatic Disease ReseArch (PANDoRA) and the PanScan consortia. We identified a significant association between a variant in TERT and pancreatic cancer risk (rs2853677, odds ratio = 0.85; 95% confidence interval = 0.80-0.90, p = 8.3 × 10(-8)). Additional analysis adjusting rs2853677 for rs401681 indicated that the two SNPs are independently associated with pancreatic cancer risk, as suggested by the low linkage disequilibrium between them (r(2) = 0.07, D' = 0.28). Three additional SNPs in TERT reached statistical significance after correction for multiple testing: rs2736100 (p = 3.0 × 10(-5) ), rs4583925 (p = 4.0 × 10(-5) ) and rs2735948 (p = 5.0 × 10(-5) ). In conclusion, we confirmed that the TERT locus is associated with pancreatic cancer risk, possibly through several independent variants.

Pancreatic fistula and postoperative pancreatitis after pancreatoduodenectomy for pancreatic cancer.

The most serious complication after pancreatoduodenectomy (PD) is pancreatic fistula (PF) type C, either as a consequence or independently from postoperative pancreatitis (PP). Differentiating between these two types of complications is often very difficult, if not impossible. The most significant factor in early diagnosis of PP after PD is an abrupt change in clinical status. In our retrospective study we also observed significantly higher levels of serum concentrations of CRP and AMS comparing to PF without PP. Based on our findings, CT scan is not beneficial in the early diagnosis of PP. Meantime PF type C is indication to operative revision with mostly drainage procedure which is obviously not much technically demanding, there are no definite guidelines on how to proceed in PP. Therefore the surgeon's experience determines not only whether PP will be diagnosed early enough and will be differentiated from PF without PP, but also whether a completion pancreatectomy will be performed in indicated cases.

Physical activity and risk of pancreatic cancer in a central European multicenter case-control study.

PURPOSE: Findings from epidemiological studies examining physical activity in relation to pancreatic cancer risk have suggested decreased risks for physical activity; however, the results are inconsistent. METHODS: The association between occupational and leisure-time physical activity and risk of pancreatic cancer was examined among 826 pancreatic cancer cases and 930 age-, sex- and center-matched controls from a large multicenter central European study in Czech Republic and Slovakia recruited between 2004 and 2012. Data on physical activity including type and dose (frequency, intensity, and duration) were examined using multivariable-adjusted logistic regression models. RESULTS: Occupational physical activity was not significantly associated with risk of pancreatic cancer [odds ratio (OR) 0.90, 95 % confidence interval (CI) 0.71-1.15]. A 35 % decrease in risk of pancreatic cancer was observed for regular leisure-time physical activity (OR 0.65, 95 % CI 0.52-0.87). The risk estimates were significant for low and moderate intensity of activity with the strongest protective effect among individuals who exercised during more than 40 weeks per year. The results for cumulated leisure-time physical activity assessed 1 year prior to diagnosis achieved the same level of risk reduction. In addition, stronger risk estimates for leisure-time physical activity were observed among women (men: OR 0.74, 95 % CI 0.54-1.01; women: OR 0.53, 95 % CI 0.37-0.75). The findings for female participants were stronger for intensity and frequency of leisure-time physical activity, in particular for light and moderate activity (OR 0.43, 95 % CI 0.25-0.75; and OR 0.57, 95 % CI 0.37-0.88, respectively). CONCLUSION: These results provide evidence for a decreased risk of pancreatic cancer associated with regular leisure-time physical activity.

Trends in stage-specific population-based survival of cancer patients in the Czech Republic in the period 2000-2008.

BACKGROUND: The objective of this study was to assess trends in overall and in stage-specific 5-year relative survival rates of the Czech cancer patients between periods 2000-2004 and 2005-2008. METHODS: All Czech cancer patients diagnosed between 1995 and 2008 were included in the analysis. Period analysis was employed to calculate 5-year relative survival for 21 cancers. RESULTS: Significant improvements in crude 5-year relative survival for 14 of 21 assessed types of cancer, including the most frequent diagnoses, such as, colorectal, prostate, breast, lung, kidney, pancreatic, and bladder cancer and melanoma, were identified. Moreover, in case of colorectal, lung, and prostate cancer, improvement in stage-specific 5-year relative survival was confirmed as statistically significant for all clinical stages. No diagnosis showed significant decrease in the 5-year relative survival. However, the 5-year relative survival remained poor in patients with metastatic cancers at diagnosis, particularly in case of liver, pancreatic, lung, and oesophageal cancer. CONCLUSIONS: The cancer-specific outcomes in the Czech Republic are improving. Nevertheless, despite the overall significant improvement in 5-year relative survival of most of the cancer diagnoses, the high proportion of patients primarily diagnosed with metastatic cancer still represents a substantial challenge for prevention and early detection.

Cerebral microdialysis reflects the neuroprotective effect of fractionated plasma separation and adsorption in acute liver failure better and earlier than intracranial pressure: a controlled study in pigs.

BACKGROUND: Cerebral edema is a well-recognized and potentially fatal complication of acute liver failure (ALF). The effectiveness of treatments that address intracranial hypertension is generally assessed by measuring intracranial pressure (ICP). The aim of this study was to determine the role of cerebral microdialysis in monitoring the efficacy of fractionated plasma separation and adsorption (FPSA) treatment for ALF. We hypothesized that in ALF cerebral microdialysis reflects the benefits of FPSA treatment on cerebral edema before ICP. METHODS: A surgical resection model of ALF was used in 21 pigs. We measured plasma ammonia concentration, brain concentrations of glucose, lactate, pyruvate, glutamate and glutamine, and ICP. Animals were randomized into three groups: in one group eight animals received 6 hours of FPSA treatment 2 hours after induction of ALF; in another group 10 animals received supportive treatment for ALF only; and in the final group three underwent sham surgery. RESULTS: The ICP was significantly higher in the ALF group than in the FPSA group 9 hours after surgery. The lactate/pyruvate (L/P) ratio was significantly lower in the FPSA group than the ALF group 5 hours after surgery, before any significant difference in ICP was detected. Indeed, significant changes in the L/P ratio could be observed within 1 hour of treatment. Glutamine levels were significantly lower in the FPSA group than the ALF group between 6 hours and 10 hours after surgery. CONCLUSIONS: Brain lactate/pyruvate ratio and concentration of glutamine measured by cerebral microdialysis reflected the beneficial effects of FPSA treatment on cerebral metabolism more precisely and rapidly than ICP in pigs with fulminant ALF. The role of glutamine as a marker of the efficacy of FPSA treatment for ALF appears promising, but needs further evaluation.

Hepatocyte growth on polycapronolactone and 2-hydroxyethylmethacrylate nanofiber sheets enhanced by bone marrow-derived mesenchymal stromal cells.

BACKGROUND/AIMS: The development of hepatocyte-based Bioartificial Liver Assist Devices, intended for the therapy of chronic and fulminant liver failure, is one of the important tasks in the area of tissue engineering. New advances in the development of semipermeable non-woven nanofiber biomaterials and the co-cultivation of bone marrow mesenchymal stromal cells (BMSC) and hepatocytes could be utilized in order to maintain hepatocyte cultures in these devices. METHODOLOGY: We have compared rat hepatocyte growth on nanofiber biomaterials from different polymers, 2-hydroxyethylmethacrylate (HEMA) and ethoxyethylmethacrylate (EOEMA) copolymers, polyurethane (PUR), chitosan and polycapronolactone (PCL) spun from different solvent mixtures. RESULTS: In all cases the adhesion of hepatocytes to nanofibers was significantly better/stronger than to unstructured polymer surfaces; coating the nanofibers with collagen did not increase cell adhesion. We found the best hepatocyte adhesion on HEMA/EOEMA copolymer nanofibers and PCL nanofibers spun from a mixture of ethylacetate and dimethyl sulphoxide. Using a migration assay, we observed the migration of BMSC towards hepatocytes; hepatocytes cocultivated with BMSC excreted lower amounts of stress enzymes. CONCLUSIONS: The results demonstrate that nonwoven nanofiber layers, particularly those containing BMSC, are a suitable biocompatible support for functional hepatocyte cultures and that they can be used in a laboratory bioreactor or potentially in clinical setting.

Natural orifice transluminal endoscopic surgery vs laparoscopic ovariectomy: complications and inflammatory response.

AIM: To compare natural orifice transluminal endoscopic surgery (NOTES) vs standard laparoscopic ovariectomy in mini pigs with respect to technical aspects, complications and parameters of systemic inflammatory response. METHODS: This was a randomized, experimental, survival study. Ten female mini pigs underwent NOTES transgastric ovariectomy (NOTES group) and ten female mini pigs underwent laparoscopic ovariectomy (LAP group). A "percutaneous endoscopic gastrostomy" approach with guidewire and sphincterotome was used for gastrotomy creation. The ovary was resected using standard biopsy forceps and a snare. The access site was closed using a "KING" closure with a single endoloop and several clips. In the laparoscopic group, a three-port laparoscopy and an ovariectomy were performed with the use of standard laparoscopic devices. C-reactive protein (CRP), white blood count and interleukin (IL)-6 plasma levels were used as indicators of systemic inflammatory response. All animals were euthanized 28 d after surgery. RESULTS: All animals survived without complications. The mean procedure time was 41.3 min ± 17.6 min (NOTES group) and 25.7 min ± 5.25 min (LAP group, P < 0.02). Postmortem examinations demonstrated that 50% and 70% of animals were free of any complications in the NOTES and LAP groups, respectively. The remaining animals developed minor complications (adhesions) in a comparable frequency between the two groups. In the NOTES group, one animal developed a small intramural gastric abscess close to the gastrotomy site. A minor serous exudate that was present in 50% and 40% of the animals in the NOTES and laparoscopy groups, respectively, was not considered a complication. In both groups CRP levels increased significantly on the 2nd and 7th postoperative days (POD) and returned to normal after 28 d. On POD 2, an increase of CRP level was significantly higher in the NOTES group compared to the LAP group. Values of IL-6 did not differ from baseline values in either of the groups postoperatively. Interestingly, the platelet count decreased significantly on POD 2, but returned close to baseline values on POD 7 and PODs 28-30. CONCLUSION: Both NOTES and laparoscopic ovariectomies had a similar frequency of minor complications. However, the NOTES technique produced an increased systemic inflammatory response on POD 2.

S-adenosylmethionine does not reduce ischaemia-reperfusion injury to a marginal liver graft in an in vivo experiment.

BACKGROUND/AIMS: There are a limited number of appropriate cadaver liver donors. One possible solution is the use of marginal liver grafts from cadaver donors for liver transplantation. METHODOLOGY: Rats with liver steatosis were divided into four containing seven animals each: I-a: steatotic liver grafts; +S-adenosylmethionine; I-b: steatotic liver grafts were transplanted; no S-adenosylmethionine; II-a: normal liver grafts, +S-adenosylmethionine; II-b: normal liver grafts. Blood samples were taken at days -1, 3 and 14. RESULTS: ALT values at day 14: 1.75 ± 1.10µkat/L (in group I-a), 1.91 ± 1.41µkat/L (in group I-b), 2.13±1.85µkat/L (in group II-a) and 2.08 ± 1.35µkat/L (in group II-b). There were no significant differences between these values. GSH values at day 14 post-transplantation were: 44.90 ± 8.61µM/mg (in group I-a), 43.82±8.58µM/mg (in group I-b), 41.65 ± 4.87µM/mg (in group II-a) and 42.71 ± 4.17µM/mg (in control group II-b). CONCLUSIONS: Our study did not demonstrate the positive effect of S-adenosylmethionine on ischaemia-reperfusion injury during liver transplantation in rats.