Histopathological changes resulting from selective internal radiotherapy (SIRT).

BACKGROUND: Selective internal radiotherapy (SIRT) has emerged as an effective therapy for patients with liver malignancies. Here, we report our analysis of histopathological changes in tumors and healthy liver tissue after SIRT and liver resection. Our main intent was to determine if specific histopathological changes occur in tumor and normal liver tissues. METHODS: We identified 17 patients in whom SIRT was applied to achieve liver resectability. Samples were taken from the resected liver tissue. The tumor, tumor peripheries, and tumor-free tissue were examined microscopically. RESULTS: Microspheres were identified in the vascular tumor bed, tumor-free liver, and portal tract. More microspheres were detected in the tumor than in the healthy liver tissue. When the effects of SIRT were analyzed, most patients showed a partial pathological response. Specific histopathological changes could not be described. We did not find any typical signs of radiation-induced hepatitis in healthy liver tissue. CONCLUSIONS: Our findings support the clinical experience of effective tumor control after SIRT together with minimal impairment of healthy liver tissue. The observed histopathological changes suggest that SIRT might play a role in preoperative downsizing of liver malignancies.

Liver resection after selective internal radiotherapy (SIRT): Proof of concept, initial survival, and safety.

BACKGROUND AND OBJECTIVES: Extent of liver resections are restricted by the volume of the future liver remnant. Different strategies have been developed to increase the frequency of curative resections. Selective internal radiation therapy (SIRT) has emerged as an effective therapy for patients with primary non-resectable malignancies of the liver. Here, we report the first clinical series of patients with curative liver resection following SIRT. METHODS: Starting 2010, patients with marginally resectable liver metastases treated by SIRT followed by liver resection were identified and prospectively documented in a database for subsequent retrospective analysis. RESULTS: Thirteen patients (five female, eight male; age 70 years [32-77 years]) with marginally resectable liver metastases were selected for liver resection after SIRT. After performing SIRT, 12 patients had potentially curative hepatic resection. In two patients, liver resection after SIRT could not be performed due to the appearance of new extrahepatic metastases. Analyzing the effect of SIRT, we observed a decrease in tumor size with central scaring. None of the patients developed liver necrosis after SIRT. Liver resection was performed safely in all patients. CONCLUSIONS: The combination of SIRT with state-of-the-art liver surgery opens up new therapeutic options in patients with liver metastases.

Intrahepatic cholangiocarcinoma in a transplant liver--selective internal radiation therapy followed by right hemihepatectomy: report of a case.

Intra- or extrahepatic cholangiocarcinomas are the second most common primary liver malignancies behind hepatocellular carcinoma. Whereas the incidence for intrahepatic cholangiocarcinoma is rising, the occurrence of extrahepatic cholangiocarcinoma is trending downwards. The treatment of choice for intrahepatic cholangiocarcinoma remains liver resection. However, a case of liver resection after selective internal radiation therapy in order to treat a recurrent intrahepatic cholangiocarcinoma in a transplant liver is unknown in the literature so far. Herein, we present a case of a patient undergoing liver transplantation for Wilson's disease with an accidental finding of an intrahepatic cholangiocarcinoma within the explanted liver. Due to a recurrent intrahepatic cholangiocarcinoma after liver transplantation, a selective internal radiation therapy with yttrium-90 microspheres was performed followed by right hemihepatectomy. Four years later, the patient is tumor-free and in a healthy condition.

Delphi Consensus on Intraoperative Technical/Surgical Aspects to Prevent Surgical Site Infection after Colorectal Surgery.

BACKGROUND: Previous studies have focused on the development and evaluation of care bundles to reduce the risk of surgical site infection (SSI) throughout the perioperative period. A focused examination of the technical/surgical aspects of SSI reduction during CRS has not been conducted. This study aimed to develop an expert consensus on intraoperative technical/surgical aspects of SSI prevention by the surgical team during colorectal surgery (CRS). STUDY DESIGN: In a modified Delphi process, a panel of 15 colorectal surgeons developed a consensus on intraoperative technical/surgical aspects of SSI prevention undertaken by surgical personnel during CRS using information from a targeted literature review and expert opinion. Consensus was developed with up to three rounds per topic, with a prespecified threshold of ≥70% agreement. RESULTS: In 3 Delphi rounds, the 15 panelists achieved consensus on 16 evidence-based statements. The consensus panel supported the use of wound protectors/retractors, sterile incision closure tray, preclosure glove change, and antimicrobial sutures in reducing SSI along with wound irrigation with aqueous iodine and closed-incision negative pressure wound therapy in high-risk, contaminated wounds. CONCLUSIONS: Using a modified Delphi method, consensus has been achieved on a tailored set of recommendations on technical/surgical aspects that should be considered by surgical personnel during CRS to reduce the risk of SSI, particularly in areas where the evidence base is controversial or lacking. This document forms the basis for ongoing evidence for the topics discussed in this article or new topics based on newly emerging technologies in CRS.

Effect of triclosan-coated sutures for abdominal wound closure on the incidence of abdominal wound dehiscence: a protocol for an individual participant data meta-analysis.

INTRODUCTION: Acute abdominal wound dehiscence (AWD) or burst abdomen is a severe complication after abdominal surgery with an incidence up to 3.8%. Surgical site infection (SSI) is the biggest risk factor for the development of AWD. It is strongly suggested that the use of triclosan-coated sutures (TCS) for wound closure reduces the risk of SSI. We hypothesise that the use of TCS for abdominal wound closure may reduce the risk of AWD. Current randomised controlled trials (RCTs) lack power to investigate this. Therefore, the purpose of this individual participant data meta-analysis is to evaluate the effect of TCS for abdominal wound closure on the incidence of AWD. METHODS AND ANALYSIS: We will conduct a systematic review of Medline, Embase and Cochrane Central Register of Controlled Trials for RCTs investigating the effect of TCS compared with non-coated sutures for abdominal wound closure in adult participants scheduled for open abdominal surgery. Two independent reviewers will assess eligible studies for inclusion and methodological quality. Authors of eligible studies will be invited to collaborate and share individual participant data. The primary outcome will be AWD within 30 days after surgery requiring reoperation. Secondary outcomes include SSI, all-cause reoperations, length of hospital stay and all-cause mortality within 30 days after surgery. Data will be analysed with a one-step approach, followed by a two-step approach. In the one-step approach, treatment effects will be estimated as a risk ratio with corresponding 95% CI in a generalised linear mixed model framework with a log link and binomial distribution assumption. The quality of evidence will be judged using the Grading of Recommendations Assessment Development and Evaluation approach. ETHICS AND DISSEMINATION: The medical ethics committee of the Amsterdam UMC, location AMC in the Netherlands waived the necessity for a formal approval of this study, as this research does not fall under the Medical Research involving Human Subjects Act. Collaborating investigators will deidentify data before sharing. The results will be submitted to a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42019121173.

CXC receptor-4 mRNA silencing abrogates CXCL12-induced migration of colorectal cancer cells.

BACKGROUND: Interactions between CXCR4 and its ligand CXCL12 have been shown to be involved in cancer progression in colorectal cancer (CRC). We performed a comparative CXCL12/CXCR4 expression analysis and assessed the effect of external CXCL12 stimulation on migration of CRC cells without and with CXCR4 inhibition. METHODS: Expression of CXCL12/CXCR4 was assessed by quantitative real-time PCR, ELISA and immunohistochemistry in resection specimens of 50 CRC patients as well as in the corresponding normal tissues and in three human CRC cell lines with different metastatic potential (Caco-2, SW480 and HT-29). Migration assays were performed after stimulation with CXCL12 and CXCR4 was inhibited by siRNA and neutralizing antibodies. RESULTS: In CRC tissues CXCL12 was significantly down-regulated and CXCR4 was significantly up-regulated compared to the corresponding normal tissues. In cell lines CXCR4 was predominantly expressed in SW480 and less pronounced in HT-29 cells. CXCL12 was only detectable in Caco-2 cells. CXCL12 stimulation had no impact on Caco-2 cells but significantly increased migration of CXCR4 bearing SW480 and HT-29 cells. This effect was significantly abrogated by neutralizing anti-CXCR4 antibody as well as by CXCR4 siRNAs (P < 0.05). CONCLUSIONS: CXCR4 expression was up-regulated in CRC and CXCL12 stimulation increased migration in CXCR4 bearing cell lines. Migration was inhibited by both neutralizing CXCR4 antibodies and CXCR4 siRNAs. Thus, the expression and functionality of CXCR4 might be associated with the metastatic potential of CRC cells and CXCL12/CXCR4 interactions might therefore constitute a promising target for specific treatment interventions.

Contribution of final-year medical students to operation room performance--economical and educational implications.

PURPOSE: The so-called "practical year" is the last part of medical students' education in Germany. Without being paid, final-year medical students have to work for 1 year under supervision in academic teaching hospitals. It is mandatory for every student to rotate to a surgical department for 4 months. The aim of the present study was to assess the working time contribution of final-year medical students on operation room performance at the surgical department of a university hospital. METHODS: Over an 8-year period, purely surgical times of 24,214 operations in 2,792 days were analyzed with special regard to final-year medical students' participation rate. Students' cumulative workload in the operating room was compared to that of surgical residents. RESULTS: Mean participation rate of final-year medical students was 47.8%, being higher in elective surgery than in emergency surgery (53.9% vs. 24.7%; p < 0.001). When students participated in operations, mean daily cumulative working time of student's cohort was 10.3 ± 0.12 h. Daily cumulative workload of medical students in the operating room strongly correlated with both medical doctors' cumulative workload (r (2) = 0.573) and daily workload of the team (r (2) = 0.740, p < 0.001 each). Final-year medical students assisted significantly more often in time-consuming operations. CONCLUSION: Final-year medical students contribute significantly to surgical operation room performance, similarly but less intensively than residents. Employment of students may counterbalance staff shortage in operating rooms. Therefore, it is likely that the German health care system relies on unpaid medical students to minimize the total cost of surgery. According to the extent of workload accomplished by final-year medical students, a remuneration of the "practical year" seems reasonable.

Triclosan-coated sutures reduce wound infections after hepatobiliary surgery--a prospective non-randomized clinical pathway driven study.

OBJECTIVES: Wound infections after abdominal surgery are still frequent types of nosocomial infections. Suture materials might serve as a vehicle for mechanical transport of bacteria into the surgical wound. To reduce bacterial adherence to surgical sutures, triclosan-coated polyglactin 910 suture materials with antiseptic activity (Vicryl plus®) were developed. The aim of this prospective non-randomized clinical pathway driven study was to ascertain if the use of Vicryl plus® reduced the number of wound infections after transverse laparotomy. PATIENTS AND METHODS: Between October 2003 and October 2007, 839 operations were performed using a transverse abdominal incision. In the first time period, a PDSII® loop suture was used for abdominal wall closure. In the second time period, we used Vicryl plus®. Risk factors were collected prospectively to compare the two groups. RESULTS: Using a PDSII® loop suture for abdominal wall closure in the first time period, 9.2% of the patients developed wound infections. In the second time period, using Vicryl plus®, the number of wound infections decreased to 4.3% (p < 0,005). Both groups were comparable regarding risk factors despite no other changes in protocols of patient care. CONCLUSION: Antiseptic-coated loop Vicryl suture for abdominal wall closure can be superior to PDSII sutures in respect to the development of wound infections after a two-layered closure of transverse laparotomy.

CCL20/CCR6 expression profile in pancreatic cancer.

BACKGROUND: CCL20 and its receptor CCR6 have been shown to play a role in the onset, development and metastatic spread of various gastrointestinal malignancies. In this study, the expression profile and clinical significance of the CCL20/CCR6 system in distinct benign, pre-malignant and malignant pancreatic tissues was investigated. METHODS: Using RealTime-PCR, enzyme-linked immunosorbent assay (ELISA), Western Blot and immunohistochemistry, we have analyzed the expression profile of CCL20/CCR6 in resection specimens from patients with chronic pancreatitis (CP) (n = 22), pancreatic cystadenoma (PA) (n = 11) and pancreatic carcinoma (PCA) (n = 25) as well as in the respective matched normal pancreatic tissues. RESULTS: CCL20 mRNA and protein was weakly expressed in normal pancreatic tissues and CP and PA specimens but significantly up-regulated in PCA (8-fold) as compared to the matched normal tissue (P < 0.05). Moreover, CCL20 mRNA and protein expression was significantly associated with advanced T-category in patients with PCA (P < 0.05). CCR6 mRNA showed a significant up-regulation in all three disease entities as compared to normal tissues (P < 0.05, respectively). CONCLUSION: CCL20 and CCR6 were significantly up-regulated in PCA as compared to the normal pancreatic tissue and CCL20 was significantly associated with advanced T-category in PCA patients. This suggests that CCL20 and CCR6 play a role in the development and progression of PCA and may constitute potential targets for novel treatment strategies.

Retroperitoneal abscess with consecutive acute renal failure caused by a lost gallstone 2 years after laparoscopic cholecystectomy.

A 70-year-old male patient presented with abdominal pain, acute renal failure, and fever 2 years after laparoscopic cholecystectomy. During the surgical drainage of the abscess formation on the patient's right flank, a huge gallstone was found in the retroperitoneum. The patient was dismissed from the hospital 11 days after admission with normal lab panel and restored renal function.

Amiodarone pretreatment of organ donors exerts anti-oxidative protection but induces excretory dysfunction in liver preservation and reperfusion.

The continuous shortage of organs necessitates the use of marginal organs from donors with various diseases, including arrhythmia-associated cardiac failure. One of the most frequently used anti-arrhythmic drugs is amiodarone (AM), which is given in particular in emergency situations. Apart from its anti-arrhythmic actions, AM provides anti-oxidative properties in cardiomyocytes. Thus, we were interested in whether AM donor pretreatment affects the organ quality and function of livers procured for preservation and transplantation. Donor rats were pretreated with AM (5 mg/kg of body weight) 10 minutes before flush-out of the liver with a cold (4 degrees C) histidine-tryptophan-ketoglutarate solution (n = 8). Livers were then stored for 24 hours at 4 degrees C before ex situ reperfusion with a 37 degrees C Krebs-Henseleit solution for 60 minutes in a nonrecirculating system. At the end of reperfusion, tissue samples were taken for histology and Western blot analysis. Animals with vehicle only (0.9% NaCl) served as ischemia/reperfusion controls (n = 8). Additionally, livers of untreated animals (n = 8) not subjected to 24 hours of cold ischemia served as sham controls. AM pretreatment effectively attenuated lipid peroxidation, stress protein expression, and apoptotic cell death. This was indicated by an AM-mediated reduction of malondialdehyde, heme oxygenase-1, and caspase-3 activation. However, AM treatment also induced mitochondrial damage and hepatocellular excretory dysfunction, as indicated by a significantly increased glutamate dehydrogenase concentration in the effluate and decreased bile production. In conclusion, AM donor pretreatment exerts anti-oxidative actions in liver preservation and reperfusion. However, these protective AM actions are counteracted by an induction of mitochondrial damage and hepatocellular dysfunction. Accordingly, AM pretreatment of donors for anti-arrhythmic therapy should be performed with caution.

Increased growth factor expression after hepatic and pancreatic resection.

Removal of the primary tumour is suggested to associate with an enhanced tumour growth of residual micrometastases. Recent data focus on growth factors that may be released in response to surgery-stimulating receptors of residual tumour cells. Vascular endothelial (VEGF) and hepatocyte growth factor (HGF) are potent inducers of angiogenesis. The two factors are necessary for wound healing and the promotion of tumour growth. This study was designed to determine growth factor serum levels in patients before, during and after major abdominal surgery. It was recently shown that simultaneous hepatic and pancreatic resection led to poor liver regeneration. As growth factors may be involved in these findings we compared the growth factor levels after liver resection with the levels in patients after pancreatic resection. Forty patients were accrued before hepatopancreatic surgery (hepatic resection n=20 and pancreatic resection n=20). Blood samples were taken from each patient immediately prior to surgery, during the operation and on the postoperative days (POD) 1-3, 5 and 10. To examine the wound fluid, liquid from the wound drains was collected on POD 3. Using ELISA the concentration of the angiogenic cytokines HGF and VEGF165 was determined. After the liver and pancreatic resections, circulating HGF and VEGF165 were increased. We found significantly higher levels of HGF on POD 1-3 (p<0.01), compared to preoperative results with a peak on POD 2. After measuring the postoperative VEGF165 levels we found significantly higher levels of circulating VEGF165 on POD 1-5 (p<0.01) compared to the preoperative levels. On comparing liver with pancreatic resection we did not detect significantly different levels of the two growth factors in the two groups. VEGF165 and HGF concentrations measured during the operation demonstrated no change. HGF and VEGF165 levels detected in the wound fluid on POD 3 were approximately 10 times higher than the preoperative serum levels, respectively. In summary, our data show increased VEGF165 and HGF levels after hepatopancreatic surgery. Notably, the lack of an impact of the type of organ resection on the concentration-time curve of the two growth factors suggest that high postoperative growth factor levels are part of normal wound healing and systemic inflammation. Thus, the proangiogenetic potential of growth factors may account for accelerated tumour growth when residual tumour cells are exposed to high levels of VEGF165 and HGF.

The standardized surgical approach improves outcome of gallbladder cancer.

BACKGROUND: The objective of this study was to examine the extent of surgical procedures, pathological findings, complications and outcome of patients treated in the last 12 years for gallbladder cancer. METHODS: The impact of a standardized more aggressive approach compared with historical controls of our center with an individual approach was examined. Of 53 patients, 21 underwent resection for cure and 32 for palliation. RESULTS: Overall hospital mortality was 9% and procedure related mortality was 4%. The standardized approach in UICC stage IIa, IIb and III led to a significantly improved outcome compared to patients with an individual approach (Median survival: 14 vs. 7 months, mean+/-SEM: 26+/-7 vs. 17+/-5 months, p = 0.014). The main differences between the standardized and the individual approach were anatomical vs. atypical liver resection, performance of systematic lymph dissection of the hepaticoduodenal ligament and the resection of the common bile duct. CONCLUSION: Anatomical liver resection, proof for bile duct infiltration and, in case of tumor invasion, radical resection and lymph dissection of the hepaticoduodenal ligament are essential to improve outcome of locally advanced gallbladder cancer.

CXCL12/CXCR4 display an inverse mRNA expression profile in gastric carcinoma that correlates with tumor progression.

Chemokines and their receptors have been shown to contribute to tumor growth and metastatic spread in various gastrointestinal cancer entities. In the present study, the mRNA expression profiles and clinical significance of chemokine ligand CXCL12 and its corresponding receptor CXCR4 were investigated in patients with gastric cancer (GC). Using quantitative polymerase chain reaction, the expression profile of CXCL12/CXCR4 was analyzed in resection specimens from the patients with GC (n=66) and in corresponding normal gastric tissues. Upon investigating CXCL12/CXCR4 mRNA expression levels in the GC tissues, significant downregulation of CXCL12 expression was demonstrated (P<0.05), whereas CXCR4 mRNA expression was shown to be significantly upregulated (P<0.05). Likewise, in gastric carcinoma patients undergoing neoadjuvant chemotherapy, CXCR4 expression was found to be significantly upregulated (P<0.05), whereas in GC patients with lymph and vein infiltration, CXCL12 mRNA expression was significantly downregulated (P<0.05). These results demonstrate a significant inverse association between the development and progress of GC and CXCL12/CXCR4 mRNA expression. CXCR4 mRNA upregulation was promoted under the effect of neoadjuvant chemotherapy prior to surgery in GC patients, whereas higher tumor stages with lymph and vein infiltration negatively affected CXCL12 mRNA expression.

Surgical-site infection after abdominal wall closure with triclosan-impregnated polydioxanone sutures: results of a randomized clinical pathway facilitated trial (NCT00998907).

BACKGROUND: Wound infections after abdominal surgery are still frequent types of nosocomial infections. Suture materials might serve as a vehicle for mechanical transport of bacteria into the surgical wound. To prevent the contamination of suture material in surgical wounds, triclosan-coated suture materials with antibacterial activity was developed. We here report a prospective randomized pathway controlled trial investigating the effect of triclosan impregnation of polydioxanone sutures used for abdominal wall closure on the rate of surgical-site infections. PATIENTS AND METHODS: A total of 856 patients included in this trial underwent a standardized clinical pathway documented abdominal wall closure after abdominal surgery. Patients were randomized to have the fascia closed with either a 2-0 polydioxanone loop or a triclosan impregnated 2-0 polydioxanone loop. The primary outcome was the number of wound infections. Risk factors for poor wound healing were collected prospectively to compare the two groups. RESULTS: When a PDS loop suture for abdominal wall closure was used, 42 (11.3%) patients with wound infections were detected. The number of patients with wound infections decreased significantly to 31 when the PDS plus for abdominal wall closure was used (6.4%, P < .05). Other risk factors for the development of side infections were comparably in the two groups. CONCLUSION: This clinical pathway facilitated trial shows that triclosan impregnation of a 2-0 polydioxanone closing suture can decrease wound infections in patients having a laparotomy for general and abdominal vascular procedures.

Incisional hernia after abdominal closure with slowly absorbable versus fast absorbable, antibacterial-coated sutures.

BACKGROUND: Incisional hernia remains among the most common complications after midline incision of the abdominal wall. The role of the suture material used for abdominal wall closure remains controversial. To decrease bacterial adherence to surgical sutures, braided suture materials with antibacterial activity (Vicryl plus, Ethicon, Inc) were developed. This is the first study to analyze long-term results using an antibacterial-braided suture material for abdominal wall closure in a large clinical trial. METHODS: To analyze the effects of Triclosan-coated suture material (Vicryl plus) on the development of incisional hernia, we performed a 36-month follow-up of 1,018 patients who had a primary midline incision for elective abdominal surgery. In the first time period, a PDS II loop suture was used. In the second observation period, we used Vicryl plus. All variables were recorded prospectively in a database. The primary outcome was the number of incisional hernias. Risk factors for the development of incisional hernias were collected prospectively to compare the 2 groups. RESULTS: The overall incisional hernia rate in the 36-month follow-up period was 14.6%. Analyzing the influence of the suture material used on the development of incisional hernia, we did not find differences between the 2 groups (PDS II, 14%; Vicryl plus, 15.2%). In the multivariate analysis of possible factors in the study population, only body mass index (BMI) showed a significant influence on the development of incisional hernias. Despite the incidence of wound infections being less in the Vicryl plus group (6.1% vs 11.9%; P < .05), there were no difference in incidence of incisional hernia between the 2 groups. CONCLUSION: Fast absorbable sutures with antibacterial coating (Tricosan) do not increase the hernia rate after midline abdominal incision compared with slowly absorbable sutures, when wound infection rates are decreased by coating the fast absorbable suture with Triclosan. The development of incisional hernia is significantly increasing in patients with a BMI >30 kg/m(2).

Thoracotomy procedures effect cytokine levels after thoracoabdominal esophagectomy.

Pulmonary complications together with surgical complications are the most frequent causes for morbidity and mortality after thoracoabdominal esophagectomy. The con-tinuous improvement of surgical techniques has led to a decrease in surgical complications, whereas up to 30% of the patients develop postoperative pulmonary complications such as acute lung injury (ALI) or even the more severe acute respiratory distress syndrome (ARDS), which are characterized by an acute inflammation in the lung parenchyma and the airspace. Evidence from several studies indicates that a complex network of inflammatory cytokines and mediators play a key role in mediation, amplification, and perpetuation of the process of lung injury and that the thoracotomy itself is a risk factor for developing ALI or ARDS. In this trial, the cytokine levels of IL6, IL8 and IL10 were measured and compared in 30 patients who had undergone an extended radical thoracoabdominal esophagectomy for esophageal cancer, via anterolateral thoracotomy (n=17) or posterolateral thoracotomy (n=13). Patients of both groups were similar in terms of age, sex and preoperative pulmonary function as well as in the anesthetic procedures they have undergone. All patients displayed significantly increased serum levels of IL6 and IL8 after thoracoabdominal esophagectomy. However, patients who were subjected to an anterolateral thoracotomy were reported with significantly higher serum levels of IL6 and IL8 compared to patients who had received a posterolateral thoracotomy. Thus, the choice of the thoracotomy method during the thoracoabdominal esophagectomy and the resultant cytokine levels may contribute to the occurrence of postoperative pulmonary complications and may have an impact on the extent and severity of the surgical stress.

Penetration of moxifloxacin into liver tissue.

Moxifloxacin is considered for treatment of pyogenic liver abscesses as well as antibiotic prophylaxis in the case of hepatobiliary interventions. The aim of this study was to provide data on the pharmacokinetic (PK) profile of moxifloxacin in serum and liver tissue of patients undergoing liver resection due to primary or secondary tumours of the liver. Patients scheduled for liver resection (n=34) received moxifloxacin 400 mg at randomised time intervals prior to surgery. Blood and healthy liver tissue were sampled 1.5-26 h after administration of moxifloxacin. Immediately after centrifugation, plasma was separated, frozen and stored until analysis. In a subgroup of 19 patients, additional plasma specimens were obtained after 2, 4, 8, 12, 24, 36 and 48 h to assess the PK profile. PK parameters of moxifloxacin were calculated applying a two-compartment model. Median (interquartile range) PK parameters were as follows: peak concentration at the end of moxifloxacin infusion (C(max)), 6.0 mg/L (4.8-7.1 mg/L); area under the concentration-time curve extrapolated to infinity (AUC(0-∞)), 51.1 mgh/L (40.3-57.7 mgh/L); elimination half-life, 13.2h (11.0-14.1 h); volume of distribution at steady state (V(ss)), 138.7 L (102.7-168.5 L); and total body clearance (CL), 7.8 L/h (6.9-9.9L/h). Mean tissue concentrations were 9.13 mg/kg after 1.6-2.4 h, 7.62 mg/kg after 2.6-4.9h, 7.48 mg/kg after 5.6-10.0 h and 6.24 mg/kg after 22.9-26.5 h. Mean tissue:serum ratios were 2.9, 3.4, 5.0 and 12.3, respectively. The lowest tissue concentration found in the study at any time point was 2.8 mg/kg. In conclusion, moxifloxacin rapidly penetrates into the liver tissue where its concentration remains high following intravenous administration. Therefore, intravenously applied moxifloxacin might be used for the treatment of bacterial liver infections such as pyogenic liver abscess as well as in pre-operative prophylaxis.

Bronchobiliary fistula: a rare complication of hepatic endometriosis.

OBJECTIVE: To report the case and surgical therapy of a patient with bilioptysis after vaginal delivery, caused by bronchobiliary fistula. Histologic analysis revealed endometrial glands embedded in the decidual stroma neighboring the liver and the lung. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 39-year-old patient, 7 days after vaginal delivery, without endometrial history. INTERVENTION(S): Synchronous liver and lung resection of a bronchobiliary fistula by laparotomy and a transdiaphragmatic approach. MAIN OUTCOME MEASURE(S): For complicated brochobiliary fistula caused by endometriosis, radical surgical treatment is mandatory. RESULT(S): Histopathologic analyses confirmed the presence of clusters of endometrial glands embedded in the decidual stroma that were neighboring the liver, and perifistulous lung tissue was shown to contain biliary pigment absorbed by macrophages and their derivatives. CONCLUSION(S): Hepatic and perihepatic endometriosis can cause a bronchobiliary fistula. Exacerbation of the symptoms can be triggered by high estrogen levels, physiologically dominating the last trimester. For such a rare case, surgery is mandatory.

Effect of preoperative FOLFOX chemotherapy on CCL20/CCR6 expression in colorectal liver metastases.

AIM: To evaluate the influence of preoperative FOLFOX chemotherapy on CCL20/CCR6 expression in liver metastases of stage IV colorectal cancer (CRC) patients. METHODS: Using Real Time-PCR, enzyme-linked immunosorbent assay, Western Blots and immunohistochemistry, we have analyzed the expression of CCL20, CCR6 and proliferation marker Ki-67 in colorectal liver metastasis (CRLM) specimens from stage IV CRC patients who received preoperative FOLFOX chemotherapy (n = 53) and in patients who did not receive FOLFOX chemotherapy prior to liver surgery (n = 29). RESULTS: Of the 53 patients who received FOLFOX, time to liver surgery was ≤ 1 mo in 14 patients, ≤ 1 year in 22 patients and > 1 year in 17 patients, respectively. In addition, we investigated the proliferation rate of CRC cells in liver metastases in the different patient groups. Both CCL20 and CCR6 mRNA and protein expression levels were significantly increased in patients who received preoperative FOLFOX chemotherapy ≤ 12 mo before liver surgery (P < 0.001) in comparison to patients who did not undergo FOLFOX treatment. Further, proliferation of CRLM cells as measured by Ki-67 was increased in patients who underwent FOLFOX treatment. CCL20 and CCR6 expression levels were significantly increased in CRLM patients who had undergone preoperative FOLFOX chemotherapy. CONCLUSION: This chemokine/receptor up-regulation could lead to increased proliferation/migration through an autocrine mechanism which might be used by surviving metastatic cells to escape cell death caused by FOLFOX.