Four DNA methylation biomarkers in biliary brush samples accurately identify the presence of cholangiocarcinoma.

UNLABELLED: Early detection of the highly aggressive malignancy cholangiocarcinoma (CCA) remains a challenge but has the potential to render the tumor curable by surgical removal. This study evaluates a biomarker panel for the diagnosis of CCA by DNA methylation analyses of biliary brush samples. The methylation status of 13 candidate genes (CDO1, CNRIP1, DCLK1, FBN1, INA, MAL, SEPT9, SFRP1, SNCA, SPG20, TMEFF2, VIM, and ZSCAN18) was investigated in 93 tissue samples (39 CCAs and 54 nonmalignant controls) using quantitative methylation-specific polymerase chain reaction. The 13 genes were further analyzed in a test series of biliary brush samples (15 CCAs and 20 nonmalignant primary sclerosing cholangitis controls), and the methylation status of the four best performing markers was validated (34 CCAs and 34 primary sclerosing cholangitis controls). Receiver operating characteristic curve analyses were used to evaluate the performance of individual biomarkers and the combination of biomarkers. The 13 candidate genes displayed a methylation frequency of 26%-82% in tissue samples. The four best-performing genes (CDO1, CNRIP1, SEPT9, and VIM) displayed individual methylation frequencies of 45%-77% in biliary brushes from CCA patients. Across the test and validation biliary brush series, this four-gene biomarker panel achieved a sensitivity of 85% and a specificity of 98%, with an area under the receiver operating characteristic curve of 0.944. CONCLUSION: We report a straightforward biomarker assay with high sensitivity and specificity for CCA, outperforming standard brush cytology, and suggest that the biomarker panel, potentially in combination with cytological evaluation, may improve CCA detection, particularly among primary sclerosing cholangitis patients.

Respiratory gated and prolonged acquisition 18F-FDG PET improve preoperative assessment of colorectal liver metastases.

BACKGROUND: Detection of small liver metastases from colorectal cancer by 18F-FDG PET/CT is hampered by high physiologic uptake in the liver parenchyma and respiratory movements during image acquisition. PURPOSE: To investigate whether two tailored 18F-FDG PET liver acquisitions (prolonged liver acquisition time [PL-PET] and repeated breath-hold respiratory gated liver acquisition [RGL-PET]) would improve detection of colorectal liver metastases, when added to a standard whole body PET (WB-PET). MATERIAL AND METHODS: Twenty consecutive patients referred to our hospital for surgical treatment of colorectal liver metastases diagnosed with contrast-enhanced CT underwent preoperative 18F-FDG PET/CT tailored for detection of liver metastases. Concordance between preoperative imaging results and true findings (histology and/or follow-up imaging) as well as changes in clinical management, based on 18F-FDG PET/CT findings, were documented. Background noise, defined as the standard deviation measured in a reference region within the normal liver parenchyma, was compared between the three 18F-FDG PET/CT protocols. RESULTS: WB-PET, PL-PET, and RGL-PET showed suspicious liver lesions in 18 out of 20 patients. Compared to WB-PET alone, the combination of PL-PET and RGL-PET showed additional lesions in the liver in seven out of the 18 patients. The combination of all three PET acquisitions changed clinical management in four patients. Two patients with negative PET results were later found to have benign liver lesions. CONCLUSION: The addition of tailored liver-specific 18F-FDG PET/CT protocols (PL-PET and RGL-PET) to a WB-PET, improved the detection of intrahepatic colorectal metastases, compared to WB-PET alone. Such add-ons can change clinical patient management of potentially resectable colorectal liver metastases.

Liver transplantation for nonresectable liver metastases from colorectal cancer.

OBJECTIVE: The objective of this pilot study was to investigate the potential for long-term overall survival (OS) after liver transplantation for colorectal liver metastases (CLMs). BACKGROUND: Patients with nonresectable CLMs have poor prognosis, and few survive beyond 5 years. CLMs are currently considered an absolute contraindication for liver transplantation, although liver transplantation for primary and some secondary liver malignancies shows excellent outcome in selected patients. Before 1995, several liver transplantations for CLMs were performed, but outcome was poor (5-year survival rate: 18%) and liver transplantation for CLMs was abandoned. Since then, the survival rate after liver transplantation in general has improved by almost 30%. On the basis of this, a 5-year survival rate of about 50% after liver transplantation for CLMs could be anticipated. METHODS: In a prospective pilot study, liver transplantation for nonresectable CLMs was performed (n = 21). Main inclusion criteria were liver-only CLMs, excised primary tumors, and at least 6 weeks of chemotherapy. RESULTS: Kaplan-Meier estimates of the OS rate at 1, 3, and 5 years were 95%, 68%, and 60%, respectively. Metastatic recurrence of disease was common (mainly pulmonary). However, a significant proportion of the recurrences were accessible for surgery, and at follow-up (after median of 27 months; range, 8-60), 33% had no evidence of disease. Hepatic tumor load before liver transplantation, time from primary surgery to liver transplantation, and progressive disease on chemotherapy were identified as significant prognostic factors. CONCLUSIONS: OS exceeds by far reported outcome for chemotherapy, which is the only treatment option available for this patient group. Furthermore, OS is comparable with liver resection for resectable CLMs and survival after repeat liver transplantation for nonmalignant diseases. Selection strategies based on prognostic factors may further improve the outcome (ClinicalTrials.gov: NCT01311453).

Prognostic relevance of number and ratio of metastatic lymph nodes in resected pancreatic, ampullary, and distal bile duct carcinomas.

BACKGROUND: Lymph node ratio (LNR) may be more useful than nodal (N) status in prognostic subclassification of adenocarcinomas after pancreatoduodenectomy. Ampullary (AC), biliary (DBC), and pancreatic (PC) adenocarcinomas are biologically distinct, and nodal involvement may have different prognostic importance among these separate cancers. METHODS: We included 179 consecutive pancreatoduodenectomies for PC, AC, or DBC, and performed standardized histopathologic evaluation, including prospective registration and retrospective reevaluation of the cancer origin. Associations between histopathologic variables and LNR, N status, and number of metastatic nodes were evaluated. Unadjusted and adjusted survival analysis was performed. RESULTS: Overall 5 year survival was 6% for PC (n=72), 26% for DBC (n=46), and 46% for AC (n=61). Lymph node involvement was more frequent in PC (75%) than in AC (48%) and DBC (57%). In PC, N status did not discriminate between prognostic groups (N1 vs. N0; p=0.31). However, increasing LNR was associated with poorer survival in unadjusted analysis, as well as when adjusting for margin involvement, degree of differentiation, and tumor diameter (p=0.032; hazard ratio 1.87, 95% confidence interval 1.06-3.31). In AC and DBC, N status clearly discriminated between subgroups of patients with different long-term survival in unadjusted and adjusted survival analysis (N1 vs. N0; p<0.001), whereas number of metastatic nodes and LNR did not predict survival among node-positive resections. CONCLUSIONS: The predictive value of nodal involvement depends on the type of cancer within the pancreatic head. In AC and DBC, N status adequately discriminates between good and poor prognosis. In PC, LNR may be more powerful in prognostic subclassification.

Long-term outcome of laparoscopic surgery for pancreatic neuroendocrine tumors.

BACKGROUND: As most pancreatic neuroendocrine tumors (PNET) are relatively small and solitary, they may be considered well suited for removal by a minimally invasive approach. There are few large series that describe laparoscopic surgery for PNET. The primary aim of this study was to describe the feasibility, outcome, and histopathology associated with laparoscopic pancreatic surgery (LS) of PNET in a large series. METHODS: All patients with PNET who underwent LS at a single hospital from March 1997 to April 2011 were included retrospectively in the study. RESULTS: A total of 72 patients with PNET underwent 75 laparoscopic procedures, out of which 65 were laparoscopic resections or enucleations. The median operative time of all patients who underwent resections or enucleations was 175 (60-520) min, the median blood loss was 300 (5-2700) ml, and the median length of hospital stay was 7 (2-27) days. The overall morbidity rate was 42%, with a surgical morbidity rate of 21% and postoperative pancreatic fistula (POPF) formation in 21%. Laparoscopic enucleations were associated with a higher rate of POPF than were laparoscopic resections. Five-year disease-specific survival rate was 90%. The T stage, R stage, and a Ki-67 cutoff value of 5% significantly predicted 5-year survival. CONCLUSION: LS of PNET is feasible with acceptable morbidity and a good overall disease-specific long-term prognosis.

Single-incision versus conventional laparoscopic distal pancreatectomy: a single-institution case-control study.

PURPOSE: Laparoscopic distal pancreatectomy is becoming increasingly established at specialized surgical institutions worldwide. The purpose of this study was to compare single-incision laparoscopic distal pancreatectomy (panLESS) with conventional laparoscopic distal pancreatectomy (panLAP) to assess feasibility and 30-day morbidity. METHODS: Eight consecutive patients who underwent panLESS were matched with patients who underwent panLAP in the same time period. Matching criteria were age, body mass index, and American Society of Anesthesiologists score. Feasibility was based on tumor size, operative time, intraoperative bleeding, resection status, and hospital stay. Thirty-day morbidity was defined by the revised Accordion Classification system and the International Study Group on Pancreatic Fistula definition. RESULTS: Over a 19-month period, 8 and 16 patients were identified for panLESS and panLAP, respectively. There were no significant differences in tumor size, operative time, intraoperative bleeding, resection status, and hospital stay between the two groups. Surgical complications developed in four panLESS patients and five panLAP patients, and out of which, two patients from each group developed a postoperative pancreatic fistula (grade B). CONCLUSIONS: This study indicates that panLESS is comparable to panLAP in terms of feasibility. More experience is needed to define what role single-incision distal pancreatectomy should have in minimal invasive pancreatic surgery.

Surgical treatment of sporadic pancreatic neuroendocrine tumors: a state of the art review.

Pancreatic neuroendocrine tumors (PNETs) are rare neoplasms. They are clinically diverse and divided into functioning and nonfunctioning disease, depending on their ability to produce symptoms due to hormone production. Surgical resection is the only curative treatment and remains the cornerstone therapy for this patient group, even in patients with advanced disease. Over the last decade there has been a noticeable trend towards more aggressive surgery as well as more minimally invasive surgery in patients with PNETs. This has resulted in improved long-term survival in patients with locally advanced and metastatic disease treated aggressively, as well as shorter hospital stays and comparable long-term outcomes in patients with limited disease treated minimally invasively. There are still controversies related to issues of surgical treatment of PNETs, such as to what extent enucleation, lymph node sampling, and vascular reconstruction are beneficial for the oncologic outcome. Histopathologic tumor classification is of high clinical importance for treatment planning and prognostic evaluation of patients with PNETs. A constant challenge, which relates to the treatment of PNETs, is the lack of an internationally accepted histopathological classification system. This paper reviews current issues on the surgical treatment of sporadic PNETs with specific focus on surgical approaches and tumor classification.

Laparoscopic resection of colorectal liver metastases: surgical and long-term oncologic outcome.

OBJECTIVE: To analyze the immediate and long-term outcome after laparoscopic resection of colorectal liver metastases and difference between observed and predicted [Fong's and Basingstoke Predictive Index (BPI) scores] survivals. BACKGROUND: : Laparoscopic liver resection has been reported safe and feasible and improves postoperative course. The oncologic outcomes after resection of colorectal metastases are poorly reported. METHODS: Between August 1998 and January 2010, 122 patients underwent laparoscopic resection for colorectal liver metastases during 135 procedures at Rikshospitalet. Patients undergoing surgery between August 1998 and June 2009 were included in research analysis. The patients had median Fong's and BPI's scores of 2 (0-5) and 7 (0-23), respectively. Mainstream analysis of hospital data was done on intent-to-treat basis. Intraoperative incidents and postoperative complications were analyzed according to the Satava and Clavien-Dindo classifications. Median follow-up was 24 (0-100) months. RESULTS: One hundred fifty-one liver resections were performed in 107 patients during 118 procedures: 117 nonanatomic and 34 anatomic liver resections. There were 5 conversions to laparotomy (4.2%). The resection margin was free of tumor tissue in 141 (93.4%) of 151 specimens, and the distance between the resection margin and tumor tissue was median 6 (0-40) mm. Intraoperative incidents occurred in 14 cases (11.9%), including 5 (4.2%), 8 (6.8%), and 1 (0.8%) cases of grades I, II, and III, respectively. Postoperative complications were observed in 16 cases (14.3%), including 2, 3, 7, 3, 0, and 1 cases of grades I, II, IIIa, IIIb, IV, and V, respectively. During follow-up, 21 patients received repeat liver resection of recurrences (11 by laparoscopy and 10 by laparotomy). The 5-year overall survival rates were 51% as laparoscopically completed cases and 47% as intent-to-treat. The observed actuarial survival values exceeded the values expected by Fong's and BPI's score, with 10.2% and 6.7% as laparoscopically completed cases and with 3.8% and 2.4% as intent-to-treat, respectively. CONCLUSIONS: Laparoscopic resection is a favorable alternative to open liver resection for patients with colorectal liver metastases. The observed actuarial survival values after laparoscopic resection surpass the values expected by major scoring systems.

Survival following resection of pancreatic endocrine tumors: importance of R-status and the WHO and TNM classification systems.

OBJECTIVE: The aim of this study was to delineate the clinical outcomes and pathological characteristics of surgically resected endocrine tumors of the pancreas and to determine the importance of the World Health Organization (WHO) and tumor-node metastasis (TNM) classifications, resection status, and Ki-67 expression for long-term survival. PATIENTS AND METHODS: Sixty-nine patients underwent surgical tumor resection with curative intent during 1990-2007. Hospital records were reviewed retrospectively for medical, surgical, pathological, and radiological data. RESULTS: Forty-one patients (59%) had non-functional tumors, 28 (41%) patients had functional tumors. Thirty-seven (54%) tumors were classified as WHO group 1 and the remaining 32 as WHO group 2. There were no poorly differentiated endocrine carcinomas. The overall R0-resection rate was 68%. Patients in whom all gross tumor was resected (R0/R1) had significantly better survival compared to patients with macroscopic residual disease (R2) (p < 0.001). There was no difference in survival between patients with R0 and R1 resections. Both the WHO (p < 0.001) and the TNM (p < 0.001) classifications significantly predicted five and 10-year survival after resection of the primary tumor. Survival analysis revealed significantly better outcome for patients with tumors with Ki-67 index < 2% (p = 0.003). CONCLUSIONS: Both WHO and TNM classifications reliably predict long-term survival in patients with resectable pancreatic endocrine tumors. R2 resection status predicted poor prognosis. R0 status did not improve prognosis relative to R1 status. Ki-67 index > 2% is a predictor of poor long-term survival.

Nordic Guidelines 2010 for diagnosis and treatment of gastroenteropancreatic neuroendocrine tumours.

The diagnostic work-up and treatment of patients with neuroendocrine tumours has undergone a major change during the last decade. New diagnostic possibilities and treatment options have been developed. These Nordic guidelines, written by a group with a major interest in the subject, summarises our current view on how to diagnose and treat these patients. The guidelines are meant to be useful in the daily practice for clinicians handling patients with neuroendocrine tumours.

Should we use laparoscopic adrenalectomy for metastases? Scandinavian multicenter study.

INTRODUCTION: Laparoscopic adrenalectomy for metastases is considered controversial. Multicenter retrospective study was performed to gain new knowledge in this issue. MATERIALS AND METHODS: From January 1997 till November 2008, 41 adrenalectomies were performed during follow-up of the patients operated for malignant tumors. The median age was 64 (52-77) years. Metastases were confirmed in 31/41 cases. Metastatic lesions were further studied and to define factors influencing on survival, patients were divided to sub-groups of metachronous/synchronous, tumor origin and tumor size. RESULTS: The median operative time was 104 (50-230) min, the median blood loss was 100 (0-500) ml. One procedure (3.2%) was converted. There were 3 (10.7%) intraoperative and 2 (7.4%) postoperative complications. The median tumor size was 6 (1.5-16) cm. Pathohistological analysis revealed 12 colorectal, 9 renal cell carcinoma, 5 lung carcinoma, 4 melanoma, and 1 hepatocellular metastases. The resection margin was not free in one case (3.7%). The median hospital stay was 2 (1-21) days. The median length of survival was 29 +/- 2.1 months for all patients. CONCLUSION: Laparoscopic adrenalectomy for metastases is feasible regardless of their sizes. However these procedures should be performed by highly skilled laparoscopic surgeon in a fully equipped operating room and with a coordinated operation team.

[Portal vein embolization before surgery for liver tumours]. / Portveneembolisering før kirurgi av leversvulster.

BACKGROUND: Radical resection is the only long-term cure for malignant liver tumours. An important contraindication for surgery is that the liver remnant would be too small. Embolization of the portal vein in the tumour-bearing side of the liver may induce growth of the healthy part and thereby render liver resection possible. MATERIAL AND METHODS: 18 patients, aged 35 - 71 years, underwent portal vein embolization in the period 2002 - 2006. An interventional radiological percutaneous transhepatic technique was used. RESULTS: The liver remnant increased with 45 % (median), range 9 - 100 %, in all patients. Liver resection could be done and was performed in 10 patients. Due to tumour progression, resection could not be done in seven patients. One patient was excluded from surgery due to serious side effects of chemotherapy. Four-year survival for patients with metastases from colorectal cancer (n=9) was 58 %. INTERPRETATION: Portal vein embolization results in a substantial increase of liver volume. The technique effectively increases the number of patients eligible for liver surgery. It is possible for patients treated with this technique to obtain the same long-term survival as those primarily regarded to be operable. Advanced radiological technology is needed to exclude patients who would not profit from the procedure.

Resectable adenocarcinomas in the pancreatic head: the retroperitoneal resection margin is an independent prognostic factor.

BACKGROUND: The retroperitoneal margin is frequently microscopically tumour positive in non-curative periampullary adenocarcinoma resections. This margin should be evaluated by serial perpendicular sectioning. The aim of the study was to determine whether retroperitoneal margin involvement independently predicts survival after pancreaticoduodenectomy within a framework of standardized assessment of the resected specimens. METHODS: 114 consecutive macroscopically margin-free periampullary adenocarcinomas were examined according to a prospective standardized protocol for histopathologic evaluation. The retroperitoneal margin was assessed by serial perpendicular sectioning. The periampullary cancer origin (pancreas, ampulla, distal bile duct or duodenum) was registered prospectively and reevaluated retrospectively. Associations between histopathologic factors were evaluated by Chi-square test, Fisher's exact test, Kruskal-Wallis test, and Mann-Whitney test, as appropriate. Survival curves were calculated by the Kaplan-Meier method and compared using the log-rank test. Associations between histopathologic factors and survival were also evaluated by unadjusted and adjusted Cox regression analysis, including stepwise variable selection, in order to identify factors that independently predict a poor prognosis after periampullary adenocarcinoma resections. RESULTS: Microscopic resection margin involvement (R1 resection) was present in 40 tumours, of which 32 involved the retroperitoneal margin. Involvement of the retroperitoneal margin independently predicted a poor prognosis (p = 0.010; HR 1.89; CI 1.16-3.08) after presumed curative (R0 and R1) resection. In microscopically curative (R0) resections (n = 74), pancreatic tumour origin was the only factor that independently predicted a poor prognosis (p < 0.001; HR 4.71 for pancreatic versus ampullary; CI 2.13-10.4). CONCLUSION: Serial perpendicular sectioning of the retroperitoneal resection margin demonstrates that tumour involvement of this margin independently predicts survival after pancreaticoduodenectomy for adenocarcinoma. Periampullary tumour origin is the only histopathologic factor that independently predicts survival in microscopically curative (R0) resections.

Pancreatobiliary versus intestinal histologic type of differentiation is an independent prognostic factor in resected periampullary adenocarcinoma.

BACKGROUND: Resectable adenocarcinomas in the pancreatic head, by definition "periampullary", originate from ampullary, duodenal, biliary, or ductal pancreatic epithelium. Typically, periampullary adenocarcinomas have either intestinal or pancreatobiliary type of differentiation, and the type of differentiation might be prognostically more important than the anatomic site of origin. The aim of the study was to determine whether the histologic type of differentiation is an independent prognostic factor in periampullary adenocarcinoma, and whether tumour origin predicts the prognosis in pancreatobiliary type carcinomas independently of resection margin involvement, tumour size, nodal involvement, perineural and vascular infiltration, and degree of differentiation. METHODS: Histopathologic variables in 114 consecutively resected periampullary adenocarcinomas of pancreatobiliary (n = 67) and intestinal (n = 47) type differentiation were evaluated using a standardized, systematic protocol for evaluation of the resected specimen (study group). Histologic type of differentiation and tumour origin were compared as predictors of survival, and the results were validated by comparison with a historical control group consisting of 99 consecutive pancreaticoduodenectomies performed before standardization of histopathologic evaluation. Associations between histopathologic variables were evaluated by Chi-square and Mann-Whitney tests. Survival was estimated by the Kaplan-Meier method, comparing curves using log-rank test, and by univariate and multivariable Cox regression analysis. RESULTS: Both in the study group (n = 114) and in the historical control group (n = 99), the histologic type of differentiation independently predicted survival, while tumour origin predicted survival only in univariate analysis. Independent adverse predictors of survival in the study group were pancreatobiliary type differentiation (p < 0.001; HR 3.1; CI 1.8-5.1), regional lymph node involvement (p < 0.001; HR 2.5; CI 1.5-4.4), vessel involvement (p = 0.012; HR 1.9; CI 1.2-3.1), and increasing tumour diameter (measured in cm, p = 0.011; HR 1.3; CI 1.1-1.5). For pancreatobiliary differentiated adenocarcinomas (n = 67), lymph node status, vessel involvement, and tumour diameter remained independent prognostic factors, while tumour origin did not independently predict the prognosis due to significant association with tumour size (p < 0.001) and lymph node involvement (p = 0.004). CONCLUSION: Pancreatobiliary versus intestinal type of differentiation independently predicts poor prognosis after pancreaticoduodenectomy for periampullary adenocarcinoma. Lymph node involvement, vessel infiltration, and increasing tumour diameter are adverse predictors of survival in tumours with pancreatobiliary differentiation.

Laparoscopic resection of an intraductal papillary mucinous carcinoma in ectopic pancreatic tissue.

Intraductal papillary mucinous neoplasia (IPMN) is a comparatively recently recognized pancreatic neoplasm with considerable malignant potential. Surgical removal is the only therapy known to provide a cure, but the extent of surgery required is still a matter of discussion. Ectopic pancreatic tissue can occur in a variety of other locations within the gastrointestinal tract and is also known to harbor pathologic conditions that affect normally located pancreatic tissue. In this paper, we present a case of an intraductal papillary mucinous carcinoma arising within the ectopic pancreatic tissue in the wall of the proximal duodenum. The lesion was removed by a laparoscopic resection. We believe this to be the first described case of a malignant IPMN to arise within ectopic pancreatic tissue and also the first report of the laparoscopic removal of any ectopic pancreatic IPMN.

[A pregnant woman with abdominal pain and fever]. / En gravid kvinne med magesmerter og feber.

Ectopic deciduosis is most often located in the ovaries, cervix and uterus, but can also be located on peritoneal surfaces of pelvic- and abdominal organs. The findings from surgical biopsies taken during pregnancy are mostly asymptomatic and incidental. Deciduosis of the appendix is rare, but it is a known differential diagnosis to acute appendicitis in pregnancy. We report a 27-year-old woman, Gravida 1, Para 0 in gestational week 35, who presented with acute right abdominal pain. She underwent an acute caesarean section for possible abruptio placentae. Acute appendicitis was a differential diagnosis. Peroperative findings revealed an inflamed and enlarged appendix suspicious for tumour. A pathological examination of the appendix showed decidual changes through the entire wall without signs of appendiceal endometriosis. In conclusion, symptomatic ectopic deciduosis in pregnancy is rare and may imitate acute appendicitis. This is an important differential diagnosis in pregnant women with tumour-suspect findings.

Heterogeneity in gamma-glutamyltransferase mRNA expression and glycan structures. Search for tumor-specific variants in human liver metastases and colon carcinoma cells.

The enzyme gamma-glutamyltransferase (GGT) is frequently overexpressed in cancer cells and tissues and has significant utility as a cancer marker. Significant heterogeneity of the enzyme has been described due to both transcriptional and post-translational variations. For possible use in diagnosis and follow-up of patients with colorectal cancer, a search was performed for specific mRNA subtypes and glycan structures of the enzyme in liver metastases. We found no differences in the distribution of three GGT mRNA subtypes (fetal liver, HepG2, placenta) in metastatic tissue and normal liver tissue. Furthermore, the three subtypes were present in leukocytes isolated from both normal individuals and cancer patients. Two colon carcinoma cell lines (Colo 205 and HCC 2998) also displayed the three forms and no consistent changes in mRNA composition were noted after butyrate-induced differentiation of the cells. Thus, neither of the GGT mRNA subforms appear to be tumor-specific, although some qualitative and quantitative variations were noted. Two distinct glycosylation features were detected for GGT in metastatic tissue in contrast to normal liver GGT; an extreme sialic acid heterogeneity and a significant increase in beta1,6GlcNAc branching. The GGT glycans from the two colon carcinoma cell lines also possessed these features. As butyrate treatment of the cells resulted in an increased sialic acid content and a reduced beta1,6GlcNAc branching, the described carbohydrate structures appear to be part of a tumor-related pattern. We were, however, unable to identify such GGT isoforms in serum from patients with advanced colorectal cancer. This indicates that their usefulness in diagnostic use is doubtful.

Lipoteichoic acid is a potent inducer of cytokine production in rat and human Kupffer cells in vitro.

BACKGROUND: Kupffer cells have been proposed to be a major cellular origin of pro-inflammatory mediators in sepsis. However, the cytokine response of Kupffer cells to gram-positive bacteria and their endotoxins peptidoglycan (PepG) and lipoteichoic acid (LTA) has never previously been studied. MATERIALS AND METHODS: Primary cultures of rat and human Kupffer cells were exposed to live Staphylococcus aureus (S. aureus) (4.0 x 10(1) to 4.0 x 10(7) CFU/mL culture medium), as well as highly purified PepG and LTA (0-100 microg/mL). Lipopolysaccharide (LPS) at 1 microg/mL was used for control. In parallel experiments, whole blood obtained from the same rats was stimulated in a similar manner. Accumulation of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in plasma or culture supernatants were assessed by enzyme immuno assays. TNF-alpha and IL-6 mRNA were analyzed by real-time RT-PCR. RESULTS: PepG and LTA, as well as live S. aureus, induced the production of TNF-alpha and IL-6 in Kupffer cells from both species in a time- and dose-dependent manner. Whereas PepG was a more potent inducer of TNF-alpha and IL-6 in whole blood, the opposite seemed to be the case in Kupffer cells. In fact, a 100-fold lower concentration of LTA (1 microg/mL) than of PepG (100 microg/mL) was sufficient to induce a substantial production of both TNF-alpha and IL-6 in the Kupffer cells. TNF-alpha and IL-6 mRNA were induced correspondingly. CONCLUSION: Our results support the contention that gram-positive bacteria may activate cytokine production in Kupffer cells during bacteremia and suggest that LTA is important in this interaction.

Hepatic autotransplantation with ex situ neoplasm extirpation and vena cava replacement.

The treatment of a 64-year-old man with a retrohepatic neoplasm deemed not accessible by conventional in situ surgical techniques is presented to illustrate the potential benefit offered by techniques adapted from liver transplantation and vascular surgery. A computed tomography scan performed for uncharacteristic abdominal discomfort revealed a hepatic or retrohepatic tumor compressing the inferior vena cava. Biopsies were interpreted as probably leiomyoma or malignant schwannoma. The liver with neoplasm and retrohepatic inferior vena cava was removed en bloc and taken to the back table where the neoplasm invading the inferior vena cava wall was removed together with the inferior vena cava. The inferior vena cava was then replaced by a 22-mm polytetrafluoroethylene graft and the 3 hepatic veins were reconstructed with anastomoses to this graft. The liver was then autotransplanted by standard transplantation technique. The postoperative course was uneventful and the patient is in good health more than 2 years after surgery.

[Extracorporeal surgery and liver autotransplantation]. / Ekstrakorporeal kirurgi og autotransplantasjon av lever.

BACKGROUND: Though the great majority of hepatic and perihepatic neoplasms may very well be treated by conventional surgical techniques, a few patients will have lesions seemingly inaccessible by traditional in situ surgical procedures. MATERIAL AND METHOD: We present two patients with retrohepatic sarcoma and liver haemangioma respectively, treated by hepatectomy, ex situ resection and hepatic autotransplantation. RESULTS: The first patient, a 64-year-old man, had a completely uneventful postoperative course and had no indication of recurrent sarcoma two years later. The second patient, a 29-year-old female with a giant hepatic haemangioma developed postoperative hepatic artery thrombosis. Following thrombectomy her further course was satisfactory and the patient was discharged with normal liver function three weeks postoperatively. INTERPRETATION: Ex situ liver surgery (bench surgery) with liver autotransplantation should be considered when traditional in situ surgery on the liver or adjacent structures is not applicable.