Hepatectomy for recurrent colorectal liver metastases after radiofrequency ablation.

BACKGROUND: The results of surgery for recurrent colorectal liver metastases (CLM) after radiofrequency ablation (RFA) have not been evaluated. METHODS: From 1993 to 2009, data on patients who underwent resection or RFA for recurrent CLM were collected prospectively. Inclusion criteria for this study were RFA as initial treatment for CLM and resection of recurrent CLM after RFA. Postoperative results and oncological outcomes were analysed. RESULTS: Twenty-eight patients (median number of tumours 1 (1-3), median size 2·8 (2·0-4·0) cm) met the inclusion criteria. Of these, 22 had recurrence at the site of RFA only, two developed new lesions, whereas four had both recurrent and de novo metastases. At the time of resection, patients had a median of 1 (1-13) CLM with a median maximum tumour diameter of 5·0 (1·8-11·0) cm, significantly larger than at the time of RFA (P = 0·021). Ninety-day postoperative morbidity and mortality rates were 46 per cent (13 of 28) and 7 per cent (2 of 28) respectively. After a median follow-up of 35 (0-70) months, 3-year overall and disease-free survival rates calculated by Kaplan-Meier analysis were 60 and 29 per cent respectively. Plasma carcinoembryonic antigen level over 5 ng/ml at the time of resection and a rectal primary tumour were associated with worse survival (P = 0·041 and P = 0·021 respectively). CONCLUSION: Resection for recurrence after RFA is associated with significant morbidity and modest long-term benefit.

Portal vein embolization before major hepatectomy and its effects on regeneration, resectability and outcome.

BACKGROUND: This study evaluated the safety of portal vein embolization (PVE), its impact on future liver remnant (FLR) volume and regeneration, and subsequent effects on outcome after liver resection. METHODS: Records of 112 patients were reviewed. Standardized FLR (sFLR) and degree of hypertrophy (DH; difference between the sFLR before and after PVE), complications and outcomes were analysed to determine cut-offs that predict postoperative hepatic dysfunction. RESULTS: Ten (8.9 per cent) of 112 patients had PVE-related complications. Postoperative complications occurred in 34 (44 per cent) of 78 patients who underwent hepatic resection and the 90-day mortality rate was 3 per cent. A sFLR of 20 per cent or less after PVE or DH of not more than 5 per cent (versus sFLR greater than 20 per cent and DH above 5 per cent) had a sensitivity of 80 per cent and a specificity of 94 per cent in predicting hepatic dysfunction. Overall, major and liver-related complications, hepatic dysfunction or insufficiency, hospital stay and 90-day mortality rate were significantly greater in patients with a sFLR of 20 per cent or less or DH of not more than 5 per cent compared with patients with higher values. CONCLUSION: DH contributes prognostic information additional to that gained by volumetric evaluation in patients undergoing PVE.

Chemotherapy-associated hepatotoxicity and surgery for colorectal liver metastases.

BACKGROUND: Preoperative systemic chemotherapy is increasingly used in patients who undergo hepatic resection for colorectal liver metastases (CLM). Although chemotherapy-related hepatic injury has been reported, the incidence and the effect of such injury on patient outcome remain ill defined. METHODS: A systematic review of relevant studies published before May 2006 was performed. Studies that reported on liver injury associated with preoperative chemotherapy for CLM were identified and data on chemotherapy-specific liver injury and patient outcome following hepatic resection were synthesized and tabulated. RESULTS: Hepatic steatosis, a mild manifestation of non-alcoholic fatty liver disease (NAFLD), may occur after treatment with 5-fluorouracil and is associated with increased postoperative morbidity. Non-alcoholic steatohepatitis, a serious complication of NAFLD that includes inflammation and hepatocyte damage, can occur after treatment with irinotecan, especially in obese patients. Irinotecan-associated steatohepatitis can affect hepatic reserve and increase morbidity and mortality after hepatectomy. Hepatic sinusoidal obstruction syndrome can occur in patients treated with oxaliplatin, but does not appear to be associated with an increased risk of perioperative death. CONCLUSION: Preoperative chemotherapy for CLM induces regimen-specific hepatic changes that can affect patient outcome. Both response rate and toxicity should be considered when selecting preoperative chemotherapy in patients with CLM.

Biallelic inactivation of the APC gene is associated with hepatocellular carcinoma in familial adenomatous polyposis coli.

BACKGROUND: Certain primary hepatic tumors have been associated with familial adenomatous polyposis (FAP), a condition caused by germline mutations of the adenomatous polyposis coli (APC) gene. However, a genetic association between FAP and hepatocellular carcinoma (HCC) has not been shown. This study tested the hypothesis that biallelic inactivation of the APC gene contributed to the development of HCC in a patient with FAP and a known germline mutation of the APC gene at codon 208, but no other risk factors for HCC. METHODS: Total RNA and genomic DNA were isolated from the tumor, and in vitro synthesized protein assay and DNA sequencing analysis were used to screen for a somatic mutation in the APC gene. RESULTS: A somatic one-base pair deletion at codon 568 was identified in the wild-type allele of the APC gene. CONCLUSIONS: To the authors' knowledge, this study provides the first evidence that biallelic inactivation of the APC gene may contribute to the development of HCC in patients with FAP.

Cytosolic phospholipase A(2)-mediated ICAM-1 expression is calcium dependent.

BACKGROUND: Some human malignancies such as virus-related hepatocellular cancer arise in a setting of chronic inflammation. Upregulation of ICAM-1 is a seminal late event in malignant transformation following chronic inflammation. Cytosolic phospholipase A(2) (cPLA(2)) is a lipid-mediator activated by inflammatory stimuli, which has been shown to mediate ICAM-1 upregulation. As lipid mediators are known to work via calcium-dependent mechanisms in nearly all mammalian cells, we hypothesize that inflammatory-mediated ICAM-1 upregulation is dependent on both cPLA(2) and intracellular calcium. MATERIALS AND METHODS: HUVEC were chosen as a representative cell line as they emulate hepatic sinusoids and are a well-established cell model. These were grown to confluence in T-25 flasks and stimulated with TNF-alpha or LPS for 6 h. Additional groups were preincubated with AACOCF3 (a specific cPLA(2) inhibitor) or BAPTA A.M. (a specific inhibitor of intracellular Ca(2+)) prior to being exposed to inflammatory stimuli. ICAM-1 expression was determined by mean fluorescent intensity (MFI) as measured by FITC-labeled moAb to ICAM-1 via FACS. The role of intracellular Ca(2+) on cPLA(2) activity was determined by thin-layer chromatography. Groups were compared using ANOVA with Scheffe's post hoc analysis; *P < 0.05 vs control, daggerP < 0.05 vs LPS and TNF-alpha was considered significant; N > or = 4 all experimental groups. RESULTS: Both cPLA(2) and Ca(2+) inhibition significantly inhibited inflammatory upregulation of ICAM-1. Pretreatment with BAPTA A.M. attenuated HUVEC cPLA(2) activity in response to LPS. These findings suggest that appropriate molecular target suppression may prevent malignant degeneration in the presence of chronic inflammation.

Portal vein embolization: rationale, technique and future prospects.

BACKGROUND: Advances in surgery have reduced the mortality rate after major liver resection, but complications resulting from inadequate postresection hepatic size and function remain. Portal vein embolization (PVE) was proposed to induce hypertrophy of the anticipated liver remnant in order to reduce such complications. The techniques, measurement methods and indications for this treatment remain controversial. METHODS: A Medline search was performed to identify papers reporting the use of PVE before hepatic resection. Techniques, complications and results are reviewed. RESULTS: Complications of PVE typically occur in less than 5 per cent of patients. No specific substance (cyanoacrylate, thrombin, coils or absolute alcohol) emerged as superior. The increase in remnant liver volume averages 12 per cent of the total liver. The morbidity rate of resection after treatment is less than 15 per cent and the mortality rate is 6-7 per cent with cirrhosis and 0-6.5 per cent without cirrhosis. Embolization is currently used for patients with a normal liver when the anticipated liver remnant volume is 25 per cent or less of the total liver volume, and for patients with compromised liver function when the liver remnant volume is 40 per cent or less. CONCLUSION: This treatment does not increase the risks associated with major liver resection. It may be indicated in selected patients before major resection. Future prospective studies are needed to define more clearly the indications for this evolving technique.

Biliary tract cancer.

Advances in cellular and molecular biology of extrahepatic cholangiocarcinoma and gallbladder adenocarcinoma are providing innovative means for the diagnosis and treatment of biliary tract cancer. Similarly, refinements in noninvasive studies--including helical computed tomography, magnetic resonance cholangiopancreatography, and endoscopic ultrasonography--are enabling more accurate diagnosis, staging, and treatment planning for these tumors. Complete resection remains the only means for cure, and recent reports from major hepatobiliary centers support aggressive wide resection for bile duct and gallbladder cancer. Palliation of malignant strictures has improved with advanced endoscopic techniques, newer polyurethane-covered stents, endoscopic microwave coagulation therapy, and radiofrequency intraluminal endohyperthermia. The preliminary data on such minimally invasive techniques suggest an improvement in quality of life and survival for selected patients.

Paraplegia following intraoperative celiac plexus injection.

The technique for percutaneous and open neurolytic celiac plexus injection, using ethanol or phenol, for relief of intractable pancreatic cancer pain has been well described. Prospective randomized studies, demonstrating safety and efficacy with few complications, have led to widespread acceptance and use of this palliative procedure. The complications of neurolytic celiac plexus injection are rare, and are usually minor. However, transient or permanent paraplegia has been reported previously in 10 cases. The case described herein represents the third reported case of permanent paraplegia following open intraoperative neurolytic celiac plexus injection using 50% ethanol. The literature surveying the indications for this procedure, routes of administration, known complications, and their pathophysiology are reviewed.

Monolobar Caroli's Disease and cholangiocarcinoma.

Caroli's Disease (CD) is a rare congenital disorder characterized by cystic dilatation of the intrahepatic bile ducts. This report describes a patient with cholangiocarcinoma arising in the setting of monolobar CD. In spite of detailed investigations including biliary enteric bypass and endoscopic retrograde cholangiography, the diagnosis of mucinous cholangiocarcinoma (CCA) was not made for almost one year. The presentation, diagnosis and treatment of monolobar CD and the association between monolobar CD and biliary tract cancer are discussed. Hepatic resection is the treatment of choice for monolobar CD.

Recent advances in the treatment and outcome of locally advanced rectal cancer.

OBJECTIVE: To compare the outcomes of treatment of locally advanced rectal cancer of the early era (1975-1990) with those of the late era (1991-1997). BACKGROUND: Preoperative therapy has been used in locally advanced rectal cancer to preserve sphincter function, decrease local recurrence, and improve survival. At the University of Florida, preoperative radiation has been used since 1975, and it was combined with chemotherapy beginning in 1991. METHODS: The records of 328 patients who underwent preoperative radiation or chemoradiation followed by complete resection for locally advanced rectal cancer defined as tethered, annular, or fixed tumors were reviewed. The clinicopathologic characteristics, adjuvant treatment administered, surgical procedures performed, and local recurrence-free and overall survival rates were analyzed. RESULTS: There were 219 patients in the early era and 109 in the late era. No significant differences were seen in patients (age, gender, race) or tumor characteristics (mean distance from the anal verge, annularity, fixation). Preoperative radiation regimens were radiobiologically comparable. No patient in the early era received preoperative chemotherapy, compared with 64 in the late era. Of those receiving any pre- or postoperative chemotherapy, three patients received chemotherapy in the early era, compared with 76 in the late era. Sphincter-preserving procedures increased from 13% in the early era to 52% in the late era. Pathologic downstaging for depth of invasion increased from 42% to 58%, but lymph node negativity remained similar. The 1-, 3-, and 5-year local recurrence-free survival rates were comparable. However, in the late era, 1-, 3-, and 5-year overall survival rates improved significantly compared with those of the early era, and also compared with each of the preceding 5-year intervals. CONCLUSION: The addition of a chemotherapy regimen to preoperative radiation therapy improves survival over radiation therapy alone. Likewise, an improvement in downstaging is associated with an increase in sphincter-preserving procedures.

Increased leptin expression in mice with bacterial peritonitis is partially regulated by tumor necrosis factor alpha.

Plasma leptin and ob gene mRNA levels were increased in mice following bacterial peritonitis, and blocking an endogenous tumor necrosis factor alpha (TNF-alpha) response blunted the increase. However, plasma leptin concentrations did not correlate with the associated anorexia. We conclude that leptin expression is under partial regulatory control of TNF-alpha in peritonitis, but the anorexia is not dependent on increased leptin production.

Arterial levels of oxidized glutathione (GSSG) reflect oxidant stress in vivo.

Neutrophil-related, oxidant-mediated injury to the pulmonary microvasculature appears to follow endotoxemia, cutaneous thermal injury, and ischemia-reperfusion injury to the liver or intestine. Glutathione is an important endogenous intracellular oxygen radical scavenger. Plasma concentrations of oxidized glutathione (GSSG) reflect oxidant injury resulting from an overdose of certain oxidatively metabolized drugs. The purpose of this investigation was to evaluate plasma GSSG as an indicator of oxidant stress resulting from activation of the endogenous inflammatory response. An established model of neutrophil- and oxidant-related acute lung injury following intestinal ischemia and reperfusion in rats was used. Intestinal ischemia was induced by clip occlusion of the superior mesenteric artery (SMA) for 120 min. Reperfusion resulted from SMA clip removal. Following reperfusion for 0, 15, or 120 min, plasma GSSG levels in portal vein, inferior vena cava (IVC), and aorta were obtained. Plasma GSSG was undetectable in sham animals and those with intestinal ischemia alone. Following reperfusion, all plasma samples had significant elevations in GSSG. Aortic plasma GSSG after 15 min of reperfusion was significantly elevated compared to both portal vein and IVC plasma GSSG. These data suggest that oxidant stress after intestinal reperfusion is reflected by elevations in plasma GSSG. The step up in plasma GSSG across the pulmonary vascular bed, a site of known oxidant injury, suggests that plasma GSSG may be a useful marker of oxidant stress in vivo, particularly with regard to the pulmonary microvasculature. This simple in vivo approach to assessing oxidant stress related to inflammatory tissue injury may have the potential to be of significant use in the clinical setting.