Adjuvant hepatic intra-arterial iodine-131-lipiodol following curative resection of hepatocellular carcinoma: a prospective randomized trial.

BACKGROUND: The purpose of the present study was to determine whether intrahepatic injection of (131)I-lipiodol (Lipiodol) is effective against recurrence of surgically resected hepatocellular carcinoma (HCC). METHODS: From June 2001 through March 2007, this nationwide multi-center prospective randomized controlled trial enrolled 103 patients 4-6 weeks after curative resection of HCC with complete recovery (52: Lipiodol, 51: Control). Follow-up was every 3 months for 1 year, then every 6 months. Primary and secondary endpoints were recurrence-free survival (RFS) and overall survival (OS), respectively, both of which were evaluated by the Kaplan-Meier technique and summarized by the hazard ratio (HR). The design was based on information obtained from a similar trial that had been conducted in Hong Kong. RESULTS: The Lipiodol group showed a small, and nonsignificant, improvement over control in RFS (HR = 0.75; 95 % confidence interval [95 % CI] 0.46-1.23; p = 0.25) and OS (HR = 0.88; 95 % CI 0.51-1.51; p = 0.64). Only two serious adverse events were reported, both with hypothyroidism caused by (131)I-lipiodol and hepatic artery dissection during angiography. CONCLUSIONS: The randomized trial provides insufficient evidence to recommend the routine use of (131)I-lipiodol in these patients.

The tumor suppressor function of LECT2 in human hepatocellular carcinoma makes it a potential therapeutic target.

Vascular invasion is one of the clinicopathologic features that are associated with early recurrence of human hepatocellular carcinoma (HCC). In this study, we have employed high-density Affymetrix oligonucleotide GeneChips (Affymetrix, Santa Clara, CA) to compare the expression profiles of HCC with and without vascular invasion. Data mining of the gene expression database established revealed that leukocyte cell-derived chemotaxin-2 (LECT2) transcripts were downregulated in HCC patients with vascular invasion. Expression of LECT2 in human HCC biopsies was significantly reduced (P < 0.0001, fold change = -7.2) when compared with non-tumorous adjacent liver tissues. The reduction of LECT2 expression was significantly correlated with the early recurrent and poor prognosis of the patient (P = 0.024). To validate the ability of LECT2 to repress the growth of HCC, an adenoviral vector encoding the secreted human LECT2 (AdLECT2) was introduced into the human HCC cell lines Hep3B and PLC/PRF/5, which do not express endogenous LECT2. Over-expression of LECT2 resulted in the significant inhibition of in vitro migration and invasion of the AdLECT2-transfected HCC cells. Additionally, over-expression of AdLECT2 in subcutaneous Hep3B tumor xenografts in athymic nude mice resulted in significant inhibition of tumor growth (P < 0.05). In summary, our data not only demonstrated that LECT2 is a candidate prognostic marker of human HCC, but also that therapeutic strategies targeting LECT2 expression is a promising therapy for human HCC.

Identification of unique and common low abundance tumour-specific transcripts by suppression subtractive hybridization and oligonucleotide probe array analysis.

Most human cancers are characterized by genetic aberrations accompanied by altered expression and function of numerous genes. Applying genome-wide, microarray gene expression analysis to identify deregulated genes in different tumour types can provide potential gene candidates as diagnostic and prognostic tools and promising targets for drug development. However, the detection of deregulated genes with low levels of expression remains a major challenge. In this study, we have designed a strategy, termed modified suppression subtractive hybridization (mSSH), to identify genes encoding rare transcripts. The strategy entails incorporating the T(7)-promoter sequence at the 5' end of the noncoding cDNA strand during first strand cDNA synthesis to generate unidirectional antisense RNA from the resultant cDNA following conventional SSH. These transcripts are subsequently analysed by Affymetrix oligonucleotide gene arrays. Here, we have used five hepatocellular carcinoma (HCC), five breast carcinoma and four nasopharyngeal carcinoma (NPC) biopsies separately as testers and their corresponding normal biopsies as drivers to enrich for low abundance tumour type-specific transcripts. The total detectable number of probe sets following mSSH was reduced almost 10-fold in comparison to those detected for the same resected tumour tissues without undergoing subtraction, thus yielding a subtraction efficacy of over 90%. Using this experimental approach, we have identified 48 HCC-specific, 45 breast carcinoma-specific, and 83 NPC-specific genes. In addition, 115 genes were upregulated in all the three cancer types. When compared to gene-profiling data obtained without mSSH, the majority of these identified transcripts were of low abundance in the original cancer tissues. mSSH can therefore serve as a comprehensive molecular strategy for pursuing functional genomic studies of human cancers.

Pedunculated HCC or adrenal metastasis: a diagnostic conundrum.

Hepatocellular carcinoma (HCC) is the commonest primary liver tumour. Recurrences are common in the liver although extrahepatic metastases can occur and frequently involve the adrenals. When this occurs in the right adrenal gland, it can be confused with an exophytic HCC arising from the posterior surface of the liver. The distinction between a primary HCC and a metastasis is important but can be difficult in this clinical setting. We report a 52-year-old man with recurrent HCC presenting as an "exophytic" posterior liver surface lesion that was actually a right adrenal metastasis. Although right-sided adrenal metastases of HCC can be difficult to distinguish from intrahepatic recurrences, even with modern diagnostic imaging, management either way involves surgical exploration and resection whenever possible.

Clinico-pathological features of cystic pancreatic endocrine neoplasms and a comparison with their solid counterparts.

AIM: Pancreatic endocrine neoplasms (PENs) may occasionally manifest as cystic lesions of the pancreas. The aim of this study is to report our experience with cystic PENs and to compare their clinico-pathological features with their solid counterparts. MATERIALS AND METHODS: From 1990 to 2004, 38 patients with PENs were reviewed. Six of these tumours appeared on radiological imaging as a cystic lesion of the pancreas. RESULTS: Of the 38 patients with a PEN, 21 of the patients were female and with a median age of 54.5 (range, 33-83) years. Sixteen patients had functional endocrine tumours of which insulinoma was the most common. The six patients with cystic PEN had a median age of 55.5 (range, 41-70) years and half were female. Cystic PENs were significantly larger [48 (range, 25-170) mm vs 19 (range, 3-120) mm, P = 0.013] and were less likely to be benign (0 vs 50%, P = 0.017) compared to their solid counterparts. There was no difference between cystic and solid PENs in terms of age, sex, presence of symptoms, proportion of functioning tumours and location of tumours within the pancreas. CONCLUSION: Cystic PENs share many clinico-pathological features with solid PENs. These differ only in the cystic appearance and tend to be of a larger size. Hence, these findings suggest that cystic and solid PENs are unlikely to be distinct pathological entities but are likely to be morphological variants of the same entity.

Cystic neoplasms of the pancreas with mucin-production.

AIM: To compare the clinico-pathological features of intraductal papillary mucinous cystic tumours (IPMT) and mucinous cystic tumours (MCT) of the pancreas. METHODS: Eighteen patients with IPMT and 18 with MCT who underwent surgical resection between 1990 and 2004 were retrospectively reviewed. Their clinico-pathological features were compared using univariate analysis. Statistical analyses of potential predictive factors of malignancy for each of these two groups were also conducted. RESULTS: Patients with IPMT were found to be older (64+/-10 vs 43+/-18 years, p<0.001) and were predominantly male (male:female ratio, 5:4 vs 1:17, p=0.003) as compared to patients with MCT. MCTs were found in the body-tail region (100%) whereas IPMTs were more evenly distributed (50% in the head) (p=0.001). Pathologically, IPMT was distinct from MCT in terms of size (3.8+/-3.2 vs 9.1+/-4.4 cm, p=0.001), association with secondary pancreatitis (50 vs 0%, p=0.011), communication with the pancreatic duct (94 vs 0%, p<0.001), presence of a dilated main pancreatic duct (61 vs 0%, p<0.001) and the presence of ovarian-type stroma (0 vs 44%, p=0.003). CONCLUSION: IPMT and MCT are distinct clinico-pathological entities. This distinction is important as management and outcome of these entities may differ.

Sclerosing haemangioma mimicking hepatocellular carcinoma.

Sclerosing haemangioma is a rare variant of hepatic haemangioma. The radiological features on computed tomography and magnetic resonance imaging may not be typical for haemangioma and can be confused with hepatocellular carcinoma. We report sclerosing haemangioma occurring in a 65-year-old woman where the radiological features raise the possibility of hepatocellular carcinoma.

Clinical mimicry of hepatocellular carcinoma: imaging-pathological correlation.

This pictorial essay aims to show the clinical mimicry of hepatocellular carcinoma (HCC) and its diagnostic difficulty, and to create awareness among clinicians and radiologists of potential diagnostic pitfalls. A selected consecutive series of hepatectomies with proven HCC over a three-year period, identifying clinical presentation, blood results and imaging of patients with difficult preoperative diagnosis, was reviewed. The imaging of the focal liver lesions is presented pictorially with pathological correlation. Six patients out of 34 cases of resected HCC were diagnosed to have benign (three liver abscesses) and neoplastic (one Klatskin tumour, one colorectal liver metastasis, one gallbladder cancer) conditions. Compared to the rest in the series, all six patients had normal serum alpha fetoprotein levels. On computed tomography, the mosaic appearance of HCC mimicked locules of liver abscess while HCC with pseudocapsule (rim enhancement) was misdiagnosed as unilocular abscess or metastatic lesion. Arterial enhancement on contrast-enhanced triphasic computed tomography was useful in diagnosis of HCC. In summary, HCC can mimic benign and neoplastic clinical syndromes. The diagnosis of liver abscess can delay subsequent diagnosis of HCC and potentially complicate the treatment plan. Contrast-enhanced triphasic computed tomography or magnetic resonance imaging is useful to resolve difficult diagnosis, especially when the serum alpha fetoprotein level is not raised.

A comparison of two surgical strategies for the emergency treatment of gallstone ileus.

INTRODUCTION: Debate currently exists regarding the appropriate surgical strategy for emergency treatment of gallstone ileus. This relates to the need for definitive biliary tract surgery after relief of mechanical obstruction. Our study reviews treatment by enterolithotomy alone and enterolithotomy combined with definitive biliary tract surgery and fistula closure to determine if there is advantage of one treatment option over the other. METHODS: The clinical, operative and follow-up data on 19 consecutive patients treated by emergency surgery for gallstone ileus from January 1992 to December 2000 was retrospectively reviewed. RESULTS: There were 15 women and four men, with a mean age of 74.6 (range 62-91) years. Pre-operative diagnosis was made in only nine of 19 patients. Enterolithotomy alone (E group) was performed in seven patients and enterolithotomy with cholecystectomy and fistula closure (E+C group) in 12 patients. In the E group, more patients had significant co-morbidity as identified by poorer American Society of Anesthesiologists (ASA) status, poorer pre-operative status (shock at presentation) than in the E+C group. Operative time was significantly shorter in the E group. However, there were no significant differences in morbidity, and both groups had zero mortality. CONCLUSION: Both procedures can be carried out safely and with zero mortality. Relief of obstruction remains the mainstay of treatment. The better surgical option in our series is enterolithotomy alone. It is safe in both low and high-risk patients, and requires a shorter operating time as it is technically less demanding. In the longer term, the remnant fistula also does not appear to lead to further complications.

Percutaneous drainage of liver abscess complicated by hepato-venous fistula.

Severe systemic sepsis after percutaneous drainage of liver abscess is rare. We report two cases of hepato-venous fistulas between hepatic abscesses and hepatic/portal veins documented on abscessography during percutaneous drainage of liver abscesses, which resulted in severe sepsis and a stormy post drainage clinical course. Liver abscesses can rupture into the portal and hepatic veins causing worsening of systemic sepsis especially when they are in close proximity to each other. During percutaneous drainage, care must also be taken to avoid overinjection of the abscess, which can worsen the fistula. The ensuing sepsis is severe and requires aggressive intensive medical care and ventilatory support to tide the patient over the septic episode.

Surgical management of colorectal metastases to the liver.

Liver metastases develop in 50% to 60% of patients with colorectal carcinoma. Surgical resection offers a good five-year survival rate and the only chance of cure. In this article, the natural history and risk factors for the development of colorectal liver metastases are discussed, followed by the diagnostic work-up towards surgical resection. Various issues pertaining to surgical management, such as patient selection, timing of resection, perioperative mortality and morbidity, prognostic factors, adjuvant and neoadjuvant therapy and repeat resection are reviewed.

Computed tomographic appearance of colorectal hepatic metastases.

INTRODUCTION: This article reviews the various computed tomography (CT) appearances of hepatic metastases from colorectal primaries and assesses the frequency of occurrence of the various patterns. MATERIALS AND METHODS: This is a retrospective study of the CT appearances of histologically proven colorectal hepatic metastases in a group of 52 patients who had undergone surgical hepatic resection between January 1994 and December 2001. A total of 74 hepatic metastatic lesions were reviewed. All lesions were examined in the portal venous phase. RESULTS: A discernible rim was seen in 54 lesions (73%). Thick rim was present in 36 lesions (48.6%) and thin rim in 18 lesions (24.3%). Enhancement of the rim was present in 62 cases (83.8%). Increased central attenuation was seen in 38 lesions (51.4%). Of these, the centre was heterogeneous in 76.3% and scar-like in 23.7%. A non-enhancing rim was seen in 12 lesions (16.2%) which appeared as lesions with "bevelled edge". Thick enhancing rim with non-enhancing centre was the most common combination in 15 lesions (20.3%). CONCLUSION: An enhancing rim could be seen in 83.8% of lesions. Increased central attenuation was present in 51.4% of the lesions. Familiarity with the various CT appearances may facilitate identification and diagnosis of colorectal liver metastases.

Hepatic resection for colorectal metastases to the liver: The National Cancer Centre/Singapore General Hospital experience.

OBJECTIVE: To review and evaluate trends for short and long-term outcomes of patients who have undergone liver resection for colorectal metastases in a single institution over a period of 7 years. MATERIALS AND METHODS: A retrospective review and analysis of clinicopathologic data and outcome of potentially curative liver resection for colorectal metastases in a series of 96 patients from January 1994 to December 2001 was done. Data were statistically analysed. Perioperative mortality, morbidity, overall survival and disease-free survival rates were reported. RESULTS: A total of 96 patients underwent potentially curative liver resection for colorectal metastases. There were 64 males (66.7%) and 32 females (33.3%) with a median age of 60 years. There was no perioperative mortality. Postoperative morbidity was 7.2%. The median length of follow-up for the entire cohort of post hepatic resection was 29 months with 1-year and 3-year overall survival rates of 99% and 71%, respectively. The disease-free survival rates were 76% and 48%, respectively. Minor resections for the liver metastases showed significantly better overall survival. Primary tumour in the colon compared to rectum, disease-free interval (DFI) < 12 months and adjuvant chemotherapy showed a trend towards shorter overall survival. Carcinoembryonic antigen (CEA) levels greater than 100 ng/mL significantly shortens the disease-free survival. CONCLUSION: Liver resection for colorectal metastases in our institution is a safe and effective treatment option in properly selected patients, which currently represents the best chance for long-term survival and possibly "cure".

Current status in the surgical management of adult polycystic liver disease.

INTRODUCTION: In patients with adult polycystic liver disease (APLD), there is considerable debate surrounding the most effective way of managing symptomatic cysts. Conservative approaches like percutaneous aspiration or cyst fenestration are associated with low morbidity but high recurrence rates. Conversely, liver resection and hepatectomy with orthotopic liver transplantation is drastic and associated with high morbidity and mortality rates. Our aim is to review the current understanding of liver cystogenesis in these patients and the therapeutic options available in order to provide a rationale guide to management of this intriguing condition. METHODS: This article summarises the findings of published papers in major international journals indexed on MEDLINE on APLD using the key words--adult polycystic liver disease, liver cysts, fenestration, liver resection, liver transplantation and polycystic kidney disease. The period of search includes papers between 1965 and 2000. RESULTS: Published studies have suggested a 'two-hit' hypothesis to explain the development of liver cysts in patients with APLD. This will provide the rationale for future management. Meanwhile, the indications, pitfalls and results of the various therapeutic options are reviewed. Management of symptoms has to be tailored to the underlying severity of the liver cystic disease, co-morbidity and procedural risks and recurrence rates. CONCLUSION: Good long-term relief of symptoms can be achieved with the correct procedure at acceptable morbidity and mortality rates. We have provided guidelines on the various options available to enable a structured approach to the management of APLD.