Portion Of Nodes Research Articles

Abstract 1694: Imaging cell cycle progression in gastric cancer lymph node metastasis indicates large fraction of proliferating cancer cells

Abstract We report here a mouse model of lymph node metastasis of stomach cancer and imaging cell cycle progression in the metastasis. FUCCI (fluorescent ubiquitination-based cell cycle indicator)-expressing human MKN45 gastric cancer cells were used to establish the lymph node metastasis nude mouse model. In this model, cell-cycle dynamics of the metastatic cells could be imaged in vivo. FUCCI cells are labeled orange in the G1 phase nuclei (monomeric Kusabira-Orange2: mKO2) and labeled green in the S/G2/M phases (monomeric Azami-Green1: mAG1). FUCCI MKN45 were injected into the mouse stomach mucosa from the serosal side. Lymph node metastasis to the para-aortic or hepatic portal region, left armpit, and brachial lymph nodes were observed. Green-yellow (G2/S) cells were predominant compared to red (G1) fluorescent FUCCI cells as observed in the lymph-node metastases using an FV1000 confocal microscope, indicating that the lymph-node metastatic cells were actively cycling. The origin of lymph node or vessel metastases was confirmed by H.E. staining. Mouse FUCCI gastric metastasis models will be used to visualize cell cycle dynamics in metastasis in lymphoid as well as hematogenous metastasis in order to optimize drug treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1694. doi:1538-7445.AM2012-1694

Corroboration of Serum Apolipoprotein J (Clusterin) as a Biomarker for Evaluating Hepatocellular Carcinoma

Background and study aim: Hepatocellualr carcinoma (HCC) is an increasing problem in Egypt. Clusterin has been reported to play a significant role in tumorigenesis. The aim of this study is to evaluate clusterin as a marker for evaluating diagnosis and metastasis potential of HCC. Patients and Methods: Eighty patients with HCC, 30 patients with liver cirrhosis, 30 patients with chronic hepatitis and 30 healthy controls were enrolled in study. The diagnosis of HCC patients was based on computed tomography. Estimation of serum clusterin was done by enzyme linked immunosorbent assay. Results: Serum clusterin levels were significantly increased in patients with HCC (P<0.001). Serum clusterin reached the lowest significant levels in cirrhotic patients. Serum clusterin was highly increased in patients with poorly differentiated tumor and in those with capsular infiltration; also it was significantly related with portal vein invasion and lymph node infiltration. In addition, serum clusterin levels were significantly increased according to the progression of Barcelona Clinic Liver Cancer and Tumor-Nodes-Metastasis staging systems. However, these findings were not observed with alpha fetoprotein (AFP). Receiver operator characteristic curve showed that clusterin had a greater area under curve value (0.95) than that of AFP (0.85). At cutoff value 128 ug/ml, serum clusterin yielded 90% sensitivity and 87% specificity for predicting HCC. While at cutoff value 100 ng/ml, serum AFP had 75% sensitivity and 80% specificity. Conclusion: We concluded that serum clusterin is a promising useful marker for diagnosis of HCC. Higher level of clusterin was closely related to capsular infiltration, venous invasion, lymph node metastasis and poorly differentiated tumor suggesting that clusterin might be deemed as a useful marker for predicting the progression and metastasis potential of HCC.

The role of liver resection for colorectal cancer metastases in an era of multimodality treatment: A systematic review

To determine the role of liver resection in patients with liver and extrahepatic colorectal cancer metastases and the role of chemotherapy in patients in conjunction with liver resection. MEDLINE and EMBASE databases were searched for articles published between 1995 and 2010, along with hand searching. A total of 4875 articles were identified, and 83 were retained for inclusion. Meta-analysis was not performed because of heterogeneity and poor quality of the evidence. Outcomes in patients who had liver and lung metastases, liver and portal node metastases, and liver and other extrahepatic disease were reported in 14, 10, and 14 studies, respectively. The role of perioperative chemotherapy was assessed in 30 studies, including 1 randomized controlled trial and 1 pooled analysis. Ten studies assessed the role of chemotherapy in patients with initially unresectable disease, and 5 studies assessed the need for operation after a radiologic complete response. The review suggests that: (1) select patients with pulmonary and hepatic CRC metastases may benefit from resection; (2) perioperative chemotherapy may improve outcome in patients undergoing a liver resection; (3) patients whose CRC liver metastases are initially unresectable may benefit from chemotherapy to identify a subgroup who may benefit later from resection; (4) after radiographic complete response (RCR), lesions should be resected if possible.

Regional lymphadenectomy for gallbladder cancer: Rational extent, technical details, and patient outcomes

To define the rational extent of regional lymphadenectomy for gallbladder cancer and to clarify its effect on long-term survival. A total of 152 patients with gallbladder cancer who underwent a minimum of "extended" portal lymph node dissection (defined as en bloc removal of the first- and second-echelon nodes) from 1982 to 2010 were retrospectively analyzed. Based on previous studies, regional lymph nodes of the gallbladder were divided into first-echelon nodes (cystic duct or pericholedochal nodes), second-echelon nodes (node groups posterosuperior to the head of the pancreas or around the hepatic vessels), and more distant nodes. Among the 152 patients (total of 3352 lymph nodes retrieved, median of 19 per patient), 79 patients (52%) had 356 positive nodes. Among node-positive patients, the prevalence of nodal metastasis was highest in the pericholedochal (54%) and cystic duct (38%) nodes, followed by the second-echelon node groups (29% to 19%), while more distant node groups were only rarely (5% or less) involved. Disease-specific survival after R0 resection differed according to the nodal status (P < 0.001): most node-negative patients achieved long-term survival (median, not reached; 5-year survival, 80%), whereas among node-positive patients, 22 survived for more than 5 years (median, 37 mo; 5-year survival, 43%). The rational extent of lymphadenectomy for gallbladder cancer should include the first- and second-echelon nodes. A considerable proportion of node-positive patients benefit from such aggressive lymphadenectomy.

Pancreatic dissection in the procedure of pancreaticoduodenectomy (with videos)

The procedure of pancreaticoduodenectomy consists of three parts: resection, lymph node dissection, and reconstruction. A transection of the pancreas is commonly performed after a maneuver of the pancreatic head, exposing of the portal vein or lymph node dissection, and it should be confirmed as a safe method for pancreatic transection for decreasing the incidence of pancreatic fistula. However, there are only a few clinical trials with high levels of evidence for pancreatic surgery. In this report, we discuss the following issues: dissection of peripancreatic tissue, exposing the portal vein, pancreatic transection, dissection of the right hemicircle of the peri-superior mesenteric artery including plexus and lymph nodes, and dissection of the pancreatic parenchyma.

A Rare Case of Erythrodysesthesia of Grafted Skin as an Adverse Reaction of Sorafenib

Purpose: Hand-foot syndrome (palmer-planter erythrodysesthesia) and other adverse reactions relating to administration of sorafenib lead to discontinuation of medication in one third of patients. We describe a rare case of erythrodysesthesia of grafted skin in hepatocellular cancer (HCC) patient treated with sorafenib. 52 year old male presented with complaints of peeling of the skin of hands and burning of tips of fingers. Patient tried different lotions without benefit. Four weeks prior, patient was initiated sorafenib 400 mg twice a day for multifocal HCC with lymph node metastasis. Past medical history was significant for cirrhosis secondary to HCV diagnosed 25 years ago. Patient was diagnosed with multi-focal HCC one year earlier with portal hepatic lymph node positive for poorly differentiated carcinoma cells on EUS-FNA. Patient was treated with transarterial chemoembolization twice as such transplant is not a possibility. Past surgical history was notable for hand surgery of left fingers for electrocution burn with skin graft. Patient is on alprazolam, Docusate® and morphine. No history of drug allergy or allergy to any substance or material. Patient is 1 pack per day active smoker for 30 years. Physical examination revealed redness, tenderness, swelling of hands, peeling of the grafted skin on the palmer surface of left hand fingers. AFP=154, platelets 66,000/ul, slight elevation of ALT&AST with normal total bilirubin, albumin and INR. Sorafenib was reduced to 200 mg one tablet twice a day. All symptoms resolved after one week. Majority of cases of Hand-foot syndrome, like our patient, presented with skin rash, swelling, redness, pain and/or peeling of the skin on the palms of hands and soles of feet. Symptoms are usually mild and start 5-6 weeks after beginning of chemotherapy. For example, 5-Fluouracil, Doxorubincin, Interleukin-2 and Sorafenib can cause this skin reaction for some patients. There are 3 grades of skin toxicity: Grade 1 = above symptoms which do not disrupt normal activities (requires symptomatic treatment with topical therapy), Grade 2 = above symptoms affecting normal activities (requires dose reduction by one dose level), Grade 3 = ulceration, blistering, or severe pain of the hands or feet or severe discomfort that prevents working or performing daily activities (requires discontinuation of treatment). Symptomatic treatment and dose reduction seems to be effective for majority of patients with Hand-foot syndrome including patient with grafted skin.

Accurate Staging for Gallbladder Cancer

This study evaluates the significance of tumor involvement of the liver in early T-stage tumors and lymph node (LN) metastases on outcome after R0 resection of gallbladder cancer (GBCA). A prospectively maintained database, supplemented with review of the medical record, was used to identify patients who underwent a complete (R0) resection for GBCA. All patients underwent definitive surgical treatment at the initial operation (1 stage) or after initial noncurative cholecystectomy (incidental tumors, 2 stage), including partial hepatectomy and portal LN dissection, with or without bile duct and/or adjacent organ resection. Clinicopathological variables, including TNM stage, histologic tumor involvement of liver (residual or direct extension in the GB fossa or discontiguous disease), and the total number of regional LNs assessed were analyzed for their association with outcome. One hundred twenty-two patients were identified and analyzed. The median follow up period was 23 months. Liver and nodal involvement by GBCA were observed in 61 (50%) and 41(34%) patients, respectively. Among patients with T2 tumors (n = 53), 48 (91%) were incidental. Liver involvement was present in 26%, and this factor was associated with decreased recurrence-free (RFS) and disease-specific survival (DSS) compared with patients with T2 tumors without liver involvement (median RFS, 12 months vs. not reached, P = 0.004, median DSS 25 months versus not reached, P = 0.003); T1b tumors (n = 10) were not associated with liver involvement. The median total lymph node count (TLNC) was 3 (range 0-20). For the entire cohort, survival of patients classified as N0 based on TLNC < 6 was significantly worse than that of N0 patients based on TLNC ≥ 6 (median RFS, 22 months versus not reached, P < 0.001, median DSS 41 months versus not reached, P < 0.001). Liver involvement and TLNC remained significant prognostic factors in a multivariate model that included TNM stage. Resection and histologic evaluation of at least 6 lymph nodes improves risk-stratification after resection of GBCA. Incidental T2 tumors are often associated with residual liver disease and should be reclassified to reflect the adverse outcome. The data suggests a need for standardized minimum requirements for adequate surgical treatment and pathological examination.

Primary malignant fibrous histiocytoma of the liver: CT findings in five histopathological proven patients

To describe imaging features of primary hepatic malignant fibrous histiocytoma (MFH), especially its dynamic enhancement pattern. The CT manifestations of five patients with histopathological proven primary hepatic MFH retrospectively reviewed. Six hepatic masses were detected in the five patients at CT examinations. All tumors were hypodense on plain CT scanning related to adjacent hepatic parenchyma. Five lesions were heterogeneous with predominantly cystic or necrosis areas and one lesion was homogeneous solid. After administration of contrast material, solid components of the four tumors with cystic or necrotic areas and the solid lesion showed a "fast rushing in and washing out" enhancement pattern with marked enhancement at the arterial dominated phase and fast decreasing at the portal vein dominated phase and the delay phase. The remaining one tumor showed slight enhancement of its solid components. Portal lymph node enlargement was observed in one patient and the inferior vena cava was invaded in one patient, respectively. The CT manifestations of primary hepatic MFH are various and nonspecific. A "fast rushing in and washing out" enhancement pattern of MFH in our series has not been reported before. These manifestations could help radiologists to include primary hepatic MFH in the differential diagnosis list.

Primary clear cell carcinoma in the liver: CT and MRI findings

To retrospectively analyze the computed tomography (CT) and magnetic resonance imaging (MRI) appearances of primary clear cell carcinoma of the liver (PCCCL) and compare the imaging appearances of PCCCL and common type hepatocellular carcinoma (CHCC) to determine whether any differences exist between the two groups. Twenty cases with pathologically proven PCCCL and 127 cases with CHCC in the Second Affiliated Hospital of Sun Yat-sen University were included in this study. CT or MRI images from these patients were retrospectively analyzed. The following imaging findings were reviewed: the presence of liver cirrhosis, tumor size, the enhancement pattern on dynamic contrast scanning, the presence of pseudo capsules, tumor rupture, portal vein thrombosis and lymph node metastasis. Both PCCCL and CHCC were prone to occur in patients with liver cirrhosis, the association rate of liver cirrhosis was 80.0% and 78.7%, respectively (P > 0.05). The mean sizes of PCCCL and CHCC tumors were (7.28 ± 4.25) cm and (6.96 ± 3.98) cm, respectively. Small HCCs were found in 25.0% (5/20) of PCCCL and 19.7% (25/127) of CHCC cases. No significant differences in mean size and ratio of small HCCs were found between the two groups (P = 0.658 and 0.803, respectively). Compared with CHCC patients, PCCCL patients were more prone to form pseudo capsules (49.6% vs 75.0%, P = 0.034). Tumor rupture, typical HCC enhancement patterns and portal vein tumor thrombosis were detected in 15.0% (3/20), 72.2% (13/18) and 20.0% (4/20) of patients with PCCCL and 3.1% (4/127), 83.6% (97/116) and 17.3% (22/127) of patients with CHCC, respectively. There were no significant differences between the two groups (all P > 0.05). No patients with PCCCL and 2.4% (3/127) of patients with CHCC showed signs of lymph node metastasis (P > 0.05). The imaging characteristics of PCCCL are similar to those of CHCC and could be useful for differentiating these from other liver tumors (such as hemangioma and hepatic metastases). PCCCLs are more prone than CHCCs to form pseudo capsules.

Hepatic Abscess Masquerading as Cholangiocarcinoma

Purpose: Highlight the importance of surgical intervention when imaging and interventional endoscopic techniques fail to delineate the nature of liver pathology. Methods: We present a thirty-seven year old Vietnamese male who presented with abdominal pain and fever. On admission his LFTs and WBC were normal. One blood culture was positive for K. Pneumoniae. Abdominal imaging revealed dilated intrahepatic ducts in the left hepatic lobe on CT. His alfafetoprotein and CEA were normal while the CA 19-9 was elevated at 879. He underwent an ERCP which showed normal intrahepatic ducts even with selective balloon occlusion cholangiography on the left side. Given the high suspicion of malignancy a left lobectomy with caudate and portal node resection was done using intra-operative ultrasound. Pathology report of the resected lesions however showed multifocal hepatic abscessess with xanthogranulomatous changes,negative for malignancy. The patient made a full recovery and was subsequently discharged. Results: This patient had a liver lesion that was associated with dilated intrahepatic ducts and elevated CA 19-9 levels. There was a high index of suspicion for cholangiocarcinoma and hence he underwent surgical exploration which showed that he had a complex abscess instead. Conclusion: Despite the advances in non invasive imaging and endoscopic intervention,exploratory surgery still has a role in the management of liver lesions.

Clinical significance of ultrasonographic imaging of the common hepatic arterial lymph node (No. 8 LN) in chronic liver diseases

In chronic liver diseases, the size of the portal lymph node and the common hepatic arterial lymph node (No. 8a LN) is often altered. The objective of this study was to investigate the relationship between the pathology of chronic liver diseases and the common hepatic arterial lymph nodes using an ultrasonographic diagnostic system. The subjects included 115 patients with hepatitis C (chronic hepatitis C, 75; liver cirrhosis C, 40), 31 patients with hepatitis B (chronic hepatitis B, 17; liver cirrhosis B, 14), 16 patients with primary biliary cirrhosis (PBC), 11 patients with autoimmune hepatitis (AIH), 29 patients with alcoholic hepatitis (Alc.LD) and 190 healthy adults with no abnormalities in liver function or inflammatory reactions (100 males and 90 females, age range 26-71 years, mean 49.2). The long and short axes of No. 8 LN were measured, and the value calculated by multiplying the two diameters was designated as the LN index (Fig. 1). The No. 8 LN appearance rate and LN index were significantly higher in the patients with hepatitis C, PBC and AIH than in the healthy subjects. When the LN index cut-off value was set to 50, alanine aminotransferase and aspartate aminotransferase were significantly higher in chronic hepatitis C (CHC) patients than in the healthy subjects. In addition, the LN and splenic indexes were significantly correlated in CHC patients, suggesting that the LX index is related to portal pressure increase with an elevation of sinusoidal pressure. The LN index after interferon therapy was significantly lower in complete responders than in non-responders. The No. 8 LN index may be closely related to the pathology of chronic liver diseases.

Incidence and risk factors for biliary sclerosis following adjuvant hepatic arterial infusion with floxuridine after hepatectomy for metastatic colorectal cancer.

3556 Background: Adjuvant hepatic arterial infusion pump chemotherapy (HAIPC) with floxuridine (FUDR) contributes to the prolonged progression-free survival of patients with resected colorectal cancer liver metastases (CRCLM). The most significant adverse event following HAIPC is biliary sclerosis (BS). We analyzed factors associated with the risk of BS. Methods: 293 consecutive pts who underwent hepatectomy followed by HAIPC and dexamethasone plus systemic therapy for CRCLM from 1991-2008 were analyzed. The incidence, demographics, clinico-pathologic factors and chemotherapy details were analyzed for their association with BS. Results: Median disease specific survival (DSS) was 83.9 months (95% CI 59.9–107.8). The incidence of BS was 5.5% (16/293). In the patients who developed BS, the median interval between the initiation of HAIPC and the development of BS was 119 days (range 13–252). The common hepatic duct was the most common site (87.5%). All patients who developed BS underwent biliary stenting with resolution of jaundice. Factors associated with BS are shown in the Table. Type of hepatectomy, type of systemic chemotherapy, portal lymph node dissection, hepatic arterial anatomy, vessels in which catheter was placed, and vessels ligated were not associated with BS. There was no difference in the median DSS between patient with BS and without BS (87.8 vs. 83.9 months, respectively p=0.707). Actual median follow-up period was 61.0 months (range 16.2–171.6) in patients with BS and 47.2 months (range 2.4–200.8) in patients without BS (p=0.316). Conclusions: BS is uncommon complication following adjuvant HAIPC and did not compromise patient survival if adequately salvaged. Technical factors related to postoperative infection and abnormal flow as well as the dose of FUDR per cycle increase the risk of BS. Factors associated with BS Patients who developed BS (n=16) Patients who did not develop BS (n=277) P value Abnormal flow scan 5 (18.8%) 3 (1.8%) 0.006 Postoperative infectious complication 8 (50.0%) 41 (14.8%) 0.002 Dose/cycle/BSA of FUDR, mg/cycle/kg, median, range 2.6 (1.4-4.9) 2.0 (0.7-3.8) 0.025 No significant financial relationships to disclose.

Salmonella in mesenteric and portal lymph nodes and faeces from normal slaughter-pigs.

Summary During the period from April to August 1969 700 normal slaughter-pigs, sampled in seven slaughterhouses in the Netherlands were examined for Salmonella spp. Examined were portal and mesenteric lymph nodes and faeces. The mean percentage of infection showed a clear increase as compared with that found in the investigation of 2100 pigs in 1960 from 25.3 % in 1960 to 30.1 % in 1969. It was concluded that the measures taken during the past few years to prevent Salmonella infections in pigs did not have the desired effect. Thirty serotypes were isolated. Of the 15 types most frequently isolated ten belonged to the 15 types most frequently isolated from humans in the Netherlands during the same period. Zusammenfassung Salmonellen in mesenterialen und pritalen Lymphknoten sowie in Faeces von normalen Schlachtschweinen In der Zeit vom April bis August 1969 wurden die Leber- und Darmlymphknoten sowie der Kot von 700 normalen Schlachtschweinen sieben verschiedener Schlachthofe der Niederlande auf Salmonellen untersucht. Der Prozentsatz infizierter Tiere zeigte einen eindeutigen Anstieg im Vergleich zu Untersuchungen von 2100 Schweinen 1960 namlich von 25,3 % im Jahre 1960 auf 30,1 % im Jahre 1969. Es wurde daraus geschlossen, das die Masnahmen zur Verhinderung der Salmonelleninfektionen der letzten Jahre nicht den gewunschten Effekt hatten. 30 verschiedene Serotypen wurden isoliert. 15 von ihnen, die am haufigsten nachgewiesen wurden, gehorten den 15 Typen an, die wahrend der gleichen Zeit in den Niederlanden am meisten beim Menschen festgestellt wurden. Resume Les salmonelles dans les ganglions lymphatiques mesenteriques et hepatiques, ainsi ques dans les excrements de porcs d'abattage normaux Dans la periode d'avril a aout 1969, on examine les ganglions lymphatiques hepatiques et intestinaux, ainsi que les excrements de 700 porcs d'abattage normaux dans sept abattoirs differents des Pays-Bas, quant a la presence de salmonelles. Le pourcentage des animaux infectes a nettement augmente, si l'on compare avec les examens de 1960 sur 2100 porcs. Ce pourcentage est de 25,3 % en 1960 et 30,1 % en 1969. On en conclut que les mesures prises ces dernieres annees pour la prevention des salmonelloses, n'ont pas eu le resultat escompte. On a isole 30 serotypes differents. Les 15 serotypes isoles le plus frequemment appartiennent aux 15 types qu'on a pu mettre le plus souvent en evidence chez les hommes aux Pays-Bas pendant cette měme periode. Resumen Salmonelas en los ganglios linfaticos mesentericos y portales, asi como en el estiercol de cerdos normales de matadero En el espacio de tiempo comprendido entre Abril y Agosto de 1969 se examinaron en cuanto a la presencia de salmonelas los ganglios linfaticos hepaticos y mesentericos, asi como el estiercol de 700 cerdos normales de abasto en siete mataderos diferentes de los Paises Bajos. El porcentaje de animates infectados mostraba un aumento inequivoco en comparacion con las pesquisas efectuadas en 1960 en 2.100 cerdos, de 25,3 % en el ano 1960 a 30,1 % en el ano 1969. De aqui se infiere que las medidas adoptadas durante los anos pasados para impedir las salmonelosis no se vieron coronadas por el efecto deseado. Se aislaron 30 serotipos diferentes. 15 de ellos, los que se identificaron con frecuencia mayor, pertenecian a los 15 tipos que durante el mismo tiempo tambien se diagnosticaron con incidencia maxima en la especie humana de los Paises Bajos.

Expression and clinical significance of EphA7 gene in hepatocellular carcinoma

Objective To quantitatively detect the expression level of EphA7 mRNA in primary hepatocellular carcinoma (HCC) and to evaluate its clinical significance. Methods Real-time fluores-cence quantitative PCR and RT-PCR were used to detect the EphA7 mRNA expression in 40 cases of HCC and their corresponding adjacent liver tissues and 10 cases of normal liver tissues. The relations between the expression of EphA7 mRNA and clinicopathological parameters were analyzed too. Results The E-phA7 mRNA was expressed in all of the 40 cases of HCC and their corresponding adjacent liver tissues and 10 cases of normal liver tissues. Real-time fluorescence quantitative PCR showed that the expression level of EphA7 mRNA in HCC (20.0711±32. 0232) was higher than that in corresponding adjacent liver tis-sues (4.5184±9.4738,P＜0.05) and normal liver tissues (4. 1764 ±4.7193,P ＜0.05). But the ex-pression level of EphA7 mRNA had no significant difference between adjacent liver tissues and normal liv-er tissues (P ＞ 0.05). The expression of EphA7 mRNA was closely correlated with histological differentia-tion, tumor thrombi in portal vein and lymph node metastasis of HCC (P ＜ 0. 05). Conclusion EphA7 mRNA expression is significantly correlated with the biological behavior of HCC. The high expression of E-phA7 may play an important role in the malignancy transformation, invasion progression and metastasis of HCC. Key words: Carcinoma; hepatocellular; EohA7; Gene expression

Lymph node evaluation is associated with improved survival after surgery for early stage gallbladder cancer

Guidelines for the current National Comprehensive Cancer Network recommend radical cholecystectomy, including hepatic resection and portal lymph node (LN) dissection, for patients with early stage gallbladder (GB) cancer. We sought to determine the survival benefit conferred by adequate LN evaluation. We used the surveillance, epidemiology and end results (SEER) neoplasm registry to identify patients who had an operation for GB cancer between 1988 and 2004. Patients were classified by stage of disease, operative procedure performed (cholecystectomy alone or radical resection), number of LNs evaluated (0, 1, >1), and receipt of radiation (RT). We included patients with T1B, T2, and T3 neoplasms who were LN positive or negative. Patients with T4 neoplasms and those with metastatic disease were excluded. Multivariate analysis included adjustment for age, race, sex, neoplasm grade, stage, operation performed, receipt of RT, and neoplasm registry. We identified 4,614 patients who underwent operative treatment for stage 1-2B GB (including T1B-T3 and LN positive or negative) cancer between 1988 and 2004. Of 4,614 patients, 9.6% (442) had radical resection, whereas 90.4% (4,172) had cholecystectomy alone. Among patients undergoing radical resection, 56% had LNs evaluated as compared with 28% of patients after cholecystectomy. For patients with T1B and T2 neoplasms who underwent radical resection, pathologic evaluation of at least 1 LN was associated with a significant improvement in median overall survival (OS) compared with those who had no LN evaluated (123 months vs 22 months; P < .0001). Radical resection with no LN evaluation provided similar OS compared with cholecystectomy alone (22 months vs 23 months; P = NS). For patients with T3 neoplasms, radical resection, including pathologic evaluation of at least 1 LN, was also associated with improved OS compared with radical resection with no LN evaluation (12 months vs 7 months; P = .0014). Again, individuals who had radical resection without LN evaluation had similar OS compared with those who had cholecystectomy alone (7 months vs 6 months; P = NS). Individuals who had radical resection with LN evaluation were more likely to receive RT than those who had radical resection without LN evaluation (33.1% vs 19.1%; P = .002). In multivariate analysis (including adjustment for RT), however, LN evaluation was still associated with a decrease in mortality compared with no LN evaluated (HR = 0.611; 95% CI = 0.484, 0.770). The pathologic evaluation of additional LN (>1) did not provide any additional benefit compared with the evaluation of a single node (HR = 0.795; 95% CI = 0.571, 1.107). Radical resection alone (without LN evaluation) did not provide any benefit over cholecystectomy alone (HR = 1.098; 95% CI = 0.971, 1.241). LN evaluation is a critical component of radical resection for GB cancer. In the absence of LN evaluation, radical resection provides no benefit over cholecystectomy alone.

Primary follicular lymphoma of the extrahepatic bile duct mimicking a hilar cholangiocarcinoma: case report and review of the literature

We report a case of a 53-year-old Asian woman who presented with abdominal pain, bloating, dysphagia, and signs of incomplete biliary obstruction, having elevated liver function tests but without increased bilirubin. Imaging studies revealed a mass measuring 6.0 x 8.0 cm at the porta hepatis extending to the right lobe of the liver and obstructing the common hepatic duct, causing mild to moderate intrahepatic biliary dilation and variable occlusion of the right portal vein. At laparotomy, an infiltrative neoplasm was noted at the hilum that involved the common bile duct, right and left hepatic ducts, and the right lobe of the liver. Extended right hepatectomy and resection of the extrahepatic bile duct and right portal vein was performed. Histologic examination revealed a high grade follicular lymphoma (grade 3A) with a predominantly follicular pattern of growth. Portal lymph nodes and a staging bone marrow biopsy showed no evidence of lymphoma. The patient subsequently received chemotherapy. Postoperative follow-up of more than 4 years has been uneventful, without disease recurrence. To the best of our knowledge, this is the third report of a primary extranodal follicular lymphoma of the extrahepatic biliary system.

Liver Resection for Metastatic Colorectal Cancer in Patients with Concurrent Extrahepatic Disease: Results in 127 Patients Treated at a Single Center

Surgical resection for patients with hepatic and extrahepatic (EHD) colorectal metastases is controversial. We analyzed our experience with hepatic resection in patients with concomitant EHD. The aims were to characterize survival, recurrence rates, and factors associated with outcome. From 1992 to 2007, 1,369 patients underwent resection of hepatic colorectal metastases, of whom 127 (9%) had concurrent resection of EHD. Survival and recurrence were compared between patients with and without EHD. Survival data were stratified by site of metastatic involvement. Variables potentially associated with survival were analyzed in univariate and multivariate analyses. Median follow-up was 24 months (range 3-152 months). The 3- and 5-year survival for patients with concomitant EHD were 47% and 26%, respectively, compared with 67% and 49%, for those without EHD (P < 0.001). Among the patients with EHD, multivariate analysis identified higher clinical risk score, incomplete resection of all EHD, EHD detected intraoperatively, and having received neoadjuvant chemotherapy to be independently associated with a worse survival. Patients with portal lymph node metastases had worse survival than those with lung or ovarian metastases. Among patients who had a complete resection of all disease, 95% recurred. Concurrent resection of hepatic and EHD in well-selected patients is associated with a possibility of long-term survival. The presence of limited and resectable EHD should not be an absolute contraindication to resection. The site of EHD and the nearly universal recurrence rate must be taken into consideration.

Effects of Baihe Recipe on expressions of vascular endothelial growth factor and p53 proteins in tumor tissues of nude mice bearing orthotopically transplanted gastric carcinoma BGC-823

To investigate the effects of Baihe Recipe, a compound traditional Chinese herbal medicine, on growth and metastasis of orthotopically transplanted gastric carcinoma and the expressions of vascular endothelial growth factor (VEGF) and p53 proteins in the tumor tissues in nude mice. Forty-five nude mice orthotopically transplanted with BGC-823 human gastric cancer cells were randomly divided into three groups: Baihe Recipe group, 5-fluorouracil (5-FU) group and untreated group. The mice in the Baihe Recipe group received intragastric administration of 0.5 mL Baihe Recipe (crude drug content was 0.2 g/mL) for 6 weeks, and the mice in the untreated group received 0.5 mL normal saline. The mice in the 5-FU group received an intraperitoneal injection of 5-FU dilution (0.2 mL, 60 mg/kg per week, for 3 weeks). All mice were sacrificed after 6-week treatment. The weights of tumor and the growth-inhibiting rate were measured and the expressions of VEGF and p53 proteins were detected by immunohistochemical method. The growth inhibition rates in the Baihe Recipe and 5-FU groups were 52.86% and 42.87% respectively. The incidence rates of metastasis to perigastric and hepatic portal lymph nodes, and to liver and peritoneum in the Baihe Recipe and 5-FU groups were lower than those in the untreated group. The metastasis rates in Baihe Recipe group, 5-FU group and untreated group were 33.33%, 35.71% and 80.00% respectively, with significant difference (P<0.05), and the expressions of VEGF and p53 proteins in tumor tissues in the Baihe Recipe group were lower than those in the untreated group and the 5-FU group (P<0.01, P<0.05). Baihe Recipe has inhibitory effects on tumor growth and metastasis of gastric cancer orthotopically transplanted in nude mice by down-regulating the expressions of VEGF and p53 proteins.

Synchronous Colorectal Liver Metastases: Triumph Of Prospective Randomized Trials Over Observational Bias Leads To Paradigm Shift

The last one and a half decade has witnessed an exciting era for the management of advanced colorectal cancer, with emergence of effective combination chemotherapy, potent biologic agents, surgical techniques for safe hepatic resection and ancillary procedures such as portal vein embolization and radiofrequency ablation. Integration of these various interventions within the context of a multidisciplinary approach has fostered an aggressive stance amongst oncologists. This approach continues to be pushed forward with attempts to ‘‘tease out’’ additional patients who may become candidate for curative hepatic resection and hence alter the natural history of their disease. In this issue, Reddy et al comprehensively review the current evidence for outcomes in the management of synchronous colorectal liver metastases (CRLM) and inquire whether a paradigm shift is necessary. Let us examine some of the controversial issues that the authors raise in this review and then determine whether a paradigm change is justified. The traditional approach to the management of the asymptomatic primary tumor with synchronous CRLM has been to resect it to avoid future obstruction, perforation or bleeding. This notion is particularly evident for rectal primaries where surgeons believe that at minimum a diverting colostomy is necessary to prevent eventual obstruction during systemic chemotherapy/chemoradiation. Given that even primary tumors are now commonly considered quite responsive to current multiagent chemotherapy, potential complications are an unlikely event as evidenced by the report from the BRiTE registry. Additional evidence will hopefully become available from the National Surgical Adjuvant Breast and Bowel Project (NSABP) C-10, a phase II trial evaluating FOLFOX6 with bevacizumab in patients who present with untreated primary colon cancer and concomitant metastatic disease not considered surgically resectable for cure. Downsizing to resectable disease has been extensively investigated by the Paul Brousse group in France. Adam et al reported their experience of a multimodality approach where patients received multiple cycles of chemotherapy and, if deemed resectable, then integrating a combination of hepatic resection, resection of extrahepatic disease, portal vein embolization, radiofrequency ablation, cryotherapy, two-stage hepatectomy, and repeat hepatectomy to achieve cure. When one critically examines this most aggressive approach for CRLM with an intention-to-treat analysis, the percentage of long-term survivors at a mean follow-up of 48.7 months was very low (3.5% alive and 2.2% alive without disease). This appears to be a long run for a short slide. When the same data are used to claim that chemotherapy will nullify the biologic effects of portal lymph node metastases, the reservations expressed by Wagman have to be echoed. Inoperable colorectal metastases may be considered a declining entity, but when one examines the published series on ‘‘conversion chemotherapy’’, patient selection is an important variable and it is clear that, the criteria for non-resectability not only differed between the studies but were often poorly defined. Until the report of the multi-institutional phase III trial by Portier et al, there had been no clear evidence from a randomized trial that adjuvant chemotherapy, either systemic or by hepatic artery infusion, added benefit over surgery alone. This trial was marred by slow accrual and inadequate sample size (173 of the planned 200 patients over a period of 10 years) but nonetheless did show The Author(s) 2009. This article is published with open access at Springerlink.com

Gut Homing Receptors on CD8 T Cells Are Retinoic Acid Dependent and Not Maintained by Liver Dendritic or Stellate Cells

Lymphocytes primed by intestinal dendritic cells (DC) express the gut-homing receptors CCR9 and alpha4beta7, which recognize CCL25 and mucosal addressin cell-adhesion molecule-1 in the intestine promoting the development of regional immunity. In mice, imprinting of CCR9 and alpha4beta7 is dependent on retinoic acid during T-cell activation. Tissue specificity is lost in primary sclerosing cholangitis (PSC), an extraintestinal manifestation of inflammatory bowel disease, when ectopic expression of mucosal addressin cell-adhesion molecule-1 and CCL25 in the liver promotes recruitment of CCR9+alpha4beta7+ T cells to the liver. We investigated the processes that control enterohepatic T-cell migration and whether the ability to imprint CCR9 and alpha4beta7 is restricted to intestinal DCs or can under some circumstances be acquired by hepatic DCs in diseases such as PSC. Human and murine DCs from gut, liver, or portal lymph nodes and hepatic stellate cells were used to activate CD8 T cells. Imprinting of CCR9 and alpha4beta7 and functional migration responses were determined. Crossover activation protocols assessed plasticity of gut homing. Activation by gut DCs imprinted high levels of functional CCR9 and alpha4beta7 on naïve CD8 T cells, whereas hepatic DCs and stellate cells proved inferior. Imprinting was RA dependent and demonstrated plasticity. Imprinting and plasticity of gut-homing human CD8 T cells requires primary activation or reactivation by gut DCs and is retinoic acid dependent. The inability of liver DCs to imprint gut tropism implies that alpha4beta7+CCR9+ T cell that infiltrate the liver in PSC are primed in the gut.