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Background: Laparoscopic simultaneous resection (LSR) of primary colorectal tumors and synchronous colorectal liver metastases (sCRLM) has been recently performed. This study aimed to evaluate the postoperative outcomes after LSR and determine the risk factors for resection surface-related complications (RSRC), such as postoperative biliary fistula and liver-transection surface abscess., Methods: Between 2009 and 2022, consecutive patients with sCRLM who underwent LSR were included. We retrospectively analyzed clinicopathological data, including intraoperative factors and postoperative outcomes. The difficulty level of all liver resections was classified according to the IWATE difficulty scoring system (DSS). We then performed univariate and multivariate analyses to identify the risk factors for RSRC., Results: Of the 112 patients, 94 (83.9%) underwent partial hepatectomy and colorectal surgery. The median DSS score was 5 points (1-11), with 12 (10.7%) patients scoring ≥ 7 points. Postoperative complications were observed in 41 (36.6%) patients, of whom 16 (14.3%) experienced severe complications classified as Clavien-Dindo grade IIIa or higher. There was no postoperative mortality. The most common complication was RSRC (19 patients, 17.0%). Multivariate analysis identified American Society of Anesthesiologists (ASA) classification ≥ 3 [odds ratio (OR) 10.3, 95% confidence interval (CI) 1.37-77.8; P = 0.023], DSS score ≥ 7 points (OR 5.08, 95% CI 1.17-20.0; P = 0.030), and right-sided colectomy (OR 4.67, 95% CI 1.46-15.0; P = 0.009) as independent risk factors for RSRC. Postoperative hospital stays were significantly longer for patients with RSRC than for those without RSRC (22 days vs. 11 days; P < 0.001)., Conclusion: Short-term outcomes of LSR for patients with sCRLM were acceptable in an experienced center. RSRC was the most common complication, and high-difficulty hepatectomy, right-sided colectomy, and ASA classification ≥ 3 were independent risk factors for RSRC., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A 70-year-old man was diagnosed with hepatocellular carcinoma (HCC) with portal vein invasion and lung metastases, for which atezolizumab plus bevacizumab (ATZ/BEV) was initiated. After two months, computed tomography revealed tumor growth accompanied by ascites, right ventricular invasion, exacerbation of the lung metastases, and main portal vein invasion. However, continuation of ATZ/BEV caused remarkable size reductions in all lesions, finally resulting in the disappearance of the vascular invasion and lung metastases after nine cycles of treatment. The tumor growth was considered to reflect pseudoprogression, which is difficult to distinguish from hyperprogression. We herein report a remarkable HCC case of pseudoprogression on ATZ/BEV.

The patient is a 70's man. Esophagogastroduodenoscopy and contrast-enhanced CT scan of the abdomen revealed gastric cancer, 2 liver metastases, and peritoneal dissemination. He was diagnosed with unresectable advanced gastric cancer and received 5 courses of chemotherapy(CapeOX plus T-mab). The primary tumor size had reduced, and liver metastases and peritoneal dissemination were not detectable, so laparoscopic distal gastrectomy and partial hepatectomy were performed. Histopathological findings revealed no viable cancer cells in either the primary tumor or the hepatic resection site, and the histological response was Grade 3. The patient has been recurrence-free for 6 months since the surgery. Even in Stage Ⅳ gastric cancer with multiple distant metastases, long-term survival may be expected by conversion surgery after response to chemotherapy.

Metformin is a commonly used drug for the treatment of diabetes. Accumulating evidence suggests that it exerts anti-cancer effects in many cancers, including colorectal cancer. However, the underlying molecular mechanisms of colorectal cancer metastasis remain unclear. Colorectal cancer cell lines were treated with metformin, and cell proliferation, invasion, and migration were analyzed in vitro. The relationship between metformin and the AMPK-mTOR axis was assessed by Western blot analysis and transfection with small interfering RNA. A colorectal cancer xenograft mouse model was used to observe the effects of metformin on liver metastasis. Immunohistochemical analysis was performed on liver metastatic tumors. In in vitro experiments, metformin significantly inhibited the proliferation, migration, and invasion only in HCT116 and SW837 cells, but not in HCT8 and Lovo cells. Only in HCT116 and SW837, a change in AMPK-mTOR expression was observed in a dose-dependent manner. In colorectal cancer xenograft mice, the liver metastatic rate (10% vs. 50%, p = 0.05) and the number of liver metastatic nodules (0.1/body vs. 1.2/body, p = 0.04) were significantly lower in the metformin group. Tumor proliferation and EMT were decreased and apoptosis was promoted only in metastatic liver tumors of mice treated with metformin. The molecular mechanism of the anti-cancer effects of metformin involves repression of mTOR pathways via AMPK activation. Moreover, the differences in metformin sensitivity depend on the response of the AMPK-mTOR pathway to metformin. Our study provides a theoretical basis for the anti-metastatic treatment of colorectal cancer using metformin., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Lymphoepithelioma-like cholangiocarcinoma (LELCC) is a rare intrahepatic tumor. There are usually no specific physical findings, and the tumors are often diagnosed incidentally and are frequently large-sized at diagnosis. The imaging findings of LELCC resemble those of hepatocellular carcinoma (HCC). Tumors are often found in large-sized and advanced at diagnosis, and the main treatment of the disease is surgical resection. Herein, we report treating a patient with early stage LELCC by radiofrequency ablation (RFA). We diagnosed this tumor in a 27-year-old Chinese female with a history of chronic hepatitis B (CHB). Based on the findings of blood examination, abdominal ultrasonography, and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI), this tumor was diagnosed as suspected HCC. Ultrasound-guided percutaneous tumor biopsy and RFA were performed at the same time. The histopathological findings finally revealed the diagnosis of LELCC. To the best of our knowledge, this is the first report, in the English-language literature, of the treatment of LELCC by RFA; we suggest that RFA might be a candidate treatment for small-sized early stage LELCC.

Here, we present the case of a 47-year-old woman with liver masses having distinct borders, which were located approximately 13 cm from the left hepatic lobe S4, as visualized on a CT scan. Hepatocellular carcinoma(HCC)was suspected from these contrast findings. Additionally, we found nodules in the right upper lobe of the lung and in the left apex. Although test results for hepatitis B and C viruses were negative, the α-fetoprotein(AFP)level was elevated. The tumor was diagnosed as a HCC with suspected multiple lung metastases. Thereafter, a resection was performed for the HCC. However, multiple recurrences were observed. Arterial embolization using transcatheterization was performed thrice 5 months after resection. Further, 6 months after resection, lenvatinib therapy was initiated as the pulmonary nodule increased in size. One year after the operation, a recurrent neoplastic lesion in the liver was detected on the contrast-enhanced MRI. Since the earlier treatment with transcatheter arterial embolization proved to be minimally effective, we opted for arterial injection chemotherapy with cisplatin plus 5-FU for approximately 3 months. The contrast-enhanced CT revealed that the lesion became a low absorption lesion in the liver outside the central area, and the AFP also decreased rapidly. Therefore, the therapy was considered effective. As a side effect of arterial injection chemotherapy, the patient developed a duodenal ulcer. However, after treating the ulcer, a pulmonary metastasectomy was performed and no obvious recurrence was noted. Typically, for treatment of extrahepatic metastases of HCC, drugs such as sorafenib or lenvatinib that have molecular targets are selected according to a treatment algorithm based on liver cancer practice guidelines. However, these drugs were not effective in this case, whereas arterial injection chemotherapy showed satisfactory therapeutic effect on the recurrences in the liver. Although there was a complication of duodenal ulcer, this case report highlights that combined modality therapy including arterial injection chemotherapy is successful in treating HCC.

Background: Copper (Cu) and zinc (Zn) are essential nutrients and cofactors of enzymatic reactions with their binding partner. Metallothionein (MT) plays an important role in protecting against heavy metals and oxidative injury, however it may also portend drug resistance and a worse prognosis for hepatocellular carcinoma (HCC) patients. The aim of this study was to determine the amount of Cu, Zn, Cu/Zn and MT in evaluating a group of patients with HCC, including those treated with lenvatinib., Methods: We enrolled 175 patients with HCC (139 men, 36 women; mean age 71.1 years; hepatitis C virus n = 85, hepatitis B virus n = 19, hepatitis C virus and hepatitis B virus n = 2, non-alcoholic steatohepatitis n = 39, alcohol n = 25, others n = 5; Child-Pugh A n = 141, Child-Pugh B n = 30, Child-Pugh C n = 4; Barcelona clinic liver cancer (BCLC) stage 0 n = 38, stage A n = 56, stage B n = 39, stage C n = 38, stage D n = 4). We evaluated the associations between Cu, Zn and MT. The study outcome was liver cancer-specific survival. Moreover, we treated 12 HCC patients with lenvatinib and investigated the changes in MT during lenvatinib therapy., Results: The serum level of Cu was positively correlated with alanine aminotransferase and the BCLC stage. The serum level of Zn decreased concordant with liver disease progression. Patients with a Cu/Zn ratio≥0.999 had significantly improved rates of survival when compared to patients with a Cu/Zn ratio<0.999 (45.3 vs. 30.1 months, p<0.001). MT was significantly correlated with the Cu/Zn ratio and increased after the administration of lenvatinib. Using multivariate Cox regression analyses, it was determined that the Cu/Zn ratio (hazard ratio [HR]: 1.442, p = 0.008), alpha-fetoprotein (HR: 1.000, p<0.001) and BCLC stage (HR: 2.087, p<0.001) were independent predictors of survival., Conclusions: The Cu/Zn ratio could serve as a useful predictive marker for survival in cases of HCC. MT levels increased in HCC patients receiving lenvatinib therapy, and maybe a predictor of reduced survival., Competing Interests: The authors have declared that no competing interests exist.

Background: Although R0 surgery is recommended for stage IV colorectal cancer, the degree of required lymphadenectomy has not been established. The aim of this study was to investigate the prognostic impact of high ligation (HL) of the feeding artery and the number of retrieved lymph nodes after R0 surgery for colorectal cancer and synchronous colorectal cancer liver metastasis (CRLM)., Methods: This was a multi-institutional retrospective analysis of patients with colorectal cancer and synchronous CRLM who had R0 surgery between January 1997 and December 2007. Clinical and pathological features were compared in patients who underwent HL and those who had a low ligation (LL). Kaplan-Meier analysis was performed to estimate the effect of HL on overall survival (OS). The impact of several risk factors on survival was analysed using the Cox proportional hazards model., Results: Of 549 patients, 409 (74·5 per cent) had HL. Median follow-up was 51·4 months. HL significantly improved the 5-year OS rate (58·2 per cent versus 49·3 per cent for LL; P = 0·017). Multivariable analysis revealed HL to be a significant prognostic factor compared with LL (5-year mortality: hazard ratio (HR) 0·68, 95 per cent c.i. 0·51 to 0·90; P = 0·007). In subgroup analysis, the positive effect of HL on OS was greatest in patients with lymph node metastasis., Conclusion: HL of the feeding artery was associated with improved OS in patients with colorectal cancer and synchronous CRLM after R0 surgery., (© 2020 The Authors. BJS Open published by John Wiley & Sons Ltd on behalf of British Journal of Surgery Society.)

Background/aim: Anti-EGFR antibodies or bevacizumab comprise first-line treatment for patients with RAS wild-type colorectal liver metastases (CLM). Which marker better predicts efficacy, early tumor shrinkage or morphologic response, still remains unclear., Patients and Methods: We retrospectively evaluated 155 patients with KRAS exon 2 wild-type CLM treated with bevacizumab (BEV group) or anti-EGFR antibodies (EGFR group). Three radiologists independently assessed early tumor shrinkage (ETS) and early optimal morphologic response (EOMR) from baseline and first follow-up CT scan., Results: Patients with ETS had longer progression-free survival (PFS) than those without ETS [hazard ratio (HR)=0.69] and ETS tended to be observed in the EGFR group, while patients with EOMR had longer PFS than those without EOMR (HR=0.64) and EOMR tended to be observed in the BEV group., Conclusion: Among patients with KRAS exon 2 wild-type CLM, EOMR and ETS may predict better PFS, especially in patients treated with bevacizumab and anti-EGFR antibodies, respectively., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The patient was a 65-year-old man who had been previously diagnosed with chronic hepatitis B, but the patient had discontinued treatment while in his thirties. The patient was admitted to the emergency department after losing consciousness due to abdominal pain. Emergency contrast CT was performed in the shock state, and the diagnosis was hemorrhagic shock due to rupture of hepatocellular carcinoma(HCC). Emergency TAE was performed, and hemostasis was successful due to left hepatic arterial embolism. The tumor was confined to the liver lateral area and it was judged to be resectable curatively, upon state restoration. Ten days after TAE, lateral segmentectomy of the liver was performed. Pathological findings indicated moderately differentiated HCC, mostly necrotic and partially viable. He was discharged on 11POD. On 69POD, the patient reexperienced sudden abdominal pain after lunch. The abdominal pain continued while emergency contrast CT was performed at the time of visit in the shock state. Recurrence of multiple dissemination via high-absorption ascites was found around the largest tumor nest with lower left diaphragm diameter of 15cm, and it was judged that the HCC disseminated recurrence had ruptured. Emergency TAE was performed again, and hemostasis was successful by embolization of the left gastric artery and lower left diaphragm artery. Subsequently, tumor growth slowed after initiating oral administration of sorafenib, and the patient is alive 8 months after re-TAE.

Background: Cancer stem cells (CSCs) have enhanced mechanisms of protection from oxidative stress. A variant form of CD44 (CD44v), a major CSC marker, was shown to interact with xCT, a subunit of cystine-glutamate transporter, which maintains high levels of intracellular reduced glutathione (GSH) which defend the cell against oxidative stress. Sulfasalazine (SSZ) is an inhibitor of xCT and was shown to suppress the survival of CD44v-positive stem-like cancer cells both in vitro and in vivo. To find the dose of SSZ which can safely reduce the population of CD44v-positive cells in tumors, a dose-escalation study in patients with advanced gastric cancer was conducted., Methods: SSZ was given four times daily by oral administration with 2 weeks as one cycle. Tumor biopsies were obtained before and after 14 days of administration of SSZ to evaluate expression of CD44v and the intratumoral level of GSH., Results: Eleven patients were enrolled and received a dosage from 8 to 12 g/day. Safety was confirmed up to a dosage of 12 g/day, which was considered the maximum tolerated dose. Among the eight patients with CD44v-positive cells in their pretreatment biopsy samples, the CD44v-positive cancer cell population appeared to be reduced in the posttreatment biopsy tissues of four patients. Intratumoral GSH levels were also decreased in two patients, suggesting biological effectiveness of SSZ at 8 g/day or greater., Conclusions: This is the first study of SSZ as an xCT inhibitor for targeting CSCs. Reduction of the levels of CD44v-positive cells and GSH was observed in some patients, consistent with the mode of action of SSZ in CSCs.

Case 1 involved an 87-year-old woman. She had increased serum amylase levels, and intraductal papillary mucinous adenocarcinoma( IPMC)in the accessory pancreatic duct was diagnosed following various medical examinations. Radical surgery is possible for such a lesion when there are no issues detected following evaluation. The patient and her family decided that she should undergo surgery; therefore, pancreatoduodenectomy was performed for Stage III IPMC. Various morbidities required medical treatment, but she was finally discharged from hospital 89 days after surgery. She has had no recurrence 2 years and 11 months after surgery. Case 2 involved a 90-year-old man. He had liver dysfunction, and progressive hepatocellular carcinoma( HCC)was diagnosed based on computed tomography(CT)findings. The tumor size reduced to around 10 cm with enforced 2 degrees TACE. The patient and his family chose for him to undergo radical surgery; therefore, right trisegmentectomy of the liver was performed for Stage III HCC. He was discharged from the hospital 22 days after surgery, and has had no recurrence for the past 1.6 years. More careful examination and a general assessment are necessary to make decisions on surgical indications in super elderly patients.

Background: The aim of this study was to clarify the influence of hepatic fibrosis on metachronous liver-specific recurrence in colorectal cancer (CRC) patients who underwent colorectal surgery with curative intent. Non-alcoholic steatohepatitis (NASH) is closely associated with hepatic fibrosis (HF). The number of patients who suffer from NASH is increasing because of the consumption of high-calorie diets. It remains unclear how much of an impact NASH and HF have on the development of liver metastasis in CRC., Methods: Patients who underwent curative surgical resection for CRC between 2000 and 2011 were included in this study. We evaluated the progression of HF by the non-alcoholic fatty liver disease fibrosis score (NFS) based on preoperative blood test results, age, body mass index, and diabetes mellitus. Patients were grouped according to high (fibrotic liver; FL) or low (normal liver; NL) NFS. The influence of HF on hepatic recurrence was assessed by survival analyses., Results: A total of 953 CRC patients were enrolled, comprising 293 in stage I, 327 in stage II, and 333 in stage III. The patients included were categorised as FL (77) or NL (876). The hepatic recurrence rates were 5.3% in the NL group and 10.4% in the FL group (P=0.02), whereas the overall recurrence rates were 16.0% in the NL group and 20.7% in the FL group (P=0.03). The 5-year liver-specific recurrence-free survival rate in the FL group was significantly poorer than that in the NL group (FL 89.1%, 95% confidence interval (CI) 78.4-94.7 vs NL 96.0%, 95% CI 94.3-97.2, log-rank test P<0.01). Multivariate analysis demonstrated that HF significantly promoted liver-specific recurrence compared with NL (HR=2.98, 95% CI 1.23-7.21; P=0.02)., Conclusion: HF is a valuable prognostic factor for hepatic recurrence after curative surgical resection of CRC.

We present a case of a 74-year-old woman treated with maintenance dialysis for chronic renal failure. She had undergone intravascular treatment of lower limb arteriosclerosis obliterans 3 times. Low anterior resection was performed for rectal cancer StageⅡ, but adjuvant chemotherapy was not administered after the operation. S5/S6 partial hepatectomy was performed after confirming a liver metastatic recurrence 7 months after the first operation. Tumor pathology examination of the resected specimen revealed necrosis in most parts of the specimen. Residual primary lesion similar to adenocarcinoma tissue was found only in a small part of the specimen. Artery wall embolism and recanalization image with cholesterol crystals indicated a Grison's lesion, which was considered to have likely developed into tumor necrosis from the embolization. Spontaneous regression of a malignant tumor is a rare condition found 1 case in 6-10 ten thousand cases. In hepatocellular carcinoma, secondary tumor infarction from tumor invasion and tumor thrombus may occur. The present case was a metastatic liver cancer, in which the cholesterol crystal embolism possibly reached the tumor necrosis. The suggested cause of the cholesterol crystal embolism in this case was intravascular treatment related.

Chemotherapy is not effective for metastatic hepatocellular carcinoma(HCC); however, prolonged survival can be expected for patients with multiple metastases who are treated with surgical resection in addition to chemotherapy. We present a case of a 36-year-old woman with hepatitis B who developed HCC with multiple intrahepatic and lung metastases after undergoing resection of HCC in 2010 in Canada. The patient returned to Japan for additional treatment. She was treated with TACE therapy and systemic chemotherapy, but her lung metastases did not improve. The patient's PIVKA-Ⅱ levels remained moderately elevated after initiation of chemotherapy. Therefore, we performed surgical resection of the lung metastases in March 2014. Five months later, the patient received additional TACE therapy when an isolated metastasis was found in the residual liver. Since then, no recurrence of HCC has been found, and the patient's PIVKA-Ⅱ levels have remained in the normal range. This case demonstrates that surgical resection for multiple lung metastases is possible in select patients.

The prognosis of Stage IV b pancreatic cancer is extremely poor; the mean survival time is 2-4 months. However, new anticancer agents can improve the outcome of advanced pancreatic cancer. We present the case of a 50-year-old female patient with Stage IV b pancreatic head cancer with invasion to the superior mesenteric vein(SMV)and multiple liver metastases. The patient received S-1 as first-line chemotherapy. Three months later, a further CT scan showed reduction of the pancreatic tumor, disappearance of the liver metastases, and reduction in SMV invasion. Therefore, a subtotal stomach-preserving pancreatoduodenectomy with partial SMV resection was performed. Following surgery, the patient received S-1 chemotherapy again. However, lung metastasis appeared. Despite the initiation of gemcitabine(GEM)treatment, the patient developed metastases in other parts of the lung and the abdominal wall. She died 46 months after surgery, but it is noteworthy that the liver metastases were manageable. The combination of chemotherapy and surgery was effective in prolonging survival in this patient with Stage IV b pancreatic head cancer.

Transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) are effective treatments for hepatocellular carcinoma (HCC). However, the extent of treatment depends on hepatic functional reserve. L-Carnitine is a vitamin-like substance and several reports have described the usefulness of L-carnitine supplementation in cases of cirrhosis, with confirmed effectiveness against refractory hepatic encephalopathy. On the other hand, we have previously reported that in patients who underwent TACE or RFA, administration of branched-chain amino acids (BCAAs) pre-intervention significantly reduced inflammatory reactions. We first determined serum levels of total, free, and acyl-carnitine before and at 7 d after performing TACE in 10 HCC patients. We administered levocarnitine (L-carnitine chloride, a biologically active form of carnitine) at 900 mg/d to 69 consecutive HCC patients hospitalized to undergo TACE and/or RFA, and compared changes in blood test values with those in 119 consecutive patients not administered this drug. Sixty-seven patients had a history of using BCAAs at the time of admission. We found that after 7 d of TACE, serum levels of total and acyl-carnitine are significantly decreased. On comparing the four groups, the carnitine+BCAA, carnitine-alone, and BCAA-alone groups showed significantly higher values for changes in NH3 when compared with the non-dosed group. The decrease in albumin (Alb) was significantly suppressed in the carnitine+BCAA and BCAA-alone groups. We also conducted the same examinations in a subset of patients classified as Child-Pugh class A, and noted the same trends. Administration of levocarnitine and/or BCAAs during invasive treatments reduced blood NH3 concentrations and suppressed decreases in Alb.

We report the case of a 69-year-old male patient with diagnoses of sigmoid colon cancer, ascending colon cancer, and metastatic liver cancer. We performed sigmoidectomy, right hemicolectomy, and central venous port placement. Because the liver metastasis was multifocal, chemotherapy was first initiated and then hepatic resection was performed. However, during chemotherapy, ileus, with a peritoneal dissemination to the small intestine, developed. Small intestine resection and radiation therapy to the pelvic region of the transition were further performed. Thereafter, obstructive jaundice due to obstruction of the bile duct in the hilar area developed, and therefore, we inserted a biliary stent. However, 2 years 9 months after the first medical examination, this patient died of colon cancer. The guidelines above, still chemotherapy developed, treatment policy of recurrent colorectal cancer, have recommended surgical resection with respect to what resectable as local therapy. This case shows that combination therapy with chemotherapy, surgical therapy, radiation therapy, and local therapy such as biliary stenting, is useful.

A 60-year-old woman receiving treatment for diabetes underwent laparoscopic-assisted low anterior resection and was diagnosed as having rectosigmoid cancer in January 2010( pSS, n2[ +], sM0 fStage IIIb, mutant-type K-ras). She refused adjuvant chemotherapy. In July, after surgery, chest-abdominal-pelvic computed tomography( CT) scans showed bilateral lobe multiple liver metastases and right lobe lung metastases. We recommended oxaliplatin and capecitabine (CapeOX) plus bevacizumab( BV) chemotherapy or surgery. The CapeOX plus BV regimen was initiated at the patient's request. After 8 cycles of chemotherapy, a partial response was observed in the metastatic liver tumors and stable disease was observed in the lung metastases. As hypertension appeared after 16 cycles of chemotherapy, we switched the treatment to CapeOX. After 10 cycles of CapeOX, the chemotherapy was changed to capecitabine at the patient's request owing to the development of grade 2 chronic peripheral neuropathy. Chest-abdominal-pelvic CT scans after 32 cycles of this regimen revealed shrinkage of the multiple liver metastases. The patient has been receiving treatment as an outpatient. Surgical resection should be considered for patients with initially unresectable colon cancer with liver and/or lung metastases if systemic chemotherapy is effective.

A 35-year-old woman underwent hemicolectomy and RFA for ascending colon cancer with multiple liver metastases in February, 2005. She received postoperative hepaticarterial infusion chemotherapy with 5-FU, and systemic hemotherapy with UFT for 10 months after the operation. A local recurrence of the anastomosis was detected in March, 2006, and she underwent a resection for it. This was followed by 6 courses of adjuvant chemotherapy with modified FOLFOX6. Because multiple liver metastases and lymph node metastases were detected in March, 2007, she received RFA and 6 courses of adjuvant chemotherapy with modified FOLFOX6 again. Liver metastases disappeared but lymph node metastases still remained. Therefore, she received 4 courses of bevacizumab plus modified FOLFOX6. The metastatic lesions disappeared and were judged to be CR. Therefore, she was followed-up with the oral administration of UFT. Metastases of liver and lymph nodes of the mediastinum were detected in May, 2008, for which she received 4 courses of bevacizumab plus FOLFIRI2. Because the effects of the chemotherapy were judged to be CR, she continued with 4 courses of the same regimen. The regimen was discontinued due to diarrhea, and she therefore began to receive 4 courses of bevacizumab plus LV/5-FU regimens. CR has been maintained at present, over 7 years after the initial surgery.

The patient was a 68-year-old man. Because sigmoid colon cancer and metastatic liver cancer was diagnosed in August 2009, an indwelling central venous port and sigmoid colon resection were implemented. The metastatic liver cancer was a huge tumor occupying the right hepatic lobe and caudate lobe. In consideration of the risk associated with the resection and the possibility of early recurrence, the postoperative chemotherapy was selected. He underwent 9 courses of bevacizumab (Bev)+FOLFOX. The tumor was observed to reduce but continued to occupy the right lobe and caudate lobe. At this point, the surgical treatment was selected because the tumor has been shrunk and there is no appearance of new metastases. In order to preserve residual liver function, he underwent percutaneous transhepatic portal embolization and then resection of the right lobe of the liver in February 2010. Although the Bev+FOLFOX treatment was started again after surgery as adjuvant chemotherapy, the metastatic liver cancer recurred in the remnant liver in August 2010. Because it was about 6 months from the first recurrence of liver resection, we decided to continue chemotherapy immediately without resection. However, the chemotherapy was insufficient to shrink the tumor, which increased because it was present at 3 locations in the liver. Therefore, partial hepatectomy at the 3 locations with positron-emission tomography was performed in February 2011. Since then, chemotherapy has not been performed in patients, and there is no recurrence as of March 2012. In the guideline for the treatment of liver metastasis of colorectal cancer, even though chemotherapy is currently developed, the surgical procedure is recommended for patients who are responsive to local therapy. If the cancer recur immediately after resection, it is difficult to decide whether to re-resect. We report the case in which the tumor-free status can be observed as a result of a combination of systemic chemotherapy and local therapy.

A 60-year-old man who had had a subtotal esophagectomy for esophageal cancer was given the diagnosis of hepatic metastases ten months after his operation. Systemic chemotherapy was stopped after a short time because of adverse effects. He refused to continue any other systemic chemotherapy. He was going to receive hepatic arterial infusion chemotherapy(HAI)with the prospect of having less systemic effects. Combination regimen of 5-FU with low-dose CDDP was administered for five days every three weeks. Hepatic metastases decreased markedly without adverse effects. The tumor was well controlled for two years until occlusion of hepatic artery. Radiation therapy and liver resection were performed subsequently. The patient lived more than 4 years after the diagnosis of hepatic metastases. HAI can be a treatment of choice for esophageal cancer when metastasis is limited to the liver.

Purpose: We retrospectively evaluated whether combined use of chemoembolization expands ablative zone sizes created by radiofrequency (RF) ablation in patients with small hepatocellular carcinomas (HCCs)., Materials and Methods: Fifty-seven patients treated with single RF ablation for solitary HCC measuring ≤2 cm were assessed. RF ablation alone was done in nine patients and in 48 patients following chemoembolization, with an interval of 0 days in 6, 1-14 days in 27, 15-28 days in 6, and ≥4 weeks in 9. Ablative zone sizes, disappearance of tumor enhancement, and creation of sufficient ablative margins (>5 mm) were evaluated on contrast-enhanced computed tomography (CT) images., Results: Both mean long-axis (4.2-4.7 vs. 3.6 ± 0.4 cm, p < 0.04) and short-axis (3.3-3.8 vs. 2.3 ± 0.5 cm, p < 0.03) diameters were expanded significantly when RF ablation was done until 4 weeks after chemoembolization than with RF ablation alone. Tumor enhancement disappeared in all patients. Frequency of achieving sufficient ablative margins was significantly higher when RF ablation was done until 4 weeks after chemoembolization than with RF ablation alone (74.0-83.3 vs. 22.2 %, p < 0.05)., Conclusion: Ablative zones created by RF ablation with chemoembolization become larger than RF ablation alone, leading to secure ablative margins.

A 61-year-old complaining of anorexia and general fatigue was admitted to our hospital for further examination. She was diagnosed as advanced sigmoid colon cancer with multiple metastases of lung, liver, and left hydronephrosis. Since curative surgery was not deemed possible, we started chemotherapy with bevacizumab/FOLFOX6 (bi-weekly drip infusion). After the 6th course, colonoscopy revealed a significant tumor reduction and changes to the scar tissues. CT did not reveal a complete disappearance, but found some reductions in metastases of lung and liver. Sigmoidectomy and lymph node resection (D1) were performed. We did not disappeared any dissemination and the histological diagnosis revealed a complete disappearance of cancer cells in the main tumor. She was discharged 13 days after surgery, following chemotherapy which included bevacizumab and XELOX. The chemotherapy using bevacizumab/FOLFOX6 is a candidate for the standard treatment strategy for inoperable advanced colon cancer. Herein we report this rare case with a review of the literature.

Background: The evolution of diagnostic procedures has resulted in an increase in early detection of pathologically T1 (pT1) colorectal cancer (CRC). However, the risk factors affecting long-term outcomes of patients with pT1 CRCs have been unclear. The aim of the present study was to identify risk factors for postoperative recurrence and overall survival in patients with pT1 CRC., Methods: Between January 1990 and January 2003, a total of 284 patients with pT1 CRC underwent radical surgery in the authors' institution. The impact of clinicopathological factors on postoperative recurrence and overall survival was estimated by univariate and multivariate analysis., Results: The median follow-up period was 55 months (interquartile range: 47.1 months). Postoperative recurrence occurred in 8 (2.8%) patients. The overall 5-year and 10-year disease-free survival rates were 98.4 and 92.7%. Multivariate analysis showed the presence of lymphatic invasion only was an independent risk factor for postoperative recurrence in pT1 CRC patients (hazard ratio: 11.622; P = 0.003). The 5-year and 10-year disease-free survival rates of the patients in N-ly- group, the N-ly + group, and the N+ group were 99.5%/98.2% and 96.3%/75.2%, and 93.3%/93.3%, respectively. Additionally, 4 of the 8 recurrences were found more than 5 years after the operation., Conclusions: Lymphatic invasion was an independent risk factor for recurrence in pT1 CRC patients.

We report a case of rectal cancer diagnosed in 2001, which enforced a rectal low anterior resection. Then, metastatic liver cancer and metastatic lung cancer recurred and we enforced an operation for both. Furthermore, metastatic lung cancer recurred again and enforced chemotherapy with radiation and systemic chemotherapy for approximately seven years. The metastatic lung cancer was reduced now in 2011, so that the chemotherapy has not been used since then. In our case, we mainly performed a surgical and radiation therapy for a local recurrent site therapy in the first half because we did not have much choice for a systemic chemotherapy like we have now. In the later half, we mainly performed a systemic chemotherapy to control the local recurrent site. A treatment policy for colon cancer recommends a surgical treatment by the guidelines, or even though chemotherapy has been developed at present, if a local therapy is practical. There were many cases where metastases had occurred right after surgery so a local site therapy by excision was good at all unconditionally. However, as a result of our case in a local site therapy combined with whole body chemotherapy, we report here that a long- term survival was obtainable. We also include a brief literature review.

The patient was a 55-year-old man with a large hepatic tumor measuring 12 × 12 cm in the left lobe. To obtain the histological diagnosis, the target liver biopsy was performed. Histologically, the tumor revealed as a neuroendocrine carcinoma. After the diagnosis, he received the chemotherapy (CTX) with etoposide and cisplatin. Serum levels of NSE and the tumor size were decreased after the first course of CTX. We here report a case of primary hepatic neuroendocrine carcinoma treated with CTX following the diagnosis by the needle biopsy.

We report on a patient who presented in 2000 with multiple hepatic metastasis of sigmoid colon cancer. We chose the hepatic arterial infusion chemotherapy for this case since there was no effective chemotherapy at that time. After the intermittent chemotherapy for one and half years, we recognized that the tumor became smaller, though it couldn't cure completely. Therefore, two years after the first medical examination, we underwent a hepatic left lobectomy and S8 hepatectomy. No recurrence has been observed until now. As a recent treatment of the hepatic metastasis of colon cancer, there is a tendency to choose chemotherapy before operation. However, there are some cases in which chemotherapy isn't acceptable because of its side effect. Besides chemotherapy, we report another treatment (the hepatic arterial infusion chemotherapy) which has a similar effectiveness with fewer side effects for the hepatic metastasis of colon cancer.

An 85 years old man was performed systemic chemotherapy after the palliative gastrectomy for unresectable gastric cancer with multiple liver metastases. The response evaluation revealed a progressive disease after 4 courses of first-line S-1 therapy and 3 courses of second-line paclitaxel therapy. At this point, metastatic lesions were still localized in the liver, so hepatic arterial infusion chemotherapy (HAI) was introduced as third-line therapy. Despite the marked reduction of all target lesions and reduced tumor marker level after 25 weeks of HAI without any adverse event, novel multiple metastatic lesions had appeared in the lung and celiac LNs, resulted in the cessation of HAI. Then he had suffered grade 3 mucositis oral and anorexia throughout 2 courses of fourth-line S-1 + CDDP therapy and fifth-line docetaxel therapy. Considering that the goal of treatment for unresectable gastric cancer patients is to delay developing symptoms and to prolong their life with the least adverse event, HAI could be an effective therapy.

We report a patient with hepatic metastasis of descending colon cancer who underwent hepatic arterial infusion chemotherapy using 5-fluorouracil (5-FU) and CDDP, with an indwelling catheter and port system by GDA coil method. Since the tumor became smaller after five months, we decided to follow her up as an outpatient. Considering the possibility of its recurrence, the catheter-port system remained in her. Two and half years later, the recurrent hepatic metastasis was recognised and the hepatic arterial infusion chemotherapy was fulfilled again. The tumor obviously reduced and the same treatment was continued. However, he was hospitalized with a complaint of hematemesis. Upper gastrointestinal endoscopy revealed a projection around the splitting catheter in the duodenal bulb. Therefore, we embolized with coil under angiographic guidance in order not to bleed from the artery and removed the port. With this experience, special attention for the catheter port system must be taken if one considers a long-term treatment. Thereby, we report on the complications of the catheter-port system.

A 65-year-old woman, who had been operated by subtotal esophagectomy for esophageal cancer, was diagnosed as multiple liver metastases and celiac lymph node metastases one year after operation. The response evaluation revealed progressive disease after she had been suffering from nausea and anorexia throughout 2 courses of FP therapy. She refused to continue any more systemic chemotherapy, so we proposed an alternative to her, hepatic arterial infusion chemotherapy (HAI) for multiple liver metastases and radiation therapy for celiac LN metastases. Despite the marked reduction of all target lesions and maintenance of tumor marker level below the normal limits after 50 Gy of irradiation and 5 courses of HAI, a novel solitary tumor had appeared in S3 of the liver and an abdominal pain during HAI had occurred at the end of 5th course of HAI. The angiogram revealed occlusion of hepatic artery, suggesting that the emergence of new lesion was attributed to unequal distribution of the drug. Six weeks after a cessation of HAI, a subsequent CT scan showed a rapidly enlarged new lesion in S3, so that a surgical resection for this tumor was performed. The patient is alive without recurrence more than 10 months after the diagnosis of multiple liver metastases (2 months after the last surgery).

Objective: The purpose of this study was to establish a new formula predicting liver metastasis in patients with colorectal cancer (CRC)., Methods: Nine previously reported predictive markers for liver metastasis and/or prognosis (COX-2, dysadherin, E-cadherin, beta-catenin, Ki-67, p53, laminin5gamma2, matrilysin and MUC-1) were immunohistochemically investigated in 439 consecutive patients with CRC. We tried to determine the combination of molecules which best predicted liver metastasis. A formula for predicting liver metastasis was constructed using a training cohort comprising 150 cases, and applied to a validation cohort comprising 190 cases and another comprising 99 cases from an outside hospital., Results: A combination of dysadherin, E-cadherin and matrilysin was identified to be best for predicting liver metastasis (area under the curve value, 0.807). The predictive formula: 3x dysadherin score [0 for low expression (50%)] + 4x E-cadherin score [0 for preserved (>80% of tumor cells positive) or 1 for reduced (30%)] was able to discriminate patients with liver metastasis in the training cohort with a sensitivity of 85.7% and a specificity of 58.9%. The discriminative capacity of the formula was validated in the first cohort with a sensitivity of 87.0% and a specificity of 66.5%, and in the second cohort with a sensitivity of 80% and a specificity of 60.0%., Conclusions: We have established a formula for predicting liver metastasis in patients with CRC, and confirmed that it has a high sensitivity potentially useful for clinical application., (Copyright 2008 S. Karger AG, Basel.)

A 64-year-old woman was diagnosed with multiple hepatic metastases from sigmoid colon cancer. She underwent resection of the colon and catheter insertion into the hepatic artery for arterial infusion in August 2006. She was then treated with postoperative combination chemotherapy consisting of UFT and CPT-11, 5-FU, l-LV. UFT was administered orally at 400 mg/body/day every day and CPT-11 was injected at 100 mg/body/week, 5-FU at 750 mg/body/week, and l-LV at 300 mg/body/week for 8 continuous weeks. After 2 months of the chemotherapy, the metastatic liver tumors disappeared. So hepatic arterial infusion with the same regimens was injected once every month 4 more times. Oral UFT was administered every day. After 6 months of the combined chemotherapy above, we judged the effects of the chemotherapy to be a complete response. Then the chemotherapy was followed by oral UFT only. As severe nausea and vomiting were seen in this patient with an initial dose of 150 mg/body/week of CPT-11 at first, we reduced the dose of CPT-11 to 100 mg/body/week. From then, outpatient care was possible because no severe events were observed. Combined chemotherapy consisting of oral UFT and CPT-11, 5-FU and l-LV by hepatic arterial infusion is suggested to be a new and effective treatment for multiple liver metastases from colorectal cancer.

A 70-year-old Japanese man presented to our hospital with a 1-month history of progressive general fatigue and anorexia. A physical examination revealed severe anemic condition, mild persistent splenomegaly, and no palpable surface lymph nodes. He had pleural effusion and ascites, though no malignant cells were detected in the effusion. He eventually died without any diagnosis of his disease. Immunohistochemical staining of his tumor after autopsy showed atypical cells that were negative for epithelial membrane antigen (EMA), keratin (AE1/3), keratin-20, vimentin, factor VIII, leukocyte common antigen (LCA/T200; CD45), myeloperoxidase (MPO), terminal deoxynucleotidyl transferase (TdT), lysozyme, CD1a, CD3, CD4, CD10, CD15, CD20 (L26), CD21, CD23, CD34, CD43, CD56, CD68, CD79a, CD138, and EBER-1 in situ. Only a few scattered cells expressed CD30, but they showed no staining for anaplastic large-cell lymphoma kinase (ALK). A few scattered cells expressed S-100 antigen and the majority of cells dominantly expressed dendritic cell-associated antigens (CD35, FDC, Ki-M1p). In conclusion, we found this unknown primary tumor to be consistent with a follicular dendritic cell tumor with anaplastic features.

A number of receptor tyrosine kinases (RTKs) are involved in angiogenesis. TSU-68 (SU-6668) was developed as an inhibitor of RTKs involved in VEGF, bFGF and PDGF signaling, which then inhibits endothelial cell proliferation. We investigated the antitumor effects of TSU-68 against human colon cancer xenografts in male SCID mice and its anti-angiogenic activity using a dorsal air-sac (DAS) assay. TSU-68 was administered orally at a dose of 200 mg/kg twice daily. Mice bearing human colon carcinoma, HT-29, or WiDr xenografts were treated for 16 days. To determine the effect on hepatic metastasis, cell suspensions of HT-29 or WAV-I were injected into the spleen of mice on day 0, and mice treated for 28 days starting from day 1. For the DAS assay, HT-29, WiDr or WAV-I cells suspended in PBS at 2 x 10(7) cells/Millipore chamber were implanted subcutaneously into SCID mice, which were then treated from day 0 to 5, On day 6, the anti-angiogenic effects were assessed. Results indicated that TSU-68 significantly inhibited the growth of subcutaneous tumors. In the hepatic metastasis model, liver weights of the TSU-68-treated group were significantly reduced, compared to those of control mice. In the DAS assay, the angiogenic indices of the treated groups were significantly decreased for HT-29, WiDr and WAV-I tumors, with T/C ratios of 13.4, 50 and 35.3%, respectively. As TSU-68 significantly inhibited tumor growth and liver metastasis formation of human colon cancer xenografts, probably through anti-angiogenic activity, this agent may be useful for the treatment of colon cancer.

Objective: The objective of our study was to investigate the effect of different iodine concentrations in contrast materials on the depiction of hypervascular hepatocellular carcinomas (HCCs) by MDCT., Subjects and Methods: This prospective study involved 100 consecutive patients with chronic liver disease, including 27 patients with hypervascular HCCs. The first 50 patients received 100 mL of iopamidol at a concentration of 370 mg I/mL (group A) and the subsequent 50, 100 mL at 300 mg I/mL (group B); in both groups, the contrast material was administered at a rate of 3.0 mL/sec. Unenhanced scanning and four-phase enhanced scanning at 25, 40, 60, and 180 sec after the start of contrast injection were performed. The enhancement of the aorta, liver, and portal vein was measured during each phase. In addition, tumor-to-liver contrast was calculated for the 27 patients with hypervascular HCCs. Of the 27 patients with hypervascular HCCs, 15 were in group A and 12 were in group B., Results: During all phases, aortic enhancement was significantly greater in group A than group B (p < 0.01). Hepatic enhancement was significantly greater in group A than group B at 60 and 180 sec (both p < 0.01). There was no significant difference in hepatic enhancement between the two groups at 25 and 40 sec. Tumor-to-liver contrast was significantly greater in group A than group B during the late arterial phase (40 sec, p = 0.02), although there was no significant difference at 25, 60, and 180 sec., Conclusion: Contrast materials with higher iodine concentration are more effective for depicting hypervascular HCCs on MDCT during the late arterial phase.

We report a case of BCL-6-positive B cell lymphoma with human herpesvirus 8 (HHV-8) infection. A human immunodeficiency virus-infected patient developed a diffuse large B cell lymphoma, which was found exclusively in the liver and spleen with the absence of lymphadenopathy and effusion in any body cavities. The lymphoma cells were composed of medium to large-sized cells positive for CD20, CD45, and BCL-6, and negative for epithelial cell membrane antigen, CD30, CD45RO, and CD138/syndecan-1, suggesting a germinal center B cell origin. The patient was serologically positive for HHV-8, and HHV-8 was detected in the liver biopsy tissue both by polymerase chain reaction and by immunohistochemistry for HHV-8-encoded latency-associated nuclear antigen. Other HHV-8-associated diseases, such as Kaposi's sarcoma, primary effusion lymphoma, or multicentric Castleman's disease were not detected in the patient. Chemotherapy was effective and reduced the size of the lymphoma dramatically. This is the first case report of a germinal center B cell-originating lymphoma with HHV-8 infection.

Liver metastases from colorectal cancer easily invade the Glisson's triad and sometimes have intrabiliary tumor growth. This behavior is by no means rare, and causes the cut end of the Glisson's triad to be positive for cancer. We report here a 72-year-old Japanese man with a medical history of ascending colon cancer in whom enhanced computed tomography (CT) showed a low-density mass in the caudate lobe of the liver and dilatation of the peripheral intrahepatic bile duct. He underwent right hemihepatectomy and caudate lobectomy. The resected specimen showed a polypoid tumor in the bile duct lumen, with minimal invasion of the liver parenchyma; the tumor was similar to cholangio-carcinoma. Histological findings proved it to be well-differentiated adenocarcinoma. Immunochemically, the tumor cells were positive for cytokeratin (CK) 20, but negative for CK7, and we finally diagnosed him with intrabiliary polypoid growth of liver metastasis from colonic cancer. For complete surgical resection, it is very important to diagnose intrabiliary tumor growth. However, we could not diagnose it preoperatively in spite of the CT detecting an intrabiliary polypoid tumor, because the CT revealed no extrabiliary tumors in the liver parenchyma. We have to pay attention to the fact that CT rarely demonstrates only intrabiliary growth without extrabiliary tumors.

Recent autopsy studies have clarified the frequency of lymph node (LN) metastases from hepatocellular carcinoma (HCC). However, LN metastases commonly occur in advanced and poorly differentiated HCC and are very rare in small HCC. We encountered a patient with skip LN metastases from a small HCC, 10 mm in diameter. An intra-abdominal tumor adjoining the duodenum was detected by follow-up ultrasonography for viral hepatitis C. Computed tomography showed, in addition to the tumor bordering the duodenum, a small low-density area of the liver (S6), 2 cm in diameter, and a swelling of LN adjacent to the common hepatic artery. Upper gastrointestinal rentogenography revealed a compression of the duodenal second portion without irregularity of the mucosa. Our pre-operative diagnosis was duodenal gastrointestinal stromal tumor with LN metastasis and HCC or liver metastasis. However, laparotomy proved them to be LN metastases from a small HCC and partial hepatectomy and LN dissection were performed. The patient is doing well 22 months after surgery with no signs of recurrence. In the cases of HCC with LN metastases, the prognosis is generally very poor. However, in small HCC, the clinical characteristics are not fully evaluated. In treatment, we have to keep LN metastases, particularly skip LN metastases, in mind, even in cases of small HCC.

Unlabelled: In a previous report we noted that cyclooxygenase-2 (COX-2) expression in clinical colorectal cancer is closely related to liver metastasis and survival. The aim of the present study was to clarify the role of COX-2 in liver metastasis and to examine the potential for a selective COX-2 inhibitor as a novel therapeutic agent in the treatment of colorectal cancer., Materials and Methods: COX-2 expression of 6 kinds of human colon cancer cell lines, with various potentials for liver metastasis, were assessed by Western blot and reverse transcriptase polymerase chain reaction (RT-PCR). In human tumor xenografts/severe combined immune-deficient (SCID) mouse, we examined the effects of a selective COX-2 inhibitor (JTE-522) on tumor growth or liver metastasis of HT-29, a highly-metastatic cell line, or on COLO205, a non-metastatic cell line. The effect of JTE-522 on vascular endothelial growth factor (VEGF) expression and the activity of matrix metalloproteinases (MMPs) in HT-29 and COLO205 were assessed by enzyme-linked immunosorbent assay (ELISA) and gelatin zymography, respectively., Results: COX-2 was expressed in all metastatic cell lines but not in the non-metastatic lines. JTE-522 prevented the liver metastasis of HT-29, but not the subcutaneous growth of HT-29 and COLO205 in SCID mice. In vitro, JTE-522 suppressed VEGF expression, but did not affect MMP production in HT-29; an inhibitory effect was not found in COLO205., Conclusion: A selective COX-2 inhibitor of JTE-522, was found to prevent liver metastases of colon cancer by suppressing VEGF expression, and therefore, COX-2 possibly plays an important role in liver metastasis of human colon cancer via the regulation of VEGF expression.

Background/purpose: Radiofrequency ablation (RFA) and microwave coagulation therapy (MCT) have been gaining acceptance as a standard method in the management strategy of liver cancer, for reasons of minimally invasive techniques and effective results. We present our experience of RFA and MCT in patients with liver cancer, and analyze retrospectively the advantages and disadvantages of both of the percutaneous and laparoscopic approaches., Methods: Thirty-two consecutive patients (23 men and 9 women) with 19 hepatocellular carcinomas (HCC), 12 metastatic liver cancers, and recurrent cholangiocellular carcinoma (CCC), were enrolled in this study. Out of these 32 patients, as a prior laparotomy, 19 underwent hepatectomy, colectomy, gastrectomy or cholecystectomy, and 15 were treated with the laparoscopic approach, 17 treated with the percutaneous approach, and 2 treated with the combined approach of those two. All of these procedures were carried out under general anesthesia with ultrasound guidance. Seven and 30 days after these procedures, an assessment helical computed tomography was done., Results: No sign of the residual tissues was noted in all patients except only one case., Conclusions: The percutaneous approach was thought to be a more practical and less invasive method regardless previous laparotomy. For the laparoscopic approach, tumors located at the hepatic surface or margin were preferable candidates.

Purpose: Epidemiologic studies indicate that the use of nonsteroidal anti-inflammatory drugs, which inhibit cyclooxygenase activity, reduce the risk of colorectal cancer. In addition, several studies demonstrate increased expression of cyclooxygenase-2 in human colorectal cancer tissues. However, the role of cyclooxygenase-2 expression in colorectal cancer has not yet been fully established. The aim of this study was to clarify the clinicopathologic significance of cyclooxygenase-2 expression in human colorectal cancer., Methods: A total of 232 surgically resected colorectal cancer specimens were analyzed immunohistochemically with the use of a murine anti-human cyclooxygenase-2 monoclonal antibody. Cyclooxygenase-2 expression was then compared with clinicopathologic background and survival outcome., Results: Cyclooxygenase-2 was expressed in the cytoplasm of the cancer cells but not in normal epithelium. Cyclooxygenase-2 expression was noted in 71.6 percent (166/232) of the cancer patients and correlated significantly with histologic type (P = 0.033), depth of invasion (P = 0.016), pathologic stage (P = 0.020), and metachronous liver metastasis (P = 0.001). Multivariate analysis for factors associated with metachronous liver metastasis showed that cyclooxygenase-2 expression was one of the independent risk factors, second only to lymph node metastasis. Patients with cyclooxygenase-2 expression showed a significantly poorer outcome compared with those without cyclooxygenase-2 expression (P = 0.002)., Conclusion: Cyclooxygenase-2 expression in the primary lesion may be a useful marker for evaluating prognosis and liver metastasis in patients with colorectal cancer.

Background/aims: The aim of this study is to clarify the limitations of hepatectomy for advanced hepatocellular carcinoma., Methodology: Fifty-six patients with Stage 4 hepatocellular carcinoma were retrospectively studied, and the prognostic factors were both univariately and multivariately analyzed. The VI score, which was defined as the degree of portal vein invasion (VP) multiplied by the degree of intrahepatic metastases (IM), was introduced as a new prognostic indicator., Results: A univariate analysis revealed the following significant variables: hypertension, esophageal varices, Child's classification B or C, a bilirubin value of over 1.0 mg/dL, a albumin value of below 3.5 g/dL, a GOT value of over 100 IU/L, an AFP value of over 1000 ng/mL, a history of tumor rupture, Stage 4B, a tumor size of over 5 cm, VP3, IM3, and the VI score of no less than 6. A multivariate analysis demonstrated the following 4 variables to be independent prognostic indicators: a Stage of 4B, a VI score of no less than 6, a Child's classification of B or C, and a tumor size of over 5 cm. Furthermore, no long-term survivors were found in patients with either Stage 4B HCC or a hepatocellular carcinoma having a VI score of more than 6. At the present time, either Stage 4B or a hepatocellular carcinoma having a VI score > or = 6 are considered to be factors which means the limitation of hepatectomy alone. Furthermore, an advanced hepatocellular carcinoma with either poor liver function or a hepatocellular carcinoma with a size of over 5 cm should be carefully evaluated before determining its appropriateness for hepatectomy., Conclusions: The VI score is therefore suggested to be a useful prognostic indicator for determining the surgical indications for advanced hepatocellular carcinomas.

Background: Assessment of clinicopathologic characteristics and postoperative prognoses for patients with multicentric hepatocellular carcinoma (HCC) is important to determine not only a need to operate, but also an appropriate treatment after hepatic resection., Study Design: Between May 1990 and April 1998, among 116 patients with an initial hepatectomy for HCC measuring 3 cm or less in maximum diameter, 34 patients had multicentric HCC (MC group), and 82 patients had single nodular HCC (SN group). To clarify the clinicopathologic features of patients in the MC group versus the SN group, we compared both the clinicopathologic parameters and the postoperative prognosis after curative hepatectomy between the two groups., Results: The percentages of patients positive for hepatitis B surface antigen and hepatitis C virus antibody were not significantly different between the two groups. No differences were noted in pathologic characteristics of the main tumor or tumor markers. On the other hand, in the MC group, the percentage of patients evaluated in a Child's classification as either B or C was significantly higher (p < 0.05) than that of patients in the SN group, indicating that patients with multicentric HCC have a poor hepatic functional reserve. Both survival and disease-free survival of patients in the MC group who underwent a curative hepatectomy did not differ statistically from those in the SN group., Conclusions: Our results indicate that hepatic resection is useful, even for patients with multicentric HCC, if a curative hepatectomy can be performed and liver function can be saved, despite their poor hepatic functional reserve.

Objective: The aim of this study was to clarify the role of telomerase activity in hepatocellular carcinoma (HCC)., Methods: Specimens from both HCC and noncancerous liver were obtained from 39 patients with HCC using a 14-gauge biopsy needle immediately after laparotomy. Telomerase activity was determined using a telomeric repeat amplification protocol assay. The 3+ of telomerase activity in HCC was defined as a high telomerase group, and 2+ or less of HCC telomerase activity was defined as a low telomerase group. In noncancerous liver, 2+ or more of telomerase activity was defined as an increased telomerase group, and 1+ or less of telomerase activity was defined as a nonincreased telomerase group. The correlation between telomerase activity in HCC or noncancerous liver and clinicopathological factors, including prognosis, was investigated., Results: Telomerase activities in HCCs were 0 in one patient, 1+ in two, 2+ in seven, and 3+ in 29 patients. The disease-free survival rate in the high telomerase group was significantly worse than that in the low telomerase group. The des-gamma-carboxy prothrombin level in a high telomerase group (median, 330 mAU/ml) was significantly higher than that in the low telomerase group (median, 150 mAU/ml). A multivariate analysis revealed that higher TNM stage, high telomerase activity in HCC, female gender, and high alpha-fetoprotein value were independent significant factors related to be early recurrence. The incidence of multicentric HCC occurrence in the increased telomerase group (53.3%) tended to be higher than that in the nonincreased telomerase group (27.3%)., Conclusion: A high telomerase activity in HCC correlated with the potential of HCC to be more malignant, which was expressed as both a high level of des-gamma-carboxy prothrombin and an earlier recurrence after hepatectomy than that of HCC with a low telomerase activity.

The role of thymidine phosphorylase (TP), an angiogenic factor, in hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to clarify the significance of TP in HCC. Thirty-seven patients with HCC, who underwent hepatectomy, were included. The TP activity in both cancerous and non-cancerous parts of livers were measured by an enzyme-linked immunosorbent assay. Another 11 patients without HCC were used to evaluate the TP activity in the non-cancerous parts of livers. Both the cancerous and non-cancerous TP activities were clinico-pathologically investigated with special reference to the multicentric occurrence of HCCs and the degree of liver fibrosis; consisting of normal, fibrosis and cirrhosis. The TP activity in the cancerous part was 94.6 +/- 70.2 U/mg protein, while that in non-cancerous parts of the liver was 80.9 +/- 48.8 U/mg protein. No significant difference was observed. The TP activity in the cancerous part did not correlate with any clinicopathological variables, such as tumor differentiation, portal vein invasion, intrahepatic metastases and prognosis. However, the TP activity in the non-cancerous parts of the liver correlated with the degree of fibrosis (normal/fibrosis/cirrhosis = 34:74:90 U/ mg protein, respectively). Furthermore, regarding the correlation between TP activity in the non-cancerous parts and the simultaneously multicentric occurrence of HCC, the TP activity in the multicentric group (n = 8; 121 U/mg protein) was significantly higher than that in the non-multicentric group (n = 29; 70 U/mg protein). The TP activity in the non-cancerous parts increased in proportion to the degree of liver fibrosis. Furthermore, it is suggested that the higher TP activity in the non-cancerous part is related to the multicentric occurrence of HCCs.

We present herein the case of a sclerosing hemangioma of the liver which was extremely difficult to differentiate from liver metastasis of rectal cancer, in a 67-year-old woman. All the radiological findings were compatible with liver metastasis; however, marginal pooling of the tumor revealed by computed tomographic angiography and magnetic resonance imaging scans was inconsistent with a diagnosis of liver metastasis. At laparotomy, the tumor was macroscopically unusual in that it was yellowish elastic-hard with a very clear margin, and thus, it did not have the appearance of a metastatic tumor. Mile's operation and a partial hepatectomy were performed, followed by an uneventful postoperative course and no signs of recurrence. The carcinoembryonic antigen (CEA) level in the peripheral blood was not elevated at any time. The postoperative pathological diagnosis was a rare hepatic tumor, namely, a "sclerosing hemangioma," based on the findings of cellular fibrous stroma containing vascular channels with flattened endothelial cells. Preoperatively differentiating between sclerosing hemangioma and a metastatic liver tumor from colorectal cancer may be very difficult; however, this case demonstrated some interesting characteristics, namely, the serum CEA level was not elevated, marginal pooling of the tumor was found in the enhanced radiological findings, and the tumor was macroscopically unusual. Therefore, the possibility of sclerosing hemangioma should be borne in mind when considering the differential diagnosis of patients suspected of having colorectal liver metastasis. A preoperative biopsy should be carried out and when a laparotomy is performed under the misdiagnosis of colorectal liver metastasis, it is advisable that either an intraoperative needle biopsy or a frozen histological analysis be undertaken to avoid unnecessary extended hepatic resection of this rare benign hepatic tumor.

Background: Matrix metalloproteinase-9 (MMP-9) has recently been reported to be related to cancer cell invasion. This study was performed to clarify the expression of MMP-9 in surgically resected intrahepatic cholangiocarcinoma (IHCC)., Methods: In 37 patients with IHCC who underwent a surgical resection, the expression of MMP-9 and the clinicopathologic characteristics of MMP-9-positive IHCC were investigated. The expression of MMP-9 was immunohistochemically detected in 16 (43%) of 37 IHCC. The patients were divided into MMP-9 (-) IHCC (n = 21), MMP-9 (+) IHCC (n = 12), and MMP-9 (++) IHCC (n = 4)., Results: The survival rate after surgical resection in patients with MMP-9 (-), (+), and (++) IHCC, was 66%, 39%, and 0% at one year, 50%, 32% and 0% at 3 years, respectively (P = .001). The incidence rate of lymph node metastasis was 6 (28%) of 21 in MMP-9 (-) patients, 7 (58%) of 12 in MMP-9 (+) patients and 4 (100%) of 4 in MMP-9 (++) patients. The incidence rate of lymph node metastasis increased in proportion to an increase in the expression of MMP-9 in IHCC (P = .02). Recurrence in the lymph node was more common in patients with MMP-9 (+) and (++) cancers than in those with MMP-9 (-) cancers., Conclusions: The expression of MMP-9 in IHCC was a prognostic factor related to lymph node metastasis.

Background/aims: Little has been documented to differentiate between recurrence originating from microscopic residual tumor cells and recurrence due to metachronous multicentric origin of hepatocellular carcinoma (HCC). The aim of this study was to clarify the risk factors of HCC recurrence closely related to residual tumor cells., Methodology: A retrospective review of hepatic resections for HCC during the period between April 1985 and April 1997 was undertaken at a University Hospital with a long history of hepatectomy for HCC. Three hundred and thirteen HCC patients without any definite multicentric recurrence, who underwent hepatectomy, were retrospectively investigated. Main outcome measures were: (Study 1) Risk factors for recurrence were univariately and multivariately investigated among various clinicopathological variables, including the vi factor as a new indicator of the potential malignancy of HCC (i.e., the presence of both microscopic portal vein invasion and intrahepatic metastasis). (Study 2). The risk factors for recurrence were then analyzed according to the period of recurrence., Results: (Study 1) Independent risk factors were: (tumor factors) a positive vi factor, alpha-fetoprotein > 100 ng/ml, and poorly differentiated histology; (host factors) albumin < 3.8 g/dl, the presence of diabetes mellitus, platelet count < 14 x 10(4)/microliter, Y-globulin fraction > 20%. In those risk factors, the relative risk of the vi factor (2.6) was the largest. (Study 2) Within 1 year after hepatectomy, only tumor factors, including the vi factor and poorly differentiated histology, were significant risk factors, tumor factors were significant only up to 2 years after hepatectomy, and thereafter only host factors were significant., Conclusions: The risk factors for non-multicentric recurrence of HCC are considered to be a positive vi factor, alpha-fetoprotein, and poorly differentiated histology, and the vi factor is considered to be a new prognostic indicator expressing the potential malignancy of HCC such as invasion and metastasis.

Background: Postoperative liver failure is a life-threatening complication after hepatic resection. Because of recent advances in liver surgery technique and a more stringent patient selection, mortality after hepatic resection has steadily decreased, but its incidence still ranges from 10% to 20%. The factors linked to postoperative liver failure in major hepatic resection in the modern era should be reevaluated., Study Design: Of 80 patients with viral markers (hepatitis C viral antibody or hepatitis B surface antigen) who underwent major hepatic resections (no less than bisegmentectomies) for hepatocellular carcinoma between 1990 and 1996, 7 patients (8.8%) died of postoperative liver failure within 6 months after hepatectomy. The cause of liver failure was analyzed based on both the preoperative data and the intraoperative findings. In addition, since all the patients who died of liver failure underwent a right hepatic lobectomy, a further data analysis was also done in 47 patients who underwent a right lobectomy of the liver. A volumetric analysis by CT was then done to evaluate the remnant liver volume., Results: Between the patients with liver failure and those without liver failure who underwent a right lobectomy, there were no significant differences in preoperative data or intraoperative findings. Volumetric analysis revealed that the remnant liver volume of patients who died of liver failure was significantly smaller than that of patients who lived (p = 0.008). The incidence of liver failure in patients with a remnant liver volume of less than 250 mL/m2 was 7 of 20 (38%), while it was 0 of 27 in patients with a liver volume of no less than 250 mL/m2 (p = 0.0012). The only significant risk factor for liver failure in patients with a remnant liver volume of less than 250 mL/m2 was diabetes mellitus (p = 0.0072)., Conclusions: The expected remnant liver volume appears to be a good predictor for liver failure in patients who undergo a right lobectomy of the liver. In patients with diabetes mellitus and an expected remnant liver volume of less than 250 mL/m2, a major hepatectomy should be avoided. Careful patient selection based on volumetric analysis in major hepatectomy cases could help prevent the occurrence of postoperative liver failure.