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Major hepatectomy combined with extrahepatic bile duct resection has gained acceptance as a standard radical procedure for hilar cholangiocarcinoma. Here, we describe an operative technique, "taping of the right hepatic artery behind Calot's triangle", for assessing the resectability of hilar lesions for which left-sided hepatectomy is planned. Briefly, after retracting the gall-bladder anteriorly, the lateral peritoneum of the hepatoduodenal ligament is incised longitudinally (3-4cm in length) behind Calot's triangle and just to the left of the fissure of Ganz. By dividing the adipose tissue, the distal portion of the right hepatic artery is identified and secured with tape. Any suspicious tissues around the right hepatic artery should be submitted to frozen-section analysis. If no cancer cells were found, the planned resection goes ahead. Conversely, if they were found, the resection should be abandoned. Since 2003, 14 patients for whom left-sided hepatectomy was planned for hilar cholangio-carcinoma involvement, underwent this technique. Three patients were judged to have irresectable tumors and the planned resection could be avoided. In conclusion, this simple technique, isolation of the right hepatic artery behind Calot's triangle before starting resection, should be applied to all hilar malignancies when a left-sided hepatectomy is planned.

BACKGROUND/AIMS This study aimed to evaluate whether wedge resection or S4bS5 resection was the more beneficial hepatectomy procedure for patients with locally advanced gallbladder carcinoma. METHODOLOGY A retrospective analysis of 70 patients who underwent either wedge resection (n=58) or S4bS5 resection (n=12) for locally advanced gallbladder carcinoma without clinically evident liver metastases was conducted. Clinicopathological characteristics, histological features of hepatic invasion and surgical outcomes were analyzed. RESULTS Sixteen patients had tumors with hepatic invasion. Of the 16 patients with hepatic invasion, 6 had direct liver invasion alone and 10 had portal tract invasion featuring intrahepatic stromal invasion (n=5), intrahepatic lymphatic invasion (n=4) and intrahepatic venous invasion (n=l). The hepatectomy procedure was not significantly associated with survival after resection (p=0.518) as patients who underwent wedge resection showed an overall cumulative 3-year survival rate of 74% compared with 60% for patients who underwent S4bS5 resection. The Cox proportional hazard regression analysis revealed that pT classification (p

In the present retrospective study, we tested the hypothesis that neoadjuvant chemotherapy (NAC) as a treatment for patients with colorectal carcinoma liver metastases (CRLM) may reduce intrahepatic micrometastases. The incidence and distribution of intrahepatic micrometastases were determined in specimens resected from 63 patients who underwent hepatectomy for CRLM (21 treated with NAC and 42 without). In addition, the therapeutic efficacy of NAC was evaluated histologically. Intrahepatic micrometastases were defined as microscopic lesions spatially separated from the gross tumor. The distance from these lesions to the border of the hepatic tumor was measured on histological specimens and the density of intrahepatic micrometastases (number of lesions/mm2) was determined in regions close to (

To overcome the conventional method based on Compositional Semantics, the Analogical Mapping Method was developed. Implementing this method requires a translation method based on sentence patterns. Although a word-level pattern-based translation system already exists in Japanese-English machine translation, this paper describes the new phrase-level pattern-based translation system. The results of translation experiments show that the quality of phrase translation is still low. However, these problems are to be resolved in our future work.

Background/aims Ribonucleotide reductase M1 (RRM1) is a key molecule for gemcitabine resistance. This study evaluated the immunohistochemical expression of RRM1 in resected specimens of intrahepatic cholangiocarcinoma (ICC) and investigated the efficacy of gemcitabine-based neoadjuvant chemotherapy in relation to RRM1 expression in tumors. Methodology A retrospective analysis was conducted on 34 consecutive Japanese patients who underwent resection of ICC. Of the 34 patients, 2 were treated with neoadjuvant chemotherapy consisting of gemcitabine 800mg/m2 every 2 weeks to address extrahepatic tumor extension. Expression of RRM1 in tumor specimens was assessed using immunohistochemistry and was classified as either positive or negative. Results RRM1-positive expression was detected in 19/34 (56%) tumor specimens. Two patients were treated with gemcitabine-based neoadjuvant chemotherapy; one had a tumor specimen showing RRM1-positive expression and showed a 14% tumor reduction rate (stable disease); another patient had a tumor showing RRM1-negative expression and showed a 68% tumor reduction rate (partial response). Surgical procedures planned before administration of neoadjuvant chemotherapy were performed in both patients. Conclusions Neoadjuvant chemotherapy with gemcitabine for locally advanced ICC was well tolerated and did not impair planned surgical resections. Tumor expression of RRM1 may determine the efficacy of gemcitabine-based chemotherapy for patients with ICC.

P53-binding protein 1 (53BP1) is an early DNA damage response-protein that is rapidly recruited to sites of DNA double-strand breaks. The presence of 53BP1 nuclear foci can be considered as a cytologic marker for endogenous double-strand breaks reflecting genomic instability. This study aimed to clarify the early DNA damage response mediated by 53BP1 in tumor specimens of ductal resection margins and to elucidate its predictive value for clinically evident local recurrence at ductal stumps in 110 patients undergoing resection for extrahepatic cholangiocarcinoma. The ductal resection margin status was classified as negative (85 patients), positive with carcinoma in situ (14 patients), or positive with invasive carcinoma (11 patients). The nuclear staining pattern of 53BP1 was evaluated by immunofluorescence. TUNEL analysis was used to calculate apoptotic index. Ductal margin status was the only independent risk factor for local recurrence (P=0.001). The cumulative probability of local recurrence at 5 years was 10%, 40% and 100% in patients with negative ductal margins, positive with carcinoma in situ and positive with invasive carcinoma, respectively (P

AIM: To define the rational extent of regional lymphadenectomy for gallbladder cancer and to clarify its effect on long-term survival. METHODS: 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. RESULTS: 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%). CONCLUSION: 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.

Ewing sarcoma/primitive neuroectodermal tumors (ES/PNETs) may arise in bone or soft tissue; however, these tumors rarely originate in the stomach. To the best of our knowledge, only four cases have previously been reported in the English-language literature. A 41-year-old Japanese woman was admitted with abdominal pain and underwent gastrectomy to remove the primary tumor. Immunohistochemistry, chromosomal karyotype and molecular analysis using reverse transcription-polymerase chain reaction were performed in the tumor specimens obtained. Tumor cells showed positive immunoreactivity for CD99, vimentin, CD117 (c-kit), S100, chromogranin A and synaptophysin. The tumor was a gastric ES/PNET with the EWS-FLI1 fusion gene translocation t(11;22)(q24;q12). Multiple repeat metastasectomies, as well as multi-agent chemotherapy and radiotherapy were performed for recurrent disease. Despite treatment, the patient succumbed due to progressive disease 110 months after the initial surgery for gastric ES/PNET. A review of the reported cases suggests that patients with gastric ES/PNETs have an unfavorable prognosis following resection due to the high propensity of these tumors to metastasize. Thus, multimodal treatment approaches including surgery, as well as multi-agent chemotherapy and radiotherapy may provide a survival benefit for patients with gastric ES/PNETs.

The aim of this study was to evaluate the effect of surgical procedures on the serum levels of 5-fluorouracil (5-FU) in patients undergoing S-1 treatment for pancreaticobiliary malignancy.From January 2003 through December 2008, 27 chemotherapy-naive patients who underwent a surgical procedure for pancreaticobiliary malignancy received S-1 chemotherapy for unresectable or recurrent disease. The primary site of disease was: the extra hepatic bile duct (n=10); gallbladder (n=8); pancreas (n=6); or ampulla of Vater (n=3). The surgical procedure was: pylorus-preserving pancreaticoduodenectomy (PPPD) (n=6); combined major hepatic and bile duct resection (n=6); bilioenteric anastomosis (n=4); or exploratory laparotomy (n=11). S-1 (80-120 mg/day) was administered orally twice daily for 28 days, followed by 14 days without therapy. Subsequently, the serum levels of 5-FU were measured using the HPLC-UV method.The median number of cycles administered per patient was 6 (range, 2-13). Although grade 3 watery eye developed in one patient, neither grade 4 toxicities nor treatment-related deaths were observed. The overall response rate was 19%, the median overall survival time was 9 months, and the 1-year cumulative survival rate was 11%. The maximum levels of 5-FU in the sera of individual patients differed significantly according to the surgical procedure (Kruskal-Wallis test; p=0. 0049); the patients who underwent PPPD had the highest 5-FU levels, as compared with the other patients (Mann-Whitney test; p= 0.003).The type of operative procedure appears to influence the serum levels of 5-FU in S-1-treated surgical patients with pancreaticobiliary malignancy. Given the possibility of elevated levels of 5-FU in the sera of patients who are treated with S-1 after PPPD, adverse events must be monitored carefully in this cohort.

The current study sought to clarify whether intracapsular venous invasion and extratumoral venous invasion confer different prognostic significance in patients undergoing hepatectomy for hepatocellular carcinoma.A retrospective study of 275 consecutive patients who underwent hepatectomy for hepatocellular carcinoma was conducted. Extratumoral venous invasion was defined as gross or microscopic involvement of vessels within the peritumoral liver tissue, whereas intracapsular venous invasion was defined as microscopic involvement of vessels within the fibrous tumor capsule. The median follow-up time was 64 months.Vascular invasion was found in 104 (38%) of the 275 patients. Intracapsular venous invasion was present in 16 patients and extratumoral venous invasion observed in 88 patients. Overall cumulative survival rates were 64% at 5 years and 45% at 10 years. Vascular invasion was a strong prognostic factor by univariate (p = 0.0001) and multivariate (p = 0.006) analyses. Survival after hepatectomy was significantly worse in patients with extratumoral venous invasion (cumulative 10-year survival rate of 28%) than in patients with intracapsular venous invasion (cumulative 10-year survival rate of 70%; p = 0.0082).Extratumoral venous invasion adversely influences survival after hepatectomy for hepatocellular carcinoma compared to intracapsular venous invasion.

We hypothesized that expression of multidrug resistance-associated protein 2 (MRP2), a major cisplatin transporter, may determine the efficacy of cisplatin as a treatment for patients with hepatocellular carcinoma (HCC). A prospective analysis was conducted of 49 consecutive patients who underwent resection for HCC (16 patients treated with cisplatin-based neoadjuvant chemotherapy and 33 patients treated without neoadjuvant chemotherapy). Expression of MRP2 in resected specimens was assessed by immunohistochemical and Western blot analyses. The extent of tumor necrosis was assessed histologically in the greatest dimension of the tumor specimen from each patient. The median percentage of tumor necrosis was 81% (range: 0-100%) and complete tumor necrosis was found in 3 patients. Overexpression of MRP2 was detected in 24/46 (52%) tumor specimens. In 16 patients treated with cisplatin, tumor size and dose of cisplatin did not correlate with tumor necrosis of the resected specimens (P=0.706 and P=0.555, respectively). Of 13 tumor specimens containing vivid tumor from 16 patients treated with cisplatin, 8 had overexpression of MRP2. Tumor specimens with overexpression of MRP2 showed a lower percentage of tumor necrosis than those with non-overexpression (median percentage of tumor necrosis, 19% vs. 99%, P=0.003). In conclusion, overexpression of MRP2 correlates with a lower percentage of tumor necrosis in patients treated with cisplatin-based neoadjuvant chemotherapy for HCC, whereas either tumor size or dose of cisplatin does not. Expression of MRP2 determines the efficacy of cisplatin-based chemotherapy in patients with HCC.

Seven Holstein-Friesian cows showing chronic nephropathy were studied by renal microangiography and its correlated histopathology. In cases of pyelonephritis associated with severe pathological lesions such as thickening of arterial walls, narrowing of the arterial and arteriolar lumen, and interstitial inflammation and abscess formation, patchy loss of the peritubular capillary plexus from the cortex to the medulla was clearly demonstrated by microangiography. Interlobular arteries were tortuous and attenuated or truncated. Opacification in the vasa rectae and interstitial capillaries was increased. Extensive non-perfused regions could be detected in the cortex. In cases of mild interstitial nephritis and moderate pyelonephritis, microangiography showed focal changes in the renal vasculature. Microangiography is thus shown to clearly demonstrate changes in the renal vasculature corresponding to the severity of the histopathological lesions.

This study was designed to compare the prognostic power of the location of positive lymph nodes with that of the number of positive lymph nodes in gallbladder carcinoma. A retrospective analysis was conducted of 116 consecutive patients who underwent an R0 radical resection for gallbladder carcinoma. A total of 2,406 lymph nodes taken from the patients were examined histologically. The location of positive regional nodes was classified according to the Japanese staging system. The number of positive regional nodes was recorded for each patient. Nodal disease was found in 49 patients, of whom 19 survived for more than 5 years after resection. Univariate analysis revealed that both the location (P

This retrospective study aimed to define the role of hepatic lymph node dissection in the surgical management of patients with resectable colorectal carcinoma liver metastases.Fourteen of the 130 consecutive patients who had hepatectomy for colorectal carcinoma liver metastases underwent concomitant hepatic lymph node dissection for nodal disease suspected during the operation. A total of 125 hepatic lymph nodes (median, 8 per patient) were examined histologically for metastases. The therapeutic value index of hepatic lymph node dissection was estimated by multiplying the incidence of hepatic lymph node metastasis by the 5-year survival rate of patients with hepatic lymph node metastasis. The median follow-up time was 98 months.Mortality occurred within 30 days after resection in 1 patient. Hepatic lymph node metastases were detected in 7 patients, of whom 2 with no residual tumor survived for 10 years. The incidence and 5-year survival rate for patients with hepatic lymph node metastases were 50% and 29%, respectively. The therapeutic value index of hepatic lymph node dissection was 14.5.Hepatic lymph node dissection provides a survival benefit for some patients with hepatic nodal disease of resectable colorectal carcinoma liver metastases, provided that a potentially curative (R0) resection is feasible.

Information concerning the pulmonary toxicity of oxaliplatin with infusional 5-fluorouracil plus leucovorin (FOLFOX) is very limited. We herein report the case of a patient with FOLFOX-induced interstitial pneumonia. An 82-year-old man with unresectable colon cancer liver metastases was referred to our department for chemotherapy with the FOLFOX protocol. After the administration of ten cycles, he visited our outpatient clinic with a 2-week history of coughing and shortness of breath; he was afebrile. A chest radiograph showed reticular shadows with ground-glass opacities mainly involving the middle and lower zones of the right lung. Computed tomography depicted ground-glass opacities with superimposed reticulation in the right lung. A diagnosis of FOLFOX-induced interstitial pneumonia was made based on the clinical course and imaging findings. The symptoms disappeared within 3 days after the cessation of the FOLFOX regimen and the initiation of high-dose corticosteroid treatment. Two months after the initiation of the corticosteroid treatment, complete remission of the radiological abnormalities was confirmed; thereafter, interstitial pneumonia did not recur despite the reintroduction of 5-fluorouracil/leucovorin alone, suggesting that 5-fluorouracil/leucovorin alone was not responsible for the development of the interstitial pneumonia. Thus, oxaliplatin, alone or in combination with 5-fluorouracil/leucovorin, may have caused the interstitial pneumonia in this patient. Once interstitial pneumonia has occurred, cessation of the regimen is mandatory, and high-dose corticosteroid treatment is commonly given to rescue patients from this potentially lethal complication.

The present study was conducted to evaluate the effects of irinotecan plus gemcitabine(IRINOGEM)on biliary malignancies.From January 2005 through January 2007, 15 consecutive patients with chemotherapy- naive, locally advanced or metastatic biliary malignancies were enrolled. The primary affected sites were the gallbladder( n=7), extrahepatic bile ducts(n=5), and intrahepatic bile ducts(n=3). All the patients received starting doses of gemcitabine at 250 mg/m /(2) and irinotecan at 25 mg/m(2) given once per 2-week cycle. In the event of progressive disease, the dosage was increased for subsequent cycles.The median number of cycles administered was 16(range, 4-24 cycles)per patient. Although one case of grade 3 neutropenia was noted, neither grade 4 toxicities nor treatment-related deaths were observed. The overall response rate was 40% and the median overall survival time was 8 months, with a 1-year cumulative survival rate of 28%.IRINOGEM shows promising antitumor activity, and may be a worthwhile treatment option for locally advanced or metastatic biliary malignancies.

Vascular invasion is an established adverse prognostic factor in hepatocellular carcinoma (HCC). The aim of the current study was to identify the preoperative predictors of vascular invasion in patients undergoing partial hepatectomy for HCC.A retrospective analysis of 227 consecutive patients who underwent partial hepatectomy for HCC was conducted. Vascular invasion was defined as gross or microscopic involvement of the vessels (portal vein or hepatic vein) within the peritumoral liver tissue.Seventy-six (33%) patients had vascular invasion. Among the preoperative factors, only the tumour size (relative risk, 16.78; p0.01) and the serum alpha-fetoprotein (AFP) level (relative risk, 3.57; p0.01) independently predicted vascular invasion. As the tumour size increased, the incidence of vascular invasion increased:or =2 cm, 3%; 2.1-3 cm, 20%; 3.1-5 cm, 38%; and5 cm, 65%. The incidence of vascular invasion was 32% in patients with serum AFP levelsor =1000 ng/mL, compared to 61% in patients with higher serum AFP levels (p0.01). Patients with both tumours5 cm and serum AFP levels1000 ng/mL had an 82% incidence of vascular invasion.The tumour size and serum AFP level, alone or in combination, are useful in predicting the presence or absence of vascular invasion before hepatectomy for HCC.

To clarify whether perimuscular connective tissue contains more lymphatic vessels than the shallower layers in human gallbladders.Lymphatic vessels were stained immunohistochemically with monoclonal antibody D2-40, which is a specific marker of lymphatic endothelium, in representative sections of 12 normal human gallbladders obtained at the time of resection for colorectal carcinoma liver metastases. In individual gallbladder specimens, nine high-power (x 200) fields with the highest lymphatic vessel density (LVD), termed "hot spots", were identified for each layer (mucosa, muscle layer, and perimuscular connective tissue). In individual hot spots, the LVD and relative lymphatic vessel area (LVA) were measured microscopically using a computer-aided image analysis system. The mean LVD and LVA values for the nine hot spots in each layer were used for statistical analyses.In the mucosa, muscle layer, and perimuscular connective tissue, the LVD was 16.1 +/- 9.2, 35.4 +/- 15.7, and 65.5 +/- 12.2, respectively, and the LVA was 0.4 +/- 0.4, 2.1 +/- 1.1, and 9.4 +/- 2.6, respectively. Thus, both the LVD and LVA differed significantly (P0.001 and P0.001, respectively; Kruskal-Wallis test) among the individual layers of the wall of the gallbladder, with the highest LVD and LVA values in the perimuscular connective tissue. Most (98 of 108) of the hot spots within the perimuscular connective tissue were located within 500 mum of the lower border of the muscle layer.The perimuscular connective tissue contains more and larger lymphatic vessels than the shallower layers in the human gallbladder. This observation partly explains why the incidence of lymph node metastasis is high in T2 (tumor invading the perimuscular connective tissue) or more advanced gallbladder carcinoma.

Aims Intrahepatic recurrence is the most common manifestation of failure after local ablation therapy for hepatocellular carcinoma. The present study evaluates the safety and efficacy of partial hepatectomy for intrahepatic recurrence after prior local ablation. Methods A retrospective analysis was conducted of 188 consecutive patients with hepatocellular carcinoma who underwent either partial hepatectomy for recurrence after prior local ablation (n = 13) or partial hepatectomy as initial local treatment (n = 175). The 13 patients with recurrence after prior local ablation were referred to our division after the resectable recurrences were considered to be resistant to non-surgical treatment modalities. Results The incidences of postoperative morbidity and mortality were similar for patients with prior local ablation and patients without prior local ablation (p = 0.75 and p = 0.52, respectively). The overall survival rates after hepatectomy were comparable between patients with prior local ablation (median survival time of 86 months; cumulative 5-year survival rate of 63%) and patients without prior local ablation (median survival time of 76 months; cumulative 5-year survival rate of 54%; p = 0.60). The disease-free survival rates after hepatectomy were significantly worse for patients with prior local ablation based on both univariate (p = 0.01) and multivariate (relative risk, 2.73; p Conclusions Hepatectomy can be performed safely and may be efficacious, in terms of overall survival, for selected patients with intrahepatic recurrence after prior local ablation for hepatocellular carcinoma. On the other hand, prior local ablation appears to increase the probability of failure after hepatectomy.

Pharmacokinetic modulating chemotherapy (PMC) is designed to boost high serum 5-fluorouracil (5-FU) concentrations via modulation by uracil. The aim of this study was to evaluate the efficacy of PMC as a second-line chemotherapy for postresectional recurrences of colorectal carcinoma.Thirteen patients with unresectable recurrences of colorectal carcinoma were treated with PMC as the second-line chemotherapy, after 5-FU or its derivatives as the first-line chemotherapy. PMC was initiated with a 400 mg combination of uracil and tegafur daily and a 24-hour continuous intravenous infusion of 600 mg/m(2) 5-FU once weekly. The 5-FU dose was increased as the disease progressed.Six (46%) of the 13 patients exhibited a partial response (PR) to PMC, based on the RECIST criteria. PR was achieved in 2 of 5, 2 of 5, and 2 of 3 patients undergoing oral administration of 5-FU derivatives, intravenous infusion of 5-FU/l-leucovorin and hepatic-artery infusion of 5-FU, respectively. The median survival time of the 13 patients was 17 months.Grade-2 toxicity was found only in 2 patients.Because PMC is chronomodulating, it is an effective and safe treatment for recurrent colorectal carcinoma. PMC with a dose increase of 5-FU is recommended as a promising second-line regimen for unresectable colorectal carcinoma resistant to 5-FU.

The nodal status is an established prognostic factor in ampullary carcinoma. The aim of this study was to compare the prognostic power of the anatomic location of positive nodes with that of the number of positive nodes.Of 73 consecutive patients treated for ampullary carcinoma, 62 underwent pancreaticoduodenectomy with regional lymphadenectomy. A survival analysis of these 62 patients by nodal status was conducted retrospectively. A total of 1942 lymph nodes taken from the patients were examined histologically for metastasis. The location of positive regional nodes was classified into 4 categories, according to the Japanese staging system. The number of positive regional nodes was recorded for each patient. The median follow-up period was 124 months.Nodal disease was found in 31 patients, of whom 23 had 1-3 positive regional nodes and 8 hador=4 positive regional nodes. Univariate analysis revealed that both the location (p0.0001) and the number (p0.0001) of positive nodes were significant prognostic factors. Multivariate analysis revealed that the number of positive nodes was an independent prognostic factor (p=0.007), while the location failed to remain as an independent variable. The median survival time was 59 months with a 5-year survival rate of 48% in patients with 1-3 positive nodes, whereas all patients withor=4 positive nodes died of the disease within 29 months of resection (p=0.0001).The number, not the location, of positive regional lymph nodes independently affects long-term survival after resection in patients with ampullary carcinoma.

This study aimed to evaluate the effect of anatomic resection on long-term outcomes in patients with pathologic T1–T2 (pT1–T2) hepatocellular carcinoma. A retrospective analysis of 158 consecutive patients who underwent either anatomic (n = 95) or nonanatomic (n = 63) resection for pT1–T2 hepatocellular carcinoma was conducted. Anatomic resection was defined as the complete removal of at least one Couinaud segment containing the tumor; nonanatomic resection was defined as removal of the tumor plus a rim of nonneoplastic liver parenchyma. The median follow-up time was 83 months. Patients who underwent anatomic resection were characterized by lower prevalence of cirrhosis (P = .015), more favorable hepatic function (P = .001), larger tumor size (P = .029), and higher prevalence of vascular invasion (P = .008) compared with patients who underwent nonanatomic resection. Anatomic resection provided better survival (median survival time, 122 months) than nonanatomic resection (median survival time, 76 months; P = .0358). Patients who underwent anatomic resection had better disease-free survival (P = .0121). Anatomic resection independently improved both survival (hazard ratio, .46; P = .003) and disease-free survival (hazard ratio, .55; P = .008). When stratified for pT classification, the effectiveness of anatomic resection remained only in patients with pT2 tumors in terms of survival (P = .0012) and disease-free survival (P = .0004). Anatomic resection independently improves long-term survival in patients with T1–T2 hepatocellular carcinoma, probably because of the clearance of venous tumor thrombi within the resected domain.

AIM: To clarify the pathogenesis of biliary dilatation associated with anomalous union of the pancreatic and biliary ducts (AUPBD). METHODS: Direct cholangiopancreatograms of 350 adult patients with or with suspicion of hepatobiliary or pancreatic disorders were reviewed. AUPBD was diagnosed cholangiopancreatographically, when the pancreaticobiliary ductal union was located above the narrow distal segment of the bile duct, which represents the action of the sphincter of Oddi. The narrow portion of the terminal choledochus was defined as symmetrical stricture of the common bile duct just above the pancreaticobiliary ductal union. RESULTS: AUPBD was found in 36 patients. Among ch-olangiopancreatographic features, the narrow portion of the terminal choledochus was the most pathognomonic for AUPBD (accuracy, 98%); it was present in 29 (81%) patients with AUPBD, but was not found in any patients without AUPBD. Among patients with AUPBD, biliary dilatation (>10 mm) was more frequent in those with the narrow portion of the terminal choledochus (23/29) than in those without (2/7; P = 0.018) AUPBD. Among the patients with both AUPBD and the narrow portion of the terminal choledochus, there was a strong negative correlation between the minimum diameter of the narrow portion and the maximum diameter of the choledochus (r = -0.78, P

Mouse thymic lymphomas induced by gamma-irradiation exhibited homozygous deletions of the Rit1/Bcl11b tumor suppressor gene on chromosome 12 at high frequencies. Internal deletions of one allele were frequently accompanied by loss of the other allele. In order to elucidate the mechanism of these internal deletions, the sites of breakage and rejoining were examined by PCR mapping and sequencing. The 5' site of the deletions clustered within an approximately 5 kb region of intron 1 and the 3' site was confined to a site in intron 3. These sites contained P and/or N nucleotides and cryptic sequences recognizable by the RAG1/2 recombinase in the vicinity. This suggests that the Rit1 intragenic deletions were generated by endogenous illegitimate V(D)J recombinase activity and such aberrant recombination was also detected by nested PCR of DNA from the thymus of unirradiated mice but not of RAG2-deficient mice. A rough estimate indicated that there reside as many as 10(3)-10(4) thymocytes having Rit1 deletions, assuming the presence of 10(8) thymocytes in the thymus of unirradiated mice. Moreover, the recombination frequency was not affected by gamma-irradiation. These results show no effect of radiation on Rit1 mutations and suggest an indirect mechanism for its role in lymphomagenesis.

The postoperative recurrence rate after colorectal liver metastases (CLM) resection often exceeds 50%.1 Chemotherapy has been associated with a significant decrease of CLM recurrence rate.2 Several prognostic factors and clinical scores have been reported from surgical series. These prognostic factors and scores allow improved patient selection for hepatic resection and identify high-risk patients for recurrence who might benefit from adjuvant chemotherapy. Among the different prognostic factors, presence of hepatic pedicle lymph nodes metastases is now recognized to be one of the strongest risk factor for tumor relapse and for deleterious effect on survival.3,4 Interestingly, the survival rate is significantly higher when lymph node involvement is limited to the hepatoduodenal ligament and the retropancreatic area compared to patients with lymph node involvement along the common hepatic artery and around the celiac axis. Specifically, three-year survivors were observed in patients with hepatoduodenal and retropancreatic lymph node metastases while no survival longer than one year was registered for patients with lymph node metastases around common hepatic artery and/or celiac axis.4,5 Finally, several factors were associated with hepatic pedicle lymph node metastases including the presence of more than three liver metastases, liver metastases located in segment 4 and/or 5, presence of a resectable peritoneal deposit, and poorly differentiated pathological aspect of liver metastases.4 Currently, there is no agreement for a systematic hepatic pedicle lymphadenectomy and/or lymph node sampling during liver resection for CLM. Intrahepatic lymphatic invasion has previously been reported as a pathway of intrahepatic spread in patients with intrahepatic cholangiocarcinoma6 and was associated with a worse outcome. For the first time, Sasaki et al. showed that intrahepatic lymphatic invasion constitutes a negative prognostic factor after liver resection for CLM.7 The article by Korita et al. published in the Annals of Surgical Oncology investigated the relationship between intrahepatic lymphatic invasion and hepatic lymph node involvement in CLM.8 Once again, the authors underlined the pejorative prognostic value of intrahepatic lymphatic invasion. They retrospectively analyzed the clinical and pathological data of 105 consecutive patients who underwent liver resection for CLM. Specimens were examined to determine the presence or absence of intrahepatic lymphatic invasion using a monoclonal antibody (D2-40) for immunohistochemical staining of intrahepatic lymphatic vessels. They observed a correlation between intrahepatic lymphatic invasion and hepatic lymph node involvement and concluded that intrahepatic lymphatic invasion is an independent prognostic factor for overall and disease-free survival and for intra- and extrahepatic recurrence. As pointed out by the authors, their study has several limitations, mainly due to its retrospective design, the small sample size, and the absence of a routine lymphadenectomy. The observed correlation between intrahepatic lymphatic invasion and hepatic lymph node involvement seems plausible and statistically significant. However, this finding should be considered with caution, since lymph nodes dissection was based on their gross appearance and texture on palpation at the time of laparotomy. Indeed, the rate of microscopic hepatic lymph nodes metastases ranged, in several studies, from 11 to 33%.3–5 Therefore, removal of only enlarged or palpable lymph nodes seems insufficient. Selective sampling of the sentinel lymph node or lymphadenectomy based on preoperative imaging particularly on positron emission tomography scan,9,10 would be more sensitive than palpation alone. Moreover, the authors proposed immunohistochemical staining to detect intrahepatic lymphatic invasion. However, it would be interesting, as a first step, to compare the sensitivity and the specificity of a standard hematoxylin–eosin histological examination with those of immunohistochemical staining before recommending wider use of the latter technique. Among the different pathways of intrahepatic invasion by CLM (portal venous invasion, hepatic venous invasion, sinusoidal invasion, bile duct invasion, perineural invasion, stromal invasion) intrahepatic lymphatic invasion is clinically relevant as it is associated with an invariably lethal outcome at three years with disease recurrence. Therefore, the most interesting message of the present study is that in the presence of intrahepatic lymphatic invasion, surgery alone is insufficient to achieve long-term survival even after a curative-intent liver resection for CLM. Further studies are required to determine whether adjuvant chemotherapy may improve outcome for these patients. The hypothesis that intrahepatic lymphatic invasion is a precursor of hepatic pedicle lymph node metastases needs further investigation. In fact, the reported intrahepatic lymphatic invasion rate of 15.4%7 seems similar to the incidence of hepatic pedicle lymph node involvement (3–33%).4 Further evidence of a correlation between intrahepatic lymphatic invasion and hepatic pedicle lymph node metastases is given by the present study. Moreover, the absence of three-year survivors in the case of intrahepatic lymphatic invasion suggests that such invasion may correlate more with distal lymph node metastases (around the common hepatic artery and the celiac axis) or other extrahepatic occult metastases. Identification of predictive factors associated with intrahepatic lymphatic invasion is mandatory. Supposing that intrahepatic lymphatic invasion is an adverse prognostic factor for tumor recurrence after hepatectomy for CLM, a prospective study analyzing the value of adjuvant chemotherapy in such high-risk patients would seem justified.

To delineate indications and limitations for "extended" radical cholecystectomy for gallbladder cancer: a procedure which was instituted in our department in 1982.Of 145 patients who underwent a radical resection for gallbladder cancer from 1982 through 2006, 52 (36%) had an extended radical cholecystectomy, which involved en bloc resection of the gallbladder, gallbladder fossa, extrahepatic bile duct, and the regional lymph nodes (first- and second-echelon node groups). A retrospective analysis of the 52 patients was conducted including at least 5 years of follow up. Residual tumor status was judged as no residual tumor (R0) or microscopic/macroscopic residual tumor (R1-2). Pathological findings were documented according to the American Joint Committee on Cancer Cancer Staging Manual (7th edition).The primary tumor was classified as pathological T1 (pT1) in 3 patients, pT2 in 36, pT3 in 12, and pT4 in 1. Twenty-three patients had lymph node metastases; 11 had a single positive node, 4 had two positive nodes, and 8 had three or more positive nodes. None of the three patients with pT1 tumors had nodal disease, whereas 23 of 49 (47%) with pT2 or more advanced tumors had nodal disease. One patient died during the hospital stay for definitive resection, giving an in-hospital mortality rate of 2%. Overall survival (OS) after extended radical cholecystectomy was 65% at 5 years and 53% at 10 years in all 52 patients. OS differed according to the pT classification (P0.001) and the nodal status (P = 0.010). All of 3 patients with pT1 tumors and most (29 of 36) patients with pT2 tumors survived for more than 5 years. Of 12 patients with pT3 tumors, 8 who had an R1-2 resection, distant metastasis, or extensive extrahepatic organ involvement died soon after resection. Of the remaining four pT3 patients who had localized hepatic spread through the gallbladder fossa and underwent an R0 resection, 2 survived for more than 5 years and another survived for 4 years and 2 mo. The only patient with pT4 tumor died of disease soon after resection. Among 23 node-positive patients, 11 survived for more than 5 years, and of these, 10 had a modest degree of nodal disease (one or two positive nodes).Extended radical cholecystectomy is indicated for pT2 tumors and some pT3 tumors with localized hepatic invasion, provided that the regional nodal disease is limited to a modest degree (up to two positive nodes). Extensive pT3 disease, pT4 disease, or marked nodal disease appears to be beyond the scope of this radical procedure.

As a result of having undergone computed tomography (CT), a 75-year-old woman with type-C liver cirrhosiswas shown to have two tumors on the ventral and dorsal sides of subsegment 3 (S3). The tumor on the ventral side was diagnosed as a classic hepatocellular carcinoma (HCC), while that on the dorsal side was considered atypical for a HCC. Although the indocyanine green (ICG) findings indicated poor hepatic reserve, the prothrombin time (PT) was relatively good. An operation was performed in February 2007; however, this resulted in exploratory laparotomy. Dynamic CT performed 12 mo after the operation revealed that the tumor on the dorsal side of S3 had apparently increased. The marginal portion of the tumor was shown to be in the early and parenchymal phases, while the internal portion was found to have grown only slightly in the delayed phase. We diagnosed this tumor as a cholangiocellular carcinoma (CCC). S3 subsegmentectomy was performed in April 2008. The tumor on the ventral side was pathologically diagnosed as a moderately differentiated HCC, and that on the dorsal side was diagnosed as a CCC. We can therefore report a rare case of synchronous development of HCC and CCC in the same subsegment of the liver in a patient with type-C liver cirrhosis. We also add a literature review for all the reported cases published in Japan and around the world, and summarize the features of double cancer exhibiting both HCC and CCC.

To determine which treatment modality--hepatectomy or percutaneous ablation--is more beneficial for patients with small hepatocellular carcinoma (HCC) (or =4 cm) in terms of long-term outcomes.A retrospective analysis of 149 patients with HCCor =4 cm was conducted. Eighty-five patients underwent partial hepatectomy (anatomic in 47 and non-anatomic in 38) and 64 underwent percutaneous ablation (percutaneous ethanol injection in 37, radiofrequency ablation in 21, and microwave coagulation in 6). The median follow-up period was 69 mo.Hepatectomy was associated with larger tumor size (P0.001), whereas percutaneous ablation was significantly associated with impaired hepatic functional reserve. Local recurrence was less frequent following hepatectomy (P0.0001). Survival was better following hepatectomy (median survival time: 122 mo) than following percutaneous ablation (median survival time: 66 mo; P=0.0123). When tumor size was divided intoor =2 cm vs2 cm, the favorable effects of hepatectomy on long-term survival was seen only in patients with tumors2 cm (P=0.0001). The Cox proportional hazards regression model revealed that hepatectomy (P=0.006) and tumorsor =2 cm (P=0.017) were independently associated with better survival.Hepatectomy provides both better local control and better long-term survival for patients with HCCor =4 cm compared with percutaneous ablation. Of the patients with HCCor =4 cm, those with tumors2 cm are good candidates for hepatectomy, provided that the hepatic functional reserve of the patient permits resection.

To estimate the incidence of catheter tract implantation metastasis among patients undergoing percutaneous transhepatic biliary drainage (PTBD) for extrahepatic cholangiocarcinoma, and to provide data regarding the management of this unusual complication of PTBD by reviewing cases reported in the literature.A retrospective analysis of 67 consecutive patients who underwent PTBD before the resection of extrahepatic cholangiocarcinoma was conducted. The median follow-up period after PTBD was 106 mo. The English language literature (PubMed, National Library of Medicine, Bethesda, MD, USA), from January 1966 through December 2004, was reviewed.Catheter tract implantation metastasis developed in three patients. The cumulative incidence of implantation metastasis reached a plateau (6%) at 20 mo after PTBD. All of the three patients with implantation metastasis died of tumor progression at 3, 9, and 20 mo after the detection of this complication. Among the 10 reported patients with catheter tract implantation metastasis from extrahepatic cholangiocarcinoma (including our three patients), two survived for more than 5 years after the excision of isolated catheter tract metastases.Catheter tract implantation metastasis is not a rare complication following PTBD for extrahepatic cholangiocarcinoma. Although the prognosis for patients with this complication is generally poor, the excision of the catheter tract may enable survival in selected patients with isolated metastases along the catheter tract.

Background The presence of extramural tumor deposits without lymph node structure (EX) is an important prognostic factor for patients with colorectal cancer. However, the clinical significance of EX in the lateral pelvic lymph node area (LP-EX) remains unclear. This study aimed to determine the prognostic implications of LP-EX for patients with low rectal cancer. Methods This retrospective study involved 172 consecutive patients with stage 2 or 3 low rectal cancer who underwent curative surgery including lateral pelvic lymph node (LPLN) dissection. The patients were classified into the following three groups according to the metastatic status of the LPLN area: patients without metastasis (no-LP-M group), patients with lymph node metastasis (LP-LNM group), and patients with EX (LP-EX group). Potential prognostic factors of overall survival (OS) and relapse-free survival (RFS) were identified in uni- and multivariate analyses. Results Classification assigned 131 patients (76 %) to the no-LP-M group, 27 patients (16 %) to the LP-LNM group, and 14 patients (8 %) to the LP-EX group. The 5-year OS rate was 80.3 % in the no-LP-M group, 61.1 % in the LP-LNM group, and 34.9 % in the LP-EX group (P

SummaryBackground and aimsTransthoracic esophagectomy using 3-field lymphadenectomy (TTE-3FL) for esophageal cancer is one of the most aggressive gastrointestinal surgeries. Early enteral nutrition (EN) for TTE-3FL patients is useful and valid for early recovery; however, EN using a fat-containing formula risks inducing chyle leak. In the present study, we retrospectively examined esophageal cancer patients treated byTTE-3FL and administered postoperative EN to elucidate the validity of lowering the fat levels in elemental formulas to prevent postoperative chyle leak and improve postoperative recovery.MethodsA total of 74 patients who received TTE-3FL for esophageal cancer were retrospectively examined. Patients were classified into two groups according to the type of postoperative EN: Group LF patients received a low-fat elemental formula, and Group F patients received a standard fat-containing polymeric formula. The following clinical factors were compared between the groups: EN start day, maximum EN calories administered, duration of respirator use, length of ICU stay, incidence of postoperative infectious complications, use of parenteral nutrition (PN), and incidence of postoperative chyle leak.ResultsPatients in Group LF were started on EN significantly earlier after surgery and they consumed significantly higher maximum EN calories compared to Group F patients (P

Idiopathic spontaneous pneumoperitoneum is a rare condition that is characterized by intraperitoneal gas for which no clear etiology has been identified. We report here a case of idiopathic spontaneous pneumoperitoneum, which was successfully managed by conservative treatment. A 77-year-old woman who was bedridden with speech disability as a sequela of brain hemorrhage presented at our hospital with a 1-day history of abdominal distention. On physical examination, she had stable vital signs and slight epigastric tenderness on deep palpation without any other signs of peritonitis. A chest radiograph and computed tomography showed that a large amount of free gas extended into the upper abdominal cavity. Esophagogastroduodenoscopy revealed no perforation of the upper gastrointestinal tract. The patient was diagnosed with idiopathic spontaneous pneumoperitoneum, and conservative treatment was selected. The abdominal distension rapidly disappeared, and the patient resumed oral intake on the 5th hospital day without deterioration of symptoms. Knowledge of this rare disease and accurate diagnosis with findings of clinical imaging might contribute towards refraining from unnecessary laparotomy.

The synthesis and palladium-catalyzed reactions of cis- and trans-3,4-benzo-1,2-diisopropyl- 1,2-dimethyl-1,2-disilacyclobut-3-ene (1a and 1b) are reported. Their reactions with diphenylacetylene in the presence of a catalytic amount of tetrakis(triphenylphosphine)palladium(0) proceeded with high stereospecificity to give cis- and trans-5,6-benzo-1,4-diisopropyl-1,4-dimethyl- 2,3-diphenyl-1,4-disilacyclohexa-2,5-diene, 2a and 2b, in 95% and 93% yield, respectively. Similar palladium-catalyzed reactions of 1a and 1b with monosubstituted acetylenes, such as 1-hexyne, tert-butylacetylene, phenylacetylene, and trimethylsilylacetylene, also proceeded stereospecifically to afford the respective cis- and trans-5,6-benzo-1,4-disilacyclohexa-2,5-dienes, 3a - 6a and 3b - 6b, in excellent yields and as the sole products. The palladium-catalyzed reaction of 1a with styrene gave a mixture consisting of two stereoisomers, cis-2- and trans-2-phenyl-substituted 5,6- benzo-(r-1),cis-4-diisopropyl-1,4-disilacyclohex-5-ene 7a and 8a in a ratio of 5 : 3 in 72% combined yield, while the reaction of styrene with 1b afforded two stereoisomers, 7b and 8b, in a ratio of 2 : 1 in 80% combined yield. With 1-hexene, 1a gave two stereoisomers, 5,6-benzo-cis-2-(nbutyl)-( r-1),cis-4-diisopropyl- and 5,6-benzo-trans-2-(n-butyl)-(r-1),cis-4-diisopropyl-1,4-dimethyl- 1,4-disilacyclohex-5-ene, 9a and 10a, in a ratio of 1 : 1 in 70% combined yield. A similar reaction of 1b with 1-hexene produced 5,6-benzo-cis-2-(n-butyl)-(r-1),trans-4-diisopropyl-1,4-dimethyl-1,4- disilacyclohex-5-ene in 81% yield and as a single isomer

Background Severe blunt hepatic injury is a major cause of morbidity and mortality in pediatric patients. Damage control (DC) surgery has been reported to be useful in severely compromised children with hepatic injury. We applied such a technique in the treatment of a case of hemodynamically unstable grade IV blunt hepatic injury in an eight-year-old girl. This case is the first to use multimodal approaches including perihepatic packing, temporary closure of the abdominal wall with a plastic sheet, transarterial embolization (TAE), and planned delayed anatomical hepatic resection in a child. Case presentation An eight-year-old girl was run over by a motor vehicle and transferred to the emergency department of the local hospital. Her diagnoses were severe blunt hepatic injury (grade IV) with left femoral trochanteric fracture. No other organ injuries were observed. Because her hemodynamic state was stable under aggressive fluid resuscitation, she was transferred to our hospital for surgical management. On arrival at our institution about 4 h after the injury, her hemodynamic condition became unstable. Abdominal compartment syndrome also became apparent. Because her condition had deteriorated and the lethal triad of low BT, coagulopathy, and acidosis was observed, a DC treatment strategy was selected. First, emergent laparotomy was performed for gauze-packing hemostasis to control intractable bleeding from the liver bed, and the abdomen was temporarily closed with a plastic sheet with continuous negative pressure aspiration. Transarterial embolization of the posterior branch of the right hepatic artery was then carried out immediately after the operation. The lacerated right lobe of the liver was safely resected in a stable hemodynamic condition 2 days after the initial operation. Bleeding from the liver bed ceased without further need of hemostasis. She was transferred to the local hospital without any surgical complications on day 42 after admission. She had returned to her normal life by 3 months after the injury. Conclusion The DC strategy was found to be effective even in a pediatric patient with hemodynamically unstable severe blunt hepatic injury. The presence of the deadly triad (hypothermia, coagulopathy, and acidosis) and abdominal compartment syndrome was an indication for DC surgery.