Search

To evaluate the surgical outcomes of patients with gallbladder cancer (GBC) with jaundice due to as-yet unelucidated prognostic factors. A total of 348 GBC patients underwent resection at our institute between 1985 and 2016. Of these, 67 had jaundice (serum total bilirubin ≥ 2 mg/dL). Preoperative biliary drainage was performed, with portal vein embolization as required. All patients underwent radical surgery. We retrospectively evaluated the outcomes, performed multivariate analysis for overall survival, and compared our findings to those reported in the literature. The 5-year survival rate of M0 (no distant metastasis) GBC patients with jaundice, who underwent resectional surgery, was 21.9%, versus 68.3% in those without jaundice (p < 0.05). Since 2000, surgical mortality in GBC patients with jaundice has decreased from 12 to 6.8%. Patients with jaundice had more advanced disease and underwent major hepatectomies and vascular resections; however, preoperative jaundice alone was not a prognostic factor. Multivariate analysis of jaundiced patients revealed that percutaneous biliary drainage (PTBD) (vis-a-vis endoscopic drainage [EBD], hazard ratio [HR] 2.82), postoperative morbidity (Clavien–Dindo classification ≥ 3, HR 2.31), and distant metastasis (HR 1.85) were predictors of poor long-term survival. The 5-year survival and peritoneal recurrence rates in M0 patients with jaundice were 16% and 44%, respectively, for patients with PTBD and 39% (p < 0.05) and 13% (p = 0.07) for those with EBD. M0 GBC patients with jaundice should undergo surgery if R0 resection is possible. Preoperative EBD may be superior to PTBD in M0 GBC patients with jaundice, although further studies are needed.

To date, postoperative prognostic factors for intraductal papillary neoplasm of the bile duct (IPNB) have not been well-established. This study aimed to examine the histopathologic features and postoperative prognosis of the two IPNB subclassifications, as well as factors affecting prognosis, based on the authors’ experience at a single institution. The study enrolled 83 patients who underwent surgical resection for pathologically diagnosed IPNB at the authors’ institution. The clinicopathologic features and postoperative outcomes for these patients were examined. The study also investigated postoperative prognostic factors for IPNB using uni- and multivariate analyses. More than half of the tumors (64%) diagnosed as IPNB were early-stage cancer (UICC Tis or T1). However, none were diagnosed as benign. The multivariate analysis showed that lymph node metastasis (hazard ratio [HR], 5.78; p = 0.002) and bile duct margin status with carcinoma in situ (D-CIS; HR, 5.10; p = 0.002) were independent prognostic factors, whereas MUC6 expression showed only a marginal influence on prediction of prognosis (HR, 0.32; p = 0.07). The tumor recurrence rate and the proportion of locoregional recurrence were significantly greater among the patients with D-CIS than among those with negative bile duct margins, including those patients with low-grade dysplasia. The patients with D-CIS showed a significantly poorer prognosis than those with negative bile duct margins (5-year survival, 38% versus 87%; p = 0.0002). Evaluation of resected IPNBs showed cancer in all cases. Avoiding positive biliary stumps during surgery, including resection of carcinoma in situ, would improve the prognosis for patients with IPNB.

Background The present study aimed to determine functional outcomes in patients undergoing deltoid muscle resection for soft tissue sarcoma. Methods Between 2002 and 2014, 18 patients with soft tissue sarcoma of the shoulder who underwent wide resection including the deltoid muscle, and were followed up for more than 12 months, were retrospectively included in the study. In all, 11 patients were male and 7 were female. The median age was 59 years, median follow-up duration was 37 months. The extent of resection of deltoid muscle, with or without rotator cuff damage, reconstruction methods, adjuvant therapy, oncological outcomes, and the International Society of Limb Salvage (ISOLS) score as functional outcomes were analyzed. Results Six patients underwent total resection, and twelve underwent partial resections of deltoid muscle. The rotator cuff was resected in four patients. Soft tissue reconstruction was performed in 17 patients using a pedicled latissimus dorsi muscle flap. Two local recurrences and three distant metastases occurred during follow-up. Median overall survival was 72 months. The mean ISOLS score was 25.0 points (±4.6points). Univariate analysis revealed that there was no significant difference in ISOLS score regarding the extent of deltoid muscle resection. Multivariate analysis identified only combined resection of the rotator cuff as a significant prognostic factor for poor functional outcomes (P Conclusions The extent of resection of the deltoid muscle might not affect the functional outcomes determined by ISOLS score. If the rotator cuff is resected concurrently, satisfactory functional outcomes might not be obtained.

Purpose: Osteochondral destruction and high recurrence rate after surgery are major concerns during the treatment course of tenosynovial giant cell tumor. The aims of this study were to elucidate rates of local recurrence and osteochondral destruction, and demographic factors correlated with osteochondral destruction and recurrence rate after surgery. Methods: Eighty surgically treated patients (knee: 49, ankle and foot: 12, hip: 10, others: 9) were included in this study. Factors including age, disease type (diffuse/localized), location, existence of osteochondral destruction were analyzed to be correlated with local recurrence or development/progression of osteochondral destruction. Results: The 5-year local recurrence free survival rate was 71.4 %. Diffuse type (n=59, localized: n=21) (P=0.023) and knee location (P=0.002) were independent risk factors for local recurrence. Diffuse type (P=0. 009) was a significant risk factor, and knee location (P=0. 001) was a negative factor for osteochondral destruction at the initial examination. Progression of osteochondral destruction was observed more often in cases with local recurrence (P=0.040) and findings of osteochondral destruction at the initial examination (P=0.029).Conclusions: Diffuse type is a factor that should be noted for both local recurrence and osteochondral destruction, and local recurrence occurs but osteochondral destruction is less observed for knee location.

The efficacy of different types of preoperative biliary drainage for cholangiocarcinoma has been debated over the past two decades. Controversy concerning the use of percutaneous transhepatic biliary drainage (PTBD) versus endoscopic biliary drainage (EBD) still exists. This study aimed to compare the long-term outcomes between PTBD and EBD in patients with distal cholangiocarcinoma. Data of patients diagnosed with distal cholangiocarcinoma who underwent preoperative PTBD or EBD from January 1999 to December 2017 were analyzed retrospectively. Post-surgical outcomes, including the incidence of post-operative complications, peritoneal metastasis, disease-free survival, and overall survival, were analyzed. Survival analyses were also performed after propensity score matching in the PTBD and EBD groups. The incidence of post-operative complications was similar in both groups. The 5-year estimated cumulative incidences for peritoneal metastasis were 14.7% and 7.2% in the PTBD and EBD groups, respectively (p = 0.192). The 5-year disease-free survival rates were 23.7% and 47.3% in the PTBD and EBD groups, respectively (p = 0.015). In the multi-variate analysis for overall survival, PTBD was an independent poor prognostic factor. The 5-year overall survival rates were 35.9% and 56.3% in the PTBD and EBD groups, respectively (hazard ratio 1.85, confidence interval 1.05–3.26, p = 0.035). The results after propensity score matching indicated a poorer prognosis in the PTBD group, with a 5-year survival rate of 35.9% in the PTBD group vs 56.0% in the EBD group (p = 0.044). PTBD should be considered as a negative prognostic factor in distal cholangiocarcinoma patients.

In advanced gallbladder cancer (GBC) radical resection, if multiple prognostic factors are present, the outcome may be poor, however, the details remain unclear. To investigate the poor prognostic factors affecting long-term surgical outcome, we examined 157 cases of resected stage 3/4 GBC without distant metastasis between 1985 and 2017. Poor prognostic factors for overall survival and treatment outcomes of a number of predictable preoperative poor prognostic factors were evaluated. The surgical mortality was 4.5%. In multivariate analysis, blood loss, poor histology, liver invasion, and &ge, 4 regional lymph node metastases (LNMs) were independent prognostic factors for poor surgical outcomes, invasion of the left margin or the entire area of the hepatoduodenal ligament and a Clavien&ndash, Dindo classification &ge, 3 were marginal factors. The analysis identified outcomes of patients with factors that could be predicted preoperatively, such as liver invasion &ge, 5 mm, invasion of the left margin or the entire area of the hepatoduodenal ligament, and &ge, 4 regional LNMs. Thus, the five-year overall survival was 54% for zero factors, 34% for one factor, and 4% for two factors (p &lt, 0.05). A poor surgical outcome was likely when two or more factors were predicted preoperatively, therefore, new treatment strategies are required for such patients.

To evaluate the surgical outcomes of patients with gallbladder cancer (GBC) with jaundice due to as-yet unelucidated prognostic factors.A total of 348 GBC patients underwent resection at our institute between 1985 and 2016. Of these, 67 had jaundice (serum total bilirubin ≥ 2 mg/dL). Preoperative biliary drainage was performed, with portal vein embolization as required. All patients underwent radical surgery. We retrospectively evaluated the outcomes, performed multivariate analysis for overall survival, and compared our findings to those reported in the literature.The 5-year survival rate of M0 (no distant metastasis) GBC patients with jaundice, who underwent resectional surgery, was 21.9%, versus 68.3% in those without jaundice (p0.05). Since 2000, surgical mortality in GBC patients with jaundice has decreased from 12 to 6.8%. Patients with jaundice had more advanced disease and underwent major hepatectomies and vascular resections; however, preoperative jaundice alone was not a prognostic factor. Multivariate analysis of jaundiced patients revealed that percutaneous biliary drainage (PTBD) (vis-à-vis endoscopic drainage [EBD], hazard ratio [HR] 2.82), postoperative morbidity (Clavien-Dindo classification ≥ 3, HR 2.31), and distant metastasis (HR 1.85) were predictors of poor long-term survival. The 5-year survival and peritoneal recurrence rates in M0 patients with jaundice were 16% and 44%, respectively, for patients with PTBD and 39% (p0.05) and 13% (p = 0.07) for those with EBD.M0 GBC patients with jaundice should undergo surgery if R0 resection is possible. Preoperative EBD may be superior to PTBD in M0 GBC patients with jaundice, although further studies are needed.

To investigate short- and long-term surgical outcomes for patients with perihilar cholangiocarcinoma and vascular invasion. Data from 249 patients who underwent perihilar cholangiocarcinoma surgery between 2000 and 2016 were retrospectively analyzed. Patient evaluations included short-term surgical outcomes following vascular resection and long-term outcomes in cases with histopathological vascular invasion. Mortality was 3.6% overall; 16% for hepatic artery resections, 5.4% for portal vein resections, and 1.7% in the absence of vascular resection (p = 0.029). No between-group differences were observed in the incidence of Clavien–Dindo grade ≥ 3 complications. The factors related to perioperative mortality were hepatic artery resection (odds ratio [OR] = 25.5), right trisectionectomy (OR = 13.0), and central bisectionectomy (OR = 13.8). Multivariate analysis for overall survival identified several prognostic factors: carcinoembryonic antigen level ≥ 5 ng/mL (hazard ratio [HR] = 1.68), poor differentiation (HR = 2.39), distant metastasis (HR = 1.97), and R1 invasive resection (HR = 2.13). Five-year overall survival for patients with portal vein invasion and M0R0/1cis was 35.6%, significantly worse than the 53.4% for patients with no portal vein invasion and M0R/1cis but better than the 0% for patients with portal vein invasion and M1 or R1. Those with hepatic arterial invasion and M0R0/1cis were 24.7%, significantly worse than the 53.4% for patients with no hepatic arterial invasion and M0R0/1cis but significantly better than the 0% for patients with hepatic arterial invasion and M1 or R1. Short-term outcomes for patients with perihilar cholangiocarcinoma and undergoing vascular resection were poor compared to those without vascular resection. Long-term survival in R0M0 disease was more favorable; aggressive surgery is recommended.

Hyaluronan (HA) has been shown to play important roles in the growth, invasion and metastasis of malignant tumors. Our previous study showing that high HA expression in malignant peripheral nerve sheath tumors (MPNST) is predictive of poor patient prognosis, prompted us to speculate that inhibition of HA synthesis in MPNST might suppress the tumorigenicity. The aim of our study was to investigate the antitumor effects of 4-methylumbelliferone (MU), an HA synthesis inhibitor, on human MPNST cells and tissues. The effects of MU on HA accumulation and tumorigenicity in MPNST cells were analyzed in the presence or absence of MU in an in vitro as well as in vivo xenograft model using human MPNST cell lines, sNF96.2 (primary recurrent) and sNF02.2 (metastatic). MU significantly inhibited cell proliferation, migration and invasion in both MPNST cell lines. HA binding protein (HABP) staining, particle exclusion assay and quantification of HA revealed that MU significantly decreased HA accumulation in the cytoplasms and pericellular matrices in both MPNST cell lines. The expression levels of HA synthase2 (HAS2) and HA synthase3 (HAS3) mRNA were downregulated after treatment with MU. MU induced apoptosis of sNF96.2 cells, but not sNF02.2 cells. MU administration significantly inhibited the tumor growth of sNF96.2 cells in the mouse xenograft model. To the best of our knowledge, our study demonstrates for the first time the antitumor effects of MU on human MPNST mediated by inhibition of HA synthesis. Our results suggest that MU may be a promising agent with novel antitumor mechanisms for MPNST.

Background Thyroid metastasis of soft tissue sarcoma is very rare, and the diagnosis is especially difficult when only a single lesion is present. Case presentation A 50-year-old man was diagnosed with myxoid liposarcoma of the right thigh and treated with wide resection. Two and a half years after the surgery, a growing low-density area was incidentally observed in the right lobe of his thyroid gland on follow-up chest computed tomography. Fine needle aspiration biopsy was performed twice, and the thyroid mass was suspected of being a sarcoma metastasis. He was treated by hemithyroidectomy, and the lesion was pathologically confirmed as a metastasis of myxoid liposarcoma. Conclusion We experienced single thyroid gland metastasis in patients with myxoid liposarcoma in whom a growing mass is observed in the thyroid gland after radical surgery of the primary site.

Pigmented villonodular synovitis (PVNS) is a benign, translocation-derived neoplasm. Because of its high local recurrence rate after surgery and occurrence of osteochondral destruction, a novel therapeutic target is required. The present study aimed to evaluate the significance of protein expression possibly associated with the pathogenesis during the clinical course of PVNS. In 40 cases of PVNS, positivity of colony-stimulated factor 1 (CSF1), its receptor (CSF1R), and receptor activator of nuclear factor kappa-B ligand (RANKL) were immunohistochemically determined. The relationship between the positivity and clinical outcomes was investigated. High positivity of CSF1 staining intensity was associated with an increased incidence of osteochondral lesions (bone erosion and osteoarthritis) (p = 0.009), but not with the rate of local recurrence. Positivity of CSF1R and RANKL staining was not associated with any clinical variables. The number of giant cells was not correlated with positivity of any of the three proteins, or with the clinical outcome. Focusing on knee cases, CSF1 positivity was also associated with the incidence of osteochondal change (p = 0.02). CSF1R positivity was high in cases which had local recurrence, but not significantly so (p = 0.129). Determination of CSF1 and CSF1R expression may be useful as a prognosticator of the clinical course and/or outcomes of PVNS.

Background Immunohistochemical staining with conventional anti-β-catenin antibody has been applied as a diagnostic tool for desmoid-type fibromatosis (DF). This study aimed to evaluate the diagnostic and prognostic value of immunohistochemical staining with anti-non-phospho β-catenin antibody, which might more accurately reflect the aggressiveness of DF, in comparison to the conventional anti-β-catenin antibody. Methods Between 2003 and 2015, 40 patients with extra-peritoneal sporadic DF were prospectively treated with meloxicam or celecoxib, a COX-2 inhibitor, therapy. The efficacy of this treatment was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST). Immunohistochemical staining was performed on formalin-fixed material to evaluate the expression of β-catenin and non-phospho β-catenin, and the positivity was grouped as negative, weak, moderate, and strong. DNA was isolated from frozen tissue or formalin-fixed materials, and the CTNNB1 mutation status was determined by direct sequencing. Results Of the 40 patients receiving COX-2 inhibitor treatment, there was one with complete remission, 12 with partial remission, 7 with stable disease, and 20 with progressive disease. The mutation sites in CTNNB1 were detected in 22 (55%) of the 40 cases: T41A (17 cases), S45F (3 cases), and T41I and S45P (1 each). The positive nuclear expression of non-phospho β-catenin showed a significant correlation with positive CTNNB1 mutation status detected by Sanger method (p = 0.025), and poor outcome in COX-2 inhibitor therapy (p = 0.022). In contrast, nuclear expression of β-catenin did not show a significant correlation with either CTNNB1 mutation status (p = 0.43) or outcome of COX-2 inhibitor therapy (p = 0.38). Conclusions Nuclear expression of non-phospho β-catenin might more appropriately reflect the biological behavior of DF, and immunohistochemical staining with non-phospho β-catenin could serve as a more useful diagnostic and prognostic tool of COX-2 inhibitor therapy for patients with DF.

Background We investigated safety-related outcomes of hepatobiliary pancreatic (HBP) surgeries performed after establishment of the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) board certification system for expert surgeons. Methods We analyzed post-HBP surgery mortality data obtained from annual safety reports provided by board-certified training institutions between 2012 and 2015. Results The 90-day mortality rate for the 53,929 high-level HBP surgeries performed at board-certified training institutions was 1.7%. The 30-day mortality rates for 2012, 2013, 2014, and 2015 were 0.9%, 0.7%, 0.6%, and 0.6%, respectively, and the 90-day mortality rates were 2.1%, 1.8%, 1.6%, and 1.3%, respectively, with significant decreases in both. The surgeries with high 4-year cumulative mortality rates were left hepatic trisectionectomy (10.3%), hepatopancreatectomy (7.6%), liver transplant recipient surgery (6.7%), hepatectomy with extrahepatic bile duct resection (4.6%), and right hepatic trisectionectomy (4.5%). Over the 4-year period, the number of operations increased, but the 90-day mortality rates for these surgeries, with the exception of right trisectionectomy, decreased. Conclusions The JSHBPS board certification system for expert surgeons has significantly decreased mortality subsequent to high-level HBP surgeries. Reducing mortality associated with high-risk HBP surgeries will be our next challenge.

Purpose. The aim was to evaluate prognostic factors and factors associated with the resectability of advanced gallbladder cancer (GBC). Methods. This was a single-institution retrospective review of 274 consecutive surgically-treated cases of advanced GBC (excluding incidental GBC and early GBC). Univariate and multivariate analysis were performed to assess prognostic variables. R0 resection and survival rates were investigated for each local extension factor. Results. Long-term survival was uncommon among patients with multiple liver metastases (H2–3: n = 22; 2-year survival, 0 %), dissemination (P1–3: n = 16; 3-year survival, 0 %), invasion through the hepatoduodenal ligament (Binf3: n = 45; 5-year survival, 4.6 %), or group 3 lymph node (LN) metastasis including of the para-aortic LN (N3: n = 52; 13.7 %). Long-term survival rates did not differ significantly between patients who did and did not undergo bile duct resection or pancreaticoduodenectomy. Survival did not differ significantly according to the type of hepatectomy performed. Conclusion. Surgery may not be indicated for patients with multiple liver metastasis, dissemination, Binf3 ,o r visible para-aortic LN metastasis. Furthermore, it is important to achieve R0 surgery in cases of GBC.

Background Few reports have assessed the accuracy of transient hepatic attenuation differences (THAD) in the arterial phase of computed tomography (CT) in diagnosing acute cholangitis (AC). We examined the diagnostic accuracy of THAD in AC in patients with malignant disease. Methods We retrospectively examined the records of 123 consecutive patients (73 men, 50 women; mean age, 69 [range, 43–91] years) who underwent dynamic CT 3 days before biliary drainage for malignant hepatobiliary disease between 2006 and 2011. We examined the diagnostic ability of THAD for AC and assessed the relationship between THAD and AC severity. Results Acute cholangitis was present in 45% of patients. The sensitivity and specificity of THAD for AC were 93% and 39%, respectively. Diffuse, hemi-hepatic, and segmental THAD for AC were seen in 84%, 4%, and 9%, respectively. In all, 64% of patients were diagnosed with severe AC and 29% with mild AC, depending on the intensity of THAD, but the patterns and degree of intensity of THAD and AC severity were not related. Conclusion Although the pattern and the degree of intensity of THAD and AC severity were not related, THAD might be useful in diagnosing AC. Thus, THAD should be considered a diagnostic criterion for AC.

N-Acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyzes the β1-6 branching of N-acetylglucosamine on asparagine-linked oligosaccharides of cellular proteins, enhances the malignant behaviors of carcinoma cells in experimental models. The aim of this study was to determine clinical significance of GnT-V expression in human pT2 gallbladder carcinoma with simple in vitro experiments. Ninety patients with pT2 gallbladder carcinoma were included for this study. The in vitro and in vivo biological effects of GnT-V were investigated using gallbladder carcinoma cells with variable GnT-V expression levels induced by a small interfering RNA. Of the 90 cases, 57 showed positive staining and the remaining 33 demonstrated negative staining, the subcellular localization in the 57 cases was classified into the granular-type in 31 cases and the diffuse-type in 26 cases. In 76 cases with curative resection, postsurgical survival was significantly poorer in those showing positive staining than in those showing negative staining (P = 0.028). In all of the 76 cases, postsurgical recurrence was significantly more frequent in those showing diffuse-type localization than in those showing negative staining. Experimental analyses demonstrated that the down-regulation of GnT-V expression in gallbladder carcinoma cells induced suppression of cell growth in vitro. The expression levels of GnT-V in the cells were highly correlated with the rapid in vivo growth coupled with the enhanced angiogenesis, and the tendency to form liver metastasis. GnT-V expression in the subserosal layer of pT2 gallbladder carcinoma is correlated with the aggressiveness of the disease.

Intrahepatic metastasis of intrahepatic cholangiocarcinoma (ICC) has not been evaluated in detail. We report a case of mass-forming type ICC with micrometastasis to the distant portal tract in a 40-year-old woman. In 2006, she was given a diagnosis of mass-forming type ICC, 4 cm in diameter, and right hepatectomy with lymph node dissection was performed. Macroscopic findings showed an irregular white mass-forming type lesion with two small daughter lesions and portal vein invasion in the S5 subsegment. Microscopically, other cancer cells within vessels had proliferated in the peripheral portal tract of the S8 subsegment, and these cancer cells in the portal tract had invaded the vessel wall. The endothelial cells of the vessels around the cancer cells were positive for CD34, but negative for D2-40 and CK19 on immunohistochemical analysis. Therefore, intrahepatic metastasis of cancer cells through the portal vein was diagnosed. Intrahepatic metastasis of cancer cells through the portal vein was demonstrated in a patient with mass-forming ICC.

We conducted this study to evaluate the optimal hepatic resection for pT2 and pT3 advanced carcinoma of the gallbladder without invasion of the hepatoduodenal ligament. We conducted a questionnaire survey regarding 4,243 cases of carcinoma of the gallbladder treated during the recent 10-year period at 112 institutions belonging to the Japanese Society of Biliary Surgery. The questionnaires included questions on preoperative-diagnosis, complications, treatment, and surgical treatment, procedures of resection, surgical result, path histological findings, mode, and site of recurrence, additional post-operative treatment. They included 293 pT2 and 192 pT3 R0 cases, which were negative for hepatoduodenal ligament invasion, and the cumulative survival rates and sites of postoperative recurrence in the form of liver metastasis, were retrospectively analyzed in these 485 cases. There were no significant differences in survival rate or recurrence rates in the form of liver metastasis between the groups that underwent resection of the gallbladder bed, the group that underwent segmentectomy 4a+5, and the group that underwent hepatectomy in patients with of both pT2 or pT3 gallbladder cancers. Our results also did not show that liver metastasis to segment 4a5 alone was particularly common. For gallbladder cancer, neither with hepatoduodenal ligament invasion nor hepatic invasion, resection of the gallbladder bed is more preferable for surgical hepatic procedure. For gallbladder cancer that invades any hepatic sites, a hepatic surgical procedure that could eliminate surgical margins would be desirable.

From 1979 to 1996, 32 patients underwent at least right hepatic lobectomy with pancreatoduodenectomy (right HPD) for advanced carcinoma of the biliary tract at our institute. Twelve of the 32 patients underwent hepatoligamentopancreatoduodenectomy (HLPD). Curative resection was achieved in 20 (63%) of the 32 patients, but the operative outcomes were not satisfactory. Operative deaths occurred in 15 (47%) of the 32 patients, and postoperative complications in 29 (91%). The overall cumulative 1-, 3-, and 5-year survival rates were 12%, 6%, and 3%, respectively. These results suggested that simultaneous hepatectomy of the right lobe and pancreatoduodenectomy is undesirable, especially when accompanied by vascular resection and reconstruction. Since 1997, we have used partial pancreatectomy and partial duodenectomy instead of pancreatoduodenectomy for access to peripancreatic lesions, and this has markedly improved the operative outcome. From 1997 to 2004, 42 patients underwent resection of the right hepatic lobe, extrahepatic bile duct, and other related organs for advanced carcinoma of the biliary tract. There were postoperative complications in 13 (31%), but no operative death occurred. Recent advances in operative procedures and perioperative management may offer greater safety for right HPD, but the appropriate applications of and the necessity for right HPD are still matters of controversy and require further discussion.

Background The Japanese Society of Hepato-Biliary-Pancreatic Surgery launched the clinical practice guidelines for the management of biliary tract and ampullary carcinomas in 2008. Novel treatment modalities and handling of clinical issues have been proposed after the publication. New approaches for editing clinical guidelines, such as the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, also have been introduced for better and clearer grading of recommendations. Methods Clinical questions (CQs) were proposed in seven topics. Recommendation, grade of recommendation and statement for each CQ were discussed and finalized by evidence-based approach. Recommendation was graded to grade 1 (strong) and 2 (weak) according to the concept of GRADE system. Results The 29 CQs covered seven topics: (1) prophylactic treatment, (2) diagnosis, (3) biliary drainage, (4) surgical treatment, (5) chemotherapy, (6) radiation therapy, and (7) pathology. In 27 CQs, 19 recommendations were rated strong and 11 recommendations weak. Each CQ included the statement of how the recommendation was graded. Conclusions This guideline provides recommendation for important clinical aspects based on evidence. Future collaboration with cancer registry will be a key for assessment of the guidelines and establishment of new evidence. Free full-text articles and a mobile application of this guideline are available via http://www.jshbps.jp/en/guideline/biliary-tract2.html.

Several studies have reported that heat stress stimulates the activity of osteoblastic cells in vitro. However, few have addressed the effects of heat stress on osteogenesis in vivo, nor have the optimal temperatures for bone formation been determined. The aim of the present study was to investigate the effects of hyperthermia treatment on osteogenesis in a rat tibial defect model. Forty-four Sprague Dawley rats were divided into two groups with or without hyperthermia treatment. A 3-mm circular defect in the proximal tibia filled with magnetite cationic liposomes embedded in alginate beads was subjected to hyperthermia treatment (43-46 °C). Radiological assessment at 2 weeks after the treatment showed that significantly stimulated osteogenesis was observed in the hyperthermia group as compared to the control group (p = 0.003). Histomorphometrical analysis at 2 weeks revealed a significant increase of newly formed bone in the hyperthermia group, compared with the control group (p < 0.001). Area of newly formed bone in each hyperthermia group was significantly increased as compared with the control group (43 °C; p = 0.005, 44 °C; p = 0.019, 45 °C; p = 0.003, and 46 °C; p = 0.003, respectively). Alkaline phosphatase was overexpressed at the surfaces of newly formed bone adjacent to magnetite cationic liposome implantation. Our results demonstrate for the first time that heat stimulus accelerates osteogenesis in vivo, and may thus be of interest as a novel and promising tool to induce osteogenesis clinically as well.

Carcinoma of the gallbladder shows diverse patterns of spread. The most appropriate surgical procedures according to the depth and extent of the spread of the tumor are still controversial. We investigated this surgical problem clinicopathologically, especially regarding the indications for pancreatoduodenectomy (PD), by retrospectively reviewing the clinical records of 216 patients who were surgically treated for advanced gallbladder carcinoma. Detailed studies of resected specimens, in our department, showed that preservation of the pancreas head carried an increased risk of residual microscopic metastases in small peripancreatic lymphatic nodes and ducts. Some patients with curative operations had shown recurrence in lymph nodes around the head of the pancreas within a few years after PD. Therefore, we performed hepatopancreatoduodenectomy (HPD) in 93 patients, some of whom underwent the HPD as a prophylactic dissection of peripancreatic lymph nodes and some of whom underwent the HPD as a curative resection due to invasion to the peripancreatic lymph nodes, duodenum, and pancreas, observed macroscopically. The surgical outcome after PD was compared with that obtained after other curative resections (non-HPD). In patients with microscopically negative lymph node metastasis without hepatoduodenal ligament invasion, PD was not necessary for a complete resection of lymphatic metastases around the pancreas head. The 5-year survival rate of these patients who had HPD was not significantly higher than that for non-HPD resections with curative intent (73% vs 63%), and lymphatic recurrence was not marked. On the other hand, in patients with positive lymph node metastases without hepatoduodenal ligament invasion, PD was necessary for a complete resection. The 5-year survival rate after HPD in these patients was significantly improved compared to that after non-HPD resections with curative intent (87% vs 17%), because lymphatic recurrence was reduced (0% vs 80%). In advanced carcinomas with positive hepatoduodenal ligament invasion, although the basic operative strategy, which inevitably includes right lobectomy, should be curative, PD should not be performed for prophylactic lymphatic resection, because local recurrence in the hepatoduodenal ligament cannot be controlled by PD, and the 5-year survival rate of curative HPD was only 4% (non-HPD resection with curative intent, 18%); moreover, frequent, lethal, major postoperative complications (hepatic failure) occurred after combined right lobectomy.

A recent study reported that heat stress stimulates osteogenesis in an in vivo rat model using alginate gel and magnetite cationic liposomes. However, for clinical use, the efficacy for promoting osteogenesis needs to be investigated using clinically approved materials, and preferably with animals larger than rats. The aim of this study was to evaluate multiple heat stimuli-triggered osteogenesis in rat tibial defect models using already clinically applicable materials (Resovist® and REGENOS®) and determine the efficacy also in the rabbit. Fifty-eight rats and 10 rabbits were divided into two groups, respectively, with or without hyperthermia treatment at 45°C for 15 min. (hyperthermia; 20 rats once a week, 8 rats three times a week, 5 rabbits once a week, control; 30 rats and 5 rabbits). Micro-CT assessment at 4 weeks revealed that a significantly stimulated osteogenesis was observed in the once a week group of both rats and rabbits as compared to the control group (p = 0.018 and 0.036, respectively). In contrast, the three times a week group did not show enhanced osteogenesis. Histological examination and image analysis showed consistent results in which the area of mineralized bone formation in the once a week hyperthermia group was significantly increased compared with that in the control group at four weeks (rat; p = 0.026, rabbit; p = 0.031). Newly formed bone was observed in the grafted materials from the periphery toward the center, and more osteoclasts were found in the once a week group. Heat stress also induced enhanced alkaline phosphatase expression in cultured osteoblastic cells, MC3T3, in vitro (p = 0.03). On the other hand, heat stress had no obvious effects on chondrogenic differentiation using ATDC5 cells. Our study demonstrates that heat-stimuli with clinically applicable novel heating materials can promote significant osteogenesis, and may thus be a promising treatment option for diseases associated with bone defects.

Mechanochemical dry conversion that only uses zinc oxide and an imidazole ligand proved to be effective and reliable for fabrication of a zeolitic imidazolate framework with a polycrystalline grain boundary and a core–shell structure. The zinc oxide crystals are converted into a zeolitic imidazolate framework to a depth of approx. 10 nm below the surface.

The patient was a 69-year-old woman with a chief complaint of melena, who had a palpable firm mass and tenderness on digital rectal examination. Colonoscopy (CS) showed a depressed hemorrhagic lesion 2cm in diameter on the left anterior wall of the anal canal near the dentate line. Biopsy examination yielded a diagnosis of basaloid cell carcinoma. On the basis of a diagnosis of clinical stage I (T1N0M0) anal canal cancer, chemoradiotherapy was performed. After treatment, no tumor cells were detected on biopsy. Basaloid cell carcinoma, accounting for about 1.6% of anal canal cancers, is rare. Only 4 among 62 reported cases (including our patient) received chemoradiation therapy.

Congenital choledochal cyst with pancreaticobiliary maljunction (PBM) is known as a high-risk factor for various complications such as cholangitis, pancreatitis, and carcinogenesis of the biliary system by mutual refluxes of bile and pancreatic juice. Furthermore, it is not rare to suffer from postoperative complications if the wrong operative procedure is chosen. Therefore, we sought to review the relationship between operative procedure for types I and IV-A (Todani's classification) congenital choledochal cyst with PBM, and long-term treatment outcome.A retrospective review was carried out of 144 patients who underwent flow diversion surgery in our institution during the 40-year period from 1968 to 2008 and who did not have a coexisting malignant tumor at the time of surgery.Of these 144 patients, 137 underwent complete cyst excision and 7 underwent pancreas head resection as flow diversion surgery. The follow-up periods ranged from 1 to 345 months and from 1 to 271 months (average, 100.2 and 94.1) in patients with type I and type IV-A cysts, respectively. Regarding surgical treatment outcome, postoperative progress was good in 130 (90.3%) of the 144 patients. Fourteen patients required hospitalization for long-term postoperative complications such as cholangitis, pancreatitis, intrahepatic calculi, pancreatic calculus, and carcinogenesis during postoperative follow-up. Of these, 2 patients who underwent surgery for type IV-A cysts died because of secondary biliary cirrhosis with liver failure and advanced intrahepatic cholangiocarcinoma, respectively.The present study shows that flow diversion surgery for congenital choledochal cysts with PBM significantly reduces the risk of subsequent development of malignancy in the biliary tract, and it is vital to choose the appropriate operative procedure to prevent occurrence of these postoperative complications.

A 34-year-old female patient was seen at the hospital because of right flank pain, back pain, and anemia. Abdominal ultrasonography demonstrated a round 10×10cm cystic retroperitoneal mass just behind the right lobe of the liver, superior to the right kidney and to the right of the vena cava. Abdominal CT and MRI confirmed these findings. Cavogram revealed compression of vena cava by the tumor. Right renal angiogram revealed feeding arteries from the adrenal arteries to the tumor. Three dimentional CT image visualized the accurate anatomical relationship between the tumor and surrounding vascular structures. A preoperative diagnosis of adrenal pseudocyst was made, and the lesion was removed surgically on July 21, 1992. The three dimentional anatomical relationship between the tumor and surrounding vascular structure was the same as preoperative determination by 3D-volume CT. Histopathologically the tumor was adrenal pseudocyst. The patient was discharged in a good clinical condition on August 5, 1992. Three dimentional CT imaging was very useful to image anatomical relationship between the tumor and surrounding vascular structure preoperatively.

Background Outcomes after hepatectomy in patients with mass-forming (MF) type intrahepatic cholangiocarcinoma (ICC) with marked enhancement within the tumor on arterial-phase computed tomography (CT) scans have not been clarified in detail. Methods We retrospectively studied 140 patients with MF type ICC who underwent hepatectomy from 1989 through 2008. Surgical outcomes were compared between 25 patients with MF type ICC with marked enhancement within the tumor (hypervascular ICC) and 109 patients without enhancement within the tumor (hypovascular ICC) on arterial-phase CT scans. Results Portal invasion and intrahepatic metastasis were significantly lower in patients with hypervascular ICC than in those with hypovascular ICC. The 5-year survival rate was significantly higher in patients with hypervascular ICC (86%) than in patients with hypovascular ICC (27%, P

Background The clinical relevance of the ductal margins in operative resection of bile duct carcinoma has not been well established. The purpose of this study was to assess the prognostic significance of ductal margins in patients with bile duct carcinoma. Method A total of 256 patients with bile duct carcinoma were analyzed retrospectively. We compared clinicopathologic features, outcomes, and recurrences among patients who underwent curative resections with free margins (D-FRE: n = 185), noncurative resections only resulting from the involvement of ductal margins with carcinoma in situ (D-CIS: n = 13), noncurative resections only caused by the involvement of ductal margins with invasive foci of carcinoma (D-INV: n = 17), and noncurative resections resulting from any other margin state and/or distant metastases (OTH: n = 41). Results Histologic grades, node involvements, T classifications, and JSBS staging were significantly associated with the ductal margin state. The 5-year survival rate by Kaplan-Meier analysis was 54.7%, 52.4%, 17.6%, and 16.7% for patients with D-FRE, D-CIS, D-INV, and OTH, respectively. A multivariate analysis by the Cox proportional hazards model has shown that, in addition to lymph node involvement (P = 6.6 × 10–4) and venous invasion (P = 2 × 10–5), D-FRE versus D-INV and D-FRE versus OTH, but not D-FRE versus D-CIS, were independently associated with survival with P values of 8 × 10–4 and 1.4 × 10–5, respectively. Taken together along with the difference in the recurrence rates, patients with D-CIS seem to have outcomes similar to D-FRE but different from D-INV or OTH. Conclusion Compared with free ductal margins, the ductal margins with invasive foci of carcinoma may involve a significant disadvantage in terms of patients' outcomes in surgical resection for bile duct carcinoma, unlike those with carcinoma in situ.

We assessed the significance of an extra bile duct resection by comparing the survival of patients with advanced gallbladder carcinoma who had resected bile ducts with those who had preserved bile ducts. A radical cholecystectomy that includes extra bile duct resections has been performed without any clear evidence of whether an extra bile duct resection is preventive or curative.We conducted a questionnaire survey among clinicians who belonged to the 114 member institutions of the Japanese Society of Biliary Surgery. The questionnaires included questions on the preoperative diagnosis, complications, treatment, and surgical treatment, resection procedures, surgical results, pathological and histological findings, mode and site of recurrence, and the need for additional postoperative treatment. A total of 4243 patients who had gallbladder carcinoma and were treated from January 1, 1994 to December 31, 2003 were identified. The 838 R0 patients with pT2, pT3, and pT4 advanced carcinoma of the gallbladder for which there was no cancer invasion to the hepatoduodenal ligament or cystic duct in the final analysis.The 5-year cumulative survival, postoperative complications, postoperative lymph node metastasis, and local recurrence along the hepatoduodenal ligament were not substantially different between the resected bile duct and the preserved bile duct groups.Our retrospective questionnaire survey showed that an extrahepatic bile duct resection had no preventive value in some patients with advanced gallbladder carcinoma in comparison to similar patients who had no such bile duct resection. An extrahepatic bile duct resection may therefore be unnecessary in advanced gallbladder carcinoma without a direct infiltration of the hepatoduodenal ligament and the cystic duct.