Multiomics identifies the link between intratumor steatosis and the exhausted tumor immune microenvironment in hepatocellular carcinoma.

BACKGROUND AND AIMS: Immunotherapy has become the standard-of-care treatment for hepatocellular carcinoma (HCC), but its efficacy remains limited. To identify immunotherapy-susceptible HCC, we profiled the molecular abnormalities and tumor immune microenvironment (TIME) of rapidly increasing nonviral HCC. APPROACHES AND RESULTS: We performed RNA-seq of tumor tissues in 113 patients with nonviral HCC and cancer genome sequencing of 69 genes with recurrent genetic alterations reported in HCC. Unsupervised hierarchical clustering classified nonviral HCCs into three molecular classes (Class I, II, III), which stratified patient prognosis. Class I, with the poorest prognosis, was associated with TP53 mutations, whereas class III, with the best prognosis, was associated with cadherin-associated protein beta 1 (CTNNB1) mutations. Thirty-eight percent of nonviral HCC was defined as an immune class characterized by a high frequency of intratumoral steatosis and a low frequency of CTNNB1 mutations. Steatotic HCC, which accounts for 23% of nonviral HCC cases, presented an immune-enriched but immune-exhausted TIME characterized by T cell exhaustion, M2 macrophage and cancer-associated fibroblast (CAF) infiltration, high PD-L1 expression, and TGF-ß signaling activation. Spatial transcriptome analysis suggested that M2 macrophages and CAFs may be in close proximity to exhausted CD8+ T cells in steatotic HCC. An in vitro study showed that palmitic acid-induced lipid accumulation in HCC cells upregulated PD-L1 expression and promoted immunosuppressive phenotypes of cocultured macrophages and fibroblasts. Patients with steatotic HCC, confirmed by chemical-shift MR imaging, had significantly longer PFS with combined immunotherapy using anti-PD-L1 and anti-VEGF antibodies. CONCLUSIONS: Multiomics stratified nonviral HCCs according to prognosis or TIME. We identified the link between intratumoral steatosis and immune-exhausted immunotherapy-susceptible TIME.

Efficacy of laparoscopic liver resection for small hepatocellular carcinoma located in the posterosuperior segments: A multi-institutional study using propensity score matching by the Kyushu Study Group of Liver Surgery.

AIM: Laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) located in the posterosuperior segments (PS) have generally been considered more difficult than those for HCC in anterolateral segments (AL), but may be safe and feasible for selected patients with accumulated experience. In the present study, we investigated the effectiveness of LLR for single nodular HCCs ≤3 cm located in PS. METHODS: In total, 473 patients who underwent partial liver resection for single nodular HCCs ≤3 cm at the 18 institutions belonging to the Kyusyu Study Group of Liver Surgery from January 2010 to December 2018 were enrolled. The short-term outcomes of laparoscopic partial liver resection and open liver resection (OLR) for HCCs ≤3 cm, with subgroup analysis of PS and AL, were compared using propensity score-matching analysis. Furthermore, results were also compared between LLR-PS and LLR-AL. RESULTS: The original cohort of patients with HCC ≤3 cm included 328 patients with LLR and 145 with OLR. After matching, 140 patients with LLR and 140 with OLR were analyzed. Significant differences were found between groups in terms of volume of blood loss (median, 55 vs. 287 ml, p < 0.001), postoperative complications (0.71 vs. 8.57%, p = 0.003), and postoperative hospital stay (median, 9 vs. 14 days, p < 0.001). The results of subgroup analysis of PS were similar. Short-term outcomes did not differ significantly between LLR-PS and LLR-AL after matching. CONCLUSIONS: Laparoscopic partial resection could be the preferred option for single nodular HCCs ≤3 cm located in PS.

[A Case of Curative Resection Following TNT for Locally Advanced Rectal Cancer with Liver Metastasis].

The standard treatment of locally advanced rectal cancer is preoperative chemoradiotherapy(CRT)in Europe and the United States, while that is surgical excision and lateral pelvic lymph node dissection followed by adjuvant chemotherapy in Japan. Recently, total neoadjuvant therapy(TNT), which combines neoadjuvant chemotherapy and preoperative CRT, have been popular. We performed curative excision for initially locally advanced rectal cancer with liver metastasis after TNT. A 61- year-old woman was diagnosed as having rectal cancer with liver metastasis and invasion of the uterus, vagina, bladder, and left ureter. The patient underwent 8 courses of FOLFOX plus bevacizumab, followed by radiotherapy, and totally pelvic excision for the primary tumor. Because of liver metastasis progression, hepatectomy was performed after 6 courses of FOLFIRI plus panitumumab. The patient has been cancer free for 20 months to date. TNT is considered to be an effective strategy for the treatment of large locally advanced rectal cancer.

Spread of lymph node metastasis and adjuvant therapy for distal cholangiocarcinoma.

BACKGROUND: Lymphatic metastasis is a major route of metastasis in distal cholangiocarcinoma (DCC). The present study aimed to elucidate the pattern of lymph node (LN) metastasis and the effectiveness of LN dissection and postoperative adjuvant chemotherapy in patients with DCC. METHODS: Patients who underwent surgical resection with curative intent for DCC were enrolled. The nomenclature of the LN stations was defined according to the Japanese Society of Hepato-Biliary-Pancreatic Surgery guidelines. Effectiveness of LN dissection of each station was calculated using frequency of LN metastasis to the station and 5-year survival rate of patients with LN metastasis to that station. RESULTS: Of the 105 patients included in the study, 46 (43.8%) had LN metastasis, and 43 (41.0%) underwent postoperative adjuvant therapy. LN metastasis, serum carbohydrate antigen (CA) 19-9 level > 37 U/mL, and positive bile duct margin were independent risk factors for shorter overall survival (OS). The most common metastatic LN station at surgery was No. 13 (32.7%), followed by No. 12 (19.2%), No. 17 (9.6%), and No. 8 (6.6%). There was no effectiveness of LN dissection of the station No. 8, 14, and 16. Adjuvant chemotherapy was significantly associated with longer OS in patients with LN metastasis but not in those with positive ductal margins or serum CA 19-9 level > 37 U/mL. CONCLUSIONS: Postoperative adjuvant chemotherapy was associated with a better prognosis in patients with DCC and LN metastasis. However, a more effective therapeutic strategy is required to improve the prognosis of patients with other negative prognostic factors.

Effectiveness of Adjuvant Therapy in Patients with Pancreatic Cancer Who Underwent Neoadjuvant Therapy.

PURPOSE: Neoadjuvant therapy (NAT) is used to treat not only advanced pancreatic cancer but also resectable lesions. The present study investigated the effectiveness of postoperative adjuvant chemotherapy for patients with pancreatic cancer who underwent surgical resection after NAT. METHODS: Patients who underwent macroscopically curative resection after NAT for pancreatic cancer were enrolled. Adjuvant chemotherapy was defined as at least 1 cycle of planned chemotherapy within 3 months after the date of surgery and included S-1, gemcitabine, or both. We retrospectively examined the effect of adjuvant chemotherapy on overall survival (OS) and recurrence-free survival (RFS) as a function of patients' clinicopathological factors. RESULTS: Ninety-seven patients were included in the study, of which 68 (70.1%) underwent adjuvant chemotherapy. Administration of adjuvant chemotherapy was significantly associated with prolonged OS and RFS in patients whose elevated levels of carbohydrate antigen 19-9 or duke pancreatic monoclonal antigen type-2 did not normalize after NAT. In patients with pathological lymph node metastasis, the administration of adjuvant chemotherapy was significantly associated with longer OS but did not improve PFS. CONCLUSIONS: Postoperative adjuvant chemotherapy was associated with prolonged postoperative survival in patients with pancreatic cancer who did not sufficiently respond to NAT as judged by tumor marker expression.

The 1-year outcomes after pancreaticogastrostomy using vertical versus horizontal mattress suturing for gastric wrapping.

PURPOSE: To investigate the differences in nutritional status 1 year after pancreaticogastrostomy (PG) using vertical suturing (VS) vs. twin square horizontal mattress (HMS) suturing in patients undergoing pancreaticoduodenectomy (PD). METHODS: The subjects of this study were 134 patients who underwent PD, followed by PG, which was closed by VS in 52 and by HMS in 82. We evaluated the peri- and postoperative factors, nutritional parameters, diameter of the remnant main pancreatic duct, and glucose intolerance 1 year postoperatively. RESULTS: Forty-five (87%) patients from the VS group and 75 (91%) patients from the HMS group survived for more than 1 year. The incidences of intraabdominal abscess and pancreatic fistula were significantly lower in the HMS group than in the VS group (19.2% vs. 6.6% and19.2% vs. 2.6%, respectively). There were no significant changes in the total protein, serum albumin, and HbA1c levels 1 year postoperatively. The postoperative expansion ratio of the main pancreatic duct diameter was significantly smaller in the HMS group than in the VS group. The strongest risk factor for body weight loss 1 year postoperatively was a non-soft pancreas texture. CONCLUSION: HMS was superior to VS for preventing early postoperative complications and did not affect pancreatic function.

Indication and Prognostic Significance of Conversion Surgery in Patients with Liver Metastasis from Gastric Cancer.

OBJECTIVE: Chemotherapy is generally recommended as the first-line standard treatment in patients with liver metastasis from gastric cancer. However, the clinical impact of surgical treatment remains unclear in responders after chemotherapy. The present study aimed to investigate the tumor response and prognosis after chemotherapy and to assess the clinical indication of conversion surgery in responders. METHODS: The study retrospectively reviewed the clinical data of 44 patients with liver metastasis from gastric cancer who were treated with chemotherapy between February 2002 and January 2019. These patients were classified into progressive disease (PD) and non-PD groups according to tumor response. RESULTS: Among the 44 patients, 7 and 26 had peritoneal dissemination and ≥5 had metastatic liver nodules. Additionally, 15 and 29 patients had PD and non-PD, respectively. Surgical treatment was significantly correlated with tumor response (p < 0.0321). Prognostic differences between the PD and non-PD groups were significant (p < 0.0001). Moreover, gastrectomy and hepatectomy were significantly correlated with the number of liver metastases (≥5 vs. <5, respectively) in the non-PD group (p = 0.0025 and p = 0.0169, respectively). The 3-year survival rates among patients with non-PD undergoing both gastrectomy and hepatectomy (n = 6), gastrectomy alone (n = 7), and nonsurgical treatments (n = 16) were 100, 66.7, and 0%, respectively (p = 0.0026). Multivariate analysis identified peritoneal dissemination as an independent prognostic factor (p = 0.0225). CONCLUSION: Our preliminary results suggest that conversion surgery for gastric cancer with liver metastasis might be clinically indicated in chemotherapy responders with <5 metastatic liver nodules and without peritoneal dissemination.

Lung recurrence and its therapeutic strategy in patients with pancreatic cancer.

BACKGROUND: /Objectives: The lung is a major metastatic site of pancreatic cancer (PC). We aimed to assess the features and prognosis of patients with PC according to the recurrence pattern and the effect of resection of recurrent lung lesion. METHODS: We enrolled 168 PC patients who had undergone macroscopically curative resection. All resected lung tumors were evaluated immunohistochemically for expressions of thyroid transcription factor-1 (TTF-1) and napsin A. RESULTS: The most common site of first recurrence was the liver and local site, followed by the lung, peritoneum, and lymph node. Lung recurrence was observed significantly later than was liver recurrence. The median survival time (MST) after recurrence in patients with first recurrence in the lung was significantly longer than MST in patients with first recurrence in the liver (15.2 months vs 5.2 months, p = 0.039). Seven patients with lung recurrence underwent resection of the recurrent lesion. Surgical resection of single metastasis limited to the lung showed favorable overall survival after recurrence (MST = 36.5 months). Patients with single metastasis limited to the lung showed significantly lower value of FDG-PET SUVmax of the primary pancreatic tumor. CONCLUSIONS: Patients with first recurrence in the lung showed better prognosis than did patients with first recurrence in the liver. Single metastasis limited to the lung could benefit from surgical resection and was significantly associated with lower FDG-PET SUVmax of the primary pancreatic tumor.

[Single Liver Metastasis of Breast Cancer Mimicking Intrahepatic Cholangiocarcinoma 13 Years after the Primary Surgery-A Case Report].

A 78-year-old woman underwent left total mastectomy for breast cancer at 65 years of age.Thirteen years after the primary surgery, CT showed a single 46mm tumor located in liver segment 4.The tumor was difficult to distinguish between cholangiocellular carcinoma and liver metastasis of the breast cancer.We did not perform biopsy, considering dissemination, and performed left hemihepatectomy and left caudate lobectomy.Pathological findings revealed liver metastasis of breast cancer.Hepatic resection is a useful option in cases of single liver metastasis from breast cancer that are difficult to distinguish from cholangiocellular carcinoma.

A nomogram to preoperatively predict 1-year disease-specific survival in resected pancreatic cancer following neoadjuvant chemoradiation therapy.

OBJECTIVE: This study aimed to develop a nomogram to predict the 1-year survival of patients with pancreatic cancer who underwent pancreatectomy following neoadjuvant treatment with preoperatively detectable clinical parameters. Extended pancreatectomy is necessary to achieve complete tumor removal in borderline resectable and locally advanced pancreatic cancer. However, it increases postoperative morbidity and mortality rates, and should be balanced with potential benefit of long-term survival. METHODS: The medical records of patients who underwent pancreatectomy following neoadjuvant treatment from January 2005 to December 2016 at Severance Hospital were retrospectively reviewed. Medical records were collected from five international institutions from Japan and Singapore for external validation. RESULTS: A total of 113 patients were enrolled. The nomogram for predicting 1-year disease-specific survival was created based on 5 clinically detectable preoperative parameters as follows: age (year), symptom (no/yes), tumor size at initial diagnostic stage (cm), preoperative serum carbohydrate antigen (CA) 19-9 level after neoadjuvant treatment (<34/≥34 U/mL), and planned surgery [pancreaticoduodenectomy (PD) (pylorus-preserving PD)/distal pancreatectomy (DP)/total pancreatectomy]. Model performance was assessed for discrimination and calibration. The calibration plot showed good agreement between actual and predicted survival probabilities; the the Greenwood-Nam-D'Agostino (GND) goodness-of-fit test showed that the model was well calibrated (χ2=8.24, P=0.5099). A total of 84 patients were used for external validation. When correlating actual disease-specific survival and calculated 1-year disease-specific survival, there were significance differences according to the calculated probability of 1-year survival among the three groups (P=0.044). CONCLUSIONS: The developed nomogram had quite acceptable accuracy and clinical feasibility in the decision-making process for the management of pancreatic cancer.

Gene regulation by antitumor miR-130b-5p in pancreatic ductal adenocarcinoma: the clinical significance of oncogenic EPS8.

Our ongoing analyses identifying dysregulated microRNAs (miRNAs) and their controlled target RNAs have shed light on novel oncogenic pathways in pancreatic ductal adenocarcinoma (PDAC). The PDAC miRNA signature obtained by RNA sequencing showed that both strands of pre-miR-130b (miR-130b-5p, the passenger strand and miR-130b-3p, the guide strand) were significantly downregulated in cancer tissues. Our functional assays revealed that miR-130b-5p significantly blocked the malignant abilities of PDAC cell lines (PANC-1 and SW1990), e.g., cancer cell proliferation, migration, and invasion. A total of 103 genes were identified as possible oncogenic targets by miR-130b-5p regulation in PDAC cells based on genome-wide gene expression analysis and in silico database search. Among the possible targets, high expression of 9 genes (EPS8, ZWINT, SMC4, LDHA, GJB2, ZCCHC24, TOP2A, ANLN, and ADCY3) predicted a significantly poorer prognosis of PDAC patients (5-year overall survival, p < 0.001). Furthermore, we focused on EPS8 because its expression had the greatest impact on patient prognosis (overall survival, p < 0.0001). Overexpression of EPS8 was detected in PDAC clinical specimens. Knockdown assays with siEPS8 showed that its overexpression enhanced cancer cell proliferation, migration, and invasion. Analysis of downstream RNA networks regulated by EPS8 indicated that MET, HMGA2, FERMT1, RARRES3, PTK2, MAD2L1, and FLI1 were closely involved in PDAC pathogenesis. Genes regulated by antitumor miR-130b-5p were closely involved in PDAC molecular pathogenesis. Our approach, discovery of antitumor miRNAs and their target RNAs, will contribute to exploring the causes of this malignant disease.

Significance of 18F-Fluorodeoxyglucose (FDG) Uptake in Response to Chemoradiotherapy for Pancreatic Cancer.

BACKGROUND: A metabolic shift to glycolysis is reportedly involved in radioresistance. We examined whether pretreatment 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), which can detect enhanced glucose uptake, was able to predict the therapeutic response to chemoradiotherapy (CRT) in patients with pancreatic cancer (PC). METHODS: Of 125 PC patients (75 unresectable and 50 borderline resectable), 37 and 26 underwent induction chemotherapy before CRT and surgical resection after CRT, respectively. FDG-PET was performed at three different institutions. RESULTS: Of the 88 patients who underwent upfront CRT, 31 (35%), 34 (39%), and 23 (26%) showed a partial response (PR), stable disease, and progressive disease, respectively. The tumor PR rate was an independent factor associated with longer overall survival (OS) on multivariate analysis. We evaluated the optimal cut-off of maximum standardized uptake values (SUVmax) at initial diagnosis to detect the tumor PR rate at the three institutions separately. The SUVmax was independently associated with tumor response rate on multivariate analysis. In the low SUVmax group, induction chemotherapy had no significant impact on OS. In contrast, induction chemotherapy was significantly associated with longer OS in the high SUVmax group. CONCLUSIONS: FDG-PET SUVmax was significantly associated with the therapeutic response to CRT in PC patients. Moreover, induction chemotherapy may improve the prognosis of patients with a high SUVmax tumor.

New scoring system for resectable hepatocellular carcinoma with a maximum tumor size of ≤5 cm based on preoperative tumor factors.

BACKGROUND: The aim of this study was to establish a new scoring system for hepatocellular carcinoma (HCC) that can be used to predict the postoperative prognosis of HCC patients. METHODS: A total of 359 HCC patients who underwent hepatectomy were included in this study. All eligible patients were randomly allocated to derivation cohort or validation cohort samples. We assigned one point each for preoperative factors identified in the derivation cohort, and the sum of the scores was used to classify the patients into high-risk and low-risk groups. The scoring system established using the derivation cohort was fitted to the validation cohort. RESULTS: The prognosis of the high-risk group was significantly poorer than that of the low-risk group in both the derivation and validation samples (p = 0.04, p < 0.01, respectively). In the high-risk group, major hepatectomy resulted in a significantly better prognosis than minor hepatectomy in both samples (p = 0.04, p = 0.03, respectively). On the other hand, the extent of hepatectomy did not influence the prognosis of the low-risk group in either sample (p = 0.14, p = 0.34, respectively). CONCLUSION: Our new scoring system can predict the treatment outcome of patients undergoing curative hepatectomy for HCC and could help determine the optimal extent of resection.

Significance of Glucose Transporter Type 1 (GLUT-1) Expression in the Therapeutic Strategy for Pancreatic Ductal Adenocarcinoma.

BACKGROUND: This study aimed to examine the prognostic relevance of glucose transporter type 1 (GLUT-1), which is a key regulator of the glucose metabolism. In particular, the study aimed to examine the association between GLUT-1 expression and the therapeutic effect of chemoradiotherapy (CRT) in pancreatic ductal adenocarcinoma (PDAC). METHODS: Patients with PDAC were enrolled in the study. Patients with distant metastases and those who received only chemotherapy as treatment were excluded from the study. Specimens for immunohistochemical evaluations were obtained through surgical resection and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of the primary tumor before any treatment. RESULTS: This study included 197 patients. Of these 197 patients, 100 underwent upfront surgery, and 97 received neoadjuvant CRT (NACRT), which was performed mainly for patients with locally advanced tumors. Of the 97 patients who received NACRT, 21 later underwent surgical resection. For the patients who underwent upfront surgery, low GLUT-1 expression was an independent factor for a better prognosis. For the patients who underwent NACRT, low GLUT-1 expression was significantly associated with greater tumor size reduction, a higher resection rate, and a better prognosis. Additionally, GLUT-1 expression was significantly increased after NACRT treatment. CONCLUSIONS: Among the patients with PDAC, those with low GLUT-1 expression in the primary tumor had a better prognosis those with high GLUT-1 expression. Moreover, the patients with low GLUT-1 expression displayed a better therapeutic response to NACRT.

Indication of extrahepatic bile duct resection for gallbladder cancer.

PURPOSE: Extrahepatic bile duct (EHBD) resection is performed as part of radical cholecystectomy for gallbladder (GB) cancer. However, the indication for EHBD resection is still controversial. The aim of the present study was to evaluate the prognostic value of this procedure. METHODS: Patients who underwent surgical resection for GB cancer with curative intent were enrolled. We divided GB cancer into two categories based on the tumor location: proximal-type and distal-type tumors. The former refers to tumors involving the neck or cystic duct, while the latter comprises tumors located between the body and fundus. RESULTS: This study included 80 patients, 40 each with proximal- and distal-type tumors. Proximal tumor location, lymph node metastasis, and a serum carcinoembryonic antigen level > 5.0 ng/mL were independent predictors of poor prognosis. The 5-year survival rates of patients with proximal-type and distal-type tumors were 33.3 and 73.5%, respectively. Patients with proximal-type tumors showed significantly lower rates of R0 resection, more frequently had ≥ 3 metastatic lymph nodes, and exhibited a higher rate of perineural invasion. EHBD resection improved prognoses only in patients with proximal-type tumors but not in those with distal-type tumors. In the former group, EHBD resection significantly reduced the rate of local or regional lymph node recurrence. CONCLUSIONS: Extended cholecystectomy with EHBD resection should be performed for patients with GB cancer involving the neck and cystic duct to reduce local and regional lymph node recurrence and achieve better prognosis.

[A Case of Adult Undifferentiated Sarcoma of the Liver with Intraatrial Metastasis].

A 24-year-old woman was admitted to the hospital for abdominal pain. Abdominal contrast-enhanced computed tomography( CT)revealed a cystic mass measuring 11×8 cm in the left lobe of the liver with extravasation. Vascular embolization was performed, but extravasation remained on CT images. She was then transferred to our hospital. We performed an emergency extended left hepatectomy. Histopathological examination revealed solid proliferation of spindle-shaped cells. Immunohistochemical staining showed that the tumor cells were positive for vimentin and negative for AE1/AE3. Thus, a diagnosis of undifferentiated sarcoma was confirmed. Multiple recurrent tumors were recognized on CT images of the lung and right atrium taken 1 year and 10 months post-surgery. Partial resection of the tumor was performed for the right atrial mass, the left lingular segment, the left inferior lobe, and the right middle lobe. Pathological diagnosis confirmed metastasis of undifferentiated sarcoma from the liver. Chemotherapy consisting of vincristine, actinomycin D, and cyclophosphamide(VAC) was not effective, and the patient died 31 months after the primary surgery. Undifferentiated sarcoma of the liver is a rare malignant mesenchymal tumor, whose occurrence is extremely rare in adults. Although surgical treatment is the first choice, outcomes remain poor. Multimodality treatment should be used to improve the outcome.

Comparison of proton beam radiotherapy and hyper-fractionated accelerated chemoradiotherapy for locally advanced pancreatic cancer.

OBJECTIVES: We compared the clinical outcomes of proton beam radiotherapy (PBRT) and those of conventional chemoradiotherapy via hyper-fractionated acceleration radiotherapy (HART) after induction chemotherapy in patients with locally advanced pancreatic cancer (LAPC). METHODS: Twenty-five consecutive patients with LAPC received induction chemotherapy comprising gemcitabine and S-1 before radiotherapy. Of these, 15 and 10 were enrolled in the HART and PBRT groups, respectively. RESULTS: Moderate hematological toxicities were observed only in the HART group, whereas two patients in the PBRT group developed duodenal ulcers. All patients underwent scheduled radiotherapy, with overall disease control rates of 93% and 80% in the HART and PBRT groups, respectively. Local progression was observed in 60% and 40% of patients in the HART and PBRT groups, respectively. However, there was no statistical significance between the two groups regarding the median time to progression (15.4 months in both) and the median overall survival (23.4 v.s. 22.3 months). CONCLUSIONS: PBRT was feasible and tolerable, and scheduled protocols could be completed with careful attention to gastrointestinal ulcers. Despite the lower incidence of local recurrence, PBRT did not yield obvious progression control and survival benefits relative to conventional chemoradiotherapy.

Relationship between the surgical margin status, prognosis, and recurrence in extrahepatic bile duct cancer patients.

PURPOSE: The purpose of this retrospective study was to evaluate the relationship between the surgical margin status of the bile duct and the prognosis and recurrence of extrahepatic bile duct (EHBD) cancer. METHODS: The clinical data of 100 patients who underwent surgery for EHBD cancer between February 2002 and September 2014 were analyzed. The ductal margin status was classified into the following three categories: negative (D-N), positive with carcinoma in situ (D-CIS), and positive with invasive carcinoma (D-INV). RESULTS: The number of patients with D-N, D-CIS, and D-INV was 69, 16, and 15, respectively. Local recurrence rates of patients with D-CIS (56.3 %) and D-INV (66.7 %) were significantly higher compared to those of patients with D-N (10.1 %; P < 0.001). D-CIS was a significant predictor of shorter recurrence-free survival (RFS). Lymph node metastasis (P = 0.037) and D-INV (P = 0.008) were independent predictors of shorter disease-specific survival (DSS). The prognostic relevance of the ductal margin status was high, particularly in patients without lymph node metastasis. CONCLUSION: The surgical margin status of the bile duct was significantly associated with RFS, DSS, and the recurrence site.

Preoperative biliary drainage-related inflammation is associated with shorter survival in biliary tract cancer patients.

BACKGROUND: An association between inflammation and patient prognosis has been reported in various types of cancer. The aim of this study was to evaluate the influence of preoperative biliary drainage-related inflammation in patients with biliary tract cancer. METHODS: The clinical data of 97 patients who underwent surgery for extrahepatic bile duct cancer between February 2002 and September 2014 were analyzed, and the prognostic significance of tube-obstructive cholangitis after preoperative biliary drainage and pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) was evaluated. RESULTS: Eighty-four (86.6 %) of the 97 patients underwent ERCP and preoperative biliary drainage. Tube-obstructive cholangitis occurred in 25 cases and post-ERCP pancreatitis in 8 cases. Collectively, 30 patients experienced preoperative biliary drainage-related inflammation consisting of tube-obstructive cholangitis and/or post-ERCP pancreatitis. Drainage-related inflammation was significant risk factor of postoperative complications (P = 0.006), and significant poor predictors of shorter progression-free survival (P = 0.003) and overall survival (OS; P = 0.006) after surgery. In multivariate analysis, drainage-related inflammation was an independent predictor of shorter OS (hazard ratio, 1.924; P = 0.037) after surgery. CONCLUSION: Preoperative biliary drainage-related inflammation was an independent prognostic factor for shorter OS in biliary tract cancer patients.

[A Case of Curative Resection for Advanced Pancreatic Acinar Cell Carcinoma with Liver Metastasis and Involvement of the Superior Mesenteric Artery after Chemoradiotherapy Following Systemic Chemotherapy].

A 52-year-old man was initially diagnosed with an unresectable acinar cell carcinoma of the pancreas with liver metastasis and involvement of the superior mesenteric artery. After 5 courses of systemic chemotherapy(gemcitabine and S-1), the size of the pancreatic tumor had decreased from 31mm to 19mm and the liver metastasis had disappeared. We initiated chemoradiotherapy( CRT: S-1+56 Gy)for further local treatment. After CRT the size of the pancreatic tumor decreased to 13mm and his serum CA 19-9 level decreased from 677.2 U/mL to 38.1 U/mL. After 2months of S-1 administration, we performed subtotal stomach-preserving pancreaticoduodenectomy with D2 lymph node dissection. Histopathological examination revealed that most of the pancreatic cancer was replaced by fibrosis and only a few atypical epithelial cells existed. No cancer cells were found at the surgical margin. The patient remains alive without any signs of recurrence 59 months after the systemic chemotherapy and 51 months after the surgical resection.