Randomized phase II/III trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer (Prep-02/JSAP05).

A randomized, controlled trial has begun to compare neoadjuvant chemotherapy using gemcitabine and S-1 with upfront surgery for patients planned resection of pancreatic cancer. Patients were enrolled after the diagnosis of resectable or borderline resectable by portal vein involvement pancreatic cancer with histological confirmation. They were randomly assigned to either neoadjuvant chemotherapy or upfront surgery. Adjuvant chemotherapy using S-1 was administered for 6 months to patients with curative resection who fully recovered within 10 weeks after surgery in both arms. The primary endpoint is overall survival; secondary endpoints include adverse events, resection rate, recurrence-free survival, residual tumor status, nodal metastases and tumor marker kinetics. The target sample size was required to be at least 163 (alpha-error 0.05; power 0.8) in both arms. A total of 360 patients were required after considering ineligible cases. This trial began in January 2013 and was registered with the UMIN Clinical Trials Registry (UMIN000009634).

PHLDA3 is a novel tumor suppressor of pancreatic neuroendocrine tumors.

The molecular mechanisms underlying the development of pancreatic neuroendocrine tumors (PanNETs) have not been well defined. We report here that the genomic region of the PHLDA3 gene undergoes loss of heterozygosity (LOH) at a remarkably high frequency in human PanNETs, and this genetic change is correlated with disease progression and poor prognosis. We also show that the PHLDA3 locus undergoes methylation in addition to LOH, suggesting that a two-hit inactivation of the PHLDA3 gene is required for PanNET development. We demonstrate that PHLDA3 represses Akt activity and Akt-regulated biological processes in pancreatic endocrine tissues, and that PHLDA3-deficient mice develop islet hyperplasia. In addition, we show that the tumor-suppressing pathway mediated by MEN1, a well-known tumor suppressor of PanNETs, is dependent on the pathway mediated by PHLDA3, and inactivation of PHLDA3 and MEN1 cooperatively contribute to PanNET development. Collectively, these results indicate the existence of a novel PHLDA3-mediated pathway of tumor suppression that is important in the development of PanNETs.

Erratum to: Impact of intra-abdominal absorbable sutures on surgical site infection in gastrointestinal and hepato-biliary-pancreatic surgery: results of a multicenter, randomized, prospective, phase II clinical trial.

In the original publication, the article category was published as "Review Article". The correct category should read as "Original Article".

Impact of intra-abdominal absorbable sutures on surgical site infection in gastrointestinal and hepato-biliary-pancreatic surgery: results of a multicenter, randomized, prospective, phase II clinical trial.

BACKGROUND: The use of absorbable sutures in wound closure has been shown to reduce the incidence of surgical site infection (SSI); however, there is no evidence that the intra-abdominal use of absorbable rather than silk sutures reduces the incidence of SSI after gastrointestinal surgery. We report the findings of a phase II trial, designed to evaluate the impact of the intra-abdominal use of absorbable sutures on the incidence of SSI. METHODS: At 19 Japanese hospitals, 1147 patients undergoing elective gastrectomy, colorectal surgery, hepatectomy, or pancreaticoduodenectomy (PD) were randomly assigned to absorbable or silk intra-abdominal suture groups. The primary efficacy endpoint was the incidence of SSI. The secondary efficacy endpoints were the locations of SSI, time to resolution of SSI, length of hospital stay, and the incidence of bile leakage in hepatectomy and pancreatic fistula. RESULTS: The incidence of SSI was 11.3%, 15.5%, 11.3%, and 36.9% after gastrectomy, colorectal surgery, hepatectomy, and PD, respectively. The incidence of SSI was higher in the absorbable suture group than in the silk suture group for all the surgical procedures, but the difference was not significant. CONCLUSION: The intra-abdominal use of absorbable sutures did not have enough of an effect on the reduction of SSI in this phase II trial to justify the planning of a large-scale phase III trial.

Mucinous micropapillary pattern in lung adenocarcinomas: a unique histology with genetic correlates.

AIMS: In lung adenocarcinoma (ADC), micropapillary carcinomas (MPCs) are associated with poor prognosis because these tumours exhibit higher metastatic potential. Despite this, there are no studies investigating the differences between mucinous and non-mucinous MPC. METHODS AND RESULTS: We evaluated the proportion of micropapillary components in lung ADCs, and compared the differences with respect to the presence or absence of associated mucin. Tumour specimens from 694 patients with consecutively resected primary lung ADC were reviewed, and 37 cases of invasive mucinous ADCs were excluded. A significant (≥5%) micropapillary component was noted in 320 (48.7%) of 657 evaluable cases. When the cases with micropapillary component were divided into 67 (20.9%) mucinous and 253 (79.1%) non-mucinous subtypes, tumours with mucinous micropapillary component exhibited significantly more aggressive pathological features, a higher proportion of HER2 mutations (P = 0.002) and ALK rearrangements (P < 0.001), and a lower proportion of EGFR mutations (P = 0.038) compared to those with a non-mucinous micropapillary component. In survival analyses, mucinous MPC tended to be more aggressive compared with non-mucinous MPC, but its prognostic value was not statistically significant (P = 0.076). CONCLUSIONS: Mucinous micropapillary pattern is an under-recognized unique growth associated significantly with HER2 mutation and ALK rearrangement.

Pancreatic neuroendocrine tumors: A single-center 20-year experience with 100 patients.

BACKGROUND/OBJECTIVES: Pancreatic neuroendocrine neoplasms (NENs) are rare tumors, exhibiting several morphological, functional, and behavioral characteristics. However, only few reports have evaluated large case series of pancreatic NEN. METHODS: We conducted a retrospective review of 100 consecutive patients with pancreatic NEN diagnosed pathologically and treated at the National Cancer Center Hospital between 1991 and 2010. RESULTS: The study included 48 males and 52 females (median age: 55 years). Fourteen patients had clinical symptoms caused by excess hormone secretion at diagnosis. Twelve patients were diagnosed with neuroendocrine tumor (NET) G1, 54 with NET G2, and 32 with neuroendocrine carcinoma (NEC) as per the 2010 World Health Organization classification. Distant metastases were observed in 25%, 43%, and 84% of the patients with NET G1, NET G2, and NEC, respectively. Serum levels of neuron-specific enolase and lactate dehydrogenase significantly increased in patients with NEC compared with those in patients with NET G1/G2. The 5-year survival rates of patients with NET G1, NET G2, and NEC were 91%, 69%, and 10%, respectively. Good performance status (PS), lower stage, and histopathological grade were identified as independent favorable prognostic factors. CONCLUSIONS: Patients with NET G1/G2 treated with surgical resection had a good prognosis. Most patients with NEC exhibited distant metastases and had a poor prognosis. Staging classification and the WHO 2010 grading are important factors for selecting the appropriate treatment strategy and predicting prognosis for patients with pancreatic NEN.

New Portal-Superior Mesenteric Vein Reconstructions Using First Jejunal Vein Flap in Pancreaticoduodenectomy.

Pancreaticoduodenectomy (PD) is the only potential treatment for pancreatic head adenocarcinomas, which are sometimes located close to or invade the portal-superior mesenteric vein (PSMV). Surgeons often attempt to obtain a negative resectional margin after resection of the PSMV. This attempt requires PSMV reconstruction through graft replacements or end-to-end anastomosis; however, possible complications should be concerned including anastomosis stenosis, damage to some of the PSMV branches, prosthetic graft infection, and that associated with autologous graft harvesting. The first jejunal artery and vein are often resected in PD with the intent of lymphadenectomy. In this study, jejunal vein flap was used for PSMV reconstruction without causing damage to any of the PSMV branches in two patients. Here, we describe the new methods of PSMV reconstruction using first jejunal vein flap in PD.

The type of preoperative biliary drainage predicts short-term outcome after major hepatectomy.

PURPOSE: Endoscopic nasobiliary drainage (ENBD) is increasingly preferred to percutaneous transhepatic biliary drainage (PTBD) for patients undergoing major hepatectomy including hemihepatectomy or trisectorectomy with extrahepatic bile duct resection. The study was aimed to evaluate whether postoperative outcomes differed according to the types of biliary drainage. METHODS: Patients who underwent major hepatectomy with bile duct resection for biliary tract cancer between December 2000 and March 2015 were classified into four groups according to their initial biliary drainage type. The preoperative management and postoperative morbidity were compared. RESULTS: Totally, 280 patients were classified into the following groups: no biliary drainage (n = 109), PTBD (n = 99), ENBD (n = 28), and endoscopic retrograde biliary drainage (ERBD; n = 44). Preoperative catheter management including tube exchange or additional tube placement due to cholangitis or poor drainage was most frequently required in the ERBD group (PTBD, 18 %; ENBD, 14 %; ERBD, 43 %; P < 0.01). By the time of hepatectomy, 141 patients underwent at least one PTBD (PTBD(+)) and 30 patients were managed only with endoscopic biliary drainage (PTBD(-)). The incidence of major postoperative morbidities (Clavien-Dindo grade ≥ III) in PTBD(+) and PTBD(-) group was 23 and 3 %, respectively (P = 0.01). A multivariate analysis among 171 patients with biliary drainage showed PTBD(+) (P = 0.04; odds ratio = 8.50; 95 % confidential interval [CI], 1.10-65.45) and red blood cells transfusion (P < 0.01; odds ratio = 2.72; 95 % CI, 1.22-6.09) were independent predictors of major morbidity. CONCLUSION: The type of preoperative biliary drainage was associated with the perioperative outcomes of major hepatectomy. Sticking to endoscopic biliary drainage was associated with lower risk of postoperative major morbidity.

Clinical significance of tumor-infiltrating immune cells focusing on BTLA and Cbl-b in patients with gallbladder cancer.

The host immune system plays a significant role in tumor control, although most cancers escape immune surveillance through a variety of mechanisms. The aim of the present study was to evaluate the clinicopathological significance of a novel co-inhibitory receptor, B and T lymphocyte attenuator (BTLA), the anergy cell marker Casitas-B-lineage lymphoma protein-b (Cbl-b), and clinical implications of tumor-infiltrating immune cells in gallbladder cancer (GBC) tissues. We investigated 211 cases of GBC, 21 cases of chronic cholecystitis (CC), and 11 cases of xanthogranulomatous cholecystitis (XGC) using immunohistochemistry to detect tissue-infiltrating immune cells and their expression of BTLA and Cbl-b, and carried out correlation and survival analyses. The density of infiltrating T cells was significantly higher in CC and XGC than in GBC. The density ratio of BTLA(+) cells to CD8(+) T cells (BTLA/CD8) and that of Cbl-b(+) cells to CD8(+) T cells (Cbl-b/CD8) were significantly higher in GBC than in CC and XGC. The FOXP3/CD4, BTLA/CD8, and Cbl-b/CD8 ratios were significantly correlated with each other, and also with malignant phenotypes. Survival analyses revealed that a lower density of tumor-infiltrating CD8(+) cells, and higher Foxp3/CD4, BTLA/CD8, and Cbl-b/CD8 ratios were significantly associated with shorter overall survival and disease-free survival in GBC patients. Multivariate analyses showed that M factor, perineural invasion, BTLA/CD8, and Cbl-b/CD8 were closely associated with shorter overall survival. These findings suggest that higher ratios of BTLA/CD8 and Cbl-b/CD8 are independent indicators of unfavorable outcome in GBC patients, and that upregulation of BTLA in cancer tissues is involved in inhibition of antitumor immunity.

Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma.

UNLABELLED: Cholangiocarcinoma is an intractable cancer, with limited therapeutic options, in which the molecular mechanisms underlying tumor development remain poorly understood. Identification of a novel driver oncogene and applying it to targeted therapies for molecularly defined cancers might lead to improvements in the outcome of patients. We performed massively parallel whole transcriptome sequencing in eight specimens from cholangiocarcinoma patients without KRAS/BRAF/ROS1 alterations and identified two fusion kinase genes, FGFR2-AHCYL1 and FGFR2-BICC1. In reverse-transcriptase polymerase chain reaction (RT-PCR) screening, the FGFR2 fusion was detected in nine patients with cholangiocarcinoma (9/102), exclusively in the intrahepatic subtype (9/66, 13.6%), rarely in colorectal (1/149) and hepatocellular carcinoma (1/96), and none in gastric cancer (0/212). The rearrangements were mutually exclusive with KRAS/BRAF mutations. Expression of the fusion kinases in NIH3T3 cells activated MAPK and conferred anchorage-independent growth and in vivo tumorigenesis of subcutaneous transplanted cells in immune-compromised mice. This transforming ability was attributable to its kinase activity. Treatment with the fibroblast growth factor receptor (FGFR) kinase inhibitors BGJ398 and PD173074 effectively suppressed transformation. CONCLUSION: FGFR2 fusions occur in 13.6% of intrahepatic cholangiocarcinoma. The expression pattern of these fusions in association with sensitivity to FGFR inhibitors warrant a new molecular classification of cholangiocarcinoma and suggest a new therapeutic approach to the disease.

Optimal indications for additional resection of the invasive cancer-positive proximal bile duct margin in cases of advanced perihilar cholangiocarcinoma.

BACKGROUND: The survival benefits of additional resection of the positive proximal ductal margin in cases of perihilar cholangiocarcinoma remain to be elucidated. The purpose of this retrospective study was to clarify the optimal indications for additional resection of the invasive cancer-positive proximal ductal margin (PM) METHODS: All patients who underwent hepatectomy for perihilar cholangiocarcinoma between 2000 and 2011 were analyzed. Surgical variables, the status of the PM, prognostic factors, and survival were evaluated. RESULTS: A total of 224 patients were enrolled. Additional resection was performed in 52 of 75 positive PMs of invasive cancer, resulting in 43 negative PMs. The survival of patients with a negative PM treated with additional resection (n = 43) was significantly worse than that of the patients with a negative PM treated without additional resection (n = 149; P = 0.031) and did not significantly differ from that of the patients with a positive PM (n = 32; P = 0.215). A multivariate analysis demonstrated that the carbohydrate antigen 19-9 (CA19-9) level (<64 or ≥64), combined vascular resection, pN, pM, the histological grade, perineural invasion, liver invasion, and R status were independent prognostic factors. Only in the subgroups of CA19-9 < 64 and pM0, the survival of the patients with a negative PM treated with additional resection was significantly better than that of the patients with a positive PM (P = 0.019 and P = 0.021, respectively). CONCLUSIONS: Additional resection of the invasive cancer-positive PMs may be warranted only in limited patients with a lower level of CA19-9 and no distant metastatic disease.

Global PROTOMAP profiling to search for biomarkers of early-recurrent hepatocellular carcinoma.

This study used global protein expression profiling to search for biomarkers to predict early recurrent hepatocellular carcinoma (HCC). HCC tissues surgically resected from patients with or without recurrence within 2 years (early recurrent) after surgery were compared with adjacent nontumor tissue and with normal liver tissue. We used the PROTOMAP strategy for comparative profiling, which integrates denaturing polyacrylamide gel electrophoresis migratory rates and high-resolution, semiquantitative mass-spectrometry-based identification of in-gel-digested tryptic peptides. PROTOMAP allows examination of global changes in the size, topography, and abundance of proteins in complex tissue samples. This approach identified 8438 unique proteins from 45 708 nonredundant peptides and generated a proteome-wide map of changes in expression and proteolytic events potentially induced by intrinsic apoptotic/necrotic pathways. In the early recurrent HCC tissue, 87 proteins were differentially expressed (≥20-fold) relative to the other tissues, 46 of which were up-regulated or specifically proteolyzed and 41 of which were down-regulated. This data set consisted of proteins that fell into various functional categories, including signal transduction and cell organization and, notably, the major catalytic pathways responsible for liver function, such as the urea cycle and detoxification metabolism. We found that aberrant proteolysis appeared to occur frequently during recurrence of HCC in several key signal transducers, including STAT1 and δ-catenin. Further investigation of these proteins will facilitate the development of novel clinical applications.

Basing treatment strategy for non-functional pancreatic neuroendocrine tumors on tumor size.

BACKGROUND: Surgical resection is advocated for all stages of pancreatic neuroendocrine tumors (PNETs); whether small PNETs can be managed by observation alone is controversial. METHODS: The prognoses of patients with non-functional PNET managed by surgical resection or observation alone were retrospectively analyzed. In patients who had undergone resection, correlation of pathologically assessed tumor extension and grade with tumor size were evaluated. RESULTS: Nineteen patients with PNET of median tumor diameters of 12 mm (range 6-38 mm) were followed up by observation for 19-162 months. Increase of tumor size >20 % occurred in three patients, resulting in 5-year progression-free survival of 83 %, but no distant metastases occurred. Surgical resection was performed in 71 patients. Tumor size correlated with the incidence of lymph node or hepatic metastases, portal vein invasion, and Ki-67 index. None of the 18 patients with a tumor size ≤15 mm developed lymph node or distant metastases, and all these patients survived without recurrence for 5-283 months. The smallest tumor size with lymph node metastases was 19 mm. The 5-year recurrence-free survivals of patients with a tumor size ≤15 mm (100 %) was significantly better than patients with tumor sizes 16-20 mm (86 %), 21-30 mm (71 %), 31-50 mm (83 %), and >50 mm (48 %). CONCLUSION: Because PNETs ≤15 mm in size have little risk of metastases or recurrence, careful observation with serial image studies is acceptable. Once the tumor size exceeds 15 mm, the risk of metastases and recurrence increases significantly.

Histopathological characteristics of hypervascular cholangiocellular carcinoma as an early stage of cholangiocellular carcinoma.

AIM: Prognosis of hypervascular cholangiocellular carcinoma (h-CCC) is reportedly better than that of ordinary hypovascular CCC (o-CCC). The aim of this study is to clarify the histopathological characteristics of h-CCC. METHODS: On the basis of the findings in the arterial phase of contrast-enhanced computed tomography, 16 cases of mass-forming-type CCC were divided into two groups (h-CCC, n = 8; o-CCC, n = 8). Areas of high (Area H-a) and low (Area H-b) attenuation in h-CCC cases and areas of low attenuation in o-CCC cases (Area O) were delineated. These areas were then evaluated histopathologically to determine the proportion of tumor cells, fibrous stroma, arterial vessel density, and immunohistochemical expression of Vascular endothelial growth factor; angiopoietin-2; cytokeratin 7, CK19, SOX9 and SOX17 genes; epithelial cell adhesion molecule; and the Bmi-1, Ki-67, epithelial membrane antigen and polyclonal carcinoembryonic antigen. RESULTS: The areal ratio of tumor cells decreased and that of fibrous stroma increased in the following order: Area H-a, Area H-b and Area O. Values for AVD and neural cell adhesion molecule positivity rate were significantly higher in Area H-a than in Areas H-b or O. Expressions of vascular endothelial growth factor and angiopoietin-2 were significantly higher in Areas H-a and H-b than in Area O. The Ki-67 labeling index increased in the following order: Area H-a, Area H-b and Area O. CONCLUSION: A high areal ratio of tumor cells and AVD as well as a high expression of stem cells and angiogenic markers were observed in cases of h-CCC, whereas the areal ratio of fibrous stroma and malignant potential were low. These results suggest that h-CCC may represent the early stage of CCC.

Early venous return in hepatic angiomyolipoma due to an intratumoral structure resembling an arteriovenous fistula.

Early venous return (EVR) is an important radiological feature of hepatic angiomyolipoma (HAML) that can aid in differential diagnosis, but the pathogenic mechanisms of EVR have yet to be elucidated. We present the first HAML case for which a probable mechanism for EVR is described. The patient was a 46-year-old woman, who had a growing 6-cm tumor with EVR in segment 3 of the liver as revealed by dynamic contrast-enhanced computed tomography. Left hepatic lobectomy was performed to prevent tumor rupture. Histopathological and immunohistochemical analyses of the excised tumor indicated HAML. Successive microsections of the tumor were stained with hematoxylin-eosin and Victoria blue to visualize the vascular structure within and around the tumor. These analyses led to three major findings. First, many well-defined thick-walled vessels, such as arteries, were found entering the tumor. Second, many thick-walled vessels within the tumor were connected directly to thin-walled vessels, resembling arteriovenous fistulae. Finally, thin-walled intratumoral vessels were connected directly to the hepatic vein. These histological findings suggested that the rich arterial flow into the tumor was being rapidly drained into the hepatic vein through intratumoral arteriovenous connections. We also detected these same anomalous circulatory pathways in tissue sections from three of four additional HAML cases with EVR. Aberrant arteriovenous fistulae within the tumor may account for many cases of EVR in HAML patients.

Intraductal dissemination of papillary adenocarcinoma of the ampulla of Vater in the pancreatic duct.

It has been speculated that intraductal dissemination, via the pancreatic duct, bile duct, or mammary duct, is a unique form of cancer cell spread. However, clinical evidence to confirm this form of dissemination has been lacking. Here we report a case of papillary adenocarcinoma of the ampulla of Vater in which retrograde dissemination to the pancreatic duct was strongly suggested. A 79-year-old woman underwent pancreatoduodenectomy for a 22 mm microinvasive papillary adenocarcinoma of the ampulla. Multiple carcinomas in situ were found in the pancreatic duct distant from the ampulla. Seven months later, she underwent a second operation for a recurrent papillary adenocarcinoma at the pancreato-jejunal anastomosis showing exophytic and expansive growth into the jejunal lumen that connected to an intraductal adenocarcinoma in the pancreatic body. None of these tumors showed invasive growth, or vascular or neural invasion, being separate from each other but sharing identical histological, immunohistochemical, and molecular features; papillary growth, a pancreatobiliary phenotype, the same pattern of genomic loss of heterozygosity, and no mutation of the KRAS, TP53, and GNAS genes. These results imply that this papillary adenocarcinoma of the ampulla of Vater had disseminated to the pancreatic duct in a retrograde manner and recurred in the remnant pancreas.

Downregulation of the microRNA biogenesis components and its association with poor prognosis in hepatocellular carcinoma.

Genetic alterations and deregulation of the miRNA biogenesis pathway components have been reported in human tumors. Tissue-specific deletion of the Dicer gene, which encodes an essential miRNA processing enzyme, promotes carcinogenesis in animal models. These features indicate that aberrant miRNA biogenesis components are directly associated with cancer. For the present study, we conducted quantitative RT-PCR of 14 genes that are related to the miRNA biogenesis pathway in 47 paired samples of primary hepatocellular carcinoma (HCC) and matched non-cancerous liver. Expression of seven genes (Dgcr8, p68, p72, Dicer, Ago3, Ago4 and Piwil4) was significantly decreased in primary HCC, especially in non-viral HCC subtypes, compared to the non-cancerous liver. Combinations of decreased expression of the miRNA biogenesis components in non-cancerous liver were related to cigarette smoking, alcohol intake and diabetes, which are known to be risk factors for HCC, and were also associated with the occurrence of multicentric tumors. Reduction of two of these genes (Dicer and p68) in HCC was associated with poor prognosis. Trimethylation of histone H3 lysine 27 in the promoters is implicated in the deregulation of these miRNA-biogenesis-related genes in non-HBV genome integrated HCC cell lines. In conclusion, deregulation of the miRNA biogenesis pathway components is frequently observed in non-viral-associated HCC and is linked to etiological risk factors and poor prognosis. Our study further showed that epigenetic regulation could be implicated in the deregulation of these genes during hepatocarcinogenesis.

Is preservation of the remnant stomach safe during distal pancreatectomy in patients who have undergone distal gastrectomy?

BACKGROUND: Whether the remnant stomach can be safely preserved when performing distal pancreatectomy (DP) in patients with a prior distal gastrectomy (DG) remains unclear because the remnant stomach and pancreatic body/tail share an arterial blood supply via the splenic artery (SPA). METHODS: A total of 18 patients with prior DG who underwent DP were enrolled in this study. Clinicopathologic data were retrospectively analyzed with a focus on management of the remnant stomach and complications related to ischemia of the remnant stomach. Additionally, intraoperative indocyanine green (ICG) fluorescence angiography was performed to visualize the blood flow and circulation in the remnant stomach. RESULTS: Ten patients underwent a standard DP (DP in conjunction with splenectomy and division of the SPA) with preservation of the remnant stomach. The entire stomach was preserved in seven patients, and three underwent concomitant partial resection of the remnant stomach. No patients in whom the entire remnant stomach was preserved developed postoperative complications associated with it, whereas two of the three patients who underwent partial resection of the remnant stomach developed severe ischemic complications. Intraoperative ICG fluorescence angiography revealed a caudally directed circulation of blood from the esophagogastric junction through the intramural capillary network in the remnant stomach. CONCLUSIONS: When performing DP in patients with a prior DG, preservation of the entire remnant stomach was a safe procedure because of the presence of an intramural network that supplies blood to the remnant stomach. In contrast, partial resection of the remnant stomach could be dangerous because of the potential for severe ischemic complications.

Perioperative and long-term outcomes after pancreaticoduodenectomy in elderly patients 80 years of age and older.

PURPOSE: Although a pancreaticoduodenectomy (PD) has been recently regarded as a safe surgical procedure at high-volume centers, the efficacy of PD for patients 80 years of age and older is controversial. The aim of this study was to evaluate the perioperative and long-term outcomes following PD in patients 80 years of age and older. METHODS: Elderly patients 80 years of age and older who underwent PD between 2001 and 2009 were identified. The perioperative and long-term outcomes were compared with patients younger than 80 years of age. RESULTS: Of 561 total patients, 22 patients (3.9 %) were 80 years of age or older. Mortality occurred in one patient (4.5 %). Postoperative major complications (Clavien-Dindo classification ≥ grade III) occurred in six patients (27.3 %) in this group, which was significantly higher than in patients younger than 80 years of age (P = 0.008). The survival of the elderly patients undergoing PD for pancreatic cancer was significantly shorter than that for the same patient group with other diseases (median survival, 13 versus 82 months; P = 0.014). Only one elderly patient with pancreatic cancer survived more than 3 years. CONCLUSIONS: PD for pancreatic cancer in patients aged 80 and older should be carefully selected, because it is associated with a higher incidence of severe postoperative complications and a small change of long-term survival.

Prognostic impact of postoperative serum CA 19-9 levels in patients with resectable pancreatic cancer.

BACKGROUND: Perioperative serum carbohydrate antigen 19-9 (CA 19-9) level has been reported to be a useful prognostic marker in pancreatic cancer. The object of this study was to investigate the predictive factors for survival, including preoperative and postoperative serum CA 19-9 levels in patients with pancreatic cancer. METHODS: Between 2003 and 2009, a total of 269 patients with pancreatic invasive ductal carcinoma underwent macroscopically curative resection, and pre- and postoperative (within 3 months after surgery) serum CA 19-9 levels were evaluated in all of them. The prognostic significance of clinicopathologic factors was evaluated by univariate and multivariate analyses. RESULTS: Preoperative serum CA 19-9 levels were higher than normal (>37 U/ml, 38-4600 U/ml) in 218 of 269 patients. Of these, after surgery, serum CA 19-9 level returned to within a normal range in 136 patients (62%), whereas 82 patients (38%) remained in the higher-than-normal range. In univariate and multivariate analyses, node metastasis (P < 0.001) and postoperative CA 19-9 level (>37 U/ml) (P < 0.0001) were independent predictors for poor survival. Postoperative CA 19-9 level was higher in patients with microscopically positive surgical margin (P = 0.02). Hepatic recurrence and peritoneal dissemination were associated with postoperative higher CA 19-9 level. CONCLUSIONS: Postoperative CA 19-9 level was associated with positive surgical margin and hepatic or peritoneal recurrence and may be a useful predictor for survival in patients with pancreatic cancer.