A genome-wide association study identifies four genetic markers for hematological toxicities in cancer patients receiving gemcitabine therapy.

OBJECTIVE: Genetic factors are thought to be one of the causes of individual variability in the adverse reactions observed in cancer patients who received gemcitabine therapy. However, genetic factors determining the risk of adverse reactions of gemcitabine are not fully understood. PATIENTS AND METHODS: To identify a genetic factor(s) determining the risk of gemcitabine-induced leukopenia/neutropenia, we conducted a genome-wide association study, by genotyping over 610 000 single nucleotide polymorphisms (SNPs), and a replication study in a total of 174 patients, including 54 patients with at least grade 3 leukopenia/neutropenia and 120 patients without any toxicities. RESULTS: We identified four loci possibly associated with gemcitabine-induced leukopenia/neutropenia [rs11141915 in DAPK1 on chromosome 9q21, combined P=1.27×10, odds ratio (OR)=4.10; rs1901440 on chromosome 2q12, combined P=3.11×10, OR=34.00; rs12046844 in PDE4B on chromosome 1p31, combined P=4.56×10, OR=4.13; rs11719165 on chromosome 3q29, combined P=5.98×10, OR=2.60]. When we examined the combined effects of these four SNPs, by classifying patients into four groups on the basis of the total number of risk genotypes of these four SNPs, significantly higher risks of gemcitabine-induced leukopenia/neutropenia were observed in the patients having two and three risk genotypes (P=6.25×10, OR=11.97 and P=4.13×10, OR=50.00, respectively) relative to patients with zero or one risk genotype. CONCLUSION: We identified four novel SNPs associated with gemcitabine-induced severe leukopenia/neutropenia. These SNPs might be applicable in predicting the risk of hematological toxicity in patients receiving gemcitabine therapy.

MUC1 is a useful molecular marker for malignant intraductal papillary mucinous neoplasms in pancreatic juice obtained from endoscopic retrograde pancreatography.

OBJECTIVES: Some intraductal papillary mucinous neoplasms (IPMNs) have no proliferation to malignant IPMNs, and benign IPMNs can observe the natural course without a surgical intervention. Therefore, an accurate assessment is required to determine the appropriate decision on managing malignant IPMNs. METHODS: Quantitative real-time reverse transcription-polymerase chain reaction was performed for pancreatic juice by a LightCycler instrument focused on carcinoembryonic antigen, MUC1, and human telomerase reverse transcriptase. RESULTS: MUC1/glyceraldehyde-3-phosphate dehydrogenase messenger RNA (mRNA) ratio in intraductal papillary mucinous carcinoma (IPMC; median, 4710.7) was significantly higher in intraductal papillary mucinous adenoma (IPMA; median, 727; P = 0.0229). Furthermore, the MUC1/glyceraldehyde-3-phosphate dehydrogenase mRNA ratio in carcinoma in situ and minimum invasive IPMC (median, 26,490) was significantly higher than that in IPMA (P = 0.0152). The cutoff level of MUC1 ratio was determined as 1600 for the division of IPMC from IPMA by the receiver-operating characteristic curve. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MUC1 mRNA were 88.9%, 71.4%, 80.0%, 83.3%, and 81.3%, respectively. CONCLUSIONS: Quantitative reverse transcription-polymerase chain reaction using MUC1 is useful for the detection of malignant IPMN in pure pancreatic juice.

A prospective randomized controlled trial of internal versus external drainage with pancreaticojejunostomy for pancreaticoduodenectomy.

BACKGROUND: A stent often is placed across the pancreaticojejunostomy. However, there is no report compared between internal drainage and external drainage. METHODS: We conducted a prospective randomized trial (NCT00628186 registered at http://ClinicalTrials.gov) with 100 patients who underwent pancreaticoduodenectomy and we compared the effects on postoperative course. RESULTS: The incidence of pancreatic fistula according to the International Study Group on Pancreatic Fistula criteria was not different (external, 20%; vs internal, 26%), and the incidence of the other complications was similar between stent types. The median postoperative hospital stay was 21 days (range, 8-163 d) in the internal drainage group, which was shorter than the median stay of 24 days (range, 21-88 d) in the external drainage group (P = .016). CONCLUSIONS: Both internal drainage and external drainage were safety devices for pancreaticojejunostomy. Internal drainage simplifies postoperative managements and it might shorten postoperative stay for pancreaticoduodenectomy.

Identifying molecular markers for chemosensitivity to gemcitabine in pancreatic cancer: increased expression of interferon-stimulated gene 15 kd is associated with intrinsic chemoresistance.

OBJECTIVES: Gemcitabine is the standard chemotherapeutic agent for pancreatic cancer. Nevertheless, the prognosis of pancreatic cancer patients is still poor. Evaluating the mechanisms of chemoresistance to gemcitabine will be helpful for the improvement of the therapeutic outcome. METHODS: Using 11 pancreatic cancer cell lines and global gene expression profiling, molecular markers were detected for acquired and intrinsic gemcitabine sensitivity. Acquired gemcitabine resistance in vitro was obtained by continual exposure to gradually increased concentrations of gemcitabine; however, intrinsic sensitivity is originally provided and differs between cell lines. RESULTS: Microarray analysis of intrinsic sensitivity showed no correlation to that of acquired resistance. Fifteen overexpressed and 49 downexpressed genes in accordance with intrinsic gemcitabine resistance were identified, and we selected those highly expressed in resected pancreatic cancer tissue. Interferon-stimulated gene 15 (ISG15), which plays a role in cellular defense from infection and carcinogenesis, was identified as the gene related to gemcitabine chemosensitivity. By inhibition of ISG15 in gemcitabine-resistant cell lines using siRNA, gemcitabine resistance was reversed. CONCLUSIONS: It was demonstrated that ISG15 is one of the genes associated with intrinsic gemcitabine sensitivity, having a possibility to be a candidate of molecular targeting for the improvement of chemotherapy against pancreatic cancer.

Molecular markers associated with lymph node metastasis in pancreatic ductal adenocarcinoma by genome-wide expression profiling.

Lymph node metastasis (LNM) is the most important prognostic factor in patients undergoing surgical resection of pancreatic ductal adenocarcinoma (PDAC). In this study, we aimed to identify molecular markers associated with LNM in PDAC using genome-wide expression profiling. In this study, laser microdissection and genome-wide transcriptional profiling were used to identify genes that were differentially expressed between PDAC cells with and without LNM obtained from 20 patients with PDAC. Immunohistochemical staining was used to confirm the clinical significance of these markers in an additional validation set of 43 patients. In the results, microarray profiling identified 46 genes that were differently expressed between PDAC with and without LNM with certain significance. Four of these biomarkers were validated by immunohistochemical staining for association with LNM in PDAC in an additional validation set of patients. In 63 patients with PDAC, significant LNM predictors in PDAC elucidated from multivariate analysis were low expression of activating enhancer binding protein 2 (AP2alpha) (P = 0.012) and high expression of mucin 17 (MUC17) (P = 0.0192). Furthermore, multivariate analysis revealed that AP2alpha-low expression and MUC17-high expression are independent prognostic factors for poor overall survival (P = 0.0012, 0.0001, respectively). In conclusion, AP2alpha and MUC17 were independent markers associated with LNM of PDAC. These two markers were also associated with survival in patients with resected PDAC. We demonstrate that AP2alpha and MUC17 may serve as potential prognostic molecular markers for LNM in patients with PDAC.

How do we predict the clinically relevant pancreatic fistula after pancreaticoduodenectomy?--an analysis in 244 consecutive patients.

BACKGROUND: The most important problem in pancreatic fistula is whether one can distinguish clinical pancreatic fistula, grade B + C fistula by the International Study Group on Pancreatic Fistula (ISGPF), from transient pancreatic fistula (grade A), in the early period after pancreaticoduodenectomy (PD). It remains unclear what predictive risk factors can precisely predict which clinical relevant or transient pancreatic fistula when diagnosed pancreatic fistula on POD3 by ISGPF criteria. METHODS: We analyzed the predictive factors of clinical pancreatic fistula by logistic regression analysis in 244 consecutive patients who underwent PD. Pancreatic fistula was classified into three categories by ISGPF. RESULTS: The rate of pancreatic fistula was 69 of 244 consecutive patients (28%) who underwent PD. Of these, 47 (19%) had grade A by ISGPF criteria, 17 patients (7.0%) had grade B, and five patients (2.0%) had grade C. The independent risk factor of incidence of pancreatic fistula is soft pancreatic parenchyma. However, soft pancreatic parenchyma did not predict underlying clinically relevant pancreatic fistula. The independent predictive factors of clinically relevant pancreatic fistula were serum albumin level 9,800 mm(-3) on POD 4. Positive predictive value of the combination of two predictive factors for clinical relevant pancreatic fistula was 88%. CONCLUSIONS: The combination of two factors on POD4, serum albumin level 9,800 mm(-3), is predictive of clinical relevant pancreatic fistula when diagnosed pancreatic fistula on POD 3 by ISGPF criteria.

A central pancreatectomy for benign or low-grade malignant neoplasms.

INTRODUCTION: A central pancreatectomy is a parenchyma-sparing procedure that is performed to reduce long-term endocrine and exocrine insufficiency. METHOD: In this study, we analyzed the perioperative course, the frequency of postoperative onset of diabetes mellitus, and long-term change of body weight in patients undergoing a central pancreatectomy, in comparison to the patients undergoing a distal pancreatectomy for low-grade neoplasms including cystic neoplasms and neuroendocrine tumors. RESULTS AND DISCUSSION: The rate of postoperative complications including grade B/C pancreatic fistula was no different between both groups. Only one patient undergoing a central pancreatectomy (4.7%) developed new onset of mild diabetes, whereas 35% in the distal pancreatectomy group developed new onset or worsening diabetes (p = 0.0129). The body weight in the distal pancreatectomy group was significant lower than that in the central pancreatectomy group at 1 and 2 years after surgery (1 year; P < 0.0001, 2 years; P = 0.0055), and the body weight in the patients undergoing a central pancreatectomy improved to preoperative values within 2 years after surgery. CONCLUSION: A central pancreatectomy is a safe procedure for the treatment of low-grade malignant neoplasms in the pancreatic body; the rate of onset of diabetes is minimal, and the body weight improves early in the postoperative course.

A pancreaticoduodenectomy is acceptable for periampullary tumors in the elderly, even in patients over 80 years of age.

BACKGROUND: Although the mortality rates for pancreaticoduodenectomy have been reported to be low for periampullary tumors at high-volume centers, postoperative results still remain unclear for elderly patients over 80 years of age. METHODS: This was a retrospective study of patients who underwent a pancreaticoduodenectomy and consisted of 335 patients who were treated for periampullary tumors between January 1994 and August 2008. The main outcomes were postoperative complications, mortality, and the length of hospital stay among the elderly patients, and they were analyzed in three groups: elderly patients over 80 years old, septuagenarians, and those under 70 years of age. RESULTS: The performance status of elderly patients was lower than that of the patients under 70 (P < 0.05), and the elderly had a higher American Society of Anesthesiologists physical status classification score (P < 0.001) as well as low hemoglobin and serum albumin levels (P < 0.01 and P < 0.001, respectively). The incidence of delayed gastric emptying in the elderly was higher; however, there was no significant difference. The other outcomes in the elderly group were similar to those of the other groups. CONCLUSIONS: Pancreaticoduodenectomy was considered to be a feasible surgical procedure for elderly patients who had a good performance status.

Treatment strategy for intraductal papillary mucinous neoplasm of the pancreas based on malignant predictive factors.

BACKGROUND: Noninvasive intraductal papillary mucinous neoplasms (IPMNs) have a favorable prognosis; however, the prognosis of invasive intraductal papillary mucinous carcinoma (invasive IPMC) is poor. Identification of predictive factors for differentiating IPMC from benign IPMNs would assist in providing appropriate treatment. DESIGN: Retrospective study (1999-2006). SETTING: Wakayama Medical University Hospital, Wakayama, Japan. PATIENTS: Fifty-four patients with IPMN who underwent surgery; histologic examination showed benign adenomas in 29, carcinoma in situ in 14, and invasive carcinoma in 11 patients. MAIN OUTCOME MEASURES: Clinical data, preoperative imaging findings, cytologic findings, tumor markers in serum and pancreatic juice, and overall survival. RESULTS: Age of 70 years or older, presence of mural nodules, mural nodule size of 5 mm or larger, and carcinoembryonic antigen (CEA) level in pancreatic juice of 110 ng/mL or higher (as obtained by preoperative endoscopic retrograde pancreatography) were predictive of a malignant IPMN by univariate analysis, and a CEA level of 110 ng/mL or higher in pancreatic juice was identified as the only independent predictive factor for the malignant entity. The presence of jaundice or body weight loss, main pancreatic duct type, presence of mural nodules, mural nodule size of 5 mm or larger, and CEA level in the pancreatic juice of 110 ng/mL or higher were all predictive of invasive IPMCs by univariate analysis. CONCLUSION: Measurement of the CEA level in pancreatic juice should be considered in the diagnosis of IPMC.

Xanthogranulomatous cholecystitis: the use of preoperative CT findings to differentiate it from gallbladder carcinoma.

BACKGROUND AND AIM: A retrospective analysis was performed on 32 patients with histologically confirmed xanthogranulomatous cholecystitis (XGC) and 21 patients with gallbladder carcinoma who underwent surgical treatment between 1998 and 2007. METHODS: All patients underwent preoperative CT scanning. The CT features analyzed were: the presence of intramural hypoattenuated nodules or bands, mucosal line, the patterns of wall thickening and enhancement, and the presence of stones in the gallbladder. The variables of the CT findings with XGC were analyzed using multivariate logistic regression analysis. RESULTS: Intramural hypoattenuated nodules were observed in 21 patients (65%) with XGC, but in only six patients (29%) with gallbladder carcinoma (P < 0.01). The mucosal line was observed in 27 patients (84%) with XGC and in only four patients (19%) with gallbladder carcinoma (P < 0.0001). Gallstones were noted in 24 patients (75%) with XGC and five patients (24%) with gallbladder carcinoma (P < 0.001). There was no significant difference in the pattern of gallbladder wall thickening (diffuse or focal) and the presence of changes outside the gallbladder. Multivariate logistic regression analysis revealed from the CT features that the enhanced continuous mucosal line (P = 0.0013) and the presence of gallstones (P = 0.0072) were independently correlated with XGC. CONCLUSION: CT features of the enhanced continuous mucosal line in a thickened gallbladder wall, together with gallstones in a patient with chronic gallbladder disease, are highly suggestive of XGC. Accurate diagnosis of XGC may therefore indicate the need to select a less aggressive surgical approach.

Pylorus-preserving pancreaticoduodenectomy versus conventional pancreaticoduodenectomy for pancreatic adenocarcinoma.

PURPOSE: A few randomized controlled trials have questioned the justification of pylorus-preserving pancreaticoduodenectomy (PpPD) for pancreatic cancer and periampullary cancer. However, the characteristics of pancreatic cancer are remarkably different from those of other periampullary cancers, so the outcomes of PD and PpPD for pancreatic cancer are being re-evaluated. METHODS: We studied retrospectively, 55 patients who underwent PpPD at Wakayama Medical University Hospital between 1999 and 2005, when PpPD was available, for pancreatic head adenocarcinoma. The main outcome measures were the postoperative complications, mortality, and survival of the patients who underwent PpPD vs. those who underwent conventional pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma. RESULTS: There were no significant differences between PD and PpPD in postoperative complications; however, the incidences of delayed gastric emptying (DGE) differed significantly according to the type of reconstruction (P < 0.01). The body weight ratio and the incidence of diarrhea 6 months after PpPD and PD were similar. Patients treated with PD had a higher duodenal invasion rate than those treated with PpPD (P < 0.05); therefore, the cause-specific survival of the PpPD patients was better than that of the PD patients (P < 0.05). CONCLUSION: The surgical outcomes and incidence of postoperative complications in this series suggest that PpPD is an appropriate surgical procedure for pancreatic adenocarcinoma.

Liver metastasis as an initial recurrence has no impact on the survival of patients with resectable pancreatic adenocarcinoma.

BACKGROUND: Prognosis of the patients with pancreatic adenocarcinoma is still poor due to a recurrence, and liver metastasis is a distant metastasis that is foreboded the short survival period. METHODS: Between 1999 and 2005, 68 patients for pancreatic adenocarcinoma underwent a pancreaticoduodenectomy (n = 17), a pylorus-preserving pancreaticoduodenectomy (n = 27), distal pancreatectomy (n = 22), or total pancreatectomy (n = 2) with an extensive lymph node dissection. RESULTS: A tumor recurrence occurred to 55 patients (13 of the liver, 21 of the local recurrence, 16 of peritoneal dissemination, three of the lymph node, and two of lung). The low tumor grade and female demonstrated a risk factor for a liver metastasis (P = 0.043, P = 0.031). A logistic regression analysis demonstrated female (P = 0.02) and low tumor grade (P = 0.04) as independent risk factors for recurrence with liver metastasis. The median survival time (MST) was 13.6 months, and MST of patients with a liver metastasis as an initial recurrent site was 13.7 months; the liver metastasis as an initial recurrent site has no impact on the MST after pancreatic resection. CONCLUSIONS: We concluded potentially supporting the hypothesis that even patients thought to be at higher risk of liver metastasis may still be given the chance of resection, considering the satisfying survival.

Phase 2 trial of oral S-1 combined with low-dose cisplatin for unresectable advanced pancreatic cancer.

OBJECTIVES: A phase 2 trial of S-1 combined with cisplatin was conducted for unresectable pancreatic cancer. PATIENTS AND METHODS: S-1 was administered for 28 days followed by a rest of 14 days. Cisplatin was infused on days 1-5, 8-12, 15-19 and 22-26 of the first course. After the second course, S-1 was administered as maintenance chemotherapy. RESULTS: Thirty patients were enrolled and the responses observed were 0 complete response, 5 partial response, 22 stable disease and 3 progressive disease, with an overall response rate of 17% (95% confidence internal (CI), 6-35%). Toxicity was tolerable, with grade 3 toxicities observed for leukocytopenia (10%), neutropenia (7%), anemia (3%), thrombocytopenia (3%), anorexia (13%), and nausea and vomiting (7%). The median survival time (MST) and the 1-year survival rate were 9.0 months (95% CI, 6.0-14.5 months) and 35.7% (95% CI, 19-55%), respectively. CONCLUSION: S-1 with low-dose cisplatin is well tolerated and effective for advanced pancreatic cancer.

A collision tumor composed of cancers of the bile duct and ampulla of Vater--immunohistochemical analysis of a rare entity of double cancer.

Collision cancer of the bile duct and the papilla of Vater is an extremely rare entity. This is the first report of a case of bile duct collision cancer. A 75-year-old man presented with jaundice. Computed tomography showed isodensity masses in the middle bile duct and the papilla of Vater. Magnetic resonance cholangiopancreatography showed a tuberous filling defect in the middle bile duct. Gastroduodenal endoscopy showed a tumor with ulceration at the papilla of Vater. The patient was diagnosed with cancers of the middle bile duct and the papilla of Vater, and a pylorus-preserving pancreatoduodenectomy was performed. On pathological examination, the tumor in the middle bile duct showed a well differentiated carcinoma that had spread to the proximal bile duct, whereas the tumor in the papilla of Vater showed a papillo-tubular carcinoma with a marked production of mucin, suggesting an intestinal type of ampullary cancer. These tumors were directly communicated by microscopic findings. Therefore, the immunohistochemical characteristics were analyzed, using several antibodies, to determine whether the origins of the 2 cancers were different or not. As a result, it was concluded that this was a case of collision cancer of the middle bile duct and the papilla of Vater.

CLIP method (preoperative CT image-assessed ligation of inferior pancreaticoduodenal artery) reduces intraoperative bleeding during pancreaticoduodenectomy.

BACKGROUND: No previous reports have prospectively discussed an operative approach to reducing intraoperative bleeding during pancreaticoduodenectomy (PD). We have established the preoperative CT image-assessed ligation of inferior pancreaticoduodenal artery (IPDA) method (CLIP), which uses a preoperative three-dimensional computed tomographic (3D-CT) image to precisely detect the IPDA root intraoperatively and ligates the IPDA before the pancreas head is isolated. The aim of this study was to clarify whether the new operative approach reduces intraoperative bleeding compared with classical PD. METHOD: Between October 2003 and May 2005, classical PD was performed (n = 48), and from June 2005 to September 2006, PD with the CLIP method was prospectively performed (n = 48) at Wakayama Medical University Hospital. The perioperative status of the patients in the two groups, including intraoperative bleeding, was compared. RESULTS: Median intraoperative bleeding in patients with the CLIP method was significantly reduced compared with classical PD (867 ml versus 728 ml; p = 0.026). Moreover, operative time, red blood cell transfusion (units), and red blood cell transfusion in patients with the CLIP method were significantly reduced compared with classical PD (p = 0.033, 0.042, 0.014, respectively). There were no differences in length from the SMA to the IPDA root when the preoperative measurement by 3D-CT image (37.9 +/- 8.9 mm) and the intraoperative findings (38.0 +/- 8.8 mm) were compared (p = 0.6283). CONCLUSIONS: The CLIP method is a useful and reliable operative technique for reducing intraoperative bleeding in PD.

Prognostic factors for long-term survival in patients with locally invasive pancreatic cancer.

BACKGROUND/PURPOSE: We aimed to investigate predictors of survival in patients with resectable locally invasive pancreatic cancer. METHODS: The patient cohort consisted of 55 patients with locally invasive pancreatic cancer (International Union Against Cancer [UICC] stage III in 36 patients and stage IV in 19) who had undergone resection. The patients were informed about the advantages and the adverse effects of postoperative chemotherapy, and prospectively selected either observation alone or postoperative chemotherapy. The postoperative chemotherapy regimen options were: (1) intraarterial chemotherapy alone, (2) systemic chemotherapy alone, or (3) intraarterial chemotherapy combined with systemic chemotherapy. RESULTS: Overall 1-year and 2-year survival rates after resection were 40.5% and 13.5%, respectively. Median survival time was 10.9 months. Twenty-nine patients (52.7%) received postoperative chemotherapy. On univariate analysis, only postoperative chemotherapy was associated with long-term survival (P < 0.01). In the patients with postoperative chemotherapy, the 1-year survival rate and MST were 61.7% and 16.3 months, compared with 20.1% and 7.9 months in the patients without postoperative chemotherapy. Multivariate analysis also showed that only postoperative chemotherapy was identified as an independent survival factor. CONCLUSIONS: It was suggested that postoperative chemotherapy was essential for the improvement of survival in patients with locally invasive pancreatic cancer.

Early removal of prophylactic drains reduces the risk of intra-abdominal infections in patients with pancreatic head resection: prospective study for 104 consecutive patients.

OBJECTIVE: The aim of this study was designed to determine whether the period of drain insertion influences the incidence of postoperative complications. BACKGROUND DATA: The significance of prophylactic drains after pancreatic head resection is still controversial. No report discusses the association of the period of drain insertion and postoperative complications. METHODS: A total of 104 consecutive patients who underwent pancreatic head resection were enrolled in this study. To assess the value of prophylactic drains, we prospectively assigned the patients into 2 groups: group I underwent resection from January 2000 to January 2002 (n = 52, drain to be removed on postoperative day 8); group II underwent resection from February 2002 to December 2004 (n = 52, drain to be removed on postoperative day 4). Postoperative complications in the 2 groups were compared. RESULTS: The rate of pancreatic fistula was significantly lower in group II (3.6%) than in group I (23%) (P = 0.0038). The rate of intra-abdominal infections, including intra-abdominal abscess and infected intra-abdominal collections, was significantly reduced in group II (7.7%) compared with group I (38%) (P = 0.0003). Eighteen of 52 (34.6%) patients in group I had an inserted drain beyond 8 days, whereas only 2 of 52 (3.7%) patients in group II had an inserted drain beyond 4 days (P = 0.0002). Cultures of drainage fluid were positive in 16 of 52 (30.8%) patients in group I, and in 2 of 52 (3.7%) patients in group II (P = 0.0002). Intraoperative bleeding (> 1500 mL), operative time (> 420 minutes, and the period of drain insertion were significant risk factors for intra-abdominal infections (P = 0.043, 0.025, 0.0003, respectively). The period of drain insertion was the only independent risk factor for intra-abdominal infections by multivariate analysis (odds ratio, 6.7). CONCLUSION: Drain removal on postoperative day 4 was shown to be an independent factor in reducing the incidence of complications with pancreatic head resection, including intra-abdominal infections.

Does postoperative chemotherapy have a survival benefit for patients with pancreatic cancer?

In our study, we investigated whether postoperative chemotherapy improved survival in patients with invasive ductal carcinoma of the pancreas. Between 1987 and 2004, 111 patients underwent pancreatic resection against invasive ductal carcinoma of the pancreas in Wakayama Medical University Hospital. Median survival time (MST) was 19.4 months, 8.6 months, and 7.2 months, in JPS Stage III (UICC Stage IIA and IIB), JPS Stage IVa (UICC Stage IIA and IIB), and JPS Stage IVb (UICC Stage IV), respectively (P < 0.01). The MST of the chemotherapy group was 12 months, and the MST of the non-chemotherapy group was 8.4 months (P < 0.05). Moreover, in JPS Stage IV (UICC Stage IIA, IIB, III, and IV) highly advanced pancreatic cancer, the MST of the chemotherapy group was 10.9 months, and the MST of the group without chemotherapy was 6.6 months (P < 0.01). Since pancreatic cancer is characterized by an aggressive tumor with a high recurrent rate, postoperative chemotherapy is effective for an improvement of survival.

Indication of hepatopancreatoduodenectomy for biliary tract cancer.

BACKGROUND: The indication for a hepatopancreatoduodenectomy (HPD) in patients with advanced biliary tract cancer is still controversial, because this aggressive surgery might be associated with high mortality and morbidity rates. In this study, we review our experience with HPD for advanced biliary tract cancer, and seek to define the indication for HPD. METHODS: Eleven patients with biliary tract cancer underwent HPD at Wakayama Medical University Hospital between 1986 and 2004. Univariate analysis was used to assess independent variables of the mortality and morbidity associated with HPD. RESULTS: The rates of mortality and morbidity were 18% and 82%, respectively. Univariate analysis showed that the total serum bilirubin level before surgery and the hepatic parenchymal resection of more than two Healey's segments correlated significantly with an increased risk of severe complications (P = 0.044, 0.0152, respectively). The 1-, 2-, and 3-year survival rates were 44%, 33%, and 11%, respectively. CONCLUSIONS: Hepatopancreatoduodenectomy might offer a chance of long survival by yielding a tumor-free margin in selected patients who are able to tolerate such an aggressive operation, but the indication for this aggressive surgery should be carefully considered.

Improvement of delayed gastric emptying in pylorus-preserving pancreaticoduodenectomy: results of a prospective, randomized, controlled trial.

OBJECTIVE: To determine if an antecolic or a retrocolic duodenojejunostomy during pylorus-preserving pancreaticoduodenectomy (PpPD) was associated with the least incidence of delayed gastric emptying (DGE), in a prospective, randomized, controlled trial. SUMMARY BACKGROUND DATA: The pathogenesis of DGE after PpPD has been speculated to be related to factors such as inflammation, ischemia, gastric atony, motilin levels, and type of surgical procedure. Previous retrospective studies have shown a lower incidence of DGE after antecolic duodenojejunostomy. A prospective trial is needed. METHODS: Forty patients were enrolled in this trial between May 2002 and April 2004. Just before duodenojejunostomy during PpPD, the patients were randomly assigned to undergo either an antecolic or a retrocolic duodenojejunostomy. RESULTS: DGE occurred in 5% of patients with the antecolic route for duodenojejunostomy versus 50% with the retrocolic route (P = 0.0014). Those with the antecolic route had a significantly shorter duration of postoperative nasogastric tube drainage than did those with the retrocolic route (4.2 days versus 18.9 days, respectively, P = 0.047). By postoperative day 14, all patients with the antecolic route could take solid foods, while only 55% (11 of 20) of the patients with the retrocolic route could take solid foods (P = 0.0007). The length of stay in the hospital was 28 days for the antecolic group versus 48 days for the retrocolic group (P = 0.018). CONCLUSIONS: Antecolic reconstruction for duodenojejunostomy during PpPD decreases postoperative morbidity and length of hospital stay by decreasing DGE. Our data suggest that PpPD with antecolic duodenojejunostomy is a safer operation.