A multicentre randomised phase II trial of gemcitabine alone vs gemcitabine and S-1 combination therapy in advanced pancreatic cancer: GEMSAP study.

BACKGROUND: This randomised phase II trial compared gemcitabine alone vs gemcitabine and S-1 combination therapy in advanced pancreatic cancer. METHODS: Patients were randomly assigned to 4-week treatment with gemcitabine alone (1000, mg m(-2) gemcitabine by 30-min infusion on days 1, 8, and 15) or gemcitabine and S-1 combination therapy (1000, mg m(-2) gemcitabine by 30-min infusion on days 1 and 15 and 40 mg m(-2) S-1 orally twice daily on days 1-15). The primary end point was progression-free survival (PFS). RESULTS: Between July 2006 and February 2009, 106 patients were enrolled. The PFS in gemcitabine and S-1 combination arm was significantly longer than in gemcitabine arm (5.4 vs 3.6 months), with a hazard ratio of 0.64 (P=0.036). Overall survival (OS) for gemcitabine and S-1 combination was longer than that for gemcitabine monotherapy (13.5 vs 8.8 months), with a hazard ratio of 0.72 (P=0.104). Overall, grade 3 or 4 adverse events were similar in both arms. CONCLUSION: Gemcitabine and S-1 combination therapy demonstrated longer PFS in advanced pancreatic cancer. Improved OS duration of 4.7 months was found for gemcitabine and S-1 combination therapy, though this was not statistically significant.

Inhibition of renin-angiotensin system affects prognosis of advanced pancreatic cancer receiving gemcitabine.

BACKGROUND: The renin-angiotensin system (RAS) is thought to have a role in carcinogenesis, and RAS inhibition may prevent tumour growth. METHODS: We retrospectively investigated the impact of angiotensin I-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) in 155 patients with pancreatic cancer receiving gemcitabine monotherapy. Patients were divided into three groups: the ACEI/ARB group (27 patients receiving an ACEI or ARB for hypertension (HT)), the non-ACEI/ARB with HT group (25 patients receiving antihypertensive drugs other than ACEIs or ARBs), and the non-HT group (103 patients receiving no antihypertensive drugs). RESULTS: Patient characteristics were not different, except for age and HT medications. Progression-free survival (PFS) was 8.7 months in the ACEI/ARB group, 4.5 months in the non-ACEI/ARB with HT group, and 3.6 months in the non-HT group. Overall survival (OS) was 15.1 months in the ACEI/ARB group, 8.9 months in the non-ACEI/ARB with HT group, and 9.5 months in the non-HT group. The use of ACEIs/ARBs was a significant prognostic factor for both PFS (P=0.032) and OS (P=0.014) in the multivariate analysis. CONCLUSIONS: The ACEIs/ARBs in combination with gemcitabine might improve clinical outcomes in patients with advanced pancreatic cancer. Prospective trials are needed to test this hypothesis.

Laboratory and imaging features of kidney involvement in autoimmune pancreatitis: incidence, correlation, and steroid therapy response.

AIM: Autoimmune pancreatitis (AIP) is a rare subtype of chronic pancreatitis. AIP has been suggested to be complicated by tubulointerstitial nephritis or glomerulonephritis, implying that the kidney is involved as a phenotype of IgG4-positive multi-organ lymphoproliferative syndrome; however, the clinical significance of this novel entity is not well-defined. METHODS: We conducted a retrospective cohort analysis of 47 (male, 39; female, 8) AIP patients. RESULTS: The patients (mean age, 70.3 +/- 9.5 years) had a mean observation period of 4.1 years. Before treatment, renal dysfunction with an eGFR of 30 and 15 ml/min/1.73 m2 developed only in 10.6% (5/47) and 2.1% (1/47) of the patients, respectively. Nevertheless, urinary N-acetyl-beta-D-glucosaminidase and alpha1-microglobulin levels were elevated in 78.6% (11/14) and 30.8% (4/13) of the patients, respectively. Renal involvement in contrast-enhanced CT imaging was present in 18.2% (8/44) of the patients and was associated with proteinuria (p = 0.04) and a decrease in eGFR (p < 0.01). Furthermore, a follow-up CT study (mean, 545 days) revealed improved kidney lesions in 80.0% (4/5) of the patients after oral corticosteroid administration. In contrast, first-time kidney involvements appeared newly in 3.6% (1/28) of the patients after steroid therapy for nonrenal AIP symptoms, and in 14.3% (1/7) of the patients under no specific therapy (p = 0.02). CONCLUSION: Although severe renal failure develops rarely in AIP patients, renal abnormalities have been significantly detected by biochemical and radiological tests. Oral corticosteroid administration, even when not targeting symptomatic nephropathy, can treat and prevent kidney involvements in AIP.

Self-expandable metallic stents for malignant biliary obstruction with an anomalous pancreaticobiliary junction.

BACKGROUND: Anomalous pancreaticobiliary junction (APBJ) is associated with pancreaticobiliary cancer. Limited data are available on endoscopic biliary drainage for unresectable malignant biliary obstruction with APBJ. This study evaluated the efficacy and safety of self-expandable metallic stents (EMSs) for the management of malignant biliary obstruction with APBJ. METHODS: Between 1993 and 2005, 324 patients with unresectable malignant biliary obstruction underwent insertion of an EMS. Six of these patients with concomitant APBJ constituted the subjects of this study. Early (30 days after EMS insertion) stent-related complications and stent patency were evaluated in these six patients. RESULTS: The cause of biliary obstruction was gallbladder cancer in four patients and pancreatic cancer in two patients. Uncovered EMSs were inserted across the common channel without performance of a biliary sphincterotomy. The diameter of the uncovered EMS used was based on the diameter of the common channel. For all six patients, endoscopic biliary drainage was successful, and their jaundice subsided steadily. None of the six patients experienced early complications, including acute pancreatitis. The mean stent-related complication-free period was 163 days. Stent occlusion caused by tumor ingrowth occurred in two patients. Acute cholangitis and cholecystitis were observed in one patient each. CONCLUSIONS: Uncovered EMSs are effective for palliation of unresectable malignant biliary obstruction in patients who have APBJ without increasing the risk of stent-related early complications.

Endoscopic transpapillary approach to the gallbladder for diagnosing gallbladder cancer.

PURPOSE: Gallbladder cancer (GBC) has a poor prognosis that is related to delayed diagnosis. The present study evaluated the efficacy of the transcystic ductal approach in diagnosing GBC. METHODS: A catheter was introduced into the gallbladder endoscopically via the cystic duct to obtain bile for cytology. Subsequently, cytology specimens were collected using a brush, and intraductal ultrasonography (IDUS) was performed using a miniature probe in patients suspected of having GBC. RESULTS: Bile cytology was performed successfully in 23 of 25 patients (92%). The sensitivity, specificity and accuracy of cytology were 44.4%, 100% and 78.3%, respectively. Brush cytology and IDUS were successful in six of eight (75%) and nine of 15 (60%) patients, respectively. Brush cytology was positive in two of five patients with GBC. In all four patients with invasive cancer, IDUS showed an irregularity or disruption of the outermost hyperechoic layer. CONCLUSIONS: The endoscopic transpapillary approach to the gallbladder was useful for the diagnosis of GBC. Brush cytology and IDUS may improve diagnostic efficacy and provide more useful information.

Duct-ectatic type of mucin producing tumor of the pancreas--new concept of pancreatic neoplasia.

BACKGROUND/AIMS: Although there have been recent reports of mucin-producing tumor of the pancreas, there has been no thorough clinicopathological analysis of a large number of cases. MATERIALS AND METHODS: Two hundred forty four cases of mucin-producing tumor of the pancreas from Japanese, European and American reports, together with 15 cases of our own, were analyzed clinicopathologically. RESULTS: Mucin-producing tumor of the pancreas was found in 177 males and 82 females (M:F = 2.2:1). The mean age was 65.5 years. Jaundice, diabetes mellitus and a past history of pancreatitis were found in 15%-19% of the cases. The tumor was most frequently (62%) found in the head of the pancreas. Pathologically, hyperplasia or adenoma was found in 58 cases, and adenocarcinoma in 160 cases. Five-year-survival rate by the Kaplan-Meier method was 82.6% in all of the cases and postoperative survival curve was much better in cases with this type of carcinoma than in cases with ordinary pancreatic duct cell carcinoma (5-year-survival rate: 82.6% vs 17.3%). Serum tumor markers such as CEA or CA 19-9 were not effective in differentiating between benign and malignant, or in determining the degree of cancerous spread, while cytology of the pancreatic juice and biopsy of the tumor could contribute to the diagnosis. CONCLUSIONS: Mucin-producing tumor has unique clinicopathological characteristics, such as the dilated main pancreatic duct or branches, dilatation of the orifice of the papilla of Vater, or good prognosis. Since a diagnosis for benign or malignant is very difficult in some cases, methods for distinguishing benign from malignant lesions or for determining cancerous spread, such as molecular biological techniques, should be established.

[Two elderly patients with Rhabdomyolysis and respiratory infection with Streptococcus pneumoniae].

Rhabdomyolysis is not common in the elderly. Two elderly patients with rhabdomyolysis and respiratory infection with Streptococcus pneumoniae. The first patient was a 71-year-old woman with bronchiectasis who admitted to our hospital due to pneumonia. The second patient was an 84-year-old man who was admitted because of appetite loss, fever, and a cough producing of yellowish sputum. In both patients, sputum cultures were positive for S. pneumoniae, but blood cultures were not. The serum creatine kinase levels peaked on the day of admission at levels ten to thirty times higher than fold above the upper limit of normal; the serum lactate dehydrogenase levels were 1.5 times higher than the upper limit of normal. The creatine kinase levels returned to normal 5 to 7 days after admission, treated with antibiotics and recovered from pneumonia. The cases of these two patients, along with those described in previous reports of rhabdomyolysis associated with pneumococcal pneumonia indicate that measuring the serum creatine kinase level is important in detecting rhabdomyolysis, especially in elderly patients with respiratory infection caused by S. pneumoniae, and detection may help to prevent renal failure.