PANCREAS ALERTS
J Surg Res 2002; 102:161-8.
Functional alterations of splenocytes in severe acute pancreatitis.
Ueda T, Takeyama Y, Yasuda T, Takase K, Nishikawa J, Kuroda Y.
First Department of Surgery, Kobe University School of Medicine, Kobe 650-0017, Japan.
Recently, the concept of "Th1/Th2 (T helper cell type 1/T helper cell type 2) balance" was introduced to explain the pathophysiologic response during septic or preseptic conditions.
The authors studied the functional alterations of the splenocyte in severe acute pancreatitis induced in rats in order to clarify the Th1/Th2 balance during acute pancreatitis.
Spleens were removed from rats 24 h after the induction of severe necrotizing pancreatitis by retrograde injection of 3% sodium deoxycholate. Total splenocytes were harvested and cultured in the presence or absence of concanavalin A for 24 h. Proliferative capacities and cytokine-releasing capacities were also evaluated.
In splenocytes harvested 24 h after the induction of pancreatitis, proliferative capacity with concanavalin A stimulation was significantly lower than that of sham operation.
The authors concluded that splenocyte function is markedly suppressed in experimental severe acute pancreatitis and that Th1/Th2 balance tends to Th1 suppression as a whole.
Interleukin-2 release with concanavalin A stimulation and interferon-gamma release with or without concanavalin A stimulation were significantly decreased in splenocytes from the rats with pancreatitis compared with those from sham operation.
Interleukin-10 release with concanavalin A stimulation was also significantly decreased in splenocytes from the rats with pancreatitis compared with those from sham operation.
The interleukin-2/interleukin-10 concentration ratio secreted by the splenocytes from the rats with pancreatitis was significantly lower than that from those undergoing the sham operation.
Dysfunction of lymphocytes including splenocytes may play a role in the development of subsequent septic complications in acute pancreatitis.
Ann Surg 2002; 235:240-5.
Pancreatic fibrosis correlates with delayed gastric emptying after pylorus-preserving pancreaticoduodenectomy with pancreaticogastrostomy
Murakami H, Suzuki H, Nakamura T.
Department of Surgery, Kainan Hospital; Department of Pathology, Aichi Prefectural Hospital; and Department of Pathology, Nagoya City University School of Medicine, Nagoya, Japan.
Delayed gastric emptying is a leading cause of complications after pylorus-preserving pancreaticoduodenectomy, occurring in 30% of patients and its pathogenesis is unclear.
The authors used surgical specimens to evaluate gastric stasis after pylorus-preserving pancreaticoduodenectomy.
Surgical specimens of the pancreas from 25 patients undergoing pylorus-preserving pancreaticoduodenectomy and pancreaticogastrostomy were collected and examined by microscopy according to progressive pancreatic fibrosis and divided into three groups: no fibrosis, periductal fibrosis and intralobular fibrosis.
Pancreatic juice output was significantly related to the degree of pathologic findings and gastric output was inversely related to them.
In conclusion, pancreatic fibrosis and increased gastric fluid production are correlated with delayed gastric emptying after pylorus-preserving pancreaticoduodenectomy with pancreaticogastrostomy.
Gastric output from the nasogastric tube and pancreatic output from the pancreatic tube were measured and the time until patients could tolerate a solid diet was also evaluated.
A significant prolongation of postoperative solid diet tolerance correlated with increased pancreatic fibrosis and gastric fluid production.
Lancet. 2001; 358(9293):1576-85.
Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial.
Neoptolemos JP, Dunn JA, Stocken DD, Almond J, Link K, Beger H, et al.
Department of Surgery, Liverpool University, Liverpool, UK.
This study, carried out by the European Study Group for Pancreatic Cancer, reports on the interim results of a randomised controlled trial whose aim was to determine whether adjuvant chemoradiotherapy or adjuvant chemotherapy alone has a role in improving the survival rate of patients with resectable pancreatic cancer.
The article reports the first look at the data when the study was closed to recruitment; the final analysis will be done when all patients have been followed up for at least 2 years.
Eighty-three clinicians in 61 centres in 11 countries recruited patients with resected pancreatic cancer between February 1994 and April 2000.
Five hundreds and 41 eligible patients were randomised: 285 were entered into a two by two factorial design, 68 into chemoradiotherapy versus no chemoradiotherapy, and 188 into chemotherapy versus no chemotherapy. Hence, 353 eligible patients were included in the analysis of the chemoradiotherapy question (175 assigned chemoradiotherapy versus 178 assigned no chemoradiotherapy) and 473 were included in the chemotherapy analysis (238 assigned chemotherapy versus 235 assigned no chemotherapy).
The median age of the patients was 60 years (IQR 53-67) . The average tumour size was 3 cm; positive resection margins were found in 19% of the patients while nodal involvement was discovered in 53%.
All analyses were done by intention to treat; the patients with protocol violations (51) were kept in the relevant randomisation treatment group. The study reports results after 314 deaths (58%).
Overall results showed no benefit for adjuvant chemoradiotherapy (median survival 15.5 [95% CI: 3.5-17.4] months in treatment group versus 16.1 [95% CI: 13.1-20.1] months in no chemoradiotherapy group). By contrast, there was evidence of a survival benefit for adjuvant chemotherapy (median survival 19.7 [95% CI: 16.4-22.4] months in treatment group versus 14.0 [95% CI: 11.9-16.5] months in untreated patients; hazard ratio 0.66 [95% CI: 0.52-0.83]; p=0.0005). There was no difference in survival due to the following factors: history of smoking, sex , age, invasion of adjacent structures or history of diabetes mellitus. Involvement of the resection margins, tumour grade, tumour size, and nodal involvement were all significant predictors of survival.
The main conclusions of this important trial were that the adjuvant chemoradiotherapy regimen did not improve the 2 year survival rate while adjuvant chemotherapy had a positive effect. These results justify further randomised controlled trials of adjuvant chemotherapy in pancreatic cancer.
Patients were eligible if they had histologically proven ductal adenocarcinoma of the pancreas, macroscopically resected, with no evidence of local spread or distant metastases.
Randomisation was stratified according to the resection margin status (positive or negative) and adjuvant therapy was started as soon as possible after full recovery from the operation (median time, 21 days).
Resection was by standard pancreatoduodenectomy (Whipple's procedure or pylorus-preserving pancreatoduodenectomy) for tumours in the head of the gland and left or total pancreatectomy for pancreatic cancer in the tail or large tumours in the body of the gland.
The chemoradiotherapy consisted of 20 Gy tumour doses in ten daily fractions over 2 weeks with 500 mg/m2 fluoruracil i.v. on the first 3 days, repeated after 2 weeks. The chemotherapy consisted of i.v. bolus folinic acid (20 mg/m2) followed by i.v. bolus fluoruracil (425 mg/m2) given on 5 consecutive days every 28 days for six cycles. Combination therapy consisted of chemoradiotherapy followed by chemotherapy, both as defined above.