Long-term survival after resection for non-pancreatic periampullary cancer followed by adjuvant intra-arterial chemotherapy and concomitant radiotherapy.

BACKGROUND: There is no consensus regarding the optimal adjuvant treatment after resection of non-pancreatic periampullary adenocarcinoma (NPPC; distal common bile duct, ampulla, duodenum). OBJECTIVES: The present study was conducted to evaluate the impacts on longterm survival and recurrence of adjuvant intra-arterial chemotherapy (IAC) and concomitant radiotherapy (RT) in patients submitted to resection for NPPC or pancreatic ductal adenocarcinoma (PDAC) in a randomized controlled trial. METHODS: A total of 120 patients with PDAC (n = 62) or NPPC (n = 58) were prestratified at a ratio of 1:1 for tumour origin and randomized. Half of these patients were treated with adjuvant IAC/RT and the other half were treated with surgery alone. Follow-up was completed for all patients up to 5 years after resection or until death. RESULTS: There was no survival benefit in either the whole group (primary endpoint) or the PDAC group after IAC/RT. In the NPPC group, longterm survival was observed in 10 patients in the IAC/RT group and five patients in the control group: median survival was 37 months and 28 months, respectively. The occurrence of liver metastases was reduced by IAC/RT from 57% to 29% (P = 0.038). Cox regression analysis revealed a substantial effect of IAC/RT on survival (hazard ratio: 0.44, 95% confidence interval 0.23-0.83; P = 0.011). CONCLUSIONS: This longterm analysis shows that median and longterm survival were improved after IAC/RT in patients with NPPC, probably because of the effective and sustained reduction of liver metastases. The present results illustrate that NPPC requires an adjuvant approach distinct from that in pancreatic cancer and indicate that further investigation of this issue is warranted.

Type I interferons as radiosensitisers for pancreatic cancer.

BACKGROUND: Radiotherapy is an established treatment for malignant localised disease. Pancreatic cancer however seems relatively insensitive to this form of therapy. METHODS: Pancreatic cancer cell lines MiaPaca-2 and Panc-1 were pre-treated with 3000 IU/ml IFNα or 100 IU/ml IFNß followed by 0, 2, 4, or 6 Gray (Gy) irradiation. Colony forming assay was used to assess the effects on cellgrowth. To measure the surviving fraction at the clinically relevant dose of 2Gy (SF2), cells were pre-treated with 1000-10.000 IU/ml IFNα or 50-500 IU/ml IFNß followed by 2Gy irradiation. RESULTS: The plating efficiency was 49% for MiaPaca-2 and 22% for Panc-1. MiaPaca-2 was more radiosensitive than Panc-1 (surviving fraction of 0.28 versus 0.50 at 4 Gray). The SF2 of MiaPaca-2 was 0.77 while the SF2 of Panc-1 was 0.70. The SF2 significantly decreased after pretreatment with IFNα 1000 IU/ml (p<0.001) and IFNß 100 IU/ml (p<0.001) in MiaPaca-2 and with IFNα 5000 IU/ml (p<0.001) and IFNß 100 IU/ml (p<0.01) in Panc-1. The sensitising enhancement ratio (SER) for IFNα 3000 IU/ml was 2.15 in MiaPaca-2 and 1.90 in Panc-1. For IFNß 100 IU/ml the SER was 1.72 for in MiaPaca-2 and 1.51 in Panc-1. CONCLUSIONS: Type I interferons have radiosensitising effects in pancreatic cancer cell lines. This radiosensitising property might lead to an improved response to treatment in pancreatic cancer. Interferon ß is the most promising drug due to its effect in clinically obtainable doses.

Phase II trial of Uracil/Tegafur plus leucovorin and celecoxib combined with radiotherapy in locally advanced pancreatic cancer.

BACKGROUND AND PURPOSE: To investigate the efficacy and toxicity of a short intensive Uracil/Tegafur (UFT) based chemoradiotherapy scheme combined with celecoxib in locally advanced pancreatic cancer. MATERIAL AND METHODS: The Academic Medical Centre, Amsterdam and the Erasmus Medical Centre, Rotterdam enrolled 83 eligible patients with unresectable pancreatic cancer in a prospective multicentre phase II study. Median age was 62 years, median tumour size 40 mm and the majority of the patients (85%) had pancreatic head cancers. Treatment consisted of 20×2.5 Gy radiotherapy combined with UFT 300 mg/m(2) per day, leucovorin (folinic acid) 30 mg and celecoxib 80 0mg for 28 days concomitant with radiotherapy. Four patients were lost to follow-up. RESULTS: Full treatment compliance was achieved in 55% of patients, 80% received at least 3 weeks of treatment. No partial or complete response was observed. Median survival was 10.6 months and median time to progression 6.9 months. Toxicity was substantial with 28% grades III and IV gastro-intestinal toxicity and two early toxic deaths. CONCLUSIONS: Based on the lack of response, the substantial toxicity of mainly gastro-intestinal origin and the reported mediocre overall and progression free survival, we cannot advise our short intensive chemoradiotherapy schedule combined with celecoxib as the standard treatment.

Quality of life after adjuvant intra-arterial chemotherapy and radiotherapy versus surgery alone in resectable pancreatic and periampullary cancer: a prospective randomized controlled study.

BACKGROUND: Adjuvant therapies for pancreatic and periampullary cancer reportedly achieve only a marginal survival benefit. In this randomized controlled trial, 120 patients with resected pancreatic or periampullary cancer received either adjuvant celiac axis infusion chemotherapy combined with radiotherapy (CAI/RT) or no adjuvant treatment. The objective of the study was to compare the quality of life (QoL) in patients who received CAI/RT after pancreatoduodenectomy with the QoL in patients who did not receive adjuvant treatment. METHODS: During and after CAI/RT, QoL was assessed using the European Organization for Research and Treatment of Cancer QoL Questionnaire C30 every 3 months during the first 24 months after randomization. RESULTS: Eighty-six percent of patients (n = 103) completed 1 or more questionnaires. In total, 355 questionnaires were completed. The results indicated that CAI/RT did not impair physical, emotional, or social functioning. During and after CAI/RT, patients had significantly less pain (P = .02) and less nausea and vomiting (P = .01). Overall QoL (global functioning) tended to be better (P = .08) after CAI/RT. CONCLUSIONS: Over a period of 24 months, CAI/RT improved QoL compared with observation alone in patients with resected pancreatic and periampullary cancer. This beneficial effect of CAI/RT was most prominent in the latter half of the follow-up.

Ischemic acute necrotizing pancreatitis in a marathon runner.

CONTEXT: Acute pancreatitis due to pancreatic ischemia is a rare condition. CASE REPORT: In this case report we describe a 57-year-old male who developed an acute necrotizing pancreatitis after running a marathon and visiting a sauna the same evening, with an inadequate fluid and food consumption during both events. CONCLUSIONS: Pancreatic ischemia imposed by mechanical and physical stress and dehydration can induce the development of acute pancreatitis. Separately, these factors are rare causes of ischemic acute pancreatitis. But when combined, as in this particular case, the risk of an acute necrotizing pancreatitis cannot be neglected.

A Single-Lumen Central Venous Catheter for Continuous and Direct Intra-abdominal Pressure Measurement.

BACKGROUND: Abdominal compartment syndrome (ACS) is associated with high morbidity and mortality rates. Therefore, the need for a good diagnostic tool to predict intra-abdominal hypertension (IAH) and progression to ACS is paramount. Bladder pressure (BP) has been used for several years for intra-abdominal pressure (IAP) measurement but has the disadvantage that it is not a continuous measurement. In this study, a single-lumen central venous catheter (CVC) is placed through the abdominal wall into the abdominal cavity to continuously and directly monitor the intraabdominal pressure (CDIAP). The aim of this study was to evaluate the use of CDIAP to measure BP as a representative of the true IAP. METHODS: Both BP and CDIAP were prospectively recorded on a variety of surgical patients admitted to the intensive care unit (ICU) from March 2003 up to December 2004. At the end of the surgical procedure, the CVC was placed through the abdominal wall and connected to a pressure transducer. In addition, the BP was measured through the urine drainage port after clamping the catheter and filling the bladder with 50 ml of 0.9% saline. At least three paired measurements (BP and CDIAP) were performed for at least one day on the ICU in a standardized manner at preset time intervals on each patient. The paired measurements were compared using the Bland-Altman (B-A) method. Data are presented as mean ± standard deviation. RESULTS: Over a period of 22 months (March 2003 until December 2004), 125 paired measurements of both BP and CDIAP were recorded on 25 patients. The mean age was 72.4 ± 6.6 years. Eighteen patients underwent central vascular surgery, and seven patients with peritonitis received laparotomy. The mean CDIAP was 11.4 ± 4.8 (range 2-30) mmHg, and the BP was 12.9 ± 5.3 (range 3-37) mmHg. The mean difference between CDIAP and BP was 1.6 ± 2.7 mmHg. There was an acceptable level of agreement (intraclass correlation 0.82) between IAP measured by BP and IAP measured via CDIAP. CONCLUSION: Continuous direct intra-abdominal pressure measurement proved that the BP measurement approach of Kron is representative of the IAP. CDIAP measurement is accurate and makes it easier for the nursing staff to be informed of the IAP.

Adjuvant intra-arterial chemotherapy and radiotherapy versus surgery alone in resectable pancreatic and periampullary cancer: a prospective randomized controlled trial.

BACKGROUND: Success of surgical treatment for pancreatic and periampullary cancer is often limited due to locoregional recurrence and/or the development of distant metastases. OBJECTIVE: The survival benefit of celiac axis infusion (CAI) and radiotherapy (RT) versus observation after resection of pancreatic or periampullary cancer was investigated. METHODS: In a randomized controlled trial, 120 consecutive patients with histopathologically proven pancreatic or periampullary cancer received either adjuvant treatment consisting of intra-arterial mitoxantrone, 5-FU, leucovorin, and cisplatinum in combination with 30 x 1.8 Gy radiotherapy (group A) or no adjuvant treatment (group B). Groups were stratified for tumor type (pancreatic vs. periampullary tumors). RESULTS: After surgery, 120 patients were randomized (59 patients in the treatment group, 61 in the observation group). The median follow-up was 17 months. No significant overall survival benefit was seen (median, 19 vs. 18 months resp.). Progressive disease was seen in 86 patients: in 37 patients in the CAI/RT group, and in 49 patients in the observation group (log-rank P < 0.02). Subgroup analysis showed significantly less liver metastases after adjuvant treatment in periampullary tumors (log-rank P < 0.03) without effect on local recurrence. Nonetheless, there was no significant effect on overall survival in these patients (log-rank P = 0.15). In patients with pancreatic cancer, CAI/RT had no significant effect on local recurrence (log-rank P = 0.12) neither on the development of liver metastases (log-rank P = 0.76) and consequently, no effect on overall survival. CONCLUSION: This adjuvant treatment schedule results in a prolonged time to progression. For periampullary tumors, CAI/RT induced a significant reduction in the development of liver metastases, with a possible effect on overall survival. Especially in these tumors, CAI/RT might prove beneficial in larger groups and further research is warranted.