Follow-up after curative surgery for pancreatic ductal adenocarcinoma: Asymptomatic recurrence is associated with improved survival

Aim

There is no consensus on the optimal follow-up schedule of patients after surgery for pancreatic cancer. In this retrospective study, recurrence and survival were investigated for patients presenting with either symptomatic or asymptomatic recurrence. Patient, tumor and treatment characteristics that predicted the length of postrecurrence survival were identified.

Methods

Clinical records of 164 patients who underwent a pancreatic resection (R0/R1) for pancreatic ductal adenocarcinoma from January 2000 to December 2010 were retrieved. Patients underwent a systematic follow-up program. Patient, tumor and treatment characteristics were compared between patients with asymptomatic and symptomatic recurrence.

Results

Of 164 consecutive patients, 144 patients (88%) had recurrence (29 asymptomatic, 115 symptomatic). The most frequent reported symptoms were abdominal pain, fatigue/weakness, back pain, weight loss, nausea/loss of appetite and jaundice. Median time to recurrence was 12.0 months for asymptomatic and 7.0 months for symptomatic patients (P = 0.036). Median postrecurrence survival was 10.0 months for asymptomatic and 4.0 months for symptomatic patients (P < 0.0001). Median overall survival was 24.5 months for asymptomatic and 11.0 months for symptomatic patients (P < 0.0001). Symptomatic recurrence, disease free survival <12 months, and no adjuvant chemotherapy were the only independent predictors of poor postrecurrence survival. 72% of asymptomatic and 37% of symptomatic patients received oncological treatment.

Conclusions

Patients with asymptomatic pancreatic cancer recurrence have improved recurrence-free, postrecurrence and overall survival. Symptoms when recurrence is diagnosed are a good surrogate marker of biological aggressiveness. Detection of asymptomatic recurrence may facilitate patient eligibility for investigational studies or other forms of treatment.     

Whole‐body fat oxidation determined by graded exercise and indirect calorimetry: a role for muscle oxidative capacity?

During whole-body exercise, peak fat oxidation occurs at a moderate intensity. This study investigated whole-body peak fat oxidation in untrained and trained subjects, and the presence of a relation between skeletal muscle oxidative enzyme activity and whole-body peak fat oxidation. Healthy male subjects were recruited and categorized into an untrained (N=8, VO(2max) 3.5+/-0.1 L/min) and a trained (N=8, VO(2max) 4.6+/-0.2 L/min) group. Subjects performed a graded exercise test commencing at 60 W for 8 min followed by 35 W increments every 3 min. On a separate day, muscle biopsies were obtained from vastus lateralis and a 3 h bicycle exercise test was performed at 58% of VO(2max). Whole-body fat oxidation was calculated during prolonged and graded exercise from the respiratory exchange ratio using standard indirect calorimetry equations. Based on the graded exercise test, whole-body peak fat oxidation was determined. The body composition was determined by DEXA. Whole-body peak fat oxidation (250+/-25 and 462+/-33 mg/min) was higher (P<0.05) and occurred at a higher (P<0.05) relative workload (43.5+/-1.8% and 49.9+/-1.2% VO(2max)) in trained compared with untrained subjects, respectively. Muscle citrate synthase activity and beta-hydroxy-acyl-CoA-dehydrogenase activity were higher (49% and 35%, respectively, P<0.05) in trained compared with untrained subjects. Both lean body mass and maximal oxygen uptake were significantly correlated to whole-body peak fat oxidation (r(2)=0.57, P<0.001), but leg muscle oxidative capacity was not correlated to whole-body peak fat oxidation. In conclusion, whole-body peak fat oxidation occurred at a higher relative exercise load in trained compared with untrained subjects. Whole-body peak fat oxidation was not significantly related to leg muscle oxidative capacity, but was related to lean body mass and maximal oxygen uptake. This may suggest that leg muscle oxidative activity is not the main determinant of whole-body peak fat oxidation.     

Renal effects of trimethoprim in ciclosporin- and azathioprine-treated kidney-allografted patients

Sixteen stable renal transplant patients on chronic ciclosporin (CS, n = 8) or azathioprine (AZA, n = 8) treatment were given trimethoprim (TMP) 160 mg twice a day for 7 days. This TMP dose did not affect glomerular filtration, as 99mTc-DTPA clearance was unchanged in both groups. TMP did, however, increase serum creatinine and reduce creatinine clearance in all patients. This effect was most pronounced in CS-treated patients. We conclude that even at the moderate dosage, as employed presently, TMP blocks tubular secretion of creatinine. This route for creatinine excretion is quite important as the clearance ratio between creatinine and DTPA averaged 1.21 in CS-treated patients and 1.05 in AZA-treated patients before TMP treatment. During TMP the ratio was reduced to 0.95 and 0.99, respectively, suggesting a complete cessation of tubular creatinine secretion by TMP. TMP did not, however, significantly affect other markers of renal tubular function.     

Influence of 4-aminopyrazolopyrimidine on morphology, synthesis of triglyceride and protein and their secretion in rat hepatocytes.

The influence of 4-aminopyrazolopyrimidine (4-APP) on morphology and on synthesis and secretion ability of isolated rat hepatocytes was investigated: 4-APP was found to inhibit both the synthesis and secretion of proteins. The synthesis of triglycerides was unaffected by 4-APP, while the secretion of triglycerides was markedly reduced. Transmission electron microscopy revealed that 4-APP induced morphological changes in the smooth membrane systems, the smooth endoplasmic reticulum and the Golgi apparatus. The possibility that 4-APP inhibits lipoprotein formation by inhibition of the apoprotein synthesis is discussed.     

The Euglobulin Clot Lysis Time,a Rapid and Sensitive Method for the Assay of Fibrinolytic Activity after Venous Stasis

For the estimation of fibrinolytic activity in euglobulin precipitates after venous stasis, the euglobulin clot lysis time (ECLT) proved to be as reproducible and probably even more sensitive than the fibrin plate method (FP). Furthermore, when euglobulin precipitates from 55 healthy individuals and 36 patients with thromboembolic disease were examined, a good correlation between the two methods was observed. The present observations indicate that the ECLT is suitable for routine screening of fibrinolytic activity after venous stasis.     

Four brief reports on long-term results of intradiscal chymopapain

Five- to 12-year statistics for 842 patients treated with intradiscal chymopapain are presented by four observers. While the results are presented in different formats, long-term satisfactory results can be reported for 81% of the patients, with a range of 71%-83%.     

Bone atrophy after plate fixation: Computed tomography of femoral shaft fractures

Twelve patients with previous femoral shaft fracture treated by rigid plate fixation were examined by computed tomography (CT) scanning 1 or 2 days after plate removal. In the previously plated segment an average reduction in cortical density of 11 per cent was found, and the reduction was most pronounced in the cortex directly beneath the plate. No reduction in cortical thickness of the plated bone occurred. Proximal and distal to the site of the plate, and in the ipsilateral tibial shaft, a slight reduction in cortical density and thickness averaging 2-3 per cent was found.     

Eight- to 13-year follow-up evaluation of chemonucleolysis patients

739 patients treated eight to 13 years previously with chymopapain injection are evaluated by questionnaire. The results were 76% satisfactory and 24% unsatisfactory. When those with prior surgery, midline discs, and spondylolisthesis were eliminated, there is a satisfactory result in 82% with 60% excellent, reinforcing the importance of patient selection for the procedure. Thirty-one percent of patients had preoperative myelograms, and all had discograms and were done under general anesthesia with the single needle technique. Of the excellent and good results, 50% had a two-level injection, while one-level injections produced only 23% and 20%, respectively. Results in midline discs are comparable to lateral displacement and the 13 patients with spondylolisthesis had 85% satisfactory outcome. In ten patients younger than 19 years of age, only one was a failure. Sixteen percent of patients had prior surgery and they reported a successful outcome of injection in 55%. Of the 179 unsatisfactory results in the series, subsequent treatment reduced the rate of failed end results to 14%. The study verifies the persistence of early satisfactory results and shows no late complications such as symptomatic iatrogenic spinal stenosis.