Prognosis following surgical bypass compared with laparotomy alone in unresectable pancreatic adenocarcinoma.

BACKGROUND: Resection with curative intent has been shown to prolong survival of patients with locoregional pancreatic ductal adenocarcinoma (PDAC). However, up to 33 per cent of patients are deemed unresectable at exploratory laparotomy owing to unanticipated locally advanced or metastatic disease. In these patients, prophylactic double bypass (PDB) procedures have been considered the standard of care. The aim of this study was to compare PDB with exploratory laparotomy alone in terms of impact on postoperative course, chemotherapy and overall survival. METHODS: This retrospective observational cohort study (2004-2013) was conducted using a prospective institutional database. Patients with histologically confirmed, unresectable PDAC were included. Relationships between PDB procedures, exploratory laparotomy alone, postoperative chemotherapy and best supportive care were investigated by means of Cox regression. Overall survival was compared using Kaplan-Meier estimations and log rank test. RESULTS: Of 503 patients with PDAC scheduled for resection with curative intent, 104 were deemed unresectable at laparotomy (resection rate 79·3 per cent). Seventy-four patients underwent PDB procedures and 30 had exploratory laparotomy alone. PDB and exploratory laparotomy were similar in terms of perioperative mortality, initiation of chemotherapy and overall survival. Compared with best supportive care, postoperative chemotherapy prolonged survival (8·0 versus 14·4 months in locally advanced PDAC, P = 0·007; 2·3 versus 8·0 months in metastatic PDAC, P < 0·001). Patients undergoing chemotherapy following exploratory laparotomy alone had longer median overall survival than patients undergoing chemotherapy following PDB procedures (16·3 versus 10·3 months; P = 0·040). CONCLUSION: Patients with pancreatic cancer deemed unresectable at laparotomy may derive survival benefit from subsequent chemotherapy as opposed to supportive care alone. At laparotomy, proceeding with a bypass procedure for prophylactic symptom control may be prognostically unfavourable.

Impact of delay between imaging and treatment in patients with potentially curable pancreatic cancer.

BACKGROUND: Locoregional pancreatic ductal adenocarcinoma (PDAC) may progress rapidly and/or disseminate despite having an early stage at diagnostic imaging. A prolonged interval from imaging to resection might represent a risk factor for encountering tumour progression at laparotomy. The aim of this study was to determine the therapeutic window for timely surgical intervention. METHODS: This observational cohort study included patients with histologically confirmed PDAC scheduled for resection with curative intent from 2008 to 2014. The impact of imaging-to-resection/reassessment (IR) interval, vascular involvement and tumour size on local tumour progression or presence of metastases at reimaging or laparotomy was evaluated using univariable and multivariable regression. Risk estimates were approximated using hazard ratios (HRs). RESULTS: Median IR interval was 42 days. Of 349 patients scheduled for resection, 82 had unresectable disease (resectability rate 76.5 per cent). The unresectability rate was zero when the IR interval was 22 days or shorter, and was lower for an IR interval of 32 days or less compared with longer waiting times (13 versus 26.2 per cent; HR 0.42, P = 0.021). It was also lower for tumours smaller than 30 mm than for larger tumours (13.9 versus 32.5 per cent; HR 0.34, P < 0.001). Tumours with no or minor vascular involvement showed decreased rates of unresectable disease (20.6 per cent versus 38 per cent when there was major or combined vascular involvement; HR 0.43, P = 0.007). However, this failed to reach statistical significance on multivariable analysis (P = 0.411), in contrast to IR interval (P = 0.028) and tumour size (P < 0.001). CONCLUSION: Operation within 32 days of diagnostic imaging reduced the risk of tumour progression to unresectable disease by half compared with a longer waiting time. The results of this study highlight the importance of efficient clinical PDAC management.

MONITORING OF RECURRENCE IN PATIENTS RADICALLY OPERATED FOR PANCREATIC CANCER.

Pancreatic cancer is a diagnosis that carries a poor prognosis. It is the fourth leading cause of cancer death in Europe and the United States, despite advances in operative technique and postoperative management. Furthermore, there is no consensus on the optimal follow-up schedule of patients after surgery for pancreatic cancer, all recommendations on surveillance being based on low level evidence or no evidence and the leading societies propose different guidelines. As a consequence, follow-up strategies may differ between hospitals depending on preference of physicians. The vast majority of patients develop recurrence within 2 years after surgery, suggesting the necessity of a more intensive follow-up the first 2 years after surgery. It usually occurs after surgery as migratory metastases along major upper abdominal arteries and veins to the liver or peritoneum (70%) and less commonly as loco regional disease as masses closely applied to the surgical margins in the neck or body of the pancreas (30%). Currently, there are no effective means to prevent pancreatic cancer recurrence, despite the fact that it is responsible for the majority of postoperative deaths.

Assessing surgical quality: comparison of general and procedure-specific morbidity estimation models for the risk adjustment of pancreaticoduodenectomy outcomes.

INTRODUCTION: The use of outcomes to evaluate surgical quality implies the need for detailed risk adjustment. The physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM) is a generally applicable risk adjustment model suitable for pancreatic surgery. A pancreaticoduodenectomy (PD)-specific intraoperative pancreatic risk assessment (IPRA) estimates the risk of postoperative pancreatic fistula (POPF) and associated morbidity based on factors that are not incorporated into POSSUM. OBJECTIVE: The aim of the study was to compare the risk estimations of POSSUM and IPRA in patients undergoing PD. METHODS: An observational single-center cohort study was conducted including 195 patients undergoing PD in 2008-2010. POSSUM and IPRA data were recorded prospectively. Incidence and severity of postoperative morbidity was recorded according to established definitions. The cohort was grouped by POSSUM and IPRA risk groups. The estimated and observed outcomes and morbidity profiles of POSSUM and IPRA were scrutinized. RESULTS: POSSUM-estimated risk (62 %) corresponded with observed total morbidity (65 %). Severe morbidity was 17 % and in-hospital-mortality 3.1 %. Individual and grouped POSSUM risk estimates did not reveal associations with incidence (p = 0.637) or severity (p = 0.321) of total morbidity or POPF. The IPRA model identified patients with high POPF risk (p < 0.001), but was even associated with incidence (p < 0.001) and severity (p < 0.001) of total morbidity. CONCLUSION: The risk factors defined by a PD-specific model were significantly stronger predictive indicators for the incidence and severity of postoperative morbidity than the factors incorporated in POSSUM. If available, reliable procedure-specific risk factors should be utilized in the risk adjustment of surgical outcomes. For pancreatic surgery, generally applicable tools such as POSSUM still have to prove their relevance.

Abdominal and total adiposity and the risk of acute pancreatitis: a population-based prospective cohort study.

OBJECTIVES: Previous research has indicated that obesity may be linked to the severity of acute pancreatitis. However, the association between abdominal and total adiposity as risk factors in the development of acute pancreatitis in a general population has not been studied. METHODS: A follow-up study was conducted, using the Swedish Mammography Cohort and the Cohort of Swedish Men, to examine the association between waist circumference and body mass index (BMI) and the risk of first-time acute pancreatitis. Severe acute pancreatitis was defined as hospital stay of >14 days, in-hospital death, or mortality within 30 days of discharge. Cox proportional hazards models were used to estimate rate ratios (RRs) with 95% confidence intervals (CIs), adjusted for confounders. RESULTS: In total, 68,158 individuals, aged 46-84 years, were studied for a median of 12 years. During this time, 424 persons developed first-time acute pancreatitis. The risk of acute pancreatitis among those with a waist circumference of >105 cm was twofold increased (RR=2.37; 95% CI: 1.50-3.74) compared with individuals with a waist circumference of 75.1-85.0 cm, when adjusted for confounders. This association was seen in patients with non-gallstone-related and gallstone-related acute pancreatitis. The results remained unchanged when stratifying the analyses with regards to sex or the severity of acute pancreatitis. There was no association between BMI and the risk of acute pancreatitis. CONCLUSIONS: Abdominal adiposity, but not total adiposity, is an independent risk factor for the development of acute pancreatitis.

Structured intraoperative assessment of pancreatic gland characteristics in predicting complications after pancreaticoduodenectomy.

BACKGROUND: The morbidity rate after pancreaticoduodenectomy remains high (20-50 per cent) and postoperative pancreatic fistula (POPF) is a major underlying factor. POPF has been reported to be associated with pancreatic consistency (PC) and pancreatic duct diameter (PDD). The aim was to quantify the risk of pancreaticojejunostomy-associated morbidity (PJAM) by means of a structured intraoperative assessment of both characteristics. METHODS: This single-centre prospective observational study included pancreaticoduodenectomies performed between 2008 and 2010 with a standardized duct-to-mucosa end-to-side pancreaticojejunostomy. PC and PDD were assessed during surgery and classified into four grades each (from very hard to very soft, and from larger than 4 mm to smaller than 2 mm, respectively). PJAM was defined as POPF (grade B or C in International Study Group on Pancreatic Fistula classification) or symptomatic peripancreatic collection of either abscess or fluid. PJAM of at least Clavien grade IIIb was considered severe. RESULTS: PJAM and POPF were observed in 24 (21·8 per cent) and 17 (15·5 per cent) of 110 patients respectively. Softer PC and smaller PDD were risk factors for POPF (both P < 0·001), symptomatic peripancreatic collections (P = 0·071 and P = 0·015) and PJAM (both P < 0·001). Combining consistency and duct characteristics in a composite classification the PJAM risk was stratified as 'high' (both risk factors, PJAM incidence 51 per cent), 'intermediate' (softer PC or smaller PDD, PJAM 26 per cent) or 'low' (no risk factors, PJAM 2 per cent). Severe PJAM was observed only in patients with smaller PDD. CONCLUSION: A high-risk pancreatic gland had a 25-fold higher risk of PJAM after pancreaticoduodenectomy than a low-risk gland. This simple classification can contribute to more individualized patient management and allow stratification of study cohorts with homogeneous POPF risk.

Cigarette smoking, smoking cessation and acute pancreatitis: a prospective population-based study.

BACKGROUND: Several studies have shown that smoking increases the risk of chronic pancreatitis. However, the impact of smoking on the development of acute pancreatitis has not been fully studied. OBJECTIVE: To clarify the association between cigarette smoking, smoking cessation and the risk of acute pancreatitis. DESIGN: A follow-up study was conducted of 84,667 Swedish women and men, aged 46-84, during 12 years to study the association between smoking status, smoking intensity and duration, duration of smoking cessation and the risk of acute pancreatitis. Only those with the first event of the disease and no previous history of acute pancreatitis were included. Cox proportional hazards models were used to estimate rate ratios (RRs) with 95% CI for different smoking-related variables, adjusted for age, gender, body mass index, diabetes, educational level and alcohol consumption. RESULTS: In total, 307 cases with non-gallstone-related and 234 cases with gallstone-related acute pancreatitis were identified. The risk of non-gallstone-related acute pancreatitis was more than double (RR=2.29; 95% CI 1.63 to 3.22, p<0.01) among current smokers with ≥20 pack-years of smoking as compared with never-smokers. The corresponding risk among individuals with ≥400 g monthly consumption of alcohol was increased more than fourfold (RR=4.12; 95% CI 1.98 to 8.60, p<0.01). The duration of smoking rather than smoking intensity increased the risk of non-gallstone-related acute pancreatitis. After two decades of smoking cessation the risk of non-gallstone-related acute pancreatitis was reduced to a level comparable to that of non-smokers. There was no association between smoking and gallstone-related acute pancreatitis. CONCLUSION: Smoking is an important risk factor for non-gallstone-related acute pancreatitis. Early smoking cessation should be recommended as a part of the clinical management of patients with acute pancreatitis.

Validation of the harmless acute pancreatitis score in predicting nonsevere course of acute pancreatitis.

BACKGROUND: The Harmless Acute Pancreatitis Score (HAPS) is a scoring algorithm to identify patients with nonsevere acute pancreatitis. The aim of this study was to evaluate the reproducibility of HAPS outside its original study setting. METHOD: Baseline information of all hospitalized patients with acute pancreatitis at Karolinska University Hospital, Stockholm, Sweden, between 2004 and 2009 was collected. The parameters constituting HAPS were signs of peritonitis, hematocrit and serum creatinine levels. Since hematocrit was not available in all patients, complete sample analysis was performed by replacing hematocrit with hemoglobin (strongly correlated with hematocrit; r = 0.86). RESULTS: In total, 531 patients with a first-time or a recurrent attack of acute pancreatitis were included. Among 353 patients with complete information on parameters constituting HAPS, 79 patients were predicted to have a nonsevere course, of whom 1 patient developed severe acute pancreatitis. The specificity of HAPS in predicting a nonsevere course of acute pancreatitis was 96.3% (95% CI: 81.0-99.9) with a corresponding positive predictive value of 98.7% (95% CI: 93.1-100). Complete sample analysis replacing hematocrit with hemoglobin level predicted a nonsevere course in 182 patients, of whom 2 patients had severe acute pancreatitis (94.3% specificity and 98.9% positive predictive value). CONCLUSION: HAPS is a highly specific scoring algorithm that predicts a nonsevere course of acute pancreatitis. Therefore, HAPS might be an additional tool in the clinical assessment of acute pancreatitis where early screening is important to treat the patients at an optimal level of care.

Effect of type of alcoholic beverage in causing acute pancreatitis.

BACKGROUND: The effect of different alcoholic beverages and drinking behaviour on the risk of acute pancreatitis has rarely been studied. The aim of this study was to investigate the effect of different types of alcoholic beverage in causing acute pancreatitis. METHODS: A follow-up study was conducted, using the Swedish Mammography Cohort and Cohort of Swedish Men, to study the association between consumption of spirits, wine and beer and the risk of acute pancreatitis. No patient with a history of chronic pancreatitis was included and those who developed pancreatic cancer during follow-up were excluded. Multivariable Cox proportional hazards models were used to estimate rate ratios. RESULTS: In total, 84,601 individuals, aged 46-84 years, were followed for a median of 10 years, of whom 513 developed acute pancreatitis. There was a dose-response association between the amount of spirits consumed on a single occasion and the risk of acute pancreatitis. After multivariable adjustments, there was a 52 per cent (risk ratio 1·52, 95 per cent confidence interval 1·12 to 2·06) increased risk of acute pancreatitis for every increment of five standard drinks of spirits consumed on a single occasion. The association weakened slightly when those with gallstone-related pancreatitis were excluded. There was no association between consumption of wine or beer, frequency of alcoholic beverage consumption including spirits, or average total monthly consumption of alcohol (ethanol) and the risk of acute pancreatitis. CONCLUSION: The risk of acute pancreatitis was associated with the amount of spirits consumed on a single occasion but not with wine or beer consumption.

The quality of randomized clinical trials in the field of surgery: studies on laparoscopic versus open appendectomy as an example.

BACKGROUND: The field of surgery undergoes rapid renewal and introduction of surgical techniques and instruments. Thus, the quality of the randomized clinical trials in this field should be evaluated. We assessed the quality of randomized trials comparing laparoscopic versus open appendectomy as a model. METHOD: Using MEDLINE and EMBASE, 42 first-time published randomized clinical trials in the English language met the inclusion criteria. Factors related to the methodological quality, e.g. blinding, sample size calculation and intention-to-treat analysis, were reviewed. RESULTS: Method of random number generation was described in only 15 (36%) of the studies, i.e., it was not clear if the remaining two thirds of the studies were actually randomized or not. Although not using blocking, the trials often reported similar sample size in the intervention and control groups. Proper concealment of the allocation status was reported in almost half of the studies. None of the trials was judged to use proper double-blinding measures. Sample size calculation was present in one of five trials and half of the studies performed analysis according to intention-to-treat. CONCLUSIONS: It seems that surgical trials do not always follow the basic methodological guidelines to maintain the high quality of randomized clinical trials. Compliance with the CONSORT statement and transparency in result reporting is strongly recommended to improve the quality of randomized trials in the field of surgery.

Genetic and environmental influences on the risk of acute appendicitis in twins.

BACKGROUND: Acute appendicitis is common but the aetiology is unclear. This study examined the heritability of acute appendicitis. METHODS: The study included twin pairs with known zygosity born between 1959 and 1985. Individuals with acute appendicitis were found by record linkage with the Swedish Inpatient Register. Comparing monodizygotic and dizygotic twins, the similarity and relative proportions of phenotypic variance resulting from genetic and environmental factors were analysed. Risks of acute appendicitis explained by heritability and environmental effects were estimated. RESULTS: Some 3441 monozygotic and 2429 dizygotic twins were identified. Almost no genetic effects were found in males (8 (95 per cent confidence interval 0 to 50) per cent), but shared (31 (0 to 49) per cent) and non-shared (61 (47 to 74) per cent) environmental factors accounted for this risk. In females, the heritability was estimated as 20 (0 to 36) per cent and the remaining variation was due to non-shared environmental factors (80 (64 to 98) per cent). For the sexes combined, genetic effects accounted for 30 (5 to 40) per cent and non-shared environmental effects for 70 (60 to 81) per cent of the risk. CONCLUSION: Acute appendicitis has a complex aetiology with sex differences in heritability and environmental factors.

Treatment of pancreatic pseudocysts.

According to the Atlanta classification an acute pseudocyst is a collection of pancreatic juice enclosed by a wall of fibrous or granulation tissue, which arises as a consequence of acute pancreatitis or pancreatic trauma, whereas a chronic pseudocyst is a collection of pancreatic juice enclosed by a wall of fibrous or granulation tissue, which arises as a consequence of chronic pancreatitis and lack an antecedent episode of acute pancreatitis. It is generally agreed that acute and chronic pseudocysts have a different natural history, though many reports do not differentiate between pseudocysts that complicate acute pancreatitis and those that complicate chronic disease. Observation--"conservative treatment"--of a patient with a pseudocyst is preponderantly based on the knowledge that spontaneous resolution can occur. It must, however, be admitted that there is substantial risk of complications or even death; first of all due to bleeding. There are no randomized studies for the management protocols for pancreatic pseudocysts. Therefore, today we have to rely on best clinical practice, but still certain advice may be given. First of all it is important to differentiate acute from chronic pseudocysts for management, but at the same time not miss cystic neoplasias. Conservative treatment should always be considered the first option (pseudocysts should not be treated just because they are there). However, if intervention is needed, a procedure that is well known should always be considered first. The results of percutaneous or endoscopic drainage are probably more dependent on the experience of the interventionist than the choice of procedure and if surgery is needed, an intern anastomosis can hold sutures not until several weeks (if possible 6 weeks).

Cigarette smoking accelerates progression of alcoholic chronic pancreatitis.

BACKGROUND: Smoking is a recognised risk factor for pancreatic cancer and has been associated with chronic pancreatitis and also with type II diabetes. AIMS: The aim of this study was to investigate the effect of tobacco on the age of diagnosis of pancreatitis and progression of disease, as measured by the appearance of calcification and diabetes. PATIENTS: We used data from a retrospective cohort of 934 patients with chronic alcoholic pancreatitis where information on smoking was available, who were diagnosed and followed in clinical centres in five countries. METHODS: We compared age at diagnosis of pancreatitis in smokers versus non-smokers, and used the Cox proportional hazards model to evaluate the effects of tobacco on the development of calcification and diabetes, after adjustment for age, sex, centre, and alcohol consumption. RESULTS: The diagnosis of pancreatitis was made, on average, 4.7 years earlier in smokers than in non-smokers (p = 0.001). Tobacco smoking increased significantly the risk of pancreatic calcifications (hazard ratio (HR) 4.9 (95% confidence interval (CI) 2.3-10.5) for smokers v non-smokers) and to a lesser extent the risk of diabetes (HR 2.3 (95% CI 1.2-4.2)) during the course of pancreatitis. CONCLUSIONS: In this study, tobacco smoking was associated with earlier diagnosis of chronic alcoholic pancreatitis and with the appearance of calcifications and diabetes, independent of alcohol consumption.

Exploratory laparoscopy at suspicion of acute appendicitis. Review.

Exploratory laparoscopy has been used since 1910 and is one of the new tools for diagnosing appendicitis on a routine basis. It can be looked upon as "semi-invasive" in comparison to on one hand ultrasonography/CT/MRI and on the other open laparotomy. According to the literature, mostly in retrospective studies, laparoscopy might reduce the frequencies of unnecessary appendectomies in 20-30 percent and an accuracy of diagnosis of appendicitis of 95-99 percent. This means that laparoscopy has a sensitivity of 92 percent in diagnosing acute appendicitis, including all cases of mucosal inflammation only. This means, however, that about one in 11 appendicitis is missed and it is still a question as to whether an appendix that looks normal at laparoscopy for acute right iliac fossa pain should be removed, or whether if it is not removed, there is a risk of missing an early case of appendicitis later leading to perforation and peritonitis? Mucosal inflammation obviously can never be determined in the appendix is left in place. However, a summery of available data seems to favour that it is distinctly uncommon that explorative laparoscopy misses any acute appendicitis that requires appendectomy. If there are cases of acute appendicitis not requiring appendectomy can only be known in prospective studies. A Cochran review was published in early 2002 and analysed 45 randomized trials, 39 of which had been carried out in adults, comparing both therapeutic and diagnostic outcomes of patients undergoing open or laparoscopic surgery for suspected appendicitis. Diagnostic outcomes favoured the laparoscopic approach in that both the negative appendectomy rate and "the frequency of an unestablished diagnosis" were reduced, most significantly in women in their reproductive years. However, in the conclusion the authors sounded a note of caution about the quality of some of the research data they had analysed, and recommended that more blinded studies be performed. Because there is a belief that laparoscopic appendectomy is less likely to cause intraperitoneal adhesions than open surgery, they also recommended longer follow-up studies to assess the relative incidences of obstruction due to adhesions resulting from the two techniques. Therefore, the conclusion can be drawn that in all equivocal cases laparoscopy is better than laparotomy as the initial step in year 2003. However, there is still a lack of data comparing non-invasive modern techniques such as ultrasonography and CT with laparoscopy, and the value of laparoscopy after the best available ultrasonography or CT.

Acute pancreatitis in Bergen, Norway. A study on incidence, etiology and severity.

BACKGROUND: Studies on the incidence and etiology of acute pancreatitis show large regional differences. This study was performed to establish incidence, etiology and severity of acute pancreatitis in the population of Bergen, Norway. METHODS: A study of all patients with acute pancreatitis admitted to Haukeland University Hospital over a 10-year period was performed. Information was obtained about the number of patients with acute pancreatitis admitted to the Deaconess Hospital in Bergen. RESULTS: A total of 978 admissions of acute pancreatitis were recorded in these two hospitals giving an incidence of 30.6 per 100,000. Haukeland University Hospital had 757 admissions of acute pancreatitis in 487 patients. Pancreatitis was severe in 20% (96/487) of patients, more often in males (25%) than in females (14%). Mortality due to acute pancreatitis was 3% (16/487). Gallstones were found to be an etiological factor in 48.5% and alcohol consumption in 19% of patients. The risk of recurrent pancreatitis was 47% in alcohol induced and 17% in gallstone induced pancreatitis. The last five years of the study period, endoscopic sphincterotomy of patients with gallstone pancreatitis, resulted in drop in relapse rate from 33% to 1.6%. CONCLUSION: The incidence of acute pancreatitis was found to be 30.6 per 100,000 with 48.5% associated with gallstones and 17% alcohol induced. Incidence of first attack was 20/100,000. Pancreatitis was classified as severe in 20% of cases with a mortality of 3%.

Recurrent pancreatitis as a late complication of endoscopic sphincterotomy for common bile duct stones: diagnosis and therapy.

Although long-term complications of endoscopic sphincterotomy (ES) have often been reported, the possible effects of the procedure on the pancreatic duct orifice remain virtually unknown. Three women patients are described who developed attacks of recurrent pancreatitis at 2, 7, and 27 months after ES for bile duct stones. The attacks were apparently caused by a partial stenosis of the pancreatic orifice, arising from post-procedure fibrosis and scarring. The patients were evaluated and treated endoscopically. All three patients benefited from endoscopic therapy; two became symptom-free and one improved. Symptoms recurred in the three patients, after 26, 41, and 23 months. In one patient, re-stenosis was documented and repeat sphincterotomy resulted in complete relief of symptoms during the ensuing 5 months. In the remaining two patients, the symptoms were mild and no further intervention was needed. Concerning complications, one patient suffered a moderately severe pancreatitis without sequelae. Recurrent pancreatitis may emerge as a late complication after ES for common bile duct stones. It is probably causally related to stenosis of the pancreatic orifice brought about by fibrosis and scarring, which may exceptionally develop after the procedure. Endoscopic therapy should probably be considered in the first instance, but the optimal treatment for this condition remains to be determined.