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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

Plasma concentrations of CA-50 in relation to tumour burden in exocrine pancreatic cancer.

The tumour-associated antigen CA-50 was analysed in plasma from 90 patients with cytologically verified exocrine carcinoma of the pancreas, and related to the size of the primary carcinoma, the largest metastasis of the liver and the degree of tumour-transformed liver parenchyme at 143 examinations. The median concentration of CA-50 in the patients with metastases of the liver was significantly higher than in the group lacking metastases. Spearman rank correlation test at three different levels of CA-50 (all values, exceeding 100 U/ml and exceeding 200 U/ml), showed a correlation between CA-50 and diameter of the primary pancreatic carcinoma in patients with liver metastases, but not in the group lacking liver metastases. No correlations were seen between CA-50 levels and size of liver metastasis or degree of tumour-transformed liver parenchyme. Hence, high plasma concentrations of CA-50 in patients with diagnosed or suspected exocrine pancreatic carcinoma could strongly indicate metastatic processes.

Expression of nerve growth factors in pancreatic neural tissue and pancreatic cancer.

One of the characteristics of pancreatic cancer is its tendency to invade neural tissue. We hypothesized that the affinity of cancer cells for nerve tissue is related to the presence of growth factors in neural tissue and their receptors in cancer cells. Sections of pancreatic cancer and normal pancreatic tissue were examined by immunohistochemistry for the expression of the neurotrophins NGF, BDNF, NT-3, NT-4, and their receptors TrkA, TrkB, and TrkC, as well as the low-affinity receptor, p75NTR. TrkA expression was found in duct, islet, and cancer cells; TrkB was found in the alpha-cells of the islet only. The anti-pan-Trk antibody (TrkB3), which is presumed to recognize all three receptors, immunoreacted with duct and acinar cells in normal tissue and with cancer cells. The staining with TrkC was similar to that of TrkA. The low-affinity receptor p75NTR was expressed in the neural tissue and in scattered duct cells of the normal tissue only. Duct and acinar cells, as well as neural tissue and cancer cells, showed weak to strong immunoreactivity with NGF. NT-3 expression was noted in capillary endothelia and erythrocytes. NT-4 showed specific staining for ductule cells. The expression and distribution of neurotrophins and their receptors suggest their role in the potential of pancreatic cancer cells for neural invasion.

Comparative histopathological findings in the pancreas of cigarette smokers and non-smokers.

Although a correlation has been suggested between cigarette smoking and pancreatic cancer, studies on pathological changes in the pancreas of smokers are fragmentary. In the present study we examined histopathologically 73 pancreases obtained by autopsy from 42 heavy cigarette smokers and 31 non-smoker patients. One invasive adenocarcinoma (2 cm in diameter) and three small carcinomas (2-5 mm in diameter) were found in smokers and one small carcinoma in a non-smoker patient. Although the incidence of pancreatic cancer in smokers was higher than in non-smokers, the difference was statistically not significant. Of smokers with pancreatic cancer, 2 had lung cancer, 1 skin cancer, 1 colon cancer and 1 was free of any malignancies. Ductal changes, including mucinous or squamous cell metaplasia and papillary hyperplasia, were found with equal frequencies in both groups of patients. The type and the incidence of these ductal alterations were not related to smoking but to the age. Our results do not indicate that cigarette smoking increases the incidence of pancreatic cancer, although, the limited number of the sections of the pancreas examined, as well as exclusion of other important variables, such as alcohol, diet and diabetes weaken the value of this study.

Pancreatic function in the essential fatty acid deficient rat.

The influence of essential fatty acid (EFA) deficiency on pancreatic endocrine and exocrine function was studied in 120-day-old rats. The plasma insulin response was determined after in vivo administration of glucose and arginine. The plasma glucagon response was assessed after infusion of arginine. Islet peptides were examined by immunocytochemistry. The exocrine function of pancreas was studied by amylase secretion in isolated pancreatic acinar cells after stimulation with the cholinergic agonist carbacholine chloride. The EFA-deficient (EFAD) rats showed higher basal plasma insulin concentrations and lower basal glucose levels than control rats (P less than .01 and P less than .01, respectively). The plasma insulin response to glucose was potentiated in the EFAD rats (P less than .001). Both insulin and glucagon responses to arginine were normal. The isolated pancreatic acinar cells showed a low basal amylase secretion, but a normal response to carbacholine chloride. There were no overt morphological changes seen in the pancreas and the immunocytochemical staining pattern of insulin, glucagon, somatostatin, and pancreatic polypeptide cells did not differ from controls. The results of the study show that the secretory function of the endocrine and exocrine pancreas is operational in EFA deficiency. The EFA deficiency was accompanied by a basal hyperinsulinemia and hypoglycemia and an exaggerated insulin response to glucose, the pathophysiology of which has to be further studied.

Chromosome abnormalities in a pancreatic adenocarcinoma.

Short-term cultures initiated from a pancreatic adenocarcinoma were cytogenetically investigated. The composite karyotype was 74-76,XX,+X,+2,+3,+del(3)(p21),+5,+5,+der(7) t(1;7)(q21;p22),+der(7),del(8)(p21),+del(8)(p21),+der(8)t(8;?)(q24; +),+9,+9,+10,+10,+11,+11,+12,+13,+14,+der(14)t(14; +)(p11;?),+der(16)t(15;16)(q11;p13),+der(16),+der(17)t(17;?) (p11;?),+der(17),+18,+20,+20,-21,-21,+22,+22,+1-3mar. A comparison with the few previously cytogenetically characterized cases of this tumor type reveals no consistent abnormalities.

Cytogenetically detected clonal heterogeneity in a duodenal adenocarcinoma.

A primary duodenal adenocarcinoma, a tumor type for which no previous chromosome data existed, was cytogenetically analyzed after short-term culture. The main tumor mass was localized in the pancreatic head, but the histopathologic examination revealed its duodenal origin. A total of six abnormal, karyotypically unrelated, clones were identified. The largest exhibited clonal evolution and consisted of two subclones with massively rearranged karyotypes in the hypodiploid and hypotetraploid range. Chromosome imbalances brought about by these complex changes were gain of 1q, losses of chromosomes 6 and 9, and total or partial losses of 1p, 3p, 3q, 9p, 10p, 17p, 17q, 18q, 20p, and 20q. The remaining five smaller clones had 1-2 numerical or balanced structural chromosome aberrations. The present study thus revealed yet another epithelial tumor type characterized by karyotypically unrelated clones. For this as for other tumors, the pathogenetic significance of such cytogenetic polyclonality remains uncertain.

Abnormal karyotypes in three carcinomas of the gallbladder.

Short-term cultures from three carcinomas of the gallbladder were cytogenetically analyzed. All three had an abnormal karyotype. The modal chromosome number was near- or hypertriploid in two tumors and near diploid in the third. Structural rearrangements of chromosomes 1 and 3, loss of material from the long arm of chromosome 18, and loss of chromosome 21 material were common to all three tumors and would seem to be the best candidates for nonrandom karyotypic changes in carcinomas of the gallbladder.

Cytogenetic characterization of a periampullary adenocarcinoma of the pancreas, its liver metastasis, and a cell line established from the metastasis and a cell line established from the metastasis in a patient with Gardner's syndrome.

A cell line was established from a liver metastasis of a periampullary pancreatic carcinoma in a patient with Gardner's syndrome. The primary tumor, the liver metastasis, and passages 6 and 15 of the cell line were characterized cytogenetically. The only aberration common to all samples was a der(15)t(8;15); this was probably the primary chromosomal abnormality. Loss of the short arm of chromosome 19 was also found in all samples but was brought about by different aberrations in the primary tumor and the metastasis. The secondary aberrations characteristic of clonal evolution often included further gain of 8q material but losses from 1p, 6q, and chromosomes 17 and 18, all of which have been seen before in sporadic pancreatic and colorectal carcinomas. This is the first cell line established from a tumor in a Gardner's syndrome patient and also the first characterization of an abnormal tumor karyotype associated with this autosomal dominant cancer syndrome.