Influence of Klebsiella pneumoniae and quinolone treatment on prognosis in patients with pancreatic cancer.

BACKGROUND: An increasing body of evidence suggests that microbiota may promote progression of pancreatic ductal adenocarcinoma (PDAC). It was hypothesized that gammaproteobacteria (such as Klebsiella pneumoniae) influence survival in PDAC, and that quinolone treatment may attenuate this effect. METHODS: This was a retrospective study of patients from the Massachusetts General Hospital (USA) and Ludwig-Maximilians-University (Germany) who underwent preoperative treatment and pancreatoduodenectomy for locally advanced or borderline resectable PDAC between January 2007 and December 2017, and for whom a bile culture was available. Associations between tumour characteristics, survival data, antibiotic use and results of intraoperative bile cultures were investigated. Survival was analysed using Kaplan-Meier curves and Cox regression analysis. RESULTS: Analysis of a total of 211 patients revealed that an increasing number of pathogen species found in intraoperative bile cultures was associated with a decrease in progression-free survival (PFS) (-1·9 (95 per cent c.i. -3·3 to -0·5) months per species; P = 0·009). Adjuvant treatment with gemcitabine improved PFS in patients who were negative for K. pneumoniae (26·2 versus 15·3 months; P = 0·039), but not in those who tested positive (19·5 versus 13·2 months; P = 0·137). Quinolone treatment was associated with improved median overall survival (OS) independent of K. pneumoniae status (48·8 versus 26·2 months; P = 0·006) and among those who tested positive for K. pneumoniae (median not reached versus 18·8 months; P = 0·028). Patients with quinolone-resistant K. pneumoniae had shorter PFS than those with quinolone-sensitive K. pneumoniae (9·1 versus 18·8 months; P = 0·001). CONCLUSION: K. pneumoniae may promote chemoresistance to adjuvant gemcitabine, and quinolone treatment is associated with improved survival.

An elevated CA 19-9 is associated with invasive cancer and worse survival in IPMN.

BACKGROUND: Current guidelines for IPMN include an elevated serum carbohydrate antigen (CA) 19-9 among the worrisome features. However, the correlation of CA 19-9 with histological malignant features and survival is unclear. Serum CEA is also currently used for preoperative management of IPMN, although its measurement is not evidence-based. Accordingly, we aimed to assess the role of these tumor markers as predictors of malignancy in IPMN. METHODS: IPMN resected between 1998 and 2018 at Massachusetts General Hospital were analyzed. Clinical, pathological and survival data were collected and compared to preoperative levels of CA 19-9 and CEA. Receiver operating characteristic (ROC) and Cox regression analyses were performed considering cut-offs of 37 U/ml (CA 19-9) and 5 µg/l (CEA). RESULTS: Analysis of 594 patients showed that preoperative CA 19-9 levels > 37 U/ml (n = 128) were associated with an increased likelihood of invasive carcinoma when compared to normal levels (45.3% vs. 18.0%, P < 0.001), while there was no difference with respect to high-grade dysplasia (32.9% vs 31.9%, P = 0.88). The proportion of concurrent pancreatic cancer was higher in patients with CA 19-9 > 37 U/ml (17.2% vs 4.9%, P < 0.001). An elevated CA 19-9 was also associated with worse overall and disease-free survival (HR = 1.943, P = 0.007 and HR = 2.484, P < 0.001 respectively). CEA levels did not correlate with malignancy. CONCLUSION: In patients with IPMN, serum CA19-9 > 37 U/ml is associated with invasive IPMN and concurrent pancreatic cancer as well as worse survival, but not with high-grade dysplasia. Serum CEA appears to have minimal utility in the management of these patients.

Risk of malignancy in small pancreatic cysts decreases over time.

BACKGROUND: Pancreatic cysts <15 mm without worrisome features have practically no risk of malignancy at the time of diagnosis but this can change over time. Optimal duration of follow-up is a matter of debate. We evaluated predictors of malignancy and attempted to identify a time to safely discontinue surveillance. METHODS: Bi-centric study utilizing prospectively collected databases of patients with pancreatic cysts measuring <15 mm and without worrisome features who underwent surveillance at the Massachusetts General Hospital (1988-2017) and at the University of Verona Hospital Trust (2000-2016). The risk of malignant transformation was assessed using the Kaplan-Meier method and parametric survival models, and predictors of malignancy were evaluated using Cox regression. RESULTS: 806 patients were identified. Median follow-up was 58 months (6-347). Over time, 58 (7.2%) cysts were resected and of those, 11 had high grade dysplasia (HGD) or invasive cancer. Three additional patients had unresectable cancer for a total rate of malignancy of 1.7%. Predictors of development of malignancy included an increase in size ≥2.5 mm/year (HR = 29.54, 95% CI: 9.39-92.91, P < 0.001) and the development of worrisome features (HR = 9.17, 95% CI: 2.99-28.10, P = 0.001). Comparison of parametric survival models suggested that the risk of malignancy decreased after three years of surveillance and was lower than 0.2% after five years. CONCLUSIONS: Pancreatic cysts <15  mm at the time of diagnosis have a very low risk of malignant transformation. Our findings indicate the risk decreases over time. Size increase of ≥2.5 mm/year is the strongest predictor of malignancy.

Intraoperative Fluid Administration and Surgical Outcomes Following Pancreaticoduodenectomy: External Validation at a Tertiary Referral Center.

BACKGROUND: While intraoperative fluid overload is associated with higher complication rates following surgery, data for pancreaticoduodenectomy are scarce and heterogeneous. We evaluated multiple prior definitions of restrictive and liberal fluid regimens and analyzed whether these affected surgical outcomes at our tertiary referral center. METHODS: Studies evaluating different intraoperative fluid regimens on outcomes after pancreatic resections were retrieved. After application of all prior definitions of restrictive and liberal fluid regimens to our patient cohort, relative risks of each outcome were calculated using all reported infusion regimens. RESULTS: Five hundred and seven pancreaticoduodenectomies were included. Nine different fluid regimens were evaluated. Two regimens utilized absolute volume cutoffs, and the remaining evaluated various infusion rates, ranging from 5 to 15 mL/kg/h. Total volume administration of >5000 mL and >6000 mL was associated with increased complications (RR 1.25 and RR 1.17, respectively) and >6000 mL with increased sepsis (RR 2.14). Conversely, a rate of <5 mL/kg/h was associated with increased risk of postoperative pancreatic fistula (POPF, RR 3.16) and sepsis (RR 3.20), <6.8 mL/kg/h with increased major morbidity (RR 1.64) and sepsis (RR 2.27), and <8.2 mL/kg/h with increased POPF (RR 2.16). No effects were observed on pulmonary complications, surgical site infections, length of stay, or mortality. CONCLUSIONS: In an uncontrolled setting with no standard intraoperative or postoperative care map, the volume of intraoperative fluid administration appears to have limited impact on early postoperative outcomes following pancreaticoduodenectomy, with adverse outcomes only seen at extreme values.

Frequency and significance of calcification in IPMN.

UNLABELLED: The frequency and significance of calcification in intraductal papillary mucinous neoplasms (IPMN) are unknown. We examined calcifications by computed tomography (CT) in a large cohort of IPMNs and correlated them with clinicopathologic characteristics. METHODS: Preoperative contrast-enhanced CT imaging studies of 164 patients with surgically resected IPMN were retrospectively reviewed. Morphologic characteristics of IPMN, presence and type of calcifications, their location, the degree of dysplasia and the epithelial subtype were recorded. Symptoms at the time of diagnosis, history of smoking, and alcohol consumption were obtained from medical records. RESULTS: Of the 164 IPMNs, 68 were branch duct type (Br-IPMN) and 96 main duct (MD-IPMN) or combined type (CT-IPMN); 78 (48%) had a malignant component (CIS and Invasive). Calcifications were present in 33 cases (20%). By type, 16 calcifications were punctate, 11 coarse and 9 eggshell, and by location, 15 were mural, 3 septal, 2 ductal, 1 in the solid component, and 13 in multiple locations. Calcifications were seen more frequently in larger lesions (44 mm vs 32 mm p = 0.002), and when MPD dilation was noted (70% vs 45%, p = 0.023). There was no association between presence of calcification and malignancy, epithelial subtype, or other clinical data. However, malignancy was present in 9/11 IPMN with coarse calcification (p = 0.04), suggesting this may be a worrisome feature. CONCLUSION: Calcification is found in 20% of IPMNs, and is more common in larger lesions. Although its overall presence has no correlation with malignancy, coarse calcification, when combined with other morphologic features, may be a radiologic sign of malignancy.

Major Complications Independently Increase Long-Term Mortality After Pancreatoduodenectomy for Cancer.

BACKGROUND: Postoperative major morbidity has been associated with worse survival gastrointestinal tumors. This association remains controversial in pancreatic cancer (PC). We analyzed whether major complications after surgical resection affect long-term survival. METHODS: Records of all PC patients resected from 2007 to 2015 were reviewed. Major morbidity was defined as any grade-3 or higher 30-day complications, per the Clavien-Dindo Classification. Patients who died within 90 days after surgery were excluded from survival analysis. RESULTS: Of 616 patients, 81.7% underwent pancreatoduodenectomy (PD) and 18.3% distal pancreatectomy (DP). Major complications occurred in 19.1% after PD and 15.9% after DP. In patients who survived > 90 days, the likelihood of receiving adjuvant treatment was 43.9% if major complications had occurred, vs. 68.5% if not (p < 0.001), and those who received it started the treatment median 10 days later compared with uncomplicated patients (median 60 days (50-72) vs. 50 days (41-61), p = 0.001). By univariate analysis, in addition to the conventional pathology-related prognostic determinants and the receipt of adjuvant treatment, major complications worsened long-term survival after PD (median OS 26 months vs. 15, p = 0.008). A difference was also seen after DP, but it did not reach statistical significance, likely related to the small sample size (median OS 33 months vs. 18, p = 0.189). At multivariate analysis for PD, major postoperative complications remained independently associated with worse survival [HR 1.37, 95%CI (1.01-1.86)]. CONCLUSIONS: Major surgical complications after pancreaticoduodenectomy are associated with worse long-term survival in pancreatic cancer. This effect is independent of the receipt of adjuvant treatment.

A novel pancreatic endocrine tumor suppressor gene locus on chromosome 3p with clinical prognostic implications.

The molecular pathogenesis of pancreatic endocrine tumors is largely unknown. Such tumors are more likely to develop in individuals with the von Hippel-Lindau (VHL) syndrome. We sought to determine whether allelic loss of the recently identified VHL tumor suppressor gene on chromosome 3p25-26 occurs in the more common sporadic forms of these tumors. Allelic loss on chromosome 3p was identified in 33% of 43 patients with endocrine tumors of the pancreas. The smallest common region of allelic loss, however, centered not at the VHL locus, but rather at 3p25, centromeric to VHL. Furthermore, no mutations of the VHL gene were identified in these tumors. Loss of alleles on chromosome 3p was associated with clinically malignant disease, whereas tumors with retained 3p alleles were more likely to be benign. Thus, the VHL gene does not appear to play a pathogenic role in the development of sporadic pancreatic endocrine tumors. Instead, a locus at chromosome 3p25 may harbor a novel pancreatic endocrine tumor suppressor gene, and allelic loss of this chromosomal region may serve as a molecular marker that helps distinguish benign from clinically malignant disease.

Isolation, characterization, and distribution of an unusual pancreatic human secretory protein.

An unusual protein was isolated from acid extracts of normal human pancreas and pancreatic secretion in the form of uniform 7-10-nm long single threads without visible axial periodicity or other structure, as seen in the electron microscope. It accounts for as much as 300 micrograms/ml in some pancreatic secretions as measured by specific radioimmunoassay. The protein undergoes a freely reversible, pH dependent, globule-fibril transformation, being stable in the fibril form between pH 5.4 and 9.2. The monomer at acid pH has an apparent molecular weight of approximately 14,000 and consists of a single polypeptide chain, the amino acid composition of which is rich in aromatic amino acids and lacks carbohydrate, fatty acid, and phosphate. The amino acid sequence of 45 residues from the amino terminus shows no homology with any other reported protein sequences other than that of the A chain of the bovine pancreas thread protein (reported elsewhere). A sensitive radioimmunoassay employing monoclonal antibodies against human pancreatic thread protein failed to detect the antigen in a wide range of human tissues other than pancreas, nor was the antigen measurable in normal human sera. Immunohistochemistry utilizing these antibodies revealed the antigen as a component of the cytoplasm of some but not all the pancreatic acinar cells. A physiologic function has not yet been determined for this protein.

Localization of putative tumor suppressor loci by genome-wide allelotyping in human pancreatic endocrine tumors.

Only two tumor suppressor gene loci, one on 3p25 and the MEN1 gene on 11q13, have thus far been implicated in the pathogenesis of sporadic human pancreatic endocrine tumors (PETs). A genome-wide allelotyping study of 28 human PETs was undertaken to identify other potential tumor suppressor gene loci. In addition to those on chromosomes 3p and 11q, frequent allelic deletions were identified on 3q (32%), 11p (36%), 16p (36%), and 22q (29%). Finer deletion mapping studies localized the smallest regions of common deletion to 3q27, 11p13, and 16p12.3-13.11. Potential candidate genes at these loci include WT1 (11p13), TSC2 (16p13), and NF2 (22q12), but no known tumor suppressor gene localizes to 3q27. The mean fractional allelic loss among these human PETs is 0.126, and no correlation was observed between allelic loss and clinical parameters, including age, sex, hormonal subtype, and disease stage. These findings highlight novel locations of tumor suppressor gene loci that contribute to the pathogenesis of human PETs, and several of these on 3p, 3q, and 22q are syntenic with loci on mouse chromosomes 9 and 16 that are implicated in a murine transgenic model of PETs.

Intraductal papillary mucinous neoplasms of the pancreas with concurrent pancreatic and periampullary neoplasms.

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMN) have been reported to be associated with concurrent, distinct pancreatic ductal adenocarcinoma (con-PDAC) in about 8% (range, 4-10%) of resected branch duct (BD) lesions. In addition, other pancreatic and ampullary tumors are occasionally diagnosed with IPMN in patients undergoing pancreatic surgery. The objective of this study is to describe the prevalence, clinicopathologic characteristics and prognosis of IPMN with concurrent pancreatic and ampullary neoplasms, especially con-PDAC. METHODS: The combined databases of pancreatic resections from the Massachusetts General Hospital and the Negrar Hospital, Italy, were analyzed for patients who had been diagnosed with IPMN and concurrent pancreatic or ampullary neoplasms. RESULTS: 2762 patients underwent pancreatic surgery from January 2000 to December 2012. Sixteen percent (n = 441) had pathologically confirmed IPMN and 11% of these (n = 50) had a different distinct synchronous pancreatic neoplasm. The majority of these, 62%, were con-PDAC, followed by neuroendocrine neoplasms (10%) and ampullary carcinoma (10%). Less frequently, mucinous (6%) as well as serous cystic neoplasms (6%), adenosquamous carcinoma (4%) and distal bile duct cancer (2%) were diagnosed. Among all patients with synchronous neoplasms, 66% harbored BD-IPMN, 28% combined IPMN and 6% main duct IPMN. Abdominal pain and/or jaundice were the leading symptoms in half of patients. CONCLUSION: IPMN, mainly BD-IPMN, are associated with con-PDAC in about 7% of patients and account for 62% of all concurrent pancreatic/ampullary neoplasms. Other synchronous neoplasms may be found sporadically with IPMN without a suspected association.

The role of misonidazole combined with intraoperative radiation therapy in the treatment of pancreatic carcinoma.

We tested the efficacy of the hypoxic cell sensitizer misonidazole in conjunction with intraoperative electron beam radiation therapy (IORT) and external beam irradiation in patients with locally advanced, nonmetastatic adenocarcinoma of the pancreas. Misonidazole was delivered intravenously (IV) at a dose of 3.5 g/m2 in conjunction with IORT of 1,500 to 2,000 cGy to the pancreas. Additional external beam radiation as administered to 4,960 cGy. The study was based on the premise that the effect of misonidazole would be maximized when a high dose of the drug was administered and, thus, high hypoxic cell sensitization could be obtained when using a high single dose of radiation where the hypoxic fraction would be expected to dominate in the survivors. In a nonrandomized study of 41 patients treated with misonidazole and 22 without, the 1-year local control was 67% and 55%, and 1-year survival was 50% and 77%, respectively. Although there was a bias towards larger tumors in the patients treated with the sensitizer, we were unable to demonstrate an advantage to misonidazole in this clinical situation.

Surgical approach to pancreatic exocrine neoplasms.

Pancreatic exocrine neoplasms represent a wide spectrum of pathophysiologic entities that challenge us as surgeons. The workup and management of these lesions continue to evolve as we better understand their complex nature. In this review, we will explore the contemporary clinical management of pancreatic adenocarcinoma, acinar cell carcinoma, and cystic neoplasms of the pancreas. The pathogenesis and epidemiology of these tumors will also be examined.

Overexpression of cyclin D1 occurs frequently in human pancreatic endocrine tumors.

The molecular pathogenesis of human pancreatic endocrine tumors (PETs) is poorly understood. Three independent animal models have pointed to the pivotal role of the G1/S cell cycle transition in pancreatic endocrine cell proliferation. We thus hypothesized that the cell cycle regulator cyclin D1 may contribute to the pathogenesis of human PETs. Overexpression of cyclin D1 was identified in 43% of cases, and no correlation was observed with clinical phenotype. The novel observation of frequent overexpression of cyclin D1 suggests that this established oncogene may be implicated in the pathogenesis of human PETs. The absence of detectable alterations in cyclin D1 genomic structure suggests that the mechanism for its oncogenic activation in PETs may be transcriptional or posttranscriptional.

Intraoperatic electron beam irradiation in pancreatic cancer.

Intraoperative electron beam radiation therapy (IOERT) is a technique in which a single high fraction radiation treatment is administered at the time of surgery. Using IOERT, the total radiation dose delivered to a tumor can be increased since sensitive normal tissues are removed from the radiation field during the surgical procedure. Furthermore, while the biologic effectiveness of this single fraction is incompletely understood, it is believed to be equivalent to that of a dose at least two times greater given by means of conventional fractionation. IOERT may improve local tumor control in patients with resectable or locally advanced pancreatic cancer. At the Massachusetts General Hospital (MGH), IOERT is being investigated in the management of pancreatic cancer as a boost treatment in combination with external beam radiation, surgery and chemotherapy.

Peritoneal exfoliative cytology and Ki-ras mutational analysis in patients with pancreatic adenocarcinoma.

This is the first description of the detection of pancreatic adenocarcinoma peritoneal metastasis by established radiolabeled polymerase chain reaction (PCR) based Ki-ras mutational analysis. The present study evaluates both routine cytology and Ki-ras mutational analysis in the detection of peritoneal micrometastases in 24 subjects with pancreatic adenocarcinoma compared to seven control cases of chronic pancreatitis and seven control cases of cholecystitis. Locoregional extension, vascular invasion, and distal metastases were confirmed in 21/24 (88%) of the subjects with pancreatic adenocarcinoma by compute tomography, angiography, endosonography, or laparoscopy. The most common site of histologically confirmed extrapancreatic involvement was the vasculature (29%), followed by the liver (25%), duodenum (17%), peritoneum (17%), and lymph nodes (12%). Peritoneal lavage cytology was positive in 3/24 (12%) cases of pancreatic carcinoma while Ki-ras codon 12 mutational analysis was positive in 2/24 (8%). Two histologically confirmed cases of peritoneal metastases were not detected by either methodology, while peritoneal lavage cytology detected malignant cells in one case with histologically confirmed lymph node metastasis.

Hypomagnesemia in patients in postoperative intensive care.

In order to study the clinical consequences of postoperative hypomagnesemia, the serum magnesium (Mg) concentration was measured in samples of blood collected from 193 patients admitted to two postoperative ICUs. On admission to the ICU, 117 patients (61 percent) had hypomagnesemia (serum Mg less than 1.5 mEq/dl), 66 patients (34 percent) had normomagnesemia (1.5 to 2.0 mEq/dl), and ten patients (5 percent) had hypermagnesemia (greater than 2.0 mEq/dl). There were no correlations between the severity of illness score (r = 0.145) or the degree of hypoproteinemia (r = 0.01) and the postoperative serum Mg level. Patients with severe hypomagnesemia (serum Mg less than or equal to 1.0 mEq/dl) experienced hypokalemia more often (p less than 0.02) than the others in the study. Furthermore, those with severe hypomagnesemia had a higher mortality rate (7/17 or 41 percent) than the remainder of the population studied (22/176 or 13 percent) (p less than 0.02). Those with severe hypomagnesemia had received aminoglycosides more often (p less than 0.001) than those with normal serum Mg concentrations. The serum Mg level was not a sensitive (68 percent) or specific (37 percent) predictor of survival. Our conclusions were as follows: (1) hypomagnesemia is common in postoperative ICU patients; and (2) patients in the postoperative ICU who have severe hypomagnesemia have a higher mortality and more hypokalemia than similarly ill patients with normomagnesemia. Because of the association between aminoglycoside therapy and severe hypomagnesemia, we recommend measurement of this variable in those patients receiving aminoglycosides. Furthermore, Mg replacement therapy is recommended for those patients with serum Mg values of 1 mEq/dl or less.

Variability in cyst fluid carcinoembryonic antigen level, fluid viscosity, amylase content, and cytologic findings among multiple loculi of a pancreatic mucinous cystic neoplasm.

The procedure of percutaneous aspiration and analysis of cyst contents has been advocated to provide a preoperative diagnosis of pancreatic cystic lesions (pseudocysts and cystic tumors), but it is not known whether variation in the contents of separate loculi of a multilocular neoplasm might misrepresent the identity of the tumor. The authors measured the cyst fluid carcinoembryonic antigen (CEA) level, fluid viscosity, and amylase content and performed cytologic analysis on aspirates rates from ten different loculi of a single mucinous cystic neoplasm of the pancreas. The CEA levels were highly variable (median, 6,326 ng/mL; range, 962-64,670 ng/mL) but in all cases were diagnostic of a mucinous tumor. Fluid relative viscosity values were also variable (median, 2.4; range, 1.3-10+) but diagnostic in eight of nine aspirates. The amylase content in all of the loculi was low (< 91 U/L), and values were consistent with a cystic tumor. Cytologic analysis showed diagnostic mucin-secreting epithelial cells in nine of ten loculi. Although cytologic examination was nondiagnostic in one loculus, there were no false-positive results for malignancy. The combination of all four tests would not have resulted in misclassification of any of the tumors. The authors conclude that the characteristics of the contents of different loculi of pancreatic cystic neoplasms may be variable, but the use of a combination of tests still ensures accurate diagnosis.

Cyst fluid cytologic analysis in the differential diagnosis of pancreatic cystic lesions.

Pancreatic cystic lesions include inflammatory pseudocysts, benign serous cystadenomas, and mucinous neoplasms, some of which are malignant. Cytologic analysis of cyst fluid has been proposed to diagnose pancreatic cysts before definitive therapy. The authors report an analysis of 31 pancreatic cyst aspirates: 9 pseudocysts, 5 serous cystadenomas, 8 mucinous cystic neoplasms, 4 mucinous cystadenocarcinomas, 2 papillary cystadenocarcinomas, 1 mucinous ductal adenocarcinoma with cystic degeneration, and 2 cystic islet cell tumors. All pseudocysts were correctly classified as probable inflammatory lesions, because of the presence of abundant acute inflammation and histiocytes and the absence of glandular epithelium. Three of five serous cystadenomas were correctly classified, based on the presence of small cuboidal cells in clusters with microvesicular cytoplasm containing glycogen. Eleven of 12 mucinous tumors contained round cells with large cytoplasmic mucin vacuoles or columnar cells containing cytoplasmic mucin. Malignancy was diagnosed in 5 of 7 carcinomas, 1 case was classified as suspicious for malignancy, and 1 case was nondiagnostic because of the absence of a cellular component. The authors concluded that pancreatic cyst fluid cytologic analysis is useful in differentiating mucinous from nonmucinous pancreatic cysts and may provide definitive evidence of malignancy. In some cases, serous cystadenoma can be diagnosed based on cytologic analysis. An inflammatory smear without epithelial cells suggests a pseudocyst, but these findings are nonspecific, as a similar pattern may occur when a cystic neoplasm undergoes degenerative changes. Therefore, pseudocyst remains a diagnosis of exclusion.

Serum ribonuclease elevations and pancreatic necrosis in acute pancreatitis.

Pancreatic necrosis is a principal determinant of the severity, duration, and infectious complications of acute pancreatitis. There has been no objective index for pancreatic necrosis, and its recognition has necessarily rested upon nonspecific clinical signs, including later deterioration or appearance of sepsis. In search of such an index, we have measured serum levels of a poly-[C]-specific acid ribonuclease (RNase) in 38 patients with acute pancreatitis, 12 patients with chronic pancreatitis, and 50 control patients. The values in chronic pancreatitis (mean, 52 units; range, 33 to 80 units) were within observed normal limits (mean, 51; range, 17 to 94). The values in acute pancreatitis segregated into two groups, normal values (group A) and high values (group B). Of 25 patients in group A (mean, 46; range, 19 to 87), only one developed evidence of pancreatic necrosis or abscess. In contrast, of the 13 patients in group B (mean, 192, range, 98 to 385), 11 required surgical debridement/drainage for pancreatic necrosis (six) or abscess (five) (P less than 0.001). Each of the other two patients had prolonged pancreatic inflammation with fever and a pancreatic mass which persisted for more than 2 weeks. RNase levels in group B patients rose within a few days after onset of pancreatitis and tended to parallel the clinical course. These findings suggest that measurement of serum RNase in acute pancreatitis gives a reliable indication of pancreatic necrosis. Therefore RNase determinations should be of value for earlier identification and monitoring of patients at high risk of late complications, and for helping to select those who will benefit from early debridement before secondary infection occurs.

Release of ribonuclease from anoxic pancreas.

Poly-[C]-specific ribonuclease (RNase) is released in large amounts from rat pancreas incubated at 37 degrees C in isotonic saline solution. Pancreatic cell disruption by homogenization releases only 10% of that RNase. The remainder, perhaps membrane-bound, is freed only after further membrane deterioration during anoxic incubation. Other tissues (small intestine, stomach, colon, liver, spleen, kidney, muscle, and skin) do not appear to contain much of this RNase or to release it during anoxic incubation. Relatively little amylase is released from the pancreas under the conditions that release RNase. The findings provide a rational basis for monitoring serum RNase levels in patients with acute pancreatitis for early detection and treatment of pancreatic necrosis in man.