Enlarged pancreas: not always a cancer

Pancreatic fat accumulation has been described with various terms including pancreatic lipomatosis, pancreatic steatosis, fatty replacement, fatty infiltration, fatty pancreas, lipomatous pseudohypertrophy and nonalcoholic fatty pancreas disease. It has been reported to be associated with type 2 diabetes mellitus, acute pancreatitis, pancreatic cancer and the formation of pancreatic fistula. The real incidence of this condition is still unknown. We report a case of pancreatic steatosis in a non-obese female patient initially diagnosed with a mass in the head of the pancreas. Magnetic resonance imaging(MRI) was carried out to define the characteristics of the pancreatic mass. MRI confirmed the diagnosis of fat pancreas. Enlarged pancreas is not always a cancer, but pancreatic steatosis is characterized by pancreatic enlargement. MRI could give a definite diagnosis of pancreatic steatosis or cancer.     

对脂肪胰的研究

脂肪胰以胰腺脂肪浸润或胰腺脂肪变性为主要表现,其病理生理学机制目前尚未完全明确,国内外也尚未形成统一的诊断标准或共识.组织学检查是脂肪胰诊断的“金标准”,临床上MRI、CT和腹部超声均能发现替代胰腺实质的脂肪组织,超声内镜（EUS）对脂肪胰的诊断具有一定优势.已有多项研究表明,脂肪胰与肥胖、T2DM、MS等疾病有关,胰腺脂肪变性的胰腺癌患者更易发生淋巴结转移及胰腺手术后的胰瘘,提示脂肪胰在以上疾病的诊断、治疗和预后判断上都有潜在价值,可能成为,如糖尿病、MS等代谢性疾病早期干预的指征之一.     

Total pancreatic lipomatosis with malabsorption syndrome

Total fat replacement of the pancreas is rare. Focal fatty replacement is the most common degenerative lesion of pancreas. Focal fatty deposits have no major clinical significance; however, extreme fat replacement is of pathologic significance, as it is associated with marked reduction in exocrine function of pancreas, resulting in malabsorption due to pancreatic enzyme insufficiency.     

Acquired Fatty Replacement of the Body and Tail of the Pancreas Diagnosed by Endoscopic Ultrasonography —A Case Report—

Abstract: A 62-year old female was admitted for a detailed study of a pancreatic abnormality detected by abdominal ultrasonography. A CT and MRI revealed a fat deposition in the body and tail of the pancreas. An ERCP demonstrated the distal main pancreatic duct as 2 fine branches in the head, and accessory pancreatic ducts were visualized. An endoscopic ultrasonography revealed a swelling of the body. In the tail, a membrane-like hyperechoic structure was noted, and probably represented the pancreatic capsule. A angiography demonstrated branches of the dorsal and transverse pancreatic artery, and the diagnosis of acquired fatty replacement of the body and tail of the pancreas was confirmed. Endoscopic ultrasonography appears to be a useful method to confirm fatty replacement of the body and tail of the pancreas.     

A case of lipomatous pseudohypertrophy of the pancreas diagnosed by EUS-FNA

We report the case of a 56-year-old female with lipomatous hypertrophy of the pancreas. Abdominal CT and MRI showed fatty replacement over the entire pancreas. The pancreatic parenchyma was completely absent. ERCP showed no abnormal findings in the main pancreatic duct. EUS-FNA was performed to achieve a definitive diagnosis. Histological features of the FNA specimens revealed that adipose tissue generally replaced the pancreatic parenchyma, and pancreatic acini were identified with a scattered distribution. To consider the differential diagnosis of lipomatous pseudohypertrophy of the pancreas, it is necessary to distinguish it from obesity, diabetes, and age-related pancreatic fat infiltration and liposarcoma. By performing EUS-FNA, it was possible to obtain a definitive diagnosis in this patient. In conclusion, EUS-FNA may be helpful to make a definitive diagnosis in patients with lipomatous hypertrophy of the pancreas.     

Fat necrosis - a cause of pancreatic parenchymal necrosis?

Acute pancreatic necrosis resulted when oleic acid or olive oil was injected into the pancreatic duct or rats. After injection of droplets of both lipids into the pancreatic interstitial tissue, coagulation-type necrosis of acinar tissue developed adjacent to these droplets. Mono-olein or paraffin oil caused no histological alterations of acinar cells. It is concluded that (1) the deleterious effect of olive oil on the pancreas is mediated through fatty acids released by pancreatic lipase, and (2) fatty acids split off in fat necrosis of acute pancreatitis may damage adjacent pancreatic acinar tissue.     

Pancreatic stone predominantly composed of fatty acid calcium.

A 41-year-old man with chronic pancreatitis and pancreatic stones predominantly composed of fatty acid calcium is reported. He had complained of occasional abdominal pain for 10 years and visited the hospital because of a severe attack of abdominal pain. Laboratory data supported a diagnosis of pancreatitis. Computed tomography (CT) showed a high-density area in the head of the pancreas, and the CT number of this high-density area was lower than usual for pancreatic stones. Ultrasonography and endoscopic retrograde pancreatography showed a cystic lesion with small pancreatic stones in the head of the pancreas and irregular dilatation of the main pancreatic duct. Pancreaticojejunostomy and resection of pancreatic cyst were carried out for repeated episodes of abdominal pain under the diagnosis of chronic pancreatitis. The pancreatic stones obtained at surgery were proved to be mainly composed of fatty acid calcium after analysis of chemical composition of the stones. Fatty acid calcium was sometimes found in the biliary stones but never in the pancreatic stones.     

Acute pancreatitis-onset carcinoma in situ of the pancreas with focal fat replacement diagnosed using serial pancreatic-juice aspiration cytologic examination (SPACE)

A 59-year-old woman was admitted for acute pancreatitis. Abdominal computed tomography and magnetic resonance imaging revealed a swollen pancreatic parenchyma with dilatation of the main pancreatic duct (MPD) of the pancreas tail, which was separated from the normal pancreas body side by a locally atrophic part of the pancreas. Magnetic resonance cholangiopancreatography showed MPD stricture in the pancreas tail with dilatation of the upstream MPD. Endoscopic ultrasonography revealed that the MPD stricture of the pancreas tail was surrounded by a blurred and hypoechoic area. Endoscopic retrograde cholangiopancreatography was performed for serial pancreatic-juice aspiration cytologic examination (SPACE). The result indicated adenocarcinoma. Distal pancreatectomy was performed, and the histopathological examination showed high-grade PanIN (carcinoma in situ of the pancreatic duct) of the pancreas tail with atrophy and fibrosis of the pancreatic parenchyma, and local fat replacement adjacent to the lesion. The final histopathological diagnosis was carcinoma in situ of the pancreatic duct of the pancreas tail. Acute pancreatitis and local fatty change of the pancreatic parenchyma with MPD stricture are important clinical manifestations of pancreatic carcinoma in situ (PCIS) and performing SPACE in cases of MPD stricture without a recognizable mass is preferable for a diagnosis of PCIS.     

Pancreas and metabolic syndrome

The functional state of the pancreas has a significant share in the development of the basic components of MS (hyperinsulinemia, insulin resistance, impaired glucose tolerance) and, conversely, the existing metabolic changes (obesity, atherogenic dyslipidemia) contribute to the violation of the endocrine and exocrine pancreatic function. It is assumed, on the one hand, the fundamental role of fatty pancreas disease in developing metabolic syndrome, with the formation of insulin resistance, on the other hand, indicates that hyperinsulinemia, hyperglycemia and dyslipidemia, as well as microcirculatory disturbances aggravate the state of the pancreas. Trigger mechanism of progression pancreatic pathology in MS appears inflammation closely accompanied with fatty infiltration of the body against obesity. Changes in pancreas specific to MS, are not only secondary to its background, but also contribute to the progression of the syndrome and the development of complications, closing the pathogenic circle.     

Pancreas head carcinoma with total fat replacement of the dorsal exocrine pancreas

We report a case of pancreas head carcinoma associated with fat replacement of the body and tail. A 68-year-old man presented with obstructive jaundice and was admitted to our hospital. Ultrasonography and computed tomography showed pancreas head tumor with a neighboring cystic lesion and fatty replacement of parenchyma of the pancreas body and tail. By endoscopic retrograde pancreatography, abruption of the main pancreatic duct and the presence of an accessory duct were detected. After percutaneous transhepatic biliary drainage, pancreatoduodenectomy was successfully performed. At laparotomy, the pancreas head was easily dissected from the replaced fatty tissue of the body and tail without continuity of the ductal system or parenchyma. Microscopic examination revealed the existence of an infiltrating ductal adenocarcinoma and a neighboring. cyst in the pancreas head. The dorsal exocrine pancreas was completely replaced by the fat tissues, in which viable Langerhans islets were scattered. The patients postoperative course was uneventful, and exogenous insulin administration was unnecessary for the maintenance of normal blood sugar level. Acquired fat replacement of the body and tail of the pancreas is an uncommon disorder, mimicking congenital agenesis of the dorsal pancreas. Though the mechanism is controversial, obstruction of the main pancreatic duct by a cystic lesion or carcinoma in the pancreas head is a possible cause of fatty degeneration of the pancreatic parenchyma.     

Histological pancreatic findings correlate with computed tomography attenuation and predict postoperative pancreatic fistula following pancreatoduodenectomy

BackgroundAlthough a soft pancreas is a widely-accepted reliable risk factor for postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD), there is no established preoperative evaluation of pancreatic texture.MethodsTwo hundred thirty-seven patients who underwent PD with histological pancreatic assessment were retrospectively enrolled. The degree of fibrosis and fatty infiltration was scored histologically as seven grades and five grades, respectively. Computed tomography (CT) attenuation of the pancreas was measured on preoperative unenhanced CT images. Correlations between the CT attenuation of the pancreas and the histological pancreatic findings, and the development of POPF were analyzed.ResultsThe fibrosis grade was significantly higher for hard pancreas than for soft pancreas (p < 0.001), whereas the fatty infiltration grade was similar between the two types (p = 0.161). CT attenuation of the pancreas was inversely correlated with both fibrosis grade (Spearman's rank correlation coefficient ([r] = ?0.609, p < 0.001) and fatty infiltration grade (r = ?0.382, p < 0.001). Multivariate analysis showed that body mass index ≥25 kg/m² (odds ratio [OR]: 5.64, p < 0.001) and fibrosis grade ≤2 (OR: 18.0, p < 0.001) were independent risk factors for clinically significant POPF.ConclusionHistological pancreatic texture can be evaluated with CT attenuation and might be helpful in preoperatively predicting the development of POPF after PD.     

Impact of pancreatic fat infiltration on postoperative pancreatic fistula occurrence in patients undergoing invagination pancreaticojejunostomy

BackgroundNo studies to date have determined the impact of pancreatic fat infiltration on postoperative pancreatic fistula (POPF) occurrence in patients undergoing invagination pancreaticojejunostomy (IV-PJ).MethodsThe medical records of patients with a soft pancreas who underwent pancreatoduodenectomy followed by IV-PJ were reviewed . The pancreatic fat ratio on computed tomography (CT) images (I-PFR) was determined using preoperative CT and verified by histologic examination. The relationship between the I-PFR and POPF occurrence was determined. Patients were classified into 2 groups based on I-PFR value (fatty and non-fatty pancreas). Postoperative outcomes were compared between the two groups, and specifically among patients who developed POPF.ResultsOf 221 patients, POPF occurred in 67 (30.3%). I-PFR was positively correlated with histologic-calculated fat ratio (ρ = 0.517, p < 0.001). This index was shown to be an independent predictor of POPF. Based on an I-PFR cut-off value of 3.2%, 92 patients were classified in the fatty pancreas group. Subgroup analysis of the patients who developed POPF showed that incidence of abscess formation and hemorrhage tended to be higher in patients with fatty pancreas than in those with non-fatty pancreas.ConclusionsPancreatic fat infiltration is highly associated with POPF and possibly causes subsequent serious complications in patients undergoing IV-PJ.     

Histological Study on Pathogenesis of Sites of Isolated Islets of Langerhans and Their Course to the Terminal State

Histological study was performed on the pathogenesis of sites of isolated islets of Langerhans and on their course to the terminal state, using the pancreas of each of 200 randomly selected autopsy cases. With regard to sites of isolated islets, we found an incidence of 26.5% (53/200, 115 sites), which increased with age until subjects were in their 80s. To further our study, we also histologically studied the pancreas in 13 cases with evident obstruction in the lower stream of the main pancreatic ducts due to pancreatic carcinoma (10 cases) and stones (three cases), and one case of mucin-producing intraductal papillary adenocarcinoma in the tail of the pancreas with abundant mucin in the main pancreatic duct. As a result, we believe its pathogenesis to be the obstructive mechanism of pancreatic ductuli, caused by epithelial papillary projection or mucin secreted by epithelial cells of mucinous metaplasia, and that the course to the terminal state of isolated islets is as follows: For the first time, we report that the atrophy and disappearance of acinar cells by obstructive mechanism of ductuli (described above) occur with fibrosis, inflammatory cellular infiltration, and fatty infiltration around the site of isolated islets, accompanied by gathering of islets. This is followed by scarring of the site with further gathering of islets and a decrease in inflammatory cells. Fibrosis is gradually displaced by fatty tissue. Fatty infiltration into the site becomes marked, and gathered islets are found in the fatty tissue.     

Insulin,pancreatic polypeptide,and glucagon release from the chicken pancreas in vitro: Responses to changes in medium glucose and free fatty acid content

The effects of glucose and fatty acids on release of insulin, pancreatic polypeptide (APP), and glucagon by the chicken pancreas were investigated in vitro. Small fragments of chicken pancreas were perifused; pancreatic hormones were measured in the effluent perifusate by radioimmunoassay. Elevation of medium glucose from 200 mg/dl to 500 mg/dl did not affect insulin release while elevation to 700 mg glucose/dl produced a sustained increase in insulin output. Glucagon release was consistently suppressed when glucose was elevated to either level. Pancreatic polypeptide secretion was not reduced by increases in medium glucose. Butyrate and valerate (5 mM) did not affect output of any of the hormones measured. Oleate and linoleate (0.3 and 1.0 mM, respectively) both stimulated insulin secretion; linoleate also stimulated APP and glucagon secretion. None of the fatty acids tested directly reduced glucagon or APP output although partial antagonistic effects of the fatty acids on pancreatic secretion were suggested by “off response” increases in the pancreatic hormone output upon removal of the long-chain fatty acids from the perifusion medium.     

Pancreatic CT density is an optimal imaging biomarker for earlier detection of malignancy in the pancreas with intraductal papillary mucinous neoplasm

BackgroundIntraductal papillary mucinous neoplasms (IPMNs) are typically detected as incidental findings by computed tomography (CT); however, the conventional surveillance is not valid for the early detection of concomitant pancreatic cancer. The pancreas of IPMN is often accompanied by fatty infiltration in the parenchyma, and pancreatic fatty infiltration could be evaluated by pancreatic CT density (pancreatic index, PI). We aimed to investigate whether PI could be an imaging biomarker for the early prediction of malignancies in the pancreas with IPMN.MethodsTwo different cohorts were investigated. (Investigation cohort): A total of 1137 patients with initially low-risk IPMN were compensated by initial IPMN findings, and 2 groups (malignancy/possible benign, 50 cases each) were investigated for yearly changes in PI and for the cutoff value of PI indicating the development of malignancies. (Validation cohort): To validate the cutoff value, 256 patients radiologically suspected of having IPMNs were investigated.Results(Investigation-cohort): The malignancy group showed a gradual decrease in PI every year, and PI significantly differed among the 2 groups 1 year prior to the last investigation. The cutoff value of PI was set at 0.65. (Validation-cohort): A total of 55% of the patients with a PI below the cutoff value had malignancy in the pancreas, including concomitant pancreatic cancer, and the cutoff value was the most significant risk factors for the development of malignancies in the pancreas compared to the conventional risk factors for IPMN.ConclusionsDecreasing PI would be an optimal imaging biomarker for earlier detection of malignancies in the pancreas with IPMN.     

非酒精性脂肪性胰腺疾病的研究进展

非酒精性脂肪性胰腺疾病(NAFPD)是指与肥胖症或代谢综合征相关的胰腺脂肪堆积。近年来随着人们生活水平的提高,NAFPD发病率也在不断增加,与其相关的研究也随之增加。目前其发病机制尚不明确,定量评估方法主要包括组织学检查、超声、CT、MRI等,近年来文献报道NAFPD与疾病的相关性主要集中于2型糖尿病、动脉粥样硬化、代谢综合征、胰腺癌、胰腺内分泌与外分泌功能、非酒精性脂肪肝、急慢性胰腺炎、胰瘘等。与肝脏脂肪变性相比,NAFPD相关研究数量依然较少。     

The prevalence and clinical implications of pancreatic fat accumulation identified during a medical check-up

Fatty pancreas (FP) is characterized by pancreatic fat accumulation and the subsequent development of pancreatic and metabolic complications. However, FP has not been categorized in the manual for abdominal ultrasound in cancer screening and health check-ups in Japan, and the pathology of FP has not been fully elucidated.Nine hundred and nineteen people who underwent a medical check-up had the severity of their pancreatic fat accumulation categorized after transabdominal ultrasonographic examination. The relationships between FP, lifestyle-related diseases, and fatty liver disease at this time were assessed using stratification analysis.The prevalence of FP was 46.8% (430/919). People with FP were more likely to be male and had higher prevalences of lifestyle-related diseases, including fatty liver disease. Men and women were similarly represented in each tertile of pancreas brightness. Older age; high waist circumference, triglyceride and glucose index, serum low-density lipoprotein-cholesterol, hepatic steatosis index; and low serum amylase were associated with the presence of severe FP. Moreover, the group with severe liver steatosis had a higher prevalence of FP and a higher pancreatic brightness score. Logistic regression analysis showed that individuals with liver steatosis were more likely to have severe FP.The severity of FP is associated with features of lifestyle-related diseases and the severity of liver steatosis. These findings suggest that high visceral fat content is associated with more severe fatty pancreas as a phenotype of ectopic fat accumulation, as well as fatty liver disease.     

Hypoplasia of exocrine pancreas with myocardial necrosis

AIM To study the clinical and pathological features of hypoplasia of exocrine pancreas with myocardialnecrosis.METHODS One ease of hypoplasia of exocrine pancreas with myocardial necrosis was autopsied. Theclinical signs and pathological changes were analyzed.RESULTS A 15-month-old boy with hypoplasia of exocrine pancreas was reported. The main clinicalfeatures were steatorrhea and marked underdevelopment. He died of acute heart failure afterhospitalization. Autopsy showed that there were aplasia of exocrine portion and fatty metaplasia ofpancreas, the myocardium revealed focal necrosis and sear formation.CONCLUSION Atrophy of exocrine pancreas and myocardial necrosis exist at the same time, suggestingthat there may be some relationship between them. It was likely that the damaged pancreatic tissue releasedsome active materials that may harm the myocardium or decrease pancreatic juice that results in lack ofnutrient and myocardial necrosis.     

Fat,epigenome and pancreatic diseases. Interplay and common pathways from a toxic and obesogenic environment

The worldwide obesity epidemic is paralleled by a rise in the incidence of pancreatic disorders ranging from “fatty” pancreas to pancreatitis and cancer. Body fat accumulation and pancreatic dysfunctions have common pathways, mainly acting through insulin resistance and low-grade inflammation, frequently mediated by the epigenome. These mechanisms are affected by lifestyle and by the toxic effects of fat and pollutants. An early origin is common, starting in pediatric age or during the fetal life in response to nutritional factors, endocrine disruptor chemicals (EDCs) or parental exposure to toxics. A “fatty pancreas” is frequent in obese and is able to induce pancreatic damage. The fat is a target of EDCs and of the cytotoxic/mutagenic effects of heavy metals, and is the site of bioaccumulation of lipophilic and persistent pollutants related with insulin resistance and able to promote pancreatic cancer. Increased Body Mass Index (BMI) can act as independent risk factor for a more severe course of acute pancreatitis and obesity is also a well-known risk factor for pancreatic cancer, that is related with BMI, insulin resistance, and duration of exposure to the toxic effects of fat and/or of environmental pollutants. All these mechanisms involve gene–environment interactions through epigenetic factors, and might be manipulated by primary prevention measures. Further studies are needed, pointing to better assess the interplays of modifiable factors on both obesity and pancreatic diseases, and to verify the efficacy of primary prevention strategies involving lifestyle and environmental exposure to toxics.