[Dysphagia and recurrent esophageal stenosis associated with intramural pseudodiverticulosis of the esophagus. A case report]. / Dysphagie et sténose oesophagienne récidivante associée à une pseudodiverticulose intramurale de l'oesophage. A propos d'un cas clinique.

Intramural pseudodiverticulosis of the esophagus is a rare benign disease of the eosphageal wall, with dilation of the submucosal glands, and the predominant symptom is dysphagia. This disorder may be associated with gastroesophageal reflux, motility disorders, candidiasis and alcoholism. Inflammation, resulting in periductal fibrosis and compression of the duct orifices, may be a causative factor. Good and long-lasting therapeutic success can be achieved by bouginage of the stenosis with concomitant treatment of the associated esophageal diseases. Esophageal intramural pseudodiverticulosis is a differential diagnosis in cases of dyspagia and/or esophageal strictures if no other causes are found.

Black pigments in the liver related to gold and titanium deposits. A report of four cases.

Black pigments are rarely described in the liver. We report four patients with chronic cholestasis and black pigments described on liver histological examination. Energy-dispersive X-ray analysis identified these black pigments as gold particles in the first three patients and titanium particles in the fourth. The origin of the gold deposits was unknown in this first patient and related to gold salts therapy in the two others. Titanium deposits was associated with hepatic granulomas and related to total knee replacement.

[Autoimmune hepatitis and CREST syndrome]. / Hépatite auto-immune associée au syndrome de CREST.

We report the case of an autoimmune hepatitis in a 59-year old woman who was referred for a progressive jaundice. The patient had an history of CREST syndrome. The particularity of this case report is the rare association between these two autoimmune diseases.

[Lactose and gluten intolerance: which to suscept?]. / Les intolérances au lactose et au gluten: quand faut-il y penser?

Lactose intolerance affects millions of people world-wide and should be suspected specially when evaluating gastrointestinal symptoms in ethnic populations in which it is prevalent. Fortunately, once a diagnosis is made, management is fairly straightforward. The authors discuss symptoms and methods of detection and offer their recommendations for helping patients with this common disorder. Coeliac disease is the end result of 3 processes that culminate in intestinal damage: genetic predisposition, environmental factors, and immunological based inflammation. Epidemiological studies based on serologic tests suggest that the prevalence of coeliac disease has been significantly underestimated. The classic sprue syndrome of steatorrhea and malnutrition may be less common than more subtle and often monosymptomatic presentations of the disease. The authors discuss the diagnostic criteria and the clinical utility of serologic tests.

Outcome after surgical resection of intraductal papillary and mucinous tumors of the pancreas.

OBJECTIVE: Treatment of intraductal papillary and mucinous tumors of pancreas (IPMT) usually requires surgery. The objective of this study was to evaluate the risk of recurrence in patients after surgery according to the histological nature of the neoplasm and the type of surgery. METHODS: The outcome of 45 patients who underwent partial pancreatectomy (n = 35) or total pancreatectomy (n = 10) for IPMT was studied according to the nature of the neoplasm (invasive carcinoma or noninvasive neoplasm), type of surgery (partial or total pancreatectomy), and lymph nodes status. RESULTS: The overall 3-yr actuarial survival rate was 83%. Death occurred in seven of 20 (35%) patients with invasive carcinoma and in one of 26 (4%) patients with noninvasive tumors (p<0.05). There were two recurrences in the seven patients with noninvasive neoplasm who underwent partial pancreatectomy with involved resection margins, and none in the 13 patients with disease-free margins. In patients with invasive carcinoma, there was one recurrence after total pancreatectomy, six after partial pancreatectomy with disease-free margins and six after partial pancreatectomy with involved margins. In patients with invasive carcinoma, total pancreatectomy and the absence of lymph nodes involvement were independently associated with a low risk of recurrence. CONCLUSIONS: IPMT may be managed as follows: 1) in patients with noninvasive neoplasms, partial pancreatic resection should be guided by frozen section examination until disease-free margins are obtained; and 2) in patients with invasive carcinoma, total pancreatectomy seems most likely to cure the patient, but should be discussed according to the general status and the age.

Mucinous cystic tumors of the pancreas: clinicopathological features, prognosis, and relationship to other mucinous cystic tumors.

The clinicopathological features of 56 patients with mucinous cystic tumors (MCTs) of the pancreas were studied. Particular attention was paid to the prognosis of MCTs and the relationship to their ovarian, hepatic, and retroperitoneal counterparts. To distinguish MCTs from pancreatic intraductal papillary-mucinous tumors, MCTs were defined as tumors lacking communication with the duct system and containing mucin-producing epithelium, usually supported by ovarian-like stroma. All 56 tumors occurred in women (mean age 48.2 years) and were preferentially (93%) located in the body and tail of the pancreas. In accordance with the WHO classification, MCTs were divided into adenomas (n = 22), borderline tumors (n= 12), and noninvasive and invasive carcinomas (n = 22). Survival analysis revealed the extent of invasion to be the most significant prognostic factor (p<0.0001). Malignancy correlated with multilocularity and presence of papillary projections or mural nodules, loss of ovarian-like stroma, and p53 immunoreactivity. Stromal luteinization with expression of tyrosine hydroxylase, calretinin, or alpha inhibin was found in 66% of the cases. We conclude that the biologic behavior of MCTs is predictable on the basis of the extent of invasion. The similarities (i.e. gender, morphology, stromal luteinization) between pancreatic MCT and its ovarian, hepatobiliary, and retroperitoneal counterparts suggest a common pathway for their development.

Multisystemic production of interleukin 10 limits the severity of acute pancreatitis in mice.

BACKGROUND: Interleukin 10 (IL-10) decreases the severity of experimental acute pancreatitis. The role of endogenous IL-10 in modulating the course of pancreatitis is currently unknown. AIMS: To examine the systemic release of IL-10 and its messenger RNA production in the pancrease, liver, and lungs and analyse the effects of IL-10 neutralisation in caerulein induced acute pancreatitis in mice. METHODS: Acute necrotising pancreatitis was induced by intraperitoneal caerulein. Serum levels of IL-10 and tumour necrosis factor (TNF), and tissue IL-10 and TNF-alpha gene expression were assessed. After injecting control antibody or after blocking the activity of endogenous IL-10 by a specific monoclonal antibody, the severity of acute pancreatitis was assessed in terms of serum enzyme release, histological changes, and systemic and tissue TNF production. RESULTS: In control conditions, serum IL-10 levels increased and correlated with the course of pancreatitis, with a maximal value eight hours after induction. Both IL-10 and TNF-alpha messengers showed a similar course, and were identified in the pancreas, liver, and lungs. Neutralisation of endogenous IL-10 significantly increased the severity of pancreatitis and associated lung injury as well as serum TNF protein levels (+75%) and pancreatic, pulmonary, and hepatic TNF messenger expression (+33%, +29%, +43%, respectively). CONCLUSIONS: In this non-lethal model, systemic release of IL-10 correlates with the course of acute pancreatitis. This anti-inflammatory response parallels the release of TNF and both cytokines are produced multisystemically. Endogenous IL-10 controls TNF-alpha production and plays a protective role in the local and systemic consequences of the disease.

[Intraductal papillary mucinous tumors of the pancreas: are there any preoperative clinical and laboratory factors predictive of degeneration. Results of a French-Belgium collective series]. / Tumeurs intracanalaires papillaires mucineuses du pancréas: existe-t-il des facteurs pré-opératoires cliniques et biologiques prédictifs de dégénérescence? Résultats d'une série collective franco-belge.

Intraductal papillary and mucinous tumors are rare. We retrospectively analysed clinical, surgical and histological features and outcome of 41 operated patients (29 males, 12 females, mean age = 63 years). The commonest presenting manifestation was acute pancreatitis (41%). Tumor was located in only one pancreatic segment in 45% cases. Forty one per cent of patients had invasive carcinoma, 20% had tumor with severe dysplasia and 39% with minimal or moderate dysplasia. Only elevated age was significantly associated with invasive carcinoma. Eleven out of 17 patients with invasive carcinoma (65%) had a recurrence after surgery and 6 (35%) died. Among 24 patients with noninvasive tumor, 2 (8%) recurred without tumor-related death in the follow-up (48 months). This study underlines the need for early surgical resection in patients with intraductal papillary and mucinous tumor because of the high frequency of invasive carcinoma and the poor outcome of patients with invasive carcinoma.

[Mucosecretory and papillary intraductal tumors of the pancreas: clinicopathological considerations and radiological aspects including computed tomography symptomatology]. / Tumeurs intracanalaires mucosecretantes et papillaires du pancreas: considerations clinico-pathologiques et aspects radiologiques comprenant la semiologie tomodensitometrique.

Intraductal papillary-mucinous tumor of the pancreas (IPMT) is an uncommon entity, defined as an intraductal papillary proliferation of mucin-producing epithelial cells. Since the original description of the disease by Ohhashi in 1982, the definition and the classification of the disease has remained confused until the recently published classification of the World Health Organisation (WHO). The purpose of this article is therefore to report the clinico-pathological features of IPMT according to the WHO classification, to illustrate the radiological features especially the computed tomographic signs and to discute of the treatment.

Intraductal papillary and mucinous tumors of the pancreas: accuracy of preoperative computed tomography, endoscopic retrograde pancreatography and endoscopic ultrasonography, and long-term outcome in a large surgical series.

BACKGROUND: Few data are available on the accuracy of preoperative imaging or on long-term outcome after surgery for intraductal papillary and mucinous tumors of the pancreas. The aims of this study were to assess the following: (1) the accuracy of preoperative computed tomography, endoscopic retrograde pancreatography, and endoscopic ultrasonography for determination of tumor invasion and pancreatic extension as compared with surgical findings; (2) the long-term outcome after surgery. METHODS: Forty-seven patients who underwent surgery between 1980 and 1995 for pathologically diagnosed intraductal papillary and mucinous tumors were included in this study. The findings of available computed tomography (n = 25), endoscopic retrograde pancreatography (n = 29), and endoscopic ultrasonography (n = 21) were reviewed by experienced clinicians blinded to pathologic diagnosis to assess tumor invasion and pancreatic extension. Pathologic specimens were reviewed by experienced pathologists. Postoperative follow-up data were analyzed. RESULTS: Histologic features of invasive carcinoma were found in 43% of patients, severe dysplasia in 21%, and mild or moderate dysplasia in 36%. The overall accuracy of computed tomography, endoscopic retrograde pancreatography, and endoscopic ultrasonography in distinguishing between invasive and noninvasive tumors were, respectively, 76%, 79%, and 76%. The overall 3-year disease-free survival rate was 63%, but it was 21% among patients with invasive carcinoma at surgery (p < 0.001). CONCLUSIONS: This study emphasizes the need for early surgical resection in patients with suspected intraductal papillary and mucinous tumors of the pancreas because of the high frequency of invasive carcinoma and the inadequacy of preoperative imaging for assessing malignancy.

Different expression of transforming growth factor beta 1 in pancreatic ductal adenocarcinoma and cystic neoplasms.

Pancreatic neoplasms harbor different prognoses according to their histological type: a benign course for serous cystadenoma, a low malignant potential for intraductal papillary mucinous neoplasms (IPMN), and high aggressiveness for ductal adenocarcinoma (ADC). Transforming growth factor beta 1 (TGF beta 1) may regulate tumor growth. The present study analyzes and compares the expression of its precursor beta 1-latency-associated peptide (beta 1-LAP), its latent binding protein (LTBP), and its mRNA in ductal adenocarcinoma (n = 10), in IPMN (n = 8), in serous cystadenoma (n = 2), and in normal tissues (n = 5). LTBP is thought to play a strategic role in the processing and active secretion of latent TGF beta 1 and its stockage in the extracellular matrix. Localization of beta 1-LAP and LTBP was assessed by immunohistochemistry using specific antibodies and expression of TGF beta 1 mRNA by reverse-transcriptase polymerase chain reaction analysis. beta 1-LAP was only slightly expressed in normal specimens, while LTBP was not detected. beta 1-LAP was detected in the cytoplasm of neoplastic cells in 9 of 10 patients with ADC. An intense staining was present in stromal cells surrounding the neoplastic glands in all cases except in one carcinoma in situ. LTBP was detected only in stromal cells and in the surrounding extracellular matrix. In IPMN with mild-grade dysplasia and in cystadenoma, beta 1-LAP was strongly expressed in the epithelial cells, while it was poorly detected in invasive IPMN; stromal cells were poorly or not all stained by beta 1-LAP, except in invasive IPMN (n = 2). LTBP was detected in neoplastic cells of three cases with benign IPMN and two of two cases with cystadenoma, while stroma was not immunostained. TGF beta 1 mRNA was strongly expressed in most of the tumors and no difference in expression was observed between the different types of neoplasms. There is no quantitative difference in expression of TGF beta 1 in ADC and in IPMN or cystadenoma. However, the latter are able to secrete TGF beta 1 efficiently, in contrast to ductal ADC as shown by the ability of the neoplastic cells to express both beta 1-LAP and LTBP. Invasive stroma reaction was associated with enhanced beta 1-LAP and LTBP expression in stromal cells and could be mediated by TGF beta 1 via LTBP

Nonfunctioning neuroendocrine tumors of the pancreas: clinical presentation of 7 patients.

BACKGROUND: Neuroendocrine tumors of the pancreas (NPT) are rare and represent less than 0.5% of all pancreatic tumors. MATERIALS AND METHODS: The authors describe the clinical presentation, the pathological findings and the treatment of 7 patients with nonfunctioning NPT. RESULTS: Non-specific symptoms were noted in 6 patients, depending on the size and the location of the tumor, and 1 patient was asymptomatic. A correct preoperative diagnosis was done in only one case. Immunohistochemical studies, most often on surgically resected tissue sample is needed for diagnosis of NPT. The treatment requires surgical resection. Among 4 patients (57%) classified No at the time of surgery, 3 (75%) are alive, free of recurrence, more than 2 years after tumor resection. CONCLUSION: The preoperative diagnosis is difficult to assess. NPT differ from pancreatic adenocarcinomas by the younger age of the patients, their immunohistochemical pattern and a better prognosis after surgical resection.

Intraductal papillary mucinous tumours of the pancreas. Clinical and therapeutic issues in 32 patients.

BACKGROUND/AIM: The clinical presentation, pancreatographic findings, and outcome of patients with intraductal papillary mucinous tumours have not been reported in a large patient series in the English literature. This study reviewed 32 patients diagnosed between 1980 and 1994, with special attention to these features. PATIENTS/METHOD: Data on 24 operated and eight non-operated patients were abstracted from inpatient, outpatient, and procedure records. RESULTS: Acute pancreatitis was the most common presentation seen in 56% of patients. Relapses occurred during an average of 43 months before diagnosis. A patulous papilla was observed in 55% of the cases. Endoscopic pancreatography showed communicating cysts, a diffusely dilated main pancreatic duct, and amorphous defects in 42, 71, and 97% respectively. An invasive carcinoma was found in nine of 24 (37.5%) of operated patients: six of the patients (66%) died or developed metastases within three years after surgery. No mortality was related to the tumour in absence of invasive carcinoma. Benign recurrence on the remaining pancreas was unusual and occurred late after surgery. CONCLUSIONS: Intraductal papillary mucinous tumours must be considered in the differential diagnosis of relapsing pancreatitis. Despite slow growing, these tumours have an obvious malignant potential and a very poor prognosis when invasive carcinoma has developed. Early recognition and resection are the cornerstones of treatment.

Localization of transforming growth factor beta 1 and its latent binding protein in human chronic pancreatitis.

BACKGROUND/AIMS: Transforming growth factor beta 1 (TGF-beta 1) is thought to be the mediator of fibrosis in liver, glomerular, and pulmonary fibrosis. This study investigated the expression of TGF-beta 1 precursor (beta 1 latency-associated peptide), latent TGF-beta 1-binding protein (LTBP), and TGF-beta 1 messenger RNA (mRNA) in chronic pancreatitis. METHODS: Beta 1 latency-associated peptide and LTBP expression were studied by immunohistochemistry, and TGF-beta 1 mRNA expression was studied by reverse-transcription polymerase chain reaction analysis in normal pancreatic parenchyma and in tissues from patients with chronic pancreatitis of different etiologies. RESULTS: In normal specimens, TGF-beta 1 precursor was present in islet cells and in a few ductal and acinar cells but not in periductal connective tissue. No immunoreactivity for LTBP was detected. In chronic pancreatitis, TGF-beta 1 precursor was detected mainly in mononuclear cells located in the fibrotic areas and also in ducts damaged by fibrosis, more frequently in calcifying chronic pancreatitis. LTBP was present predominantly in mononuclear cells and in the extracellular matrix around them. TGF-beta 1 mRNA was either not expressed or was faintly expressed in normal tissue, whereas intense signals were detected in chronic pancreatitis. CONCLUSIONS: The findings suggest the involvement of TGF-beta 1 in the development of fibrosis in chronic pancreatitis and the important role of inflammatory cells.

Detection of c-Ki-ras gene codon 12 mutations from pancreatic duct brushings in the diagnosis of pancreatic tumours.

Differential diagnosis of pancreatic cancer and chronic pancreatitis is sometimes difficult and cytological examination of brushings or aspirated material collected during endoscopic retrograde cholangiopancreatography (ERCP) remains disappointing. As point mutations in codon 12 of the c-Ki-ras 2 gene are found in most pancreatic adenocarcinoma and not in chronic pancreatitis, this study analysed prospectively the presence of these mutations in brushing samples collected during ERCP in 45 patients (26 males, 19 females) showing a dominant stricture of the main pancreatic duct at pancreatography: 24 with pancreatic adenocarcinoma, 16 with chronic pancreatitis, and five intraductal mucin hypersecreting neoplasms. Twenty of 45 patients presented equivocal ERCP findings that did not permit a definite diagnosis. Ki-ras mutations at codon 12 were detected using a rapid and sensitive method based on polymerase chain reaction mediated restriction fragment length polymorphism analysis and confirmed by direct sequencing of polymerase chain reaction products. Results were compared with those provided by routine brush cytology. A definitive diagnosis was established for each patient. Mutations were detected in 20 of 24 patients with pancreatic adenocarcinoma (83%), but in none of the chronic pancreatitis patients and intraductal mucin hypersecreting neoplasms, irrespective of their location. By contrast, only 13 of 24 pancreatic adenocarcinoma (54%) were detected by conventional cytological examination, which yielded four false negative and seven non-contributive results. Sensitivity, specificity, and accuracy of molecular biological and cytological methods were 83%-76%, 100-83%, and 90%-58%, respectively. Notably the mutations could be detected in six patients with small tumour size (< or = 2 cm). In conclusion, Ki-ras analysis performed on pancreatic brushing samples is an efficient procedure, more accurate than cytology in the diagnosis of pancreatic adenocarcinoma, and highly specific in the differentiation between neoplastic and chronic inflammatory ductal changes, especially in patients showing inconclusive ERCP findings.

Intraductal papillary-mucinous tumours represent a distinct group of pancreatic neoplasms: an investigation of tumour cell differentiation and K-ras, p53 and c-erbB-2 abnormalities in 26 patients.

Intraductal papillary growth of mucin producing hypersecreting, columnar cells characterizes a group of rare pancreatic exocrine neoplasms which we propose to call intraductal papillary-mucinous tumors (IPMT). We analysed the histopathology of 26 IPMT in relation to gastro-enteropancreatic marker expression, genetic changes and biology. Four IPMT showing only mild dysplasia were considered to be adenomas. Nine tumours displayed moderate dysplasia and were regarded as borderline. Severe dysplasia-carcinoma in situ changes were found in 13 IPMT which were therefore classified as intraductal carcinomas. Six of these carcinomas were frankly invasive and two of these had lymph node metastases. The invasive component resembled mucinous non-cystic carcinoma in all but one tumour which showed a ductal invasion pattern. Immunohistochemically, an intestinal marker type was found in most carcinomas, while gastric type differentiation prevailed among adenomas or borderline tumours. K-ras mutations (seven at codon 12 and one at codon 13) were found in 31% of IPMT (2 adenomas, 1 borderline, 5 carcinomas). Nuclear p53 overexpression was detected in 31% of IPMT (6 carcinomas and 2 borderline IPMT) and correlated with p53 mutations (one at exon 8 and the other at exon 5) in two carcinomas. p53 abnormalities were unrelated to K-ras mutation. c-erbB-2 overexpression was observed in 65% of IPMT, with various grades of dysplasia. Twenty-two of 24 patients are alive and well after a mean post-operative follow-up of 41 months. Only two patients, both with invasive cancer at the time of surgery, died of tumour disease. It is concluded that pancreatic IPMT encompass neoplasms which, in general, have a favorable prognosis, but are heterogeneous in regard to grade of dysplasia and marker expression. Adenoma, borderline tumour, intraductal carcinoma and invasive carcinoma can be differentiated. p53 changes but not K-ras mutation or c-erbB-2 overexpression are related to the grade of malignancy. Most IPMT differ in histological structure, marker expression and behaviour from ductal adenocarcinoma.

Listeria monocytogenes hepatitis in a liver transplant recipient: a case report and review of the literature.

Listeria is an uncommon cause of hepatitis in adults. We report the case of a liver transplant recipient who presented with a clinical picture of acute hepatitis, 8 months after grafting. Blood cultures yielded Listeria monocytogenes. The patient made a full clinical recovery after adequate antimicrobial therapy (ampicillin and gentamicin intravenously for 4 weeks). Hepatitis was attributed to the Listeria infection. We believe this is the first reported case of Listeria hepatitis in an organ transplant recipient.

Vascular graft infection caused by Aspergillus species: case report and review of the literature.

We report an unusual case of vascular graft infection caused by Aspergillus fumigatus that began with a false aneurysm, major arterial emboli, and septic arthritis. Successful treatment included resection of the infected graft, restoration of circulation by extraanatomic bypass, and administration of amphotericin B and itraconazole, a new antifungal agent. Graft infection in the case reported herein most likely occurred during surgery and took place during an insidious outbreak of postoperative infection.

Computerized morphonuclear characteristics and DNA content of adenocarcinoma of the pancreas, chronic pancreatitis, and normal tissues: relationship with histopathologic grading.

We report the morphonuclear characteristics of normal (13 cases), benign (ie, chronic) pancreatitis (six cases), and neoplastic (ie, ductal) adenocarcinoma (22 cases) tissues of the pancreas. This description is based on computerized cell image analysis, which permits the determination of parameters related to the morphometric (nuclear area), densitometric (nuclear DNA content), and chromatin texture features of Feulgen-stained nuclei from paraffin-embedded archival material. We observed that nuclear area discriminates between normal and benign (ie, chronic pancreatitis) as opposed to neoplastic cell nuclei. Morphonuclear parameters describing chromatin pattern characteristics made it possible to discriminate between grade I pancreatic carcinoma and normal and benign cell nuclei on the one hand, and grades I and III carcinoma on the other hand. The nuclear DNA content increased in a continuous manner from normal and benign through low-grade to high-grade neoplastic tissues of the pancreas. Combining the morphometric, densitometric, and textural parameters into one equation, we were able to calculate a score (ie, the malignancy level index) that showed a close relationship to conventional histopathologic grading. Thus, the computer-aided diagnosis of cytologic specimens from pancreatic lesions offers information of the same significance as that obtained by conventional histopathologic grading.

Intraductal mucin-hypersecreting neoplasms of the pancreas. A clinicopathologic study of eight patients.

Intraductal mucin-hypersecreting neoplasms of the pancreas with extreme dilatation of the main duct were studied in eight patients. They included five men and three women, aged 47-85 years. Five patients had a history of symptoms mimicking pancreatitis; four developed steatorrhea and/or diabetes. At endoscopic retrograde pancreatography, five patients showed an open ampulla filled with mucin, and six patients showed patchy filling defects in the ectatic main duct. Morphological examination showed extreme dilatation of the entire pancreatic duct in six patients and its tail segment in two patients. The duct segments filled with viscous mucin were lined by well-differentiated mucin-secreting cells, forming papillary foldings and occasionally showing cellular atypia. None of the patients had invasive tumor or metastasis. Six patients whose lesions were resected are alive and doing well (mean follow-up, 5.5 years). It is concluded that intraductal mucin-hypersecreting neoplasm is a pancreatic tumor with favorable prognosis. Because it shares many features with intraductal papillary neoplasm, a common pathogenesis of these pancreatic tumors is suggested.