Clinicopathologic view of intraductal papillary-mucinous tumor of the pancreas

Intraductal papillary-mucinous tumors (IPMTs) of the pancreas form a special group of neoplasms characterized by intraductal papillary growth of mucin-producing columnar cells. Included among these neoplasms are papillary and villous adenomas, lesions with mucinous duct ectasia and mucin-producing carcinomas. Most patients are males and present with episodic pancreatitis-like symptoms, which may have been noted for years. These symptoms are due to incomplete and later complete duct obstruction by papillary proliferations and/or mucin, which eventually cause fibrotic atrophy of the normal parenchyma. At the time of diagnosis, malignant non-invasive IPMTs are observed in 5-30% of the cases. Fifteen to forty percent of the IPMTs show invasion and half of the invasive IPMTs have metastases. Pre-operatively, invasiveness cannot be predicted. Patients with non-invasive IPMT survive for long periods after surgery, as do many patients with invasive, non-metastatic IPMT, although intraductal proliferation with a mild degree of atypia may be present at the resection margin. In patients with invasive and metastatic IPMT, survival ranges from a few months up to 3 years.     

Mucin-hypersecreting intraductal neoplasms of the pancreas: a precursor to cystic pancreatic malignancies

BACKGROUND: Muncin-hypersecreting intraductal pancreatic neoplasms were first described in 1982 and have been observed in increasing numbers since. They are observed primarily by endoscopic retrograde cholangiopancreatography (ERCP) and are characterized by an intraductal papillary neoplasm that secretes thick mucin, causing pancreatic duct dilatation and obstructive pancreatitis. METHODS: Twenty patients are presented, 14 male and six female, with an average age of 59 +/- 11 years. All patients presented with abdominal pain, and most had nausea and vomiting, weight loss, and documented pancreatitis. Of the preoperative studies, ERCP was positive in all patients. Computed tomography scan, endoscopic ultrasonogram, and cytologic findings were less sensitive. Tumor markers were only positive in one patient. All 20 patients were treated surgically. Nine underwent Whipple procedure, one patient had a total pancreatectomy, and nine had distal pancreatic resections. The first patient in the series did not have a pancreatic resection, and his disease evolved into a lethal cystadenocarcinoma causing his death 99 months later. RESULTS: Histopathologic findings were interpreted as borderline malignant in 17 of the 20 patients, and three patients had evidence of invasive adenocarcinoma. Two of these three patients had nodal or distant metastases at the time of diagnosis, and all three died of adenocarcinoma. Seventeen of the patients are alive and well, although two of three with positive pancreatic margins have had recurrent symptoms and have been successfully reresected. CONCLUSIONS: The mucin-producing intraductal papillary tumor of the pancreas is a newly described variant of pancreatic cancer. It presents with symptoms of pancreatitis and has a progressive but more indolent course than the more lethal invasive ductal cancers. Patients with unexplained pancreatitis should undergo ERCP investigation, and aggressive surgical therapy should be carried out because the prognosis for this lesion, when appropriately treated, is more favorable than the usual pancreatic cancer.     

Intraductal papillary-mucinous tumours of the pancreas. Clinical and radiological aspects

From March 1994 to March 1995, 14 cases of refractory advanced breast cancers were treated with Navelbine (NVB). NVB as a single agent was given weekly 40-60mg (24.9mg-33.3 mg/m2), every 2 weeks for one cycle. Six of fourteen cases (42.9%) achieved partial response (PR). The median remission duration of PR patients was 5 months (range 2-10 months). NVB was given 85 times, the main side effects were myalgia and arthralgia (80.0%), phlebitis (57.6%). Sixty-five of eighty five pretreatment WBC counts were below 4.0 x 10(9)/L, and the severity of leukopenia was related to pretreatment WBC level. No patient died of infection.     

Observations on the pathogenesis of porcine parvovirus infection

Differences in the pathogenesis of porcine parvovirus (PPV) were shown when pregnant gilts were infected by the oral and intramuscular (i.m.) routes. By the oral route, PPV took 23-32 days to cross the placenta following infection of the dam, as compared to 15 days by the i.m. route, Successful transplacental infection occurred following oral infection of dams only in the second third of gestation, whilst i.m. infection resulted in infection of foetuses in both first and second thirds of gestation. Foetal infection resulted in death and mummification only where infection of foetuses occurred before onset of immune competence--estimated at 70 days gestation. Infected foetuses either died before onset of immune competence, or survived to mount an immune response with subsequent death or survival to farrowing. It is suggested in discussion that reproductive failure due to PPV, characterised by mummification or occasional stillbirth, is associated in nature with oral infection, and occurs only when dams are infected in the first part of the midthird of gestation.     

Psychosomatic factors in the etiology of neoplasms.

Several psychogenic theories have been developed to explain the onset of cancer. Much of the research used to support them suffers from methodological weaknesses, particularly the absence of control groups and/or the use of criterion samples already suffering from malignancies. In the present study, the psychiatric diagnoses and MMPI performances of psychiatric patients who later developed malignant and benign neoplasms were compared to controls. No differences (beyond a chance level) appeared in the diagnostic composition, the MMPI clinical scale scores, or the individual MMPI-item performances of the groups. Results do not offer support for the major psychogenic-origin theories of the development of neoplasms. (15 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A note on psychosomatic factors in the etiology of neoplasms.

C. G. Watson and D. Schuld (see record 1978-03712-001) attempted to study the relationship between psychopathology and subsequent development of neoplasms. It is argued that their results, which indicated no apparent connections between these variables, are limited due to methodological flaws, both relating to sample selection. Though there is no empirical evidence of psychological causation of neoplasms, the Watson and Schuld study is not the one to lay this issue to rest. (2 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

L-tryptophan and the eosinophilia-myalgia syndrome: current understanding of the etiology and pathogenesis

The eosinophilia-myalgia syndrome (EMS) is a newly recognized illness that occurred in an epidemic form during the summer of 1989. The illness was characterized in the acute phase by myalgia and eosinophilia, followed in many patients by chronic cutaneous lesions, progressive neuropathy, and myopathy. EMS was associated with ingestion of L-tryptophan, an essential amino acid marketed as a nutritional supplement but widely used as a therapeutic agent. Evidence of abnormal L-tryptophan metabolism has been described in patients with EMS, and most likely reflects increased activity of indoleamine 2,3-dioxygenase, the rate-limiting enzyme of tryptophan metabolism. A contaminant identified in EMS-associated L-tryptophan preparations has been isolated and characterized, but its biologic effects and role as the etiologic agent in EMS remain to be established. Pathologic observations and experimental studies indicate that eosinophils, mononuclear inflammatory cells, and fibroblasts are potential effector cells, and interleukin-5 and transforming growth factor-beta are important mediators in the pathogenesis of the syndrome. Although few new cases of EMS occurred following the withdrawal of L-tryptophan, affected patients continue to manifest late sequelae of the disease, including dermal fibrotic conditions. This tragic outbreak of a newly recognized illness has focused interest on the role of chemical and environmental agents in the pathogenesis of various idiopathic illness characterized by tissue inflammation and fibrosis.     

Advances in the study of the etiology and pathogenesis of middle ear cholesteatoma

Ninety-three consecutive treadmill exercise stress test were performed for the assessment of peripheral vascular function. Thirty-one were for atypical claudication-like symptoms including pain on standing, relief on sitting and back pain. Pedal pulses were palpable in 24 patients. Twenty-five patients (81%) had a negative stress test, suggesting a non-vascular aetiology and this finding was subsequently confirmed in 24 of the 25. The final diagnoses were spinal stenosis 13, [CT = 3, myelogram = 5, neurosurgeon opinion = 4, MRI = 1], myositis 2, restless leg syndrome 2 and osteoarthritis 7. Four patients had symptoms due to a combination of peripheral occlusive arterial disease and spinal stenosis; the latter was considered the predominant disorder in all four. Of the original 31 patients with atypical symptoms, spinal stenosis was present in 13 (42%). Atypia- in the common syndrome of intermittent claudication should alert the surgeon to the possibility of spinal canal disorders. Further investigation may identify significant pathology spinal stenosis in particular.     

A newly recognized entity: intraductal "oncocytic" papillary neoplasm of the pancreas

Intraductal papillary-mucinous tumors of the pancreas are increasingly recognized, and their characteristic endoscopic and radiological features are well reported in the literature in recent years. Oncocytic features in these tumors are uncommon and unrecognized. Intraductal oncocytic papillary neoplasm is a distinct pancreatic tumor and is a recently recognized entity. We report a case of a 69-yr-old patient who presented with symptoms mimicking pancreatitis, resulting in delay in the diagnosis of her pancreatic tumor. She underwent a successful Whipple's procedure and subsequently has remained well. The resected specimen showed an intraductal oncocytic papillary-mucinous neoplasm. The entity is new and the literature information is inadequate at present to judge the biological behavior of this tumor. We discuss this recently recognized entity.     

The role of genetic factors in the pathogenesis of thyroid neoplasms

This paper summarizes the current knowledge on the role of genetic factors in the development of thyroid neoplasms. The introduction of the methods and concepts of molecular genetics (as, e.g. recombinant DNA technology) have elucidated etiopathogenesis of the majority of thyroid tumours and, in the future, can make the diagnosis easier. Mutations of genes involved in the control of cellular growth and/or differentiation (ras, c-myc, RET, met) affect the development of thyroid neoplasms. Loss of heterozygosity (LOH) may suggest the presence of tumor suppressor genes and has been reported in thyroid follicular carcinomas. Activation of tyrosine kinase, whether by specific oncogene amplification or by rearrangement, appears to be highly specific for the transformation of thyroid follicular cells into papillary tumours. Cytogenetic studies have shown frequent clonal abnormalities in thyroid follicular adenomas and carcinomas.     

Pancreatic mucinous ductal ectasia and intraductal papillary neoplasms. A single malignant clinicopathologic entity

OBJECTIVE: The purpose of the study is to review a single institutional experience with mucinous ductal ectasia (MDE) and intraductal papillary neoplasms (IPNs) and to compare the clinicopathologic features of the two groups of tumors. SUMMARY BACKGROUND DATA: Mucinous ductal ectasia and IPNs represent newly recognized categories of pancreatic exocrine tumors, previously confused with pancreatic cystic neoplasms. The natural history of MDE and IPN is not well understood, and it is unclear whether MDE and IPN represent two distinct tumors or the same clinicopathologic entity. METHODS: The authors reviewed the clinical presentation, treatment, histopathology, and outcomes of 23 patients diagnosed with MDE or IPN at their institution over the past 6 years. RESULTS: The mean age at presentation for the cohort of patients with MDE and IPN was 62.5 years. The prevalence of abdominal pain was 75%, jaundice 25%, weight loss 42%, steatorrhea 37.5%, diabetes 37.5%, and history of pencreatitis 29%. Serum CA 19-9 levels ranged from 0 to 5350 units/mL with high levels reflecting advanced disease. There were no significant differences between MDE and IPN with respect to these parameters. Both MDE and IPN comprised papillary villous epithelial neoplasms involving the main and large pancreatic ducts. The tumors ranged from a few millimeters in size to panductal and were distinguished easily from cystic neoplasms in all cases. Invasive carcinoma was present in 11 (46%) of 24 patients, carcinoma in situ in an additional 10 (42%) of 24 patients, and low grade dysplasia in the remaining 3 (12%) of 24 patients. Mucinous ductal ectasia and IPN differed histopathologically only in degree of mucin secretion and tumor location. Mucinous ductal ectasia, but not IPN, was characteristically mucin-hypersecreting and more frequently involved the head of the gland than did IPN (11/16 vs. 1/8 p < 0.04). All patients were explored surgically and 20 (83%) of 24 of the tumors were resectable with frozen section control of the duct margins (9 pancreatoduodenectomies, 4 distal pencreatectomies, 7 total pancreatectomies). Despite the 88% prevalence of cancer, the overall survival at a mean follow-up of 21 months was 13 (87%) of 15 for MDE and 5 (71%) of 7 for IPN. CONCLUSIONS: Intraductal papillary neoplasms with or without MDE represent a spectrum of main duct papillary tumors ranging from adenoma to carcinoma with differing amounts of extracellular mucin production. Malignant IPNs with or without MDE typically exhibit extensive intraductal growth but are slow to invade the periductal tissues and slow to metastasize. The majority of patients with these tumors have resectable disease and a favorable prognosis; endoscopic therapy is inappropriate. The encompessing term intraductal papillary-mucinous tumors is appropriate.     

Motor neuron disease: etiology, pathogenesis and treatment--a review

This study was conducted in order to determine the effects of body position on integrated electromyographic (IEMG) activity of sternocleidomastoid and masseter muscles in 17 patients with myogenic cranio-cervical-mandibular dysfunction. EMG recordings at rest and during swallowing of saliva and maximal voluntary clenching were performed by placing surface electrodes on the sternocleidomastoid and masseter muscles (contralateral to the habitual side of sleeping of each patient), in the following body positions: standing, seated, supine, and lateral decubitus position. Significant higher EMG activities were recorded in the sternocleidomastoid muscle in the lateral decubitus position and in the supine position (except during swallowing), whereas a significant higher EMG activity was recorded in the masseter muscle during maximal voluntary clenching in standing and seated positions. The EMG pattern observed suggests that the presence of parafunctional habits and body position could be closely correlated with the clinical symptomatology in the sternocleidomastoid and masseter muscles at wakening and during waking hours, respectively, in patients with myogenic cranio-cervical-mandibular dysfunction.     

Ductectatic mucinous cystic neoplasms of the pancreas: evaluation with MR cholangiopancreatography

OBJECTIVE: The aim of the present study was to investigate the efficacy of two frequently used physiotherapies (PTs) for the removal of bronchial secretions in cystic fibrosis (CF) lung disease: autogenic drainage (AD) and the Flutter (Desitin in Germany). AD is believed to improve mucus clearance from peripheral to central airways due to airway caliber changes in combination with a special breathing technique. The Flutter is an easy-to-use physiotherapy device based on oscillations of a steel ball during expiration through a pipe-type device. MATERIALS AND METHODS: To evaluate the acute and chronic physiotherapy effects of these two techniques, 14 CF patients underwent either twice daily AD or Flutter treatment for 4 consecutive weeks in a randomized crossover design. Prior to each therapy interval, for a 1-week wash-out period, no PT was administered, but patients continued regular medication. At the beginning and end of each 4-week interval, pulmonary function was measured before and after an acute 30-min therapy. At the end of the PT session, sputum was collected, weighed, and deep frozen until analyzed. The viscoelasticity of the sputum was evaluated using a magnetic microrheometer. RESULTS: No significant changes were noted for FVC, FEV1, or sputum volume throughout the study. Sputum viscoelasticity (rigidity index), however, was significantly lower (p<0.01) after therapy with the Flutter in comparison with AD, predicting improvements in mucociliary and cough clearability of the secretions. In a companion in vitro experiment, oscillations generated by passing humidified air over CF sputum lining an acrylic tube connected to a Flutter de-ice were found to decrease sputum elasticity, as measured by a filancemeter. These findings suggest that applied oscillations are capable of decreasing mucus viscoelasticity within the airways at frequencies and amplitudes achievable with the Flutter device, and provide direct evidence that PT can reduce the viscoelasticity of sputum.