Implementation of a pharmaceutical care programme for patients receiving new molecular-targeted agents in a clinical trial unit.

A pharmaceutical care programme was implemented at our hospital in early 2013. The main objectives were to analyse and describe the pharmaceutical interventions made, to calculate adherence, interventions and to evaluate patient satisfaction with the care programme. We performed a single-centre descriptive and prospective intervention in cancer patients who received oral chemotherapy as part of a clinical trial in 2013. Eighty-three patients were included. Median age was 58 years (range, 31-80) and 42 patients (50.6%) were men. We recorded 23 interventions, 13 of which were associated with drug interactions. The mean percentage of adherence was 98.9%. The interview with the pharmacist was considered to be very important by 84.6% of the respondents. A total of 92.3% said that they would like to speak to the pharmacist at subsequent visits. The doubts detected during the visits enable us to conclude that the information patients receive with respect to their study medication is usually incomplete. An integrated pharmaceutical care programme for cancer patients participating in clinical trials with oral cytostatic drugs was successful in terms of adherence and patient satisfaction and makes it possible to guarantee the safety and effectiveness of treatment on an individual basis.

A self-adaptive hardware with resistive switching synapses for experience-based neurocomputing.

Neurobiological systems continually interact with the surrounding environment to refine their behaviour toward the best possible reward. Achieving such learning by experience is one of the main challenges of artificial intelligence, but currently it is hindered by the lack of hardware capable of plastic adaptation. Here, we propose a bio-inspired recurrent neural network, mastered by a digital system on chip with resistive-switching synaptic arrays of memory devices, which exploits homeostatic Hebbian learning for improved efficiency. All the results are discussed experimentally and theoretically, proposing a conceptual framework for benchmarking the main outcomes in terms of accuracy and resilience. To test the proposed architecture for reinforcement learning tasks, we study the autonomous exploration of continually evolving environments and verify the results for the Mars rover navigation. We also show that, compared to conventional deep learning techniques, our in-memory hardware has the potential to achieve a significant boost in speed and power-saving.

Ascites revealing peritoneal and hepatic extramedullary hematopoiesis with peliosis in agnogenic myeloid metaplasia: case report and review of the literature.

A 61-year-old man presented with ascites in the course of agnogenic myeloid metaplasia (AMM). Ascitic fluid was exudative and contained mature and immature leukocytes, erythroid cells, and megakaryocytes as observed on a bone marrow smear. Peritoneal biopsy showed myeloid metaplasia, and liver biopsy revealed intrasinusoidal myeloid metaplasia and peliosis. Ascites cleared after abdominal radiotherapy but treatment resulted in transient aplasia. Subsequently, portal hypertension was demonstrated by hepatic transjugular catheterization. Complications of splenomegaly led to splenectomy and splenorenal shunt followed by fatal acute hepatitis and septic shock. A review of the literature and an analysis of mechanisms of ascites occurring in AMM, especially peritoneal implants of myeloid tissue and occurrence of peliosis in myeloproliferative disorders, are presented.

Superficial squamous cell carcinoma of the esophagus. A report of 76 cases and review of the literature.

Superficial squamous carcinoma of the esophagus, defined as carcinoma limited to mucosa or submucosa regardless of lymph node status, is being increasingly recognized in the Western hemisphere. Seventy-six cases of this entity are herein presented. Five macroscopic types were recognized: normal flat (eight cases), coarse (21 cases), verrucous (25 cases), polypoid (17 cases), and ulcerating infiltrating (five cases). Histological typing included 65 conventional squamous cell carcinomas, six squamous carcinomas with spindle cell features, and five adenoid cystic carcinomas. Four cases were strictly intraepithelial, 10 cases were confined to the mucosa, nine cases encroached onto the muscularis mucosae, and 53 extended into the submucosa. Cases with intraepithelial and infiltrating carcinomas confined to the mucosa showed no lymph node involvement. Thirty percent of cases extending into the submucosa developed lymph node metastases. Thirty-eight patients survived surgical resection from 1 to 96 months; 34 of these 38 were free of neoplastic disease. Fourteen patients had an associated bronchial or oropharyngolaryngeal carcinoma either simultaneously or asynchronously. We conclude that patients with superficial squamous carcinoma of the esophagus can benefit from early diagnosis and prompt surgery.

Pathological features and mucin histochemistry of primary gastric stump carcinoma associated with gastritis cystica polyposa. A study of six cases.

Six unusual cases of primary gastric stump carcinoma associated with gastritis cystica polyposa and arising in old gastrojejunostomy stomas are presented. The clinical data, the gross and microscopic pathological features, and the histochemical mucin profile of these two lesions are described in detail. A review is undertaken of the most relevant and previously published reports concerning, separately, either primary gastric stump carcinoma or gastritis cystica polyposa. The findings available in these reports are compared with those observed in our six cases. Some aspects of gastritis cystica polyposa are not unlike those seen in the solitary ulcer syndrome of the rectum and Ménétrier's disease. The histological type and mucin profile of primary gastric stump carcinoma parallel those recorded in gastric cancer arising in the unoperated stomach. However, the role of intestinal metaplasia and its histochemical typing appear somewhat different in primary gastric stump carcinoma.

Intraductal papillary mucinous tumors of the pancreas confined to secondary ducts show less aggressive pathologic features as compared with those involving the main pancreatic duct.

Intraductal papillary mucinous tumors (IPMTs) of the pancreas are rare tumors characterized by a malignant potential. Because of the progress of imaging procedures, smaller cystic pancreatic lesions are now detected and some of them correspond to IPMTs that involve ectatic pancreatic branch ducts but spare the main pancreatic duct. To investigate differences in morphology and clinical behavior of branch and main duct types of IPMT, a surgical series of 43 cases was studied. All pathologic specimens of IPMT, surgically resected in our institution between October 1987 and July 1998, were analyzed. In all cases, the entire pancreatic specimen was systematically examined. IPMT of the branch type was found in 13 (30%) patients, whereas IPMT of main pancreatic duct type that involved the main pancreatic duct and branch ducts was observed in 30 (70%) patients. Patients with IPMT of the branch type were younger (median age, 55 yrs vs 64 yrs), and all but one of the lesions were located in the head and neck of the pancreas (vs 17 of 30 patients with the main duct type). The size of the cysts ranged from 4 to 55 mm, and the major duct showed a mild dilation in most cases. In contrast to the main pancreatic duct type, which showed invasive carcinoma and in situ carcinoma in 11 (37%) of 30 patients and 6 (20%) of 30 patients, respectively, IPMT of the branch type showed significantly less aggressive histologic lesions with five (39%) patients with simple hyperplasia, six (46%) patients with atypical hyperplasia, and two (15%) patients with in situ carcinoma. No invasive carcinoma was observed in this group. IPMT of the branch type occurs in younger patients and is associated with less aggressive histologic features than is the main pancreatic duct type. Our findings raise the difficult issue of clinical management of IPMT of the branch type as a distinctive group.

Recurrence of Fabry's disease in a renal allograft eleven years after successful renal transplantation.

A case of Fabry's disease in a renal transplant recipient with a follow-up period of 11 years is reported. The patient suffered from renal, skin, peripheral nerve lesions, and asymptomatic cardiomegaly. Fabry's disease symptoms disappeared after transplantation. Improvement of renal function was rapidly observed, and it remained satisfactory during the whole posttransplantation period. The patient died of a severe, uncontrolled infection and of biliary peritonitis. Autopsy showed a polyvisceral accumulation of sphingolipids deposits. The engrafted kidney was histologically free of disease. Ultrastructurally, it revealed numerous sphingolipid inclusions in the endothelial cells of capillaries. The explanation of this complication could be attributed to: (1) high circulating levels of plasma substrates locally overwhelming the enzymatic capability of the graft endothelial cells; and (2) the endothelial cells originated from the recipient but not from the donor, an occurrence that has been described after transplantation. Rejection and the newly formed deposits in the endothelial cells may lead to the loss of the engrafted organ. As a consequence of the increasing possibility of organ transplantation, this complication should be detected by studying the blood vessels ultrastructurally in order to evaluate the condition of the transplant.

Gastrointestinal Richter's syndrome.

The development of a diffuse large cell lymphoma of the stomach in a patient who had chronic lymphocytic leukemia is reported. Richter's syndrome localized to the gut has not been described previously. Morphologic and immunologic studies suggest that the diffuse large cell lymphoma arose from the same clonal proliferation, IgG lambda, as the initially detected serum monoclonal protein associated with the chronic lymphocytic leukemia.

The ciliated hepatic foregut cyst, an unusual bronchiolar foregut malformation: a histological, histochemical, and immunohistochemical study of 7 cases.

The ciliated hepatic foregut cyst is an unusual solitary cystic lesion of the liver. In a series of 7 cases of hepatic ciliated cysts, we performed a histological, histochemical, and immunohistochemical study to better define the histogenesis of this rare entity. The patients were 4 women and 3 men, aged 39 to 75 years. Four patients presented with abdominal pain. In 3 cases the cyst was discovered incidentally on ultrasonography. The cysts measured from 1 to 4 cm in diameter. Microscopically, the lining of the columnar epithelium was composed of ciliated cells and mucin secreting goblet cells. The wall was composed of bands of smooth-muscle fibers surrounded by an outer fibrous capsule. The goblet cells stained with PAS, alcian blue, and high-iron diamine. The immunohistochemical study showed that endocrine cells were present within the cyst epithelium, positive for chromogranin, synaptophysin, bombesin, and calcitonin, and negative for serotonin, somatostatin, glucagon, insulin, gastrin, and pancreatic polypeptide. In all the cases, immunoreactivity of some cells for CC10 strongly suggested the presence of Clara cells. Our study shows that the epithelium lining ciliated hepatic foregut cysts has histological, histochemical, and immunohistochemical features similar to those observed in the bronchiolar epithelium. This lesion is a developmental ventral foregut abnormality that could arise from a bronchiolar bud of the tracheobronchial diverticulum.

Tracheal malacoplakia.

Malacoplakia is a rare granulomatous disease well described in the urinary tract but which rarely involves the lung. We report for the first time, to our knowledge, tracheal localization of this unusual disorder. The larynx and probably kidneys were also involved. Differential diagnosis, physiopathology, and treatments are discussed.

Lymphoid stromal reaction in gastrointestinal lymphomas: immunohistochemical study of 14 cases.

The lymphoid stromal reaction, particularly the T lymphoid reaction, was studied immunohistochemically on cryostat sections in 14 cases of primary gastrointestinal B lymphomas, and compared with the type and distribution of lymphoid cells in three cases of gastric lymphoid hyperplasia. A pronounced T lymphoid reaction, mainly of the T helper phenotype, occurred in both lesions. Most of these T cells bore HLA-DR antigens, but only a few of them had the receptor for interleukin 2. The T lymphoid reaction was observed inside the lymphomas in seven of a total of 14 cases, and around the lymphomas in four of the six cases clinically classified as stage I. Perivascular mucosal and submucosal nodules, entirely composed of T cells, seemed characteristic of gastric lymphoid hyperplasias. A T lymphoid reaction in lymphoid hyperplasias suggests an amplification of the cell mediated immune response; in lymphomas it could represent a host reaction against the lymphomatous infiltrate, therefore favouring a better prognosis.

Role of nonesterified fatty acids in necrotizing pancreatitis: an in vivo experimental study in rats.

INTRODUCTION: In acute pancreatitis, nonesterified fatty acids (NEFA) might be released by lipase and cause tissue necrosis by their detergent properties, but this has not been established in vivo. AIMS: To measure the release of NEFA in the blood stream, pancreatic tissue, and peritoneal cavity during taurocholate-induced acute necrotizing pancreatitis in rats. METHODOLOGY: Ascites and blood were repeatedly sampled; after 24 hours, pancreatic lesions were scored, and NEFA were measured in the pancreas. The effects of a specific lipase inhibitor (Tetrahydrolipstatin [THL]) were also studied. RESULTS: A slight transient increase (22%) of NEFA concentration was observed in systemic circulation but did not parallel the time course of lipase activity, arguing against an intravascular production of NEFA by circulating lipase. Pancreatic NEFA did not differ between rats with pancreatitis and control rats. NEFA in ascites increased to threefold the basal value immediately after taurocholate and decreased rapidly thereafter, whereas lipase increased later in ascites and remained elevated during the 24-hour duration of the experiment. Lipase inhibition by THL neither modified the early increase of NEFA in ascites, nor altered the macroscopic, enzymatic, and histologic evolution of pancreatitis. CONCLUSION: This in vivo study does not confirm the hypothetical role of NEFA produced by pancreatic lipase in the necrotic process and its systemic complications, up to now mainly suggested on the basis of ex vivo experiments.

In vivo assessment of lipid peroxidation in experimental edematous and necrotizing rat pancreatitis.

Lipid peroxidation, which may be involved in the pathogenesis of acute pancreatitis, is usually assessed in vitro or indirectly using antioxidants or free radical scavengers. We assessed lipid peroxidation in an in vivo model by measuring ethane exhalation in two models of acute pancreatitis. Edematous acute pancreatitis was induced by a supramaximal intraperitoneal injection of cerulein. Necrotizing acute pancreatitis was induced by retrograde infusion of sodium taurocholate into the pancreaticobiliary duct. Rats were placed in closed chambers and ethane exhalation was measured in aliquots. Ethane exhalation was significantly increased (p < 0.002) in cerulein (n = 12)- but not in taurocholate (n = 6)-induced pancreatitis compared to controls (n = 12 and 6, respectively). Our results suggest that free radicals may play a role in the pathogenesis of edematous pancreatitis but do not play an important role in the progression to necrotizing pancreatitis.

Calcitonin-secreting tumors of the pancreas: about six cases.

Calcitonin release has rarely been reported in patients (pts) with neuroendocrine pancreatic tumors (NPT). The aim of this study was to describe the characteristics of calcitonin-secreting tumors (CST) of the pancreas. Serum calcitonin determination was part of the prospective evaluation of 66 pts with NPT referred to our institution over a 3-year period. Six pts (9%) had elevated calcitonin levels [at least twice the limit of the normal value (N)]. Abdominal ultrasonography, computed tomography scan, and endoscopic ultrasound were performed to identify the primary tumor(s) and metastases. Immunostaining using anticalcitonin and other antibodies was performed on the surgical resection specimen (four pts) or biopsy of liver metastases (two pts). Three of the six pts (four males, two females; median age, 51.5 years) had diarrhea. Serum calcitonin levels (median, range) were 17.5 N (6N-40N). Slight elevations in serum somatostatin (1.2N-2.3N) were associated in three pts. Pancreatic tumors were single in five of six pts and evenly distributed in the head and in the tail. Five pts had metastases, mainly in the liver. Multiple endocrine neoplasia type I was present in one pt. Immunostaining using calcitonin and somatostatin antibodies was positive in four pts each, respectively, and areas that were positive for one peptide were negative for the other. Diarrhea disappeared in the two pts who responded to treatment of the tumor(s). Three of the four pts with liver metastases died from tumor progression after 2, 10, and 24 months, respectively. CST of the pancreas are often malignant and can be considered as functional in half of the cases, irrespective of the serum calcitonin levels. Somatostatin secretion is often associated. Although rare, calcitonin secretion should be investigated in NPT pts presenting with diarrhea that cannot be explained by an increase in other hormone levels or in patients with nonfunctioning NPT.

Pleomorphic carcinoma of the small bowel. The limitations of immunohistochemical specificity.

We report 3 cases of poorly differentiated tumors of the small bowel with histological, immunohistochemical, and ultrastructural studies. The patients were male, aged 45, 57, and 63. In all 3 cases, histological features of spindle cell, epithelioid cell and giant cell areas favoured a diagnosis of carcinoma, although a malignant stromal tumor could not be firmly excluded. Immunohistochemistry demonstrated in the 3 cases a strong expression of both "epithelial" (cytokeratin) and "stromal" (vimentin) markers; one tumor expressed the epithelial membrane antigen, and another one desmin. Electron microscopy showed no specific features in one case. The case positive for desmin demonstrated intracytoplasmic lumina, allowing the diagnosis of carcinoma. In spite of a non-specific immunohistochemical pattern, we finally considered these 3 tumors as of epithelial origin, corresponding to the rare and recently described pleomorphic carcinoma of the small bowel. This report emphasizes the difficult diagnosis of some poorly differentiated tumors, particularly in the gastro-intestinal tract. Such problems had until recently been resolved by ultrastructural and mostly by immunohistochemical studies. However, an increasing number of reports, together with our 3 cases, show unexpected reactivity of tumors with theoretically specific immunoreactions, such as those directed against intermediate filaments. Coexpression of intermediate filaments could be due to cross reactivity of molecules bearing common epitopes, or to the presence of different filaments in the same cell type; recent immunoblotting studies favour this latter hypothesis.

Adenomas arising in Barrett's esophagus with adenocarcinoma. Report of three cases.

Adenocarcinoma of the esophagus is a well known complication of Barrett's esophagus, and results from a dysplasia-carcinoma sequence. This report describes 3 patients with adenomatous polyps arising in Barrett's esophagus. One patient presented with multiple sessile or pedunculated polyps giving a polyposis appearance; the other two patients had single polyps associated with distinct adenocarcinoma arising in Barrett's esophagus. Polyps consisted of adenomatous proliferation with adenocarcinoma in the 3 patients. Review of the literature identified twelve previously reported cases. These cases show that although rare, adenomas may arise in Barrett's esophagus, and are most likely premalignant lesions such as other adenomas of the gastrointestinal tract.

Collagenous colitis. Ultrastructural study and collagen immunotyping of four cases.

We studied four cases of collagenous colitis (CC), which is characterized by thickening of the subepithelial collagenous layer of the colorectal mucosa and is associated with chronic watery diarrhea. Eighteen cases of CC have been previously reported in the literature, to our knowledge. In our four patients, ultrastructural study and collagen immunotyping demonstrated that the basement membrane over the thickened collagen was normal. We found no similar collagenous thickening in a series of 96 biopsy specimens of chronic inflammatory bowel diseases, but collagenous thickening was noted in 17 (25%) of 68 colonic metaplastic polyps. The cause of CC is unknown. The pericryptal fibroblastic sheath of the colonic mucosa has a probable role in the development of CC and metaplastic polyps. The role of the numerous mast cells present in our four cases of CC is currently unknown.

Epithelioid hemangioendothelioma, multiple focal nodular hyperplasias, and cavernous hemangiomas of the liver.

Malignant vascular neoplasms of the liver are uncommon. We report the case of a young woman who developed an epithelioid hemangioendothelioma of the liver associated with multiple focal nodular hyperplasias and hepatic cavernous hemangiomas. Such an unusual association is probably not fortuitous and could support the theory that focal nodular hyperplasia is a reaction to an abnormal vascular supply rather than a true neoplasm.

[Focal lymphoid hyperplasia (pseudolymphoma) of the terminal ileum in adults]. / Hyperplasie lymphoïde focale (pseudo-lymphome) de l'iléon terminal chez l'adulte.

We report two cases of focal lymphoid hyperplasia (FLH) of terminal ileum in adult patients. Both cases showed identical morphological findings. The first was discovered during cholecystectomy in a 75-year-old woman who complained mild non-specific abdominal discomfort. The second was manifested by right lower quadrant abdominal pain in a 32-year-old man. The surgical specimens revealed a thickened wall, a narrowed lumen and multiple ulcerations. The histologic features were small cell, well differentiated lymphocyte infiltration, with several follicles showing large germinal centers; regional lymph nodes revealed a conspicuous reactive size enlargement. Further clinical investigations revealed no other abnormalities. Clinical course showed benign evolution after 6 and 3 years of respective follow-up. FLH should be differentiated from terminal ileum inflammatory and infectious diseases. It can be differentiated from Crohn's disease by the absence of characteristic histological features; from Yersinia infection by the absence of significant rates of specific serum antibodies. Moreover, FLH can be differentiated from malignant lymphoma by the presence of follicles and enlarged germinal centers and by the long-term benign evolution. The nature of FLH in terminal ileum, as well as those of the stomach and colo-rectum is still to be determined. Several hypothesis are proposed: reactive, benign neoplastic, or prelymphomatous lesion?

[Intramural diverticulosis and cancer of the gallbladder]. / Diverticulose intramurale et cancer de la vésicule biliaire.

Two cases of gallbladder carcinoma occurring in intramural diverticulosis (adenomyomatosis) are reported. The first was adenocarcinoma associated with cholesterolosis without gallstone formation. The second was squamous cell carcinoma. Four other carcinomas developing on diverticulosis were reported in the literature, none of them being squamous cell carcinoma. Our cases and those of the literature show that diverticulosis, a benign condition, can be associated with carcinoma which can make the pathological diagnosis difficult.