The Trend of CEACAM3 Blood Expression as Number Index of the CTCs in the Colorectal Cancer Perioperative Course.

Pathological stage seems to be the major determinant of postoperative prognosis of solid tumors, but additional prognostic determinants need to be better investigated. The most important tumor marker for colorectal cancer (CRC) is the cell-surface antigen, Carcinoembryonic Antigen (CEA), and its assessment is considered a valuable index of circulating tumor cells (CTCs). In this paper, CEACAM3 evaluation was applied given its great specificity in the CRC. Whole blood from the basilic vein of 38 CRC patients was collected before and at various time intervals after the curative resection. Also, from 20 of them, we have obtained two additional intraoperative samples. CEACAM3 expression was evaluated in all the samples by RT-PCR. CEACAM3 duct values showed a decreasing trend from preoperative through early and later postoperative to 6th-month samples (p < 0.001). The average values of CEACAM3 were related to the cancer size (T stage) (p = 0.034) and WHO stage (p = 0.035). A significant effect of the baseline value of CEACAM3 dCt on the temporal trend has been observed (p < 0.001). In this study, we have demonstrated the CEACAM3 specificity and a perioperative trend of CTCs which is coherent with the clinical/pathological considerations and with previous experimental findings in different cancer types.

Transverse loop colostomy and colonic motility.

BACKGROUND: The motility of the defunctionalized colon, distal to transverse loop colostomy, has never been studied "in vivo." The aim of our study was to evaluate the influence of transverse loop colostomy on colonic motility. METHODS: Thirteen patients were examined before stoma closure by means of clinical evaluation and colonic manometry; we studied both the right and distal colon in both fasting and fed patients in order to detect motor activity. RESULTS: Quantitative and qualitative manometric analyses showed that the diverted colon had motor activity even if no regular colonic motor pattern was observed. The spreading of aboral propagated contractions (PCs) was sometimes recorded from the right colon to the distal colon. The response of the proximal and distal colon to a standard meal, when compared to fasting values, increased more than 40 and 35 %, respectively. Stool and gas ejections from the colostomy were never related to a particular type of colonic motility: Motor quiescence such as PCs was chaotically related to stool escape. CONCLUSIONS: In conclusion, motility of the defunctionalized colon is preserved in patients with transverse loop colostomy.

Gemcitabine plus irinotecan as first-line weekly therapy in locally advanced and/or metastatic pancreatic cancer.

Single-agent gemcitabine has been established as standard treatment for advanced pancreatic cancer since clinical studies have shown an improvement in overall survival and significant clinical benefit when compared to the best supportive care despite low overall objective response. Several phase II studies have tested other single agents and different gemcitabine-based regimens in pancreatic cancer, but both response and survival rates have remained low. Irinotecan, a topoisomerase I inhibitor currently approved for the treatment of metastatic colon cancer, has also demonstrated improved response rate in patients with pancreatic cancer. Our purpose was to determine the activity and toxicity of this regimen in patients with unresectable or metastatic pancreatic cancer. Patients with histologically confirmed pancreatic adenocarcinoma received gemcitabine 1000 mg/m2 plus irinotecan 100 mg/m2 IV on days 1, 8, and 15 of a 28-day cycle for 6-8 months. From February 2004 to April 2006, 33 patients were entered into this study, 32 of whom were evaluable for treatment response, toxicity, median time to progression, and median survival. Characteristics included a median age of 63 years (range 41-79), 21 males (64%), and 12 females (36%). One patient discontinued treatment due to adverse effects. The total number of cycles administered was 188 and the median number of cycles for patients was 5.6 (range 2-7). Thirty-two patients were assessable for toxicity and response. Grade 3 hematological toxicity occurred in 9% of patients and was primarily neutropenia. No grade >2 gastrointestinal toxicities or death due to treatment were observed. The most frequent nonhematological adverse event was fatigue. Ten patients responded to treatment with two complete responses (6.3%) and eight partial responses (25.0%), for an overall response rate of 31.3%; 11 patients achieved stable disease (34.3%). The median time to tumor progression and the median survival were 9.2 (95% CI: 6.0-12.4) and 11.8 (95% CI: 7.7-15.9) months, respectively, with a 2-year survival of 22%. On the basis of this trial, the combination of gemcitabine plus irinotecan, administered in a weekly schedule and at this dose, is well tolerated and offers encouraging activity in the treatment of advanced and/or metastatic pancreatic cancer.

Key factors for best control of the systemic leakage during hyperthermic isolated limb perfusion (HILP) in ECC. A critical synthesis of our experience.

The L-PAM-ILP procedures under true hyperthermal regime (41.5-41.8 degrees C) require both close control of the physical parameters of the treatment (temperatures profiles and time duration, artero-venous pressure, perfusate flow rate) and medical rationale (drug, dosage, fractioning, timing). All the above essential procedures must be supported by rigorous methodology, reliable operation of the medical devices and apparatus and real-time monitoring of the treatment parameters. Real-time monitoring is essential for proper trimming and modulation of the parameters during treatment. This paper delineates the technical improvements that we have implemented for drug leakage monitoring and control in the systemic circulation aimed at improving the therapeutic efficacy and at reducing the occurrence of unexpected complications.

Advanced thyroid carcinoma: an experience of 385 cases.

AIMS: To report clinical outcomes of a large series of cases with advanced thyroid cancer. STUDY DESIGN: Three hundred and eighty-five patients at the UICC stages III and IV were selected for the study with thyroid cancer. RESULTS: Papillary carcinoma and sclerosing carcinoma have better survival than the Hürthle cell and insular types. Lymphatic metastasis does not appear to worsen the prognosis. All the tumour forms offer the chance of long survival. CONCLUSIONS: Surgical treatment is the primary treatment of thyroid carcinoma. The combined treatments of surgery, metabolic beam therapy, suppressive hormone therapy, radiotherapy and chemotherapy cure a high percentage of patients with the tumour at an advanced stage.

Dislocation of central venous catheters in paediatric patients.

Children have limited venous access possibilities; therefore, when long-term therapy is necessary, it is better to place a catheter in a central vein. The Port catheter, totally implanted, is less exposed to the risk of infection and permits a normal life. However, there is the possibility of the displacement or fragmentation of the catheter that can be diagnosed initially only by clinical symptoms and later by a chest X-ray. We report a case of disconnection between the Port catheter and the reservoir resulting in catheter migration to the left pulmonary artery.

Clinical efficacy and tolerability of nimesulide compared with naproxen in the treatment of posthaemorrhoidectomy pain and inflammation.

The efficacy and tolerability of nimesulide and naproxen were compared in a randomised double-blind study of patients with pain and inflammation after haemorrhoidectomy. Both drugs appeared similarly effective in reducing pain and oedema and no adverse reaction was detected. These data extend the information on the anti-inflammatory and analgesic efficacy of nimesulide in the postoperative setting.

Interstitital cells of Cajal in the human stomach: distribution and relationship with enteric innervation.

Interstitial cells of Cajal (ICC) are distributed throughout the gastrointestinal muscle coat with a region-specific location, and are considered to be pace-maker and/or mediators of neurotransmission. Little is known about their shape, size, distribution and relationships with excitatory and inhibitory nerves in human stomach. With this aim, we labeled the ICC, using c-Kit immunohistochemistry, followed by a quantitative analysis to evaluate the distribution and area occupied by these cells in the circular and longitudinal muscle layers and at the myenteric plexus level in the human fundus, corpus and antrum. Furthermore, by NADPH-d histochemistry and substance P (SP) immunohistochemistry, we labeled and quantified nitric oxide (NO)-producing and SP-containing nerves and evidenced their relationships with the ICC in these three gastric regions. In the fundus, the ICC appeared as bipolar cells and in the corpus and antrum they mainly appeared as multipolar cells, with highly ramified processes. The networks formed by ICC differed in the three gastric regions. The ICC number was significantly higher and cell area smaller in the fundus compared to the corpus and antrum. The area occupied by the ICC was significantly higher at the myenteric plexus level compared with circular and longitudinal muscle layers. Everywhere, NADPH-d-positive nerves were more numerous than SP-positive ones. Both kinds of fibers were closely apposed to the ICC in the corpus and antrum. In conclusion, in the human stomach, the ICC have region-specific shape, size and distribution and in the corpus and antrum have close contact with both inhibitory and excitatory nerves. Presumably, as suggested for laboratory mammals, these differences are in relationship with the motor activities peculiar to each gastric area.

Gastric symptoms and duodenogastric reflux in patients referred for gastroesophageal reflux symptoms and endoscopic esophagitis.

BACKGROUND: The role of excessive duodenogastric reflux (DRG) in the genesis of gastric symptoms in patients primarily referred for both gastroesophageal reflux (GER) symptoms and esophagitis is poorly understood. METHODS: The study is based on the clinical, endoscopic, histologic, and 24-hour gastric data from the Bilitec optoelectronic device (Prodotec, Florence, Italy, licensed by Synectics Medical, Stockholm, Sweden) from 49 patients having both typical GER symptoms and gastric symptoms suggestive of excessive DGR (i.e., epigastric pain, nausea, or bilious vomiting) in the absence of previous esophageal or gastric surgery (group 1). Helicobacter pylori organisms were searched for on antral biopsy specimens with use of the Giemsa method. The percentages of total, upright, and supine time during which absorbance exceeded various thresholds through all the working range of the Bilitec device were calculated. Bilitec data from group 1 were compared with those from 16 patients with endoscopic esophagitis and GER symptoms only (group 2) and 25 healthy subjects (group 3). RESULTS: The prevalence of an abnormal Bilitec test result in group 1 increased from 27% (13/49) at the 0.25 absorbance threshold to 36% (18/49) at thresholds ranging from 0.40 to 0.60 and to 41% (20/49) when multiple thresholds ranging from 0.25 to 0.60 were considered. In group 2 one patient had an abnormal Bilitec test result at the 0.25 to 0.30 threshold, whereas the other 15 patients had a normal test result. H pylori antral infection was present in 14 group 1 patients. None of these had an abnormal Bilitec test result, whereas the test was positive in 40% of the H pylori-negative patients without endoscopic gastritis and in 70% of H pylori-negative patients with endoscopic gastritis (P = .001). CONCLUSIONS: Twenty-four-hour intragastric bile monitoring provides the clinician with unequivocal evidence of excessive DGR in 41% of patients with an intact stomach having endoscopic esophagitis, GER symptoms, and gastric symptoms suggestive of DGR. The most dependable data are obtained when absorbance thresholds higher than 0.40 are considered. H pylori antral infection and excessive DGR at 24-hour intragastric bile monitoring are mutually exclusive.

Neuron density and distribution of NADPH-diaphorase positive neurons in the human stomach.

Neuron density and distribution of the NADPH-diaphorase positive neurons were studied in the fundus, corpus and antrum of adult human stomach using cresyl violet staining and NADPH-diaphorase histochemistry. The submucous plexus contained significantly less neurons than the myenteric plexus. Submucous NADPH-d positive neurons were mostly located in ganglia close to the circular muscle layer. Myenteric NADPH-d positive neurons represented 50-60% of the neurons in all the three regions; their density, however, was significantly lower in the fundus. NADPH-d positive fibers formed a rich plexus in the innermost portion of the circular muscle layer of the corpus.

Analysis of the optical properties of bile.

Invasive bile determination is very useful in the diagnosis of many gastric pathologies. At the moment, this measurement is performed with Bilitec 2000, an optical fiber sensor, that is based on absorption by bilirubin. Nevertheless, erroneous evaluations are possible, due to the different configurations which the bilirubin molecule can adopt. The optical behavior of human samples of pure bile and bile+gastric juice has been examined using an optical fiber spectrophotometer and two suitably modified Bilitec 2000 units. A protocol has been established for the treatment of biological fluids, in order to make it possible to study the behavior of their optical properties as a function of pH and concentration without causing any alteration in the samples. The analysis of pH dependence evidenced the presence of different calibration curves at different pH values: the self-aggregation of the bilirubin molecules observed in pure bile samples was almost totally absent in the gastric samples. Measurements carried out on Bilitec 2000 showed that the most appropriate wavelength for bilirubin detection in the stomach should be 470 nm.

Proliferative activity in normal colon mucosa and tumor tissue: clinical implications.

The study deals with the analysis of proliferative activity in colon carcinomas and adjacent normal appearing mucosa, evaluated with in vitro 3H-Thymidine and autoradiography. In the colonic mucosa no significant differences in 3H-Thymidine Labelling Index (TLI) were observed in relation to the distance of the sample from the neoplasia. The distribution of S-phase cells along the crypt length is low at the bottom, increases rapidly with a maximum within the lower 25% and decreases in the highest positions. When the proliferative activity is increased there is the possibility of expanding the proliferative compartment towards the luminal region of the crypt. The division of the crypt into 5 parts makes it possible to identify 2 different patterns: the first with a very high TLI in the lower fifth, then a sharp decrease and without labelled cells in the highest parts; the second with labelled cells present also in the luminal fifth. These 2 aspects are characteristic of specimens with the lowest and the highest TLI values respectively. The analysis of TLI in colo-rectal cancers shows that cell kinetics parameters are not related to clinical and histopathological features such as sex, age, Dukes and TNM stages and grade of differentiation.

Duodenogastric reflux of bile in health: the normal range.

Duodenogastric reflux (DGR) is suspected to be an aetiological factor in the pathogenesis of foregut disease. The 'Bilitec' bile probe allows continuous detection of bilirubin, based on spectrophotochemical properties. We aimed to describe duodenogastric bile reflux in healthy, normal volunteers in a Western European population, as a basis for the future study of DGR in disease. An international multicentre study was established. DGR was measured using 24 h ambulatory bile and pH monitoring in the proximal stomach, in 43 normal volunteers from the third to the seventh decades. Subjects adhered to a standard protocol. The total test period, supine and upright components, were analysed. The 90th percentile values for absorbance thresholds of 0.14, 0.25, 0.3, 0.4 and 0.5 were 40.5%, 20.9%, 19.6%, 11.6% and 4.6% of the total time respectively. There was a wide range of absorbance within each threshold. Supine DGR was greater than upright, and associated with an alkaline tide. The upright phase was further subdivided into upright fasting, prandial and post prandial phases, and ranges for these periods are also described. No relationship between age, weight, or body mass index and duodenogastric reflux was seen. The results of this study form a range which allows further investigation into the contribution of duodenogastric bile reflux in the pathogenesis of foregut disease.

Technical aspects and clinical indications of 24-hour intragastric bile monitoring.

Bilitec 2000 is a new device which spectrophotometrically detects the presence of bilirubin in the refluxate. It is, up to date, the only method able to monitor for 24 hours the exposure time of esophageal and/or gastric mucosa to bilirubin-containing reflux. From the technical point of view, a particularly relevant aspect is the necessity of associating pH and Bilitec monitorings. The reason why is that, even in the stomach where Bilitec itself is adequate for assessing the exposure time to duodenogastric reflux, the damaging capability of the different components of reflux strictly depends upon pH. The most correct position inside the stomach for gastric monitoring is the 5 cm-below-the-LES-distal-border-position. The diet needs to be standardized in order to avoid false positive results due to the ingestion of foods with absorption close to bilirubin absorption. Ranges of normality will soon be available from a collaborative European Study. At variance with the indications for esophageal monitoring which are wide (the same as for pH-monitoring), indications for gastric Bilitec monitoring are represented only by severe dyspeptic symptoms possibly related to duodenogastric reflux. An antrum-confined C gastritis in the absence of history of consumption of gastro-lesive drugs strongly suggests the possibility of duodenogastric reflux. In this case, Bilitec monitoring can provide further evidence by measuring the time of exposure of the gastric mucosa to reflux.

Combined 24-hour intraluminal pH and bile monitoring of the denervated whole stomach as an esophageal substitute.

BACKGROUND/AIMS: The study aims to evaluate the pH and the presence of bile in the denervated whole stomach pulled up to the neck after subtotal esophagectomy. METHODOLOGY: The pH and the presence of bile in the gastric cavity were monitored by combined 24-hour pH and bilimetry in 16 patients having their whole stomach as an esophageal substitute (i.e., 8 with and 8 without a gastric drainage procedure) and in 25 healthy control subjects. The percentage of time during which pH was < 2 as well as the percentage of time during which bile absorbance was > 0.25 for the total, upright, and supine periods of recording were considered for each subject studied. Seven patients underwent a gastroscopy with biopsies. RESULTS: Intragastric acidity was normal in 50% of patients while it was reduced in the other 50%. Ten of the 16 patients (62.5%), i.e., 4 with (50%) and 6 without (75%) a drainage procedure, had excessive exposure of the gastric mucosa to bile. No significant correlation was found between the existence of a high intraluminal pH profile and excessive bile exposure (p = 0.9163). Bile exposure was significantly higher in whole stomach patients than in controls in both the upright and supine positions, irrespective of the existence or absence of a drainage procedure (p ranging from 0.0272-0.0001). Bile exposure in the supine position tended to be longer in patients without than in those with a drainage procedure (p = 0.0929). Helicobacter pylori-negative chemical gastritis was present in 3 of the 7 patients who underwent a gastroscopy, all 3 having excessive bile exposure and no food retention in the transplant lumen. CONCLUSIONS: Gastric denervation and transposition up to the neck increased exposure of the gastric mucosa to bile, irrespective of the patient's position and of the presence of a gastric drainage procedure. The absence of gastric drainage procedure tends to ensure exposure to bile prolongeLow gastric acidity, if present, is due to a reduction in acid secretion rather than to a buffering effect from duodenal juice having refluxed. Gastritis is more likely to be related to excessive exposure of the gastric mucosa to bile than to food retention.

Gastric hyperplastic changes and thymidine uptake after partial gastrectomy in rats.

Foveolar hyperplastic changes have been recently considered to be the most distinctive histological findings following partial gastrectomy, and their relationship to bile reflux has been proven. The present study was undertaken in order to determine whether an increase in 3H-thymidine uptake, which is an expression of increased gastric mucosal proliferative activity, might correspond to these hyperplastic changes. Histology and thymidine uptake values were assessed and compared in nineteen rats operated upon either with a Polya gastrectomy (11) or with a Roux-en-Y biliary diversion (8). Thymidine uptake values and the extent of gastric hyperplastic changes were greater in the Polya than in the Roux-en-Y group. Moreover, a significant correlation was found between thymidine uptake values and the extent of hyperplastic changes. Therefore, the relationship between hyperplastic changes and increased mucosal proliferative activity post-gastrectomy would seem to have been proven. Since bile acids have been shown to be able to stimulate cell proliferation in ileal and colonic mucosa, a role for bile reflux in the increased cell proliferation activity in the gastric stump can be hypothesized.

Gastric hyperplastic changes and thymidine uptake after partial gastrectomy in rats.

Foveolar hyperplastic changes have been recently considered to be the most distinctive histological finding after partial gastrectomy, and their relationship with bile reflux has been proven. The present study was undertaken to establish whether an increase in 3H-thymidine uptake--which is an expression of increased gastric mucosal proliferative activity--might correspond to these hyperplastic changes. Histology and thymidine uptake values were assessed and compared in nineteen rats operated upon either by means of a Polya gastrectomy (11), or with a Roux-en-Y biliary diversion (8). Thymidine uptake values and the extent of gastric hyperplastic changes were greater in the Polya than in the Roux-en-Y group. Moreover, a significant correlation was found between thymidine uptake values and the extent of hyperplastic changes. The relationship between hyperplastic changes and post-gastrectomy increased mucosal proliferative activity would thus seem to have been demonstrated. Since bile acids have been shown to stimulate cell proliferation in ileal and colonic mucosa, a rôle for bile reflux can be hypothesized for the increased cell proliferation activity in the gastric stump.

Results in the radical surgical treatment of Crohn's disease.

A series of 60 patients were operated on, in our hospital, for Crohn's disease over a ten-year period. Three main groups of patients were distinguished according to the kind of intestinal involvement at surgery; those with the classical disease (involvement of the terminal ileum), those with Crohn's ileocolitis and those with Crohn's colitis. Operations, in which all the affected bowel with a free margin of at least 15 cm on each side of the lesions was resected, were considered "radical" surgical procedures. All patients who underwent surgery for the classical disease were treated radically and 54.4% of those affected with Crohn's ileocolitis underwent radical surgery. From our data early surgery seems to have an important effect upon radicality. In the follow-up study, mortality, percentage recurrence, quality of life and biochemical findings were separately assessed and evaluated for each group of subjects. Only radically operated subjects were evaluated for recurrence. The percentage recurrence was 12.9% in the classical disease group (mean postoperative follow-up time: 44.2 months), 27.3% in Crohn's ileocolitis group (mean follow-up time: 21.1 months), 0% in Crohn's colitis group (mean follow-up time: 61.5 months). Over-all operative mortality was 0%.

[Esophageal motor abnormalities, gastroesophageal reflux and duodenogastric reflux in patients with Raynaud's disease]. / Anomalie motorie esofagee, reflusso gastroesofageo e reflusso duodenogastrico in pazienti con fenomeno di Raynaud.

Twenty-four patients with Raynaud's phenomenon, without ARA criteria for classification, were examined, after clinical history, by means of esophageal manometry, combined gastric and esophageal pH-monitoring, endoscopy. The results showed in these patients a high incidence of esophageal motor abnormalities (66.6%), of gastroesophageal reflux (50%), and of duodenogastric reflux (45.8%).

[Barrett esophagus. Diagnosis and treatment]. / Esofago di barrett. Diagnosi e terapia.

Columnar epithelial metaplasia of the distal esophagus (i.e. barrett's esophagus) is an acquired condition showing a prevalence of 4%. It is probably due to abnormal reparative processes of the esophageal squamous epithelium after gastroesophageal reflux damage. "Mixed" (both acid and biliary) reflux seems more relevant for the pathogenesis of Barrett's esophagus than acid reflux alone, as shown by recent studies with Bilitec 2000. Its diagnosis is not easy for the "cardiac", "fundic" or "indeterminate" types of columnar metaplasia and needs a close cooperation between the endoscopist and the pathologist. On the contrary, it is less difficult for the "distinctive" type of metaplasia. Barrett's esophagus surveillance represents a major challenge in the perspective of its malignant degeneration (adenocarcinoma risk 350 times greater than in the general population). Therapy of Barrett's esophagus includes drugs and surgical treatment. Among the drugs proton pump inhibitors such as Omeprazole seem, at the moment, the most effective for reflux control, as well as the Nissen-Rossetti operation seems the most widely accepted among the anti-reflux surgical procedures. The novelty concerning Barrett's esophagus therapy is represented by laser photoablation associated with proton pump inhibiting therapy. But the experience with this treatment is still at a preliminary stage. For Barrett's esophagus with severe dysplasia and/or adenocarcinoma and/or squamous cell carcinoma esophagectomy is needed with a different extent and approach, according to the extent of Barrett's esophagus and to the stage and site of the neoplastic changes.