Morphogenetic events in the perinodal connective tissue in a metastatic cancer model.

BACKGROUND: The modifications of connective tissue surrounding metastatic lymph nodes in a murine model of rectal cancer are described. METHODS: Athymic nude mice (n=36) were inoculated with 10×10(5) ht-29 cancer cells into the submucosal layer of the rectum. Control mice (n=5) were treated with a sterile buffer. Tumor and the involved lymph nodes were visualized in vivo by magnetic resonance imaging at 1 to 4 weeks after cell injection. After the sacrifice, the excised samples were processed for histology. RESULTS: After one week from cell injection all treated animals developed rectal cancer. Since the first week, neoplastic cells were visible in the nodes. In the surrounding connective tissue, the diameter of the adipocytes was reduced and a mesenchymal-like pattern with stellate cells embedded in an oedematous environment was visible. Since the second week, in the perinodal connective an enlargement of the stroma was present. The tissue was organized in cords and areas with extracellular accumulation of lipids were found. At the fourth week, we observed an enlargement of multilocular areas and lobules of elongated elements almost devoid of lipid droplets. In control animals, in absence of neoplastic masses, pelvic nodes were surrounded by a typical connective tissue characterized by unilocular adipocytes with groups of multilocular adipocytes. CONCLUSIONS: We have developed a model of rectal cancer with nodal metastases. Using this model, the work demonstrates that around secondary lesions, the morphogenetic events follow a standard evolution characterized by an early phase with lipolysis and mesenchymalization and later phases with a brown-like phenotype acquisition.

One stage or two stage treatment of colorectal cancer associated to abdominal aortic aneurysm: morbidity and mortality.

The coexistence of colorectal cancer and abdominal aortic aneurysm has been observed with increasing frequency, raising several questions about therapeutic and surgical strategies for management of both diseases. This study has reviewed 440 cases (359 cases analyzed) of colorectal cancer associated with abdominal aortic aneurysm recovered in the literature from year 1987 to 2010. In 120 cases, patients were treated in one stage; in 239 cases, they were treated in two stages. The treatment in two stages was associated with a morbidity of 26.4%, with a mortality of 5% and prosthetic infection of 0.8%. The treatment in one stage had rates of complications and mortality of 13.3% and 4.2% respectively and no cases of prosthetic infection. Analysis of the literature shows that the treatment in two stages exposes patients to a higher risk of complications and prosthetic infection.

Shape and volume of internal anal sphincter showed by three-dimensional anorectal ultrasonography.

PURPOSE: The aim of this work is to characterize the shape and the volume of the internal anal sphincter (IAS) in normal subjects by three-dimensional anorectal ultrasonography. METHODS: Thirty-nine normal volunteer males (mean age 58.5 ± 18.7) and 25 females (mean age 59.4 ± 14.1) were submitted to anorectal ultrasonography. The tissue is defined by a semiautomatic procedure. Measurements of thickness, length and volume were assessed automatically. The software provides an average number of 57,600 thickness measurements, 360 length measurements for each zone (90 for each quadrant) and seven volume measurements (one for each anatomical area).The mean values of magnitudes were calculated for the entire volume in each quadrant and zone. Age and gender-related variations were analyzed. RESULTS: In assessments of the whole tissue, only thickness was gender-related, with greater thickness for females (male thickness: 1.81 ± 0.47 mm, female thickness 2.16 ± 0.57 mm, P-value<0.01).In the distal zone: thickness, length and volume were all larger in females (for male and female respectively: 1.83 ± 0.49 mm vs 2.34 ± 0.58 mm, P-value<0.01, for the thickness; 10.87 ± 2.10mm vs 12.18 ± 2.21 mm, P-value<0.02 for the length and 1501 ± 605 mm(3) vs 2169 ± 871 mm(3), P-value<0.01 for the volume). In the medial zone, only thickness was gender-related, with greater thickness in females (male thickness: 2.04 ± 0.60mm, female thickness:2.44 ± 0.74 mm, P-value<0.02).The only variation observed in the proximal zone concerned length, larger in males (respectively: 11.27 ± 2.84 mm vs 9.55 ± 2.43 mm, P-value<0.02). The male population was significantly positively correlated with ageing for volume in the whole tissue (ρ = 0.32, P-value<0.05), and for both thickness and volume in the medial zone (ρ = 0.33, P-value<0.05 for thickness; ρ = 0.39, P-value<0.02 for the volume). CONCLUSION: This new method is useful to understand both functional anal disorders and local damage which may affect only part of the muscle tissue.

A new model of rectal cancer with regional lymph node metastasis allowing in vivo evaluation by imaging biomarkers.

OBJECT: The work is aimed to develop a murine model of rectal cancer, which could be used to monitor lymph node metastasis development by magnetic resonance imaging (MRI) and optical imaging (OI) techniques. SUBJECTS AND METHODS: Ht-29 cancer cells were directly injected into the submucosal layer of the rectum of athymic nude mice using trans-anal rectal cancer cell injection (TARCI). Thirty-six mice were inoculated with 10×10(5) cells and five mice were treated with sterile phosphate buffer solution. One to 4 weeks after cell injection, tumor growth was evaluated in vivo using T2-weighted MRI at 4.7T. A further group of animal (n=6) treated with ht-29_luc cells, with the same protocol, was monitored by optical imaging. In both groups, the presence of the primary tumor and of lymph nodes metastasis was confirmed by histology. RESULTS: In all animals, primary tumors were detectable by MRI, 1 week from TARCI. After 4 weeks primary tumors showed a mean longitudinal diameter of about 2cm. All animals developed regional lymph node metastases. Others organs (e.g. lung or liver) were not affected. In fat-suppressed, T2-weighted MRI, lymph nodes appeared as small areas characterized by hyper-intense signal compared to muscle. OI permitted evaluation of the primary tumor growth in perineal region. CONCLUSIONS: TARCI of ht-29 cells into the rectum of nude mice is a feasible way to obtain a easily reproducible model of regional lymph node metastases could be monitored by magnetic resonance and optical imaging techniques.

From endothelial dysfunction to atherosclerosis.

It has recently emerged that endothelial dysfunction is an early step in the development of atherosclerosis and is mainly characterised by a reduction in the bioavailability of nitric oxide. All of the traditional cardiovascular (CV) risk factors (dyslipidemia, arterial hypertension, hyperglycemia and diabetes) are associated with endothelial dysfunction, and oxidised low-density lipoproteins, the renin-angiotensin axis and insulin resistance play important roles in the pathogenesis of impaired endothelial function. The increased expression of adhesion molecules and pro-inflammatory cytokines leads to abnormal endothelium-dependent vasodilation which could be investigated using vasoreactivity tests such as flow-mediated dilation in the brachial artery. Recently, new evidences showed that the immune system plays an important role in the pathogenesis of endothelial dysfunction and atherosclerosis with a particular regard towards autoimmunity. The high prevalence of the atherosclerotic process in systemic autoimmune diseases supports the hypothesis of the immune pathogenesis. Evaluating coronary microvascular dysfunction by means of transthoracic echocardiography with non-invasive coronary flow reserve assessment is particularly interesting as it could detect preclinical impairment of coronary microvascular function. The discovery that the mechanisms responsible for endothelial damage have a genetic basis could improve the approach to CV diseases. This review summarises the most important aspects of the pathogenesis and development of endothelial dysfunction, with particular attention to the role of traditional CV risk factors, the usefulness of vasoreactivity tests, and the future perspectives opened by genetic studies.

New method for internal anal sphincter measurements: feasibility study.

PURPOSE: The aim of this paper is to provide a method for measuring the internal anal sphincter on the basis of the quantitative analysis of three-dimensional endosonographic images. A software calculates a large set of measurements which are able to describe the three-dimensional shape of the muscle. METHODS: A software provides four types of measurements: thickness, length, area and volume. The different magnitudes are estimated using the same reference system. The measurements obtained are modeled by functions that describe their spatial trend. The precision and reproducibility of the method was tested on a phantom before a study was performed on fifteen healthy patients. The measurements were carried out by two different operators. The inter-observer variability were assessed. RESULTS: In the phantom measurements the mean errors and the standard deviation were: 0.05 +/- 0.1 mm for the thickness, 0.02 +/- 0.12 mm for the length, -4.43 +/- 2.4 mm(2) for the area, -20.69 +/- 20.83 mm(3) for the volume. The maximum absolute differences between the measurements carried out by the two operators was: 0.18 mm for the thickness (in the 95% of the case), 1.69 mm(2) for the area (in the 95% of the case), and 0.25 mm for the length, and 29.46 mm(3) for the volume. The human IAS assessments were evaluated on each segment. The mean of the all tissue measurements carried out were (mean +/- SD): 1.71 +/- 0.34 mm for the thickness, 33.24 +/- 6.10 mm for the length, 111.28 +/- 29.08 mm(2) for the area. The mean of the volume measurements of the entire tissue was: 4124 +/- 1160 mm(3). Inter-observer variability was observed only in the anterior proximal segment for the thickness measurements by Wilcoxon's signed rank test (P value = 0.048) and for the volume assessments by the limits of agreement method (-118 to 78 mm(3)). The mean percentage errors and the limit of agreement for the measurements of the entire tissue were: 0.27 and (-0.11 to 0.12 mm) for the thickness, -2.32 and (-3.88 to 2.33 mm) for the length, -0.05 and (-9.71 to 9.83 mm(2)) for the area, -1.89 and (-366 to 240 mm(3)) for the volume. CONCLUSION: The assessments of accuracy and precision of the method result satisfactory for all four type of measurements. The reproducibility analysis confirms very good inter-observer agreement for the phantom measurements and for the most part of the IAS segments evaluations. Inter-observer variability was seen only for the thickness and volume measurements of the anterior-proximal segment. Our method provides a high number of measurements with good accuracy enabling a very detailed study of IAS morphology.

Early laparoendoscopic rendezvous for acute biliary pancreatitis: preliminary results.

INTRODUCTION: Early restored patency of the papilla has been hypothesized to reduce complications and mortality of acute biliary pancreatitis. The aim of this study was to evaluate the role of urgent laparoscopic cholecystectomy with intraoperative cholangiography and rendezvous when necessary in acute biliary pancreatitis natural history. PATIENTS AND METHODS: Patients observed in the early stage of an acute biliary pancreatitis were included in the study. Operative risk assessment based on American Society of Anesthesiologists (ASA) score allowed the performance of urgent laparoscopic cholecystectomy within 72 h from onset of symptoms in 55 patients and a delayed intervention during the same admission in 21 patients. Intraoperative cholangiography was performed in all cases, and clearance of common bile duct was performed by flushing when possible, or rendezvous when necessary. Evolution of pancreatitis was evaluated with clinical and radiological monitoring. RESULTS: Urgent laparoscopic cholecystectomy was performed in all cases without conversion. At intraoperative cholangiography common bile duct was free in 25 patients, a papillary spasm was observed in 9, and common bile duct stones in 21 patients. Patency of the papilla was restored by flushing in 13 patients, while a rendezvous was necessary in 17 patients. The rate of organ failure and pancreatic necrosis was 1.8%, overall mortality was 1.8%, and overall morbidity 21.8%. No infectious complications of peripancreatic collections were observed. CONCLUSION: Urgent laparoscopic cholecystectomy with selective intraoperative rendezvous may be considered as a treatment option in the early stage of acute biliary pancreatitis.

Software for hepatic vessel classification: feasibility study for virtual surgery.

PURPOSE: The detection and classification of hepatic vessels in diagnostic images are essential for hepatic pre-surgery planning. Our team has developed a tool for classification, analysis, and 3D reconstruction of the hepatic and portal systems. METHODS: Our software first extracts a graphic representation of a set of connected voxels, representing both systems. It then calculates two binary volumes representing the main part of the two venous systems. Finally, it combines these results to obtain the correct vessel classification. RESULTS: Segmentation steps are semi-automatic and require about 40 min to complete. Schematization and classification steps are automatic and require about 17 min for results. CONCLUSION: The software provides a correct and detailed reconstruction even where pathologies have caused morphological and geometrical variations in the vessels. The time required for the entire procedure is compatible with clinical requirements, providing an efficient tool for diagnosis and surgical planning.

Specific alloantigen self-control by regulatory T cells in organ transplantation: a review.

Multidrug immunosuppressive protocols have increased short-term patient and graft survival rates from 50% to 90% in the past two decades. Unfortunately, chronic graft rejection still remains the main cause of long-term failure and patients must undergo lifelong immunosuppression. The severe side effects such as life-threatening infections, secondary malignancies, and cardiovascular dysfunction all together include roughly 50% of deaths among kidney transplant patients with functioning grafts. Therefore, it should be of crucial importance to reduce immunosuppression and seek induction of specific tolerance to donor alloantigens. Several investigations have suggested that the acquisition of tolerance to self and/or foreign antigens is dependent on the number and function of naturally occurring and acquired regulatory T cells, which can control all aggressive T cells. The regulatory T cells together with their receptors, costimulatory molecules, cytokines, chemokines, and growth factors all contribute to maintain an equilibrium between aggressive and suppressive effector immune responses. As a consequence of increased knowledge, new immunosuppressive approaches based on either alloantigen-specific regulatory T-cell expansion in vivo or in vitro have been proposed to achieve donor-specific transplantation tolerance in kidney allograft recipients. This contribution attempted to summarize knowledge about regulatory T cells and developing methods to induce specific tolerance in kidney transplantation.

Surgical treatment of abdominal aortic aneurysm with concomitant renal cell carcinoma: a single-centre experience with review of the literature.

AIM: The association between abdominal aortic aneurysm (AAA) and renal cancer is becoming more frequent, raising several questions about therapeutic and surgical strategies of management for both diseases. METHODS: Between October 1988 and May 2004, 913 AAA patients underwent surgical or endovascular repair at the I Division of General Surgery of the University of Verona (Italy). In 61 cases (6.7%) an association with a solid neoplasm was found; in 12 cases (1.3%) the neoplasm was a renal cell carcinoma. RESULTS: Ten patients underwent a simultaneous approach to AAA and renal cancer, with aneurismectomy performed first. In 2 cases a two-stage procedure was preferred; 1 patient underwent aneurismectomy first for AAA rupture while a second patient was even affected by gastric cancer and was submitted to nephrectomy and total gastrectomy as primary procedures. There was no mortality and only one postoperative complication was registered. CONCLUSIONS: A simultaneous surgical approach can be done safely, performing aneurismectomy as first step without significant risk of graft infection. Simultaneous treatment has the advantage of avoiding a second major abdominal procedure and eliminate the risk of postoperative aortic aneurysm rupture. Performing a two-stage approach, the procedure for the disease regarded as life-threatening is performed first. Priority should be given to renal cell neoplasm in selected cases.

Peritoneal cytology does not increase the prognostic information provided by TNM in gastric cancer.

BACKGROUND: This study aimed at verifying whether peritoneal cytology could improve the prognostic information provided by TNM staging in gastric cancer patients. METHOD: The presence of free peritoneal tumor cells was investigated in 168 patients who underwent curative resection for gastric cancer from January 1992 to July 2002 in Verona, Italy. The influence of peritoneal cytology on survival was evaluated by a Cox regression model, controlling for potential confounders. RESULTS: Twenty-three patients (14%) had positive peritoneal cytology. Patients with positive lavage were more likely to present serosal infiltration (100 vs. 46%) and nodal metastases (91 vs. 67%; P < 0.001). Positive lavage was associated with a very poor prognosis: 3-year survival was only 9% (95% CI 2-27%) when peritoneal cancer cells had been detected, whereas survival reached 50% (95% CI 42-59%) in patients with a negative cytology. In multivariate survival analysis, peritoneal cytology was an independent predictor of mortality when controlling for sex, age, site, histology, and nodal metastases, but not when adjusting also for depth of tumor invasion (RR of positive versus negative = 1.2, 95% CI 0.7-2.0). Similarly, the influence of peritoneal cytology on survival was no longer significant when univariate analysis was restricted to T3/T4 patients (RR = 1.5, 0.9-2.5). CONCLUSIONS: Positive peritoneal cytology was a marker of poor prognosis in gastric cancer patients. Nevertheless, peritoneal lavage did not increase the prognostic information already provided by the TNM staging system in this Italian series.

High pathological response rate in locally advanced esophageal cancer after neoadjuvant combined modality therapy: dose finding of a weekly chemotherapy schedule with protracted venous infusion of 5-fluorouracil and dose escalation of cisplatin, docetaxel and concurrent radiotherapy.

BACKGROUND: This phase I study was aimed at defining the toxicity profile and pathological response rate of a neoadjuvant schedule including weekly docetaxel and cisplatin, protracted venous infusion (PVI) of 5-FU and concomitant radiotherapy (RT) in locally advanced esophageal cancer. PATIENTS AND METHODS: The schedule consisted of a first phase of chemotherapy alone and a second phase of concurrent chemoradiation. Initial doses were: docetaxel and cisplatin 20 mg/m2 on days 1, 8, 15, 29, 36 and 43 plus 5-FU 150 mg/m2 PVI on days 1-21 and 29-49; RT (40 Gy) started on day 29. In the following steps the doses were escalated up to docetaxel 35 mg/m2 and cisplatin 25 mg/m2 on days 1, 8, 15, 29, 36, 43, 50 and 57 plus 5-FU 180 mg/m2 PVI on days 1-21 and 150 mg/m2 PVI on days 29-63 concurrently with RT 50 Gy. RESULTS: Forty-seven patients were enrolled and 46 completed the planned treatment. During the concomitant phase, grade 3-4 hematological toxicities occurred in three patients (6.5%) (or 3/174 cycles) and non-hematological toxicities in six patients (13%) (or 7/179 cycles). A pathological downstaging was obtained in 59.6% of the cases (28/47): complete remission (pCR) in 14 patients, near pCR (residual microfoci on the primary pN0) in eight patients, pT2 pN0 in three patients and partial response on the primary with positive lymph nodes in three patients. Six (13%) and 13 (28%) patients were considered stable and non-responders, respectively. In the last dose level, eight pCR and four near-pCR were obtained out of 15 patients. The maximum tolerable dose was not formally defined because dose escalation was stopped at the last dose level. CONCLUSION: This schedule represents a feasible treatment and the high pathological response rate is extremely encouraging; the doses found in the last dose-level are the basis for an ongoing phase II study at our institution.

Comparison of old and new TNM systems for nodal staging in adenocarcinoma of the gastro-oesophageal junction.

BACKGROUND: Adenocarcinoma of the gastro-oesophageal junction is considered a distinct clinical entity, although the current pathological tumour node metastasis (pTNM) classification does not consider this tumour specifically. A prospective study was undertaken to determine the prognostic importance of lymph node involvement in adenocarcinoma of the gastro-oesophageal junction, analysing both a number- and site-based classification, in order to develop a clinically useful nodal staging system. METHODS: Two classification systems were analysed in 116 patients who underwent resection for adenocarcinoma of the gastro-oesophageal junction from January 1988 to August 2001. The Cox regression model was used to evaluate the prognostic significance of the site and number of positive nodes. RESULTS: The number- and site-based staging systems coincided only in 42 (56 per cent) of 75 patients; in particular, the old pN1 classification was upstaged in 13 of 41 patients and the old pN2 was downstaged in 13 of 34 patients. Lymph node involvement was the most important prognostic factor in both classifications (P < 0.001). The risk of death was significantly influenced by the site of nodal metastasis among patients with a similar number of involved nodes (relative risk with respect to pN0: 2.18 for pN1 with one to six nodes; 6.53 for pN2 with one to six nodes; 7.53 for pN1 with more than six nodes; 39.13 for pN2 with more than six nodes). CONCLUSION: Adenocarcinoma of the gastro-oesophageal junction requires a specific lymph node classification which should take into account both the number and site of nodal metastases.

Pattern of recurrence after surgery in adenocarcinoma of the gastro-oesophageal junction.

AIMS: This study reports mode, timing and predictive factors of recurrence after curative surgery for cardia cancer. METHODS: A prospective study in a series of 92 curatively (R0) resected patients from 1988 to 2002. RESULTS: The 5-year recurrence rate was 71%. Lymph node involvement was the only predictor of recurrence. No patients with more than 6 metastatic nodes were free from relapse 2 years after surgery. Locoregional, peritoneal and haematogenous relapses showed a similar median recurrence time (12, 10 and 12 months, respectively), 80% occurred within 24 months. CONCLUSIONS: Few patients can be cured by surgery, lymph nodal involvement is the only predictor of recurrence.

Risk assessment and prediction of rebleeding in bleeding gastroduodenal ulcer.

BACKGROUND AND STUDY AIMS: The aims of this study were to identify risk factors for recurrence of hemorrhage in bleeding gastroduodenal ulcers after endoscopic injection therapy, and to develop a simple and relevant prognostic score which could be used to assess the early risk of recurrence and the residual risk of rebleeding. PATIENTS AND METHODS: A prospective study was conducted from January 1995 to December 1998, in 738 patients who were admitted to our department for acute bleeding peptic ulcer and who underwent endoscopic examination. Ulcers with active bleeding or signs of recent bleeding were treated with injection therapy using epinephrine (1/10,000) and 1% polidocanol. RESULTS: Multivariate analysis revealed that liver cirrhosis, recent surgery, systolic blood pressure below 100 mmHg, hematemesis, Forrest classification, and ulcer size and site were significantly predictive variables for the recurrence of hemorrhage. Among these, Forrest classification was the most important. The overall accuracy of the predictive model was 71% (95% CI = 63 - 79%). The model showed a better sensitivity of 90% for early rebleeding (< 48 hours) than for late rebleeding (> or = 48 hours) where the sensitivity was 65 %. A prognostic score was obtained and patients were classified into four risk classes: very low (VL), low (L), high (H), and very high (VH). The rebleeding rates for the four classes were 0%, 7.9%, 31.8% and 67.9%, and the mortality rates were 5.9%, 8.6%, 13.9% and 35.7%, respectively. The residual risk of rebleeding after 48 hours was 0%, 3.3%, 10.4%, and 14.3% in the VL, L, H and VH classes, respectively. After 5 days the residual risk was under 4% in all classes. CONCLUSIONS: This study demonstrates that the proposed prognostic score, which is easily obtained after emergency endoscopy, is useful in clinical practice because it can identify patients with different levels of rebleeding risk. It can be helpful in patient management and decision making for discharge.

[Endoscopic, percutaneous and laparoscopic treatment for acute biliary pancreatitis]. / Traitement endoscopique, percutané et coelioscopique des pancréatites aiguës biliaires.

AIM OF THE STUDY: The aim of this study is to evaluate the results of acute gallstone pancreatitis treatment and to discuss indications in relation with the different forms of the disease. MATERIAL AND METHOD: From january 1992 to june 2001, 137 patients have been treated for an acute gallstone pancreatitis. Diagnostic criteria were given by the history, clinical examination, biochemical and radiological findings. After exclusion of patients with a systemic disease, a group of 129 patients have been enrolled in a treatment regimen with an endoscopic retrograde cholangiopancreatography (ERCP) and eventual sphincterotomy, a percutaneous US-guided cholecystostomy (PC) when necessary and an elective laparoscopic cholecystectomy. RESULTS: ERCP has been successfully performed in 121/129 patients. A PC has been performed in 5/8 patients of the failed endoscopic procedure and in 14 with acute cholecystitis. Retrograde and percutaneous cholangiographies showed main bile duct stones in 89 patients, a dilatation of the main bile duct without stones in 26 patients and a negative finding in 6 patients. An endoscopic sphincterotomy has been performed in 117 patients. A laparoscopic cholecystectomy has been performed in 118 patients. Mortality and morbidity rates were 1.6 and 10.3%, respectively. CONCLUSION: ERCP and sphincterotomy seem to be indicated in all patients observed during the first 72 hours. Endoscopic treatment and percutaneous procedure make it possible to reduce at a very low rate the cases with an unfavourable course of the disease. A definitive treatment may then be performed by the way of a laparoscopic cholecystectomy.

Ultrastructural phenotype of "intestinal-type" cells in columnar-lined esophagus.

An intestinal-type epithelium is often present at columnar-lined esophagus, gastroesophageal junction or within the so-called short segment Barrett's esophagus, but ultrastructural study failed to detect enterocytes in columnar-lined esophagus. The authors have analyzed the intestinal aspects present in areas of columnar-lined esophagus in a population of patients with reflux esophagitis to better understand the morphology and histogenesis of the proliferating elements. Columnar-lined mucosa was studied in 35 patients. Columnarsurface cells displayed a wide spectrum of ultrastructural features. Well-differentiated columnar secretory cells, secretory-absorptive cells, poorly differentiated columnar cells, atypical columnar cells, and goblet cells were detected. Well-differentiated absorptive cells were never found, These results demonstrate that the areas of intestinal metaplasia show a wide spectrum of ultrastructural phenotypes, ranging from poorly to well-differentiated cells. However, true enterocytes were not found and the most represented phenotype is that of secretory-absorptive cells, whose principal characteristic is the presence of secretory and absorptive aspects together. They can be described as secretory enterocytes or cells with double specialization. To the authors' knowledge, similar cells were not previously described in normal intestinal mucosa, and ultrastructural studies are consistent in describing a broad spectrum of ultrastructural features, suggesting that Barrett's specialized metaplasia is derived from cells with the capacity for a wide range of differentiation. Therefore, despite the wide use of term intestinal metaplasia in the medical literature, experimental data clearly failed to detect enterocytes in the columnar-lined esophagus, and ultrastructural data do not support the concept of intestinal metaplasia. The cellular heterogeneity seems to be the result of a "phenotypic shift" of undifferentiated elements, which show a different pattern of evolution. The result of this process is the formation of new cell types dissimilar from those normally present in esophageal, gastric, or duodenal mucosa.

The presence of bone marrow cytokeratin-immunoreactive cells does not predict outcome in gastric cancer patients.

The independent prognostic significance of isolated tumour cells in bone marrow is still a matter of debate. This study evaluated the possible association of bone marrow micrometastases with tumour progression and prognosis in patients affected by gastric cancer. Bone marrow aspirates from both iliac crests were obtained from 114 consecutive patients operated on for gastric cancer. The specimens were stained with monoclonal antibody CAM 5.2 which reacts predominantly with cytokeratin filaments 8 and 19. Among 114 cases analysed, 33 cases (29%) had cytokeratine-positive cells in the bone marrow. There was no significant relationship between the presence of bone marrow micrometastases and site, depth of tumour invasion, lymph node metastases, presence of metastases. Patients with cytokeratine-positive cells had a trend towards a diffuse type histology (P=0.06). Among the 88 curatively resected patients, median survivals were 40 months and 36 months for cytokeratine-negative and cytokeratine-positive subsets respectively (P=0.9). Recurrence of the disease was observed in 39 cases (44.3%); 11 of 24 (45.8%) in the cytokeratine-positive subset and 28 of 64 (43.7%) in the cytokeratine-negative subset. In conclusion in our experience the presence of cytokeratine-positive cells in the bone marrow of curatively resected gastric cancer patients did not affect outcome and its independent prognostic significance remains to be proven before its official acceptance in the TNM classification.

Intraoperative US staging of T in gastric cancer: final results of a blind prospective study.

BACKGROUND: In order to improve the accuracy in the assessment of depth of tumor invasion, we performed an ultrasound examination of the resected specimen intraoperatively just after removal by the surgeon (Intraoperative Ultrasonography (IUS). This prospective blind study reports the results obtained with the IUS in the staging of T in a group of 281 patients who underwent curative gastrectomy for gastric cancer. METHODS: After the removal by the surgeon, the portion of the stomach harboring the tumor was submitted to ultrasonography with a linear 7.5 Mhz probe. An echo-free standoff pad was placed between the probe and the organ; a second echo-free standoff pad was interposed between the stomach and the support surface. The diagnosis of depth of invasion was based on the degree of disruption of the five-layer sonographic structure of the gastric wall. RESULTS: The IUS staging of T corresponded to the pathological diagnosis in 256 out of 281 cases (overall accuracy 91.1%). The sensitivity in the different classes of T was, respectively, 91.2 in T1m cases, 83.3 in the T1sm cases, 89.6 in the T2 cases, and 93.5% in the T3 cases. CONCLUSION: The IUS on the resected specimen has a high degree of accuracy in the assessment of depth of tumor invasion and seems to be an important advance in the clinical staging of gastric cancer.

Risk factors for lymph node metastases and their prognostic significance in early gastric cancer (EGC) for the Italian Research Group for Gastric Cancer (IRGGC).

BACKGROUND: Lymph node metastases are present in only about 15% of patients with early gastric cancer (EGC) and for this reason, the majority of these patients do not require lymphadenectomy. In Japan, EGC patients undergo less invasive treatment (endoscopic mucosal resection, wedge resection, laparoscopy). However, the indications for and results of these types of treatment are still uncertain. METHODS: In a multicentre retrospective study, we analysed the clinicopathological data referring to 584 early gastric cancer patients who underwent D2 gastrectomy. A comparison was made between patients with and without lymph node metastases in relation to numerous pre- and postoperative variables. Long-term survival and risk factors for lymph node metastases were analysed. The primary aim was to compare our results with those of Western and Japanese authors; we also evaluated the possibility of identifying a subset of patients at low risk of lymph node metastases who may be candidates for endoscopic treatment. RESULTS: The incidence of lymph node metastasis was 14.4%. Univariate and multivariate analyses showed that submucosal infiltration, diffuse histotype, tumour size and Kodama Pen A type were all related to the presence of lymph node metastases. Patients with types I, IIa and IIb mucosal tumours did not present lymph node metastases. Postoperative mortality was 2.2%. Five-year survival in relation to lymph node groups was 95% in N0 patients, 77% in N1 patients and 60% in N2 patients (p = 0.0001, Japanese N-stage). The number of positive lymph nodes also had a prognostic value. Patients with three or fewer positive lymph nodes presented a better 5-year prognosis (83%) than those with more than three positive lymph nodes (48%) (p = 0.0001). CONCLUSIONS: Our study confirms that lymph node involvement is an extremely important prognostic factor. For this reason, the therapeutic strategy of our surgical units is as follows: 1) D2 gastrectomy is the standard treatment even in early gastric cancer (EGC); 2) endoscopic mucosal resection (EMR) could be considered first in types I, IIa and IIb tumours that are diagnosed as limited to the mucosal layer.