MRI prediction of pathological response in locally advanced rectal cancer: when apparent diffusion coefficient radiomics meets conventional volumetry.

AIM: To investigate the role of diffusion-weighted imaging (DWI), T2-weighted (W) imaging, and apparent diffusion coefficient (ADC) histogram analysis before, during, and after neoadjuvant chemoradiotherapy (CRT) in the prediction of pathological response in patients with locally advanced rectal cancer (LARC). MATERIALS AND METHODS: Magnetic resonance imaging (MRI) at 1.5 T was performed in 43 patients with LARC before, during, and after CRT. Tumour volume was measured on both T2-weighted (VT2W) and on DWI at b=1,000 images (Vb,1,000) at each time point, hence the tumour volume reduction rate (ΔVT2W and ΔVb,1,000) was calculated. Whole-lesion (three-dimensional [3D]) first-order texture analysis of the ADC map was performed. Imaging parameters were compared to the pathological tumour regression grade (TRG). The diagnostic performance of each parameter in the identification of complete responders (CR; TRG4), partial responders (PR; TRG3) and non-responders (NR; TRG0-2) was evaluated by multinomial regression analysis and receiver operating characteristics curves. RESULTS: After surgery, 11 patients were CR, 22 PR, and 10 NR. Before CRT, predictions of CR resulted in an ADC value of the 75th percentile and median, with good accuracy (74% and 86%, respectively) and sensitivity (73% and 82%, respectively). During CRT, the best predictor of CR was ΔVT2W (-58.3%) with good accuracy (81%) and excellent sensitivity (91%). After CRT, the best predictors of CR were ΔVT2W (-82.8%) and ΔVb, 1,000 (-86.8%), with 84% accuracy in both cases and 82% and 91% sensitivity, respectively. CONCLUSIONS: The median ADC value at pre-treatment MRI and ΔVT2W (from pre-to-during CRT MRI) may have a role in early and accurate prediction of response to treatment. Both ΔVT2W and ΔVb,1,000 (from pre-to-post CRT) can help in the identification of CR after CRT.

Could perfusion heterogeneity at dynamic contrast-enhanced MRI be used to predict rectal cancer sensitivity to chemoradiotherapy?

AIM: To evaluate whether perfusion heterogeneity of rectal cancer prior to chemoradiotherapy (CRT) using histogram analysis of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) quantitative parameters can predict response to treatment. MATERIALS AND METHODS: Twenty-one patients with histologically proven rectal adenocarcinoma were enrolled prospectively. All patients underwent 1.5 T DCE-MRI before CRT. Tumour volumes were drawn on Ktrans and Ve maps, using T2-weighted (W) images as reference, and the following first-order texture parameters of Ve and Ktrans values were extracted: 25th, 50th, 75th percentile, mean, standard deviation, skewness, and kurtosis. After CRT, patients underwent surgery and according with Rödel's tumour regression grade (TRG), they were classified as poor responders "non-GR" (TRG 0-2) and good responders "GR" (TRG 3-4). Differences between GR and non-GR in DCE-MRI first-order texture parameters were evaluated using the Mann-Whitney test, and their role in the prediction of response was investigated using receiver operating characteristic (ROC) curve analysis. RESULTS: Sixteen (76%) patients were classified as GR and five (24%) were non-GR. Skewness and kurtosis of Ve was significantly higher in non-GR (4.886±1.320 and 36.402±24.486, respectively) than in GR patients (1.809±1.280, p=0.003 and 6.268±8.130, p= 0.011). Ve skewness <3.635 was able to predict GR with an area under the ROC curve (AUC) of 0.988, sensitivity 93.8%, specificity 80%, and accuracy 90.5%. Ve kurtosis <21.095 was able to predict response with an AUC of 0.963, sensitivity 93.8%, specificity 80%, and accuracy 90.5%. Other parameters were not different between groups or predictors of response. CONCLUSION: Ve skewness and kurtosis seem to be promising in the prediction of response to CRT in rectal cancer patients.

Could early tumour volume changes assessed on morphological MRI predict the response to chemoradiation therapy in locally-advanced rectal cancer?

AIM: To investigate the potential role of an additional magnetic resonance imaging (MRI) examination performed during neoadjuvant chemoradiation therapy (CRT) in the prediction of pathological response in locally advanced rectal cancer (LARC). MATERIAL AND METHODS: Forty-eight consecutive patients with LARC underwent neoadjuvant CRT. MRI studies at 1.5 T, including high-resolution T2-weighted sequences that were acquired parallel and perpendicular to the main axis of the tumour were performed before (preMRI), during (midMRI), and 6-8 weeks after the end of CRT (postMRI). Cancer volumes (Vpre, Vmid, Vpost) were drawn manually and the reduction rate calculated (ΔVmid, ΔVpost). According to Rödel's pathological tumour regression grade (TRG), patients were considered non-responders (NR; TRG0-2), partial responders (PR; TRG3), and complete responders (CR; TRG4). Multivariate regression analysis was performed to identify the best MRI predictors of NR, PR, and CR. RESULTS: Twenty-five patients were considered PR (52%), 13 CR (27%), and 10 NR (22%). Tumour shrinkage mainly occurred shortly after CRT (ΔVmid: CR: 80±10% versus PR: 56±19% versus NR: 28±22%, p=2.2×10-16). Vmid, Vpost, ΔVmid, and ΔVpost correlated with TRG (p<0.001). At multivariate analysis, the combined assessment of Vmid and ΔVmid was selected as the best predictor of response to CRT, in that it distinguishes CR, PR, and NR early and accurately (81.5%). CONCLUSION: MidMRI allows final response assessment to neoadjuvant CRT earlier and better than the MRI performed after the end of CRT. MRI findings at midMRI may be useful to tailor patient treatment.

Early regression index (ERI) on MR images as response predictor in esophageal cancer treated with neoadjuvant chemo-radiotherapy: Interim analysis of the prospective ESCAPE trial.

PURPOSE: The early regression index (ERI) predicts treatment response in rectal cancer patients. Aim of current study was to prospectively assess tumor response to neoadjuvant chemo-radiotherapy (nCRT) of locally advanced esophageal cancer using ERI, based on MRI. MATERIAL AND METHODS: From January 2020 to May 2023, 30 patients with esophageal cancer were enrolled in a prospective study (ESCAPE). PET-MRI was performed: i) before nCRT (tpre); ii) at mid-radiotherapy, tmid; iii) after nCRT, 2-6 weeks before surgery (tpost); nCRT delivered 41.4 Gy/23fr with concurrent carboplatin and paclitaxel. For patients that skipped surgery, complete clinical response (cCR) was assessed if patients showed no local relapse after 18 months; patients with pathological complete response (pCR) or with cCR were considered as complete responders (pCR + cCR). GTV volumes were delineated by two observers (Vpre, Vmid, Vpost) on T2w MRI: ERI and other volume regression parameters at tmid and tpost were tested as predictors of pCR + cCR. RESULTS: Complete data of 25 patients were available at the time of the analysis: 3/25 with complete response at imaging refused surgery and 2/3 were cCR; in total, 10/25 patients showed pCR + cCR (pCR = 8/22). Both ERImid and ERIpost classified pCR + cCR patients, with ERImid showing better performance (AUC:0.78, p = 0.014): A two-variable logistic model combining ERImid and Vpre improved performances (AUC:0.93, p < 0.0001). Inter-observer variability in contouring GTV did not affect the results. CONCLUSIONS: Despite the limited numbers, interim analysis of ESCAPE study suggests ERI as a potential predictor of complete response after nCRT for esophageal cancer. Further validation on larger populations is warranted.

Factors influencing liver fibrosis and necroinflammation in HIV/HCV coinfection and HCV monoinfection.

OBJECTIVES: To define differences in liver histology between HIV/HCV coinfection and HCV monoinfection, and to investigate possible causative factors. METHODS: Liver biopsies (LBs) from 440 consecutive HIV/HCV-coinfected patients (Group HIV/HCV) and 374 consecutive HCV-monoinfected patients (Group HCV) were evaluated for necroinflammation and fibrosis (Ishak) by a pathologist unaware of the clinical and laboratory data. All patients were HBsAg-negative, with no history of alcohol abuse and naïve to anti-HCV treatment. At LB, 78.4% of patients in Group HIV/HCV were on an antiretroviral regimen. RESULTS: HIV/HCV-coinfected patients compared to the HCV-monoinfected patients were younger (p < 0.0001), more frequently males (p < 0.0001), and had HCV genotype 3 (p < 0.0001); they showed a good immunological condition (CD4+ cell count: 518 ± 166 cells/mm(3)). Patients in Group HIV/HCV more frequently showed a fibrosis score ≥4 (27.5 vs. 20.6%, p < 0.05) and a necroinflammation score ≥9 (25.9 vs. 13.4%; p < 0.0001). The prevalence of patients with fibrosis score ≥4 was significantly higher in older age classes in both Group HIV/HCV (p < 0.005) and Group HCV (p < 0.05). A necroinflammation score ≥9 was significantly higher in older age classes only in Group HIV/HCV (p < 0.05). A multivariate analysis for Group HIV/HCV revealed that the patient age and nadir of CD4+ cell count were independently associated to higher degrees of fibrosis, the patient age and antiretroviral treatment were associated to higher degrees of necroinflammation, and HCV genotype 3 was associated to higher degrees of steatosis. CONCLUSION: The data suggest a need for early anti-HCV treatment in both HCV-monoinfected and HIV/HCV-coinfected patients.

No evidence of enteroviruses in the intestine of patients with type 1 diabetes.

AIMS/HYPOTHESIS: The purpose of this study was to investigate whether the gut mucosa is a reservoir for enterovirus persistence in patients with type 1 diabetes. METHODS: Small intestine biopsy samples from 25 individuals at different stages of type 1 diabetes, 21 control individuals and 27 individuals with coeliac disease were analysed for the presence of enterovirus RNA by using both radioactive in-situ hybridisation and real-time RT-PCR and for the presence of enterovirus proteins by immunostaining with antibodies against VP1 and VP4-2-3 capsid proteins and virus polymerase. Lymphocytic enteropathy and serum anti-VP1 antibodies were also evaluated at the time of biopsy. Moreover, high-throughput sequencing was performed to identify viral transcripts or genomes. RESULTS: Enterovirus was not detected by in-situ hybridisation or RT-PCR in any of the individuals tested. Immunohistology revealed a few stained cells in the intestinal epithelium in a low number of individuals, with no difference between diabetic and non-diabetic individuals. Levels of serum IgG against VP1 did not differ between control individuals and those with diabetes or coeliac disease and no evidence of diabetes-related lymphocytic enteropathy was detected. High-throughput sequencing did not reveal specific enterovirus sequences in the gut mucosa of individuals with type 1 diabetes. CONCLUSIONS/INTERPRETATION: Prolonged/persistent enterovirus infections in gut mucosa are not common in patients with type 1 diabetes.

Ghrelin-producing epsilon cells in the developing and adult human pancreas.

AIMS/HYPOTHESIS: While the mechanisms of specification and the reciprocal relationships of the four types of endocrine cell (alpha, beta, delta and pancreatic polypeptide cells) within the human endocrine pancreas are well described in adults and during fetal development, ghrelin-immunoreactive cells (epsilon cells) remain poorly understood. METHODS: We studied epsilon cells in 24 human fetal pancreases between 11 and 39 weeks of development and in 32 pancreases from adult organ donors. RESULTS: We observed single epsilon cells scattered in primitive exocrine tissue from gestational week 13 in developing pancreas. Later in the developmental process, epsilon cells started to aggregate into clusters. From gestational week 21, epsilon cells were observed located around developing islets, forming an almost continuous layer at the peripheral rim of the islets. They remain localised on the mantle of the islets, although at different amounts, in the adult pancreas. Co-production of ghrelin with insulin, glucagon or somatostatin was not detected during fetal development. Co-production with pancreatic polypeptide was evident sporadically. Epsilon cells co-produced NK2 homeobox 2 and ISL LIM homeobox 1, but not NK6 homeobox 1 and paired box 6. A quantitative analysis was performed in the adult pancreas: there was an average of 1.17 + 1.17 epsilon cells per islet, the relative epsilon cell volume was 0.14 + 0.16% and the epsilon cell mass was 0.13 + 0.15 g. Neither sex nor age affected the epsilon cell mass, although there was a significant inverse correlation with BMI. CONCLUSIONS/INTERPRETATION: During fetal development epsilon cells show an ontogenetic and morphogenetic pattern that is distinct from that of alpha and beta cells.

Collagenous colitis: a case series with confocal laser microscopy and histology correlation.

Confocal laser endomicroscopy (CLE) was carried out in seven patients with chronic watery diarrhea (three men; age range 68 - 84 years) to find the correspondence between CLE and histological findings in collagenous colitis. On the basis of the CLE images, two to five biopsies were performed in various segments of the colon. The endoscopic and histological diagnoses of collagenous colitis were made blindly. The quality of the CLE images was quantified from 0 (the endoscopist could not visualize the corresponding histologic equivalent) to 3 (the endoscopist could identify >or= 80 % of the corresponding histologic equivalent). Four out of seven patients had histological findings of collagenous colitis. Correspondence between histology and CLE images yielded the following scores: 3 for epithelial architecture, 3 for goblet cells, 3 for vessels, and 2 for inflammatory infiltrate. In collagenous colitis patients, CLE identified a well-defined "shell" around the crypts, corresponding to the increase in the thickness of the subepithelial collagenous plate evidenced by histology. CLE appears to be a promising means of identifying typical collagenous colitis features.

Endoscopic ultrasound-guided application of a new internally gas-cooled radiofrequency ablation probe in the liver and spleen of an animal model: a preliminary study.

BACKGROUND AND STUDY AIMS: In a previous study, a new flexible bipolar hybrid cryotherm probe was applied with success to the pancreas of a living pig. Here we evaluated feasibility, efficacy, and safety of its application to the porcine liver and spleen. MATERIAL AND METHODS: Ten applications to the liver and nine to the spleen were performed in 19 pigs. Power input (16-18 W) and simultaneous cooling with CO(2) (standardized pressure: 675 psi) as the cryogenic agent were investigated. Application time varied from 120 seconds to 900 seconds. The ablation area was measured by endoscopic ultrasound (EUS) after ablation (T0), and before euthanasia (T1). Gross pathology (T2) and histology after necropsy represented the gold standard. The interval from treatment to euthanasia was 1 or 2 weeks. RESULTS: For both organs the correlation between EUS and gross pathology was good (correlation coefficient R(liver) = 0.71; R(spleen) = 0.73). EUS tended to overestimate the area of the ablated zone. EUS observed a time-dependent ablation area: we demonstrated a positive trend of lesion size (T1) over time in liver tissue (R = 0.51 (P = 0.1)). In the spleen we found a clear correlation of lesion area T2 and application time (R = 0.75, P = 0.01). There were no complications. CONCLUSIONS: Selective EUS-guided transgastric cryotherm ablation of the liver and spleen in a pig model is feasible and safe. The new bipolar probe creates a time-dependent ablation area without any complications, and opens a field of new potential indications of RF-ablative therapies.

Endoscopic ultrasound-guided application of a new hybrid cryotherm probe in porcine pancreas: a preliminary study.

BACKGROUND AND STUDY AIMS: Open, laparoscopic, or percutaneous radiofrequency (RF) ablation of the pancreas is still dangerous, whereas endoscopic ultrasound (EUS)-guided ablation might reduce risk because it is less invasive and provides real-time monitoring. We aimed to demonstrate the feasibility of transluminal RF ablation and to evaluate the efficacy and safety of a new flexible bipolar ablation probe combining RF and cryotechnology. METHODS: 14 ablations were performed in 14 pigs. Energy input (16 W) and simultaneous cryogenic cooling with carbon dioxide (650 psi) were standardized. Application time range was 120 - 900 seconds. Ablation area was measured by EUS immediately after ablation (area T0), and before euthanasia (area T1). Macroscopic findings (area T2) and histological findings after necropsy served as gold standard. The interval from application to euthanasia was either 1 or 2 weeks. RESULTS: The correlation between EUS findings (area T1) and macroscopic appearance (area T2) was good ( R = 0.89). The correlation between the T2 ablation area and the application time showed a fitted ratio of 2.3 ( P < 0.0001) with a 1-week interval and 0.2 ( P = 0.01) with a 2-week interval. No pig died because of the procedure. Two pigs showed histochemical pancreatitis, which was clinically overt in one. Necropsy additionally revealed one burn to the gastric wall and four gut adhesions. CONCLUSIONS: Selective transluminal RF ablation of the pancreas under EUS control in a living pig model is feasible. The new flexible bipolar probe creates an ablation area with extent related to the duration of application, and with fewer complications than conventional RF ablation techniques.

Sentinel node mapping during laparoscopic distal gastrectomy for gastric cancer.

BACKGROUND: The goal of this study was to evaluate the feasibility and accuracy of sentinel node (SN) mapping with endoscopic submucosal blue dye injection during laparoscopic distal gastrectomy for gastric cancer. METHODS: Thirty-four patients affected by gastric adenocarcinoma without gross clinical serosal invasion and distant metastasis were prospectively enrolled. At the start of the surgery, 2 ml of 2% patent blue was endoscopically injected into the submucosal layer at four points around the site of the primary tumor. Sentinel nodes were defined as nodes that were stained by the blue dye within 5-10 min after the dye injection. After identification and removal of sentinel lymph nodes, each patient underwent laparoscopic distal gastrectomy with D1 (n = 2) or D2 (n = 32) lymphadenectomy. RESULTS: Of the 34 patients, 14 had positive nodules (41%). SNs were detectable as blue nodes in 27 (80%) of 34 patients. The mean number of dissected lymph nodes per patient was 31 +/- 10 (range = 16-64) and the mean number of blue nodes was 1.5 (range = 1-4). Only five (sensitivity 36%) of 14 N(+) patients had at least one metastatic lymph node among the SNs identified. In these 14 patients the sentinel node was traced in 12 cases. Sentinel node status diagnosed the lymph node status with 74% accuracy. In early gastric cancer (n = 18), three patients had lymph node metastasis. These early gastric cancer patients with nodal metastases had at least one metastatic lymph node among the SNs identified (sensitivity 100%). CONCLUSIONS: Blue dye SN mapping during laparoscopic distal gastrectomy seems to be a feasible and accurate diagnostic tool for detecting lymph node metastasis in patients with early-stage gastric cancer in which the accuracy of the method was 100%. However, in more advanced gastric cancer the results are not satisfactory. Validation of this method requires further studies on technical issues, including selection of the tracers.

Optical coherence tomography compared with histology of the main pancreatic duct structure in normal and pathological conditions: an 'ex vivo study'.

BACKGROUND AND STUDY AIMS: Optical coherence tomography permits high-resolution imaging of tissue microstructures by a probe inserted into the main pancreatic duct through a standard ERCP catheter. The aim of this study was to compare optical coherence tomography images of the main pancreatic duct with histology and identify the optical coherence tomography pattern of the normal and pathological structure of the main pancreatic duct. PATIENTS AND METHODS: Multiple sections of neoplastic and non-neoplastic segments of 10 consecutive surgical pancreatic specimens obtained from patients with pancreatic head adenocarcinoma were investigated by optical coherence tomography scanning within 1h of resection. One hundred optical coherence tomography findings were then compared with the corresponding histopathological diagnoses. RESULTS: Main pancreatic duct wall architecture appeared at optical coherence tomography investigation as a three-layer structure with a different back-scattered signal from each layer. Optical coherence tomography imaging was concordant with histology in 81.8% and 18.75% of sections with normal tissue and chronic inflammatory changes. The K statistic between the two procedures was equal to 0.059 for non-neoplastic main pancreatic duct wall appearance. In all neoplastic sections optical coherence tomography showed a subverted layer architecture with heterogeneous back-scattering of the signal and was concordant with histology. CONCLUSIONS: Optical coherence tomography provided images of main pancreatic duct wall structure that were concordant with histology in 100% of cases in presence of neoplastic ductal changes and did not have false-positive or negative results. Optical coherence tomography images were also concordant with histology in about 80% of cases with normal main pancreatic duct structure; however, the differential diagnosis between normal tissue and chronic pancreatitis or dysplastic changes appeared very difficult.

Main pancreatic duct, common bile duct and sphincter of Oddi structure visualized by optical coherence tomography: An ex vivo study compared with histology.

BACKGROUND: Optical coherence tomography has been proposed to obtain high-resolution imaging of tissue structure of GI tract. Up till now, the optical coherence tomography appearance of the common bile duct, main pancreatic duct and sphincter of Oddi wall structure has not yet been defined. AIMS: To compare, in a prospective study, optical coherence tomography images of pancreato-biliary ductal system with histology and identify the optical coherence tomography pattern of the normal wall structure of the ducts. METHODS: Multiple sections of non-neoplastic segments of five consecutive ex vivo human pancreatic specimens were investigated by optical coherence tomography scanning within 1h of resection. Sixty optical coherence tomography images were compared with the corresponding histological findings. RESULTS: Optical coherence tomography appearance of normal common bile duct, main pancreatic duct and sphincter of Oddi is characterized by a differentiated three-layer architecture with a regular surface and a homogeneous back-scattered signal, corresponding to the single layer of epithelial cells, the connective-muscular layer and the muscular or acinar structure, respectively. Optical coherence tomography and histology findings were concordant in all cases. CONCLUSIONS: Optical coherence tomography was able to provide in real-time images of wall structure of the normal common bile duct, main pancreatic duct and sphincter of Oddi that are similar to those obtained by histology. These results suggest that optical coherence tomography could enable high-resolution images to be obtained from the pancreato-biliary system during an ERCP procedure.

Immunohistochemical pattern of hMSH2/hMLH1 in familial and sporadic colorectal, gastric, endometrial and ovarian carcinomas with instability in microsatellite sequences.

Alterations of DNA mismatch repair (MMR) genes are involved in carcinogenesis of sporadic and inherited human cancers characterised by instability of DNA microsatellite sequences (MSI). MSI tumours are usually identified using molecular analysis. In the present investigation, hMLH1 and hMSH2 immunohistochemistry was tested in order to evaluate the utility of this method in predicting MMR deficiency. Colorectal (72), gastric (68), endometrial (44) and ovarian (17) carcinomas were independently evaluated for familial history, histological type of tumour, MSI status and immunohistochemical results. Loss of expression of either hMLH1 or hMSH2 was observed in 51 of 55 (92.8%) MSI tumours, while 145 of 146 microsatellite stable (MSS) tumours expressed both the hMLH1 and hMSH2 gene products. Independently of tumour site, an overall agreement between immunohistochemical and molecular results was observed in 15 hereditary non-polyposis colorectal cancer-related tumours. Among sporadic tumours, only 2 of 60 colorectal and 2 of 66 gastric carcinomas, displaying MSI, expressed both hMLH1 and hMSH2 gene products. All 39 endometrial and 16 ovarian tumours presented a concordant molecular and immunohistochemical profile. These data show that immunohistochemistry is an accurate and rapid method to predict the presence of defective DNA MMR genes and to identify both sporadic and familial MSI tumours.

[Diagnostic criteria and classification of gastro-intestinal pancreatic endocrine tumors]. / Criteri diagnostici e classificativi dei tumori endocrini gastroenteropancreatici.

In this presentation the gastrointestinal pancreatic endocrine tumors (ETs) are subdivided into well differentiated ETs and poorly differentiated ETs. Well differentiated ETs are subclassified into ETs with benign behavior, ETs with uncertain behavior and well differentiated endocrine carcinomas. The criteria allowing a distinction among these main types of neoplasms are listed according to the site of origin of the ETs. In addition, the main functional types of ETs of the pancreas, stomach, duodenum, jejunum, ileum, appendix and large bowel are briefly described.

Low incidence of hereditary nonpolyposis colorectal cancer syndrome in a selected area of the Lombardy Cancer Registry.

AIMS AND BACKGROUND: Epidemiological investigations on the frequency of hereditary nonpolyposis colorectal cancer (HNPCC) syndrome are few and have shown a variable worldwide incidence ranging from 1% to 7% of all colorectal cancers (CRCs). In Italy, relevant differences have been observed: 2.8-3% of all CRCs in northern regions and less than 1% in southern regions. The aim of the present study was to investigate the HNPCC incidence in a selected area of northern Italy belonging to the Lombardy Cancer Registry. METHODS AND STUDY DESIGN: We analyzed 197 consecutive patients with newly diagnosed CRCs, histologically verified, and resident in two areas of the Lombardy Cancer Registry. For each case, genetic counseling with at least three generations pedigree reconstruction, HNPCC classification according to Amsterdam criteria, molecular analysis for microsatellite instability and immunohistochemistry for hMLH1 and hMSH2 were performed. RESULTS: A very low frequency (0.5%) of HNPCC fulfilling the Amsterdam criteria was found in comparison to the other Italian areas. Such an incidence seems to be due to actual population differences and reflects a genetic heterogeneity. CONCLUSIONS: The data underline the importance of a precise knowledge of actual HNPCC incidence in different populations in order to optimize effectiveness and efficiency of screening programs for the disease.

TNM staging of neoplasms of the endocrine pancreas: results from a large international cohort study.

BACKGROUND: Both the European Neuroendocrine Tumor Society (ENETS) and the International Union for Cancer Control/American Joint Cancer Committee/World Health Organization (UICC/AJCC/WHO) have proposed TNM staging systems for pancreatic neuroendocrine neoplasms. This study aims to identify the most accurate and useful TNM system for pancreatic neuroendocrine neoplasms. METHODS: The study included 1072 patients who had undergone previous surgery for their cancer and for which at least 2 years of follow-up from 1990 to 2007 was available. Data on 28 variables were collected, and the performance of the two TNM staging systems was compared by Cox regression analysis and multivariable analyses. All statistical tests were two-sided. RESULTS: Differences in distribution of sex and age were observed for the ENETS TNM staging system. At Cox regression analysis, only the ENETS TNM staging system perfectly allocated patients into four statistically significantly different and equally populated risk groups (with stage I as the reference; stage II hazard ratio [HR] of death = 16.23, 95% confidence interval [CI] = 2.14 to 123, P = .007; stage III HR of death = 51.81, 95% CI = 7.11 to 377, P < .001; and stage IV HR of death = 160, 95% CI = 22.30 to 1143, P < .001). However, the UICC/AJCC/WHO 2010 TNM staging system compressed the disease into three differently populated classes, with most patients in stage I, and with the patients being equally distributed into stages II-III (statistically similar) and IV (with stage I as the reference; stage II HR of death = 9.57, 95% CI = 4.62 to 19.88, P < .001; stage III HR of death = 9.32, 95% CI = 3.69 to 23.53, P = .94; and stage IV HR of death = 30.84, 95% CI = 15.62 to 60.87, P < .001). Multivariable modeling indicated curative surgery, TNM staging, and grading were effective predictors of death, and grading was the second most effective independent predictor of survival in the absence of staging information. Though both TNM staging systems were independent predictors of survival, the UICC/AJCC/WHO 2010 TNM stages showed very large 95% confidence intervals for each stage, indicating an inaccurate predictive ability. CONCLUSION: Our data suggest the ENETS TNM staging system is superior to the UICC/AJCC/WHO 2010 TNM staging system and supports its use in clinical practice.

Optical coherence tomography in pediatric patients: a feasible technique for diagnosing celiac disease in children with villous atrophy.

BACKGROUND AND AIM: Celiac disease is a common condition with many atypical manifestations, where histology serves as the "gold standard" for diagnosis. A useful new technique, optical coherence tomography, can depict villous morphology in detail, using light waves. This study examined the correlation between the sensitivity and specificity of optical coherence tomography in pediatric patients undergoing esophago-gastro-duodenoscopy for the diagnosis of celiac disease. MATERIALS AND METHODS: A total of 134 children were prospectively enrolled, 67 with a serological suspicion of celiac disease (group 1) and 67 with negative histology for celiac disease (group 2). During a diagnostic esophago-gastro-duodenoscopy we acquired multiple images and films in the four quadrants of the second part of the duodenum, and biopsies were taken in the area where optical coherence tomography had been done. Three patterns of villous morphology were considered: pattern 1=no atrophy (types 0, 1 or 2 of the Marsh classification); pattern 2=mild atrophy (type 3a or 3b); pattern 3=marked atrophy (type 3c). RESULTS: The diagnosis of celiac disease was histologically confirmed in all 67 children with positive antiendomysium and/or antitransglutaminase antibodies. Optical coherence tomography correlated with pattern 1 histology in 11/11 cases, pattern 2 in 30/32 (93.8%) and pattern 3 in 22/24 (91.6%). Sensitivity and specificity were 82% and 100%. In the control group there was 100% concordance between optical coherence tomography and histology. The overall concordance between optical coherence tomography and histology in determining patchy lesions was 75%. CONCLUSION: Optical coherence tomography could be a helpful diagnostic tool in children with mild or marked villous atrophy for diagnosing celiac disease during upper gastrointestinal (GI) endoscopy, avoiding biopsies. However, duodenal biopsies are mandatory if the optical coherence tomography shows normal villous morphology in patients with positive antibodies.