Correlation Between the Nancy Histopathology Index and Markers of Disease Activity in Pediatric Ulcerative Colitis.

The Nancy Histological Index (NHI) was developed to assess histological disease activity in adult ulcerative colitis (UC) patients. However, data in pediatrics is limited. Our aim was to determine whether the NHI correlates with different indices of disease activity in pediatric UC patients. We retrospectively reviewed the NHI in rectal biopsies from 61 pediatric UC patients (median age 14.3 years), of whom 34 (55.7%) were newly diagnosed. The median Pediatric Ulcerative Colitis Activity Index (PUCAI) score among participants was 30 (interquartile range 5-55). Most patients exhibited an NHI of 3 (41/61, 67.2%) or 4 (8/61, 13.1%), reflecting moderate-severe histologic inflammation. A moderate positive correlation was identified between the NHI and PUCAI, fecal calprotectin, and Mayo endoscopic scores ( r = 0.60, 0.54, and 0.56 respectively, P ≤ 0.001), but not with CRP or albumin. These results indicate that the NHI has a modest correlation with clinical, laboratory and endoscopic indices of disease activity in pediatric UC patients.

Sarcopenia as a Predictor of Survival in Patients with Pancreatic Adenocarcinoma After Pancreatectomy.

OBJECTIVE: To determine whether sarcopenia can potentially predict worse survival after resection of pancreatic ductal adenocarcinoma. BACKGROUND: Sarcopenia is correlated with poor outcomes in hepatopancreatobiliary malignancies, but the relationship of both its qualitative and quantitative features with patient survival after pancreatectomy has not been investigated in a western population. PATIENTS AND METHODS: Preoperative cross-sectional computed tomography scans of consecutive patients who underwent pancreatectomy in 2005-2017 were evaluated for skeletal muscle index (SMI), intramuscular adipose tissue content (IMAC), and visceral-to-subcutaneous adipose tissue area ratio (VSR). Sex-specific categorical cut-offs were determined. Findings were correlated with outcome. RESULTS: The study included 111 patients, 47% of whom were female, with a median age of 67 years (range: 35-87 years), and median body mass index of 23 kg/m2 (range: 16-40 kg/m2); 77% had a Whipple procedure and 66% received adjuvant chemotherapy. Low SMI correlated with poor overall survival (OS) (P = 0.007), disease-specific survival (DSS) (P = 0.006), and recurrence-free survival (RFS) (P = 0.01). High IMAC correlated with poor OS (P = 0.04). Patients with high IMAC tended to have a shorter DSS (P = 0.09), with no correlation with RFS (P = 0.6). VSR was not associated with survival. Multivariable analysis yielded an independent association of low SMI with OS (HR = 1.7, 95%CI: 1.1-2.8, P = 0.02), DSS (HR = 1.8, 95%CI: 1.03-3.2, P = 0.04), and RFS (HR = 1.8, 95%CI: 1.1-2.8, P = 0.01), and of high IMAC with OS (HR = 1.9, 95%CI: 1.1-3.1, P = 0.01). CONCLUSION: Both qualitative and quantitative measures of skeletal muscle were independently associated with impaired survival in patients with resectable PDAC. Sarcopenia might serve as an early radiographic surrogate of aggressive tumor behavior, with potential implications for clinical decision-making and future study.

Real-life Performance of Multiplex Celiac Antibody Test in the Diagnosis of Pediatric Celiac Disease.

OBJECTIVE: Tissue-transglutaminase antibodies (TGA) may be used to diagnose celiac disease (CD) without biopsy in selected cases. We aimed to investigate real-life performance of a CD serology automated analyzer (Bioplex2200), and to explore the correlation between TGA levels and intestinal biopsies in children. METHODS: A retrospective review was performed in 2 pediatric gastroenterological centers, between November 1, 2018 and April 1, 2020 and included patients with both TGA serology testing and duodenal biopsies. Retrieved data included patients' demographics, medical background, TGA levels, and biopsy results. RESULTS: Overall, 538 children were evaluated, 256 with positive TGA (68.4% girls, median age 6.4 years), and 282 with negative TGA (53.9% girls, median age 13.4 years). Among patients with positive TGA, intestinal biopsies confirmed CD in 219 (85.5%). Overall, positive serology with normal histology was found in 14.5% of the cohort, with 52%; 21.6%; 21.1%; and 4.2% in TGA ranges of 1 to 3 times upper limit of normal (ULN); 3 to 5 ULN; 5 to 10 ULN; and above 10 times ULN, respectively, P < 0.001. Area under the receiver-operating characteristic curve (AUC) was 0.963 (95% CI 0.947-0.980). Among patients with positive TGA, 216 (84.4%) had positive anti-endomysial antibodies. In this sub-group, the overall diagnostic performance was inferior, with AUC of 0.737 (95% CI 0.834-0.839). CONCLUSIONS: The Multiplex TGA assay had a very high diagnostic accuracy in real-life. Among patients with positive TGA, adding EMA did not improve the diagnostic performance of the test. False-positive rates differed between different ranges of TGA and were low with TGA above 10 times ULN.

Neutrophil-to-Lymphocyte Ratio Predicts Recurrence Pattern in Patients with Resectable Colorectal Liver Metastases.

BACKGROUND: Studies have suggested that neutrophil-to-lymphocyte ratio (NLR) has value as a predictor of long-term outcomes in various cancer types. Its prognostic potential in patients with CRLM has not been thoroughly investigated. This original, retrospective study assessed the relationship between the preoperative NLR, survival outcomes, and recurrence patterns in patients after colorectal liver metastasis resection (CRLM). METHODS: The prospectively maintained database of a tertiary medical center was queried for all patients who underwent CRLM resection between 2005 and 2017. Patients were divided into two groups: NLR <3 (normal) or >3 (high). Recurrence risk was analysed using Fine and Gray correction for competing risk method and cause specific analyses. RESULTS: The cohort included 231 patients of whom 53 (23%) had a high neutrophil-to-lymphocyte ratio. At presentation, 35% had synchronous disease and 48% had a solitary metastasis; median tumor size was 2 cm. Patients with a high NLR had a significantly higher rate of simultaneous colorectal resection (P = 0.01). A high NLR was independently associated with worse OS (P = 0.02), worse DFS (P = 0.03), and higher risk of recurrence (P = 0.048), specifically recurrence with an extrahepatic pattern (P = 0.03). CONCLUSIONS: A high preoperative NLR was independently associated with poorer survival outcomes and extrahepatic recurrence pattern. The NLR appears to have prognostic importance in CRLM and may serve as a surrogate marker of aggressive systemic disease after resection. These findings warrant external validation, preferably in a prospective design.

Signet Ring Cell Features are Associated with Poor Response to Neoadjuvant Treatment and Dismal Survival in Patients with High-Grade Esophageal Adenocarcinoma.

BACKGROUND: While the prognosis of patients with locoregional esophageal adenocarcinoma (EAC) has improved in the neoadjuvant treatment (NAT) era, high-grade histology (G3) is still associated with a limited treatment response. We sought to investigate oncologic outcomes in patients after esophagectomy for G3 EAC and to identify predictors of poor survival among these patients. METHODS: Patients with EAC who underwent resection with curative intent in 2011-2018 were divided by histologic grade (G3, G1/2) and compared for overall survival (OS). Cox regression was performed to analyze the response to NAT and the predictive role of signet ring cell (SRC) features. RESULTS: The cohort included 163 patients, 94 (57.7%) with G3 histology. NAT was administered to 69 (73.4%) patients. Following resection, OS in the G3 EAC group was 30 months (95% confidence interval [CI] 23.9-36.1). On univariate analysis, G3 disease (p = 0.050) and SRC features (p = 0.019) predicted low OS. Median survival in the G3 EAC group was worse in patients with SRC histology (18 months, 95% CI 8.6-27.4) than those without (30 months, 95% CI 23.8-36.1; p = 0.041). No patients with SRC histology were alive at 5 years of follow-up. Among all patients administered NAT, 88.2% of those with SRC showed minimal or no pathologic response and only 27.8% were downstaged. CONCLUSIONS: High-grade histology was found in most patients with EAC and predicted poor survival and treatment response. SRC features in patients with G3 disease were associated with lower OS. The benefit of NAT for G3 EAC in patients with SRC histology appears limited.

The Transition from Gastric Intestinal Metaplasia to Gastric Cancer Involves POPDC1 and POPDC3 Downregulation.

Intestinal metaplasia (IM) is an intermediate step in the progression from premalignant to malignant stages of gastric cancer (GC). The Popeye domain containing (POPDC) gene family encodes three transmembrane proteins, POPDC1, POPDC2, and POPDC3, initially described in muscles and later in epithelial and other cells, where they function in cell-cell interaction, and cell migration. POPDC1 and POPDC3 downregulation was described in several tumors, including colon and gastric cancers. We questioned whether IM-to-GC transition involves POPDC gene dysregulation. Gastric endoscopic biopsies of normal, IM, and GC patients were examined for expression levels of POPDC1-3 and several suggested IM biomarkers, using immunohistochemistry and qPCR. Immunostaining indicated lower POPDC1 and POPDC3 labeling in IM compared with normal tissues. Significantly lower POPDC1 and POPDC3 mRNA levels were measured in IM and GC biopsies and in GC-derived cell lines. The reduction in focal IM was smaller than in extensive IM that resembled GC tissues. POPDC1 and POPDC3 transcript levels were highly correlated with each other and inversely correlated with LGR5, OLFM4, CDX2, and several mucin transcripts. The association of POPDC1 and POPDC3 downregulation with IM-to-GC transition implicates a role in tumor suppression and highlights them as potential biomarkers for GC progression and prospective treatment targets.

Accuracy, predictability and prognostic implications of fine-needle aspiration biopsy for parotid gland tumours: A retrospective case series.

OBJECTIVE: To evaluate the precision and utility of fine-needle aspiration (FNA) in differentiating between benign and malignant parotid tumours, and the implications of FNA results on management and outcomes. DESIGN: Retrospective case series. SETTING: Tertiary medical centre. PARTICIPANTS: All adults who underwent preoperative FNA, followed by postoperative histological examination, between 1986 and 2014. MAIN OUTCOME MEASURES: Differences in clinical management and outcomes of patients with parotid masses in light of FNA results. RESULTS: We analysed 505 samples from 485 patients. According to histopathological results, preoperative FNA successfully identified benign tumours in 89% of the cases (362/405) and only 59% of malignant tumours (59/100). Overall sensitivity and specificity of FNA in distinguishing between different subtypes of benign lesions were 80% and 99%, respectively, whereas positive predictive value (PPV) and negative predictive value (NPV) were 85% and 98%. Moreover, malignant lesions subtyping had high false-positive and false-negative rates with sensitivity, specificity, PPV and NPV of 44%, 100%, 75% and 99%, respectively. Additionally, when FNA falsely classified malignant tumours as benign, surgeries were inappropriately delayed and the durations of surgeries and hospitalisations were shorter, compared to true malignant FNA results. Interestingly, survival was not affected in falsely benign lesions that were mostly low-grade, conversely non-diagnostic FNA for malignant tumours resulted in decreased survival. CONCLUSIONS: Our findings highlight the limitations of FNA as a decision-making tool in preoperative evaluation of parotid masses. Clinicians should take into account that FNA is inaccurate for identifying specific subtypes of malignant lesions, which may eventually delay treatment and influence outcome.

Young-onset gastric cancer and Epstein-Barr Virus (EBV) - a major player in the pathogenesis?

OBJECTIVE: Gastric cancer (GC) is a leading cause of cancer death, occurs predominantly in older age, with increasing incidence in young patients. The Cancer Genome Atlas indicates four subtypes for GC among which Epstein-Barr virus (EBV) subtype is estimated at 8.7%. We aim to determine the prevalence of EBV subtype in young GC patients (≤45 years) compared with an average-onset cohort (≥55 years) and characterize the clinicopathologic pattern of young-onset GC. METHODS: Gastric cancer samples of patients of both cohorts were screened for EBV by qPCR. Additional staining was done for Human epidermal growth factor receptor 2 (HER2), microsatellite instability (MSI) status and Programmed death-ligand 1 (PD-L1). Demographics and clinical data were retrieved from the medical records. RESULTS: Thirty-nine young-onset and 35 average-onset GC patients were reviewed. There was no apparent difference in tumor location, family history, histology and HER2 status between the cohorts. More young-onset patients were diagnosed with metastatic disease (27% vs 9%, p = 0.0498). EBV was significantly more prevalent in the young-onset cohort (33% vs 11%, p = 0.025). 15/17 EBV positive patients were under the median age of diagnosis for GC in the US (68 years). MSI-H was found only in the average-onset cohort [0% vs 27%, p = 0.001). PD-L1 positivity was higher in the young-onset cohort (31% vs 3%, p = 0.002). CONCLUSION: Our study indicates that EBV subtype is more prevalent in young-onset GC and may play a key role in the pathogenesis. Higher rate of PD-L1 positivity in young-onset GC could change treatment strategies. We are currently evaluating these findings in a prospective trial.

Automated Analyzers Are Suited for Diagnosing Celiac Disease Without a Biopsy.

OBJECTIVES: The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) 2012 guidelines, enabled for the first time, a nonbiopsy approach in the diagnosis of celiac disease (CD). We aimed to prospectively assess 4 tissue-transglutaminase (tTg) IgA assays of 4 random-access analyzers and examine their accuracy in diagnosing CD without a biopsy. METHODS: We enrolled 186 consecutive children referred to upper endoscopy and intestinal biopsy. One group included 109 patients with positive tTg that was referred for suspected CD. Another group included 77 patients with negative tTg referred because of other indications. All participants had a blood sample taken at the time of endoscopy. Samples were tested with 4 tTg IgA assays on automated analyzers and 1 Elisa kit. All intestinal biopsies were evaluated by a local pathologist, a central pathologist, and a CD expert blinded to each other. CD was diagnosed when full agreement was reached. Analytical performance of the assays included precision with controls and samples, lot to lot variation, and carryover. RESULTS: In our cohort, all tested tTg IgA-automated assays showed sensitivities above 98% and specificities above 99%. ROC analysis demonstrated AUC (area under the curve) >0.99 for all 4 analyzers. The positive-predictive values (PPV) were all >0.99 and negative-predictive values (NPV) were >0.97. The Elisa kit had sensitivity of 95%, specificity of 96%, AUC of 0.96, PPV of 0.98 and NPV of 0.93. CONCLUSION: CD can be accurately diagnosed without biopsy based on tTg IgA levels at least 10 times the ULN using the 4 high-volume random-access analyzers used in our study.

Sidedness Matters: Surrogate Biomarkers Prognosticate Colorectal Cancer upon Anatomic Location.

BACKGROUND: Anatomic location of primary tumors across the colon correlate with survival in the metastatic setting, whereas left-sided tumors may exhibit superior survival compared with right-sided tumors. The Oncotype Recurrence Score (RS) assay is a clinically validated predictor of recurrence risk in patients with stage II colorectal cancer (CRC). Previous studies had indicated that without adjuvant chemotherapy, CDX2-negative stage II CRC tumors are associated with a lower rate of disease-free survival than CDX2-positive stage II CRC tumors. We aimed to evaluate whether these two validated prognostic biomarkers may correlate with primary tumor location, and whether tumor location may reflect differential prognosis in stage II CRC. MATERIALS AND METHODS: We retrospectively analyzed patients with T3 mismatch repair-proficient (MMR-P) stage II CRC for whom RS assay was performed. Pathological report was reviewed for exact primary tumor location and CDX2 immunostaining. RS and CDX2 expression were correlated with primary tumor location. RESULTS: The analysis included 1,147 patients with MMR-P stage II CRC (median age 69 years [range 29-93]). Tumor distribution across the colon was as follows: 46% (n = 551) were right-sided and 54% (n = 596) were left-sided. RS was higher in right-sided tumors (p = .01). The RS results gradually decreased across the colon (cecum, highest score; sigmoid, lowest score; p = .04). Right-sided tumors exhibited more CDX2-negative tumors (p = .07). CONCLUSION: Our study indicates that right-sided colorectal tumors may display worse prognosis compared with left-sided tumors in MMR-P stage II CRC. Primary tumor location may serve as a prognostic factor that should be taken into account for recurrence risk assessment and consideration of adjuvant treatment. IMPLICATIONS FOR PRACTICE: Sidedness matters, even in stage II colorectal cancer (CRC). Using two previously established prognostic tools, the Oncotype DX assay and CDX2 expression, this study found that right-sided tumors may display worse prognosis compared with left-sided tumors in mismatch repair-proficient stage II CRC. Therefore, primary tumor location should be taken into account for recurrence risk assessment and consideration of adjuvant treatment.

Stercoral colitis: a lethal disease-computed tomographic findings and clinical characteristic.

OBJECTIVE: The aim of this study was to describe the radiographic findings in stercoral colitis. METHODS: The computed tomographic scans and abdominal radiographs of 13 patients with surgically and pathologically confirmed stercoral colitis from 4 affiliated hospitals were reviewed by a board-certified abdominal radiologist blinded to the official imaging, surgical, and pathologic findings. RESULTS: The median age was 66 years. The patients presented mainly with constipation (100%) and an acute inflammatory process (85%); 5 patients (38%) had frank septic shock. Mortality was 46%. Imaging scans showed that the colon dilated proximally to the impaction site in 6 patients (50%). Other findings included fat stranding (100%), mucosal sloughing (58%), mesenteric hyperemia (58%), and extraluminal gas (17%). CONCLUSIONS: Computed tomography is an important diagnostic modality for stercoral colitis. The presence of a large fecaloma with distention of the affected colon and wall thickening and pericolonic fat stranding should alert radiologists and surgeons to the presence of this potentially fatal condition.

Histology proved malpositioning of dextranomer/hyaluronic acid in submucosal ureter in patients after failed endoscopic treatment of vesicoureteral reflux.

PURPOSE: We histologically investigated the cause of failed endoscopic treatment of vesicoureteral reflux with dextranomer/hyaluronic acid injections in children. MATERIALS AND METHODS: A total of 192 children underwent dextranomer/hyaluronic acid injection at our institution between January 2008 and September 2010. The study population consisted of 13 children (22 ureters) with vesicoureteral reflux who underwent ureteroneocystostomy following failed endoscopic injections (1 to 2) of dextranomer/hyaluronic acid. In all cases the dextranomer/hyaluronic acid was implanted in the mucosa of the mid to distal ureteral tunnel following hydrodistention of the ureter. The medical records were reviewed, and specimens of the archived distal ureters removed during surgery were examined histologically. RESULTS: Mean patient age was 4.1 years. Mean dose of dextranomer/hyaluronic acid was 0.9 ml (both treatments) and mean lag between treatments was 13.4 months. Indications for open surgery were recurrent urinary tract infections and/or residual or aggravated reflux grade IV or higher. Histological study revealed that the dextranomer/hyaluronic acid was malpositioned in 21 of 22 ureters, residing in the muscle fibers in 2, adventitia in 14 and periureteral space in 5. CONCLUSIONS: This is the first known study to provide a histologically proved cause of failure of endoscopic treatment of vesicoureteral reflux with dextranomer/hyaluronic acid injections in children. Malpositioning of the material outside the submucosal ureter was identified in a high percentage of cases. Larger studies are needed to corroborate these findings.

Presence of JC virus DNA in the tumor tissue and normal mucosa of patients with sporadic colorectal cancer (CRC) or with positive family history and Bethesda criteria.

INTRODUCTION: JC virus (JCV) may infect the gastrointestinal tract in childhood, and, by encoding a gene for T-antigen (T Ag), can initiate chromosomal instability in epithelial cells. AIM: We looked for JCV DNA in the cancer tissue of patients with sporadic colorectal cancer (CRC, Group A) and with positive family history and Bethesda criteria (Group B). We hypothesized that the role of JCV may be different between these two groups. METHODS: Fifty-six patients were randomly selected from our database, 30 in Group A and 26 in Group B. DNA was isolated from the tumor, normal mucosa, and plasma, and JCV DNA sequences were looked for with specific polymerase chain reaction (PCR) assays for T Ag primers. Immunohistochemistry for hMLH1, hMSH2, hMSH6, and PMS2 was performed on paraffin-embedded tissue. RESULTS: In Group A, T Ag was demonstrated in 6 (20.00%) and 3 (10.00%) of the tumors and adjacent normal mucosa, respectively (P = 0.094). In Group B, the corresponding observations were 10 (38.46%) and 6 (23.07%), respectively (P < 0.001). Immunohistochemistry for hMLH1, hMSH2, hMSH6, and PMS2 was performed in all of the Group A and B patients. All patients of Group A (100%) showed expression of these proteins, while only 19 patients of Group B did so (73.1%), P = 0.009. JCV T Ag DNA was found in 20, 28.5, and 42.1% of the tumors in Group A, Group B with negative staining for DNA repair genes, and Group B with a positive staining, respectively (NS). CONCLUSION: CRC patients with positive family history have a higher incidence of JCV T Ag, but this did not correlate with specific DNA repair gene mutations. We could not conclude that, on the background of genetic mutation in one of the DNA repair genes, JCV acts as the missing link in the chain of events leading to CRC.

Membrane-bound mucins and mucin terminal glycans expression in idiopathic or Helicobacter pylori, NSAID associated peptic ulcers.

BACKGROUND: The ratio of Helicobacter pylori/NSAID-negative gastric ulcers is increasing. Idiopathic gastric ulcers have unique clinical and endoscopic features, and are associated with more bleeding complications and a higher mortality. Alterations in gastric mucin expression and sialylation pattern may be important in ulcer pathogenesis. AIMS: The purpose of this study was to determine the expression pattern of membrane-bound mucins and side chain sugars in H. pylori associated-, NSAID-, and idiopathic-gastric ulcers. METHODS: We randomly selected 92 patients with H. pylori (group 1, n = 30), NSAID (group 2, n = 18), combined H. pylori and NSAID associated gastric ulcers (group 3, n = 24), and patients with idiopathic gastric ulcers (group 4, n = 20). Immunohistochemistry for T-cell CD4/CD8, MUC1, MUC4, MUC17, and ECA and SNA lectins staining was performed on sections from the ulcer margins. Inflammation score was assessed according to the Sydney system. RESULTS: Bleeding and mortality rates were significantly higher in group 4. CD4 positive T cell count was higher in H. pylori positive patients (P = 0.009). Staining intensity of MUC17 was higher in group 1 than in group 4, foveola and glands alike, with 11.50 ± 3.47 versus 6.80 ± 4.02, and 9.61 ± 4.26 versus 7.59 ± 3.26, respectively (P < 0.0001). This was a mirror image with MUC1. SNA lectin staining was increased in group 4, in parallel to MUC1 expression, indicating more abundant α2-6 sialylation in that group. CONCLUSIONS: Cytoplasmic MUC17 staining was significantly decreased in the cases with idiopathic ulcer. The opposite was demonstrated for MUC1. This observation might be important, since different mucins with altered sialylation patterns likely differ in their protection efficiency against acid and pepsin.

[Nodular regenerative hyperplasia as a complication of thiopurine treatment in a patient with inflammatory bowel disease].

Immunomodulator therapy with thiopurine analogues azathioprine or 6-mercaptopurine is commonly prescribed for the treatment of organ transplantation, inflammatory bowel disease, autoimmune diseases and malignancies. Hepatotoxicity due to thiopurine analogues usually presents as an increase in serum transaminase levels. Toxicity is usually not severe, and a dose reduction is effective in most patients. Nodular regenerative hyperplasia (NRH) is a very rare but potentially severe complication of thiopurine-containing therapy. NRH is often asymptomatic, neither biochemical nor molecular markers are indicative for NRH. The suspicion rises when there are clinical symptoms of portal hypertension or increases in transaminases levels orthrombocytopenia. Liver biopsy is essential for definitive diagnosis. This is a case report of a 40-year-old male patient with Crohn's disease who developed increased serum levels of liver enzymes and thrombocytopenia following the administration of thiopurine. Although treatment with thiopurine was discontinued, he has further progressed and presented with acute variceal bleeding due to portal hypertension. The diagnosis of nodular regenerative hyperplasia was proven by a liver biopsy. In conclusion, NRH is a very rare but potentially severe complication of thiopurine-containing immunosuppressive therapy for IBD.

Early prediction of residual disease after neoadjuvant chemoradiotherapy and cetuximab for locally advanced esophageal cancer using 18F-FDG PET-CT imaging: a prospective cohort study.

Background: Previous studies in locally advanced esophageal cancer (LAEC) suggested that a change in the tumor's metabolic response, i.e., decrease of its interim 18F-FDG uptake compared with baseline, may predict histopathological response. We evaluated the possible predictive correlation between various PET-CT and histopathological parameters following a neoadjuvant biological-containing chemoradiotherapy (CRT) regimen. Methods: Patients with resectable LAEC received neoadjuvant cisplatin/5-fluorouracil-based CRT and cetuximab following one cycle of induction chemotherapy and cetuximab. Changes in maximum and mean standardized uptake values (ΔSUV-max and ΔSUV-mean, respectively) and metabolic tumor volume (ΔMTV), measured by PET-CT at baseline and 2 weeks after the onset of treatment, were compared with histopathological findings at surgery. Histopathological response was defined by tumor regression grade (TRG), pathological complete response (pCR) and microscopic or macroscopic residual disease (RD). Results: Of 18 patients, 13 (72%) with adenocarcinoma (AC) and 5 (28%) with squamous cell carcinoma (SCC), were included. None of the changes in the parameters of PET was associated with pCR; only ΔSUV-mean was associated with TRG in the AC cohort. In contrast, both ΔSUV-mean% and ΔSUV-max% were significantly associated with RD, both in the whole cohort and in the AC cohort. Changes in FDG-uptake predicted RD2 at surgery: only patients with less than 13% decrease in SUV-mean% or less than 29% decrease in SUV-max% had RD2, while all patients with RD0 or RD1 had greater reductions [100% specificity and 100% positive predictive value (PPV)]. Conclusions: Changes in ΔSUV-max and ΔSUV-mean after two weeks of onset of cetuximab-based neoadjuvant chemotherapy for LAEC may predict macroscopic RD but not TRG or pCR at surgery.

The role of duodenal bulb biopsy in the diagnosis of celiac disease in children.

BACKGROUND AND STUDY AIMS: It is suggested that for celiac disease (CD) diagnosis, biopsies should also be taken from the duodenal bulb. Whether bulb biopsies suggestive of CD can be found on upper gastrointestinal endoscopy (EGD) done for reasons other than CD diagnosis is not clear. The aim of our study was to evaluate the contribution of routine bulb biopsies to the diagnosis of CD, when taken regardless of prior suspicion of CD. METHODS: The study included 96 children who underwent EGD for suspected CD and a control group of 69 children who underwent EGD for reasons other than CD. The mucosal changes were evaluated using the Marsh-Oberhuber classification. RESULTS: Among the 87 children diagnosed with CD, we identified 6 patients (7%) with typical histologic findings only in the bulb (Marsh 3), but also 1 patient (1.1%) with findings only in the distal duodenum (Marsh 2). In 20 patients (23%) the histological changes were more severe in the bulb. One patient had more prominent findings in the second part of the duodenum. None of the control patients had histological changes compatible with CD in the bulb or the second part of the duodenum. CONCLUSIONS: Our findings suggest that when CD is suspected, biopsies should be taken from both locations (bulb and second part) as mucosal changes may emerge only at one site. Nevertheless, the presence of characteristic histology on duodenal bulb biopsies might be sufficient for the diagnosis of CD.

Follow-up of children with celiac disease - lost in translation?

BACKGROUND: Celiac disease (CD) is a prevalent condition with a broad spectrum of presentations requiring a lifelong gluten-free diet (GFD). Our aims were to examine the presentation and adherence to a GFD as well as the adequacy of follow-up of children diagnosed with CD at a tertiary referral center. METHODS: A retrospective electronic chart review of pediatric patients suspected of CD (n = 581) who were seen at our institute between January 1999 and December 2008 was performed. RESULTS: 387 children were diagnosed with CD (F/M ratio of 1.54, median age: 6.25 years). Presenting symptoms were iron deficiency anemia (n = 82, 34%), short stature (n = 59, 24.5%) and abdominal pain (n = 59, 24.5%). In 63 patients (16.3%) an associated autoimmune disease was recorded. Only 42.7% of the patients (165/387) had regular out-patient gastroenterologist visits; 22% (86/387) were followed by their primary care physician. Over 35% (136/387) were completely lost to follow-up. Negative serology on follow-up was present in 91% of the CD patients(150/165) followed at our center in comparison to 70% (60/86) in those followed up by their primary physician (p = 0.0002). CONCLUSIONS: At least in our referral center, follow-up of children diagnosed with CD is far from satisfactory. Initiatives aimed at improving adherence to regular follow-up are needed as this intervention is associated with a significant increase in patient compliance with a long-term GFD.

Expression of MMP-1 in invasive well-differentiated thyroid carcinoma.

The objective of this study is to examine the expression of matrix metalloproteinase 1 (MMP-1) in invasive well-differentiated thyroid carcinoma (WDTC) and its relation to clinicopathological features. This retrospective case study group included 26 patients with invasive WDTC who were treated at our center between January 1985 and May 2007. Clinical data were collected from the medical files. MMP-1 expression was tested in samples from paraffin-embedded tumor by immunohistochemical staining. MMP-1 expression correlated with laryngotracheal invasion (p = 0.032), multifocality of the tumor (p = 0.044), and presence of regional (p = 0.034) and distant metastases (p = 0.048). In conclusion, the expression of MMP-1 in invasive WDTC is consistent with tumor aggressiveness, manifested by laryngotracheal invasion, multifocality, and regional and distant metastases. MMP-1 expression may serve as a prognostic marker and an indicator for the need for more aggressive surgical treatment.

[Eosinophilic esophagitis--the experience in a tertiary pediatric center].

BACKGROUND: Eosinophilic esophagitis (EoE) is an inflammatory disorder with increasing prevalence. It typically presents with swallowing difficulties, heartburn or dyspepsia, and in toddlers, failure to thrive. EoE is characterized by eosinophilic infiltrates of the esophageal mucosa, and endoscopies with tissue diagnosis are mandatory. Hypersensitivity has been implicated in the pathogenesis, therefore, most treatment options include steroids and allergen avoidance. AIMS: To summarize a tertiary pediatric clinic's experience with EoE in children and adolescents, describe the spectrum of clinical presentations and treatment options, and raise awareness of this disorder among medical personnel. METHODS: A retrospective, descriptive study of patients diagnosed with EoE at our institute over the past 5 years. Demographic details, presenting symptoms, laboratory studies, endoscopic and pathologic findings were analyzed. Information regarding medical and nutritional therapies and response to treatment were summarized. RESULTS: Fifteen cases of EoE in children and adolescents are described. Average age at diagnosis was 9 years (range 0.7-161. The most common complaint was dysphagia (60%e. The majority demonstrated food allergies 19/121. Most of the patients were treated with topical ingested steroids, while others had either elemental formula or allergen elimination. Favorable responses were seen in most patients treated with steroids (8/11). Long-term results of nutritional therapy are insufficient to draw conclusions on its efficacy. CONCLUSIONS: EoE causes major eating difficulties and affects quality of life in children, sometimes accompanied by failure to thrive. There is a clear association with food allergies, and positive responses to steroids are common. A high index of suspicion and referral to a gastroenterologist for definite diagnosis are required. Combining medical with nutritional treatment seems promising but further studies regarding the long-term outcome are needed.