Lin Jt

Narrow-band imaging with magnifying endoscopy for the screening of esophageal cancer in patients with primary head and neck cancers.

BACKGROUND AND STUDY AIMnAlthough narrow-band imaging (NBI) in endoscopy can improve detection of early-stage esophageal malignancies in patients with head and neck cancers, false-positive results may be obtained in areas with nonspecific inflammatory changes. This study evaluated the feasibility of primary screening with NBI and magnification for the presence of esophageal malignancies in these cancer patients.nnnPATIENTS AND METHODSnSixty-nine patients with documented head and neck cancers were enrolled from April 2008 to January 2009. All patients underwent a meticulous endoscopic examination of the esophagus using a conventional white-light system followed by re-examination using the NBI system and final confirmation with NBI plus magnification.nnnRESULTSnTwenty-one patients (30.4 %) were confirmed to have esophageal neoplasia. Among these 21, 16 (76.2 %) had synchronous lesions, 9 (42.9 %) were asymptomatic, and 10 (47.6 %) had early-stage neoplasia. The incidence of multiple esophageal neoplasia was 57.1 %. NBI was more effective than conventional endoscopy in detecting neoplastic lesions (35 lesions in 21 patients vs. 22 lesions in 18 patients) and was particularly effective in patients with dysplasia (13 lesions in 9 patients vs. 3 lesions in 3 patients). The sensitivity and accuracy of detection were 62.9 % and 64.4 % for conventional endoscopy, 100 % and 86.7 % for NBI alone, and 100 % and 95.6 % for NBI with high magnification, respectively.nnnCONCLUSIONSnCompared with current approaches, NBI followed by high magnification significantly increases the accuracy of detection of esophageal neoplasia in patients with head and neck cancers. The result warrants conducting prospective randomized controlled study to confirm its efficacy.

Loss of heterozygosity and microsatellite instability in hepatocellular carcinoma in Taiwan

SummaryElucidation of the basic genetic changes of human hepatocellular carcinoma is important for the understanding and treatment of this cancer. We used microsatellite polymorphism markers to study 30 cases of hepatocellular carcinoma (34 tumours) on all human chromosomes. DNA from 34 pairs of hepatocellular carcinomas and corresponding non-tumour parts was prepared. Loss of heterozygosity (LOH) and microsatellite instability on 23 chromosomes were investigated by 231 sets of microsatellite markers. More than 20% LOH was shown for loci on 16q (47.1%), 13q (32.4%), 17p (32.4%), 5q (26.5%), 11p (23.5%) and 9p (20.6%). The commonly affected regions were mapped to 16q12.1, 16q12.2, 16q24, 13q12.1–32, 17p13, 5q32, 5q34, 5q3, 11p15, 11q23–24 and 9p21. Hepatitis B virus carriers had a significantly higher frequency of LOH on chromosomes 5q, 11p and 16q. Furthermore, larger tumour size tended to have higher frequency of LOH at D16S409 locus (16q12.1). Microsatellte instability was only found in 12 of 231 markers and the frequency is very low. These data suggest that the chromosomes 16q, 13q, 17p, 5q, 11p and 9p might participate in hepatocarcinogenesis. However, microsatellite instability might play little role in the development of this cancer in Taiwan.

Gastric cancer risk in relation to Helicobacter pylori infection and subtypes of intestinal metaplasia

Helicobacter pylori (H. pylori) infection and intestinal metaplasia (IM) are each associated with an increased risk of gastric cancer (GC). To explore further the influences of H. pylori and IM on GC, H. pylori and subtypes of IM were evaluated in 135 sex and age-matched case and control pairs. Odds ratios (ORs) with 95% confidence intervals of developing GC were calculated for each risk factor using multiple logistic regression analysis. ORs for H. pylori infection and IM were 2.43 (1.29-4.65) and 4.59 (2.58-8.16), respectively, and those for different IM subtypes gave values of 0.82 (0.28-2.36) for type I, 2.03 (0.95-4.34) for type II and 39.75 (14.34-110.2) for type III. Stratification analysis by histological subtype and stage of GC showed a particularly high OR for IM in intestinal type (12.8, 4.73-34.83) and early GC (6.40, 2.25-18.18). Our data indicate that both H. pylori and IM are related to GC risk. Type III IM is a more specific marker of premalignancy, with relevance, in particular, to the early and intestinal type of GC.

Randomised clinical trial: high‐dose vs. standard‐dose proton pump inhibitors for the prevention of recurrent haemorrhage after combined endoscopic haemostasis of bleeding peptic ulcers

The optimal dosage of intravenous proton pump inhibitors (PPIs) for the prevention of peptic ulcer rebleeding remains unclear.

Systematic review with meta‐analysis: the efficacy of levofloxacin triple therapy as the first‐ or second‐line treatments of Helicobacter pylori infection

Levofloxacin triple therapy has been used for the first‐line and second‐line treatment of Helicobacter pylori infection for more than 10 years.

Overexpression of p53 in different subtypes of intestinal metaplasia and gastric cancer.

p53 immunostaining was evaluated in cancerous epithelia and adjacent intestinal metaplasia of 135 gastric cancer specimens. The differential p53 overexpression in different subtypes of intestinal metaplasia and gastric cancer suggests that type III intestinal metaplasia is the commonest lesion in dysplasia-carcinoma transition, particularly in the intestinal type of gastric cancer.

Differential response to H. pylori eradication therapy of co-existing diffuse large B-cell lymphoma and MALT lymphoma of stomach—significance of tumour cell clonality and BCL10 expression†

We recently reported that low‐grade mucosa‐associated lymphoid tissue lymphoma (MALToma) and diffuse large B‐cell lymphoma (DLBCL) with MALToma (DLBCL[MALT]) of stomach are equally responsive to H. pylori eradication therapy (HPET) and that H. pylori‐independent status is closely associated with nuclear translocation of BCL10. However, co‐existing MALToma and DLBCL components of gastric DLBCL(MALT) may respond differentially to HPET and the underlying mechanism remains unclear. Tumour tissue samples from 18 patients with microdissectable co‐existing MALToma and DLBCL cells were studied. The clonality of lymphoma cells was examined by polymerase chain reaction‐based amplification of the CDR3 region of the IgH gene and confirmed by DNA sequence analysis. BCL10 expression was determined by immunohistochemistry. Differential response of co‐existing MALToma and DLBCL to HPET was defined as complete eradication of one component while the other component remained. Five (27.8%) of the 18 patients showed different IgH gene rearrangements in the two components and three (60%) of these five patients had differential response of MALToma and DLBCL to HPET. By contrast, 13 patients showed identical IgH gene rearrangements and only one (8%) of them had differential response of the two components to HPET (p = 0.044). Further, all four patients with differential response of MALToma and DLBCL to HPET showed nuclear expression of BCL10 in the H. pylori‐independent component and cytoplasmic expression of BCL10 in the H. pylori‐dependent component while the expression patterns of BCL10 were identical in both of these components in the 14 patients who had similar tumour response to HPET. We conclude that different clonality is a common reason for the differential response of co‐existing MALToma and DLBCL of gastric DLBCL(MALT) to HPET and that immunohistochemical examination of BCL10 expression may help to identify the co‐existence of these components. Copyright

Genetic polymorphisms and tissue expression of interleukin-22 associated with risk and therapeutic response of gastric mucosa-associated lymphoid tissue lymphoma

Chronic Helicobacter pylori-stimulated immune reactions determine the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. We aimed to explore the genetic predisposition to this lymphoma and its clinical implication. A total of 68 patients and 140 unrelated controls were genotyped for 84 single-nucleotide polymorphisms in genes encoding cytokines, chemokines and related receptors that play important roles in T cell-mediated gastrointestinal immunity. Five genotypes in IL-22, namely CC at rs1179246, CC at rs2227485, AA at rs4913428, AA at rs1026788 and TT at rs7314777, were associated with disease susceptibility. The former four genotypes resided in the same linkage disequilibrium block (r2=0.99) that conferred an approximately threefold higher risk. In vitro experiments demonstrated that co-culturing peripheral mononuclear cells or CD4+ T cells with H. pylori stimulated the secretion of interleukin-22 (IL-22), and that IL-22 induced the expression of antimicrobial proteins, RegIIIα and lipocalin-2, in gastric epithelial cells. Furthermore, patients with gastric tissue expressing IL-22 were more likely to respond to H. pylori eradication (14/22 vs 4/19, P<0.006). We conclude that susceptibility of gastric MALT lymphoma is influenced by genetic polymorphisms in IL-22, the product of which is involved in mucosal immunity against H. pylori and associated with tumor response to H. pylori eradication.

Gastrointestinal: Burkitt's lymphoma

Lymphomas are solid malignancies of lymphoid tissue that can be categorized as either Hodgkin’s disease or nonHodgkin’s lymphoma. It is rare for Hodgkin’s disease to involve the gastrointestinal tract. Although the majority of non-Hodgkin’s lymphomas are thought to arise from lymph nodes, at least 30% arise in other organs and are called extranodal or primary lymphomas. Of these extranodal lymphomas, up to 40% are located in the gastrointestinal tract, particularly in the stomach and small bowel. Most of these lymphomas are of B-cell lineage. The most common are the diffuse large cell lymphoma and the marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). Other B-cell lymphomas include Burkitt’s lymphoma, mantle cell lymphoma and follicular lymphoma. The images shown below were from a 76-year-old man who was admitted to hospital with malaise, weight loss and pain in the left flank. He subsequently had two significant episodes of hematemesis and melena. Upper gastrointestinal endoscopy revealed bleeding from multiple doughnut-like tumors in the body and antrum of the stomach (Fig. 1). He also had giant gastric folds. A computed tomography scan of the abdomen showed thickening of the wall of the jejunum and tumor infiltration of the left renal pelvis and parts of the right kidney. Histopathological examination of gastric biopsy specimens showed sheets of intermediate-sized lymphoid cells crowding between glands with an interspersed starry-sky pattern (Fig. 2; HE: ×200). Immunohistochemical stains were positive for CD20 (indicating B-cell lineage) and almost all cells were positive for Ki-67 (indicating an extremely high proliferation rate). The diagnosis was that of Burkitt’s lymphoma. Apart from Burkitt’s lymphoma, multiple gastric polypoid lesions with central ulceration can be seen in Kaposi’s sarcoma, stromal cell tumors, metastatic gastric tumors and other lymphomas. Although only 1‐2% of adult non-Hodgkin’s lymphoma are of the Burkitt’s variety, substantially higher percentages have been described in the pediatric setting and in patients with HIV. Blackwell Science, LtdOxford, UKJGHJournal of Gastroenterology and Hepatology0815-93192005 Blackwell Publishing Asia Pty LtdOctober 2005201016161616Images of Interest Images of InterestImages of Interest

Gastrointestinal: Sister Mary Joseph nodule

Rarely, patients with advanced cancer develop a metastasis in the umbilicus. This has been called a Sister Mary Joseph nodule after Sister Mary Joseph, a Franciscan nun, who worked as head nurse and surgical assistant to Dr William Mayo. The term Sister Mary Joseph nodule may not have been widely used in her lifetime but was included in a textbook by Sir Hamilton Bailey in 1949 entitled “Physical Signs in Clinical Surgery I”. The most common primary sites for umbilical metastases are stomach, ovary, pancreas and colon. The mode of spread to the umbilicus is debated but direct spread, perhaps along ligaments of embryonic origin, may be the most important. Other possible modes of spread include lymphatic spread and spread along persistent paraumbilical veins. The cardinal clinical feature is the development of a firm, mobile nodule or nodules in the umbilicus. The skin covering the nodule is usually of normal color but may be red or purple and can progress to a malignant ulcer. The sign almost always indicates advanced cancer and facilitates a histological diagnosis. Survival rates vary with the primary site but are usually less than 12 months. In the images shown below, umbilical metastases were associated with a malignant stromal cell tumor in the stomach. The patient was a 54-year-old man who was investigated because of lower abdominal pain and weight loss. There was a firm nodule in the umbilicus that was non-tender and relatively fixed (Figure 1). An abdominal computed tomography (CT) scan showed an irregular mass, 4 cm in diameter, with central calcification in the upper abdomen and numerous nodules in the peritoneum and mesentery. A sagittal, contrast-enhanced CT scan (Figure 2) showed both mesenteric nodules and the umbilical nodule (arrow). He was treated surgically by wedge resection of the stomach, debulking of mesenteric metastases and excision of the umbilical nodule. At histology, there were spindle cells with marked nuclear pleomorphism and increased mitotic activity that were positive for CD117 and CD34. He was diagnosed with a malignant stromal cell tumor of the stomach and is currently in remission after treatment with imatinib mesylate.