and HBeAg(-) patients - World Journal of Gastroenterology

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ment, t (3;14) (p27;q32) with BCL6-rearrangement and t (8;14) (q24;q32) with MYC rearrangement, respectively. Variability has been observed in CD45, CD5 and CD10 expression, with the CD10 expression in particular referred as a prognostic indicator [33] . Endoscopy cannot distinguish gastric lymphoma from the more common gastric carcinoma. The three main patterns that can be recognized at endoscopy include ulceration, diffuse infiltration, and polypoid mass, which are, however, not specific [34] . Endoscopy, however, is an indispensable tool for the initial diagnosis and follow-up of cases as well as for obtaining biopsy specimens. EUS can assess the extent of lesion and its invasion. Lesions are usually hypoechoic although few hyperechoic cases have been reported [34] . Infiltrative carcinoma tends to have a vertical growth in gastric wall, while lymphoma tends to show mainly a horizontal extension and more involvement of perigastric lymph nodes [35] . EUS is highly accurate in detecting the depth of lymphomatous infiltration and the presence of perigastric lymph nodes, thus providing additional information for treatment planning, and can differentiate lymphoma from carcinoma both in early stage and in advanced stage [36] . Radiographic patterns of gastric lymphoma observed in double-contrast UGI studies include ulcers, polypoid mass, thickened fold, mucosal nodularities or infiltrating lesions, which are not conclusive, thus posing a diagnostic challenge while differentiating from other malignant and benign lesions, hence requiring pathological confirmation. Preservation of gastric distensibility and pliability, despite the extensive infiltration with gastric fold thickening, is a finding more suggestive of lymphoma. Gastric wall thickening is much less severe in low-grade lymphoma than in high-grade lymphoma on CT images, and abdominal lymphadenopathy is less common in low-grade lymphoma. Preservation of the fat plane with no invasion of surrounding structures may be suggestive of lymphoma, although it is, however, not specific. Transpyloric spread and extension of lymphadenopathy below the renal hilum and the presence of bulky lymph nodes are more suggestive of lymphoma than carcinoma [37] . The patterns of gastric involvement observed can be segmental or diffuse infiltration, or localized polypoid. Tumor infiltration is usually homogeneous although areas of low attenuation may be present in larger tumors. Diffuse infiltration involving more than 50% of the stomach and segmental infiltration are the most common features of gastric NHL on CT images [38] . The MRI features include irregularly thickened mucosal folds, irregular submucosal infiltration, annular constricting lesion, exophytic tumor growth, mesenteric masses and mesenteric/retroperitoneal lymphadenopathy. The tumors are usually homogeneous and intermediate in signal intensity on T1-weighted images. Heterogeneously increased signal intensities are noted on T2-weighted images. The enhancement is usually mildmoderate after intravenous administration of gadolinium dimeglumine [39] . Application of 18F-FDG PET/CT in diagnosis of gastric lymphoma is challenging due to the physiologic FDG activity in the stomach and variability WJG|www.wjgnet.com Ghimire P et al . Primary GI lymphoma in the degree of uptake in various histologic subtypes. It was reported that aggressive gastric lymphoma has more intense uptake than low grade MALT lymphoma [40] . Small intestine lymphoma Primary malignant tumors of the small intestine are very rare, accounting for less than 2% of all gastrointestinal malignancies. Lymphoma constitutes 15%-20% of all small intestine neoplasms and 20%-30% of all primary gastrointestinal lymphomas. Ileum is the most common site (60%-65%) involving small intestine lymphoma followed by jejunum (20%-25%), duodenum (6%-8%) and other sites (8%-9%) [41] . The age of presentation varies with the histological subtype of lymphoma. The clinical presentation of small intestinal lymphoma is non specific and the patients have symptoms, such as colicky abdominal pain, nausea, vomiting, weight loss and rarely acute obstructive symptoms, intussusceptions, perforation or diarrhea [42] . Primary small intestine lymphomas that are more heterogeneous than those in stomach include MALT lymphoma, DLBCL, EATL, MCL, follicular lymphoma and immunoproliferative lymphoma, and can be divided into immunoproliferative small intestinal disease (IPSID) [43] . IPSID, also known as alpha chain disease, is a MALTassociated lymphoma due to C. jejuni infection and characterized by “centrocyte like” mucosal infiltration with plasma cells that secrete monotypic and truncated immunoglobulin, a heavy chain lacking of an associated light chain. IPSID mainly affects older children and younger adults with a predominant involvement of proximal small intestine, the symptoms of its patients are diarrhea and abdominal pain [44] . MCL primarily affects individuals at the age of over 50 years, and involves terminal ileum and jejunum appearing as numerous polyps, hence called multiple lymphomatous polyposis [45] . The prototype MCL is positive for pan B-cell antigens, although few cases of CD5- MCL have been reported [44] . Cytogenetic analysis of MCL has shown the rearrangement of bcl-1 locus on chromosome11 due to t (11;14) (q13;q32) translocation, accompanying cyclin D1 antigen overexpression. Few cases of cyclin D1-negative MCL, however, have been reported with up-regulated cyclin D2 or D3 [46] . Burkitt’s lymphoma mainly affects children and is associated with EBV and HIV/AIDS [47] . T cell lymphoma of the small intestine accounts for approximately 10%-25% of all primary intestinal lymphomas primarily occurring as enteropathyassociated T cell lymphoma, and most of them are often complicated by Crohn’s disease [48,49] . Although follicular lymphoma is very rare, it expresses SIg (frequently IgM) and pan B-cell antigens with CD10 and bcl-2 expressed in almost 90% of cases. It is negative for CD5 and cyclin D1 differentiating it from MCL. IgH/BCL2 rearrangement with t (14;18) (q32;q21) can be demonstrated by FISH or PCR analysis in the majority of cases [50] . Lymphocytic lymphoma (chronic lymphocytic leukemia) rarely arises primarily from the gastrointestinal tract. Evaluation of the small intestinal lymphoma has been revolutionized since the introduction of capsule endoscopy (CE) and double-balloon technique of push-and- 701 February 14, 2011|Volume 17|Issue 6|
Ghimire P et al . Primary GI lymphoma pull enteroscopy which is capable of enabling biopsies as well as performing interventions, and limiting major surgical interventions. Small intestine lymphoma appears as a mass, polyp and ulcer on CE which cannot be distinguished from other lesions [51] . Radiologic findings of small intestinal lymphoma are not specific, thus posing a difficulty in distinguishing it from other benign and malignant lesions. The common features of small intestine lymphoma seen in barium studies and CT include polypoid form, multiple nodules, infiltrative form, endoexoenteric form with excavation and fistulization, and mesenteric invasive form with an extraluminal mass. The radiological findings usually do not correlate to its pathological subtypes. Certain features are, however, peculiarly noted. MCL, follicular lymphoma and MALT lymphoma rarely present with multiple polyps (multiple lymphomatous polyposis) [52] . Burkitt lymphoma usually presents as a bulky mass in the right lower quadrant. IPSID tends to affect proximally with a disseminated nodular pattern leading to mucosal fold thickening, irregularity and speculation. EATL, usually proximal or diffuse, shows nodules, ulcers or strictures [53] . PTCL preferentially involves the jejunum with an increased tendency to perforate [54] . Colorectal lymphoma Colorectal lymphoma constitutes 6%-12% of all gastrointestinal lymphomas. Most colorectal lymphomas are secondary involvement of the wide spread diseases. Primary colorectal lymphoma is very rare, constituting only 0.2% of all malignant tumors arising from the colorectal region with caecum, ascending colon and rectum more often affected [55] . The disease predominantly affects males in the fifth-seventh decade of life with abdominal pain, loss of weight, palpable abdominal mass or lower gastrointestinal bleeding. Obstruction and perforation are relatively rare in patients with colorectal lymphoma [56] . Lymphoma of the colorectal region is mostly the B-cell lineage as other sites of the gastrointestinal tract. Primary colorectal lymphoma comprises low grade B-cell lymphoma arising from MALT, MCL and T-cell lymphoma besides large B cell lymphoma. The role of H. pylori in the pathogenesis of colorectal lymphoma has not been fully established [57] . Colorectal MALT-lymphoma is less common in colon and rectum than in small intestine. MCL in the colorectal region presents usually in the setting of diffuse systemic diseases. Peripheral T-cell lymphoma is rare in Western countries with an increasing frequency in many Asian countries, and is more aggressive in nature than other types with perforation as its common feature, and its prognosis is poor [58] . Endoscopically, lymphoma appears to be fungating, ulcerative, infiltrative, ulcerofungating, and ulceroinfiltrative types, with fungating and ulcerofungating types being more common [59] . The radiologic appearances of colorectal lymphoma are variable and significantly overlapped with other benign and malignant condition of the colorectal region. The imaging findings during double-contrast barium enema can be divided into focal and diffuse lesions. The observed focal lesions include polypoid mass, WJG|www.wjgnet.com circumferential infiltration with smooth mucosal surface or extensive ulceration, cavitary mass, mucosal nodularity, and mucosal fold thickening. Diffuse lesions encompass diffuse ulcerative and nodular lesions. Peripheral T-cell lymphoma presents as a diffuse or focal segmental lesion with extensive mucosal ulceration similar to that observed in granulomatous conditions as Crohn’s disease or tuberculosis. MALT lymphoma is manifested as multiple mucosal nodularity [60,61] . TREATMENT The treatment strategy for gastrointestinal lymphoma is dependent on the age of patients, clinical scenario, histological subtype, extent and burden of the disease, and comorbidity, besides other factors. Surgery, chemotherapy, radiotherapy and radioimmunotherapy are the different modalities for its management and can be applied in different combinations. A detailed discussion on the treatment of all subtypes is beyond the scope of this article, thus the most common treatment modalities are highlighted in brief based on the region of presentation. Oropharyngeal lymphoma The definite management protocol for oropharyngeal lymphoma has not yet been established. Unlike the majority of other malignancies in this region, surgery does not play a primary role in the management of oropharyngeal lymphoma [62] . Combined chemotherapy and radiotherapy for localized oropharyngeal lymphoma is recommended in most studies [14] . Advanced oropharyngeal lymphoma is usually treated with aggressive chemotherapy with or without radiotherapy. Esophageal lymphoma Due to the rarity of esophageal lymphoma, no standardized approaches to its management have been formulated. Secondary lymphoma involving the esophagus can be treated with chemotherapy, while primary esophageal lymphoma can be managed with surgery, chemotherapy and radiotherapy or their combination. Treatment protocols vary depending on its histological subtypes and extent. Although surgery is the initial treatment modality, it has been recently reserved for cases with their diagnosis not possibly made at endoscopic biopsy or for those who warrant surgical intervention due to complications such as perforations. Esophageal lymphoma can be treated with local resection and chemotherapy with or without radiotherapy as its initial therapy. However, chemotherapy or radiotherapy alone can be also used as its initial therapy. The commonly employed chemotherapy regimen is CHOP in combination with Rituximab. It was reported that external beam radiation at the dose of 40 Gy can also be used [63] . Gastric lymphoma Treatment strategies for gastric lymphoma have changed dramatically over the last two decades. However, they are still very controversial. The most widely recommended 702 February 14, 2011|Volume 17|Issue 6|
Page 1 and 2: World Journal of Gastroenterology W
Page 3 and 4: Robert JL Fraser, Daw Park Jacob Ge
Page 5 and 6: Italy Donato F Altomare, Bari Piero
Page 7 and 8: Fernando Azpiroz, Barcelona Ramon B
Page 9 and 10: S Contents EDITORIAL REVIEW ORIGINA
Page 11 and 12: Contents ACKNOWLEDGMENTS APPENDIX A
Page 13 and 14: Jahn KA et al . Colon cancer and li
Page 23 and 24: Săftoiu A. Imaging techniques in E
Page 29 and 30: Ghimire P et al . Primary GI lympho
Page 31: Ghimire P et al . Primary GI lympho
Page 37 and 38: Ghimire P et al . Primary GI lympho
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Page 42 and 43: Table 2 Comparison of hepatitis B e
Page 45 and 46: Utama A et al . HBV core promoter m
Page 47 and 48: Utama A et al . HBV core promoter m
Page 49 and 50: Motoki T et al . Glutamine depletio
Page 51 and 52: Table 2 Nutrient composition of mou
Page 53 and 54: A Motoki T et al . Glutamine deplet
Page 55 and 56: A Counts B % of sub-G0 cell populat
Page 57 and 58: Motoki T et al . Glutamine depletio
Page 59 and 60: Hu JD et al . Urinary metabolomic p
Page 61 and 62: Abundance/× 10 6 Abundance/× 10 6
Page 63 and 64: A Regression factor scores 2 for an
Page 65 and 66: Hu JD et al . Urinary metabolomic p
Page 67: Fu JF et al . NAFLD and metabolic s
Page 70 and 71: developing hypertension (OR: 2.18,
Page 72 and 73: obese and exhibited higher insulin
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Page 77 and 78: Roberts SE et al . Perinatal factor
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Oksaharju A et al . Probiotics regu
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Factors associated with improved su
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Koehler-Santos P et al . Identifica
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Koehler-Santos P et al . Identifica
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Goenka MK et al . Capsule endoscopy
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Tatsuki M et al . Hypermagnesemia a
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Chang CC et al . Parity and gastric
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Chang CC et al . Parity and gastric
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Zhang XQ et al . EEA model of guine
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Table 3 Measurement of common bile
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Zhang XQ et al . EEA model of guine
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Zhao R et al . Gene expression anal
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Zhao R et al . Gene expression anal
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Qiu HB et al . HBV infection and li
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Qiu HB et al . HBV infection and li
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Shen H et al . K-ras and BRAF mutat
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Instructions to authors Indexed and
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