Double balloon endoscopy as a useful tool for the diagnosis and treatment of four cases of primary small intestinal lymphoma

Primary small intestinal lymphoma (PSIL) is a relatively rare form of non-Hodgkin lymphoma, often complicated by bleeding, obstruction, or perforation of the intestine during the clinical course. The initial diagnosis and management of these complications are often difficult in PSIL, because the small intestine is usually inaccessible in routine endoscopy. Recently, total enteroscopy with a double-balloon method, called double balloon endoscopy (DBE), has been developed for the diagnosis and treatment of small intestinal disorders. We report herein on 4 cases of PSIL (2 diffuse large B-cell lymphomas and 2 follicular lymphomas [FLs]). In these cases, DBE was useful in the diagnosis, decision to perform surgery after assessment of bleeding lesion, and treatment of the intestinal stenosis using enteroscopic balloon dilatation. Combination chemotherapy consisting of anthracycline, cyclophosphamide, vincristine, and prednisolone with rituximab was administered in 3 cases, and all achieved complete remission. One patient with FL of the duodenum was treated with rituximab alone, but with little effect. We conclude that DBE is useful in the management of PSIL. More PSIL cases must be analyzed to establish the optimal management of patients with this form of lymphoma.     

Gastrointestinal follicular lymphoma: review of the literature

Gastrointestinal follicular lymphoma (GI-FL) is a relatively rare disease, accounting for only 1%-3.6% of gastrointestinal non-Hodgkin’s lymphoma. Although the duodenum and terminal ileum are considered to be the most common sites of origin, the development of wireless capsule endoscopy and double-balloon enteroscopy has increased the detection of GI-FL in every part of the small intestine. Approximately 70% of patients with GI-FL are estimated to have multiple lesions throughout the entire gastrointestinal tract. FL is a low-grade lymphoma that usually develops very slowly. If the lymphoma causes no symptoms, immediate treatment may not be necessary. Standard therapy has not yet been established for GI-FL, but chemotherapy, radiotherapy, monoclonal antibody therapy, or a combination of these therapies, is sometimes performed based on the therapeutic regimens for nodal FL. Regimens including conventional chemotherapy with rituximab, which achieve high response rates in nodal FL, are commonly used for GI-FL. The long-term clinical outcome of GI-FL is unclear. The results of a few series on the long-term outcomes of patients with GI-FL treated with conventional therapy indicate a median relapse-free time ranging from 31 to 45 months. On the other hand, in patients with GI-FL who were followed without treatment, the median time to disease progression was 37.5 months. Thus, whether to initiate aggressive therapy or whether to continue watchful waiting in patients with GI-FL is a critically important decision. Ongoing research on biomarkers to guide individualized GI-FL therapy may provide invaluable information that will lead to the establishment of a standard therapeutic regimen.     

Double-balloon endoscopy for the diagnosis and treatment of small intestinal disease

Evaluation of the small bowel has long been hampered because of its long and multiple complex loop configurations. Yamamoto et al have developed a new method of inserting an endoscope, known as the double-balloon method of enteroscopy, the Fujinon double-balloon endoscopy system being specialised for this application. Two types of endoscope are currently available for this technique. The EN-450 P5 is a thin endoscope for regular use, whereas the EN-450 T5 is a therapeutic double-balloon endoscope with a larger accessory channel of 2.8mm in diameter. Double-balloon endoscopy enables visualisation of the entire small bowel and also allows for interventional therapy in the small intestine. This method can be used either from an oral or an anal insertion. Observation of an affected area with controlled movement of the endoscope enables interventions, including biopsies, haemostasis, balloon dilatation, stent placement, polypectomy and endoscopic mucosal resection, to be performed. In our large study series, it was demonstrated that double-balloon endoscopy permitted exploration of the small intestine with the high success rate of total enteroscopy. The procedure is safe and useful, and it provides high diagnostic yields and therapeutic capabilities.     

Two cases of discordant lymphomas consisting of MALT lymphoma and follicular lymphoma

We report here rare cases of discordant lymphoma consisting of MALT lymphoma and follicular lymphoma. Case 1: A 53-year-old woman was diagnosed with MALT lymphoma of the left parotid gland and follicular lymphoma of the duodenum and small intestine. Case 2: A 38-year-old woman was diagnosed with MALT lymphoma of the intestine and follicular lymphoma of the duodenum and bone marrow. Recently, it has been suggested that duodenal follicular lymphoma has intermediate characteristics of nodal follicular lymphoma and MALT lymphoma. It is interesting that both of these cases demonstrated duodenal follicular lymphoma. These cases suggest that MALT lymphoma and duodenal follicular lymphoma share some common pathological condition.     

Follicular Lymphoma with Extensive Gastrointestinal Tract Involvement: Follow-up by Capsule Endoscopy

Follicular lymphoma with gastrointestinal tract involvement is rare. We describe the case of a young woman with follicular lymphoma with multiple nodular lesions involving segments of the proximal jejunum and terminal ileum. The presenting symptom was chronic diarrhea. The diagnosis was made by endoscopy with histologic examination of the mucosal lesions of the proximal and distal small intestine, immunohistochemical staining, and molecular analysis. The initial spread and pattern of the small bowel involvement, as well as treatment response, were evaluated by videocapsule endoscopy. The application of molecular analysis along with immunophenotypic evaluation has made it possible to precisely diagnose follicular lymphoma. In the present case, the use of capsule endoscopy improved the evaluation of the extent of small bowel involvement prior to and following treatment.     

Magnifying Endoscopy for Intestinal Follicular Lymphoma Is Helpful for Prompt Diagnosis

The representative endoscopic features of primary intestinal follicular lymphoma are well known as small whitish polypoid nodules, but a magnified view has only been described in a few case reports. Herein, we report a case with intestinal follicular lymphoma in which magnifying endoscopy with narrow band imaging was helpful for prompt diagnosis. A 57-year-old Japanese woman underwent surveillance esophagogastroduodenoscopy. The endoscopic examination revealed confluent whitish granules in the duodenum, distinct from the nodules or polyps that are typical findings of intestinal follicular lymphoma. Magnifying endoscopy visualized whitish enlarged villi, and narrow band imaging emphasized an elongated and coiled vascular pattern. Based on these features, intestinal follicular lymphoma was highly suspected, and subsequent histological study confirmed the diagnosis. This case demonstrates that magnifying endoscopy with narrow band imaging was useful for the detection and prompt diagnosis of intestinal follicular lymphoma. The pathological features of intestinal follicular lymphoma are also discussed.     

Histological diagnosis of follicular lymphoma by biopsy of small intestinal normal mucosa

Due to advances in double‐balloon endoscopy, various types of malignant lymphoma of the small intestine have been observed at very early stages. We report here that after remission of diffuse large B‐cell lymphoma, follicular lymphoma recurred in the mucosa of the small intestine. Furthermore, these lesions were diagnosed by biopsy from normal mucosa as diminutive erosions and reddish looking. If a small intestinal lesion is suspected of being a malignant lymphoma, a double‐balloon endoscopy should be carried out, and a biopsy should be taken and inspected.     

Enteroscopy

Wireless capsule endoscopy and double-balloon endoscopy are new methods of enteroscopy that have been introduced in recent years. Wireless capsule endoscopy is an epoch-making examination method that makes possible an endoscopic imaging examination of the entire small intestine without discomfort and without confining patients to a medical facility. Although it is expected to be useful as an initial examination for finding diseases of the small intestine, it cannot be used for biopsy or treatment. One risk associated with the capsule endoscopy technique is entrapment by strictures. Double-balloon endoscopy is based on a new insertion technique in which two balloons, one at the distal end of the endoscope and the other at the distal end of an overtube, are operated in combination, and the endoscope is inserted while simultaneously shortening the intestine. It can be inserted through either the mouth or the anus, allowing the observation of the entire gastrointestinal tract. It features excellent maneuverability even in the distal small intestine, and enables back-and-forth observation, biopsy, and endoscopic treatment at any given site. These two new enteroscopy techniques are expected to lead to innovations in how diseases of the small intestine are approached.     

Gastrointestinal mantle cell lymphoma with isolated mass and multiple lymphomatous polyposis: report of two cases

We herein report two patients with mantle cell lymphoma (MCL), who had isolated mass and multiple lymphomatous polyposis (MLP) in the gastrointestinal tract. In case 1, esophagogastroduodenoscopy revealed a protruding mass in the duodenum and double-balloon endoscopy disclosed numerous polypoid lesions in the ileum. Case 2 had polyposis in the duodenum and a large mass-forming lesion in the ascending colon. Based on the histologic and immunohistochemical findings of the biopsy specimens, the diagnosis of MCL was made in both patients. A combination of isolated mass and MLP is considered as characteristic endoscopic findings of intestinal lesions of MCL.     

Clinical outcomes of double-balloon endoscopy for the diagnosis and treatment of small-intestinal diseases.

BACKGROUND & AIMS: A specialized system for a new method for enteroscopy, the double-balloon method, was developed. The aim of this study was to evaluate the usefulness of this endoscopic system for small-intestinal disorders. METHODS: The double-balloon endoscopy system was used to perform 178 enteroscopies (89 by the anterograde approach and 89 by the retrograde approach) in 123 patients. The system was assessed on the basis of the rates of success in jejunal and ileal insertion and the entire examination of the small intestine, diagnostic yields, ability to perform treatment, and complications. RESULTS: Insertion of the endoscope beyond the ligament of Treitz or ileocecal valve was possible in all 178 procedures. It was possible to observe approximately one half to two thirds of the entire small intestine by each approach, and observation of the entire small intestine was possible in 24 (86%) of 28 trials. The source of bleeding was identified in 50 (76%) of 66 patients with GI bleeding, scrutiny of strictures was possible in 23 patients, and a tumor was examined endoscopically in 17 patients. Two complications (1.1%) occurred. Endoscopic therapies in the small intestine including hemostasis (12 cases), polypectomy (1 case), endoscopic mucosal resection (1 case), balloon dilation (6 cases), and stent placement (2 cases) were performed successfully. CONCLUSIONS: Double-balloon endoscopy permits the exploration of the small intestine with a high success rate of total enteroscopy. The procedure is safe and useful, and it provides high diagnostic yields and therapeutic capabilities.     

Extranodal diffuse follicular center lymphoma mimicking mantle cell lymphoma of the intestine

We report a case of diffuse follicular center lymphoma (FCL), which is a morphological variant of follicular lymphoma, resembling multiple lymphomatous polyposis (mantle cell lymphoma of the intestine). The patient was a 48-year-old Japanese man who was found, by colonoscopy, to have numerous small polypoid lesions along the entire large intestine. Abdominal computed tomography revealed hepatosplenomegaly and enlargement of multiple mesenteric lymph nodes. Histologically, the lesion was characterized by diffuse proliferation of small- to medium-sized lymphocytes with cleaved nuclei in the mucosa and submucosa. Immunohistochemical studies showed that the tumor cells were CD20+, CD10+, BCL-2+, CD5-, surface IgM-, and cyclin D1-. Moreover, a cytogenetic study showed a translocation at (14;18)(q32;q21). Finally, this case was diagnosed as diffuse FCL, although the tumor was mimicking mantle cell lymphoma.     

Double-Balloon Endoscopy Depicts Diminutive Small Bowel Lesions in Gastrointestinal Lymphoma

The aim was to determine the prevalence of small bowel involvement in patients with gastrointestinal (GI) lymphoma by double-balloon endoscopy (DBE). We examined 29 patients with primary GI lymphoma by oral and anal DBEs. Clinicopathologic features related to the prevalence of diminutive small bowel involvement and the clinical outcome were retrospectively investigated. Diminutive small bowel lesions were found in 14 patients. The prevalence of the lesions was not different between patients with primary small bowel lymphoma and those with primary extra-small bowel lymphoma (50% versus 47%, P = 0.6). However, clinical stage was more advanced in patients with the lesions than in those without (P < 0.05). The lesions were more frequently found in T-cell lymphoma (100%) and follicular lymphoma (77%) than in the other types of lymphoma (15%) (P < 0.05). Diminutive small intestinal lesions occur in patients with GI lymphoma, especially in those with follicular lymphoma and T-cell lymphoma. GI lymphomas of these histologic types are candidates for scrutiny by DBE.     

Current and future diagnostic approaches: From serologies to imaging

Advances in serologic markers and imaging modalities continue to revolutionize diagnostic approaches to inflammatory bowel disease (IBD). Autoimmune and antimicrobial antibodies demonstrate diagnostic value in those patients with a moderate pretest probability of disease. Emerging data also support the use of antimicrobial antibody levels as a predictive tool for small bowel complications and the need for future surgery. In addition to being a prognostic marker in patients with acute severe colitis, serum C-reactive protein has been shown to correlate with clinical, endoscopic, and radiologic measures of disease activity. Capsule endoscopy and double-balloon endoscopy allow for visualization of the entire small bowel, and double-balloon endoscopy also has the capability to treat lesions. CT enterography is beginning to replace small bowel follow-through because of its high sensitivity and specificity for disease of the small intestine. Both CT and magnetic resonance enterography detect luminal and extraluminal abnormalities, with MRI serving as a safe imaging option in cases of pregnancy and renal insufficiency. These newer modalities add to the armamentarium clinicians can use for evaluation of IBD.     

Case of Zollinger-Ellison syndrome diagnosed three years after ulcer perforation in the third portion of the duodenum]

A 61-year-old woman was referred to our hospital for a double balloon endoscopy (DBE) examination of small intestine. She had undergone laparotomy for a perforated ulcer of the 3rd portion in the duodenum 3 years prior to this admission. Esophagogastroduodenoscopy at the previous hospital revealed multiple ulcers in the 2nd and 3rd portions in the duodenum. DBE revealed multiple ulcer scars in the proximal jejunum. Zollinger-Ellison syndrome was suspected from the distribution of the ulcers and scars. Serum gastrin was high and a selective arterial calcium injection test showed a step up of gastrin level only in the gastroduodenal artery area. We diagnosed a gastrinoma located on the ventral side of the 2nd portion of the duodenum from imaging studies. The tumor was extirpated and histologically found to be a neuroendocrine tumor in a lymph node. Serum gastrin level decreased to the normal range a day after surgery.     

Removal of a sewing needle penetrating the wall of the third portion of the duodenum by double-balloon endoscopy

We describe successful removal a sewing needle penetrating the wall of the third portion of the duodenum by means of double-balloon endoscopy (DBE). The patient was a 47-year-old woman who accidentally swallowed a sewing needle and was admitted to our hospital. Abdominal radiography and abdominal computed tomography revealed a metallic object in the third portion of the duodenum. DBE performed by the antegrade approach, revealed that the sewing needle had penetrated the duodenal wall. The sewing needle was retrieved with biopsy forceps and pulled out together with the endoscope through the flexible overtube that remained positioned in the duodenum. There was no injury to the patient’s esophagus or gastrointestinal wall. Our experience in this case suggests that sharp foreign bodies in the gastrointestinal tract can be safely removed by means of DBE.     

Extranodal NK/T cell lymphoma, nasal type, of the small intestine diagnosed by double-balloon endoscopy

Extranodal NK/T-cell lymphoma (ENKL), nasal type, is rare and the small intestine is quite extraordinary as a primary lesion site. We report a 47-year-old man with ENKL of the small intestine. He was referred to our hospital because of bloody stool and the diagnosis was made by double-balloon endoscopy (DBE) of the small intestine without surgical procedure. His clinical stage was IVB and he was categorized in group 4 by prognostic index of ENKL. He went into complete remission (CR) after intensive chemotherapy (DeVIC) and subsequently underwent allogeneic bone marrow transplantation (BMT). Although he remained in CR for about 8 months after BMT, he died of disease recurrence 14 months after the diagnosis was made. ENKL of the small intestine follows a highly aggressive course. We describe the usefulness of DBE for diagnosis and management for ENKL of the small intestine. Additional cases, however, should be accumulated to establish optimal treatment strategy.     

A Case Report of the Histologic Transformation of Primary Follicular Lymphoma of the Duodenum

A 46-year-old woman underwent upper endoscopy for evaluation of anemia, which revealed whitish granules at the duodenal papilla, diagnosed as duodenal follicular lymphoma (DFL) by biopsy. Computed tomography and abdominal ultrasonography revealed that follicular lymphoma was confined to the duodenum. Seven years after the diagnosis, fluorine-18 fluorodeoxyglucose positron emission tomography scanning revealed multiple lesions including in bone marrow and lymph nodes. Bone marrow biopsy of the right iliac bone revealed diffuse large B-cell lymphoma, indicating systemic dissemination and histologic transformation of the DFL. The patient responded to chemotherapy and has been progression-free for 2.5 years. Although DFL is usually indolent even without any treatment, systemic dissemination with histologic transformation can occur. This case suggests that the life-time follow-up that is usually done for patients with nodal follicular lymphoma should be provided to patients with DFL.     

PARTIAL REGRESSION OF DUODENAL LESIONS OF INTESTINAL FOLLICULAR LYMPHOMA AFTER ANTIBIOTIC TREATMENT

A 51‐year‐old man was referred to our hospital because of duodenal lesions of lymphoma. Endoscopy showed multiple tiny smooth whitish granules in the second portion of the duodenum including the papilla of Vater. Biopsy specimens showed medium‐sized centrocyte‐like cells forming lymphoid follicles, and immunohistology showed positive staining for bcl‐2 and CD10. A small bowel series showed multiple granular lesions extending from the second portion of the duodenum to the proximal jejunum and the proximal ileum. On the basis of these findings, the tumor was diagnosed as stage I follicular lymphoma (FL). Although the patient was negative for Helicobacter pylori, he underwent antibiotic treatment. The lesions improved 3 months after antibiotic treatment, but biopsy specimens showed residual lymphoma cells. The patient therefore received combination chemotherapy with rituximab. Endoscopy 4 months later showed regression of FL, and there was no evidence of recurrence during 3 years of follow up. The partial regression of duodenal lesions of intestinal FL may be due to the effect of antibiotic treatment.     

Double-balloon enteroscopy in patients with GI bleeding of obscure origin

BACKGROUND: Small-bowel bleeding is difficult to treat and diagnose. The recent introduction of wireless capsule endoscopy permits examination of the entire small intestine, but this method lacks tissue sampling and therapeutic capabilities. Recently, Yamamoto et al established a double-balloon insertion method for enteroscopy that allows examination of the entire small bowel and interventional options. OBJECTIVE: To evaluate double-balloon enteroscopy in patients with obscure GI bleeding. SETTING: Single-center prospective study. PATIENTS: Thirty-one consecutive patients with obscure GI bleeding (13 females, 18 males; mean age 56.4 +/- 3.2 years). Criteria for inclusion in the study were documented iron deficiency anemia (hemoglobin level <10 g/dL or a decrease of >2 g/dL over > or =2 months); upper endoscopy not revealing a site/cause of blood loss; and similarly uninformative lower endoscopy including examination of the terminal ileum. INTERVENTIONS: Endoscopic biopsy or therapy was performed as clinically indicated. MAIN OUTCOME MEASUREMENTS: Diagnostic yield for patients with obscure GI bleeding and patient follow-up. RESULTS: Double-balloon enteroscopy was completed without complications in all patients. Bleeding points were identified in 23 patients (74.2%). In 21 (91.3%) of these 23 patients the cause of blood loss was identified and treated with no further bleeding at 8.5 +/- 0.6 months of follow-up. LIMITATIONS: Small number of patients. CONCLUSIONS: These data suggest that double-balloon enteroscopy is useful for evaluation and treatment of patients with GI bleeding of obscure origin.     

Clinical analysis of eight patients with primary follicular lymphoma in the duodenum

We performed a clinical analysis on 8 patients with primary follicular lymphoma in the duodenum taken from among 26 cases of primary gastrointestinal malignant lymphoma treated in our division. The median age was 60 years (range 48 to 82 yr). The ratio of males to females was 4:4. The chief complaints were no symptoms in 4 cases, heartburn in 2 cases, lower abdominal pain in 1 case, and back pain in 1 case. All patients were in clinical stage I EA. Gastroendoscopic findings showed multiple whitish granules around the ampulla of Vater in all patients. Involvement of the site in 6 cases was only located at the second portion; lesions in the other 2 cases were located at the second portion, and at the third portion or fourth portion, respectively. A histological study showed follicular lymphoma grade 1, and an immunohistological study demonstrated that the lymphoma cells were positive for CD79a, CD10, CD20, and bcl-2. Five patients were positive for the FISH analysis fusion signal of IgH/bcl-2 genes. Rituximab with CHOP therapy was performed for 7 patients. Seven patients are currently alive, and one died of uterine cancer. At the medium-term 39 month-follow-up, 7 patients were in complete remission, and 1 patient was in partial remission. Rituximab with CHOP (CVP) therapy is a possible treatment for primary follicular lymphoma in the duodenum. Further consideration of appropriate therapy for this disease might be necessary.