clinical obesity

doi: 10.1111/cob.12045

Case Report

Diffuse large B-cell lymphoma (DLBCL) in the bypassed stomach after obesity surgery M. J Courtney, D. Chattopadhyay, M. Rao, D. Light and B. Gopinath

Upper GI/Bariatric Surgery, University

Summary

Hospital of North Tees, Cleveland, UK

Laparoscopic Roux-en-Y gastric bypass is the most commonly performed surgical procedure for obesity and, consequently, post-operative patients are increasingly encountered by all specialties. This is a case of a patient presenting with abdominal pain, nausea and fever 9 months following gastric bypass surgery caused by diffuse large B-cell lymphoma (DLBCL) in the bypassed stomach. It demonstrates well that symptoms that may normally be considered ‘red-flags’ may not be as obvious or specific following an operation. The case also indicates the importance of considering diagnoses unrelated to surgery presenting in the post-operative period (especially when conventional investigation methods are not feasible), and the potential danger of assuming they are due to the operation alone; had this occurred in this patient then a malignancy may have been missed. This is only the second reported case of DLBCL in the bypassed stomach, and the third for lymphoma of any type.

Received 10 November 2013; revised 9 January 2014; accepted 15 January 2014

Address for correspondence: Mr M J Courtney, 11 Winterton Avenue, Sedgefield, Co. Durham TS21 3NJ, UK. E-mail: [email protected]

Keywords: Bariatric, bypass, lymphoma, Roux-en-Y.

Introduction A diagnosis of cancer is one that all patients fear, and one that all healthcare providers fear missing. Many referral and management guidelines and pathways are available for suspected malignancy, but they generally work on the assumption of ‘normal’ patterns of presentation. What happens if a patient presents in an atypical way, or if usual investigation pathways cannot be followed? Bariatric surgery is a growing specialty in the UK (in 2010/2011 over 8000 procedures were performed in the UK (1)), and so patients who have undergone bariatric surgery are becoming ever more frequently encountered. One common bariatric procedure is the laparoscopic Rouxen-Y gastric bypass (LRYGB). In LRYGB the stomach is divided, creating a small ‘pouch’ of stomach (restricting intake), which is then anastomosed to the jejunum. The remainder of the stomach is left in situ and the small bowel 116

still attached to it is anastomosed distal to the gastro– jejunal anastomosis, making the gastric and pancreatic juices bypass a segment of the jejunum before mixing with ingested food. The consequent result of this bypass is malabsorption of fat (and subsequent fat-soluble vitamins), protein and other micronutrients (including iron, copper, calcium, vitamin B12, folic acid and thiamine) (2–4). Although resulting in significant weight loss, the resulting change in anatomy may create diagnostic problems as: 1. The bypassed stomach is no longer in continuity with the rest of the upper gastrointestinal tract, and so patients may not experience symptoms otherwise typical of gastric pathology (e.g. heartburn, as gastric secretions cannot enter the oesophagus, or early-satiety, as food does not enter the remnant); 2. The bypassed stomach is inaccessible by conventional endoscopy (oesophago-gastro-duodenoscopy), a test which

© 2014 The Authors Clinical Obesity © 2014 International Association for the Study of Obesity. clinical obesity 4, 116–120

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is often easily accessible, used early in the investigation of possible upper gastrointestinal disease (for example gastritis, ulcers and malignancy) and allows for direct visualization and biopsy. This is a case of a patient presenting with abdominal pain, nausea and fever 9 months following gastric bypass surgery caused by gastric lymphoma in the bypassed stomach.

Case Mrs OA, a 56-year-old Middle Eastern woman, was referred to the outpatient bariatric services with a 1-month history of abdominal pain following gastric bypass surgery for obesity. She was 9 months post-procedure and had achieved satisfactory excess weight loss of 80%, making her current BMI 27 (preoperative body mass was 87.8 kg and BMI 36). She had been clinically well at 6-week, 3-month and 7-month reviews, and no concerns were highlighted at those times. Her current complaint was of central-to-lower abdominal pain, nausea (no vomiting), night sweats, fever and fatigue. Bowel habit was unchanged, her abdomen was not distended and she did not have any uro-gynaecological symptoms. She had no significant family history. She had recently visited mainland Europe but had not visited anywhere with a high prevalence of tropical disease. Her only other medical history was osteoarthritis and previous bilateral mastectomies for ductal carcinoma in situ in 2000 followed by bilateral breast reconstructions. She did not smoke or consume alcohol. Clinical examination was unremarkable. Given her recent surgery, an urgent outpatient computed tomography (CT) scan of the abdomen and pelvis was requested to assess for bowel dilation or herniation. Due to the presence of fevers and her ethnic origin, a full set of bloods was sent for additional tests, including for Epstein–Barr virus, along with samples for acid-fast bacilli. In the week following clinic review, Mrs OA presented as an emergency with worsening abdominal pain; she was reviewed by both medical and surgical teams regarding her ongoing symptoms to optimize appropriate workup. CT scan of chest/abdomen/pelvis was performed as an in-patient and importantly did not reveal bowel obstruction or any hernias. The CT did, however, reveal thickening, oedema and possible ulceration of the bypassed stomach, along with a 9-mm hypodensity in the liver and multiple small hypodensities in the spleen (Fig. 1). The liver lesion was typical of a cyst but the splenic lesions, although likely benign, required further investigation due to Mrs OA’s history of breast cancer. Subsequent magnetic resonance imaging (MRI) scan was done, which confirmed features typical of both liver and spleen haemangiomas.

Figure 1 Computed tomography (CT) scan of upper abdomen demonstrating thickened bypassed stomach with possible ulceration (arrowed).

Whilst an in-patient, Mrs OA also underwent conventional endoscopy to assess the oesophagus and stomach pouch; this revealed a small ulcer in the stomach pouch (benign appearance and hence not biopsied) and dose of her proton pump inhibitor (PPI) was doubled. Mrs OA found some symptomatic benefit from the increased PPI dosage and felt well enough for discharge. Following her discharge, she had urgent clinic review where the findings on CT and MRI were discussed and she was advised to have a laparoscopy with open gastroscopy and biopsying to diagnose the cause of the gastric thickening. Approximately 1 month after initial clinic attendance, Mrs OA underwent a scheduled laparoscopy. This laparoscopy revealed thickening of the lesser curvature of the bypassed stomach, and subsequent gastroscopy through the remnant stomach revealed an ulcer on the mucosal surface of the lesser curve. Biopsies were taken. Histology from the specimens diagnosed the pathology to be gastric lymphoma, specifically diffuse large B-cell lymphoma (DLBCL). Mrs OA was commenced on rituximab, cyclophosphamide, doxorubicin and vincristine (R-CHOP) chemotherapy for this.

Discussion LRYGB has many recognized benefits, including weight loss (around 70% of excess within 2 years) as well as marked improvements in glycaemic control, hypertension, high cholesterol, sleep apnoea and acid reflux (5,6). As previously mentioned, however, the anatomical changes resulting from the surgery render the bypassed stomach inaccessible via conventional endoscopy methods. For this reason, patients have to be carefully risk-stratified for gastric cancer and be counselled preoperatively regarding the risk (albeit low) of late diagnosis should it occur in the

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future. In our trust, all patients undergo screening by upper gastrointestinal (GI) endoscopy prior to bariatric surgery to assess for pathology, but this is not standard throughout the UK or worldwide. As yet there is no clear evidence on whether preoperative endoscopy in asymptomatic patients is necessary, with counter arguments including low diagnostic yield and benign findings not changing management (7–9). The patient in this case had a normal preoperative endoscopy, performed by an experienced, Joint Advisory Group on GI Endoscopy UK (JAG)-approved endoscopist, and so it is very unlikely that a preoperative lesion was missed. It cannot be said, however, that this case renders the preoperative endoscopy worthless, as it ruled out other gastric pathology (such as ulceration), which could have led to more common causes of post-operative morbidity. In post-operative patients, there is a paucity of data on incidence of pathology in the bypassed stomach; in the few studies published, however, the incidence of gastritis and Helicobacter pylori was high (10–12). Although theories regarding carcinogenesis of the bypassed stomach exist, with reasons including lack of alkali, bile reflux and microbacteria (13,14), no definite association has ever been proven. Furthermore, obesity surgery has been shown to reduce both the incidence and mortality of all cause cancers in patients who have and those who have not undergone surgery (15). Gastric lymphoma is a relatively rare disease, only representing approximately 4% of gastric cancers (16). NonHodgkin’s lymphoma (NHL), of which gastric lymphoma is one, is the sixth most common cancer in the UK, with an incidence of 21 and 18 cases per 100 000 population in men and women, respectively (17). The incidence of DLBCL (an aggressive type of NHL) is around 9 per 100 000, making it the most common type of NHL (17). Traditionally, NHL presents with lymphadenopathy; however, 40% of DLBCL presents as ‘extra-nodal disease’ arising from a solid organ, commonly the stomach (18). Typical symptoms of DLBCL include lymphadenopathy and B-symptoms (including weight loss, fevers and sweating). Extra-nodal disease symptoms may also be organspecific, so in the case of the stomach, present with abdominal pain, loss of appetite and early satiety (18,19). Risk factors are limited to age (middle- to late-), male sex and white ethnicity, long-term immunosuppressant use and human immunodeficiency virus (HIV) (18,19). Treatment depends on stage, but involves chemotherapy ± immunotherapy or radiotherapy (20). Prognosis, like other malignancies, is determined by grade and stage, and so prompt diagnosis is paramount. Although H. pylori is causative in the majority of gastric mucosa-associated lymphoid tissue lymphomas (10% of which may transform into DLBCL (21)), to date there is no known cause for DLBCL (22). Meta-analysis of randomized controlled trials concerning LRYGB shows an overall estimated complication rate

clinical obesity

of 21% (23). Late complications include internal hernias (incidence 1–9%), anastomatic strictures (incidence 2.9– 23%), marginal ulceration (incidence 1–16%) and gastrogastric fistula formation (incidence 1.5–6%); pain is a common feature of hernias, ulcers and fistulae, and nausea/vomiting a feature of all (24). As complications can lead to significant morbidity (and mortality), prompt investigation and treatment is essential. It is clear, however, that there is similarity between the symptoms of complications of gastric bypass surgery and systemic symptoms of lymphoma. Furthermore, symptoms such as fatigue and weight loss, which may be considered red flags for malignancy in the non-operative patient, may be normal following LRYGB (the 80% excess weight loss that the patient in this case achieved is not extraordinary; previous studies have reported similar percentage losses 1 year post-operatively, and so this loss in itself would not suggest a problem (25,26)). More difficulty may result from absence of any stomach-specific symptoms due to the anatomic changes resulting from LRYGB. These factors together make diagnosing malignancy, and especially haematological malignancy, challenging. This case is rare: literature review revealed only five cases of gastric carcinoma (27–31) and two cases of lymphoma (32,33) in the bypassed stomach following LRYGB (see Table 1), all of which developed later than our case (up to 22 years post-op); lessons learnt from the case are, however, relevant for a wider spectrum of disease. This case highlights a few important points. Firstly, in patients who have had LRYGB, the gastric remnant is inaccessible and so clinicians must remain vigilant for any symptoms which may indicate pathology there; this may include considering gastric malignancy as a cause of nonspecific symptoms in patients following LRYGB. Similarly, patients should be counselled regarding altered patterns of presentation and potential future difficulty in diagnosis. Secondly, in patients who have had procedures which will change the way that investigations are performed, diagnoses typically excluded by tests that are no longer feasible must not be forgotten. When normal investigation algorithms and ‘gold-standard’ investigation methods can not be utilized, investigative laparoscopy may be the required alternative. Finally, clinicians must be aware of the spectrum of diseases that present similarly to (much more) commonly encountered post-operative complications, and remember that pathology unrelated to an operation may present in the post-operative period. Care must be taken not to assume that all new symptoms are due to the operation, as this would risk missing more rare but serious diseases.

Conflicts of Interest Statement No conflict of interest was declared.

© 2014 The Authors Clinical Obesity © 2014 International Association for the Study of Obesity. clinical obesity 4, 116–120

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Table 1 Previously reported cases of neoplasms in the bypassed stomach following gastric bypass for obesity

DLBCL in the bypassed stomach after LRYGB M. J. Courtney et al.

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Neoplasms of the gastric remnant after RYGB Study

Year reported

Cancer type

Time since operation

Raijman I, Strother SV, Donegan WL (27) Lord RV, Edwards PD, Coleman MJ (28) Khitin L, Roses RE, Birkett DH (29) Escalona A et al (30) Corsini DA et al (31) De Roover A, Detry O, de Leval L(32) Jawad A, Bar A, Merianos D, Zhou J(33)

1991 1997 2003 2005 2006 2006 2012

Adenocarcinoma Adenocarcinoma Adenocarcinoma Adenocarcinoma Adenocarcinoma DLBCL MALT lymphoma

5 years 13 years 22 years 8 years 4 years 3 years 20 years

DLBCL, diffuse large B-cell lymphoma; MALT lymphoma, mucosa-associated lymphoid tissue lymphoma; RYGB, Roux-en-Y gastric bypass.

Author contributions M. Courtney was the main writer of the manuscript, with D. Chattopadhyay contributing throughout the drafting. M. Rao and D. Light critically reviewed the manuscript during its production. B. Gopinath supervised the project overall, including background research, writing and revision.

Acknowledgements Authors as listed. No other persons were involved.

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© 2014 The Authors Clinical Obesity © 2014 International Association for the Study of Obesity. clinical obesity 4, 116–120

Diffuse large B-cell lymphoma (DLBCL) in the bypassed stomach after obesity surgery.

Laparoscopic Roux-en-Y gastric bypass is the most commonly performed surgical procedure for obesity and, consequently, post-operative patients are inc...
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