Complications of Primary Upper Gastrointestinal Lymphoma

Introduction

Gastrointestinal lymphoma, mainly in the form of primary upper gastrointestinal lymphoma (PUGIL), represents one of the common forms of extranodal non-Hodgkin's lymphomas which is relatively common in the Middle East ^[1–5]. A few studies from Saudi Arabia have reported the clinicopathological features of this entity. Abdominal pain and weight loss are the most common presenting manifestations ^[6–8]. Complications of this disease are described in patients reported from the Western world ^[9–12]. These complications are primarily due to the disease itself or to its treatment and include perforation, jaundice, hemolysis and intestinal obstruction.

Although PUGIL is common in the Middle Eastern countries, there is little information on its complications in our population. Therefore, the present analysis was undertaken to report the frequency of gastrointestinal complications among 33 patients with PUGIL treated and followed at King Khalid University Hospital (KKUH), Riyadh.

PATIENTS AND METHODS

Between 1405H and 1409H (1985 and 1989), thirty-three patients were diagnosed as having PUGIL (involving the stomach, duodenum and/or proximal jejunum) on the basis of histopathological features identified on examination of biopsy specimens. The clinical and laboratory features in some of these patients have been reported previously ^[8]. All patients were treated with chemotherapy alone or in combination with surgery and/or radiotherapy. The patients were followed at regular intervals over a period ranging from six to 60 months (median 1.87 years). During the follow-up visits, routine investigations including complete blood count, bilirubin, albumin, serum aspartate transaminase, serum alanine transaminase and alkaline phosphatase, electrolytes and urea, were obtained. Upper gastrointestinal (UGI) endoscopy was performed on all the patients at six month intervals during the follow-up, or earlier, if so indicated. Multiple biopsies were taken from both the grossly abnormal and normal mucosa of the fundus, corpus, antrum, first, second and third parts of the duodenum. These biopsy specimens were processed and examined microscopically. Blood and other body fluids were cultured if sepsis was suspected. Complications at presentation or during the follow-up period were diagnosed and managed accordingly. Upper gastrointestinal bleeding was diagnosed by the history of hematemesis and/or melena with endoscopic confirmation of bleeding sites within the UGI. The diagnosis of malabsorption was based on the occurrence of weight loss, steatorrhea, hypoproteinemia and abnormal D xylose test. Patients with recurrent vomiting and narrowing of the UGI lumen on endoscopic examination were deemed to have UGI obstruction. Obstructive jaundice was confirmed by ultrasound, computed tomographic (CT) scan and/or endoscopic retrograde cholangiopancreatography (ERCP).

RESULTS

Gastrointestinal complications were documented in 21 of the 33 patients with PUGIL. Of the 21 patients with complications, 17 were male and 4 female. Their median age was 38.5 years. The disease was limited to the stomach in seven patients and ten to the duodenum and prox-imal jejunum. Another four patients had gastric, duodenal and proximal jejunal lymphoma which was associated with immunoproliferative small intestinal disease (IPSID) in three.

The most frequent complications were upper gastrointestinal bleeding and narrowing of the lumen in 11 and nine patients, respectively (Table 1). Malabsorption ^[5] and obstructive jaundice ^[4] were also frequent. The least common complications were perforation and fistula formation in one patient each. Some patients had more than one complication accounting for a total of 31 complications. Ten of these patients presented with gastrointestinal emergencies in the form of acute upper gastrointestinal hemorrhage in six, acute intestinal obstruction in one, free intestinal perforation in one and severe malabsorption with cachexia necessitating total parenteral nutrition in two patients. The vast majority of gastrointestinal complications occurred before the initiation of treatment. Only two patients developed complications in the form of hemorrhage and perforation within the first week of chemotherapy. None of the patients who underwent surgery followed by chemotherapy developed gastrointestinal complications. Mortality was encountered in four patients with malignant large-cell lymphoma of the small intestine. The mortality was due to gastrointestinal complication in only one patient in the form of severe upper gastrointestinal bleeding and three patients died with refractory septicemia.

Table 1. Gastrointestinal complications of primary upper gastrointestinal lymphoma (PUGIL).

DISCUSSION

This study documents a relatively high gastrointestinal complication rate of 64% in patients with PUGIL. The most common complication was upper gastrointestinal hemorrhage which occurred in about half of these patients and was the cause of death in one. This frequency of bleeding was higher than the reported figures ranging from 15% to 30% in other populations ^[10]. Al-Bahrani et al ^[1] and Grey et al ^[10] reported intestinal obstruction as the most common presentation and complication. In contrast, we found acute intestinal obstruction in one patient only despite the presence of stenosis in 43% of our patients.

Obstructive jaundice was present in four patients in this series. The common bile duct obstruction was primarily distal due to lymphadenopathy, infiltration of the terminal bile duct and/or papilla of Vater. Birrer and Young ^[12] found obstruction of the bile duct most commonly at the porta hepatis or at the head of the pancreas due to enlargement of involved lymph nodes. They also reported that hepatocellular jaundice was infrequent despite hepatic involvement by small-cell non-Hodgkin's lymphoma. This type of jaundice was not recorded in any of our patients who had, in the vast majority, diffuse large-cell type of non-Hodgkin's lymphoma.

Although perforation has been considered as an important complication ^{[9,11,13–15]}, only one of our patients suffered perforation following chemotherapy. Similarly, a blind duodenal fistula was present in one patient, a complication which has been reported infrequently.

Despite the occurrence of complications, the response to the different modaiities of treatment mentioned above was fair. The mortality in one of our patients during the follow-up period was due to severe gastrointestinal bleeding, a potentially treatable condition. On the other hand, it has been reported that ten percent of patients surgically treated for non-Hodgkin's gastric lymphoma ^[11] died postoperatively. In the present series, none of our patients died during or after surgical intervention. However, the small number involved will not permit any firm conclusion on the morbidity and mortality of surgical treatment of PUGIL.

It is concluded that gastrointestinal complications of PUGIL are common and mostly not related to treatment. The majority of these are treatable conditions. Efforts should be made to identify and treat such complications in order to improve the prognosis of this entity. The prognosis of PUGIL is relatively fair and may depend mostly on the prompt arrest of complications usually due to chemotherapy.