A 57-year-old man with severe abdominal pain is evacuated from a cruise ship and presents to a local emergency department (ED).

The pain, which is most severe in the right lower portion of his abdomen, started soon after he boarded the cruise ship 2 days before presentation. Since onset, the pain has worsened, and the patient has noticed his abdomen becoming progressively “bloated.” The pain is associated with nausea and vomiting, and the patient has not been able to have a bowel movement. On further questioning, he reports having night sweats, low-grade fevers, intermittent abdominal discomfort with constipation, and a 30-lb weight loss over the past 2-3 months. He has no significant medical history, is not taking any medications, and is not on any weight-loss regimen. He does have a significant family history of colon cancer, soft tissue sarcoma, pancreatic cancer, chronic myeloid leukemia (CML), and prostate cancer.

On physical examination, the patient is alert and oriented. His temperature is 98.8°F (37.1°C), his pulse is 65 bpm, his respiratory rate is 18 breaths/min, and his blood pressure is 104/67 mm Hg. The abdominal examination reveals localized tenderness to palpation in the right lower quadrant (RLQ) with a palpable mass. He has generalized abdominal distention but no guarding, rebound, or percussion tenderness. His rectal examination reveals brown stool that is guaiac-positive. The findings from the respiratory and neurologic portions of the physical examination are unremarkable.

Laboratory investigations are ordered and reveal a hemoglobin value of 9.4 g/dL (94 g/l), with a corresponding hematocrit of 30.8% (0.308). His white blood cell (WBC) count is 6.2 × 10³/μL
(6.2 × 10⁹/L), and his lactate dehydrogenase (LDH) level is elevated at 285 U/L. The results of an electrolyte panel, liver function tests, and renal function tests are within normal limits.

An abdominal computed tomography (CT) scan (see Figure 1) demonstrates a large mass in the patient’s RLQ. The mass is causing a small-bowel obstruction, and several enlarged retroperitoneal and mesenteric nodes are noted (not pictured).

The contrast-enhanced CT scan demonstrates homogeneous soft tissue infiltrating and thickening the wall of a bowel segment in the RLQ.

DISCUSSION:

Figure 1. (Click to enlarge)

A needle biopsy of the affected portion of the bowel in the RLQ revealed a diffuse large B-cell lymphoma (DLBCL) involving the intestinal wall. Prophylactic surgery to remove the RLQ mass was scheduled because the patient was at a relatively high risk of ileocecal bowel perforation during and after chemotherapy as a result of the lymphoma’s extensive infiltration of the entire bowel wall (as seen on the CT scan). The preoperative diagnosis was non-Hodgkin lymphoma (NHL) (ie, DLBCL of the small bowel). After surgery, lymphoma of the terminal ileum, the right colon, and the mesentery of the small bowel were confirmed. The terminal ileum and the proximal right colon were resected, and an ileocolic anastomosis was made.

Lymphomas are categorized as Hodgkin lymphoma (HL) or NHL. HL is most often localized to a single axial group of nodes, spreads contiguously, and rarely causes extranodal involvement. In contrast, NHL is a heterogenous group of lymphoproliferative malignancies with differing patterns of behavior and responses to treatment, and it most frequently involves several peripheral nodes, has a noncontiguous or disseminated spread, and commonly results in extranodal involvement. NHL usually originates in the lymphoid tissues and can spread to other organs. The prognosis of NHL depends on the histologic type, stage, and treatment. In the United States, there are an estimated 56,200 new cases of NHL diagnosed annually, and there are 26,300 deaths from it each year.^[2] NHL accounts for 5% of new cancers in men and 4% of new cancers in women; the lifetime risk of being diagnosed with NHL is about 2.08%.^[2] Interestingly, the incidence rate is increasing approximately 3% per year, and it has increased by more than 80% since the early 1970s. There are probably several contributing factors to this increase in incidence, including better classification systems and techniques, improved imaging and biopsy techniques, an aging population, the AIDS epidemic, and an increasing number of patients on immunosuppressive medications. Internationally, certain endemic geographical factors appear to influence the development of NHL in specific areas, such as Burkitt lymphoma in Africa, heavy chain disease (alpha) in the Middle East, follicular lymphomas in North America and Europe, and HTLV-1–associated adult T-cell lymphoma/leukemia in Japan and the Caribbean.

NHL can be further categorized into B-cell lymphomas and T-cell lymphomas. Diffuse large cell lymphoma (DLCL) is the most common lymphoma, representing 31% of NHLs. In the classification of DLCLs, approximately 79% of DLCLs are of B-cell origin, 16% of T-cell origin, and 5% unclassifiable. Exceptional DLCL cases express both B-cell and T-cell markers. Although DLCLs can occur at any age, they generally occur in middle-aged and older adults. DLBCL is a malignancy of mature B-cells originating from the germinal center or marginal-zone B cells. It is the most common histologic subtype of B-cell NHL, accounting for 20% of all NHLs and 60-70% of aggressive lymphoid neoplasms. On histologic evaluation, DLBCL-involved lymph nodes show a diffuse pattern of involvement, with loss of normal structures, such as sinuses and lymphoid follicles.

The constitutional symptoms associated with DLBCL, and with lymphomas in general, include fever, weight loss, and drenching night sweats; these symptoms occur in 30% of patients. Lymphadenopathy is the most common manifestation of lymphoma, with the possibility of waxing and waning lymphadenopathy. Systemic symptoms known to be associated with an adverse prognosis include unexplained fevers, night sweats, and weight loss. The initial evaluation of a patient with known or suspected lymphoma should include an assessment for these constitutional symptoms. Pruritus has also been observed in patients with lymphoma.

Organ-specific symptoms, such as shortness of breath, chest pain, cough, abdominal pain and distention, or bone pain, may lead to the identification of specific sites of involvement. Careful evaluation for neurologic symptoms is necessary in order to rule out central nervous system (CNS) involvement, which may occur with aggressive histologies.

The laboratory workup for NHL includes a complete blood count (CBC) with differential. An examination of a peripheral smear is essential to assess bone marrow function and to investigate for the presence of abnormal circulating cells in the peripheral blood. Screening chemistries to ascertain renal and hepatic function, serum glucose, calcium, albumin, and lactate dehydrogenase (LDH) are also indicated, as they are frequently found to be abnormal. In fact, more than 50% of patients have elevated serum LDH levels. An elevated beta2-microglobulin level is associated with a poor prognosis. A serum protein electrophoresis should also be part of the workup. An HIV serology should be ordered for patients with lymphoma who have risk factors for HIV infection.

The median age range for the onset of DLBCL is 60-70 years, and patients often present with a rapidly enlarging symptomatic mass, typically in the neck or abdomen. As many as 40% of patients present with extranodal involvement. The ileum is the most common site of extranodal lymphoma, which accounts for 5% of all lymphomas. As in this case, mass effect can lead to small bowel obstruction. Depending on the extranodal location of the lymphoma, other presentations resulting from mass effect include superior vena cava syndrome, tracheobronchial compression leading to respiratory distress, and spinal cord compression related to destruction of bone in the vertebral column. Detection of tumor in the bone marrow is associated with spread to the CNS in 10-20% of patients. The histologic features of DLBCL include a relatively large cell size (usually 4-5 times that of a small lymphocyte) and a diffuse pattern of growth. A fair degree of morphologic variation exists, but in most cases, the tumor cells have a round or oval nucleus that appears vesicular because of margination of chromatin at the nuclear membrane. In some cases, large multilobulated or cleaved nuclei predominate. Multiple nucleoli may be seen, usually located adjacent to the nuclear membrane; however, they may also be single and centrally placed. Cytoplasm is usually present in moderate abundance, and it may appear pale or basophilic.

The International Non-Hodgkin’s Lymphoma Prognostic Factors Project reports a 5-year survival rate of 26-73%; the exact survival rate depends on the number of risk factors and the histologic type. The risk factors for increased mortality and relapse include age older than 60 years, increased serum LDH level, Ann Arbor stage III or IV (see Lymphoma, Non-Hodgkin for more information on Ann Arbor staging of NHL), and more than 1 extranodal disease site. The mean long-term disease-free survival rate is about 40%. Relapse is most common in the first 2-3 years after diagnosis; it becomes relatively uncommon after 4 years.

In this case, a bone marrow aspiration taken after the surgery revealed normocellular marrow negative for lymphoma. The patient received a round of CHOP chemotherapy, which consisted of cyclophosphamide, hydroxydaunomycin (doxorubicin), oncovin (vincristine), and prednisone, along with dexamethasone and granulocyte colony-stimulating factor (G-CSF).

UPI The U.S. Food and Drug Administration approved the drug rilonacept to treat a group of rare diseases causing rash, fever, chills and joint pain.

Rilonacept, marketed under the name Arcalyst by Regeneron Pharmaceuticals, received marketing approval for the treatment of Cyropyrin-Associated Periodic Syndromes, including Familial Cold Auto-inflammatory Syndrome and Muckle-Wells Syndrome in adults and children ages 12 and older.

The familial cold syndrome is an “orphan” hereditary disease affecting only about 300 people in the United States, 90 percent of whom can trace their ancestry to a single person who came to America in the 1600s, the University of California’s San Diego School of Medicine said Wednesday in a news release. Symptoms can be triggered at any time by exposure to cold temperatures, stress or exercise,

The drug is based on a discovery by Dr. Hal Hoffman, a professor at the medical school, who identified the genetic basis of the disease as a mutation that causes alterations in the protein cryopyrin.

MedPage Today (3/5, Smith) reported that “[u]sing a cell phone while driving — even a hands-free model — sharply decreases activity in the brain regions used to control the vehicle,” according to a study published in the journal Brain Research. Marcel Just, D.O., of Carnegie Mellon University, and colleagues, recruited “29 volunteers [who] underwent fMRI [functional magnetic resonance imaging] scanning while they guided a virtual vehicle down a winding road, either undistracted or having to listen to recorded sentences, and decide if they were true or false.”

During the experiment, “the researchers calculated how well the volunteers kept their virtual cars on an ideal path, and how often they had ‘road maintenance errors’ such as hitting a simulated guardrail.” The authors found that on average, participants deviated more from the ideal path when driving and listening, that “[m]ean road maintenance errors increased from 8.7 to 12.8,” and that “[t]here were large decreases in activity in the areas of the brain involved in the spatial processing associated with driving when listening was added.”

Reuters, 3/5/08:  A once-a-week pill to treat rheumatoid arthritis significantly reduces the risk of heart attack and stroke for people with the painful joint condition, an international team of researchers said on Thursday.The findings published in the journal Arthritis & Therapy provides further evidence of the benefits of the generic drug methotrexate and underscores the importance of prescribing it early on, the researchers said.

“This shows that we are really making a difference in patients’ lives,” said Tuulikki Sokka, a researcher at Jyvaskyla Central Hospital in Finland, who worked on the study.

About 20 million people worldwide have rheumatoid arthritis, an autoimmune disease caused when the body confuses healthy tissue for foreign substances and attacks itself.

Some drugs used to treat it reduce inflammation directly while others tone down immune system response — leaving patients vulnerable to infections and cancer.

Methotrexate was developed as a cancer drug and works by altering the body’s use of folic acid, which is needed for cell growth. It may begin to work as early as three to six weeks after treatment starts.

The results are part of a long-term study of more than 4,300 people in 15 countries examining the causes and effects of rheumatoid arthritis and the potential benefits of medications.

The team — which included researchers from Spain, Argentina and the United States — adjusted for traditional risk factors such as exercise, smoking and diabetes and found potential health benefits for people given methotrexate . 

Using methotrexate for one year cut the risk of heart attack by 18 percent and the risk of a stroke by 11 percent, the researchers said.

Results also suggested that newer drugs that block an inflammatory protein called tumor necrosis factor, or TNF, were also effective at reducing heart attack and stroke risk, although more research is needed, Sokka said.

This class of drugs includes Johnson & Johnson’s Remicade, Amgen Inc’s Enbrel, and Abbott Laboratories Inc’s Humira. The drugs are expensive, which is why people often do not get them right away.