[align=center]Green Urine[/align]



A 76-year-old man with renal failure from nephroangiosclerosis received a kidney transplant from a deceased donor. The transplant was functioning well when the patient underwent a radical laryngopharyngoesophagectomy, with colopharyngeal anastomosis, for esophageal carcinoma. He was transferred to the intensive care unit 5 days after surgery, where his urine was noted to be green (right-hand specimen, next to a normal urine specimen), with unremarkable sediment and a creatinine level of 1.4 mg per deciliter (123.8 µmol per liter). Owing to the presence of mucous drainage from the proximal surgical wound, the patient had received an injection of methylene blue (also called aniline violet and tetramethylthionine chloride) through his nasogastric tube, to look for a possible fistula; a fistula was found. Methylene blue is a water-soluble dye that can be used to assess whether a fistula is present or used as a medication. It is filtered by the kidneys and has no pathologic effects but may cause the urine to have a bluish or greenish hue. Once the dye has been passed (after 2 days, in this patient), the color of the urine returns to normal. The patient had no clinical problems after the dye was passed.



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An Atypical Cause of Gastrointestinal Bleeding

A 53-year-old man who was diagnosed with multiple myeloma (IgAκ) 18 months ago is admitted to the hospital via the emergency department (ED) with a 1-week history of melena, hematemesis, and lethargy. There is no associated weight loss, abdominal pain, dysphagia, or history of upper gastrointestinal (GI) hemorrhage. The patient has no risk factors for peptic ulcer disease, does not drink alcohol or smoke, and is not regularly taking any medications (including no recent nonsteroidal anti-inflammatory drugs [NSAIDs] or steroid use). He has no allergies of note, and his family history and social history are unremarkable. Other than multiple myeloma, which resulted in spinal cord compression that required radiotherapy (with full resolution of symptoms), the patient has no significant past medical history. He has not needed chemotherapy to date. On direct questioning, he does not describe any symptoms suggestive of active multiple myeloma and organ involvement.

On presentation, the patient appears clinically well, with no evidence of anemia, jaundice, lymphadenopathy, or peripheral signs of GI disease. He is hemodynamically stable, with a pulse of 90 bpm, blood pressure of 150/70 mm Hg (with no postural blood pressure drop), and a urine output of approximately 30 mL/hr. On examination, there is no evidence of active GI bleeding, his abdomen is soft and without any peritonitis or organomegaly, and a rectal examination shows evidence of melena, with no masses and a normal-sized prostate. His respiratory examination is unremarkable, with a clear chest and no evidence of aspiration pneumonia. The cardiac and neurologic examinations reveal nothing of significance.

The initial laboratory examinations show a hemoglobin of 8.5 g/L (0.85 g/dL); a low mean corpuscular volume (79 fL), with an iron deficiency picture; a normal international normalized ratio of 1.0; and mild dehydration, with urea nitrogen 10.1 mmol/L (28.29 mg/dL), creatinine 160 µmol/L (1.81 mg/dL), sodium 136 mmol/L (136 mEq/L), and potassium 3.9 mmol/L (3.9 mEq/L). Liver tests showed a normal screen with alanine aminotransferase 30 U/L, albumin 40g/L (4 g/dL), alkaline phosphatase 50 U/L, and bilirubin 12 µmol/L (0.70 mg/dL). The patient is treated with intravenous fluid and 2 units of blood. He remains hemodynamically stable and is subsequently able to undergo an esophagogastroduodenoscopy


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Biopsies of the polyps taken at the time of the endoscopy showed evidence of multiple myeloma type IgA κ. Multiple myeloma is a debilitating malignancy that is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. First documented in 1848, multiple myeloma is a disease characterized by a clonal proliferation of malignant B cells in the bone marrow (in which the predominant cell type is plasma cells) that results in an overabundance of monoclonal paraprotein. It is predominantly a disease of the elderly (median age: 60 years), with an incidence of 9.5 per 100,000 population and a slight male predominance. It is the second most common hematologic cancer (10%), representing 1% of all cases of cancer; despite new advances, multiple myeloma still carries a poor prognosis, with a median survival of 2-3 years.

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The clinical manifestations of multiple myeloma are varied because multiple organs can be involved. The clinical manifestations are related to substances secreted by the plasma cells and the effects of bone marrow infiltration; these effects can be classified into 3 categories:

   1. Direct effects of plasma cell infiltration: The activation of osteoclasts by IL-6 causes bone destruction and lytic lesions, with resulting bone pain (especially headache); pathologic fractures and cord compression; symptomatic hypercalcemia; and osteopenia. The infiltration of bone marrow leads to a pancytopenia, hypogammaglobulinemia, and paraproteinemia, which result in immunosuppression and susceptibility to pneumonias (especially Streptococcus pneumoniae and Staphylococcus aureus) and Escherichia coli pyelonephritis.

   2. Plasma protein abnormalities: The elevated production of paraproteins causes a hyperviscosity syndrome, with associated neurologic, renal, immunologic, and vascular complications.

   3. Multifactorial: Extra-osseous spread of multiple myeloma is mainly to the kidneys, although involvement of the GI tract—most frequently the small intestines—has been occasionally reported. The immunoglobulin involved is mainly IgG; however, in this case, the subgroup was IgA. Renal failure is a multifactorial clinical manifestation that is caused by direct infiltration, hypercalcemia, hyperviscosity, glomerular deposition of amyloid, recurrent pyelonephritis, and light-chain precipitation in the renal tubules.

Investigations include a complete blood count (CBC; to evaluate for anemia, thrombocytopenia, or leukopenia); a comprehensive metabolic panel (to assess a patient's total protein, albumin and globulin, blood urea nitrogen [BUN], creatinine, and uric acid); tests for elevated inflammatory markers (erythrocyte sedimentation rate); and tests for renal failure. The results of these tests should prompt an investigation for multiple myeloma using protein electrophoresis, with evidence of paraproteins and, occasionally, immune paresis, immunoglobulins, serum β2 microglobulin, and urine Bence-Jones protein. The workup for suspected multiple myeloma should then include a skeletal survey, a bone marrow biopsy, and immunohistochemistry, plus magnetic resonance imaging (MRI) scans, if cord compression is a concern.

Multiple myeloma can, in theory, produce all classes of immunoglobulin; IgG paraproteins are the most commonly produced, followed by IgA and IgM. IgD and IgE myeloma are very rare. In addition, light and/or heavy chains (the building blocks of antibodies) may be secreted in isolation: κ or λ light chains or any of the 5 types of heavy chains (α, γ, δ, ε, or μ heavy chains). Early involvement of hematologists should be sought for a possible bone marrow biopsy to estimate the percentage of bone marrow occupied by plasma cells. This percentage is used in the diagnostic criteria for myeloma. Bone marrow examination will reveal plasma cell infiltration, often in sheets or clumps. The plasma cells are 2-3 times larger than typical lymphocytes, and they have eccentric nuclei that are smooth and round or oval in contour. They often have clumped chromatin, with a perinuclear halo or pale zone and basophilic cytoplasm. Immunohistochemistry is then used to detect plasma cells that express immunoglobulins in the cytoplasm but not usually on the surface; the specific markers for multiple myeloma are typically CD56, CD38, CD138 positive, CD19 negative, and CD45 negative.

The diagnosis for symptomatic and asymptomatic multiple myeloma should be made in accordance with the International Myeloma Working Group criteria, as follows6:

Symptomatic myeloma

    * Clonal plasma cells >10% on bone marrow biopsy

    * Monoclonal protein in serum or urine

    * Evidence of end-organ damage, such as hypercalcemia, renal damage, anemia, frequent infections, amyloidosis, or hyperviscosity

Asymptomatic myeloma

    * Serum paraprotein >30 g/L and/or clonal plasma cells >10%

    * No myeloma-related organ impairment

The International Staging System for multiple myeloma is as follows7:

    * Stage 1 - β2microglubulin <3.5 mg/L; albumin >3.5 g/dL (mean survival, 62 months)

    * Stage 2 - β2microglubulin <3.5 mg/L; albumin <3.5 g/dL (mean survival, 45 months)

    * Stage 3 - β2microglubulin >5.5 mg/L; albumin <3.5 g/dL (mean survival, 29 months)

Management is focused on disease containment and suppression; it involves supportive therapy and treatment of complications. This includes pain control, treatment of fractures and cord compression with use of rehydration, loop diuretics, and bisphosphonates for hypercalcemia. A multidisciplinary team approach is used when there is any evidence of end-organ damage. Specific therapy includes combination chemotherapy (dexamethasone, thalidomide, cyclophosphamide, vincristine, and melphalan); if tolerated, high-dose chemotherapy and autologous stem cell transplantation can be used, although this does confer a 5-10% risk of mortality. Despite the availability of current treatments, the natural history of multiple myeloma involves relapse following treatment. Depending on the patient's condition, the prior treatment modalities and time of relapse will guide the suitability of further chemotherapy and stem cell transplantation. The prognosis is still poor, however, and new cytogenetic analyses of myeloma cells are being investigated for prognostic value; the deletion of chromosome 13, nonhyperdiploidy, and the balanced translocations t(4;14) and t(14;16) confer a poorer prognosis. The cytogenetic abnormalities 11q13 and 6p21 are associated with a better prognosis.

This patient subsequently underwent melphalan chemotherapy and stem cell transplantation, and he made a full recovery. He did not have any further upper GI hemorrhages, and a repeat endoscopy showed resolution of his myeloma polyps.

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