Medicine

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Cancer Center Pain Board

Stephen Abram, MD
The Palliative Care Outpatient team is collaborating with Stephen Abram, Professor in Anesthesiology and a specialist in pain management, to provide a monthly interdisciplinary review board for providers caring for patients with cancer-related pain.

The Palliative Care Outpatient clinic assessed over 500 patients last year. Most of these visits involved treatment of complex pain syndromes. Medical management with opioids and adjuvants remain the mainstay of treating cancer-related pain, however, in some patients these medications may be inadequate or too poorly tolerated to satisfactorily relieve the patient’s symptoms. Furthermore, care for cancer patients who are experiencing pain is made more challenging when concomitant chronic pain and substance use disorders complicate their care.

The good news is that overall, cancer patients are living longer. According to the Centers for Disease Control and Prevention, approximately two-thirds of individuals with cancer are expected to live at least 5 years after initial diagnosis. However, cancer survivors often face ongoing pain syndromes either directly related to their cancer or treatment-related. In the past, it was difficult for many providers to know where to send patients for help with acute and chronic pain management issues. The on-site presence of Dr. Abram in the Clinical Cancer Center has provided opportunities for better collaborative pain management.

Our goal is to provide a venue for recommendations from an interdisciplinary team for managing cancer-related pain. Monthly meetings include short didactic presentations and discussion on new, innovative, or interesting pain treatment topics.

Sean Marks, MDThe palliative care outpatient team includes Jonathan Gully, MD and Sean Marks, MD, Assistant Professors in the Division Jonathan Gully, MDof Hematology and Oncology, Wendy Peltier, MD, Associate Professor in the Department of Neurology, Margaret Donegan, NP and Sandy Muchka, CNS.


To refer a patient to the pain board, please page Dr. Steve Abram from the Pain Management Clinic or Margaret Donegan from Palliative Care.

Kidney Stones: from the Clinic to the Laboratory

The Stone Clinic in the Division of Nephrology is one of several “disease specific” clinics in the Department of Medicine, and it offers a unique educational experience to both patients and trainees. While the clinic initially opened as an interdisciplinary clinic staffed by Jack Kleinman, MD (Nephrology), Frank Begun, MD (Urology) and myself, it has subsequently become exclusively a Nephrology clinic, though we maintain a close working relationship with our Urology colleagues, lead now by Carley Davis, MD. The clinic was opened in the Nephrology/Transplant Surgery clinic on the 4th floor of FEOB in 1999, as a clinical extension of a longstanding research emphasis on kidney stone formation by MCW faculty within the Division of Nephrology going back more than 40 years. MCW was brought to prominence in stone research by the late Jacob Lemann, MD, who was the Division Chairman from 1970, until his retirement from MCW in 1994. The clinic has survived the initial name confusion with the “Small Stones” public education program from Froedtert Hospital, though its profile remains relatively low, and it remains one of only a handful of clinics in the state with emphasis on the metabolic evaluation of stone forming patients. Despite the high prevalence of this disease in both the Milwaukee area and around the country (affecting 10-15% of men and 5-10% of women in the United States), most primary care doctors receive very little training in the management and prevention of kidney stones, and some confusion still exists regarding even the most basic issues, such as the recommended consumption of calcium rich foods in the diet.


To briefly summarize the clinical syndrome, kidney stones (aka, nephrolithiasis or urolithiasis) are aggregates of crystals that form in the renal pelvis, typically attached to the surface of the kidney near the papillary tip. In the most common manifestations of the disease, these crystal aggregates are slow growing and generally asymptomatic until one of the aggregates becomes detached and floats downstream, interfering with urine flow in the ureter, frequently first occurring in midlife. Nephrocalcinosis is a related condition that can be seen in conjunction with nephrolithiasis, but this condition refers specifically to crystal deposits within the kidney itself. Kidney stones are a recurring problem in most patients with an interval between stones of 3 to 5 years, though they can recur as frequently as every few weeks in some unfortunate individuals, frequently requiring surgical interventions to correct acute kidney injury due to obstruction of the flow of urine.


While the disease process is straightforward to describe, the picture is made complex by the fact that a variety of substances can crystallize, leading to stone formation with links to various metabolic disturbances. Classically, the disease is associated with calcium oxalate and calcium phosphate crystal formation, since the various crystalline forms of these two calcium salts affect about 80% of the stone forming patients, and in most cases these patients lack any clear metabolic derangements of the their blood or urine. Other crystal types seen commonly are uric acid crystals which are present in about 10-15% of patients, most commonly associated with gout, defects in purine metabolism, the metabolic syndrome (obesity and type II diabetes), and also during treatment of tumors with chemotherapy. Struvite crystals (magnesium ammonium phosphate crystals) occur in about 10% of stone afflicted individuals associated with chronic urinary tract infections. Less frequently seen are stones formed of crystals derived from a variety of drugs (including acyclovir, indinavir, sulfa drugs and many others) or from cystine in patients with cystinuria, a condition caused by rare genetic defects interfering with the renal reuptake of the amino acid cystine from the urine.


The unifying feature for prevention of all forms of stones is to make the urine more dilute with respect to the chemicals forming the crystals. Thus, drinking more water or other fluids works for all stone types, but only to the extent that the patients actually increase their urine volumes significantly; we recommend doubling the volume. Beyond that, efforts can be made to alter urine features that favor crystallization. Obviously, with exogenous substances like drug crystals, stopping the offending agent will cure the disorder. Since uric acid crystals are poorly soluble at low urine pH, ingestion of alkali salts (sodium bicarbonate or potassium citrate) can dramatically reduce stone formation or even dissolve existing stones. Reduction of protein-rich (purine-rich) foods and addition of more fruit in the diet can achieve both an elevation in urine pH and a reduction in uric acid excretion, and the latter can be improved with xanthine oxidase inhibitors (allopurinol or febuxostat). Similarly, cystine stones respond somewhat to the same diet and drug interventions, but the increase in cystine solubility requires a much larger increase in pH to be useful, which is difficult to achieve. Cystine binding drugs (i.e., tiopronin, penicillamine, captopril) can be given in severe cases, but these drugs all have limited efficacy and are poorly tolerated. Struvite stones frequently require interventions (medical and surgical) to eradicate urinary tract infections, since bacteria synthesizing urea splitting enzymes trigger the chemical changes (particularly high pH) required for struvite precipitation.


In many ways, the most interesting category of stone disease is the largest group of calcium (oxalate and phosphate) stone formers, where only a minority of patients demonstrate an altered urine composition due to either an identifiable genetic defect of metabolism or transport (in only a very small fraction of patients, i.e., hyperoxalosis, Dent’s disease, distal RTA) or chronic diarrhea or malabsorption syndromes (a minor but growing fraction, i.e., inflammatory bowel disease, surgical short gut, post-bariatric surgery). These conditions predispose to stone disease through various combinations of high urine oxalate or phosphate, low urine volume, and low urine citrate (potent inhibitor of calcium crystallization); factors which can be explicitly addressed through diets and supplements. Disorders of calcium metabolism (i.e., hypercalciuria, hyperparathyroidism, sarcoidosis) are also predisposing factors to stone formation due to increased calcium concentrations in urine, but these conditions are not generally sufficient to cause stone formation without some underlying predisposition. In fact, the vast majority of calcium stone formers (hypercalciurics and idiopathic, i.e., no identifiable abnormality) actually suffer more frequent recurrences on low calcium diets, than they do on a normal (1,000 to 1,500mg per day) diet, though these evidence-based results have been slow to penetrate general medical practice. Consequently, the recommended diet modifications for prevention of calcium based stones includes only the addition of adequate dietary calcium intake to the high fluid (high urine volume), reduced protein and enhanced intake of fruit recommended above. Hypercalciuria (higher than normal urine calcium excretion, typically taken as >250mg/day) can be treated with thiazide class diuretics, and may respond to dietary salt and protein restriction.


As evident from the summary of clinical features above, research in the field is imperative to find a cure for calcium stone disease, and MCW currently has 3 funded investigators working on various aspects of the mechanism of stone formation, including Neil Mandel, PhD, Jack Kleinman, MD and myself. We, similar to most researchers in the field, feel that these common kidney stones likely result from the influence of more than one gene defect simultaneously. Our efforts have emphasized studies of the interactions between the biological components (i.e., urine proteins, lipid bilayers, basement membranes) and the crystals that contribute to the aggregate formation. We have also focused on the attachment of crystals to the epithelial surfaces leading to retention in the kidney, since the individual crystals are otherwise microscopic and would easily be flushed asymptomatically from the system by the normal flow of urine. These experiments include studies in animal models (rat and pig), cell cultures, isolated urinary components and synthetic analogs of urinary macromolecules (proteins) and have highlighted the importance of not only alterations in the biological components with regard to their interaction with the crystal surfaces, but also interactions between biological components (protein aggregation) that may drive the process of crystal aggregation and attachment. Many patients from the Stone Clinic have participated in these research projects, though progress is slow with such a diverse array of factors involved.


We certainly welcome your referrals of patients for metabolic evaluation and treatment for prevention of kidney stones, and we would be happy to consult with you as individuals or small groups to facilitate management of stone-forming patients.

 

Article written by Jeffrey Wesson, MD, PhD, Associate Professor

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Page Updated 06/13/2012