Cancer

Does tuberculosis (TB) increase the risk of cancer?

FA Manian MD, MPH, , , , , , , , , , , , , , , , Leave a comment

Ample reports in the literature suggest that TB is associated with the development of certain cancers, including lung cancer, lymphoma and urothelial cancers of the genitourinary tract. 1-5

A 2010 literature review including 9 retrospective studies found that several (not all) studies reported a significant association between prior history of TB and lung cancer, with odds ratios as high as 20.5 ( C.I. 8.1-51.8) at 1-5 years following TB.1 One study involving non-smoking women found a lung cancer (mostly adenocarcinoma) prevalence of 18% among those with prior history of TB (O.R. 5.9, CI 1.3-25.9).5 Cases of “pyothorax-associated lymphoma” of the pleural cavity have also been attributed to TB diagnosed as remote as 40 years or greater before the diagnosis of cancer.1

Urinary tuberculosis was associated with the development of urothelial carcinoma (including bladder, ureteral, renal pelvic transitional cell carcinoma) but not renal cell carcinoma in a nationwide cohort study from Taiwan (hazard ratio 3.4, C.I. 2.0-5.7). 2 The mean interval between the index date of TB and the diagnosis of urinary tract cancer was about 5 years in this study.

Several potential mechanisms for TB predisposing to malignancy have been proposed.1,6 Chronic inflammation associated with higher rate of cell turnover may increase the risk of genetic mutation and subsequent malignancy, as observed in other conditions such as gastroesophageal reflux disease and esophageal cancer and inflammatory bowel disease and colon cancer. The ability of Mycobacterium tuberculosis to induce DNA damage, inhibit apoptosis and augment concentrations of leukotrienes, prostaglandins and vascular endothelial growth factors have also been implicated.

And don’t forget that active TB may not only coexist with but may also mimic malignancy (see related pearl on P4P).

 

Bonus Pearl: Did you know that the association of TB with cancer was first described in 1810 by Gaspard Laurent Bayle, a French physician who considered “cavitation cancereuse” as a distinct TB category? 1

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 References

  1. Falagas ME, Kouranos VD, Athanassa Z, et al. Tuberculosis and malignancy. Q J Med 2010;103: 461-87. Doi:10.1093/qjmed/hcq068 https://pubmed.ncbi.nlm.nih.gov/20504861/
  2. Lien YC, Wang JY, Lee MC, et al. Urinary tuberculosis is associated with the development of urothelial carcinoma but not renal cell carcinoma: a nationwide cohort study in Taiwan. B J Cancer 2013;109:2933-2940. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3844900/
  3. Chin SN, Foster T, Char G, et al. Concomitant urothelial cancer and renal tuberculosis. Case Reports in Urology. Volume 2014, Aricle ID 625153. https://www.hindawi.com/journals/criu/2014/625153/
  4. Dobler CC, Cheung K, Nguyen J, et al. Risk of tuberculosis in patients with solid cancers and haematological malignancies: a systematic review and meta-analysis. Eur Respir J 2017;50:1700157. https://doi.org/10.1183/13993003.00157-2017.
  5. Ko YC, Lee CH, Chen MJ, et al. Risk factors for primary lung cancer amng non-smoking women in Taiwan. Int J Epidemiol 1997;26:24-31. https://pubmed.ncbi.nlm.nih.gov/9126500/
  6. Ling S, Chang X, Schultz L, et al. An EGFR-ERK-SOX9 signaling cascade links urothelial development and regeneration to cancer. Cancer Res 2011;71:3812-21. https://pubmed.ncbi.nlm.nih.gov/21512138/ 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Does tuberculosis (TB) increase the risk of cancer?

Should I consider a direct oral anticoagulant (DOAC) for my patient with pancreatic cancer and pulmonary embolism?

FA Manian MD, MPH, , , , , , , , , , , , Leave a comment

Classically, anticoagulant (AC) of choice in active malignancy with venous thromboembolism (VTE) has been low-molecular weight heparin (LMWH) (eg, enoxaparin) because of trials showing its superiority over warfarin. But now the pendulum is swinging toward DOACs as an alternative mode of treatment.

A 2018 trial found that oral edoxaban (an Xa inhibitor) was noninferior to subcutaneous dalteparin (a LMWH) with the composite outcome of recurrent VTE or major bleeding.1 Overall, recurrent VTE was significantly lower in edoxaban (7.9% vs 11.3%) but had higher major bleeding (6.9% vs 4.05). Of note, edoxaban was initiated after 5 days of treatment with LMWH.

More recently, the 2020 Caravaggio trial, showed non-inferiority of apixaban (at a dose of 10 mg twice daily for the first 7 days, followed by 5 mg twice daily) to dalteparin with recurrent VTE of 5.6% in the apixaban group vs 7.9% in the dalteparin.2 There was no significant difference in rates of major bleeding (3.8% vs 4%). A prior small study, the ADAM-VTE trial, compared apixaban to dalteparin in patients with malignancy and VTE.3 Apixaban had significantly lower VTE recurrence rates (0.7% to 6.3%) and non-significant lower major bleeding (0% vs 1.4%, p=0.138) consistent with the newer and larger trial. Of note, this trial excluded patients with brain tumor and had few patients with upper GI or hematologic malignancy.  

In addition, a pilot study, the SELECT-D trial, compared rivaroxaban to dalteparin.4 Rivaroxaban had significantly lower VTE recurrence (4% vs 11%), without a significant increase in major bleeding (6% vs 4%), but had an increased number of clinically relevant non-major bleeds (13% vs 4%), particularly in cancers of the upper GI tract.

Although decision regarding use of DOACs in patients with malignancy should be made on case-by-case basis, they are increasingly considered for treatment of VTE in this patient population with the strongest evidence supporting apixaban or the initial use of LMWH for 5 days followed by edoxaban.  

Contributed by Sean Mendez MD, Mass General Hospital, Boston, MA.

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References:  

  1. Raskob GE, van Es N, Verhamme P, Carrier M, Di Nisio M, Garcia D, Grosso MA, Kakkar AK, Kovacs MJ, Mercuri MF, Meyer G, Segers A, Shi M, Wang TF, Yeo E, Zhang G, Zwicker JI, Weitz JI, Büller HR. Edoxaban for the Treatment of Cancer-Associated Venous Thromboembolism. N Engl J Med. 2018 Feb 15;378(7):615-624. doi: 10.1056/NEJMoa1711948. Epub 2017 Dec 12. PubMed PMID: 29231094.
  2. McBane Ii R, Loprinzi CL, Ashrani A, Perez-Botero J, Leon Ferre RA, Henkin S, Lenz CJ, Le-Rademacher JG, Wysokinski WE. Apixaban and dalteparin in active malignancy associated venous thromboembolism. The ADAM VTE Trial. Thromb Haemost. 2017 Oct 5;117(10):1952-1961. doi: 10.1160/TH17-03-0193. Epub 2017 Aug 24. PubMed PMID: 28837207.
  3. Agnelli G, Becattini C, Meyer G, Muñoz A, Huisman MV, Connors JM, Cohen A, Bauersachs R, Brenner B, Torbicki A, Sueiro MR, Lambert C, Gussoni G, Campanini M, Fontanella A, Vescovo G, Verso M. Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer. N Engl J Med. 2020 Mar 29;. doi: 10.1056/NEJMoa1915103. [Epub ahead of print] PubMed PMID: 32223112.
  4. Young AM, Marshall A, Thirlwall J, Chapman O, Lokare A, Hill C, Hale D, Dunn JA, Lyman GH, Hutchinson C, MacCallum P, Kakkar A, Hobbs FDR, Petrou S, Dale J, Poole CJ, Maraveyas A, Levine M. Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism: Results of a Randomized Trial (SELECT-D). J Clin Oncol. 2018 Jul 10;36(20):2017-2023. doi: 10.1200/JCO.2018.78.8034. Epub 2018 May 10. PubMed PMID: 29746227.

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Should I consider a direct oral anticoagulant (DOAC) for my patient with pancreatic cancer and pulmonary embolism?

The chest CT of my patient with “B” symptoms shows hilar mass and mediastinal lymphadenopathy, highly suspicious for lymphoma or malignancy per radiology report. Should I still consider tuberculosis (TB) as a possibility?

FA Manian MD, MPH, , , , , , , , , , , , Leave a comment

Absolutely! TB often mimics malignancy, particularly lymphoma, both clinically and radiographically, even when sophisticated imaging techniques are used.1  

There are ample reports of TB being confused with mediastinal lymphoma, 1-6 with several reports also stressing abdominal TB mimicking malignancy. 7-10 As early as  1949, a  NEJM autopsy study emphasized “the difficulty in differentiating primary progressive TB and some types of lymphoma” and metastatic neoplasms, clinically and radiographically.  Over half-century later, despite major advancement in imaging techniques, TB is often confused for lymphoma or malignancy.

One reason for confusing TB with lymphoma is that primary TB can involve any pulmonary lobe or segment and is often associated with hilar and mediastinal adenopathy. 1 TB may also be overlooked in the differential diagnosis of mediastinal mass that often highlights neoplasms such as lymphoma, thymoma and germ cell tumors. 3 Lack of concurrent pulmonary infiltrates in the presence of mediastinal adenopathy may also veer clinicians away from TB diagnosis. 2,3,6 Unfortunately, even more sophisticated PET/CT scans may not be able to differentiate TB from lymphoma.5,6,9

Besides chest and abdomen, TB can also mimic malignancy in cervical nodes, bones (particularly the spine), bowels, and brain.1,2,6,8,9  To make matters worse, splenomegaly 2,10 and elevated LDH 3 may also be seen with TB and TB may coexist with lymphoma and other malignancies. 7,9,11

One of the best advices I ever received from a radiologist was “Think of TB anytime you think of lymphoma.”

Bonus Pearl: Did you know that TB lymphadenitis is the most common form of extrapulmonary TB with the majority involving the mediastinum? 4

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References

  1. Tan CH, Kontoyiannis DP, Viswanathan C, et al. Tuberculosis: A benign impostor. AJR 2010;194:555-61. https://www.researchgate.net/publication/41509877_Tuberculosis_A_Benign_Impostor
  2. Smith DT. Progressive primary tuberculosis in the adult and its differentiation from lymphomas and mycotic infections. N Engl J Med 1949;241:198-202. https://www.ncbi.nlm.nih.gov/pubmed/18137399
  3. Maguire S, Chotirmall SH, Parihar V, et al. Isolated anterior mediastinal tuberculosis in an immunocompetent patient. BMC Pulm Med 2016;16:24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4739107/
  4. Tang SS, Yang ZG, Deng W, et al. Differentiation between tuberculosis and lymphoma in mediastinal lymph nodes: evaluation with contrast-enhanced MDCT. Clin Radiol 2012;67:877-83. https://www.sciencedirect.com/science/article/abs/pii/S0009926012001079
  5. Hou S, Shen J, Tan J. Case report: Multiple systemic disseminated tuberculosis mimicking lymphoma on 18F-FDG PET/CT. Medicine 2017;96:29(e7248). https://journals.lww.com/md-journal/Pages/ArticleViewer.aspx?year=2017&issue=07210&article=00005&type=Fulltext
  6. Tian G, Xiao Y, Chen B, et al. Multi-site abdominal tuberculosis mimics malignancy on 18F-FDG PET/CT: Report of three cases. World J Gastroenterol 2010;16:4237-4242. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2932932/
  7. Dres M, Demoule A, Schmidt M, et al. Tuberculosis hiding a non-Hodgkin lymphoma “there may be more to this than meets the eye”. Resp Med Case Rep 2012;7:15-16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920344/
  8. Banerjee Ak, Coltart DJ. Abdominal tuberculosis mimicking lymphoma in a patient with sickle cell anemia. Br J Clin Pract 1990;44:660-61. https://www.ncbi.nlm.nih.gov/pubmed/2102179?dopt=Abstract
  9. Gong Y, Li S, Rong R, et al. Isolated gastric varices secondary to abdominal tuberculosis mimicking lymphoma: a case report. Gastroenterology 109;19:78. https://www.ncbi.nlm.nih.gov/pubmed/31138138
  10. Uy AB, Garcia Am Manguba A, et al. Tuberculosis: the great lymphoma pretender. Int J Cancer Res Mol Mech 2016; 2(1):doi http://dx.doi.org/10.16966/2381-3318.123
  11. Nayanagari K, Rani R, Bakka S, et al. Pulmonary tuberculosis with mediastinal lymphadenopathy and superior veno caval obstruction, mimicking lung malignancy: a case report. Int J Sci Study 2015;2:211-14. https://www.ncbi.nlm.nih.gov/pubmed/31138138
The chest CT of my patient with “B” symptoms shows hilar mass and mediastinal lymphadenopathy, highly suspicious for lymphoma or malignancy per radiology report. Should I still consider tuberculosis (TB) as a possibility?

My patient with brain tumor suffered a myocardial infarction (MI) just before having a diagnostic brain surgery. Could the tumor have placed him at higher risk of a coronary event?

FA Manian MD, MPH, , , , , , , , , , , , , , , , Leave a comment

Yes! Arterial thromboembolism—just as venous thromboembolism— is more common in patients with cancer.

In a large 2017 epidemiologic study involving patients 66 years of age or older, the 6-month cumulative incidence of MI was nearly 3-fold higher in newly-diagnosed cancer patients compared to controls, with the excess risk resolving by 1 year. 1 These findings were similar to a previous report involving patients with newly-diagnosed cancer, although in that study the overall coronary heart disease risk remained slightly elevated even after 10 years. 2

In addition, the incidence of coronary events and unstable ischemic heart disease during the 2 year period prior to the diagnosis of cancer is 2-fold higher among cancer patients suggesting that ischemic heart disease may be precipitated by occult cancer. 3

The association of cancer and thromboembolic coronary events may be explained through several mechanisms, including development of a prothrombotic or hypercoagulable state through acute phase reactants, abnormal fibrinolytic activity and increased activation of platelets which are also significantly involved in the pathophysiology of acute coronary syndrome (ACS). 4 Coronary artery embolism from cancer-related marantic endocarditis may also occur.5

More specific to our case, primary brain tumors may be associated with a hypercoagulable state through expression of potent procoagulants such as tissue factor and tissue factor containing microparticles, with a subset producing carbon monoxide, another procoagulant. 6

So our patient’s MI prior to his surgery for brain tumor diagnosis might have been more than a pure coincidence!

Bonus Pearl: Did you know that cancer-related prothrombotic state, also known as  “Trousseau’s syndrome” was first described in 1865 by Armand Trousseau, a French physician who diagnosed the same in himself and died of gastric cancer with thrombotic complications just 2 years later? 7,8

References

  1. Navi BB, Reinder AS, Kamel H, et al. Risk of arterial thromboembolism in patients with cancer. JACC 2017;70:926-38. https://www.ncbi.nlm.nih.gov/pubmed/28818202
  2. Zoller B, Ji Jianguang, Sundquist J, et al. Risk of coronary heart disease in patients with cancer: A nationwide follow-up study from Sweden. Eur J Cancer 2012;48:121-128. https://www.ncbi.nlm.nih.gov/pubmed/22023886
  3. Naschitz JE, Yeshurun D, Abrahamson J, et al. Ischemic heart disease precipitated by occult cancer. Cancer 1992;69:2712-20. https://www.ncbi.nlm.nih.gov/pubmed/1571902
  4. Lee EC, Cameron SJ. Cancer and thrombotic risk: the platelet paradigm. Frontiers in Cardiovascular Medicine 2017;4:1-6. https://www.ncbi.nlm.nih.gov/pubmed/29164134
  5. Lee V, Gilbert JD, Byard RW. Marantic endocarditis-A not so benign entity. Journal of Forensic and Legal Medicine 2012;19:312-15. https://www.ncbi.nlm.nih.gov/pubmed/22847046
  6. Nielsen VG, Lemole GM, Matika RW, et al. Brain tumors enhance plasmatic coagulation: the role of hemeoxygenase-1. Anesth Analg 2014;118919-24. https://www.ncbi.nlm.nih.gov/pubmed/24413553
  7. Thalin C, Blomgren B, Mobarrez F, et al. Trousseau’s syndrome, a previously unrecognized condition in acute ischemic stroke associated with myocardial injury. Journal of Investigative Medicine High Impact Case Reports.2014. DOI:10.1177/2324709614539283. https://www.ncbi.nlm.nih.gov/pubmed/26425612
  8. Samuels MA, King MA, Balis U. CPC, Case 31-2002. N Engl J Med 2002;347:1187-94. https://www.nejm.org/doi/pdf/10.1056/NEJMcpc020117?articleTools=true

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My patient with brain tumor suffered a myocardial infarction (MI) just before having a diagnostic brain surgery. Could the tumor have placed him at higher risk of a coronary event?

My middle-aged patient with a history of mediastinal irradiation for Hodgkin’s lymphoma in his 20s now has moderate aortic regurgitation. Could his valvular disease be related to the radiation he received over 20 years ago?

FA Manian MD, MPH, , , , , , , , , , , , , , , , Leave a comment

Absolutely! Mediastinal irradiation is associated with several cardiac complications, including coronary artery disease, pericarditis, systolic or diastolic dysfunction and valvular disease. Valvular disease may occur in 2-37% of patients after mediastinal irradiation, is dose-dependent, and generally does not manifest until 10-20 years after the radiation exposure.1 Since mediastinal irradiation is common in young adults diagnosed with Hodgkin’s lymphoma, these complications may be seen in early middle-age or later.

Valvular retraction is usually the first radiation-induced valvular change, and most commonly leads to mitral and aortic valve regurgitation.2 This retraction tends to occur within 10 years of the radiation therapy, followed by fibrosis and calcification of the valves after 20 years.

Although the pathophysiology of radiation-induced valvular disease is not entirely understood, activation of fibrogenic growth factors (eg, tissue growth factor β1 and myofibroblasts) which promote the synthesis of collagen has been postulated.1 Additionally, irradiation of aortic interstitial cells has been shown to cause transformation to an osteogenic phenotype that produces bone morphogenic protein 2, osteopontin and alkaline phosphatase, all important factors in bone formation and possibly valvular calcification.3

Since radiation-induced heart disease is the most common cause of non-malignant morbidity and mortality in patients who have undergone mediastinal irradiation, some have recommended screening of asymptomatic patients for valvular disease every 5 years by echocardiography beginning 10 years after radiation therapy. 2  If an abnormality is found, the screening frequency should increase to every 2-3  years,  if the valvular abnormality is mild, or annually if the abnormality is moderate. For severe valvular abnormalities, the patients should be considered for valve replacement.

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References

    1. Gujral DM, Lloyd G, Bhattacharyya S. Radiation-induced valvular heart disease. Heart 2016;102:269–276. https://heart.bmj.com/content/heartjnl/102/4/269.full.pdf
    2. Cuomo JR, Sharma GK, Conger PD, Weintraub NL. Novel concepts in radiation-induced cardiovascular disease. World J Cardiol. 2016; 8 (9):504-519. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039353/
    3. Nadlonek NA, Weyant MJ, Yu JA, et al. Radiation induces osteogenesis in human aortic valve interstitial cells. J Thorac Cardiovasc Surg 2012;144:1466–70. doi:10.1016/j.jtcvs.2012.08.041 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3665422/

Contributed by Rachel Wallwork, MD, Mass General Hospital, Boston, MA

 

My middle-aged patient with a history of mediastinal irradiation for Hodgkin’s lymphoma in his 20s now has moderate aortic regurgitation. Could his valvular disease be related to the radiation he received over 20 years ago?

Does erythrocyte sedimentation rate (ESR) have diagnostic utility in my patient with chronic renal failure?

FA Manian MD, MPH, , , , , , , , , , Leave a comment

Short answer: often not! This is because most studies have shown frequently high ESR’s in stable “uninflamed” patients with chronic renal failure (CRF) (including those on dialysis) at levels often associated with infection, connective tissue disease, or malignancy. 1-4  

In fact, in a study involving patients with CRF, 57% of patients had markedly elevated ESR (greater than 60 mm/h), with 20% having ESR greater than 100 mm/h; type or duration of dialysis had no significant effect on ESR levels.1 Another study reported a specificity for abnormal ESR of only 35% for commonly considered inflammatory conditions (eg, infections or malignancy) among patients with CRF. 2

But is it the chronic inflammation in diseased kidneys or the uremic environment that elevates ESR? A cool study compared ESR in CRF in patients who had undergone bilateral nephrectomies with those with retained kidneys and found no significant difference in the ESR between the 2 groups. 4  So it looks like it’s the uremic environment, not diseased kidneys themselves that result in elevated ESR in these patients.

The mechanism behind these observations seem to reside entirely within the patients’ plasma, not the erythrocytes. Within the plasma, fibrinogen (not gammaglobulins) seem to be the most likely factor explaining elevated ESR among patients with CRF. 1,2

Bonus pearl:  Did you know that ESR is nearly 100 years old, first described in 1921? 5

References

  1. Barthon J, Graves J, Jens P, et al. The erythrocyte sedimentation rate in end-stage renal failure. Am J Kidney Dis 1987;10: 34-40. https://www.ncbi.nlm.nih.gov/pubmed/3605082
  2. Shusterman N, Morrison G, Singer I. The erythrocyte sedimentation rate and chronic renal failure. Ann Intern Med 1986;105:801. http://annals.org/aim/fullarticle/700910
  3. Arik N, Bedir A, Gunaydin M, et al. Do erythrocyte sedimentation rate and C-reactive protein levels have diagnostic usefulness in patients with renal failure? Nephron 2000;86:224. https://www.ncbi.nlm.nih.gov/pubmed/11015011
  4. Warner DM, George CRP. Erythrocyte sedimentation rate and related factors in end-stage renal failure. Nephron 1991;57:248. https://www.karger.com/Article/PDF/186266
  5. Fahraeus R. The suspension stability of the blood. Acta Med Scan 1921;55:70-92. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.0954-6820.1921.tb15200.x

 

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Does erythrocyte sedimentation rate (ESR) have diagnostic utility in my patient with chronic renal failure?

Can non-steroidal anti-inflammatory drugs (NSAIDs) suppress cancer metastasis?

FA Manian MD, MPH, , , , , , , , , , , Leave a comment

A 2017 meta-analysis reported that NSAIDs are associated with lower risk of distant metastasis in patients with breast, prostate, lung, and colorectal cancer.1

The mechanism accounting for this observation is not fully understood. However, since inflammation has been implicated as a driving force for tumor metastasis 2, blunting the inflammatory microenvironment that surrounds tumors may explain NSAIDs’ reported beneficial effect.

NSAIDs may also have a direct effect on cancer cells. In-vitro studies demonstrate that NSAIDs induce the expression of a protein (p75 neurotrophic receptor, p75NTR) associated with suppression of tumor growth and metastasis in prostate cancer; this protein also suppresses growth of bladder cancer cells.3,4

Ibuprofen and indomethacin are among the commonly available NSAIDS shown to exhibit such anti-tumor effect. Interestingly, non-COX-inhibiting NSAIDS (eg, [R] flurbiprofen, an enantiomer of ibuprofen) may also be effective suggesting that inhibition of cell survival may not be COX-mediated.

Although these findings and observations are promising, randomized-controlled trials are clearly needed to better define the role of NSAIDs in the clinical management of cancer.

 

References: 

  1. Zhao X, Xu Z, Li H. NSAIDs use and reduced metastasis in cancer patients: Results from a meta-analysis. Sci Rep 2017; 7:1875. https://www.ncbi.nlm.nih.gov/pubmed/28500305
  2. Qian BZ. Inflammation fires up cancer metastasis. Semin Cancer Biol 2017; 47:170-176. https://www.ncbi.nlm.nih.gov/pubmed/28838845
  3. Khwaja F, Allen J, Lynch J, Andrews P, Djakiew D. Ibuprofen inhibits survival of bladder cancer cells by induced expression of the p75NTR tumor suppressor protein. Cancer Res 2004; 64:6207-6213. https://www.ncbi.nlm.nih.gov/pubmed/15342406
  4. Krygier S, Djakiew D. Neurotrophin receptor p75NTR suppresses growth and nerve growth factor-mediated metastasis of human prostate cancer cells. Int J Cancer 2002; 98:1-7. https://www.ncbi.nlm.nih.gov/pubmed/11857376

Contributed by Camilo Campo, Medical Student, Harvard Medical School, Boston, MA.

Can non-steroidal anti-inflammatory drugs (NSAIDs) suppress cancer metastasis?

My patient with COPD has new clubbing of his finger tips. What is the mechanism of clubbing?

FA Manian MD, MPH, , , , , , Leave a comment

The mechanism behind digital clubbing has yet to be fully elucidated, with hypotheses ranging from a circulating vasodilator, tissue hypoxia, a neurocirculatory reflex, and genetic factors. 1 Although hypoxemia is often cited as a cause of clubbing, it is often absent in the presence of clubbing and many patients with hypoxemia do not have clubbing.

A potentially unifying pathophysiologic mechanism of clubbing revolves around platelet clustering and associated growth factor release. 2.3 Platelet clumps/megakaryocytes—either because of circumvention of the lung capillary network (eg, in intracardiac shunts or lung cancer) or increased production (eg, in left-sided endocarditis or chronic inflammatory conditions)—may wedge in the fine vasculature of distal fingertips or toes and cause release of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF).

Together, PDGF and VEGF promote neovascularization, increase vessel dilation and permeability, and modify connective tissue to create the distinct club-like appearance. Local hypoxic condition from reduced capillary perfusion is thought to further stimulate the release of these growth factors.

Potential causes of clubbing in our patient include lung cancer, interstitial lung disease, bronchiectasis, core pulmonale and secondary polycythemia, among many others. 1

Fun Fact: Did you know that clubbing, also known as “Hippocratic finger”, was first described by Hippocrates in a patient with chronic empyema (don’t ask how chronic empyema was diagnosed in 400 BC!)?1

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References

  1. McPhee SJ. Clubbing. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths;1990. Chapter 44. Available from https://www.ncbi.nlm.nih.gov/books/NBK366/
  2. Dickinson CJ, Martin JF. Megakaryocytes and platelet clumps as the cause of finger clubbing. Lancet 1987;2:1434-4. https://www.ncbi.nlm.nih.gov/pubmed/2891996/ 
  3. Atkinson S, Fox SB. Vascular endothelial growth factor (VEGF)-A and platelet-derived growth factor (PDGF) play a central role in the pathogenesis of digital clubbing. J Pathol 2004;203:721-8. https://www.ncbi.nlm.nih.gov/pubmed/15141388

 

Contributed by George Bugarinovic, Medical Student, Harvard Medical School

My patient with COPD has new clubbing of his finger tips. What is the mechanism of clubbing?

My patient is asking about the benefits of smoking cessation. How soon should she realize the health benefits of quitting her habit?

FA Manian MD, MPH, , , , , , , , , , , , Leave a comment

She should realize the health benefits of smoking cessation (SC) almost immediately! As the effect of nicotine wears off, just 15-20 minutes after her last cigarette, her heart rate and blood pressure should begin to fall.1,2Other health benefits, some within a year others longer, soon follow. 3,4 Between 2-12 weeks after SC, your patient may notice an improvement in her breathing and pulmonary function tests.

Between 1-9 months, the cilia in the lungs should begin to regenerate and regain normal function, allowing her to adequately clear mucus and bacteria with a decrease in cough and shortness of breath.

At 1 year, the risk of cardiovascular disease (eg, myocardial infarction, stroke) falls by one-half.

At 5 years, the risk of mouth, throat, esophagus, and bladder cancer also drops by one-half.

It takes 10 years for the risk of lung cancer to drop by one-half, and 15 years for it to approach that of non-smokers asymptotically. 4

 

Fun fact: Did you know that in hypertensive patients who smoke, the blood pressure lowering effect of beta-blockers may be partly abolished by tobacco smoking,  whereas alpha-blockers may maintain their antihypertensive effects? 5

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References

  1. Omvik P. How smoking affects blood pressure. Blood Press. 1996;5:71–77. https://www.ncbi.nlm.nih.gov/pubmed/9162447
  2. Mahmud A, Feely J. Effect of smoking on arterial stiffness and pulse pressure amplification. Hypertension. 2003;41(1):183-187. https://www.ncbi.nlm.nih.gov/pubmed/12511550
  3. US Surgeon General’s Report, 1990, pp. 193, 194, 196, 285, 323
  4. US Surgeon General’s Report, 2010 and World Health Organization. Tobacco Control: Reversal of Risk After Quitting Smoking. IARC Handbooks of Cancer Prevention, Vol. 11. 2007, p. 341.
  5. Trap-Jensen. Effects of smoking on the heart and peripheral circulation. Am Heart J 1988;115:263-7.   https://www.ncbi.nlm.nih.gov/pubmed/3276115

Contributed by Felicia Hsu, Medical Student, Harvard Medical School

My patient is asking about the benefits of smoking cessation. How soon should she realize the health benefits of quitting her habit?

My middle age patient complains of night sweats for several months, but she has had no weight loss and does not appear ill. What could I be missing?

FA Manian MD, MPH, , , , , , , , , , , , , , , Leave a comment

Night sweats (NS) is a common patient complaint, affecting about a third of hospitalized patients on medical wards1.  Despite its long list of potential causes, direct relationship between the often- cited conditions and NS is usually unclear2, its cause may remain elusive In about a third to half of cases in the primary care setting, and its prognosis, at least in those >65 y of age, does not appear to be unfavorable 2,3.

Selected commonly and less frequently cited conditions associated with NS are listed (Table)2-9.  Although tuberculosis is one of the first conditions we think of when faced with a patient with NS, it should be emphasized that NS is not common in this disease (unless advanced) and is rare among hospitalized patients as a cause of their NS1,9.

In one of the larger study of adult patients seen in primary care setting, 23% reported pure NS and an additional 18% reported night and day sweats5; the prevalence of NS in both men and women was highest in 41-55 y age group. In multivariate analyses, factors associated with pure NS in women were hot flashes and panic attacks; in men, sleep disorders. 

Table. Selected causes of night sweats

Commonly cited Less frequently cited
Neoplastic/hematologic (eg, lymphoma, leukemia, myelofibrosis)

Infections (eg, HIV, tuberculosis, endocarditis)

Endocrine (eg, ovarian failure, hyperthyroidism, orchiectomy, carcinoid tumor, diabetes mellitus [nocturnal hypoglycemia], pheochromocytoma)

Rheumatologic (eg, giant cell arteritis)

 Gastroesophageal reflux disease

B-12 deficiency

Pulmonary embolism

Drugs (eg, anti-depressants, SSRIs, donepezil [Aricept], tacatuzumab)

Sleep disturbances (eg, obstructive sleep apnea)

Panic attacks/anxiety disorder

Obesity

Hemachromatosis

Diabetes insipidus

References

  1. Lea MJ, Aber RC, Descriptive epidemiology of night sweats upon admission to a university hospital. South Med J 1985;78:1065-67.
  2. Mold JW, Holtzclaw BJ, McCarthy L. Night sweats: A systematic review of the literature. J Am Board Fam Med 2012; 25-878-893.
  3. Mold JW, Lawler F. The prognostic implications of night sweats in two cohorts of older patients. J Am Board Fam Med 2010;23:97-103.
  4. Mold JW, Holtzclaw BJ. Selective serotonin reuptake inhibitors and night sweats in a primary care population. Drugs-Real World Outcomes 2015;2:29-33.
  5. Mold JW, Mathew MK, Belgore S, et al. Prevalence of night sweats in primary care patients: An OKPRN and TAFP-Net collaborative study. J Fam Pract 2002; 31:452-56.
  6. Feher A, Muhsin SA, Maw AM. Night sweats as a prominent symptom of a patient presenting with pulmonary embolism. Case reports in Pulmonology 2015. http://dx.doi.org/10.1155/2015/841272
  7. Rehman HU. Vitamin B12 deficiency causing night sweats. Scottish Med J 2014;59:e8-11.
  8. Murday HK, Rusli FD, Blandy C, et al. Night sweats: it may be hemochromatosis. Climacteric 2016;19:406-8.
  9. Fred HL. Night sweats. Hosp Pract 1993 (Aug 15):88.
My middle age patient complains of night sweats for several months, but she has had no weight loss and does not appear ill. What could I be missing?