Case Discussion: A Man with Two Synchronous and Symptomatic Malignancies Related to Smoking: The Case for Surgery

By: Renzo Colombo

EU Focus, Volume 1 Issue 1, November 2015, Pages 92-93

Published online: 13 November 2015

Abstract Full Text Full Text PDF (69 KB)

Refers to article:

Case Presentation: A Man with Two Synchronous and Symptomatic Malignancies Related to Smoking

Alberto Briganti and Gianluca Giannarini

1. Clinical features

This unusual and challenging clinical case concerns an elderly patient with negative clinical history who presented at the emergency unit due to a recent appearance of severe symptoms including abdominal pain, jaundice, and gross haematuria.

Ultrasound and computed tomography scan were strongly suggestive of the presence of two concomitant major cancers: an advanced biliary neoplasm involving adjacent organs and organ-invasive carcinoma at the left renal pelvis. To relieve the acute clinical symptoms and overcome the increasing jaundice, biliary duct drainage with biliary stent placement was successfully performed and restored both an acceptable clinical status and a normal blood-test setting.

2. Discussion

The two cancers identified in this patient share some interesting clinical findings. First, both neoplasms were diagnosed only at an advanced clinical stage after a long period of clinical silence. It is recognised that for biliary tract cancer, carcinogenesis follows a progression through a metaplasia–dysplasia–carcinoma sequence that generally takes years [1]. Vagueness of symptoms is generally responsible for the delay of diagnosis, which contributes to the overall progression of the disease. In contrast, haematuria is a unique and late sign of an upper tract urinary urothelial cancer in almost all cases. In this context, the impact of imaging on early diagnosis is known to be marginal.

Second, cigarette smoking is recognised to be a substantial risk factor for both neoplasms. This patient can be classified as a strong smoker based on both the number of cigarettes per day and the period of abuse. For upper tract urinary urothelial cancer, smoking has been definitively associated with pathologic stage pT2 or higher, high grade, and multifocality at first diagnosis [2] and [3]. In addition, local and distant recurrence rates are expected to be higher in persistent smokers after nephroureterectomy [4] and [5]. Although the level of evidence is lower, cigarette smoking is also a risk factor (with increased risk up to 45%) for pancreatic and liver cancer. A recent meta-analysis of 11 selected case–control and cohort studies [6], including a total of 1178 cases, showed that smokers are at increased risk of development of biliary tract cancer compared with nonsmokers, regardless of alcohol abuse and history of gallstones.

Third, both kinds of cancer have poor prognoses when diagnosed at an advanced stage. In particular, for advanced biliary cancer (stage T3–T4), the overall mortality rate closely follows incidence. For this tumour, overall mean survival is a mere 6 mo, whereas the 5-yr survival rate does not exceed 5% [7]. This means that surgery is expected to be curative only in the subset of patients found with stage pT1–pT2 and negative surgical margins and would be palliative in the remaining cases.

Fourth, for both kinds of cancer at advanced clinical stage, major international guidelines lack grade A recommendations for treatment. Based on reduced clinical evidence, the administration of a combined chemotherapy regimen with cisplatin and gemcitabine in neoadjuvant or adjuvant settings is suggested for both cancers [8] and [9].

3. Treatment recommendation

Left nephroureterectomy with or without retroperitoneal lymph node dissection may be proposed but will not influence patient survival, which is predominantly driven by biliary cancer. In the absence of severe haematuria, I would avoid nephroureterectomy at this time. If, based on imaging, hepatic artery and vena porta involvement leads to consideration of the biliary cancer as unresectable, I would not recommend an upfront palliative surgery.

Due to normal renal function and the absence of comorbidities, I would propose that the patient be given first-line palliative chemotherapy with a combination of gemcitabine and cisplatin for 6–8 cycles. This treatment may prolong disease-free survival from 6.5 mo to 8.4 mo [8]. If the patient is able to complete the scheduled chemotherapy regimen with bulky tumour response, according to the general clinical conditions, combined surgery including hepatic and biliary tract resection and left nephroureterectomy could be reconsidered.

In the case of completion of scheduled chemotherapy without significant clinical response but with proven stabilised disease, I would consider this patient to be a candidate for observation.

Conflicts of interest

The author has nothing to disclose.


  • [1] R. Hundal, E.A. Shaffer. Gallbladder cancer: epidemiology and outcome. Clin Epidemiol. 2014;6:99-109
  • [2] A. Simsir, B. Sarsik, I. Cureklibatir, S. Sen, G. Gunaydin, C. Cal. Prognostic factors for upper urinary tract urothelial carcinomas: stage, grade, and smoking status. Int Urol Nephrol. 2011;43:1039-1045
  • [3] M. Rink, E.C. Zabor, H. Furberg, et al. Impact of smoking and smoking cessation on outcomes in bladder cancer patients treated with radical cystectomy. Eur Urol. 2013;64:456-464 Crossref
  • [4] M. Hagiwara, E. Kikuchi, N. Tanaka, et al. Impact of smoking status on bladder tumor recurrence after radical nephroureterectomy for upper tract urothelial carcinoma. J Urol. 2013;189:2062-2068 Crossref
  • [5] J.D. Raman, C.K. Ng, S.A. Boorjian, E.D. Vaughan Jr., R.E. Sosa, D.S. Scherr. Bladder cancer after managing upper urinary tract transitional cell carcinoma: predictive factors and pathology. BJU Int. 2005;96:1031-1035 Crossref
  • [6] D. Wenbin, C. Zhuo, M. Zhibing, et al. The effect of smoking on the risk of gallbladder cancer: a meta-analysis of observational studies. Eur J Gastroenterol Hepatol. 2013;25:373-379 Crossref
  • [7] S. Jayaraman, W.R. Jarnagin. Management of gallbladder cancer. Gastroenterol Clin North Am. 2010;39:331-342 Crossref
  • [8] J. Valle, H. Wasan, D.H. Palmer, et al. ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362:1273-1281 Crossref
  • [9] S.F. Matin, V. Margulis, A. Kamat, et al. Incidence of downstaging and complete remission after neoadjuvant chemotherapy for high-risk upper tract transitional cell carcinoma. Cancer. 2010;116:3127-3134 Crossref


Division of Oncology/Urology Unit, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy

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