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Year : 2015  |  Volume : 5  |  Issue : 1  |  Page : 29-32

Dual malignancies: Do they have a worse prognosis than their individual counterparts

Department of Surgical Gastroenterology, Narayana Medical College, Chintareddipalem, Nellore, Andhra Pradesh, India

Date of Web Publication13-Mar-2015

Correspondence Address:
TVA Chowdary
Department of Surgical Gastroenterology, Narayana Medical College, Chintareddipalem, Nellore - 524 002, Andhra Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2278-9596.153151

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Background: The incidence of multiple primary cancers is reported to be between 0.734% and 11.7%. The occurrence of another malignancy of different organ in patients with known malignant tumor is known as double malignancy and is categorized into synchronous; in which the cancer occurs at the same time or within 6 months and metachronous; in which cancer follows in sequence more than 6 months apart. We review the presentation and management of synchronous malignancies in two different organs.
Patients and Methods: All the patients who underwent surgery for malignancy between July 2009 and July 2013 were reviewed and the patients who had synchronous malignancies were identified. Their clinical presentation, treatment and outcome were evaluated.
Results: Out of a total of 286 patients with malignancies treated in our institute, four had synchronous primary malignancies (1.39%). Three of them underwent surgery simultaneously for both the malignancies and were given adjuvant chemotherapy. One patient presented with colonic obstruction due to sigmoid carcinoma which was operated in an emergency setting and was later in the postoperative period found to have a synchronous periampullary carcinoma. Two of the patients who were managed with surgery followed by chemotherapy are doing well. Whereas the other two patients have died.
Conclusion: Treatment strategies in cases of double malignancy depend on treating the malignancy that is more advanced first, or sometimes both malignancies could be treated simultaneously. If both are amenable to surgical resection as in two of our cases both the malignancies may be dealt with at the same time. The prognosis of the patients with dual malignancies depends on the aggressiveness and the stage of presentation of the more advanced tumor.

Keywords: Dual malignancies, multiple primary malignancy, outcome of synchronous primary malignancy, synchronous primary malignancy

How to cite this article:
Chowdary T, Sivaraj S M, Rao G V, Thirunavukkarasu S. Dual malignancies: Do they have a worse prognosis than their individual counterparts . Arch Int Surg 2015;5:29-32

How to cite this URL:
Chowdary T, Sivaraj S M, Rao G V, Thirunavukkarasu S. Dual malignancies: Do they have a worse prognosis than their individual counterparts . Arch Int Surg [serial online] 2015 [cited 2024 Mar 1];5:29-32. Available from:

  Introduction Top

Malignancies occurring in two different organs are relatively rare and both presenting at the same time are even rarer. The incidence of multiple primary cancers is reported to be 0.734% to 11.7%. [1] The occurrence of another malignancy of different organs in patients with known malignant tumor is known as dual or multiple primary malignancies. Multiple primary malignancies are divided according to Moertel's [2] definition into synchronous and metachronous. 1) Synchronous refers to tumors diagnosed within 6 months 2) Metachronous refers to tumor which are diagnosed after 6 months of diagnosis of the first tumor.

Patients who present with such tumors, especially with synchronous tumors present a unique clinical scenario with regard to the treatment. Metachronous malignancies are said to have a better prognosis than synchronous malignancies [3],[4] whilst that of synchronous malignancies is said to be worse. Which malignancy must be dealt with first or are both to be dealt with at the same time are questions yet to be answered.

Two hundred and eighty-six patients with malignancy have been treated at our institute between July 2009 and July 2013 and four patients with dual malignancies were identified, which are reported here.

  Case Report Top

Case 1

A 47-year-old male with symptoms of obstructive jaundice. Upper gastro-intestinal (GI) endoscopy and contrast-enhanced computed tomography (CECT) revealed a periampullary growth, operable with no enlarged lymph nodes. A Whipple's pancreaticoduodenectomy was performed [Figure 1]a-c] Postoperative period was uneventful. Histopathology of the specimen revealed two distinct foci of malignancy. One focus of duodenal adenocarcinoma and another separate focus of acinar cell carcinoma of the head of pancreas. Patient underwent postoperative chemotherapy and is recurrence free for a follow-up period of 2 years.
Figure 1: Whipples specimen (a) with duodenal adenocarcinoma (b) and acinar cell carcinoma of pancreas (c)

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Case 2

A 68-year-old male non alcoholic with vague abdominal pain whose investigations revealed hepatocellular carcinoma segments 5, and 8 of the liver. His upper GI endoscopy showed a periampullary growth. He was assessed and was fit for surgery. A right hepatectomy with a whipple's pancreatico duodenectomy [Figure 2]a-d] was done. Patient died on 10 th postoperative day due to liver failure. His biopsy revealed hepatocellular carcinoma (HCC) of the liver and duodenal adenocarcinoma.
Figure 2: Right Hepatectomy for HCC (a), HPE of HCC (b), whipples procedure for duodenal adenocarcinoma (c), HPE of duodenal adenocarcinoma (d)

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Case 3

A 50-year-old female, presented with bleeding per vaginum and abdominal pain to a practitioner elsewhere. She was diagnosed to have endometrial carcinoma and a total hysterectomy and bilateral salpingo-oophorectomy was done. On the 15 th postoperative day she developed features of intestinal obstruction and was sent to our institute. An emergency laparotomy was performed which revealed a growth in the sigmoid for which an anterior resection was done. The postoperative course was uneventful. Biopsy was that of endometrial carcinoma for the uterus and sigmoid adenocarcinoma. She was given chemo-radiotherapy postoperatively. She is on follow-up for 3 years, recurrence free.

Case 4

A 55-year-old male patient presented with features of intestinal obstruction. Emergency laparotomy revealed a growth in the ascending colon so a right hemi colectomy was performed. Biopsy was that of a colonic adenocarcinoma. In the postop period he had prolonged ileus and oral intake was tolerated only on the 14 th day. He continued to be asthenic and had weight loss, upper GI endoscopy was done which was normal. Two months after the surgery he developed jaundice of an obstructive pattern. An endoscopy done then showed a growth at the periampullary region which proven to be pancreatic adenocarcinoma. A CECT done 4 months after surgery showed multiple liver metastases. He developed cholangitis and expired.

  Discussion Top

The occurrence of multiple primary malignancies, which was thought to be a rare occurrence seems to occur or is probably being diagnosed more frequently than thought earlier. The reported prevalence of multiple primary malignant neoplasms (MPMN) varies between 0.734-11.7%. The incidence at our institution was 1.39%.

The occurrences of such multiple primary tumors was first identified by Renaud in 1847 and Rokitansky in 1855 but were poorly documented. [5] It was Billroth [6] who first reported patients with such primary tumors in 1860.

The diagnosis of multiple primary tumors is now increasing due to an increased awareness of possibility of a second malignancy, the higher use and sensitivity of diagnostic methods as well as the recent improvements in cancer treatment and survival will further lead to higher prevalence of multiple cancers. As patients with history of cancer tend to undergo regular follow-up, this could lead to earlier diagnosis of new malignancies at curable stages. [7] It is well-known that individuals who suffered from malignancy exhibit a 14-20% [8],[9] higher risk of subsequent primary malignancies. Thus, as the number of cancer survivors increases with the current strategies of management of cancer, the number of patients with multiple primary cancers will increase as well. Cancer survivors who develop a second malignancy have a higher risk of dying [10] and experience a worsening in their quality of life.

To define a second primary malignancy International Agency for Research on Cancer (IARC) has laid down a few rules and guidelines [11],[12] which include 1. The existence of two or more primary cancers does not depend on time; 2. Both tumors are confined to primary sites, and no direct connections between the tumors exist; 3. One tumor should only be recognized in an organ or a pair of organs or tissue (as defined by the code of the International Classification of Diseases, ICD); 4. Rule 3 does not apply if tumors in an organ are of a different histology; 5. Be different in histological type when diagnosis of pathology available.

Warren and Gates [13] have defined multiple primary malignancies as follows

  1. The tumor has to have definite features of malignancy.
  2. The tumor has to be separate and distinct from the index tumor.
  3. The possibility of the tumor being a metastasis of the index tumor has to be ruled out.

Though the mechanism involved in the development of multiple primary cancer has not been clarified, some factors such as heredity, constitution, environmental and immunological factors, carcinogenic, viruses, radiological and chemical treatments have been implicated. [14],[15],[16]

Microsatellite instability is a condition of genetic hyper mutability that results from impaired DNA mismatch repair. Newer technology has enabled us to analyze various genetic and epigenetic alterations such as point mutations, loss of heterozygosity and genetic instabilities. Horii et al., has observed that the incidence of microsatellite instability in multiple primary cancers was more frequent that in sporadic cancers. [17] P53 tumor suppressor gene is known as the 'guardian of the human genome' because of its role in conserving the stability by preventing genome mutations. [18] Kimura et al., [19] Landosi et al., [20] Miyaki M et al., [21] have all described the presence of p53 mutations in multiple primary malignancies.

The early diagnosis and management of patients with various chemotherapeutic drugs [22] and radiation [23],[24] has shown a predisposition to a second primary malignancy. The outcome of management of patients with dual malignancies should be determined independently based upon the stage of each cancer. [25] The choice of treatment should depend upon the tumor location, involved curative surgical resection of each cancer, radiotherapy and chemotherapy. If surgery is required for both the tumors, it can be done so in a majority of cases with low rate of morbidity and mortality. [26]

In our series we have observed that patients who presented early, underwent surgery and adjuvant therapy had a good recovery and are doing well. Patients who presented late with an aggressive biological behavior of the disease faired poorly. Irat Mehdi et al., [27] has shown that second primary tumors are usually more aggressive, treatment resistant and metastasize early, and require a more aggressive treatment strategy and usually have a poor outcome. On the other hand Agarwal [28] has noted that synchronous malignancies can be treated successfully. The outcome of the patients that we managed successfully is similar to the observation of Agarwal.

The treatment strategy for managing these complex cases of dual malignancies should be aimed at treatment of the more advanced malignancy first or both the malignancies simultaneously in amenable patients. In our series three of our patients at presentation were amenable to surgery for the primary tumors at the same time and this was what was performed.

We conclude that all hope is not lost when a patient presents with dual malignancy. The prognosis of these patients does not depend upon the occurrence of two primary tumors but on the aggressive biology of the tumor and the stage of presentation of each individual tumor. Successful management of these tumors is possible given the stage of presentation of the individual tumors given the armamentarium of therapeutic options that we have nowadays.

  References Top

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Moertel CG. Multiple primary malignant neoplasms: Historical perspectives. Cancer 1977;40(Suppl 4):1786-92.  Back to cited text no. 2
Marrano D, Viti G, Grigioni W, Marra A. Synchronous and metachronous cancer of the stomach. Eur J Surg Oncol 1987;13:493-8.  Back to cited text no. 3
Kim JH, Rha SY, Kim C, Kim GM, Yoon SH, Kim KH, et al. Clinicopathologic features of metachronous or synchronous gastric cancer patients with three or more primary sites. Cancer Res Treat 2010;42:217-24.  Back to cited text no. 4
Campbell LV Jr, Watne AL. Multiple primary malignant neoplasms. Arch Surg 1969;99:401-5.  Back to cited text no. 5
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Ecimovic P, Pompe-Kirn V. Second primary cancers in laryngeal cancer patients in Slovenia, 1961-1996. Eur J Cancer 2002;38:1254-60.  Back to cited text no. 12
Warren S, Gates O. Multiple primary, malignant tumors: A survey of the literature and statistical study. Am J Cancer 1932;16:1358-414.  Back to cited text no. 13
Koubková L, Hrstka R, Dobes P, Vojtesek B, Vyzula R. Second primary cancers - causes, incidence and the future. Klin Onkol 2014;27:11-7.  Back to cited text no. 14
Pedersen-Bjergaard J, Larsen, S. Incidence of acute nonlymphocytic leukemia, preleukemia, and acute myeloproliferative syndrome up to 10 years after treatment of Hodgkin's disease. N Engl J Med 1982;307:965-71.  Back to cited text no. 15
Hemminki K, Boffetta P. Multiple primary cancers as clues to environmental and heritable causes of cancer and mechanisms of carcinogenesis. IARC Sci Publ 2004:289-97.  Back to cited text no. 16
Horii A, Han HJ, Shimda M, Yanagisawa A, Kato Y, Ohta H, et al. Frequent replication errors at microsatellite loci in tumors of patients with multiple primary cancers. Cancer Res 1994;54:3373-5.  Back to cited text no. 17
Strachan T, Read AP. Human Molecular Genetics. 2 nd edition. New York: Wiley-Liss; 1999. Chapter 18, Cancer genetics. Available from:  Back to cited text no. 18
Kimura K, Shinmura K, Hasegawa T, Beppu Y, Yokoyama R, Yokita J. Germline p53 mutations in a patient with multiple primary cancers. Jpn J Clin Oncol 2001;31:349-51.  Back to cited text no. 19
Landolsi S, Gharbi O, Zrig M, Gribaa M, Njim L, Zakhama A, et al. Li Fraumeni syndrome: A case with multiple primary cancers and presenting a germline p53 mutation. Ann Biol Clin (Paris) 2010;68:346-50.  Back to cited text no. 20
Miyaki M, Iijima T, Ohue M, Kita Y, Hishima T, Kuroki T, et al. A novel case with germline p53 gene mutation having concurrent multiple primary colon tumours. Gut 2003;52:304-6.  Back to cited text no. 21
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  [Figure 1], [Figure 2]

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