Multiple primary neoplasms in a single patient have been well documented in the literature over the past hundred years. The lesions can be limited to a single organ or involve multiple organs systems. It is relatively common for patients with colorectal carcinoma or carcinoid tumours to have more than one primary neoplasm.2

We report an unusual case of double primary synchronous neoplasms of the gastrointestinal tract, involving the stomach and sigmoid colon associated with chronic cholecystitis and cholelithiasis. The patient had no evidence of metastatic disease and underwent resection of all the lesions.

An eighty four year old female presented with abdominal pain, vomiting and constipation since two days. There was no history of fever. Her appetite was normal. There was history of feeling out of breath on climbing one flight of stairs and swelling of feet on sitting for a long time. There was no history of chest pain or palpitations.

The patient had old history of hysterectomy with bilateral oopherectomy, haemorroidectomy and anal fissurectomy. She was on antihypertensive medication for the past five years. The patient was a New Zealander by origin but was staying in India for the past fifty years.

On examination the patient was obese, had normal vital signs and mild pedal oedema. Her cardiovascular system examination revealed grade 2 ejection systolic murmur in the left parasternal region. Per abdomen examination revealed mild tenderness in all the quadrants of abdomen and percussion note was tympanitic.

A film of the abdomen showed air filled distended colon and a repeat X-ray taken four days later showed dilated loops of small bowel and ascending colon. Ultrasonography (USG) showed multiple gallstones. A computed tomography (CT) after intravenous contrast showed a mass in the sigmoid colon causing complete distal colonic obstruction with proximal loop dilatation without any evidence of distal metastasis, a round sharply demarcated soft tissue mass 3 cm in diameter apparently in the fundus of stomach, and multiple gall stones.

Subsequently the patient underwent upper gastrointestinal (GI) endoscopy, which revealed a large polypoid mass in the body of stomach along greater curvature and sigmoidoscopy revealing a large mass in mid sigmoid colon completely occluding its lumen.

Subsequently the patient underwent surgery when gastric polypectomy, cholecystectomy and sigmoid colonic growth resection were done.

Histopathological examination of post-operative specimens of sigmoid colonic growth showed moderately differentiated adenocarcinoma with transmural infiltration, gastric polyp showed features of a neoplastic lesion - possibly carcinoid / poorly differentiated carcinoma; and specimen of gallbladder showed chronic cholecystitis.

The serum level of Carcinoembryonic antigen (CEA) and 24-hours urinary level of 5-Hydroxy Indole Acetic Acid (5-HIAA) in the patient were also checked and were found to be within limits.

The patient thus had tumour growth at two different sites in the gastrointestinal tract (GIT) associated with multiple gallstones.

The patient was doing well with no evidence of recurrence six months after surgery.

Multiple primary cancers generally fall into two categories: (1) synchronous, in which the cancers occur at the same time (like in our case) or within two months and (2) metachronous, in which the cancers, follow in sequence (more than two months apart) (Fig. 1).1

Fig. 1 : Patients with multiple primary cancers.
	Fig. 2 : CT Scanogram shows gas distended stomach and small and large bowel.

The incidence of multiple primary cancers is reported to be 0.3-4.3%.3 Nearly 10% of cancer patients develop a second primary cancer within 10 years after surgical removal of the first tumour.6 Almost 5% of gastric and colorectal cancer patients develop other primary gastrointestinal cancers synchronously or metachronously.7 Hence it was proposed that detection of genetic markers to identify high-risk patients for multiple primary cancers of the gastrointestinal tract would be of clinical importance and may lead to better prognosis.7

Multiple synchronous cancers have become more common because of an increase in the number of elderly patients and improvements in diagnostic techniques. Though the mechanism involved in the development of multiple primary cancers has not been clarified, some factors such as heredity, constitution, environmental and immunological factors, carcinogenic, viruses, radiological and chemical treatments have been implicated.4

Fig. 3 : Contrast enhanced axial CT section shows a sharply marginated,              circular, well defined mass in the stomach (arrow).	Fig. 4 : Contrast enhanced axial CT section shows multiple calculi in the                      gallbladder, an incidental finding (arrows).

In individuals developing multiple primary malignancies in functionally and anatomically allied organs, environmental factors are thought to play a major role in carcinogenesis. An individual developing more than one primary tumour in anatomically and functionally unrelated organs may be considered as ‘cancer prone’.10

It has been proposed that genetic instability may play an important role in development of multiple primary cancers. In this context, testing for Microsatellite Instability (MSI) and Replication Errors (RER) in a primary cancer may be an appropriate approach in detection of patients at high risk of developing multiple primary cancers.6

Microsatellites are ubiquitous short repetitive DNA sequences, which exhibit length polymorphisms and show variation between individuals. MSI occurs when novel sized alleles are detected in microsatellite sequences derived from carcinoma DNA, which are absent in the normal constitutional DNA from the same person. The presence of MSI at least at one locus may be termed MSI Positive.8

Fig. 5 : Contrast enhanced axial CT section at the level of sacral promontory              shows a heterogeneously enhancing mass in the sigmoid colon, which              has narrowed the lumen causing large bowel obstruction (arrow).	Fig. 6 : Post-operative specimen of patient. Cut-opened gallbladder along with                multiple calculi is seen in the kidney tray. The mass in the centre was                resected from the sigmoid colon and was found to be adenocarcinoma on                histopathology. The circular mass on the extreme right was a gastric polyp.

The importance of MSI as a mechanism in human carcinogenesis first became apparent with the study of a rare dominant cancer predisposition syndrome - Hereditary Non-Polyposis Colorectal Cancer (HNPCC).9

Hori et al have reported that MSI was observed in 89% of patients with multiple primary cancers of various organs.6,7

Microsatellite instability (MSI) has been more frequently observed in multiple primary cancers than in sporadic cancers.4 The discovery of microsatellite instability (MSI) made evident that there was more than one mechanism underlying this process.9,10

It has been proposed that a case displaying MSI in at least 29% of microsatellite loci examined can be classified as Replication Error Positive (RER+) case. Carcinomas demonstrating instability in less than 29% of loci may be referred to as manifesting low frequency MSI.8

The prognosis of patients with multiple primary cancers can be determined independently by the stage of each cancer. The surgical treatment of choice for multiple primary cancers is curative resection of each cancer.4 It was followed in our case.

The possibility of multiple primary cancers should be kept in mind during the pre-operative examination. Thus the importance of screening procedures in the early detection of malignancy, before the appearance of clinical symptoms cannot be over emphasized.

As colorectal cancer patients have chances of developing metachronous cancers postoperatively, it is an effective measure to follow up with barium enema or colonoscopy for diagnosing such cancers earlier. It has been reported that surveillance colonoscopy once every three years after surgery together with a faecal occult blood test, would be an efficient and appropriate way to detect metachronous cancer.11

It is likely that in the future, by analyzing the genetic alterations in pathological specimens, we will be able to identify patients at high risk for developing multiple primary cancers.4

This case illustrates the need for a thorough search for additional neoplasms in the treatment of patients with cancer. The finding of a gastric mass in our patient was incidental on the CT scan of abdomen. Thus for detection of synchronous tumours with surety; once the primary tumour is detected, requires greater degree of awareness about this entity both on the part of treating surgeon as well as the radiologist. This may help to ensure diligent use of imaging modalities especially in a country like ours where the resources are sparse and all the required modern imaging modalities may not be available.

Postoperatively also, in cancer patients, screening procedures should be performed at regular intervals for early detection of recurrence and metachronous tumours and this holds true especially for the gastric and colorectal cancers.