35T. Ito et al.: Gastroenterological screening in dialysis patientsJ Gastroenterol 1999; 34:35–40

Abstract: To screen for gastroenterological malignan-cies in dialysis patients, we used the fecal occult bloodtest, examined the upper and lower gastrointestinaltract, and used abdominal ultrasonography in 178 pa-tients starting dialysis (171 on hemodialysis and 7 oncontinuous ambulatory peritoneal dialysis (CAPD))and 34 patients on maintenance dialysis (27 onhemodialysis and 7 on CAPD). Screening disclosed tencancers (one esophageal cancer, three gastric cancers,four colorectal cancers, and two hepatocellular carcino-mas) in 9 of the patients starting dialysis. Six cancers(one esophageal, three gastric, one colorectal, and onerenal) were detected in 5 of the patients on maintenancedialysis. Since an increased incidence of malignancy hasbeen reported in dialysis patients, gastroenterologicalscreening appears to be worthwhile.

Key words: chronic renal failure, gastroenterologicalscreening, malignancy

Introduction

Since Matas et al.1 reported in 1975 that uremic patientsseem to develop malignancies more often than the gen-eral population, a number of authors have presentedsimilar findings.2–8

Since 1989, we have periodically performed imagingand fecal occult blood studies in patients with chronicrenal failure to screen for gastroenterological malignan-

cies at the time dialysis is initiated and during mainte-nance dialysis. The present study was done to assess thevalue of such screening examinations.

Subjects and methods

The subjects consisted of 178 patients starting dialysis(hemodialysis in 171 and continuous ambulatory perito-neal dialysis (CAPD) in 7) and 34 patients on mainte-nance dialysis (hemodialysis in 27 and CAPD in 7)who were treated at the Artificial Kidney Center ofHiroshima Prefectural Hiroshima Hospital during the 6years from January 1989 to December 1994. The meanage of the patients starting dialysis was 60.8 6 13.3years, while that of the maintenance dialysis patientswas 57.0 6 13.1 years, with the in mean duration ofdialysis being 35.1 6 17.7 months. The primary dis-eases in the patients starting dialysis were chronicglomerulonephritis in 81, diabetic nephropathy in 68,nephrosclerosis in 15, polycystic kidney in 6, rheuma-toid arthritis in 3, and others in 5. In the maintenancedialysis patients, the primary disease was chronicglomerulonephritis in 20, diabetic nephropathy in 11,nephrosclerosis in 2, and polycystic kidney in 1. Thepatients in the new and maintenance dialysis groupsoverlapped substantially (34 patients). Patients in themaintenance dialysis group were defined as those whohad been receiving dialysis at Hiroshima PrefecturalHiroshima Hospital since the introduction of thescreening system in 1989.

The patients starting dialysis underwent fecal occultblood testing (human hemoglobin immuno-detectionmethod; Dainascreen Hemo [Dainabot, Tokyo, Japan])on two occasions, examination of the upper gastro-intestinal tract (gastroscopy or gastric radiography, asdecided by the patients themselves) and the lower gas-trointestinal tract (colonoscopy or barium enema, asdecided by the patients themselves), and abdominal

Screening for gastroenterological malignancies in new andmaintenance dialysis patients

Takafumi Ito1,3, Issei Tanaka1, Takayuki Kadoya1, Mari Kimura1, Takafumi Ooshiro1, Kouichi Ooishi1,Junko Tanaka2, and Noriaki Yorioka3

1 Hiroshima Prefectural Hiroshima Hospital, Artificial Kidney Center, Hiroshima, Japan2 Department of Hygiene, Hiroshima University School of Medicine, Hiroshima, Japan3 Second Department of Internal Medicine, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan

Reprint requests to: T. ItoPresent address: Second Department of Internal Medicine,Hiroshima University School of Medicine(Received Nov. 17, 1997; accepted July 6, 1998)

36 T. Ito et al.: Gastroenterological screening in dialysis patients

ultrasonography. Maintenance dialysis patients under-went fecal occult blood testing at 3-month intervals.Patients who had positive test results, as well asthose who had gastroenterological symptoms, under-went endoscopic or radiographic studies. Abdominalultrasonography was performed at 6-month intervals.

The prevalence of each malignancy was calculated atthe time dialysis was initiated, with the 1990 nationwidesurvey data of the Japanese Society of GastrointestinalScreening used as the control. The incidence of eachmalignancy was also determined during maintenancedialysis, using the “Cancer Mortality and Morbidity Sta-tistics” of the Japanese Cancer Association as the con-trol. Statistical analysis of data was performed with theø2 test for goodness of fit.

Results

New dialysis patients

Upper gastrointestinal tract (Table 1). When dialysis wasinitiated, examination of the upper gastrointestinal tractwas performed in 162 of the 178 patients, and 152abnormalities were found. Esophagitis, gastritis, andduodenitis were the most common lesions (87 casestogether). There were 7 ulcers and 25 polyps, one ofwhich was diagnosed as group III on biopsy. Ten tumorswere also detected, including one esophageal cancer,three gastric cancers, and six submucosal tumors of thestomach. The prevalence of gastric cancer in the groupwas particularly high, at 3/162 (1.85%), and statisticalanalysis showed that it was significantly more prevalentin the dialysis patients than in the control population(0.26%) (P , 0.01).

A positive fecal occult blood test was associated with48 of the 152 abnormal findings. Positive tests wereassociated with five of seven ulcers and four of tentumors.Lower gastrointestinal tract (Table 2). Examination ofthe lower gastrointestinal tract was carried out in 84patients, and 64 abnormalities were detected. Therewere 51 colonic polyps, one of which was diagnosed as acarcinoma in adenoma after polypectomy. Larger tu-mors were also detected, including three colorectal can-cers and one small-bowel adenoma. The prevalence ofcolorectal cancer was very high, at 4/84 (4.76%) andstatistical analysis revealed that it also was significantlymore prevalent in the dialysis patients than in the con-trol population (0.29%) (P , 0.01).

A positive fecal occult blood test was associated with37 of the 64 abnormal findings. It was positive in 30 ofthe 51 colonic polyps and 4 of the 5 tumors (includingthe carcinoma in adenoma).Abdominal ultrasonography (Table 3). Abdominalultrasonography was done in 131 patients, and 76 ab-normal findings were observed, including 9 cases of livercirrhosis, 2 cases of hepatocellular carcinoma, 18 casesof cholelithiasis, 6 cases of polycystic kidney, and 9 casesof acquired cystic kidney disease.Patients with gastroenterological cancer (Table 4). Tencancers were detected in 9 of the 178 patients startingdialysis, including one esophageal cancer, three gastriccancers, four colorectal cancers, and two hepatocellularcarcinomas. Five of the 9 patients underwent surgeryand 4 have survived. One of the four colorectal cancerswas a carcinoma in adenoma, which was completelyremoved by endoscopic polypectomy. There has beenno recurrence of this tumor. The two patients with

Table 1. Results of upper gastrointestinal screening at the start of dialysis

No. of Positive Negativeabnormal occult occult blood

Findings findings blood test test

Normal 43 13 30Esophagitis/gastritis/duodenitis 87 24 63Ulcers 7 5 2Polyps 25 11 14

No biopsy 6 2 4Group I 5 2 2Group II 13 6 7Group III 1 1 0

Tumors 10 4 6Esophageal cancer 1 0 1Gastric cancer 3 1 2Gastric submucosal tumor 6 3 3

Other (including esophageal varix) 23 4 19

Total 152 48 104

Of 178 patients, 162 (91.0%) were examined

37T. Ito et al.: Gastroenterological screening in dialysis patients

Table 2. Results of lower gastrointerstinal screening at the start of dialysis

No. of Positive occult Negative occultFindings abnormal findings blood test blood test

Normal 33 11 22Colonic polyps 51 30 21

No biopsy 13 4 9Group I 6 5 1Group II 24 (3) 15 9Group III 7 (6) 6 1Group V 1 (1: CIA) 0 1

Tumors 4 4 0Colorectal cancer 3a 3 0Small-bowel adenoma 1a 1 0

Other 9 3 6

Total 64 37 27

Of 178 patients, 84 (47.2%) were examinedThe number of polypectomies is shown in parentheses. CIA, Carcinoma in adenomaa Number of patients who underwent surgery

hepatocellular carcinoma were treated by intra-arterialchemotherapy, but 1 of them died.

Maintenance dialysis patients

Results of screening examinations (Table 5). Examina-tion of the upper gastrointestinal tract disclosed 24 casesof esophagitis, gastritis, and duodenitis. There was alsoone esophageal cancer and two gastric cancers. Thegroup III polyp observed at the initiation of dialysis hadprogressed to group V on subsequent examination, sototal gastrectomy was performed. Examination of thelower gastrointestinal tract revealed eight colonic pol-yps; endoscopic polypectomy was performed for two of

Table 3. Findings of abdominal ultrasonography (US) at thestart of dialysis

Findings No. of abnormal findings

Normal 70Hepatic cysts 3Cirrhosis 9Hepatocellular carcinoma 2Cholecystitis 2Cholelithiasis 18Gallbladder polyps 2Polycystic kidney 6Acquired cystic kidney disease 9Nephrolithiasis 3Ascites 13Splenomegaly 5Other 4

Total 76

Of the 178 patients, 131 (73.6%) were examined by abdominal US

them and one of these two was found to be carcinomain adenoma. Abdominal ultrasonography disclosedcholelithiasis in four patients; one of them was treatedby cholecystectomy simultaneously with surgery forgastric cancer, and the other three have remained underobservation. Renal cancer was detected in one patientand nephrectomy was performed.Detection of cancer during maintenance dialysis (Table6). Six cancers were detected in 5 of the 34 patients onmaintenance dialysis, including one esophageal, threegastric, one colorectal, and one renal. The incidence ofgastric cancer and colorectal cancer was particularlyhigh, at 3/207.3 and 1/124.3 person-years, respectively,and both cancers were significantly more common in thedialysis patients than in the control population (gastriccancer 105.2/100 000; colorectal cancer, 45.2/100000)(both P , 0.01).

All of the bowel cancers were associated with a posi-tive fecal occult blood test.

Patient 1 was found to have both esophageal andgastric cancers when dialysis was initiated (Table 4), butdid not undergo surgery due to concomitant severecirrhosis. The lesions have since recurred repeatedly,despite laser irradiation and radiotherapy havingbeen performed. Patient 2 underwent endoscopicpolypectomy and the lesion was found to be a carci-noma in adenoma. Patient 3 was on CAPD, but re-ceived hemodialysis for 2 weeks after gastrectomy andsubsequently resumed CAPD. This patient has beenmaintained on CAPD without any worsening of perito-neal function. Patient 4 had a group III polyp, as re-ported above. Patient 5 underwent nephrectomy for asolitary renal cancer that was not associated with ac-quired cystic disease.

38 T. Ito et al.: Gastroenterological screening in dialysis patients

Table 4. Clinical profile of patients with cancer detected at the start of dialysis

Age Method ofSex (years) dialysis Tumor Positive tests Treatment Outcome

Patient 1 Male 59 Hemodialysis Gastric cancer Fecal occult blood test Gastric cancer: Alive withEsophageal cancer Gastroscopy Laser irradiation esophageal

Esophageal cancer: cancerradiotherapy

Patient 2 Male 62 Hemodialysis Gastric cancer Fecal occult blood test Gastrectomy AliveGastroscopy

Patient 3 Male 66 Hemodialysis Rectal cancer Fecal occult blood test Colorectomy AliveColonoscopy

Patient 4 Male 68 Hemodialysis Colon cancer Fecal occult blood test Colorectomy DiedColonoscopy

Patient 5 Female 78 Hemodialysis Colon cancer Fecal occult blood test Colorectomy AliveColonoscopy

Patient 6 Male 68 Hemodialysis Hepatocellular carcinoma Abdominal US Transarterial infusion AlivePatient 7 Male 60 Hemodialysis Colon polyp Colonoscopy Polypectomy Alive

Carcinoma in adenomaPatient 8 Male 60 Hemodialysis Hepatocellular carcinoma Abdominal US Transarterial infusion DiedPatient 9 Male 76 Hemodialysis Gastric cancer Gastroscopy Gastrectomy Alive

US, Ultrasound

Table 5. Results of gastroenterological screening during maintenance dialysis

Upper GI tract Lower GI tract Abdominal ultrasonography

Findings No. Course Findings No. Course Findings No. Course

Normal 5 Under observation Normal 4 Under observation Normal 14 Under observation

Esophagitis/gastritis 24 Under Diverticular 7 Under observation Hepatic cysts 1 Under observation/duodenitis observation disease

Ulcers 1 Under Polyps 8 Polypectomy [n 5 2 Cirrhosis/ 3 Under observationobservation (1 carcinoma in adenoma)] Splenomegaly

Polyps 6 Under Cholelithiasis 4 Cholecystectomyobservation during surgery for

gastric cancer (n 5 1)

Polyp, group III 1 Surgery

Esophageal cancer 1 Radiotherapy

Gastric cancer 2 Surgery Gallbladder polyps 3 Under observation(n 51)Laser irradiation Renal cysts 9 Under observation(n 5 1)

Polycystic kidney 1 Under observation

Gastric submucosal 1 Under Renal cancer 1 Surgerytumors observation

Other 4 Under Chronic 1 Under observationobservation pancreatitis

Total 40 Total 15 Total 23

GI, GastrointestinalThirty-four patients were screened

Discussion

Malignancy is the fourth leading cause of death amongchronic dialysis patients in Japan,9 and lives couldbe saved if cancer was detected at an early stage. Itis unforgivable for physicians to overlook cancerin hemodialysis patients who attend hospital two tothree times a week. Since 1989, we have performedgastroenterological imaging studies and fecal occultblood testing both at the initiation of dialysis and during

maintenance dialysis to screen for malignancies of thedigestive tract. We found malignant tumors in 9 of 178patients starting dialysis and in 5 of 34 patients on main-tenance dialysis. The incidence of malignancy in pa-tients with chronic renal failure was reported to be 7%by Matas et al.,1 12.8% by Miach et al.,2 and 3.3% bySutherland et al.3 The present study revealed a higherprevalence and higher incidence, which may be relatedto the fact that our maintenance dialysis patients weremainly those whose condition was not good enough

39T. Ito et al.: Gastroenterological screening in dialysis patients

for transfer to satellite institutions. Whereas a largescreened population was the source of the control data,elderly patients predominated at our institution. Thetotal number of subjects was only 178, so the detectionof even one cancer could have a great effect on ourresults, and this may also have been responsible for thehigh rates of some malignancies. Gastric cancer showeda particularly high incidence when compared with therate of approximately 0.1% in the Japanese population.Inamoto et al.10 reported that, although the mostcommon site of malignancy in Japan was the stomach,dialysis patients more commonly developed renal can-cer compared with the general population, while thestomach and esophagus actually showed lower rates.Iseki et al.11 found that cancer of the uterus, colon, andbreast had a relatively high prevalence in dialysis pa-tients. Since blood transfusion was previously per-formed for the treatment of anemia in dialysis patients,hepatitis B and C infection was common. Accordingly,ultrasound may be an effective screening procedure forhepatocellular carcinoma in these patients.

With regard to the development of malignancy, noincrease has been reported in patients with renal failurenot requiring dialysis,12 while the incidence increasesafter dialysis is instituted.10 In the present study, tencancers were detected in nine patients at the initiationof dialysis, and six cancers were detected in five patientsduring maintenance dialysis, supporting the above-mentioned reports that the incidence of malignancyincreases during dialysis. However, the prevalence ofcancer was also high at the initiation of dialysis, unlikefindings in the reports mentioned above, suggesting thatpatients with end-stage renal failure already show anincreased cancer incidence before dialysis is instituted.Although the reasons for the increased incidence of

malignancy in dialysis patients have yet to be fully elu-cidated, dialysis-related carcinogens,4 and the decreasedcellular immunity that accompanies chronic renalfailure have been suggested as possible causes.13,14

Renal cancer may be induced by chemical substances inthe cysts created by acquired cystic kidney disease;colorectal cancer may be caused by constipation relatedto restriction of fluid intake and dietary fiber; and hepa-tocellular carcinoma may develop as a result of chronichepatitis B or C caused by blood transfusions to treatanemia. Most patients undergo dialysis at clinics, sothe chance of review by a physician is increased, andthis may also contribute to the increased detection ofmalignancy.

Among the patients with carcinoma of the largebowel and stomach, the lesions were discovered rela-tively early and radical surgery was performed in all butone patient, demonstrating the value of screening forgastroenterological malignancy. We have previouslyfound that radical surgery for gastroenterologicalcarcinoma can be performed as safely in dialysispatients as in non-dialysis patients.15 However, dialysispatients show a higher incidence of postoperative infec-tion due to reduced immunity as well as delayed woundhealing, and they have various metabolic abnormalities.Thus, they are a high-risk group, and the outcome oftreatment is less predictable, although the prognosishas been improved. We used fecal occult bloodtesting as one of the screening procedures. Despitethe low positive rate in patients with carcinoma of theupper gastrointestinal tract, positive test rates werehigher in those with large-bowel cancer. Marple andMcDougall16 reported similar findings, so this test ap-pears to be a useful screening procedure for colorectallesions.

Table 6. Clinical profile of patients with cancer detected during maintenance dialysis

Time to Method ofSex Age (years) detection dialysis Tumor Positive tests Treatment Outcome

Patient 1 Male 63 17 Months Hemodialysis Gastric cancer Fecal occult blood test Alive with34 Months Esophageal cancer Gastroscopy Gastric cancer: esophageal

Laser irradiation cancerEsophageal cancer:radiotherapy

Patient 2 Male 54 53 Months Hemodialysis Colonic polyps Fecal occult blood test Endoscopic Alivepolypectomy

Carcinoma in adenoma Colonoscopy

Patient 3 Male 49 35 Months CAPD Gastric cancer Fecal occult blood test Gastrectomy Alive(stage Ia)

Gastroscopy (Still on CAPD)

Patient 4 Female 63 29 Months Hemodialysis Group III Fecal occult blood test Gastrectomy Alive→gastric cancer Gastroscopy (stage Ia)

Patient 5 Female 66 92 Months Hemodialysis Renal cancer Abdominal US Nephrectomy Alive

CAPD, Continuous ambulatory peritoneal dialysis

40 T. Ito et al.: Gastroenterological screening in dialysis patients

Inflammation of the esophagus, stomach, and duode-num, as well as gastric and duodenal ulcers, were com-mon both at the start of dialysis and during maintenancedialysis. In the 1970s, this was suggested to be caused byincreased gastric acid secretion,17 but a decrease ingastric mucosal defense factors is now considered to bethe main cause. Recent reports have also suggested theassociation of Helicobacter pylori infection with uppergastrointestinal lesions in dialysis patients.18,19 These dis-eases frequently produce gastrointestinal bleeding andoften require emergency surgery, causing 5%–9% ofall deaths among dialysis patients. In our experience,emergency surgery for gastrointestinal hemorrhage isassociated with a poor outcome. Thus, although thesediseases are benign, there is a considerable impacton the prognosis of dialysis patients, and emergencysurgery should be avoided by appropriate conservativetreatment.

In conclusion, screening of dialysis patients forgastroenterological malignancies appears to be worth-while. Although screening is not cheap, our high cancerdetection rates suggest that it is particularly importantfor all patients to undergo these examinations beforestarting dialysis and to receive periodic assessmentduring maintenance dialysis.

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