A 51-Year-Old Man with Gastric Cancer and Lung Nodules

T h e new england journal o f medicine

case records of the massachusetts general hospital

Founded by Richard C. Cabot Nancy Lee Harris, m.d., Editor Eric S. Rosenberg, m.d., Associate Editor Jo-Anne O. Shepard, m.d., Associate Editor Alice M. Cort, m.d., Associate Editor Sally H. Ebeling, Assistant Editor Christine C. Peters, Assistant Editor

Case 29-2007: A 51-Year-Old Man with Gastric Cancer and Lung Nodules

Edward T. Ryan, M.D., Suzanne L. Aquino, M.D., and Richard L. Kradin, M.D.

Presentation of Case

Dr. Allison L. McDonough (Internal Medicine): A 51-year-old man with a history of From the Division of Infectious Disease gastric cancer was admitted to the hospital because of a new pulmonary lesion. (E.T.R.) and the Departments of Radiology (S.L.A.) and Pathology (R.L.K.), Massa- The patient had been in good health until approximately 5 years before admis- chusetts General Hospital; and the De- sion, when he had a decreased appetite and epigastric discomfort; evaluation at partments of Medicine (E.T.R.), Radiology another facility revealed a hiatal hernia, gastroesophageal reflux, and a duodenal (S.L.A.), and Pathology (R.L.K.), Harvard Medical School. ulcer. Testing for Helicobacter pylori was positive. Omeprazole and metoclopramide were administered, and the hiatal hernia was surgically repaired. Pain, persistent N Engl J Med 2007;357:1239-46. gastroesophageal reflux, and weight loss developed approximately 2.5 years before Copyright © 2007 Massachusetts Medical Society. admission. A primary care physician at this hospital prescribed combination therapy (lansoprazole, amoxicillin, and clarithromycin) for 2 weeks to treat the H. pylori infection; this therapy was repeated 3 months later because of noncompliance, but the symptoms persisted. At that time, the hematocrit was 38.8%, and the remainder of the complete blood count was normal. The phosphorus level was 1.3 mg per deciliter (0.4 mmol per liter; reference range, 2.6 to 4.5 mg per deciliter [0.8 to 1.5 mmol per liter]), the lipase level was 77 U per liter (reference range, 13 to 60), and the amylase level was 164 U per liter (reference range, 3 to 100). Electrolyte levels and the results of renal- and liver-function tests were normal. Ultrasonography of the abdomen was normal. Abdominal pain recurred intermittently, and 2 years before admission, upper gastrointestinal endoscopy revealed distal esophagitis; a nonbleeding linear ulceration, 10 mm in the greatest dimension, in the gastric antrum; marked edema in the prepyloric antrum; a nonbleeding, cratered ulcer, 12 mm in diameter, in the pyloric channel; and partial gastric-outlet obstruction. Pathological examination of biopsy specimens from the pylorus revealed poorly differentiated adenocarcinoma with signet-ring cells. Thiazine staining of biopsy specimens was negative for H. pylori. Computed tomography (CT) of the abdomen showed thickening of the wall of the antrum, without evidence of local invasion or intraabdominal metastases. A subtotal gastrectomy was performed. Pathological examination revealed a poorly differentiated signet-ring–cell adenocarcinoma of the pylorus, 4.0 cm in the greatest dimension, leading to a diagnosis of stage II cancer (T2,N1,MX), with 2 of 12 lymph nodes positive for tumor and

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perineural invasion, with no vascular or lym- small parenchymal cysts in the lungs, with no phatic invasion. The tumor had invaded the sub- evidence of metastatic disease in the abdomen serosa but did not involve the serosal surface. The or pelvis. The patient had pain in the abdominal proximal, distal, and radial margins were free wall at the site of the surgical scar, early satiety, of tumor. Reactive gastropathy with mild nausea, fatigue, and weight loss. He appeared chronic inflammation and intestinal metaplasia thin and chronically ill, with a weight of 56.7 kg. was present. Thiazine staining for H. pylori was There was clubbing of all digits, and a small, negative. The hematocrit was 37.7%, the white- tender, firm nodule consistent with a keloid was cell count was 12,000 per cubic millimeter, with palpated in the surgical scar. The hematocrit was 12% eosinophils (normal range, 0 to 8%), and 40.1%, and the white-cell count 7700 per cubic the remainder of the complete blood count was millimeter, with 9% eosinophils. The remainder normal. The phosphorus level was 2.2 mg per of the complete blood count was normal. Mea- deciliter (0.7 mmol per liter), and the calcium surements of serum electrolytes and liver-func- level was 8.8 mg per deciliter (2.2 mmol per li- tion tests were normal. The urea nitrogen level ter). The results of renal- and liver-function tests was 21 mg per deciliter (7.5 mmol per liter), the were normal. The patient was referred for an on- creatinine level 1.0 mg per deciliter (88.4 μmol cology evaluation but did not keep the appoint- per liter), and the lipase level 163 U per liter. ments. Upper gastrointestinal endoscopy revealed mild Eleven months before admission, the patient reactive gastropathy and a nodule, 1 cm in diam- came to the emergency department of this hos- eter, in the gastric body; biopsy specimens of the pital because of a 3-month history of back and nodule and of gastric and small-intestine mu- chest pain, as well as bilateral sharp, pleuritic, cosa at the anastomosis site showed both acute subscapular pain that had occurred occasionally. and chronic inflammation. He had had early satiety since his abdominal sur- Two weeks before admission, a CT scan of the gery. A chest radiograph showed a nodule, 4 mm abdomen and pelvis was unchanged, but CT of in diameter, with the density of metal that was the chest showed a new nodule, 4.5 mm in diam- overlying the fifth posterior rib; the nodule was eter, in the lower lobe of the left lung, with a rim thought to represent a foreign body outside the of ground-glass opacification. The small ground- chest cavity. The radiograph was otherwise nor- glass nodules and cysts were unchanged as com- mal. The hematocrit was 40.2%. The remainder pared with those on the previous scans. He was of the complete blood count and measurements admitted to this hospital. of electrolytes and renal function were normal. The patient did not have cough, hemoptysis, One month later, the patient was seen by pul- bone pain, or headaches, and his weight had been monary and gastroenterology specialists. He re- stable for the previous 4 months. His medications ported that his weight had increased after his included metoclopramide, omeprazole, and cyclo- partial gastrectomy but that he had lost weight benzaprine; he had no allergies. He had been in recent months. The subscapular pain had re- born in Brazil and had immigrated to the United solved spontaneously, and he had no respiratory States more than 20 years earlier. He visited symptoms, fever, or chills. Physical examination Brazil approximately annually, and 7 years earlier, showed that he was a thin, anxious man with he had lived in Japan for 1 year. He was married to mild temporal wasting. The weight was 58.1 kg, a woman of Japanese–Brazilian ancestry and had and the oxygen saturation was 97% while the lived with his wife and children until 4 months patient was breathing ambient air. The abdominal before admission, when his family returned to scar was well healed, and there was moderate Brazil after he left his job in a factory because of clubbing of the fingers; the remainder of the poor health. He ate cooked, but not raw, shell- examination was normal. CT of the chest revealed fish. His father had died at 39 years of age from multiple, small centrilobular nodules and small gastric cancer, and his mother had died at 65 cysts, each less than 3 mm in diameter. The years of age from bronchitis. His children and patient was advised to have a follow-up CT scan siblings were healthy. He had smoked cigarettes 3 months later. for 25 years but had stopped 3 months before A follow-up CT scan obtained 5.5 months later admission. (4.5 months before admission) revealed persistent The vital signs were normal, and the physical centrilobular ground-glass nodules and scattered, examination was unchanged. An electrocardio-

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For instance, normal. certain polymorphisms in genes coding for pro- A diagnostic procedure was performed. inflammatory cytokines have been associated with gastric cancer, suggesting that differences First Differential Diagnosis in host inflammatory responses to H. pylori infection may affect the development of gastric carci- Dr. Edward T. Ryan: I was involved in the care of noma.6 This patient has a family history of gas- this patient and am aware of the diagnosis. I be- tric cancer and infection with H. pylori; both are lieve that this 51-year-old man originally from risk factors for distal gastric adenocarcinoma. Brazil, with gastric cancer and a new pulmonary Persons of Japanese–Brazilian ancestry have a nodule, has sequelae of two common infectious high risk of gastric cancer, which remains relative diseases. ly high even after emigration; however, although Is this patient’s gastric cancer a sequela of an the patient has lived in Japan, he is not of Japa- infection? The World Heath Organization current nese descent.7-9 ly estimates that approximately one fifth of all Although the majority of H. pylori infections cancer cases worldwide are due to chronic infec- are asymptomatic, this patient had multiple com- tions, including cases of liver cancer associated plications. H. pylori strains that are positive for with hepatitis B, cervical cancer associated with CagA, a toxin injected by the bacteria into eukary- the human papillomavirus, lymphoma associated otic cells, are most likely to cause illness in hu- with the human immunodeficiency virus and Ka mans, including chronic gastritis, peptic ulcer posi’s sarcoma, bladder cancer associated with disease, and gastric adenocarcinoma, all of which schistosomiasis, cholangiocarcinoma associated this patient had.10-12 Chronic gastritis caused by with liver-fluke infection, and gastric cancer as- infection with H. pylori is associated with intesti- sociated with H. pylori infection.1 Gastric adeno- nal metaplasia and loss of production of gastric carcinoma has historically been the most common acid, and the strains of H. pylori that cause gastri- nonskin cancer and the most common cause of tis and gastric cancer have been associated with cancer-related deaths in humans, and a number a protective effect against gastroesophageal reflux of prospective and retrospective studies have clear disease, Barrett’s esophagus, and adenocarcino- ly linked H. pylori colonization of the stomach to ma of the distal esophagus.13,14 The incidence both distal gastric adenocarcinoma and gastric of gastric cancer has decreased in resource-rich B-cell lymphoma.2‑5 areas in recent decades, predominantly because of a decrease in the incidence of adenocarcino- H. pylori Infection and Gastric Cancer mas of the distal stomach, and concomitantly, Five years before admission, the patient had re- there has been an increase in the incidence of ceived a diagnosis of H. pylori infection, based on adenocarcinomas of the proximal stomach and symptoms of gastroesophageal reflux and peptic distal esophagus, cancers associated with gastro- ulcer disease and evidence of H. pylori on exami- esophageal reflux disease.15 Therefore, paradoxi- nation of gastric tissue. H. pylori is a motile gram- cally, an adverse effect of H. pylori infection may negative bacillus that infects more than half the be replaced by an adverse effect of its eradication. human population. Infection usually occurs in Not surprisingly, our patient’s symptoms of gas- childhood and is associated with crowding, poor troesophageal reflux persisted after the H. pylori sanitation, and residence in resource-poor areas infection was treated. of the world, suggesting oral–oral or fecal–oral At the time of the diagnosis of gastric adeno- transmission. This patient was raised in Brazil, carcinoma, no organisms were seen in the patho- where both H. pylori infection and gastric cancer logical specimens. This finding is not infrequent. are relatively common. Persons with H. pylori in- In studies in Brazil, 15 to 45% of patients with fection have a risk of gastric cancer that is three gastric carcinoma had no evidence of active H. py to six times that of persons without such infec- lori infection on microscopical examination at the tion, as well as an attributable risk of 50 to 80% time of treatment of their gastric cancer.16,17

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Pulmonary Nodules In summary, this patient’s gastric carcinoma is in A all likelihood a complication of an infectious disease ― namely, infection with H. pylori. One year after his gastrectomy, he presented with symptoms of pleuritic chest pain and abnormalities on imaging studies of the chest. May we review the imaging studies? Dr. Suzanne L. Aquino: The chest radiograph obtained 11 months before admission was normal. CT of the thorax 10 months and 4.5 months before admission did not show evidence of metastatic cancer. High-resolution CT with the use of B 1.25-mm slices, however, showed bilateral centrilobular nodules (Fig. 1A) and cysts; some cysts were clustered and showed perceptible walls (Fig. 1B). The differential diagnosis of these lesions includes centrilobular emphysema with respiratory bronchiolitis caused by smoking, Langerhans’-cell histiocytosis, and less likely, a disseminated infectious process. The lesions are not typical of a neo- plasm, sarcoidosis, Wegener’s granulomatosis, tu- berculosis, or fungal infection. The CT scan obtained 2 weeks before admission showed a new nodule in the left lower lobe (Fig. 1C), which was solid in the center with sur- C rounding ground-glass opacification — suspi- cious for a metastatic lesion with surrounding hemorrhage or mucin. The clustered centrilobular cysts and ground-glass nodules were unchanged. Dr. Ryan: This patient had two types of pulmonary lesions, which were probably not related. Pulmonary nodules and cysts can have many causes, including cancer, infections, and nonin- fectious inflammatory conditions. Sarcoidosis and Wegener’s granulomatosis are not likely, given the findings on imaging. Langerhans’-cell histio- Figure 1. CT of the Thorax. cytosis occurs in smokers and could explain the A high-resolution CT scan with lung windows performed small nodules. Infection with Mycobacterium tuber 4.5 months before admission shows scattered centrilob- ularICM ground-glassAUTHOR nodules Ryan (Panel A, arrows)RET andAKE centrilob1st culosis or other mycobacteria, as well as invasive 2nd ularREG cysts, F FIGUREsome of 1a-cwhich of 2are clustered (Panel B, arrows). fungal infections such as cryptococcosis, histo- CASE 3rd A CT scan TITLEof the thorax 2 weeks before admissionRevised plasmosis, coccidioidomycosis, and paracoccidi- (PanelEMail C) shows a new solidLine nodule 4-C(arrow) in the left SIZE oidomycosis, could be considered. The small size lowerEnon lobeARTIST with surrounding: mst H/T ground-glassH/T opacification. 16p6 and scattered nature of most of the lesions and FILL Combo AUTHOR, PLEASE NOTE: the absence of characteristic symptoms or signs Figure has been redrawn and type has been reset. make most infections unlikely. 3 years, and thisPlease patient check carefullytraveled. frequently to This patient initially had pleuritic, subscapular Brazil and had resided in Japan. Although these JOB: 35712 ISSUE: 9-20-07 pain, and laboratory evaluation showed a slight- factors could prompt consideration of infection ly elevated peripheral-blood eosinophil count on with lung parasites, such as in dirofilariasis and several occasions. Peripheral eosinophilia (de- paragonimiasis, given this patient’s history of fined as an eosinophil count of >400 per cubic gastric cancer and smoking, his caregivers were millimeter) had actually been present for at least concerned that the new pulmonary nodule could

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Clinical Diagnoses

Adenocarcinoma of the stomach, associated with H. pylori infection. Possible metastasis of the cancer to the lung.

First Pathological Discussion B Dr. Richard L. Kradin: Examination of the specimen from the wedge resection of the left lung (Fig. 2A) revealed two tracts of necrotizing granulomatous inflammation with eosinophilic debris at their centers. There was centriacinar emphysema of the surrounding lung and pigmented macrophages, which are typically found in the lungs of smokers. Within the debris at the center of the granu- lomas, examination at a higher magnification showed a severely degenerated helminth with tegument composed of layers of smooth muscle C and dead tegumental cells (Fig. 2B). The morphologic characteristics were consistent with those of a trematode or fluke, but given the degree of degeneration, it was impossible to accurately mea- sure the size. A second fluke was seen in an ad- jacent section. Ova with refractile cortexes (Fig. 2C) were surrounded by granulomatous inflammation and foreign-body giant cells. Paragonimus is the most common fluke to infect the lung. It is a plump, oval fluke that on average is approximately 10 mm long and 5 mm wide, with both oral and ventral suckers. The Figure 2. Lung-Biopsy Specimen (Hematoxylin and Eosin body wall is composed of a tegument that in- Stain). cludes two layers of smooth muscle and tegu- A linear tract of necrotizing granulomatous inflammation mental cells and is characteristically covered with withICM eosinophilicAUTHOR debris Ryan is shown (Panel A).RET AKEAt a higher1st magnificationREG F FIGURE (Panel 2a-c B), of 2the degenerating tegument2nd of spines, which were not seen in this case. The 3rd CASE TITLE eggs are ovoid, varying in size among species a trematode, coated with dense eosinophilicRevised material, is visibleEMail (arrow). This appearance,Line called4-C the Splendore– from 80 to 120 μm in length, and birefringent, SIZE HoeppliEnon phenomenon,ARTIST: mst is causedH/T by H/Tthe deposition of 16p6 with a double-layered cortex. The ova in this case immunoglobulinFILL and other Coplasmambo proteins at the host were highly refractile, but they did not show interface with theAUTHOR, organism. PLEASE There NOTE: was also granulo- Figure has been redrawn and type has been reset. strong birefringence under polarized light. matous inflammationPlease with check multinucleated carefully. giant cells. Schistosomiasis can also involve the lung, The refractile cortex of a degenerating ovum is visible within a granuloma, with surrounding tissue eosino- typically through translocation of ova into the JOB: 35712 ISSUE: 9-20-07 philia (Panel C). pulmonary arterial system, but aberrant migra- tion of adult schistosomes into the lung does occasionally occur. Adult schistosoma are typi- the ova of Schistosoma mansoni or S. haematobium cally longer and thinner than adult paragonimus, may exhibit prominent lateral or terminal spines, and their ova are larger. The cortical surfaces of respectively, but these were not evident in the

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case under discussion. The degree of degeneration infect humans include intravascular, hepatic, pul- of both the parasites and ova in this case made monary, and intestinal flukes (Table 1). World- it impossible to establish a specific morphologic wide, the majority of the illness and death related diagnosis with certainty. to human infection with trematodes is due to In summary, the large lung nodule is due to schistosoma species; however, the vast majority infection with a trematode, which cannot be de- of the approximately 20 million persons world- finitively identified but is most consistent with wide infected with lung flukes are infected with paragonimus. The small centrilobular nodules paragonimus species, usually Paragonimus wes seen on CT most likely represent changes caused termani. by smoking, with respiratory bronchiolitis, centriacinar emphysema, and peribronchiolar scarring. Paragonimiasis The majority of paragonimus infections in humans Second Differential Diagnosis are reported in East and Southeast Asia, including Japan, where this patient had lived. Most peo- Dr. Ryan: I first saw this patient after examination ple become infected after eating raw or under- of the lung-biopsy specimen showed evidence of cooked crabs or crayfish or the meat of infected a worm. Helminths that infect humans include paratenic hosts such as pigs or boars. Although roundworms (nematodes), flatworms (tapeworms this patient ate shellfish, he reported that he did or cestodes), and flukes (trematodes). Flukes that not eat uncooked shellfish.

Table 1. Common Trematode (Fluke) Infections in Humans.*

Usual Location Means of of Adult Passage of Route of Human Means of Fluke Flukes in Eggs from Usual Manifestations Species Animal Reservoir Infection Reproduction Humans Humans in Humans Blood flukes Schistosoma mansoni, Usually humans Exposure to fresh Male–female Blood Feces, Colonic inflammatory pol- S. haematobium, (especially for water, with direct pairing vessels urine yps, hepatosplenomeg- S. japonicum, S. mansoni); also skin penetration aly, hepatic cirrhosis, S. mekongi, nonhuman pri- by cercariae hematuria, urinary ob- S. intercalatum mates, other struction and scarring, mammals bladder cancer Lung flukes Paragonimus spp. Cats, dogs, other Ingestion of infective Hermaphroditic Lungs Sputum, Chronic cough, blood- mammals freshwater crus- feces tinged sputum, chest taceans pain, or none Liver flukes Opisthorchis viverrini, Cats, dogs, pigs, Ingestion of infective Hermaphroditic Biliary tract Feces Cholangitis, biliary obstruc- O. felineus, rats, fish-eating freshwater fish tion, cholangiocar Clonorchis sinensis mammals cinoma Fasciola hepatica, Sheep, goats, cattle, Ingestion of infective Hermaphroditic Biliary tract Feces Abdominal pain, cholangi- F. gigantica buffalo, camels, freshwater plants tis, biliary obstruction pigs, horses, other herbivores Intestinal flukes Fasciolopsis buski Pigs Ingestion of infective Hermaphroditic Intestines Feces None or abdominal pain freshwater plants or diarrhea Heterophyes hetero Mammals, birds Ingestion of infective Hermaphroditic Intestines Feces None or abdominal pain phyes, Metagoni freshwater fish or diarrhea mus yokogawai Echinostoma spp. Mammals Ingestion of infective Hermaphroditic Intestines Feces None or abdominal pain freshwater fish, or diarrhea snails, or mussels

* The intermediate host in all cases is freshwater snails.

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After the ingestion of paragonimus, metacer- mesenteric veins; a local inflammatory response cariae penetrate the intestinal wall, cross the dia- to the eggs permits passive transit of the eggs phragm, and migrate through the lungs, where into the intestinal lumen (where they are shed in they may cause pneumothorax, pleural effusions, feces) and also into the liver (where they may cause and diffuse or nodular pulmonary infiltrates.16 inflammation, fibrosis, and cirrhosis). Eggs may Eventually, cystic structures from 1 to 5 cm in passively enter the pulmonary circulation, usually diameter form; these structures often contain by means of portal shunting caused by hepatic two or three worms, are filled with thick bloody schistosomiasis, where they can lead to pulmo- fluid, and typically have bronchopulmonary fistu- nary inflammation, fibrosis, hypertension, and las. During the acute phase of the disease, ab- cor pulmonale. Rarely, pairs of adult schistosom- dominal pain, pleurisy, cough, fever, eosinophilia, al worms may migrate aberrantly into the pulmo- and urticaria may develop. Chronic pulmonary nary vasculature, and they have been identified paragonimiasis is usually relatively asymptomat- within pulmonary nodules.20 ic, but patients may have cough, with brown or The pathological evaluation shows the pres- blood-tinged sputum. ence of lung flukes and eggs that could be due to A presumptive diagnosis of pulmonary para- paragonimiasis or schistosomiasis. The sequence gonimiasis is made on the basis of characteristic of events, epidemiologic factors, and exposure findings on imaging, persistent cough, and epi- history are most consistent with pulmonary schis- demiologic and geographic risk factors. This pa- tosomiasis caused by a worm pair that entered tient had resided in Japan and had a history of the pulmonary circulation at about the time of abdominal pain, pleurisy, and mild eosinophilia, the onset of the pleurisy. To distinguish between but no cough; the radiologic findings are consis- paragonimiasis and schistosomiasis, we recom- tent with paragonimiasis, although the absence mended the analysis of stool specimens for ova of a central cavity in the lung nodule makes para- and parasites and conducted serum antibody test- gonimiasis less likely. A specific diagnosis rests ing. The treatment for both infections involves the on the identification of eggs in sputum, bron- same drug, praziquantel; it has a favorable side- chial washings, gastric aspirates, or stool speci- effect profile and is highly effective.21 mens or on the pathological identification of worms in resected tissue, as in this case. Sero- Dr. Edward T. Ryan’s Diagnosis logic assays17 and antigen-detection assays18 are also available. Infection with a lung fluke. Although the diagnosis of paragonimiasis is tempting in this case, a number of atypical fea- Second Pathological Discussion tures raise questions about this diagnosis. Where and when could this patient have acquired this Dr. Kradin: A serum sample from the patient was infection? Although paragonimiasis is endemic in sent to the Centers for Disease Control and Pre- some areas of Latin America, to my knowledge, vention. An immunoblot for the paragonimus human acquisition has not been convincingly doc antibody was negative (this assay has a 96% sen- umented in Brazil. Although this patient could sitivity in egg-proven cases of P. westermani infec- have acquired the infection in Japan, his last visit tion in Southeast Asians, with a 99% specificity). was 7 years earlier, and it is difficult to link the In contrast, S. mansoni antibodies were detected new pulmonary nodule with such a distant pos- with both an enzyme-linked immunosorbent as- sible exposure to paragonimus. There have been say and an immunoblot assay, confirming the rare case reports of paragonimiasis in the United diagnosis of S. mansoni infection. No antibodies States,19 usually after ingestion of undercooked against S. haematobium were detected. No stool crayfish. specimen was submitted for analysis. Dr. Ryan: Dr. McDonough, can you tell us about Schistosomiasis the treatment and follow-up of this patient? Could the degenerated trematodes in the lung Dr. McDonough: The patient was treated with a represent another type of fluke? Schistosomiasis 2-day course of praziquantel. Follow-up CT scans due to S. mansoni is endemic in many areas of of the chest showed no change in the diffuse Brazil. Pairs of adult worms usually reside in the ground-glass cystic lesions and no further large

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nodules. Unfortunately, 8 months after the lung is associated with an increased risk of squamous- biopsy, symptoms of pancreatic and biliary-duct cell carcinoma of the bladder. obstruction developed; laparotomy showed exten- sive metastatic adenocarcinoma within the abdo- Anatomical Diagnoses men. Treatment with chemotherapy was initiated, and 10 months later, the patient has relatively Schistosoma mansoni infection with pulmonary in- asymptomatic, stable metastatic disease. He in- volvement. tends to return to Brazil to be with his family. Respiratory bronchiolitis, peribronchiolar scar- A Physician: Both gastric cancer and infection ring, and centrilobular emphysema. with schistosoma are prevalent in Asia. Is there any Adenocarcinoma of the distal stomach, after link between gastric cancer and schistosomiasis? Helicobacter pylori infection. Dr. Ryan: There is no recognized association of Chronic gastritis with intestinal metaplasia. schistosomiasis with gastric or intestinal cancer. No potential conflict of interest relevant to this article was re- This contrasts with S. haematobium infection, which ported.

References

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