Folate, alcohol and the adenoma-carcinoma sequence

A450

AGA ABSTRACTS

GASTROENTEROLOGY, Vol. 108, No. 4

GASTRIC L Y M P H O M A : CAN T R E A T M E N T A D E Q U A C Y EXPLAIN OUTCOME? H.Boot, P.van Heerde, D.de J u n g , L S o m e r $ ,

J.V.M.Burgers,

F.van

Coevorden,

B.G.Taal.

Depts.of

Gastroenterology, Pathology, Medical Onenlogy, Radiotherapy and Surgery. Netherlands Cancer Institue, Amsterdam, The Netherlands. Gastric lymphoma arises from mucesa-associated lymphoid tissue (MALT)• Prognostic factors can be related to patient characteristics, tumor-stage/mass, histology and treatment. Surgery, chemo- and radiotherapy can be used to treat gastric lymphoma (GL). Achievement of a complete remission is the basis of lung-term survival. We developed a treatment model in which we assigned a given treatment as adequate and non-adequate based on literature data, tumor stage (Ann Arbor) and histology (low- and high-grade MALT-lymphorna:lg-hg). In localized GL radiotherapy, gastric resection with adjuvant radio- or chemotherapy (CT)is considered adequate. CT is the primary modality in bulky disease and advanced GL, including anthracyclines in hg GL. We retrospectively analysed the prognostic value of our treatment model in 139 patients treated during 1978-92. Localized GL (stage I+lI~) was seen in n=104 (51-1g,53-hg), advanced GL (stage II2-1V) in n=35 (13-1g,22hg). The administration of adequate treatment was not related to sex or tumor stage, but inadequate treatment was given more often with increasing age ( < 5 0 y:4%; 50-65 y:17% "~, >65 y:44%), lag G L (1g:13%; hg:37%) and bulky disease (non-bulky: 13%; bulky: 56%). Inadequate treatment was delivered because of age, underestimate of stage and fear of complications of CT more often in patients with hg GL (lg - 4x and hg - 30x GL). Administration Of adequate treatment resulted in a CR-rate of 99% in stage I-II~ and 73% in stage II2-W'versus 63% and 44% after inadequate treatment. NHL-related death was increased after indequate treatment both in lg (13%-63%) and hg GL (34-54%). Non-NHL related death was 16% and was independent of lymphoma and' treatment related factors. Almost 50% was due to a another malignancy. Conclusions: ~Administration of adequate treatment in GL was dependent on histology, bulky disease and age. 2After adequate treatment a high rate of CR and survival can be obtained. SAdequate treatment is the cornerstone to long-term survival in GL.

MALIGNANT DYSPHAGIA AND I~'I~-i.~LAS: EVOLVING POSSIBILITIES

OF

"DOUBLE"STENTING.H.Boot, P.Baas, N.van Zandwijk, B.G.Taal. Department of Gastroenterology and Pulmonary Diseases, Netherlands Cancer Institute, Amsterdam, The Netherlands. Insertion o f esophageal endoprostheses for malignant esophageal, respiratory fistulas may induce significant airway compression. "Combined" stenting of bronchi/trachea and esophagus with a variety of (expandable) airway and esophageali~tents may overcome this problem. During 1992'94 20 patients (18 fig'ttilas) were evaluated for "combined" stenting. In 5 of them only esophageal stenting sufficed for palliation. In 7 of them destruction of the trachen/bronehi was to extensive, precluding airway stenfing and they received an esophageal stent only. Complete sealing of the fistula was achieved in !1/12 patients. The other 8 patients (fistula 6x), with both dysphagia and strider receive~ "combined" stenting. Initially Dumon-typa (silicone) traeheobronchial stent (4x) were combined with conventional tygon prostheses; Recently Wall stents for intratracheal stenting are combined with coated Gianturcotype esophageal expandable stents. In every case the two types of stents were inserted on separate occasions. The Dumon stent is introduced under general anesthesia using a specialized rigid bronchoseope. The Wall stent can be introduced under local anesthesia using the flexible bronchosenpe and fluoroscopy. Esophageal protheses were introduced under intravenous sedation. One esophageal stent caused airway compression due to tumor growth distal to a tracheal stent, No other early complications of the procedures were observed. Immediate improvement of respiratory symptoms (strider) were observed in all patients. Improved swallowing was seen in all but one patient. Once the conventional tygon tube was not tolerated and had to be replaced. No significant pressure necrosis between both stents were observed. Median survival was 3-4 months. Conclusions: 1. Combined stenting of trachea/main bronchi and the esophagus nan give useful and instantaneous palliation in patients in whom respiratory and esophageal obstruction or fistulas necessitate immediate palliation. 2. Expandable endoprostheses are easier to insert then previous non-expandable stents.

• FAMILY HISTORY OF CANCER AND THE ADENOMA-CARCINOMA SEQUENCE. M.C. Boutron. P. Senesse, J. Faivre. Registre Bourguignon des Cancers Digestifs, Facult6 de M6decine~ 21000 Dijon, and INSERM U290 Paris, France.

• FOLATE, ALCOHOL AND THE ADENOMA-CARCINOMA SEQUENCE. M.C. Boutrort, P. Senesse, J: Faiwe. Registre Bourguignon des Cancers Digestifs, Facult6 de M6decine, 21000 Dijon, France and INSERM U290 Paris,

Although a family history of eoloreetal cancer is recognised as a risk factor for sporadic colorectal cancer, it is not well known which step of the adenomacarcinoma sequence it influences. We investigated in a case-control study the relationship between family history of cancer in first degree relatives and the different steps of the adenoma-earcinoma sequence. The adenoma groups and the polyp-free controls were recrnited, after colenoscopic examination, through all public and private endoscopy units in a well defined geographical area, and patients with colorectal cancer were obtained through all gastroanterologists and digestive surgeons. General population controls were a random sample from the census list for the arev. Relative risks were computed with a logistic regression controlling for age and sex. A family history of colorectal cancer (FHCRC) was observed in a similar proportion of smali adenoma patients (11.7 %, n=154) and of polyp-free patients (10.6 %; n=g26), whereas 4t was more frequent in patients with large (>9mm) adenoma(s) (18.8 %; n=208; pO.10) for small adenomas and 2.1 (p<0.01) for large adenomas. There was no difference among the groups regarding their family history of noncolorectal cancer (FHNC), nor regarding their family history of multiple cancers (more than one first degree relative with a cancer). Patients with a coloreetal cancer (n=171) had a higher proportion of both family history of colorectal cancer (15.8 %; p<0.O1) and family history of noncolorectal cancer (35.7 %; p<0.001) as compared to general population controls (n= 309; FHCRC: 8.1% and FHNC: 21.7 %)..When including FHCRC and FHNC in a model adjusted on age and sex, both factors were independently related to the risk of colorectal cancer, with Odds Ratios of 1.9 (p<0.05) for a family history of colorectal cancer and 2.1 (p<0.001) for a family history of non-colorectal cancer. There was no significant difference between cancer patients and controls regarding family history of multiple cancers. These data suggest that a fmnily history of colorectal cancer w6uld be a risk factor for large adenomas or cancers, but not for small adenomas. We observed an unexpected risk of cancer, but not of adanomas, in case of a family history of cancers whatever the type ; this should be further investigated in light of the recent findings about genes controlling for reparation of replication errors in the DNA, which are not specific to colurectal cancers.

Epidemiological studies have suggested that high alcohol and low relate intake might be associated with coloreetal tumors, through hypomethylation of DNA, an early event, or reduced availability of thymidine and purines for DNA repair, a later event in the carcinogenic process: We investigated in a caseControl study the relationship between relate and alcohol intakes, and the ~tifferent steps of the adenoma-carcinoma sequence All case groups and the polyp-free controls were recruited through all public and private gastroenterologists in a well defined geographical area. General population Icontrols were a random sample from the census list for the area. Consumptions Iwere classified into quintiles according to the consumption in each control pgroup, and separately by sex. Relative risks were computed with a logistic Iregression controlling for age. Odds ratios (OR) are given for the highest versus ~lowest quintile of intake ; p values (p) correspond to the test for linear trend. Comparing sinai! adenoma patients (n=154) with polyp-flee controls ~n=427), relate intake was inversely related to adenoma risk (OR=0.5; p<0.01), he association being stronger in women (OR=0.4; p=0.02) than in men OR=0.6; p=0.2) ; risk of small adenomas was not related to alcohol (p=0.9), peither in men (p=0.9) nor in women (p=0.8). Alcohol was positively associated ~vith the rink of large adenomas (n=208) as compared to the small adenoma ,~oatients(OR=3.9; p<0:0001), more so in men, where consumption was higher, R=5.1; p=0.0003), than in women (OR=2.6; p=0.08) ; folates were not lassociated with large adenomas (p=0.7), neither in men (0.9) nor in women l(p=0.5), or when studying a subgroup of men with an alcohol intake over 20 g [per day (cases=101, controls=46; p=0.6). For cancer patients (n=I71) Fompared to general populatior/controls (n=309) neither alcohol (p=0.2), nor ]relates (p=0.3) were related to risk. Our data support a protective effect of relate intake in colorectal Carcinogenesis, but limited to an early step of the adenoma-carcinoma sequence. The already described effect of alcohol was restricted to large adenomas and ~ndependent of relate intake. As for /:ancers, alcohol was not significantly associated with risk and relate was not a protective factor. Additional ~nformation is needed to understand the differencial effect of these nutrients amongsexes and along the adenoma-carcinoma segluence.

I