Journal of Surgical Oncology 2005;89:67–74

Clinical Outcome of Esophageal Cancer PatientsWith History of Gastrectomy

HIROSHI WADA, MD,1 YUICHIRO DOKI, MD,1* KIYONORI NISHIOKA, MD,2 OSAMU ISHIKAWA, MD,1

TOSHIYUKI KABUTO, MD,1 MASAHIKO YANO, MD,2 MORITO MONDEN, MD,2 AND SHINGI IMAOKA, MD1

1Department of Digestive Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan2Department of Surgery and Clinical Oncology, Osaka University Medical School, Osaka, Japan

Background: Surgery for thoracic esophageal cancer after gastrectomy involves acomplicated reconstruction procedure. A surgeon’s hesitation is further increasedbecause the clinical outcome of surgical treatment of these patients has not beenelucidated.Objectives: Among 948 thoracic esophageal cancer patients who underwent curativeoperation, 72 (7.6%) had a history of gastrectomy. Their clinico-pathological featuresand survival (follow-up average 881 days) were compared with those withoutgastrectomy.Results: Esophagectomy for patients after gastrectomy was performed via rightthoracotomy (66), left thoracotomy (4), and transhiatal resection (2), and reconstruc-tion was done using the right-side colon (57) or jejunum (15). Compared to non-gastrectomized patients, gastrectomized patients were exposed to longer operationtime (523 min vs. 460 min), but no significant difference was observed in operativemortality (4.2% vs. 2.5%) or blood loss (1,189 ml vs. 990 ml). Pathologicalexamination showed no significant difference in depth of tumor invasion, lymph nodemetastasis, and TNM staging between gastrectomized and non-gastrectomizedpatients, while tumors were located at lower position in the gastrectomized patients(P¼ 0.046). The overall and cause-specific 5-year survival rates were 56% and 65%for gastrectomized esophageal cancer patients, which were significantly better than fornon-gastrectomized patients (36% and 44%, P¼ 0.0235 and 0.024, respectively).Multivariate analysis showed gastrectomy as a marginally independent factor for afavorable prognosis (hazard ratio 1.832, P¼ 0.0324). With respect to tumor recur-rence, hematogenic metastasis tended to be less frequent in gastrectomized patientsthan in non-gastrectomized patients. In gastrectomized patients, neither disease(peptic ulcer or gastric cancer) nor reconstruction (Billroth-I, Billroth-II, and Roux-Y)for gastrectomy affected the clinicopathological findings or post-operable survival.Conclusions: Surgical treatment of esophageal cancer patients after gastrectomy wascomplicated but tolerable, and should be considered as a reliable therapeutic modalitybecause of favorable patient prognosis.J. Surg. Oncol. 2005;89:67–74. � 2005 Wiley-Liss, Inc.

KEY WORDS: esophageal cancer; gastric cancer; peptic ulcer; gastrectomy;prognostic factor

INTRODUCTION

Gastrectomy is the most common type of major abdo-minal surgery in Japan. Therefore, patients with thoracicesophageal cancer frequently have a history of gastrect-omy, ranging from 2.8% to 10.4% of all esophagealcancer patients who underwent surgery [1–6], but it is

*Correspondence to: Yuichiro Doki, MD, Department of Digestive Surgery,Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3Nakamichi, Higashinari-ku, Osaka 537-8511, Japan. Fax: 81-6-6981-8055.E-mail: ydoki@fj8.so-net.ne.jp

Accepted 3 November 2004

DOI 10.1002/jso.20194

Published online in Wiley InterScience (www.interscience.wiley.com).

� 2005 Wiley-Liss, Inc.

still controversial whether or not post-gastrectomy statusinduces esophageal carcinogenesis [7]. The most trou-blesome problem of esophageal cancer operation aftergastrectomy is that the gastric tube cannot be used foresophageal replacement. Substitution of the gastric tubewith the colon or jejunum requires complicated operativeprocedures and leads higher operative morbidity andmortality [6,8–10]. Surgery to remove thoracic esopha-geal cancer is one of the most stressful therapeuticmodalities and the development of chemotherapy andradiotherapy has occasionally shown an equivalentclinical benefit. Thus, the surgical indication for esopha-geal cancer has recently been discussed more seriouslywith respect to its survival benefit [11,12]. There havebeen many studies concerning esophageal cancers aftergastrectomy, which revealed some differences in theclinicopathological features in comparison with esopha-geal cancer without a history of gastrectomy, such as forsex [13], tumor location [2,5,13], and multiple cancers[14]. However, the survival benefit of surgical therapy forgastrectomized esophageal cancer patients has not beensufficiently discussed, probably because the number ofpatients in these studies was not adequate. One studyreported by Kato in 1992 gave a 5-year survival rate of35.9% for 50 cases of gastrectomized esophageal cancerpatients [2]. This was a little better than that of non-gastrectomized esophageal cancer patients (25.2%) intheir study although the difference was not statisticallysignificant. In this decade, the operative risk of recons-truction using the colon and jejunum has been decreasedby the use of vessel supercharged anastomosis [15–17]and the post-operative risk of tumor relapse has beendecreased by upper mediastinal and cervical lymph nodedissection [18–20]. Thus, in the present study, we evalu-ated the clinical significance of surgery for 72 gastrecto-mized esophageal cancer patients. This is the largestcohort study thus far, including patients who mostlyunderwent surgery in this decade and should providenovel insights for the treatment of this disease.

MATERIALS AND METHODS

Patients

A total of 948 patients with primary thoracic esopha-geal cancer underwent curative (R0) surgical treatment atOsaka Medical Center for Cancer and CardiovascularDiseases or Osaka University Medical School, Depart-ment of Surgery and Clinical Oncology, from 1985 to2001. Among them, 72 patients (7.6%) had a history ofgastrectomy prior to esophagectomy. There were 70 menand 2 women with an average age of 62.4 years. Partialgastrectomy had been performed for 66 patients (92%)due to either peptic ulcer or gastric cancer, and total gas-trectomy had been performed on the remaining 6 patients

(8%) due to gastric cancer. Reconstruction for gastrect-omy included 34 cases (47%) of Billroth-I, 30 cases(42%) of Billroth-II, 7 cases (10%) of Roux-Y, and 1(1%) of esophagogastrostomy after proximal gastrect-omy. Patient records of the 72 gastrectomized patientswere retrospectively compared with those of the remain-ing 876 non-gastrectomized patients. Pathological eva-luation of surgically resected specimens was based on theTNM classification [21] and Japanese classification [22].

Surgical Treatment

Various procedures of radical operation were perform-ed for gastrectomized esophageal cancer patients. Thewhole thoracis esophagus was removed via right thoraco-tomy with standard mediastinal lymph node resection in66 cases (91.6%). The anal side of the esophagus wasremoved via left thoracotomy in four cases (5.6%) withmiddle and lower mediastinal lymph node resection.Transhiatal blunt dissection was performed in two cases(2.8%). All patients underwent standard upper abdominallymph node resection including the perigastric and celiacnodes, whereas some of them had been previouslyremoved by prior gastric surgery due to gastric cancer.Supra clavicular node resection was optionally done in13 cases (18%) when the primary tumor was located atthe middle or more proximal esophagus, metastasis wassuspected by pre-operative examination or tumor invol-vement in upper mediastinal node was found duringoperation. Abdominal paraaortic nodes were resected infour cases (5.6%), when metastasis was suspected, orceliac nodes were extensively involved. Gastric remnantswere removed in the early period of this study. However,in the later period, they were preserved as much as possi-ble unless cancer involvement was evident (25 cases,34%). Reconstruction using the right-side colon alongwith the terminal ileum via the subcutaneous route wasthe most common method (56 cases, 78%). Super-charging of the blood supply was introduced in 22 cases(39%) by anastomosing the ileo–caecal and the internalmammalian artery and the accompanying vein [15,17].Cervical anastomosis by jejunal Roux-Y reconstructionwas performed, either with supercharged blood supplyanastomosis of the internal mammalian artery and vein(six cases) or without it (three cases). Intrathoracic ana-stomosis after removal of the anal-side thoracic esopha-gus was performed by jejunal Roux-Y or interpositionreconstruction.

For 876 non-gastrectomized patients, subtotal eso-phagectomy via right thoracotomy was performed for834 cases (95.2%). Standard 2-field lymph node resectionwas done together with optional cervical node resectionand abdominal paraaortic node resection, according tothe criteria described above. Anal-side esophagectomy

68 Wada et al.

and total gastrectomy via left thoracotomy followed byRoux-Y reconstruction was performed in seven cases,which included middle and lower mediastinal and upperabdominal lymph node resection. Also included in thenon-gastrectomized group were 35 cases of transhiatalresection. The following cases were excluded from thisstudy: synchronized cancer of other organs, adenocarci-nomas in the esophago–gastric junction, non-curativesurgery with residual tumors, and transhiatal blunt resec-tion for advanced cancer, which was not regarded ascurative surgery.

Pre-operative chemotherapy and pre-operative che-moradiation therapy were performed in 4 and 10 of gas-trectomized and 111 and 83 of non-gastrectomizedpatients, although the survival benefit of these pre-operative adjuvant therapies has not been significant inour series. Patients who underwent curative operation weresurveyed every month by physical examination, every3 months using serum tumor markers, every 6 months byCT scan and abdominal ultrasonography, and every yearby fiberscopy, until tumor recurrence was evident. Theaverage follow-up period was 881 days for gastrectomiz-ed patients and 889 days for non-gastrectomized patients.

Statistical Analysis

To evaluate the association between the history ofgastrectomy and clinicopathological parameters, Mann–Whitney U-test, Student t-test, and Fisher exact test wereused. The cumulative survival of gastrectomized and non-gastrectomized patients was calculated by the Kaplan–Meier method, and the differences between the twocurves were analyzed by log-rank test. A Cox propor-tional hazard model was used to assess the risk ratio withsimultaneous contribution from several covariates. Allstatistical analyses were performed with the softwarepackage StatView ver.5.0 (Abacus Concepts, Berkeley,CA) and P-values of less than 0.05 were considered toindicate statistical significance.

RESULTS

Clinicopathological Features of Gastrectomized

Esophageal Cancer Patients

Before evaluating surgery for esophageal cancer aftergastrectomy, the clinicopathological features of thiscancer were compared with those of non-gastrectomizedesophageal cancer patients (Table I). A significant dif-ference was observed in the gender of the patients andlocation and gross feature of the primary tumor. Femalepatients were rare among the gastrectomized patients(2.8%), and more frequently found in non-gastrectomizedpatients (14.8%) (P¼ 0.0022). The location of the cancerafter gastrectomy was lower than that without gastrect-

omy (P¼ 0.0201), being less frequent in the upperesophagus (6.9% vs. 16.2%) and more in the lower eso-phagus (40.3% vs. 28.5%). With respect to gross tumormorphology, esophageal cancers after gastrectomy fre-quently showed expansive growth pattern (44.5%), whilethose without gastrectomy dominantly showed infiltrative

TABLE I. Relationship Between History of Gastrectomy andClinicopathological Parameters

Parameters Gastrectomized Non-gastrectomized P-value

Gender

Male 70 (97.2%) 746 (85.2%)

Female 2 (2.8%) 130 (14.8%) 0.0022

Location

Upper 5 (6.9%) 142 (16.2%)

Middle 38 (52.8%) 484 (55.3%)

Lower 29 (40.3%) 250 (28.5%) 0.0201

Histological type

Well SCCa 19 (26.4%) 189 (21.6%)

Mod SCC 27 (37.5%) 431 (49.2%)

Poor SCC 22 (30.6%) 205 (23.4%)

Othersb 4 (5.5%) 51 (5.8%) 0.2595

Gross featurec

Superficial 24 (33.3%) 213 (24.3%)

Expansive 32 (44.5%) 239 (27.3%)

Infiltrative 16 (22.2%) 351 (40.1%)

Unknown 0 (0%) 73 (8.3%) 0.0015

Primary tumord

T1 30 (41.7%) 292 (33.3%)

T2 15 (20.8%) 131 (15.0%)

T3 21 (29.2%) 303 (34.6%)

T4 6 (8.3%) 150 (17.1%) 0.2032

Lymph node

metastasis

Absent 30 (41.7%) 335 (38.3%)

Present 42 (58.3%) 539 (61.7%) 0.5761

TNM stagingd

I 19 (26.4%) 192 (21.9%)

II 29 (40.3%) 261 (29.8%)

III 14 (19.4%) 223 (25.5%)

IV 10 (13.9%) 200 (22.8%) 0.0957

Tumor lengthe

Total 4.9� 2.8 5.0� 2.6 0.7496

T1 3.9� 3.2 3.7� 2.3 0.6273

T2, T3, T4 5.7� 2.3 5.8� 2.4 0.8134

Total 72 (100%) 876 (100%)

aWell-, Mod-, Poor-SCC: well, moderately, and poorly differentiated

squamous cell carcinoma, respectively.bOthers, including basaloid cell carcinoma, small cell carcinoma,

adenosquamous cell carcinoma, adenocarcinoma, carcinosarcoma, and

malignant melanoma.cGross feature is classified according to Japanese classification [22];

‘‘Expansive’’ includes type 1 (protruding) and type 2 (ulcerative and

localized), and ‘‘Infiltrative’’ includes type 3 (ulcerative and infiltrat-

ing) and type 4 (diffuse infiltrating).dClassification of primary tumor and TNM staging according to TMN

classification (6th edition, 2002) [21].eTumor length was described as average (cm) and standard deviation,

and separately evaluated in superficial (T1) and advanced (T2, T3, T4)

tumors.

Esophageal Cancer After Gastrectomy 69

growth pattern (40.1%) (P¼ 0.0015). There were nodifferences in the histological grade of cancer cells.Adenocarcinoma of the esophagus was not observed inthe gastrectomized group and was also rare (0.4%) in thenon-gastrectomized group as reported for the generalJapanese population [23]. Very little difference wasobserved in the depth of tumor invasion and frequency oflymph node metastasis, although superficial cancer (T1)and node-negative observations were slightly morefrequent for gastrectomized patients. Due to these smalldifferences, gastrectomized patients showed a tendencyto harbor cancers of a less advanced pathological stage,that is, more stage I and II cases and fewer stage III andIV cases (P¼ 0.0957). Tumor length was quite the samebetween gastrectomized and non-gastrectomized esopha-geal cancers in all tumors, as well as evaluated separatelyin the superficial and the advanced tumors.

Next, we compared the clinical background of gas-trectomized patients according to disease for gastrect-omy, that is peptic ulcer (n¼ 39) or gastric cancer(n¼ 33) (Table II). As previously reported, the age forgastrectomy was lower in peptic ulcer patients than ingastric cancer patients (37 years old and 52 years old),and the interval from gastrectomy and esophagectomywas longer for peptic cancer patients than gastric cancerpatients (24.6 years vs. 11.5 years). The age for esopha-gectomy was 3 years lower for peptic ulcer group than thegastric cancer group, though this difference was notsignificant (P¼ 0.0903). As for the gastrectomy proce-dure, Billroth-I was more frequent for gastric cancerpatients while Billroth-II was more frequent for pepticulcer patients (P¼ 0.0066). There was no difference inthe status of esophageal cancers after gastrectomy, inclu-

ding location, histological grade, depth of tumor inva-sion, lymph node metastasis, and TNM stage, betweenpeptic ulcer and gastric cancer group (data not shown).

Risk of Surgical Treatment for Gastrectomized

Esophageal Cancer Patients

The operative risk of radical surgery for gastrecto-mized esophageal cancer patients was compared with thatfor non-gastrectomized patients in Table III. Operativetime was longer and blood loss was greater for gas-trectomized patients than non-gastrectomized patients,however the difference was statistically different only inthe former (523 min vs. 460 min, P¼ 0.0051), and wasnot significant in the latter (1,189 ml vs. 990 ml,P¼ 0.2216). Three patients died of post-operativecomplications within 30 days after surgery in gastrecto-mized patients, however this mortality rate (4.2%) wasnot significantly different from that of non-gastrecto-mized patients (2.5%, P¼ 0.4292). The post-operativehospital stay was significantly longer in gastrectomizedpatients than in non-gastrectomized patients (median69 days vs. 40 days, P< 0.0001). Anastomotic leakagewas the highest risk factor for prolonging the hospitalstay of the gastrectomized patients, with median hospitalstay of 19 patients with leakage being 147 days and thatwithout it being 65 days (P< 0.0001). Among 56 cases ofright-side colon reconstruction, supercharged bloodsupply by anastomosing ileo–caecal–internal mamma-lian artery and vein was performed in 22 cases. Theincidence of anastomotic leakage tended to be lessfrequent and the hospital stay to be shorter in patientswith supercharged anastomosis than in those without it

TABLE II. Clinical Background of Esophageal Cancer Patients Gastrectomized due to EitherPeptic Ulcer or Gastric Cancer

Disease treated by gastrectomy

P-valuePeptic ulcer Gastric cancer

Age for gastrectomy (year) 37.1� 10.1 52.4� 9.8 <0.0001

Age for esophagectomy (year) 60.8� 6.74 63.8� 7.1 0.0903

Interval (year)a 24.6� 9.2 11.5� 8.2 <0.0001

Resection and reconstraction

Partial gastrectomy 39 27

Billroth-I 16 18

Billroth-II 22 8

Othersb 1 1 0.0066*

Total gastrectomyc 0 6

Total number 39 (54.2%) 33 (45.8%)

*Chi-square test among 66 cases of partial gastrectomy patients.aInterval, period from gastrectomy to esophagectomy.bOthers, including one Roux-Y reconstruction after distal gastrectomy in peptic ulcer group and one

jejunal interpositional reconstruction after proximal gastrectomy in gastric cancer group.cAll total gastrectomy patients were reconstructed by Roux-Y method.

70 Wada et al.

(major leakage 22.7% vs. 26.5% and median hospital stay63 days vs. 77 days), although these differences were notstatistically significant.

Post-Operative Survival of Gastrectomized

Esophageal Cancer Patients

As shown in Figure 1, the overall 5-year survival ratesof gastrectomized and non-gastrectomized patients were56% versus 36%, and their cause-specific survival ratewere 65% versus 44%. Thus, both overall and cause-specific survival rates were significantly better ingastrectomized esophageal cancer patients than in non-gastrectomized patients (P¼ 0.0235 and 0.024, respec-tively). Gender, depth of tumor invasion, lymph nodemetastasis, and history of gastrectomy were significantprognostic factors in the univariate analysis of cause-specific survival (Table IV). In the multivariate analysis,gastrectomy was an independent factor for favorableprognosis (hazard ratio 1.832, P¼ 0.0324) as well assuperficial (T1), node-negative, and female counterparts.Among gastrectomized patients, the disease for gastrect-omy treatment, either peptic ulcer or gastric cancer, didnot affect the post-operative survival. The mode of firsttumor recurrence was classified as lymph node metastasis13 (68%), hematogenic metastasis 3 (15%), and local4 (21)% in 19 gastrectomized patients (1 had both lymphnode and hematogenic metastasis). Comparison withthose of non-gastrectomized patients (lymph node 56%,hematogenic 37%, and local 20%, respectively), show-ed the tendency hematogenic metastasis to be lesser andlymph node metastasis to be greater in gastrectomizedpatients.

DISCUSSION

Surgery for esophageal cancer patients who haveundergone gastrectomy is an old issue and has becomemore important since its incidence is increasing recently.In our series, the proportions of gastrectomized patientsof the total operated esophageal patients were 4.4%(until 1990), 5.0% (1991–1995), and 13.5% (1996onwards), and, as consistently demonstrated to be 4.4%[3], 5.0% [2] in the early period until the early 90s and

10.4% [4], 10.1% [6] in the latest study. With regard toprevious diseases for gastrectomy, the proportion ofpeptic ulcer and gastric cancer was similar in this studyand the latest one [6], while peptic ulcer was dominant inthe earlier studies [3,4,13]. Therefore, the improvement

TABLE III. Clinical Features of Radical Operation for Esophageal CancerWith orWithout Historyof Gastrectomy

Gastrectomized (72 cases) Non-gastrectomized (876 cases) P-value

Operation time (min) 522.9� 160.8 460.4� 160.2 0.0051

Blood loss (ml) 1,189� 944 990� 1,197 0.2216

Mortality rate 4.2% (3 cases) 2.5% (22 cases) 0.4292

Hospital stay after operation

Average (median) 93.0� 79.5 (69 days) 54.0� 48.4 (40 days) <0.0001

Fig. 1. Post-operative survival of esophageal cancer patients with orwithout history of gastrectomy. Cause-specific survival curves ofesophageal cancer patients with a history of gastrectomy (n¼ 72) orwithout it (n¼ 876) and those of were plotted by Kaplan–Meiermethod and their difference was evaluated by log-rank test. Five-yearsurvival rate and P-value were indicated. Cause-specific survivalcurves were also plotted and tested among gastrectomized patientsaccording to the disease for gastrectomy, that is either peptic ulcer(n¼ 39) or gastric cancer (n¼ 33).

Esophageal Cancer After Gastrectomy 71

of gastric cancer treatment should be the greatest reasonfor the increase of gastrectomized esophageal cancerpatients. On the other hand, gastrectomy for peptic ulcerdramatically decreased in the early 80s [24,25]. However,the interval to esophageal cancer in these patients averag-ed 24 years in this study, therefore, it will take severalmore years to determine whether there is a decrease in theincidence of esophageal cancer patients gastrectomizeddue to peptic ulcer.

What has been controversial is whether or not post-gastrectomy status contributes to esophageal carcinogen-esis. The high incidence of esophageal cancer in thelower esophagus might suggest the involvement of gas-troesophageal reflux in esophageal carcinogenesis aftergastrectomy. It has been demonstrated that bile acidtreatment induces cycloxgenase-2 (Cox-2), a potentmediator for carcinogenesis, in normal squamous epithe-lium and squamous cell carcinoma of the esophagus[26,27], and that human squamous cell carcinomas in thelower thoracic esophagus expresses stronger Cox-2 thanthose located in the upper thoracic esophagus [28].Moreover, we have experimentally found that a low doseof bile acid can stimulate the proliferation of squamouscell carcinoma of the esophagus (Nishioka et al. un-published observation). Taken together, we speculate thatthe gastroesophageal reflex, where the components havechanged to include more bile acid and less gastric acidafter gastrectomy, induces squamous cell carcinoma inthe lower esophagus. A large cohort epidemiologicalstudy, that can directly prove the association of post-gastrectomy status and esophageal carcinogenesis, isneeded in the future.

Various parameters exhibited more surgical stress ofesophagectomy after gastrectomy than that withouthistory of gastrectomy. More blood loss was observedduring resolving adhesion in the upper abdominal cavitycaused by gastrectomy. Longer operative time wasneeded due to complicated reconstruction, that is onlyesophagogastrostomy for non-gastrectomized patientsbut esophago-ileostomy, colo-gastrostomy, ile-colost-omy, and microscopic anastomosis of ileo–caecal arteryand vein for gastrectomized patients treated by repre-sentative right-side colon reconstruction. The operativemortality was tolerable although slightly higher in thegastrectomized patients than in the non-gastrectomizedpatients. A longer post-operative hospital stay was main-ly due to anastomotic leakage, which was more frequentand sometime persistent in gastrectomized patients, butwas slightly improved after administration of blood flowsupercharge. For the operative procedure, we recentlypreserve the gastric remnant as much as possible becauseno tumor involvement was observed grossly or micro-scopically in gastric remnants, removed in the earlyperiod, and since we began this preservation, none of ourpatients has experienced tumor recurrence in the gastricremnant. Preservation of the gastric remnant would aidthe absorption of vitamin B12 and Fe and secretion ofgastric hormone such as ghrelin [29].

The final purpose of this study was to elucidate theclinical significance of surgical treatment for esophagealcancer patients after gastrectomy. Surprisingly, despitethe greater surgical stress in esophagectomy for gas-trectomized patients than that for non-gastrectomizedpatients, the former showed better overall and cause-

TABLE IV. Prognostic Factors Analyzed by the Cox Proportional Hazards Model

Variable

Univariate analysis Multivariate analysis

Hazard

ratio 95% CI P-value

Hazard

ratio 95% CI P-value

Gender

Female Ref. Ref.

Male 1.483 1.064–2.06 0.0199 1.457 1.044–2.032 0.0267

Primary tumor

T1 Ref. Ref.

T2–T4 4.354 3.274–5.791 <0.0001 3.105 2.309–4.175 <0.0001

Lymph node metastasis

Absent Ref. Ref.

Present 3.756 2.911–4.845 <0.0001 2.618 2.009–3.411 <0.0001

Location

Upper Ref.

Middle 0.779 0.588–1.032 0.0817

Lower 0.899 0.663–1.219 0.4933

Gastrectomy

Gastrectomized Ref. Ref.

Non-gastrectomized 1.872 1.076–3.256 0.0263 1.832 1.052–3.191 0.0324

Ref., reference; CI, confidence interval.

72 Wada et al.

specific post-operative survival than the latter. Kato [2]had collected data on 50 gastrectomized esophagealcancer patients who had undergone surgery mostly in the1970s and 1980s and reported their 5-year survival rate tobe 35.9%, which was better than that of non-gastrecto-mized patients (25.2%), though not statistically signifi-cant. After the mid 80s, radical lymph node resectionimproved the prognosis of operation of esophageal cancerpatients [18,20], showing 5-year survival to be 40% forJapanese institutions as a whole registration [23] and 44%in our institute, whereas gastrectomized patients showedbetter prognosis with the cause-specific 5-year survivalrate being 65%. Gastrectomized patients tended to showless advanced pathological stages, although we do notknow whether this was due to the surgeon’s selection orthe biological property of this tumor. The former isunlikely since size of tumor is the same, rather the lattermay be involved since, for example, gastrectomizedtumors showed more expansive growth pattern. What isof importance is that in multivariate analysis, gastrect-omy is an independent prognostic factor, as are sex, depthof invasion, and lymph node metastasis. Kato has specu-lated the reason for good prognosis of gastrectomizedesophageal cancer patients as metastasis to abdominalnodes, especially below the stomach [2], being limitedbecause of alteration of lymphatic flow after gastrectomy[30]. In this study, less tumor recurrence in hematogenicmetastasis was observed in gastrectomized patients andmicroscopic venous involvement was consistently lessfrequent in the surgical specimens of gastrectomizedpatients than in those of non-gastrectomized patients(24% vs. 38%). This might suggest the differentbiological behaviors of esophageal cancer after gastrect-omy. Further study with a larger number of patients isrequired to elucidate this issue.

In the present study, we have shown that surgicaltreatment for esophageal cancer after gastrectomy wascomplicated but tolerable and can be expected to havefavorable prognosis, which seems to be better than sub-stitutive therapeutic modalities including radiotherapy,chemotherapy, or chemoradio therapy [11,12]. Surgicaltreatment for these patients is warranted and it is nowunder investigation as to whether or not adjuvant orneoadjuvant use of chemotherapy or radiotherapy canoffer further survival benefit.

CONCLUSION

Recently, the incidence of thoracic esophageal cancersdeveloping after gastrectomy has been increasing. Theirsurgical treatment was shown to be safe and to offerconsiderably favorable prognosis, which should encou-rage surgeons to attempt this complicated operation.

REFERENCES

1. Hsu NY, Chen CY, Chen JT, et al.: Oesophageal squamous cellcarcinoma after gastrectomy for benign ulcer disease. Scand JThorac Cardiovasc Surg 1996;30:29–33.

2. Kato H, Tachimori Y, Watanabe H: Surgical treatment for thoracicesophageal carcinoma in patients after gastrectomy. J Surg Oncol1992;51:94–99.

3. Kuwano H, Matsuda H, Nagamatsu M, et al.: Occurrence of eso-phageal carcinoma after gastrectomy. J Surg Oncol 1989;41:77–80.

4. Tachibana M, Abe S, Yoshimura H, et al.: Squamous cellcarcinoma of the esophagus after partial gastrectomy. Dysphagia1995;10:49–52.

5. Alexandrou A, Davis PA, Law S, et al.: Esophageal cancer inpatients with a history of distal gastrectomy. Arch Surg 2002;137:1238–1242.

6. Aiko S, Yoshizumi Y, Sugiura Y, et al.: Clinical characteristics ofesophageal cancer after gastrectomy and the pertinence ofchemoradiotherapy. Nihon Rinsho Geka Gakkai Zasshi 2002;63:813–820.

7. La Vecchia C, D’Avanzo B, Negri E, et al.: Gastrectomy andsubsequent risk of oesophageal cancer in Milan. J EpidemiolCommunity Health 1994;48:310–312.

8. Cerfolio RJ, Allen MS, Deschamps C, et al.: Esophagealreplacement by colon interposition. Ann Thorac Surg 1995;59:1382–1384.

9. Kolh P, Honore P, Degauque C, et al.: Early stage results afteroesophageal resection for malignancy-colon interposition vs.gastric pull-up. Eur J Cardiothorac Surg 2000;18:293–300.

10. Davis PA, Law S, Wong J: Colonic interposition after esopha-gectomy for cancer. Arch Surg 2003;138:303–308.

11. Urschel JD, Ashiku S, Thurer R, et al.: Salvage or plannedesophagectomy after chemoradiation therapy for locally advancedesophageal cancer—a review. Dis Esophagus 2003;16:60–65.

12. Urba S: Combined modality therapy of esophageal cancer-standard of care? Surg Oncol Clin N Am 2002;11:377–386.

13. Maeta M, Koga S, Shimizu T, et al.: Possible association betweengastrectomy and subsequent development of esophageal cancer.J Surg Oncol 1990;44:20–24.

14. Kitabayashi K, Nakano Y, Saito H, et al.: Multicentric occurrenceof esophageal cancer after gastrectomy: A preliminary report.Surg Today 2001;31:670–674.

15. Fujita H, Yamana H, Sueyoshi S, et al.: Impact on outcome ofadditional microvascular anastomosis—supercharge—on coloninterposition for esophageal replacement: Comparative andmultivariate analysis. World J Surg 1997;21:998–1003.

16. Furst H, Hartl WH, Lohe F, et al.: Colon interposition foresophageal replacement: An alternative technique based on theuse of the right colon. Ann Surg 2000;231:173–178.

17. Inoue Y, Tai Y, Fujita H, et al.: A retrospective study of 66esophageal reconstructions using microvascular anastomoses:Problems and our methods for atypical cases. Plast Reconstr Surg1994;94:277–284; discussion 285–277.

18. Akiyama H, Tsurumaru M, Udagawa H, et al.: Radical lymphnode dissection for cancer of the thoracic esophagus. Ann Surg1994;220:364–372; discussion 363–372.

19. Shiozaki H, Yano M, Tsujinaka T, et al.: Lymph node metastasisalong the recurrent nerve chain is an indication for cervical lymphnode dissection in thoracic esophageal cancer. Dis Esophagus2001;14:191–196.

20. Nishimaki T, Suzuki T, Suzuki S, et al.: Outcomes of extendedradical esophagectomy for thoracic esophageal cancer. J Am CollSurg 1998;186:306–312.

21. Sobin LH, Wittekind Ch, editors: TNM classification ofmalignant tumours. New York: Wiley Liss, 2002.

22. The Japanese Society for Esophageal Diseases. Guide lines forclinical and pathologic studies on carcinoma of the esophagus.Tokyo: Kanehara Print, Inc., 1999.

23. The Japanese Society for Esophageal Diseases. Comprehensiveregistry of esophageal cancer in Japan. Tokyo: The JapaneseSociety for Esophageal Diseases, 2001.

Esophageal Cancer After Gastrectomy 73

24. Jensen MO, Bubrick MP, Onstad GR, et al.: Changes in the surgicaltreatment of acid peptic disease. Am Surg 1985;51:556–558.

25. Gustavsson S, Nyren O: Time trends in peptic ulcer surgery, 1956to 1986. A nation-wide survey in Sweden. Ann Surg 1989;210:704–709.

26. Shirvani VN, Ouatu-Lascar R, Kaur BS, et al.: Cyclooxygenase 2expression in Barrett’s esophagus and adenocarcinoma: Ex vivoinduction by bile salts and acid exposure. Gastroenterology 2000;118:487–496.

27. Zhang F, Altorki NK, Wu YC, et al.: Duodenal reflux inducescyclooxygenase-2 in the esophageal mucosa of rats: Evidence for

involvement of bile acids. Gastroenterology 2001;121:1391–1399.

28. Kawabe A, Shimada Y, Uchida S, et al.: Expression ofcyclooxygenase-2 is associated with carcinogenesis of the lowerpart of thoracic esophageal squamous cell carcinoma and p53expression. Oncology 2002;62:46–54.

29. Cummings DE, Weigle DS, Frayo RS, et al.: Plasma ghrelin levelsafter diet-induced weight loss or gastric bypass surgery. N Engl JMed 2002;346:1623–1630.

30. Noguchi Y, Imada T, Abe S, et al.: Lymphatic flow of the remnantstomach. Nippon Geka Gakkai Zasshi 1988;89:852–862.

74 Wada et al.