Intraoperative Radiation Enhances Decline of Pancreatic Exocrine Function After Pancreatic Head Resection

Intraoperative Radiation Enhances Declineof Pancreatic Exocrine Function After

Pancreatic Head ResectionKOJI YAMAGUCHI, MD, KATSUMASA NAKAMURA, MD, MASAHIKO KIMURA, MD,

KAZUNORI YOKOHATA, MD, HIROKAZU NOSHIRO, MD, KAZUO CHIJIIWA, MD, andMASAO TANAKA, MD

Intraoperative radiation therapy has been introduced to improve survival rates after resectionof biliopancreatic cancer. Early and late effects of intraoperative radiation on the exocrineand endocrine functions of the residual pancreas were examined in 54 patients with pancre-atic head resection. Of the 54 patients, 20 underwent intraoperative radiation (A group) andthe other 34 did not (B group). Fasting blood sugar level, a 120-min value of the 75-g oralglucose tolerance test, N-benzol-L-tyrosyl-p-aminobenzoic acid (BT-PABA) excretion value(a pancreatic exocrine function test), and amount of postoperative pancreatic juice drainagewere compared between groups A and B at preoperative and early and late postoperativetimes. Fasting blood sugar level and a 120-min value of the 75-g oral glucose tolerance test(OGTT) showed no change at the early (,2 months) postoperative period of the two groups.At the late (.6 months) postoperative period, fasting blood sugar showed no alteration, whilethe 75-g OGTT 120-min value increased compared to the preoperative level in both groups.In the group A, the 75-g OGTT 120-min value at the late postoperative period wassignificantly higher than those at the preoperative and early postoperative periods (289.4 6104.9 vs 193.0 6 58.2 mg/dl, P 5 0.0198 and 289.4 6 104.9 vs 184.4 6 104.9 mg/dl, P 50.0285). Preoperative BT-PABA excretion value was not different between the two groups.It decreased at the early postoperative period and returned to the preoperative level at thelate postoperative period in both the groups. The decline of BT-PABA in group A was 23 621%, which was significantly larger than 11 6 24% in group B. The total amount ofpostoperative pancreatic juice drainage from postoperative days (POD) 4–13 in group A wasabout half as much as that in group B (720.8 6 916.4 vs 1433.8 6 962.1 ml, P 5 0.0128).Univariate and multivariate regression analysis of factors concerning the decline of BT-PABA values at the early postoperative period showed that intraoperative radiation was asignificant independent determinant. In conclusion, these results suggest that intraoperativeradiation causes significant deterioration of pancreatic exocrine function at the early post-operative period. Intraoperative radiation for resectable periampullary carcinoma should bereappraised based on the decline of the pancreatic exocrine function as well as the improve-ment of the survival curve.

KEY WORDS: intraoperative radiation therapy; pancreatic exocrine function; pancreatic endocrine function; pan-createctomy.

Manuscript received December 14, 1998; accepted July 12, 1999.From the Departments of Surgery and Oncology and Clinical

Radiology, Graduate School of Medical Sciences, Kyushu Univer-sity Faculty of Medicine, Fukuoka 812-8582, Japan.

Address for reprint requests: Dr. Koji Yamaguchi, Departmentof Surgery I, Kyushu University, 812-8582 Fukuoka, Japan.

Digestive Diseases and Sciences, Vol. 45, No. 6 (June 2000), pp. 1084–1090

1084 Digestive Diseases and Sciences, Vol. 45, No. 6 (June 2000)0163-2116/00/0600-1084$18.00/0 © 2000 Plenum Publishing Corporation

Intraoperative radiation therapy (IORT) has beenintroduced into the treatment of unresectable andresectable periampullary carcinoma. In unresectablecases, the purpose of IORT is to cause shrinkage oflocally advanced carcinoma and relieve abdominalpain. In resectable cases, IORT is employed to con-trol local residual cancer cells and/or local recurrenceafter pancreatectomy. The merit of IORT is to delivera large dosage of radiation directly to the targetorgans, while preventing untoward damage to thesurrounding structures. Chemoradiation has alsobeen expected to improve the clinical course of un-resectable localized periampullary carcinoma (1, 2).The effects of IORT after resection of pancreaticcarcinoma remain controversial. The majority of pre-vious papers have referred to the clinical course ofpatients with and without IORT (3–7). Ishikawa et al(8) mentioned that preoperative radiation preventspancreatic fistula after pancreatoduodenectomy.Since then few have addressed pancreatic exocrineand endocrine functions after pancreatoduodenec-tomy with or without radiation therapy. In this series,retrospective review of the pancreatic exocrine andendocrine functions was conducted in patients withpancreatectomy in relation to the presence or ab-sence of IORT.

MATERIALS AND METHODS

This series is composed of 54 Japanese patients withpancreatic head resection. Exocrine and endocrine functionof the residual pancreas was examined at preoperative,early postoperative (within two months after operation),and late postoperative (more than six months after opera-tion) periods. They were treated in the Department ofSurgery I, Kyushu University Hospital, Fukuoka Japan,from May 1992 to January 1998. The clinical charts werereviewed concerning the following factors: age; sex; benignor malignant condition; operative procedure; peripheralwhite blood cell count; hematocrit; preoperative serumlevels of albumin, total bilirubin, blood urea nitrogen, andamylase; operation time; operative blood loss; presence orabsence of perioperative blood transfusion; octreotide;IORT (intraoperative radiation therapy); and ERT (exter-nal radiation therapy). The 54 patients consisted of 18 witha benign mucin-hypersecreting tumor, 16 with pancreatichead carcinoma, 7 with chronic pancreatitis, 6 with ampul-lary carcinoma, 3 with serous cystadenoma, 2 with endo-crine tumor of the pancreas (1 benign and 1 malignant), 1with gastric carcinoma, and 1 with distal bile duct carci-noma. Of them, 37 patients underwent pylorus-preservingpancreatoduodenectomy, 9 pancreatoduodenectomy, 4 du-odenum-preserving pancreatic head resection, 2 segmentalpancreatic resection, 1 pylorus-preserving pancreatoduode-nectomy with distal pancreatectomy, and 1 extended rightlobectomy of the liver and pylorus-preserving pancre-atoduodenectomy. In patients with malignant diseases,

lymph node dissection including the skeletonizing of thehepatoduodenal ligament was invariably performed. Thediameter of the main pancreatic duct at the presumablytransected line was measured on endoscopic retrogradepancreatography, ultrasonography and/or endoscopic ultra-sonography.

Of the 27 patients with malignant diseases, 20 patientsreceived IORT with 6–15 MeV electron beams. The IORTfield using treatment applicators of 7–10 cm in diametercovered the gross tumor or the tumor bed plus a .1-cmmargin. The IORT dose was 18–30 Gy. We usually includedthe resected edge of the pancreas within the IORT field.Postoperatively, ERT (36–40 Gy at 1.5–2.0 Gy/fraction)was given by 6 MV x-rays in 13 of the 20 after the surgicalprocedures.

The N-benzol-L-tyrosyl-p-aminobenzoic acid (BT-PABA) test was used to assess the exocrine pancreaticfunction. After an overnight fast, 500 mg of BT-PABA(Eisai Co. Ltd., Tokyo, Japan) was administered orally, anda urine sample was collected over a 60-hr period for thetest. BT-PABA is a synthetic tripeptide that is speciallycleaved by the pancreatic enzyme chymotrypsin (9). Thep-aminobenzoic acid (PABA) released in the presence ofchymotrypsin is rapidly absorbed from the small intestine,partially conjugated in the liver, and finally excreted in theurine. The recovery rate of PABA in the urine indirectlyreflects the amount of intraluminal chymotrypsin (10). Atour institution, the 6-hr urinary PABA excretion rate wasmeasured (Otsuka Assay Laboratories, Otsuka Pharmaceu-tical Co., Ltd., Tokushima, Japan) and a rate of ^70% wasconsidered normal. Since the specificity of the BT-PABAtest is influenced by several nonpancreatic factors such asliver dysfunction, renal insufficiency, and abnormal glucosemetabolism (11), all hematological, biochemical, and nutri-tional abnormalities were collected before the test.

An oral glucose tolerance test (OGTT) was performed inpatients who were not insulin dependent before surgery.Blood samples were taken before loading of 75 g glucoseand at 30-min intervals thereafter up to 120 mins. In thisstudy, fasting blood sugar (FBS) and blood sugar at 120 minafter glucose loading were utilized as a marker of thepancreatic exocrine and endocrine functions. A diagnosis ofdiabetes mellitus was made based on the criteria set by the1985 World Health Organization study group on diabetesmellitus (12).

The values were expressed as mean 6 standard deviation.The mean value was examined by chi-square test and thedistribution of case was examined by Student’s t test. A Pvalue less than 0.05 was considered statistically significant.

RESULTS

Clinicopathological Findings of 20 Patients withIORT and 34 Without IORT. Clinicopathological fea-tures were compared between those with and withoutIORT (Table 1). The age of the 20 patients withIORT was 66.2 6 9.1 years, that of the 34 withoutIORT was 58.9 6 13.1 years (P , 0.0336). A historyof jaundice was present in nine of the 20 with IORT,and in three of the 34 without IORT (P 5 0.0020).

IORT ENHANCED DECLINE OF PANCREATIC ENDOCRINE FUNCTION

1085Digestive Diseases and Sciences, Vol. 45, No. 6 (June 2000)

The mean operation time in those with IORT was 130min longer than that in those without IORT (P ,0.0001). Perioperative blood transfusion was re-quired in 16 of 20 IORT patients, and in 12 of 34without IORT (P 5 0.0015). The consistency of thepancreas was normal to intermediate in 10 of the 20and hard in the other 10 patients, while it was normalin 19, intermediate in 9 and hard in 6 of the 34 (P 50.0279). The other factors were not significantly dif-ferent between the 20 patients with IORT and the 34without IORT.

Pancreatic Endocrine and Exocrine Function atPreoperative and Early and Late Postoperative Peri-ods. FBS and the 120-min value of 75-g OGTTshowed no change between the preoperative andearly postoperative periods irrespective of the pres-ence or absence of IORT. At the late postoperativeperiod, FBS showed no change, while the 120-minvalue increased in patients with or without IORT.The preoperative and early and late postoperative

fasting blood sugar values and 120-min value were notdifferent between the 20 patients with IORT and the34 without IORT (Table 2). In the 20 patients withIORT, the 120-min level at the late postoperativeperiod was significantly higher than those at the pre-operative and early postoperative periods (289.4 6

TABLE 1. CLINICOPATHOLOGIC ASPECTS OF 54 PATIENTS WITH PANCREATECTOMY

IORT(1) (20) IORT(2) (34) P

Age (yr) 66.2 6 9.1 58.9 6 13.1 0.0336Sex (M/F) 14/6 21/13 0.5406Jaundice 9/20 3/34 0.0020Diabetes mellitus 9/20 7/34 0.0578Benign/malignant 0/20 27/7 ,0.0001White blood cells 5818.0 6 2850.4 5669.7 6 1860.7 0.8178Hematocrit (%) 37.1 6 3.4 38.6 6 4.3 0.1898Albumin (g/dl) 3.8 6 0.4 3.9 6 0.4 0.3892BUN (mg/dl) 14.8 6 5.7 14.6 6 6.9 0.9207Total bilirubin (mg/dl) 1.6 6 2.4 0.9 6 1.2 0.1692Amylase (IU/liter) 105.7 6 43.0 144.2 6 102.1 0.1149ASA score 0.2303

I 3 10II 16 24III 1 0

Operation time (min) 614.6 6 49.6 486.7 6 114.2 ,0.0001Operative blood loss (g) 1865.5 6 890.3 1385.6 6 977.6 0.0778Perioperative blood transfusion 16/20 12/34 0.0015Consistency of pancreas 0.0279

Normal 5 19Intermediate 5 9Hard 10 6

Diameter of MPD (mm) 6.6 6 4.5 5.4 6 3.8 0.3153Anastomosing organ 0.4076

PG 1 4PJ 19 30

Anastomosing method 0.6429Mucosa-to-mucosa 13 21Total tube drainage 4 10Invagination 3 3

Operative procedure 0.1506PpPD 14 25PD 6 3DPPHR 0 4SR 0 2

External radiation 13/20 0/34 ,0.0001Octreotide 4/20 12/34 0.2346

TABLE 2. PREOPERATIVE, EARLY POSTOPERATIVE, AND LATEPOSTOPERATIVE PANCREATIC ENDOCRINE FUNCTION WITH OR

WITHOUT IORT*

Period IORT(1) IORT(2) P

PreoperativeFBS (mg/dl) 120.5 6 51.6 98.2 6 30.4 0.0510120-min (mg/dl) 193.0 6 58.2a 172.4 6 82.4 0.4131

Early postoperativeFBS (mg/dl) 117.4 6 29.7 102.7 6 28.0 0.0818120-min (mg/dl) 184.4 6 76.7b 172.0 6 81.4 0.6392

Late postoperativeFBS (mg/dl) 104.9 6 19.2 97.7 6 13.2 0.4329120-min (mg/dl) 289.4 6 104.9a,b 214.0 6 125.7 0.3582

* a, P 5 0.0198; b, P 5 0.0285, FBS, fasting blood sugar, 120-min,oral glucose tolerance test 120-min value.

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1086 Digestive Diseases and Sciences, Vol. 45, No. 6 (June 2000)

104.9 vs 193.0 6 58.2, P 5 0.00198; 289.4 6 104.9vs 184.4 6 76.7, P 5 0.0285). In the 34 patients withIORT, the FBS and 120-min values were not differentbetween the preoperative and early and late postop-erative periods.

The pancreatic juice drainage increased from post-operative day (POD) 0 to POD 5 in both groups andbecame constant thereafter (Figure 1). The totalamount of postoperative pancreatic juice drainagefrom POD 4–13 in the 20 patients with IORT wasabout half that in the 34 without IORT (720.8 6 916.4g vs 1433.8 6 962.1, P 5 0.0128) (Table 3).

The BT-PABA value decreased at the early post-operative period and returned to the preoperativelevel at the late postoperative period irrespective ofthe presence or absence of IORT (Table 4). TheBT-PABA values at the preoperative period and atthe late postoperative period were not significantlydifferent between the 20 patients with IORT and 34without IORT, 61.2 6 22.4 vs 70.0 6 16.3 at thepreoperative period and 67.9 6 19.0 vs 68.4 6 171.1at the late postoperative period). The BT-PABAvalue at the early postoperative period in the 20patients with IORT was 38.0 6 19.8, which was sig-nificantly smaller than 58.7 6 23.5 in the 34 withoutIORT (P 5 0.0027). In the 20 patients with IORT,the BT-PABA levels at the early postoperative periodwas significantly lower than at the preoperative pe-riod and late postoperative periods (38.0 6 19.8 vs61.2 6 22.4, P 5 0.0019, 38.0 6 19.8 vs 67.9 6 19.0,

P 5 0.0015). In the 34 patients without IORT, theBT-PABA value at the early postoperative period wassignificantly lower than at the preoperative period(58.7 6 23.5 vs 70.0 6 16.3, P 5 0.0252).

Univariate and Multivariate Regression AnalysisConcerning Early Postoperative Decline of BT-PABAValue. Univariate regression analysis (Table 5) con-cerning the decline of the BT-PABA values at thepreoperative and postoperative periods using the var-ious factors showed that age, preoperative BT-PABAvalue, ERT, and IORT were significant variants.

Fig 1. Pancreatic juice output from POD 0 to POD 15.

TABLE 3. TOTAL AMOUNT OF PANCREATIC JUICE DRAINAGE INPATIENTS WITH OR WITHOUT IORT FROM POD 4 TO 13

IORT(1) (20) IORT(2) (34) P

Pancreatic juicedrainage (ml/10 days) 720.8 6 916.4 1433.8 6 962.1 0.0128

TABLE 4. PREOPERATIVE, EARLY POSTOPERATIVE, AND LATEPOSTOPERATIVE PANCREATC EXOCRINE FUNCTION WITH OR

WITHOUT IORT*

Period

BT-PABA values (%)

IORT(1) IORT(2) P

Preoperative 61.2 6 22.4a,b 70.0 6 16.3c 0.1039Early postoperative 38.0 6 19.8a 58.7 6 23.5c 0.0027Late postoperative 67.9 6 19.0b 68.4 6 17.1 0.9580

* a, P 5 0.0019; b, P 5 0.0015; c, P 5 0.0252.

TABLE 5. UNIVARIATE ANALYSIS OF DIFFERENCES BETWEENPREOPERATIVE AND EARLY POSTOPERATIVE BT-PABA TEST

CoefficientStandardized

coefficient t P

Age 20.723 20.375 22.832 0.0067Sex 4.538 0.091 0.637 0.5273WBC 21.277 E-4 20.012 20.087 0.9312Hematocrit 20.193 0.841 20.229 0.8199Albumin 24.333 20.073 20.516 0.6083Bilirubin 23.256 20.247 21.782 0.0810Jaundice 28.809 20.153 21.087 0.2825BUN 20.683 20.187 21.332 0.1891Serum amylase 0.001 0.003 0.022 0.9822FBS 0.042 0.072 0.506 0.6149Diabetes mellitus 22.143 20.041 20.290 0.7733Benign/malignant 28.483 20.180 21.278 0.2074Preoperative

BT-PABA20.472 20.354 22.652 0.0107

Diameter of mainpancreatic duct

0.065 0.011 0.079 0.9373

Octreotide 210.074 20.190 21.357 0.1809ASA score 5.994 0.116 0.816 0.4182Operation time 20.037 20.176 21.248 0.2179Operative blood

loss0.001 0.043 0.299 0.7659

Blood transfusion 21.592 20.034 20.236 0.8144IORT 213.789 20.279 22.034 0.0474ERT 218.285 20.336 22.453 0.0175Pancreatic

consistency5.525 0.195 1.391 0.1704

Type of operation 4.250 5.225 0.813 0.4199Anastomosis

organ7.078 0.081 0.566 0.5741

Anastomosis type 3.596 0.106 0.747 0.4588Anastomosis

leakage211.170 20.152 21.079 0.2857



Thereafter, multivariate regression analysis (Table 6)using these four valuables showed that IORT was asignificant independent parameter regarding the dif-ference between preoperative and early postoperativeBT-PABA values.

DISCUSSION

Early and late postoperative effects of IORT on theexocrine and endocrine functions of the remnantpancreas were examined in the 54 Japanese patientswho underwent pancreatic head resection. At thepreoperative and early postoperative periods, theFBS and 75-g OGTT 120-min values were not differ-ent between the two groups with and without IORT.At the late postoperative period, FBS showed nochange, while the 75-g OGTT 120-min value in-creased in both groups. The BT-PABA excretionvalue, which was not different between the twogroups, decreased at the early postoperative period inboth groups. The decline of the BT-PABA value wassignificantly larger in 20 patients with IORT than inthe 34 without IORT. At the late postoperativephase, the BT-PABA values returned to the preoper-ative levels in both groups. Univariate and multivar-iate regression analysis of the decline of the BT-PABA values at the early postoperative periodshowed that IORT was a significant independent de-terminant.

A few previous reports have described the impair-ment of the exocrine pancreatic function at short timeintervals after pancreatic head resection and the re-covery at long time intervals. Tanaka et al (13) re-ported that the BT-PABA test values in 35 patientswho underwent pancreaticoduodenectomy were sig-nificantly reduced two months after operation com-pared to those in a control group. Matsuno et al (14)and Kodama and Tanaka (15), using the BT-PABAtest, also demonstrated exocrine insufficiency shortly(,2 months) after pancreatoduodenectomy. With re-gard to the long-term outcome of the exocrine pan-creatic function, Tanaka et al (13) showed that BT-PABA test results in 13 patients one year after

pancreatoduodenectomy were remarkably improvedcompared to those before and ,2 months after sur-gery. They suggested that postoperative impairmentof the pancreatic exocrine function was transient andreversible. In contrast, Hall et al (16) described fourpatients who required enzyme supplement for a long-term period after pancreatoduodenectomy anddoubted the reversibility of the reduced exocrinefunction. In the present series, the 34 patients withoutIORT showed a decline of the pancreatic exocrinefunction shortly after operation but this returned tothe preoperative level .6 months after the operation,supporting the previous reports (13).

Studies addressing the endocrine pancreatic func-tion after pancreatectomy are few and controversial(17, 18). Kendall et al (17) reported that hemipan-createctomy in healthy organ donors resulted in adeterioration of insulin secretion and abnormal glu-cose tolerance one year after the procedure. Miyataet al (18) also demonstrated the impairment of glu-cose metabolism and insulin secretion after surgery inpatients who underwent radical pancreatoduodenec-tomy. In contrast, patients undergoing pancreatic re-section for malignant diseases actually show a signif-icant improvement in preexisting abnormal glucosemetabolism (19, 20). The present series showed thatthe 34 patients without IORT showed no change inthe pancreatic endocrine function at the early andlate postoperative periods.

Previous studies of the effect of irradiation on theexocrine function of the pancreas have yielded incon-clusive results. In 1952, Rauch and Stenstrom (21)demonstrated a temporary reduction in the volume ofsecretion from a pancreatic fistula following a singleexposure of 400 or 600 R. In 1976, Pieroni et al (22)reported that in dogs that received a dose equivalentto that in patients with Hodgkin’s disease (4000 rad insix weeks), hypersecretion with increased volume butunchanged biocarbonate an enzyme output initiallyoccurred at two weeks. Thereafter, there was progres-sive reduction in volume, bicarbonate, and enzymeoutput (.90%) after three months. An earlier paperby Orndoff et al (23) in 1926 also reported initialhypersecretion followed by reduced secretion. In thepresent study, pancreatic juice output in the IORTgroup was decreased compared to that in the non-IORT group from POD 4 to POD 13 and the pan-creatic exocrine function in the IORT group was alsoreduced much more than in the non-IORT group twomonths after operation. On the other hand, at the latephase, the pancreatic exocrine function in the IORTgroup was similar to that in the non-IORT group. The

TABLE 6. MULTIPLE REGRESSION ANALYSIS OF DIFFERENCE OFPREOPERATIVE AND EARLY POSTOPERATIVE BT-PABA VALUES

CoefficientStandardized

coefficient t P

IORT 219.917 20.408 22.024 0.0485ER 11.622 0.214 1.053 0.2976Age 0.041 0.021 0.248 0.8051Preoperative

BT-PABA20.229 20.186 21.694 0.0966

YAMAGUCHI ET AL


effects of IORT on the pancreatic exocrine functionwere limited to the early postoperative period.

Bagne and Samsami (24) reported that in mas-sive doses of IORT, even a relatively small percent-age of scattered or leakage radiation outside theapplicator could be clinically significant. In addi-tion, we included the resected edge of the pancreaswithin the IORT field. Therefore, IORT may havepossibly enhanced the decline of the exocrine func-tion of the pancreas not only within the irradiatedfield but also outside the field of the applicator. Inthis study, univariate regression analysis showedthat the age, preoperative BT-PABA value, ERT,and IORT were significant parameters in explain-ing the decline of the pancreatic exocrine functionat the early postoperative period. However, multi-ple regression analysis revealed that IORT was theonly significant independent factor.

Nishimura et al (6) reported histopathologic find-ings of the noncancerous pancreas adjacent to thearea irradiated in intraoperative radiotherapy for ad-vanced carcinoma of the pancreas. There was mod-erate to marked atrophy of the glandular cells distin-guished by a sharp line of demarcation from thenonirradiated area. Any extensive destruction of theislet tissue was not detected in the irradiated field, butinterstitial fibrosis was seen in the atrophied glandu-lar tissue. Fibrous thickening of the intima resulted inluminal stenosis of blood vessels. These observationsmight possibly explain the fact that irradiation of theremnant pancreas about 5 cm from the line of pan-creatic transection by IORT, which was included inthe IORT field in this study caused deterioration ofpancreatic exocrine function and decreased pancre-atic juice output at the early postoperative period.The area of the remnant pancreas irradiated by IORTor ERT was not so large that the exocrine pancreaticfunction at the late postoperative period was notdifferent between the two groups.

In conclusion, IORT enhances the decline of thepancreatic exocrine function at the early postopera-tive period of pancreatic head resection. Indication ofIORT for resectable periampullary carcinoma shouldbe reappraised based on the effects on the residualpancreatic function after pancreatectomy as well asthe clinical course of the patients.

REFERENCES

1. The Gastrointestinal Tumor Study Group: Therapy of locallyunresectable pancreatic carcinoma; A randomized comparisonof high dose (6000 rads) radiation alone, moderate dose radi-

ation (4000 rads 1 5-fluorouracil), and high dose radiation 15-fluorouracil. Cancer 48:1705–1710, 1981

2. The Gastrointestinal Tumor Study Group: Treatment of locallyunresectable carcinoma of the pancreas: Comparison of com-bined-modality therapy (chemotherapy plus radiotherapy) tochemotherapy alone. J Natl Cancer Inst 80:751–755, 1988

3. Komaki R, Wilson F, Cox JD, Kline RW: Carcinoma of thepancreas: Results of irradiation for unresectable lesions. Int JRadiat Oncol Biol Phys 6:209–212, 1908

4. Abe M, Takahashi M: Intraoperative radiotherapy: The Japa-nese experience. Int J Radiat Oncol Biol Phys 7:863–868, 1981

5. Castro JR, Woodruff KH, Saunders WM, Lyman JT, QuiveyJM, Twomey P, Chen GT, Frey C, Collier JM, Phillips TL:Clinical problems in radiotherapy of carcinoma of the pan-creas. Am J Clin Oncol 5:579–587, 1982

6. Nishimura A, Nakano M, Otsu H, Nakano K, Iida K, Sakata S,Iwabuchi K, Maruyama K, Kihara M, Okamura T, Todoroki T,Iwasaki Y: Intraoperative radiotherapy for advanced carci-noma of the pancreas. Cancer 54:2375–2384, 1984

7. Shipley WU, Wood WC, Tepper JE, Warshaw AL, Orlow EL,Kaufman D, Battit GE, Nardi GL: Intraoperative electronbeam irradiation for patients with unresectable pancreatic car-cinoma. Ann Surg 200:289–296, 1984

8. Ishikawa O, Ohigashi H, Imaoka S, Teshima T, Inoue T, SasakiY, Iwanaga T, Nakaizumi A: Concomitant benefit of preoper-ative irradiation in preventing pancreas fistula formation afterpancreatoduodenectomy. Arch Surg 126:885–889, 1991

9. Imondi AR, Stradley RP, Wolgemuth R: Synthetic peptides inthe diagnosis of exocrine pancreatic insufficiency in animals.Gut 13:27–32, 1972

10. Lankisch PG: Exocrine pancreatic function tests. Gut 23:777–798, 1982

11. Niederau C, Grendell JH: Diagnosis of chronic pancreatitis.Gastroenterology 26:1257–1262, 1985

12. Alberti KGMM, Hochaday TAR: Diabetes mellitus. In OxfordTextbook of Medicine. DJ Weatherall, YGG Ledingham, DAWarrell (eds). New York; Oxford Medical, 1987

13. Tanaka T, Ichiba Y, Fujii Y, Kodama O, Dohi K: Clinical andexperimental study of pancreatic exocrine function after pan-creaticoduodenectomy for periampullary carcinoma. Surg Gy-necol Obstet 166:200–205, 1988

14. Matsuno S, Tanaka K, Miyashita E, Miyagawa K, Imamura M,Sato T: Pancreatic function and rehabilitation after pancreati-coduodenectomy. Jpn J Surg 18:23–30, 1988

15. Kodama M, Tanaka T: Residual pancreatic exocrine functionbefore and after pancreaticoduodenectomy for periampullarycancer. World J Surg 8:335–339, 1983

16. Hall RI, Rhodes M, Isable-Martinez L, Kelleher J, VenablesCW: Pancreatic exocrine function after a sutureless pancre-atico-jejunostomy following pancreatico-duodenectomy. Br JSurg 77:83–85, 1990

17. Kendall DM, Sutherland DER, Najarian JS, Goetz FC, Rob-ertson RP: Effects of hemipancreatectomy on insulin secretionand glucose metabolism tolerance in healthy humans. N EnglJ Med 322:898–903, 1990

18. Miyata M, Takao T, Okamoto E, Manabe H: An appraisal ofradical pancreatoduodenectomy based on insulin secretion.Am J Surg 133:577–581, 1977

19. Ahren B, Andren-Sandberg A: Capacity to secrete islet hor-mones after subtotal pancreatectomy for pancreatic cancer.Eur J Surg 159:223–227, 1993

20. Permert J, Ihse I, Jorfeldt L, vonSchenk H, Arnquist HJ,



Larsson J: Improves glucose metabolism after subtotal pancre-atectomy for pancreatic cancer. Br J Surg 80:1047–1050, 1993

21. Rauch RF, Stenstrom KW: Effects of x-ray radiation on pan-creatic function in dogs. Gastroenterology 20:595–603, 1952

22. Pieroni PL, Rudick J, Adler M, Nacchiero M, Rybak BJ,Perlberg H, Dreiling DA: Effect of irradiation on the canineexocrine pancreas. Ann Surg 184:610–614, 1976

23. Orndoff BH, Farrell JI, Ivy AC: Studies on the effect ofroentgen rays on glandular activity. V. The effect of roentgenrays on the external pancreatic secretion. Am J Roentgenol16:349–354, 1926

24. Bagne FR, Samsami N: Radiation contamination and leakageasessment of intraoperative electron applicators. J Med Phys15:530–537, 1988

YAMAGUCHI ET AL


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Intraoperative Radiation Enhances Decline of Pancreatic Exocrine Function After Pancreatic Head Resection