Is curative gastrectomy justified for gastric cancer with cytology positive as the only stage IV factor?

AIMS: The prognosis of patients with gastric cancer and stage IV factors is poor. However, several recent studies have identified that curative surgery followed by S-1 chemotherapy for cytology positive (CY1) only patients contributed to a better prognosis. This study was designed to compare the prognosis between curative and palliative gastrectomy followed by chemotherapy in CY1 only stage IV gastric cancer. METHODS: Between 2001 and 2016, 1507 patients underwent gastrectomy for gastric cancer. Of these, 51 consecutive patients with only CY1 factor who underwent gastrectomy followed by chemotherapy were enrolled in this study. RESULTS: (1) Twenty three (45%) patients underwent curative D2 or D2+ gastrectomy, and the remaining 28 (55%) patients underwent palliative gastrectomy, followed by S-1 based or another historical recommended chemotherapy postoperatively. (2) Compared with patients undergoing palliative gastrectomy, patients undergoing curative gastrectomy had a significantly better prognosis (P = 0.042; median survival time: curative vs. palliative, 22.6 months vs. 11.8 months) and a lower incidence of recurrences (P = 0.091). Two- and five-year overall survival rates of patients following curative gastrectomy were 48.2% and 18.2%, respectively. A multivariate analysis showed that venous invasion [P = 0.006; hazard ratio (HR), 3.70 (95% CI: 1.27-9.43)] and curative gastrectomy [P < 0.005; HR, 0.28 (95% CI: 0.12-0.87)] were independent prognostic factors. CONCLUSION: Curative gastrectomy followed by chemotherapy might be justified to improve the prognosis of patients with only CY1 Stage IV gastric cancer.

Self-expandable Metallic Stents Contribute to Reducing Perioperative Complications in Colorectal Cancer Patients with Acute Obstruction.

BACKGROUND/AIM: The self-expandable metallic stent (SEMS) is an excellent non-invasive tool for emergent bowel obstruction. This study was designed to evaluate the clinical usefulness of the SEMS for avoiding perioperative complications. PATIENTS AND METHODS: We analyzed a total of 47 consecutive patients who had a bowel obstruction due to colorectal cancer at initial diagnosis between 2012 and 2017 from hospital records. RESULTS: Perioperative complications occurred in 30% (14/47) of patients. Univariate and multivariate logistic regression analyses identified an age of more than 75 years [p=0.037, OR=6.84 (95% CI=1.11-41.6)] and the absence of an SEMS treatment [p=0.028, OR=18.5 (95% CI=1.36-250.0)] as independent risk factors for perioperative complications. Pneumonia (12.7% (6/47)) was the most common complication. There were no pneumonia patients (0% (0/15)) who were treated with the SEMS. In contrast to patients with the non-SEMS treatment, 18.7% (6/32) of all patients and 35.7% (5/14) of elderly patients had pneumonia. CONCLUSION: The SEMS is a safe and effective treatment for avoiding perioperative complications, particularly pneumonia, and may be a crucial strategy in elderly patients with acute obstruction due to colorectal cancer.

Diagnostic impact of computed tomography cholangiography and magnetic resonance cholangiopancreatography on pancreaticobiliary maljunction.

BACKGROUND/PURPOSE: The aim of this study was to investigate the diagnostic potential of computed tomography cholangiography (CTC) and magnetic resonance cholangiopancreatography (MRCP) in children with pancreaticobiliary maljunction (PBM). METHODS: Fifty-three children with PBM were consecutively treated between 1997 and 2009. Among them, the patients who underwent CTC and/or MRCP preoperatively were enrolled in this study. Computed tomography cholangiography was examined after infusion of meglumine iodoxamate with subsequent 3-dimensional rendering. The visualization of the biliary and pancreatic duct systems was evaluated and compared with that visualized with MRCP. The findings of direct cholangiography were used as the standard of reference. RESULTS: Of the 53 cases with PBM, 17 cases were examined by CTC, 10 cases by MRCP, and 17 with both. The extrahepatic bile tract was visualized in 32 (94.1%) of 34 patients in CTC and in all 27 patients in MRCP. The intrahepatic bile duct was more frequently demonstrated by MRCP than by CTC (96.3% vs 70.6%, P = .02). Pancreaticobiliary maljunction was noted in 13 (38.2%) of 34 with CTC and in 12 (44.4%) of 27 with MRCP. The minimum age for visualization of PBM was at 10 months in CTC and at 1 year and 11 months in MRCP, respectively. The main pancreatic duct was more frequently visualized by MRCP than by CTC (81.5% vs 8.8%, P < .001). CONCLUSIONS: Magnetic resonance cholangiopancreatography provides superior visualization of the intrahepatic duct and the pancreatic system when compared with CTC. However, it is still challenging to perform a good-quality examination in young infant. The great advantage of CTC is its ability to produce high-quality images without respiratory artifacts and that it allows accurate assessment of the presence of PBM equivalent to MRCP.

Establishment of a rescue program for anorectal malformations induced by retinoic acid in mice.

AIMS OF STUDY: Retinoid-mediated signal transduction plays a crucial role in the embryogenesis of various organs. We previously reported the successful induction of anorectal malformations in mice using retinoic acid (RA). Retinoic acid controls the expression of essential target genes for cell differentiation, morphogenesis, and apoptosis through a complicated interaction in which RA receptors form heterodimers with retinoid X receptors. In the present study, we investigated whether the retinoid antagonist, LE135, could prevent the induction of anorectal malformations (ARMs) in mice. METHODS: Retinoic acid was intraperitoneally administered as 100 mg/kg of all-trans RA on E9; and then the retinoid antagonist, LE135, was intraperitoneally administered to pregnant ICR strain mice on the eighth gestational day (E8), 1 day before administration of RA (group B) or on E9, simultaneously (group C) with RA administration. All of the embryos were obtained from the uteri on E18. Frozen sections were evaluated for concentric layers around the endodermal epithelium by hematoxylin and eosin staining. RESULTS: In group A, all of the embryos demonstrated ARM with rectoprostatic urethral fistula, or rectocloacal fistula, and all of the embryos showed the absence of a tail. In group B, 36% of the embryos could be rescued from ARM. However, all of the rescued embryos had a short tail that was shorter than their hind limb. The ARM rescue rates in group B were significantly improved compared to those in group A (P < .01). In group C, 45% of the embryos were rescued from ARM, but all of the rescued embryos had short tail. The ARM rescue rate in group C was significantly improved compared to that in group A (P < .01). However, there was no significant difference in the ARM rescue rate between group B and Group C. CONCLUSION: The present study provides evidence that in the hindgut region, RAR selective retinoid antagonist, LE135, could rescue embryos from ARM. However, the disturbance of all-trans RA acid was limited to the caudal region. Further study to establish an appropriate rescue program for ARM in a mouse model might suggest a step toward protection against human ARM in the future.

Laparoscopic versus open abdominoperineal rectoplasty for infants with high-type anorectal malformation.

BACKGROUND/PURPOSE: There has not been any study comparing laparoscopic abdominoperineal rectoplasty (ARP) with open ARP. This study investigated the true benefits of the laparoscopic approach in infants with high anorectal malformation. PATIENTS AND METHODS: A retrospective analysis was performed in 28 infants with high anorectal malformation treated between 1990 and 2007. Fifteen were treated by open ARP, and 13 were treated by laparoscopic ARP. Surgical durations, amount of bleeding, complications, anorectal pressure measurements, barium enema study, and clinical assessment were compared between the 2 groups. RESULTS: The amount of intraoperative bleeding was significantly less in laparoscopic ARP (12 ± 11 g) than in open ARP (65 ± 44 g) (P = .003). Anal resting pressure was 34 ± 9 cm H(2)O after laparoscopic ARP and 31 ± 14 cm H(2)O after open ARP. Anorectal reflex was positive in 1 (7%) of 15 after open ARP and 3 (23%) of 13 after laparoscopic ARP. There was no significant difference in barium enema study and clinical assessment between the 2 groups. With regard to postoperative complications, mucosal prolapse occurred in 10 (67%) of 15 after open ARP and in none of 13 after laparoscopic ARP (P = .003). CONCLUSION: Benefits of the laparoscopic approach were reduced intraoperative bleeding and a lower incidence of postoperative anal mucosal prolapse. These results indicate that minimal dissection of the mesorectum in laparoscopic ARP may provide those better outcomes.

Usefulness of magnetic resonance imaging for congenital prepubic fistula.

Congenital prepubic fistula is a rare congenital anomaly. Complete removal of the fistular tract remains challenging because of the complicated course. Although conventional fistulography has been used widely as a diagnostic tool for congenital prepubic fistula, more detailed information such as accurate localization of the fistular end or relative position to the urinary tract cannot be preoperatively obtained because the conventional contrast studies have insufficient capability. In this article, we reported the complete removal of congenital prepubic fistula based on preoperative magnetic resonance imaging findings, especially T2-weighted imaging. Magnetic resonance imaging clearly displayed not only the tract of the prepubic fistula originating from a subcutaneous cyst but also the tract extending and ending near the top of the urinary bladder.

Predicting factors on the occurrence of cystic dilatation of intrahepatic biliary system in biliary atresia.

PURPOSE: Cystic dilatation of intrahepatic biliary system (CDIB) is an intractable complication of biliary atresia (BA). In this study, we investigated the predicting factors of CDIB development after jaundice resolved following hepatoportoenterostomy (HPE). METHODS: From 1988 to 2008, 28 (80.0%) of 35 uncorrectable type of BA patients became jaundice-free after HPE. Of these 28 patients, this retrospective study included comparisons of the preoperative characteristics, postoperative jaundice period, cumulative steroid dose, outcome, and liver fibrosis grade at the time of HPE between CDIB-positive and -negative groups, divided by postoperative ultrasonography findings. RESULTS: There were no differences between groups in perioperative characteristics. Liver fibrosis in the CDIB-positive group (n = 7) included grade II in two patients, grade III in four patients, and grade IV in one patient. On the contrary, the CDIB-negative group (n = 21) included 8, 11, 2, and 0 patients with grades I-IV, respectively, with a significant difference (p < 0.05) between groups. Survival rate with native liver in CDIB-positive group was significantly lower than that in CDIB-negative group (p < 0.05). CONCLUSION: Postoperative CDIB might be a poor prognostic factor, and the liver fibrosis grade at the time of HPE could be helpful to predict the development of CDIB after HPE.

Management strategies for infants with total intestinal aganglionosis.

PURPOSE: This study investigated appropriate management strategies for infants with total intestinal aganglionosis (TIA), focusing on surgical and medical managements. METHODS: Six infants with TIA or near TIA treated in our institution between 1980 and 2007 were reviewed retrospectively. Surgery was performed as a simple jejunostomy, 65 to 70 cm below the ligament of Treitz (LOT) in 2 infants, and 30 cm below LOT in 1 without extended myectomy-myotomy (EMM). Jejunostomy with EMM 30 to 35 cm below LOT were performed in 3. RESULTS: Two infants with jejunostomy 65 cm or 70 cm distal from LOT died of sepsis at 7 months and 8 months of age, respectively. One infant with jejunostomy 30 cm from LOT without EMM died of cholestatic liver failure at the age of 1 year and 8 months. To date, the remaining 3 infants with jejunostomy 30 cm or 35 cm distal from LOT in addition to EMM have survived 10 years, 3 years and 10 months, and 2 years of age, respectively. Nutritional managements such as parenteral nutrition with 80 to 100 kcal/kg/day and oral feeding with elemental diet (ED) were preferable to reduce the occurrence of enteritis, sepsis, and cholestatic liver dysfunction. CONCLUSION: A good combination of cyclic parenteral nutrition and oral intake with elemental diet after short proximal jejunostomy with EMM may be a key for the survival of infants with TIA. In addition, in infants whose absorptive function was not ameliorated by EMM, medical management such as GH administration might be worth trying.

Significance of ductal plate malformation in the postoperative clinical course of biliary atresia.

PURPOSE: Ductal plate malformation (DPM) is one of the etiologic theories for the development of biliary atresia (BA). In this study, we investigated the significance of DPM in the postoperative clinical course of BA, especially as a predictive factor of jaundice clearance. METHODS: Between 1988 and 2005, 31 patients with uncorrectable BA underwent hepatoportoenterostomy and steroid therapy. Immunohistochemistry was used to characterize biliary structures using cytokeratin 19. Specimens were defined as DPM-positive if a concentric cellular arrangement was detected. This retrospective study included comparisons of preoperative characteristics, the postoperative jaundice period, and cumulative steroid doses between patients with and without DPM. RESULTS: Of the 31 patients with uncorrectable BA, 25 (80.6%) became jaundice-free. Ductal plate malformation was detected in 11 (35.5%) of the 31. Between the 2 groups, there were no differences in preoperative characteristics or in the postoperative jaundice-free rate. Among those who became anicteric, the postoperative jaundice period was 145.3 +/- 69.9 days in the DPM-positive group (n = 9) and 81.8 +/- 44.7 days in the DPM-negative group (n = 16) (P < .05). The total administered steroids were 149.7 +/- 78.2 and 95.0 +/- 60.2 mg/kg, respectively (P = .09). CONCLUSION: Ductal plate malformation may disturb bile flow and require more steroid to improve bile drainage. Therefore, the presence of DPM in the liver predicts poor bile flow after hepatoportoenterostomy in infants with BA.

The inv mouse as an experimental model of biliary atresia.

BACKGROUND/PURPOSE: The causation of biliary atresia (BA) remains unclear. However, ductal plate malformation (DPM), maldevelopment of the intrahepatic bile ducts, is 1 of the preferred theories. The inv homozygous mouse (inv mouse), created by insertional mutagenesis, shows situs inversus and jaundice. This study investigated whether the inv mouse could be an experimental model of human BA. METHODS: In the inv mice (n = 12) and wild-type littermates (n = 12), we examined the liver function and morphologic changes in the biliary tract through serum biochemical study and morphological study. RESULTS: The level of serum total and conjugated bilirubin in the inv mouse was 8.1 +/- 3.8 and 4.4 +/- 2.4 mg/dL, respectively, significantly higher than in the wild type. Macroscopically, 11 (92%) of 12 inv mice had situs inversus, and 3 (25%) of 12 mice had preduodenal portal vein. Histologically, the continuity of the extrahepatic bile duct was preserved. However, DPM, showing proliferative biliary epithelium around the intrahepatic portal vein, was found in the liver of the inv mouse. CONCLUSION: In the inv mouse, the pathologic changes in DPM were found in the intrahepatic biliary system, which were observed in some clinical cases of BA. Therefore, the intrahepatic biliary system of the inv mouse could be an experimental model of human BA with DPM.

Clinical significance of the confluence of the cystic duct in patients with anomalous arrangement of the pancreaticobiliary duct.

BACKGROUND/PURPOSE: In anomalous arrangement of the pancreaticobiliary duct (AAPBD), there is anatomical diversity of the cystic duct. In this study, we evaluated the influence of the level of insertion of the cystic duct into the extrahepatic bile duct on the pathophysiology of AAPBD. METHODS: Thirty-two children with AAPBD were examined using cholangiopancreatography. If the cystic duct entered the hepatic duct at the lower middle point of the extrahepatic bile duct, it was defined as low confluence; otherwise, it was considered as high confluence. Clinical details and radiological variables were compared between these 2 groups. RESULTS: Low confluence was noted in 8 of the 32 patients. Seven of the 8 had fusiform-type or nondilatation-type choledochus, and the cystic-type was significantly less frequent than in the high-confluence group. The diameter of the common bile duct was significantly smaller and the main pancreatic duct was significantly greater than in the high-confluence group. Pancreatitis was more common and biliopancreatic reflux on computed tomography combined with intravenous infusion cholangiography was more often seen in the low-confluence group than in the high-confluence group. CONCLUSIONS: Bile juice could regurgitate into the pancreatic duct via the low confluence of the cystic duct, resulting in severe pancreatitis in patients with AAPBD.

Social quality of life for adult patients with anorectal malformations.

BACKGROUND/PURPOSE: Pediatric surgeons who performed the initial surgery on anorectal malformations (ARM) lose contact with the patients as they become adults. In the present study, we examined 20- to 40-year-old adult patients with a history of surgery for ARM and analyzed them from the points of social quality of life. PATIENTS AND METHODS: Twenty-nine patients with ARM, aged 20 to 40, were surveyed by questionnaire or personal interview. Thirteen with high-type and 9 with intermediate-type anomalies underwent abdominoperineal rectoplasty, and 7 with low-type anomalies underwent perineoplasty between 1965 and 1985. Responses were analyzed from the perspectives of bowel, urinary, and sexual functions and social activity. RESULTS: One third of patients with high- or intermediate-type anomalies occasionally complained of fecal soiling. However, the other patients gained good bowel function and enjoyed occupational or student life without problems. Fecal soiling was the key factor disturbing occupational life, although the problem remained within a socially manageable level. All of the patients with ARM had normal urinary function. Three of the 18 male patients had sexual problems such as erectile or ejaculatory dysfunction because of associated genitourinary anomalies. Nine of the 11 female patients had regular menstruation and the other 2 had irregular menstrual periods. Five female patients were married and 4 of the 5 had children (1-5 children). Modes of delivery were normal vaginal delivery in 8 and cesarean section in 1. Only one of the 5 had a slight sacral anomaly. However, she had no apparent abnormality of bladder function and got through pregnancy and delivery without difficulty. CONCLUSION: One third of adult patients with high- or intermediate-type anomalies after abdominoperineal rectoplasty had some problems in bowel function. Fecal soiling was the key factor that disturbed their occupational life. Most of the patients had normal urinary and sexual functions if they did not have associated genitourinary anomalies and enjoyed social activities.

Spontaneous rupture of choledochal cyst with pseudocyst formation-report on 2 cases and literature review.

Spontaneous rupture and subsequent bile peritonitis are rare complications of choledochal cysts. Of these complications, the formation of a biliary pseudocyst is an unusual form, and its preoperative diagnosis is difficult. In this report, we describe 2 cases showing spontaneous rupture with biliary pseudocyst formation. Inflammatory tissue surrounded those pseudocysts, one of which was adjacent to the perforation and the other formed in the transverse mesocolon apart from the biliary tract. These pseudocysts were removed by careful dissection, and single-stage cyst excision with biliary reconstruction was successfully performed in both cases.

Developmental study of tethered spinal cord in murine embryos with anorectal malformations.

BACKGROUND/PURPOSE: Tethered spinal cord is frequently associated with anorectal malformations (ARMs). However, it remains unknown how the tethered spinal cord develops and relates to the severity of ARM. We studied the development of the spinal cord in ARM mouse embryos induced by all-trans retinoic acid (ATRA). METHODS: Pregnant ICR-Slc mice were administered 100 mg/kg of ATRA on the ninth embryonic day (E9.0). Embryonic specimens were obtained from the uteri between E11.0 and E18.5. Midsagittal histologic sections focusing on the spinal cord and pelvis were prepared for immuonhistochemistry specific for neurofilament and Protein Gene Product 9.5 molecules. RESULTS: More than 98% of ATRA-treated embryos demonstrated ARM with rectourethral or rectocloacal fistula. Normal embryos exhibited progressive ascent of the spinal cord from E14.5. However, in ARM embryos, the distal spinal cord ended with meningomyelocelelike or atypical hamartomatous lesions at E11.5 to E13.5, which later caused stretch force that damaged the spinal cord, resulting in tethered cord between E16.0 and E16.5. CONCLUSIONS: In ATRA-induced ARM mouse embryos, tethered spinal cord was mostly established, accompanied by caudal neural maldevelopment, during early fetal development. This experimental model may be useful for researching detailed neuropathologic conditions in ARM children accompanied with tethered spinal cord.

Estrogen receptor expression in anomalous arrangement of the pancreaticobiliary duct.

BACKGROUND/PURPOSE: Anomalous arrangement of the pancreaticobiliary duct (AAPBD) is a malformation of the bile and pancreatic ducts which is commonly associated with congenital biliary dilatation and predominantly occurs in girls. Estrogen receptor (ER) is reported to modulate cholangiocyte proliferation and play a role in tumorigenesis of estrogen-dependent malignancies. The present study investigated the presence of ER in the gallbladder of patients with AAPBD to elucidate whether ER expression is correlated with sexual specificity and biliary histology. METHODS: Specimens comprised samples of 29 gallbladders from patients with AAPBD (21 girls and 8 boys; mean age at surgery, 5.3 years). Medical records were retrospectively reviewed, and sex, age, radiographic parameters, and laboratory data were collected for this study. Immunohistochemistry was performed using anti-ER and anti-MIB-1 antibodies, and MIB-1 score was calculated for evaluation of cell proliferation. RESULTS: ER expression was observed in both the nuclei and cytoplasm of gallbladder epithelium in 12 of 29 specimens. No difference in background characteristics were noted between ER-positive and ER-negative groups. Mucosal hyperplasia was found in 17 specimens. ER-positive cases were significantly more common in AAPBD with mucosal hyperplasia than without (P <0.03). MIB-1 score did not differ significantly between ER-positive and ER-negative groups. CONCLUSIONS: ER expression seems to be related to hyperplastic mucosa of the gallbladder in AAPBD. ER might play a role in the proliferation of gallbladder epithelium.

Impaired expression of myogenic regulatory molecules in the pelvic floor muscles of murine embryos with anorectal malformations.

BACKGROUND/PURPOSE: Recent biological studies have elucidated the molecular mechanism of muscle development, in which various regulatory factors (myogenic regulatory factors [MRFs]) play key roles during embryogenesis. To investigate the development of anorectal malformations (ARMs), we studied MRF expressions in myogenic cells in the pelvic floor using murine embryos affected with ARM. METHODS: Anorectal malformation embryos were obtained from the 10.5th embryonal day (E10.5) to the 7.0th postnatal day (D7.0) in a natural mutant strain (Sd/+, RSV/Le). Serial frozen sections were prepared for immunohistochemistry using specific antibodies to M-cadherin, myoD, Myogenin, myosin heavy chain, and alfa-actin molecule. RESULTS: In normal mice, embryonal caudal somites differentiated into myogenic stem cells and migrated to the pelvic floor between E11.0 and E14.0. In the ARM mice, however, caudal somites were irregularly arranged and MRF expressions in myogenic cells were markedly decreased in the dorsocaudal region at E11.5 to E13.0, leading to hypoplastic pelvic floor muscles. CONCLUSIONS: The maldevelopment of pelvic floor muscles in ARM is derived from a deficient supply of myogenic stem cells, with impaired MRF expression. These results suggest that myogenic stem cells, available from bone marrow contents, may be used for postnatal muscle regeneration to reinforce the pelvic floor muscle function in children with ARM.

Intralobar pulmonary sequestration diagnosed by MR angiography.

A definitive diagnosis of pulmonary sequestration necessitates evidence of a systemic arterial supply to the sequestered lung segment by aortography. We report a case of intralobar pulmonary sequestration in an 11-month-old girl in whom the diagnosis was made by contrast-enhanced magnetic resonance (MR) angiography. Contrast-enhanced MR angiography is the most reliable noninvasive method for the definitive diagnosis of pulmonary sequestration in children.

Mucoepidermal carcinoma of the lung detected by positron emission tomography in a 5-year-old girl.

The authors describe a rare case of mucoepidermal carcinoma of the lung incidentally identified in preoperative assessments for inguinal hernia repair in a 5-year-old girl. This patient was referred for right external inguinal hernia, and a 3.0-cm round-shaped lesion was found in the right lower lung field of a chest x-ray film. She had no respiratory tract complaints, but her serum carcinoembryonic antigen concentration was markedly elevated (21.2 ng/mL). Chest and abdominal computed tomography/magnetic resonance images could not determine the nature of the lesion, but 2-[18 F]fluoro-2-deoxy- d -glucose positron emission tomography (FDG-PET) indicated a malignant tumor pattern. The patient underwent a computed tomography-guided needle biopsy of the lesion (S8), which was soon followed by a right lower pulmonary lobectomy. Histopathology of the resected specimen showed mucoepidermal carcinoma with no regional lymph node metastasis. In childhood asymptomatic pulmonary lesions, it is often difficult to rule out the possibility of malignancy. In the present case, FDG-PET scanning appropriately indicated the therapeutic priority of pediatric thoracic surgery.

Surgical treatment for anomalous arrangement of the pancreaticobiliary duct with nondilatation of the common bile duct.

BACKGROUND/PURPOSE: For anomalous arrangement of the pancreaticobiliary duct (AAPBD) with nondilatation of the common bile duct (CBD), the optimal surgical procedure remains controversial. The authors investigated which procedure would be most effective for AAPBD with nondilatation of the CBD. METHODS: The authors encountered 60 children with AAPBD in our institution between 1979 and 2002. Six of the 60 were classified as the nondilated type (CBD diameter; less than 8 mm), whereas the other 54 were classified as the dilated type (CBD diameter; more than 9 mm). Amylase levels in serum, CBD, and gallbladder were examined. Cellular activity of the resected gallbladder was examined for the incidence of hyperplasia and Ki-67 labeling index (Ki-67 LI). RESULTS: The amylase level in the nondilated type was elevated as in the dilated type. Epithelial hyperplasia of the gallbladder was present in 4 of the 6 with the nondilated type (67%). 10 of the 20 with the dilated type (50%), and none of the 6 controls (0%). The Ki-67 LI of the dilated type was significantly higher than that of control. CONCLUSIONS: A free reflux of pancreatic juice into the biliary system was found regardless of dilatation, and cellular proliferative activity of the gallbladder mucosa was increased in both the nondilated and dilated type. Therefore, excision of the extrahepatic bile duct including cholecystectomy is recommended for AAPBD with nondilatation of the CBD.