Stimulating peristalsis improves esophagogastric junction observation during sedated esophagogastroduodenoscopy in children and adolescents.

Background and study aims: Sedation impairs full visualization of the esophagogastric junction (EGJ) and Z line (the squamocolumnar junction) during esophagogastroduodenoscopy (EGD). The aim of this study was to determine whether induction of esophageal peristalsis could improve the ability to evaluate the Z line in children and adolescents. Patients and methods: Study 1: Consecutive patients (10-15 years) undergoing EGD with propofol or midazolam sedation were enrolled. The proportion of Z line observed was compared between the two groups. Study 2: The effect of an air infusion near the EGJ following deflation of the stomach to induce esophageal peristalsis was investigated in the patients (15-18 years), undergoing EGD with propofol sedation. The proportion of Z line observed was compared between the stimulated group and control group. Results: Study 1: 149 patients were evaluated; 87 received propofol (43 boys; average age 13.2 years (range, 10-15)) and 62 received midazolam (30 boys; average age 12.8 years (range, 10-15)). The proportion of the Z line visualized was low but was greater with propofol vs. midazolam sedation (36.8% vs 16.1%, P=0.0059). Study 2: 102 patients were evaluated; 62 had induction of peristalsis (34 boys; average age 16.2 years (range, 15-18)) and 40 controls (20 boys; average age 16.8 years (range, 15-18)). Complete visualization of the Z line achieved in 95% (59 of 62) following induction of peristalsis vs. 37.5% (15 of 40) of controls (P>0.001). Conclusions: Induction of esophageal peristalsis greatly improved visualization of the Z line during sedated EGD in children and adolescents.

Pedunculated colorectal polyps with heads ≤ 1 cm in diameter can be resected using cold snare polypectomy.

BACKGROUND AND STUDY AIMS: Cold snare polypectomy (CSP) is not recommended for the resection of pedunculated colorectal polyp. The aim of this study was to examine the adequacy of CSP compared to hot snare polypectomy (HSP) for the complete resection of pedunculated polyps with heads ≤ 1 cm in diameter. PATIENTS AND METHODS: This was a retrospective study of a cohort of consecutive outpatients who had resection of pedunculated polyps with heads 6-10 mm in diameter using either dedicated CSP or HSP from 2014 through 2019. The primary outcome measure was occurrence of delayed bleeding. Secondary outcome measures included total procedure time, en bloc resection rate, immediate bleeding, and number of clips used. RESULTS: 415 patients with 444 eligible polyps were enrolled; the CSP group (363 patients; 386 polyps) and HSP group (52 patients; 58 polyps). Patient characteristics, polyp characteristics and en bloc resection rate were similar between groups. The mean total procedure time and mean number (range) of hemostatic clips/ patient used were significantly lower with CSP than with HSP (18± 8 min vs. 25± 9 min, P<0.001; 1.1 ± 0.6 (1-3) vs.3.1 ± 1.6 (1-5), respectively, P<0.001). Delayed bleeding occurred significantly less frequently in the CSP, 0% (0/363 vs.3.8% (2/52) in the HSP group (P<0.001), although immediate bleeding was significantly higher in CSP than HSP (84% (325/386) vs. 12% (7/58), P<0.001). CONCLUSION: Pedunculated colorectal polyps with heads ≤ 1 cm can be removed using CSP, which has several advantages over HSP.

Effectiveness and safety of a new regimen of polyethylene glycol plus ascorbic acid for same-day bowel cleansing in constipated patients.

BACKGROUND AND STUDY AIMS: In an exploratory study we compared a new regimen of low-volume polyethylene glycol plus ascorbic acid (PEG-Asc) with the standard regimen for same-day bowel cleansing in constipated patients. PATIENTS AND METHODS: Between January and June 2015 we studied consecutive patients with constipation (Rome III constipation criteria) scheduled for colonoscopy. The initial group received the standard regimen of PEG-Asc. The subsequent group received the new regimen. The new regimen involved ingestion of 10 mL of sodium picosulfate and 50g of magnesium citrate dissolved in 0.2 L of water followed by 0.2 L of PEG-Asc +0.2 L of water given 6 or 7 times over 3 hours. Bowel cleansing was prospectively evaluated using the Boston bowel preparation scale (BBPS). Bowel cleansing, adenoma detection rates and adverse events were reviewed using electronic medical records and endoscopic filing system. RESULTS: Sixty-two patients used the standard regimen and sixty used the new regimen. The basic characteristics of the two groups were similar. The mean volume of PEG-Asc and total liquid intake was less with the new regimen compared to the standard regimen (1.3 L vs. 2.0 L, P<0.001; 2.6 L vs. 3.0 L, P<0.001). The proportion of patients with a BBPS score ≥ 6 was significantly greater with the new than the standard regimen (93% vs. 76%, P=0.008). Nausea and/or vomiting was also significantly less frequent than with the standard regimen (5% vs. 16%, P=0.046). CONCLUSIONS: The new regimen of PEG-Asc gave improved same-day bowel cleansing for colonoscopy in constipated patients.

Safety and factors contributing to the difficulty of laparoscopic surgery for rectal cancer treated with preoperative chemoradiotherapy.

BACKGROUND: The safety of laparoscopic surgery for rectal cancer following chemoradiotherapy (CRT) has not been fully established. The aim of our retrospective study was to examine the outcomes and the factors contributing to the difficulty of laparoscopic surgery after CRT. METHODS: Eighty-seven consecutive rectal cancer patients treated with CRT were analyzed. Clinicopathological factors were compared between laparoscopic surgery (n = 57) and open surgery (n = 30) groups, and factors that correlated with operation time and blood loss were analyzed in low anterior resection (LAR) cases in the laparoscopic surgery group (n = 46). RESULTS: There was less blood loss in the laparoscopic surgery group than in the open surgery group (191 vs. 1,043 ml, p = 0.0001), and the operation time in the two groups was similar (329 vs. 322 min, p = 0.8). The rate of conversion from laparoscopic surgery to open surgery was 1.8 %. There was no significant difference in the morbidity rate (laparoscopic surgery 22.8 % vs. open surgery 33.3 %, p = 0.3). All circumferential resection margins were clear. Three-year cumulative rates of local recurrence were as follows: laparoscopic surgery: 1.9 % vs. open surgery: 8.4 % (p = 0.4), and distant recurrence was 28.5 % in laparoscopic surgery vs. 22.7 % in open surgery (p = 0.8) and these rates were not significantly different. In laparoscopic LAR cases, a shorter distance of the tumor from the anal verge was associated with a longer operation time. A high computed tomography Hounsfield units value of the mesorectum (CTV) was associated with increased blood loss in the first 23 cases, but not in the other 23 cases. CONCLUSIONS: Laparoscopic surgery following CRT was safe and feasible. A shorter anal verge was associated with a longer operation time. Blood loss increased in cases with high CTV, but this can likely be mitigated by experience.

Colonoscopic enema as rescue for inadequate bowel preparation before colonoscopy: a prospective, observational study.

AIM: Colonoscopy may need to be rescheduled because of inadequate bowel preparation. We evaluated the effectiveness of colonoscopic enema as rescue for an inadequate 1-day bowel preparation before colonoscopy. METHOD: Patients referred for afternoon colonoscopy were prospectively enrolled in the study during a 1-year period. Patients took bowel preparation (polyethylene glycol) solution on the morning of the endoscopy. If during colonoscopy the bowel preparation was poor, an enema of polyethylene glycol solution (500 ml) was instilled into the colon at the level of the hepatic flexure via the biopsy channel of the colonoscope which was then removed. The patient was allowed to recover from the propofol sedation and used the bathroom to evacuate the enema. The colonoscope was then introduced and the examination continued. RESULTS: Of 504 patients undergoing colonoscopy, 26 (4.9%) received an enema. The median age was 59 (29-79) years and 19 (73%) were female. A subsequent successful colonoscopy was achieved in 25/26 (96%). There were no complications. The mean time spent for the entire colonoscopy from the initial preparation to the end of the examination including the enema was 7.6± 1.1h (5.4 h preparation, 0.2h first colonoscopy+enema, 0.66h waiting in the lavatory, 0.33h second colonoscopy and 1 h for recovery). CONCLUSION: Colonoscopic enema was highly successful as rescue for patients with inadequate bowel preparation and avoided postponement of the procedure.

Endoscopic decompression of benign large bowel obstruction using a transanal drainage tube.

AIM: Endoscopic decompression of malignant colorectal obstruction is often dealt with using expandable metallic stents. Endoscopic decompression of benign large bowel obstruction is more difficult. We report the technique and outcome of transanal endoscopic decompression for benign large bowel obstruction. METHOD: From January 2001 to June 2010, endoscopic decompression using a transanal drainage tube placement was attempted in consecutive patients with benign large bowel obstruction. The clinical features, technical success, complications, treatment after the tube placement and clinical success were retrospectively evaluated. RESULTS: There were 13 patients (seven males, age 47-87, mean 69 years). The sites of obstruction were transverse colon [5 (38%)], sigmoid colon [3 (23%)], ileocecal valve [2 (15%)], splenic flexure [1 (8%)], descending colon [1 (8%)] and rectum [1 (8%)]. The most common cause of obstruction was anastomotic stricture [9 (69%)]. In 12 (92%) patients transanal decompression was technically successful with one perforation. An overtube, the reinsertion of colonoscope along the decompression tube, or the use of a small-diameter endoscope was required for the tube placement in seven (54%). In seven (54%) patients tube placement alone resulted in relief of bowel obstruction without operation. CONCLUSION: Endoscopic decompression using a transanal drainage tube is effective for the management of benign large bowel obstruction.

Invasive colorectal cancer within 5 years of negative colonoscopy in a Japanese population.

AIM: Colonoscopy provides imperfect protection against colorectal cancer (CRC). In an attempt to improve cancer detection we evaluated the clinical features of invasive CRC detected within 5 years of a negative colonoscopy. METHOD: The details of colonoscopies performed in a rural hospital in Japan were prospectively recorded at the time of the examination. The patients were followed over 5 years for the subsequent occurrence of cancer. RESULTS: In a 5-year period, 10148 patients underwent colonoscopy and 202 without previous colonoscopy were diagnosed with invasive CRC. Of 3212 patients with a colonoscopy negative for cancer, nine developed invasive cancer within 5 years. The ratios for invasive CRC detected without/with previous colonoscopy were 60:1 in the rectum, 54:1 in the sigmoid colon, 15:1 in the descending colon, 28:0 in the transverse colon, 31:5 in the ascending colon and 14:1 in the caecum (P=0.041). The ratio between left- and right-sided colonic cancer was also significantly different (129:3 and 45:6, P=0.0078). Six (67%) of the invasive CRCs were in the ascending colon or caecum. Five of six patients with invasive CRC in the ascending colon and caecum had right-sided small adenomas at prior colonoscopy. CONCLUSION: The majority of early/missed CRCs were right-sided and associated with prior right-sided colonic adenomas. Repeated colonoscopy of patients with right-sided adenomas at a shorter surveillance interval deserves consideration.

Video capsule retention in a Zenker diverticulum.

We report the case of a video capsule endoscope lodged within a Zenker diverticulum. The system that was equipped with a real-time viewer showed an unchanging image unlike esophageal or gastric mucosa, suggesting that the capsule was elsewhere. The presence of cervical discomfort suggested video capsule retention in a Zenker diverticulum. The capsule was removed endoscopically and reinserted using a hood-assisted endoscope and the procedure was completed.

Two cases of diverticulitis in patients with Williams syndrome.

Williams syndrome is rare and associated with physical anomalies and mental retardation. It is a disease resulting from a gene deletion of chromosome 7. The main concurrent medical conditions typically associated with Williams syndrome are heart defects such as supravalvular aortic stenosis, mental retardation, and unusual physical characteristics. It is also associated with colon diverticulosis and diverticulitis. In the present article, we report on 2 cases of diverticulitis in patients with Williams syndrome, in whom surgery was performed. In many cases of diverticulitis in patients with Williams syndrome, surgical treatment is indicated. It is important to take diverticulitis into consideration when examining a patient with Williams syndrome presenting with abdominal pain and consider surgical treatment if necessary.

A case of fulminant amebic colitis with multiple large intestinal perforations.

Amebic colitis normally causes mucous and bloody diarrhea stool as predominant symptoms, thus leading to a course of chronic colitis. However, though rare, there exists a fulminating type that causes intestinal perforations due to wide necrosis of the large intestine. We encountered a case of fulminant amebic colitis that lead to death due to multiple large intestinal perforations. The patient was a 72-year-old female. The patient was admitted to our hospital with symptoms of fever, abdominal pain, and diarrhea. She continued to have a fever of over 38 degrees C and increased left abdominal pain. An abdominal computed tomography scan revealed free gas on the abdominal side of the kidney. Therefore, gastrointestinal perforations were diagnosed and surgery was performed. In surgery, many perforated parts were observed from the appendix to the descending colon, and subtotal colectomy was performed. However, sepsis and disseminated intravascular coagulation occurred, and the patient died on the eighth postoperative day.

Prospective randomized trial comparing the direct method using a 24 Fr bumper-button-type device with the pull method for percutaneous endoscopic gastrostomy.

BACKGROUND AND STUDY AIMS: Percutaneous endoscopic gastrostomy (PEG) is the preferred route for long-term enteral feeding. The aim of this study was to compare a direct, modified introducer method using a bumper-button-type device with the standard pull method for PEG. PATIENTS AND METHODS: Between October 2005 and January 2007 consecutive patients with dysphagia were randomly assigned to PEG using either the direct method or the pull method. The direct method directly placed a 24 Fr bumper-button-type device assisted by dual gastropexy. The primary outcome measure was the rate of peristomal infections. Secondary measures included success rates, procedure times, and other complications. The long-term outcome measure was the need for catheter change within 180 days of the PEG procedure. RESULTS: Of the 140 patients enrolled, 68 were assigned to the direct method and 72 to the pull method. There were no significant differences between the two groups with respect to clinical baseline parameters. The occurrence of peristomal infection within 30 days was significantly lower following the direct method (0 vs. 6, P = 0.028). The success rates and duration of both methods were similar (100% vs. 100%; 10.5 vs. 9.6 minutes, P = 0.48). The catheters used in the direct method required replacement significantly less often than those placed using the pull method (no catheter change in 180 days: 75% vs. 45.2%, P = 0.0019). CONCLUSIONS: The direct method using a 24 Fr bumper-button-type device was associated with reduced peristomal infections in the early phase and reduced catheter changes compared with a 20 Fr catheter placed using the standard pull method.

Psychiatric, somatic, and gastrointestinal disorders, and Helicobacter pylori infection in children with recurrent abdominal pain.

AIMS: To examine the utility of the Rome II criteria in children with recurrent abdominal pain (RAP) and compare them to those who met Apley's criteria and those who met neither criteria. METHODS: Prospective study in general paediatric clinics in Komagane, Japan. Children with abdominal pain were classified into those who met Rome II criteria, those who met Apley's criteria, and those who met neither. RESULTS: A total of 182 children with RAP participated; 45 children met Rome II criteria, 55 met Apley's criteria, and 82 met neither. Children who met Rome II criteria had a significantly higher prevalence of psychiatric and somatic disorders compared to the group met neither (36% v 6%, 22% v 10%, respectively). The overall prevalence of H pylori was 7%; prevalence increased with age from 3% at age < or = 10 to 10% for children >10 years. Children who met Rome II criteria had a significantly higher prevalence of H pylori infection than the reference group (18% v 4%). In a logistic regression model, all the study variables were included in the model specifying first the Rome II criteria group as the independent variable; psychiatric disorders, H pylori infection, and older age group were independent risk factors. CONCLUSIONS: More than half the children suffering from recurrent abdominal pain met neither Apley's nor Rome II criteria. Children who meet Rome II criteria should be evaluated for psychiatric disorders and should be tested for H pylori infection. Despite the overall trend for a fall in the prevalence of H pylori infection among children in Japan, there are subpopulations of sick children where the prevalence of the infection is relatively high.

Pitavastatin prevents bacterial translocation after nonpulsatile/low-pressure blood flow in early atherosclerotic rat: inhibition of small intestine inducible nitric oxide synthase.

BACKGROUND: Cardiopulmonary bypass decreases intestinal mucosal blood flow because of nonpulsatile and low-pressure blood flow resulting in bacterial translocation (BT) and atherosclerosis also has peripheral blood flow deficiency. The risk of nonpulsatile and low-pressure blood flow for atherosclerotic animals and the effect of statin administration, which has pleiotropic effects, were studied. METHODS: Wistar rats were divided into four groups: group N (normal diet), group C (high-cholesterol diet), group S (group C plus pitavastatin therapy), and group I [group C plus inducible nitric oxide (iNOS) inhibitor therapy]. First of all, vascular responses were measured. Then the rats underwent nonpulsatile/low-pressure blood flow in the intestine, and the serum peptidoglycan concentration as a parameter of BT, the small intestinal PO(2) ratio (intestinal PO(2)/PaO(2)) as a parameter of mucosal blood flow, and NO concentrations were measured before surgery (T0), at the end of 90 min of stenosis (T1), and 90 min after the release of stenosis (T2). Immunostaining for nitrotyrosine was also performed at T2. RESULTS: Group C had vascular endothelial dysfunction without histological changes, which indicated early atherosclerosis. The serum peptidoglycan concentration increased significantly at T2 only in group C. The intestinal PO(2) ratio was decreased at T1 in all the groups, and retuned to baseline at T2 in group N and group S, but not in group C or group I. Jejunal NO only in group C was significantly higher at all time points and ileal NO production at T1 and T2. There tended to be a positive stain for nitrotyrosine along the mucosal epithelium in group C. CONCLUSION: In the setting of early atherosclerosis, intestinal blood flow does not only improve after nonpulsatile/low-pressure blood flow but causes BT because of a large amount of NO from high enzymatic intestinal iNOS activity, and pitavastatin treatment can prevent BT by improving both issues.

[Congenital cystic adenomatoid malformation detected by prenatal sonography; report of 2 cases].

We report 2 cases of congenital cystic adenomatoid malformation (CCAM) detected by prenatal sonography. The first CCAM was diagnosed by fetal sonography in a female fetus at 30 weeks' gestation. The infant was born at 37 weeks' gestation, with a body weight of 2,770 g. After birth, chest computed tomography (CT) showed a multicystic mass in the middle lobe of the lung. She remained asymptomatic until age 21 months, when she suffered pneumonia. Two months later, middle lobectomy was performed. The second CCAM was diagnosed by fetal sonography in a female fetus at 25 weeks' gestation. She was born at 39 weeks' gestation, with a body weight of 3,292 g. Four days after birth, CCAM type II was diagnosed by chest CT. The infant was asymptomatic, and left lower lobectomy was performed 11 months after birth.

Significance of coupling device for vessel anastomosis in esophageal reconstruction.

BACKGROUND/AIMS: To prevent an anastomotic failure due to impaired blood supply, several trials have been performed such as preoperative ischemic conditioning by transarterial embolization of the left gastric, right gastric and splenic arteries or microvascular anastomosis. We assess the significance of an automatic anastomotic coupling device for vessel anastomosis, which we have continuously utilized, to simplify the task and shorten the anastomotic time since March 1999. METHODOLOGY: 8 patients who underwent venous anastomosis by an automatic anastomotic coupling device were evaluated for the time of anastomosis, total ischemic time and outcomes. RESULTS: Venous anastomosis was completed within 5 minutes on average. Microscopic arterial anastomosis by hand took 35 minutes on average. For gastric tube reconstruction, venous anastomosis by an automatic coupling device took only 5 minutes. The top of the gastric tube showed congestion before venous anastomosis, but rapidly recovered from it after anastomosis. Postoperative endoscopic observation of the mucosal color of the replaced intestine or gastric tube was started 3 days after surgery and revealed no ischemia or congestion. The postoperative course was uneventful except one case suffering from pneumonia but leakage was not observed in any case. CONCLUSION: An automatic anastomotic coupling device can perform an easy and reliable vascular anastomosis for patients who undergo esophageal reconstruction. The device may shorten the operating time and consequently the ischemic time of the gastric tube or jejunal or colonic graft, which in turn may lead to a decrease of complications.

Horizontal and vertical distribution of estrogenic activities in sediments and waters from Tokyo Bay, Japan.

Endocrine-disrupting chemicals with estrogenic activity (e.g., alkylphenols) have been detected in coastal Japan. We aimed to determine estrogenic activity in extracts of river water, seawater, sediments, and sediment cores from Tokyo Bay by in vitro gene expression assay. Fifty-one of 57 extracts had some estrogenic activity. E2 equivalents (ng E2 equivalents per gram dry weight or per liter above the limit of detection) in river water samples ranged from 0.70 to 4.01 ng/L; in seawater samples from 0.34 to 2.52 ng/L; and in surface sediments from 2.07 to 12.1 ng/g. The relationship between salinity and estrogenic activity in water samples suggested that fresh water is one source of environmental estrogens in Tokyo Bay. Fractionation of sediment extracts showed that the highest estrogenic activity was observed in the midpolar fraction. The observed activities were compared with activities mediated by known concentrations of nonylphenol, bisphenol-A, estrone, and 17beta-estradiol. In sediment collected near the sewage treatment plants, the estrogenic activity of the midpolar fraction could be explained about 34% by nonylphenol and estrone contained in this fraction. Core sediment measurements detected estrogenic activity from as far back as the 1960s. The regulations on the industrial wastewater in early 1970s would be one of the main reasons for the lower estrogenic activity in the upper section of the sediment core. The high estrogenic activities as measured in water and sediment samples from Tokyo might be restricted to certain coastal areas.

[Lung cancer associated with the right aortic arch; report of a case].

We report a rare case of lung cancer associated with the right aortic arch. A 72-year-old male was admitted to our hospital for surgical treatment of squamous cell carcinoma arising from left B3. The patient had a right aortic arch with the type of mirror-image branching. He underwent a left upper lobectomy and lymph node dissection. We easily resected the lymph nodes in the left side of the upper mediastinum without rotating aortic arch because the aortic arch was positioned on the other side.

Concomitant laparoscopic splenectomy and cholecystectomy as an effective and minimally invasive treatment of pyruvate kinase deficiency with gallstones.

A 4-year-old girl with pyruvate kinase deficiency underwent partial splenic embolization initially. However, even after this procedure, she still had to be transfused every 2 months and then every month. At 5 years of age, she was admitted to our hospital to undergo splenectomy. She underwent laparoscopic splenectomy and concomitant cholecystectomy for gallstones. The hemogram recovered to the normal range after surgery, and her postoperative course was uneventful. Considering the absence of morbidity, the short hospitalization, the quick return to normal activity, the good cosmetic result, and the improved clinical and hematologic results, we consider that simultaneous laparoscopic splenectomy and cholecystectomy is safe and effective for the management of hemolytic anemia resulting from pyruvatre kinase deficiency and associated with cholelithiasis.

Ruthenium-catalyzed hydration of 1-alkynes to give aldehydes: insight into anti-Markovnikov regiochemistry.

The mechanism of the selective conversion of 1-alkynes to aldehydes by hydration was investigated by isolating organic and organometallic byproducts, deuterium-labeling experiments, and DFT calculations. The D-labeled acetylenic hydrogen of 1-alkyne was found exclusively in the formyl group of the resulting aldehydes. After the reaction, the presence of metal-coordinated CO was confirmed. All of the experimental results strongly suggest the involvement of a metal-acyl intermediate with the original acetylenic hydrogen also bound to the metal center as a hydride, with the next step being release of aldehyde by reductive elimination. Theoretical analyses suggest that the first step of the catalytic cycle is not oxidative addition of acetylene C [bond] H or tautomerization of eta(2)-alkyne to a vinylidene complex, but rather protonation of the coordinated 1-alkyne at the substituted carbon to form a metal-vinyl intermediate. This cationic intermediate then isomerizes to Ru(IV)-hydride-vinylidene via alpha-hydride migration of the vinyl group to the metal center, followed by attack of the vinylidene alpha-carbon by OH(-) to give the metal-hydride-acyl intermediate.

Up-regulation of p27Kip1 by progestins is involved in the growth suppression of the normal and malignant human endometrial glandular cells.

Progestins are known to suppress the growth of normal human endometrial glands and endometrial carcinomas possessing PRs. To elucidate the molecular mechanisms of progestin-induced growth inhibition, the expression and functional involvement of p27Kip1 (p27), a cyclin-dependent-kinase inhibitor, was investigated using cultured normal endometrial glandular cells and endometrial carcinoma cell lines (Ishikawa; PR-positive, KLE; PR-negative). Growth of the normal endometrial glandular cells and Ishikawa cells was suppressed by treatment with progesterone and medroxyprogesterone acetate, respectively, in association with an increase in p27 protein expression. Immunoprecipitation revealed that progestins accelerated the complex formation of p27 and cdk2 in both types of cells. However, treatment with progestins did not show any marked alterations in the mRNA expression of p27 in either normal glandular cells or Ishikawa cells. On the other hand, p27 protein degradation experiments indicated that treatment with progesterone and medroxyprogesterone acetate prolonged the degradation time of the normal endometrial glandular cells and Ishikawa cells, respectively. Forced expression of the p27 protein using a p27 expression plasmid reduced the growth activity of normal endometrial glandular cells. These findings suggest that p27 is functionally involved in progestin-induced growth suppression of normal and malignant endometrial epithelial cells and that up-regulation of the p27 protein by progestins possibly occurs via posttranslational mechanisms.