Prevalence of Double Incontinence and Lower Urinary Tract Symptoms in Patients with Fecal Incontinence: A Single-center Observational Study.

Objectives: Double incontinence (DI), which is the co-occurrence of fecal incontinence (FI) and urinary incontinence (UI), increases with age and has a greater negative impact on the quality of life (QOL) than either incontinence alone. We aimed to assess lower urinary tract symptoms (LUTS) in patients with FI to elucidate the prevalence and characteristics of DI. Methods: This study enrolled consecutive patients who visited our hospital with FI symptoms. FI was evaluated using the Cleveland Clinic Florida Fecal Incontinence Score (CCFIS). LUTS were assessed using the International Prostate Symptom Score (IPSS), QOL score (IPSS-QOL) and Overactive Bladder Symptom Score (OABSS). Results: This study evaluated 140 patients (96 women [mean age: 70.7 years] and 44 men [mean age: 74.4 years]). The mean IPSS was significantly higher in men than in women (12.0 vs. 7.5, p = 0.003). A positive correlation was found between IPSS and CCFIS in women (r = 0.256, p = 0.012) but not in men. For both sexes, the older group (aged ≥70 years) had higher OABSS scores and more urge UI instances than the younger group (aged ≤69 years). Of the 140 patients with FI, 78 (55.7%) had DI, and DI was more common in women than in men (63.5% vs. 38.6%, p = 0.006). Conclusions: The characteristics of LUTS and UI in patients with FI were comparable to those in the general population for both sexes; however, the prevalence of DI was much higher among patients with FI than that in the general population.

Long-term Efficacy and Safety of Controlled Manual Anal Dilatation in the Treatment of Chronic Anal Fissures: A Single-center Observational Study.

Objectives: Conventional anal dilatation for anal fissures has long been abandoned because of the high incidence of anal incontinence. However, less invasive and more precise dilation techniques have been developed that have shown high healing and low incontinence rates. This study aimed to evaluate the efficacy and safety of controlled anal dilatation (CAD) using a standardized maximum anal diameter. Methods: This study included 523 patients who underwent CAD for chronic anal fissures between January 2010 and December 2014. CAD was performed under sacral epidural anesthesia. The index fingers of both hands were placed in the anus and dilated evenly in various directions. CAD was completed when the anus was dilated to the sixth scale (35 mm in diameter) using a caliber ruler. Results: The mean anal scale size expanded from 3.1 to 5.8 (p<0.001). Non-healing was observed in nine patients (1.7%) at 1 month postoperatively, six of whom underwent additional CAD. The mean maximal anal resting pressure (mmHg) decreased from 90.2 to 79.7 at three months postoperatively (p<0.001). Postoperative complications were observed in 11 (2.1%) patients, of whom three patients with thrombosed hemorrhoids underwent resection. None of the patients complained of anal incontinence during the mean follow-up period of 16.6 months. The cumulative recurrence-free rates at three and five years were 87.9% and 69.2%, respectively. Conclusions: CAD is technically simple and safe and can achieve reasonable long-term outcomes. Thus, CAD appears to be the preferred procedure for patients with chronic anal fissures who do not respond to conservative treatments.

Are There Sex Differences in Defecation Patterns in Patients with Defecation Disorders? - A Single-center Observational Study.

Objectives: Defecation disorders (DD) are characterized by impaired rectal evacuation due to inadequate defecatory propulsion and/or dyssynergic defecation. DD are assessed by rectal and anal pressures during attempted defecation using anorectal manometry (ARM). Thus far, at least four types of dyssynergic patterns have been recognized on ARM. This study aimed to compare the manometric parameters and dyssynergic patterns between men and women with DD. Methods: This study enrolled consecutive patients undergoing anorectal tests for symptoms of DD. Anorectal pressure was measured using a waveform ARM system. DD were diagnosed based on the results of ARM, balloon expulsion tests, and barium defecography. Dyssynergic patterns were defined as a paradoxical increase in anal pressure with (type I) or without (type II) an adequate increase in rectal pressure and failure of a reduction in anal pressure with (type III) or without (type IV) an adequate increase in rectal pressure. Results: This study evaluated 324 women and 234 men. Based on anorectal tests, 73.1% men and 54.6% women were diagnosed with DD. Rectal and anal pressures during attempted defecation in patients with DD were significantly higher in men than in women. Type I patterns were more common in men (64.9%) than in women (28.2%). Conversely, type II (42.9% vs. 24.0%) and IV (20.9% vs. 5.8%) patterns were observed more frequently in women than in men. Conclusions: Men were more likely to experience dyssynergic defecation whereas women were more likely to experience inadequate defecatory propulsion. However, future studies are warranted to confirm these results.

Effects of Age and Sex on the Anorectal Sensory Threshold to Electrical Stimulation: A Single-center Observational Study.

Objectives: Anorectal sensation is an essential component for maintaining normal defecation and continence. This study aimed to investigate changes in anorectal sensation with age and sex using the anorectal sensory threshold to electrical stimulation in a large population with a broad age spectrum. Methods: This study enrolled consecutive adult patients (20-89 years old) who underwent anorectal physiology tests to screen for functional or organic anorectal disease. Anorectal sensitivity was measured using an endoanal electrode with a 45-mm long bipolar needle. A constant electrical current was delivered to the lower end of the rectum and the anal canal. The minimum current in milliamperes at which the initial sensation was felt was defined as the sensory threshold. Results: Overall, 888 patients were included in this study. The most frequent comorbidities were constipation and hemorrhoids. The median sensory threshold for all patients was 0.5 (interquartile range, 0.2-1.5) mA, and the overall sensory threshold was significantly higher in men than in women. The 95% confidence interval of the sensory threshold for men and women were 0.1-6.8 and 0.1-5.1 mA, respectively. The sensory threshold increased significantly with age in both sexes (men, r = 0.384; women, r = 0.410). There was no sex difference in the sensory threshold between ages 20 and 40 years; however, between ages 50 and 70 years, men had a higher sensory threshold than women. Conclusions: The anorectal sensory threshold to electrical stimulation increased with age, and the influence of aging was more significant in men than in women.

Efficacy and safety of anal encirclement combining the Leeds-Keio artificial ligament with injection sclerotherapy using aluminum potassium sulfate and tannic acid in the management of rectal prolapse: a single-center observational study.

PURPOSE: Perineal procedures are an important surgical option for frail and high-risk patients with rectal prolapse. This study aimed to evaluate the efficacy and safety of combined therapy using injection sclerotherapy, with aluminum potassium sulfate and tannic acid (ALTA), and the Thiersch procedure, using the Leeds-Keio ligament (ALTA-Thiersch). METHODS: This study included 106 consecutive patients (mean age, 81.2 years) who underwent ALTA-Thiersch for rectal prolapse. The procedure was performed under caudal epidural anesthesia. ALTA was injected into the submucosa from the tip of the prolapsed rectum down to the dentate line, circumferentially, at 20 to 40 locations. The ligament tape was placed outside the external sphincter muscle and at an approximate depth of 2 cm into the middle anal canal. RESULTS: Of 106 patients, rectal prolapse was cured shortly after surgery in 105 patients. An additional tape was inserted in 1 patient who had persistent prolapse. Postoperative complications were observed in 27 patients (25.5%). Fecal impaction occurred in 12 patients; however, since it was temporary, no tape removal was required. Of the 12 cases in which the tape was infected or exposed, 11 required tape removal. There were 18 cases of recurrence at a mean follow-up of 22.1 months. Cumulative recurrence rates at 3 and 5 years were 21.3% and 38.6%, respectively. CONCLUSION: ALTA-Thiersch is a simple and safe procedure for rectal prolapse, having reasonable outcomes. The use of the Leeds-Keio ligament for anal encircling can help compensate for the disadvantages of the Thiersch operation.

Simple Anal Reinforcement with Anal Encirclement Using an Artificial Ligament in Patients with fecal Incontinence: A Single-center Observational Study.

Objectives: Surgical repair of anal sphincter defects in patients with fecal incontinence (FI) has been associated with excellent or good short-term results; however, its benefits have been shown to deteriorate over long-term follow-up. When sphincteroplasty fails or is not feasible, the subsequent surgical options are limited. This study aimed to evaluate the efficacy of anal encirclement using the Leeds-Keio ligament in patients with FI. Methods: The inclusion criteria for the procedure were failure of or unsuitability for sphincteroplasty and the presence of a patulous anus (diameter, ≥35 mm). The artificial ligament was routed outside the external anal sphincter at the depth of the middle anal canal under caudal epidural anesthesia. Results: Fourteen patients (mean age, 79.4 years; 8 females) with FI were included. Of these, seven (50%) showed a ≥50% reduction in the Cleveland Clinic Florida Fecal Incontinence Score (CCFIS). The mean CCFIS of 13.6 at baseline significantly improved to 7.9 3 months after surgery. The mean maximal anal resting pressure significantly increased from 16.8 mmHg to 22.6 mmHg. Postoperatively, temporary fecal impaction was observed in one patient (7%). None of the cases required removal of the artificial ligament or additional operative interventions for FI during the mean follow-up period of 31.9 months. Conclusions: Anal encirclement using the Leeds-Keio ligament was technically simple and safe and achieved good short-term outcomes. Therefore, this technique appears to be a simple solution for sphincter defects and may become an important surgical option for patients with FI and a patulous anus.

Long-term Outcomes of Aluminum Potassium Sulfate and Tannic Acid Sclerotherapy for Prolapsed Hemorrhoids: A Single-Center, Observational Study.

BACKGROUND: Aluminum potassium sulfate and tannic acid sclerotherapy for hemorrhoids produced almost the same effects as excisional hemorrhoidectomy. However, its long-term effectiveness remains unknown. OBJECTIVE: The purpose of this study was to investigate the long-term results of sclerotherapy using aluminum potassium sulfate and tannic acid for treating prolapsed hemorrhoids. DESIGN: This was a retrospective review of a single-institution experience. SETTINGS: This study was conducted within a coloproctology unit at a community-based hospital. PATIENTS: In total, 1180 patients with grade II to IV hemorrhoids treated with injection sclerotherapy were enrolled. MAIN OUTCOME MEASURES: Efficacy measures included cumulative recurrence rates and postoperative complications. RESULTS: Recurrence rates at 3, 6, and 9 years were 7.4%, 27.2%, and 47.5%. Postoperative complications included fever ≥38°C in 16 (1.4%) patients, rectal ulcer in 10 (0.9%) patients, rectal stricture in 5 (0.4%) patients, and perianal abscess in 4 (0.3%) patients. LIMITATIONS: This was a retrospective, nonrandomized, single-center study. In addition, office visits after 3 years were optional and the number of follow-ups steadily decreased. CONCLUSIONS: Sclerotherapy using aluminum potassium sulfate and tannic acid offers reasonable long-term results and is associated with low complication rates. Therefore, it seems to be an attractive alternative for patients with prolapsed hemorrhoids. See Video Abstract at http://links.lww.com/DCR/B733.RESULTADOS A LARGO PLAZO DE LA ESCLEROTERAPIA CON SULFATO DE ALUMINIO Y POTASIO, Y ÁCIDO TÁNICO PARA LAS HEMORROIDES PROLAPSADAS: ESTUDIO OBSERVACIONAL DE UN SOLO CENTRO. ANTECEDENTES: La escleroterapia con sulfato de aluminio y potasio, y ácido tánico para las hemorroides produjo casi los mismos efectos que la hemorroidectomía por escisión. Sin embargo, se desconoce su eficacia a largo plazo. OBJETIVO: El propósito de este estudio fue investigar los resultados a largo plazo de la escleroterapia con sulfato de aluminio y potasio, y ácido tánico para tratar las hemorroides prolapsadas. DISEO: Revisión retrospectiva de la experiencia de una sola institución. ENTORNO CLINICO: Este estudio se realizó dentro de una unidad de coloproctología en un hospital comunitario. PACIENTES: En total, 1.180 pacientes fueron inscritos con hemorroides grado II a IV tratados con inyecciones esclerosantes. PRINCIPALES MEDIDAS DE VALORACION: Las medidas de eficacia incluyeron tasas acumulativas de recurrencia y complicaciones posoperatorias. RESULTADOS: La tasa de recurrencia a los 3, 6 y 9 años fue del 7,4%, 27,2% y 47,5%, respectivamente. Las complicaciones posoperatorias incluyeron fiebre ≥ 38 grados Celsius en 16 pacientes (1,4%), úlcera rectal en 10 (0,9%), estenosis rectal en 5 (0,4%) y absceso perianal en 4 (0,3%) pacientes. LIMITACIONES: Este fue un estudio retrospectivo, no aleatorio, de un solo centro. Adicionalmente, las visitas al consultorio después de 3 años eran opcionales y el número de seguimientos disminuyó constantemente. CONCLUSIONES: La escleroterapia con sulfato de aluminio y potasio, y ácido tánico ofrece resultados razonables a largo plazo y está asociada con bajas tasas de complicaciones. Por tanto, parece ser una alternativa atractiva para pacientes con hemorroides prolapsadas. Consulte Video Resumen en http://links.lww.com/DCR/B733. (Traducción- Dr. Francisco M. Abarca-Rendon).

Injection of aluminum potassium sulfate and tannic acid in the treatment of fecal incontinence: a single-center observational study.

PURPOSE: Perianal injection of bulking agents is an attractive treatment option for patients with mild to moderate fecal incontinence (FI). Various bulking agents have been used for injection therapy, but the optimal injection materials and methods are yet to be standardized. This study aimed to evaluate the effects of injection therapy using aluminum potassium sulfate and tannic acid (ALTA) in the management of FI. METHODS: This study included consecutive patients who underwent ALTA injection therapy for FI at our institution. The procedure was performed with the patient in the jackknife position, under caudal epidural anesthesia. The procedure consisted of a 4-step injection to the 3 main cushions and a multipoint injection to the remaining submucosa of the anal canal. RESULTS: Seventy-seven patients (mean age, 76 years) were enrolled in the study. The mean Cleveland Clinic incontinence score of 11.9 ± 4.1 at baseline significantly improved to 7.3 ± 5.2 at 3 months following treatment. The mean maximal resting pressure also increased significantly 3 months after the intervention. Postoperative complications were observed in 3 patients (3.9%), and all events were mild. The mean duration of postoperative follow-up was 17.5 months. The cumulative recurrence-free rate at 3 years was 72.4%. CONCLUSION: ALTA injection for FI is safe, easy to perform, and provides reasonable mid-term outcomes. Moreover, concomitant anorectal diseases that may be contraindicated by other injectable bulking agents could be treated simultaneously. Therefore, ALTA injection is a promising alternative in the absence of other injectable agents.

Tolerance and Efficacy of Polyethylene Glycol 4000 in Elderly Patients with Chronic Constipation: A Retrospective, Single-center, Observational Study.

OBJECTIVES: This retrospective, observational study aimed to evaluate the tolerance and efficacy of polyethylene glycol 4000 plus electrolytes (PEG 4000) in elderly patients with chronic constipation. METHODS: PEG 4000 powder was orally administered once daily at a dose of one or two 6.9 g sachets as the initial dose. The outcome measures were changes in the Cleveland Clinic Constipation Score (CCCS) and the Bristol Stool Form Scale (BSFS) value before and 2 weeks after drug administration. RESULTS: This study included 324 patients aged ≥65 years (mean age: 78.6 ± 7.6 years, range: 65-100 years) with chronic constipation. The total CCCS was noted to significantly improve from 11.5 ± 4.6 at baseline to 7.4 ± 5.2 after drug administration. All CCCS sub-scores also improved significantly. The average BSFS value at baseline (2.5 ± 1.6) significantly improved to 4.3 ± 1.1 after treatment. Side effects (16 events) were observed in 13 patients (4.0%), with the most common being diarrhea (6 patients, 1.9%). All events were mild in severity, with none of the symptoms being serious. The cumulative treatment continuation rate at 1 year was 83.1%. CONCLUSIONS: PEG 4000 treatment was safe, effective, and well tolerated in elderly patients with chronic constipation. Thus, it appears to be a promising drug that can be continued for a long time.

Rectosigmoid Localization of Radiopaque Markers for Identifying Defecation Disorders in Patients With Chronic Constipation: A Retrospective Cohort Study.

BACKGROUND/AIMS: Defecation disorders (DD) are part of the spectrum of chronic constipation with outlet obstruction. Although anorectal physiologic tests are required for the diagnosis of DD, these tests are not available in many institutions. This study aims to investigate the predictivity of DD using rectosigmoid localization of radiopaque markers in a colonic transit study. METHODS: A total of 169 patients with refractory constipation with a mean age of 67 years were studied. All patients underwent anorectal manometry, a balloon expulsion test, and a colonic transit study. Barium defecography was performed if needed. The relationship between DD diagnosed by these anorectal tests and the rectosigmoid accumulation of markers was examined. RESULTS: Seventy-nine (46.7%) patients were identified to have DD based on anorectal test combinations. Rectosigmoid accumulation of markers was observed in 39 (23.1%) patients. The sensitivity and positive predictive value of rectosigmoid accumulation for identifying DD were 31.6% and 64.1%, respectively. Rectosigmoid accumulation provided poor discrimination of DD from normal transit constipation, at a specificity of 82.1% but with a sensitivity of only 10.6%. In discriminating DD from slow transit constipation, rectosigmoid accumulation was found to be useful with a positive likelihood ratio of 5.3. CONCLUSION: s Rectosigmoid accumulation of markers can differentiate DD from slow transit constipation. However, non-rectosigmoid accumulation does not exclude the presence of DD.

Efficacy and Safety of Elobixibat in Elderly Patients with Chronic Constipation: A Single-center, Observational Study.

OBJECTIVES: A retrospective, observational study was conducted to examine the efficacy and safety of elobixibat, a novel therapeutic agent for chronic constipation, in Japanese elderly patients aged ≥ 65 years with chronic constipation. METHODS: The study was conducted at Kunimoto Hospital. Patients who visited the hospital from April 2018 to March 2019 due to symptoms of chronic constipation and who took elobixibat were enrolled. The outcome measures were changes in the Constipation Scoring System (CSS) score and the Bristol stool form scale (BSFS) before and after elobixibat administration. RESULTS: The study included 150 patients. The total CSS score significantly improved from 11.7±4.5 at baseline to 9.3±5.2 two weeks after drug administration. The improvement was confirmed in six out of eight CSS items. The BSFS at baseline of 2.5±1.8 was improved to 3.4±1.7 two weeks after treatment, nearly close to the normal stool consistency of 4. Adverse reactions were observed in 18 of 150 patients (12.0%) with 21 events, most commonly diarrhea in nine patients (6.0%) and abdominal pain in eight patients (5.3%). CONCLUSIONS: Elobixibat improved not only the frequency of bowel movements but also alleviated various symptoms of constipation, such as difficulty with evacuation and sensations of incomplete evacuation in elderly patients with chronic constipation. All adverse drug reactions were mild in severity with no safety concerns.

Clinical efficacy of Japanese herbal medicine daikenchuto in the management of fecal incontinence: A single-center, observational study.

OBJECTIVES: The purpose of this study was to investigate whether the symptoms of fecal incontinence (FI) or anal sphincter dysfunction are improved by daikenchuto (DKT). METHODS: This is a retrospective observational study that analyzes the effects of DKT. The study was conducted at Kunimoto Hospital. Patients who visited the hospital from January 2012 to December 2016 due to symptoms of FI with a certain degree of chronic constipation and who took DKT were enrolled. The drug to be evaluated was "Tsumura Daikenchuto Extract Granules for Ethical Use (TJ-100)" manufactured by Tsumura & Co., Tokyo, Japan. The primary outcome measures were changes in the scores of the Cleveland Clinic Incontinence Score (CCIS) and Constipation Scoring System (CSS) before and after the administration of DKT. RESULTS: A total of 157 patients were enrolled. On the CCIS, "leakage of solid stool," "leakage of liquid stool," "pad use," and "total score" were significantly improved. On the contrary, on the CSS, the score of "type of assistance" was significantly improved after the administration of DKT, but no significant difference was found in the total score. On the Bristol Stool Form Scale, the administration of DKT showed a tendency to normalize stool consistency. Maximum resting anal pressure and maximum squeeze anal pressure significantly increased after the administration of DKT. No side effects caused by DKT were observed during the study. CONCLUSIONS: DKT appears to be a safe and useful agent for the management of FI in patients with defecation disorders and internal anal sphincter dysfunction.

Progressive fibrosis significantly correlates with hepatocellular carcinoma in patients with a sustained virological response.

AIM: Hepatocellular carcinoma develops even in some patients who achieve a sustained virological response following treatment for hepatitis C virus infection. This study investigated the relationship between changes in fibrosis, as assessed by sequential biopsies, and development of hepatocellular carcinoma in patients who achieved a sustained virological response for hepatitis C virus. METHODS: We enrolled 97 patients with sustained virological response who had undergone initial biopsies before therapy and sequential biopsies at an average of 5.8 ± 1.9 years after the initial biopsy. Factors associated with hepatocellular carcinoma were retrospectively analyzed. RESULTS: The liver fibrotic stage regressed in 44 patients (45%), remained stable in 47 patients (48%) and progressed in six patients (6%). The fibrotic stage significantly decreased, from 1.54 ± 0.86 to 1.16 ± 1.07 units. Hepatocellular carcinoma was identified in 12 patients (12.4%). The cumulative incidence of hepatocellular carcinoma in patients with progressive fibrosis was significantly higher than that in patients with regressed or stable fibrosis (P < 0.001). A Cox proportional hazards regression analysis confirmed that progressive fibrosis in sequential liver biopsies (hazard ratio [HR], 8.30; P = 0.001) and low platelet counts before treatment (HR, 8.69; P = 0.006) were significant independent factors associated with the development of hepatocellular carcinoma in patients with a sustained virological response. CONCLUSION: Progressive fibrosis, assessed by sequential biopsies, was significantly correlated with development of hepatocellular carcinoma in patients who had achieved a sustained virological response for hepatitis C virus.

Involvement of Girdin in the determination of cell polarity during cell migration.

Cell migration is a critical cellular process that determines embryonic development and the progression of human diseases. Therefore, cell- or context-specific mechanisms by which multiple promigratory proteins differentially regulate cell migration must be analyzed in detail. Girdin (girders of actin filaments) (also termed GIV, Gα-interacting vesicle associated protein) is an actin-binding protein that regulates migration of various cells such as endothelial cells, smooth muscle cells, neuroblasts, and cancer cells. Here we show that Girdin regulates the establishment of cell polarity, the deregulation of which may result in the disruption of directional cell migration. We found that Girdin interacts with Par-3, a scaffolding protein that is a component of the Par protein complex that has an established role in determining cell polarity. RNA interference-mediated depletion of Girdin leads to impaired polarization of fibroblasts and mammary epithelial cells in a way similar to that observed in Par-3-depleted cells. Accordingly, the expression of Par-3 mutants unable to interact with Girdin abrogates cell polarization in fibroblasts. Further biochemical analysis suggests that Girdin is present in the Par protein complex that includes Par-3, Par-6, and atypical protein kinase C. Considering previous reports showing the role of Girdin in the directional migration of neuroblasts, network formation of endothelial cells, and cancer invasion, these data may provide a specific mechanism by which Girdin regulates cell movement in biological contexts that require directional cell movement.

Safeguards against acute pancreatitis associated with endoscopic papillary balloon dilatation.

BACKGROUND/PURPOSE: Endoscopic papillary balloon dilatation (EPBD) is one of the methods used to remove bile duct stones. EPBD may preserve the function of the sphincter of Oddi in spite of the potential risk of acute pancreatitis caused by the procedure. There are only few reports of attempts to reduce the risk of acute pancreatitis in EPBD. METHODS: We performed EPBD for bile duct stone removal in 201 patients. We used an 8-mm balloon followed by drip infusion of isosorbide dinitrate (ISDN) at a rate of 5 mg/h for low-pressure EPBD. The function of the minor duodenal papilla, the inflation pressure required for the disappearance of the notch sign in the bile duct, and the serum amylase level after EPBD were observed. RESULTS: The median serum amylase level after the procedure was 367 IU/l. Acute pancreatitis occurred in two patients (1.0%). The two patients with acute pancreatitis had poor function of the minor duodenal papilla, a high inflation pressure (over 5 atm) required for disappearance of the notch, sign, and severe abdominal pain during balloon inflation; as well, the procedure took a long time. The rate of duct clearance was 99.5%. CONCLUSIONS: EPBD with gradual inflation of the balloon at a low pressure, followed by ISDN drip infusion, could decrease the risk of acute pancreatitis associated with the procedure. Poor function of the minor duodenal papilla, high inflation pressure required for disappearance of the notch, sign, severe abdominal pain, and a lengthy procedure increase the risk of acute pancreatitis after EPBD.

Two cases of partial trisomy 21 (pter-q22.1) without the major features of Down syndrome.

We report two cases of partial trisomy 21 with clinical features distinct from Down syndrome (DS). These patients presented with moderate mental retardation and short stature, but the typical facial appearance of DS was not observed. Each patient had a similarly sized extra chromosome 21. We performed FISH analysis to examine whether deletions of reported approximately 5 Mb DS critical region (DSCR) might be associated with unusual clinical features in these cases. The results showed that each of their extra chromosomes 21 contained a distal part of chromosome 3p or 14q at the telomeric region of chromosome 21q. The translocation breakpoint of 21q for each patient was located on the centromeric side of DSCR (DSCR was deleted) and the sizes of partial trisomy 21 in respective patients are approximately 34.5 (21pter-q22.12) and approximately 33.0 Mb (21pter-q22.11). In one patient, the additional region of the short arm of chromosome 3 was 3pter-p26.1 from maternal origin, measuring approximately 9 Mb in size. The second patient had an extra 14q32.1-qter of maternal origin, measuring approximately 14 Mb in size. These are one of the shortest partial distal trisomy among reported cases. Taken together, two patients with partial trisomy 21 lack all of DSCR on 21q22, and their distinct clinical features are likely caused by the genes located at 21pter-q22.1 and the distal part of chromosome 3p or 14q.

[A case report of advanced cardiac cancer showing a complete response to TS-1 as neoadjuvant chemotherapy].

A 69-year-old female had complaints of vomiting, appetite loss and feeling of pharyngeal obstruction. She was diagnosed with a 3'-shaped advanced cardiac cancer with esophageal invasion. A biopsy revealed poorly differentiated adenocarcinoma. The tumor was T3 (SE) N2, Stage IIIB indicating a poor prognosis. After informed consent, TS-1 was administrated as preoperative chemotherapy. Chemotherapy with TS-1 was very effective, and the tumor noticeably decreased. Next, total gastrectomy was performed. Histopathological findings revealed that the primary tumor and lymph node had become scarred and fibrous, indicating a complete response (Grade 3). In the future, TS-1 can be expected to display efficacy in neoadjuvant chemotherapy for patients with advanced gastric cancer who have poor prognoses.

Acetic acid-derived prostaglandin-dependent colonic adaptive cytoprotection is preserved in chronic colitis: role of cyclo-oxygenase.

BACKGROUND AND AIMS: We recently reported the phenomenon of prostaglandin-dependent colonic adaptive cytoprotection (CAP) against acute colonic injury induced by acetic acid (AA) in the normal colon. This study investigated whether the CAP is preserved in the chronic inflamed colon. MATERIALS AND METHODS: Normal rats and a chronic colitis model, induced by trinitrobenzene sulfonic acid, received an intracolonal administration (0.5 ml) of saline or AA at low concentration (1%) followed by high concentration (8%) 30 min later. The distal colon was removed 48 h after 8% AA administration, and colitis was assessed by macroscopic scoring and measurement of the myeloperoxidase (MPO) activity. Indomethacin (5 mg/kg), a nonselective cyclo-oxygenase (COX) inhibitor, or N-[2-cyclohexyloxy-4-nitrophenyl] methane-sulfonamide (NS398, 1 mg/kg), a COX type 2 selective inhibitor, was injected intraperitoneally 1 h before pretreatment with 1% AA. RESULTS: Intracolonal administration of 8% AA induced colonic mucosal damage (macroscopic score 10.0+/-0.9) and elevated MPO activity (2.8+/-0.2 U/g), which were significantly reduced to 3.3+/-0.8 and 1.8+/-0.2 U/g by 1% AA pretreatment, respectively. Indomethacin abolished the gross mucosal protective effect by 1% AA pretreatment in 8% AA-derived colitis in normal rats while the NS398 had no effect. Both indomethacin and NS398 reversed the MPO activity reduction induced by 1% AA pretreatment. In chronic inflamed colon 8% AA treatment resulted in an increase in the macroscopic score to 11.5+/-0.4 from 4.7+/-0.4, but not the MPO activity, which was significantly reduced to 5.7+/-0.9 by 1% AA pretreatment. This gross mucosal protective effect by 1% AA pretreatment in chronic inflamed colon was reversed by indomethacin while the NS398 had no effect. CONCLUSION: These data show that COX-1 and COX-2 derived prostaglandins induced by low concentration AA pretreatment reduce the colonic mucosal injury and the increase in the MPO activity in colitis, respectively. The protective effect of COX-1 is preserved in chronic inflamed colon. These findings support the existence of a low concentration of AA-derived prostaglandin-dependent CAP and suggest that colonic AA, which is derived from bacterial breakdown of carbohydrate and protein in the colon, plays a crucial role in the endogenous defense mechanisms.

Protective effect of pretreatment with low-dose lipopolysaccharide on D-galactosamine-induced acute liver failure.

BACKGROUND AND AIMS: The effect of low-dose lipopolysaccharide (LPS) induced nitric oxide (NO) on liver damage and survival in rats with acute liver failure caused by a lethal dose of D-galactosamine (D-gal) was studied. RESULTS: Ninety percent of control animals died within 4 days after D-gal injection, but pretreatment with low-dose LPS significantly decreased mortality to 5%. There was marked elevation in serum aspartate aminotransferase and alanine aminotransferase levels 24 h after D-gal injection. These aminotransferases were significantly improved in low-dose LPS pretreated rats 24 h after the administration of D-gal. NG-Nitro-L-arginine-methyl ester, but not NG-nitro-D-arginine-methyl ester, reversed this cytoprotection. CONCLUSION: Pretreatment with low-dose LPS prevents experimental liver failure induced by D-gal through activation of endogenous NO synthesis.