Selective interference of mTORC1/RAPTOR protects against human disc cellular apoptosis, senescence, and extracellular matrix catabolism with Akt and autophagy induction.

OBJECTIVE: The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that integrates nutrients to execute cell growth and protein synthesis. We hypothesized that mTOR is essential for the intervertebral disc, the largest avascular, low-nutrient organ. Our objective was to elucidate roles of mTOR signaling in human disc cells. DESIGN: The mTOR exists in two complexes: mTORC1 containing the regulatory-associated protein of mTOR (RAPTOR) and mTORC2 containing the rapamycin-insensitive companion of mTOR (RICTOR). To analyze their functions in human disc nucleus pulposus cells, RNA interference (RNAi) of mTOR targeting mTORC1 and mTORC2, RAPTOR targeting mTORC1, or RICTOR targeting mTORC2 or rapamycin, a pharmacological mTORC1 inhibitor, was applied. First, mTOR signaling including Akt, p70/ribosomal S6 kinase (p70/S6K), and autophagy were assessed. Then, apoptosis, senescence, and matrix metabolism were evaluated under pro-inflammatory interleukin-1 beta (IL-1ß) stimulation. RESULTS: Western blotting showed significant decreases in specific proteins by each RNAi (all P < 0.0001). In mTOR signaling, RNAi of mTOR and RICTOR decreased p70/S6K and Akt phosphorylation, whereas RAPTOR RNAi decreased p70/S6K but increased Akt phosphorylation. All RNAi treatments increased light chain 3 (LC3)-II and decreased p62/sequestosome 1 (p62/SQSTM1), indicating enhanced autophagy. In apoptosis, IL-1ß-induced terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells and poly (ADP-ribose) polymerase (PARP) and caspase-9 cleavage decreased by RAPTOR RNAi. In senescence, IL-1ß-induced senescence-associated beta-galactosidase (SA-ß-gal)-positive cells and p16/INK4A expression also decreased by RAPTOR RNAi. In matrix metabolism, RAPTOR RNAi reduced IL-1ß-induced catabolic matrix metalloproteinase (MMP) release and activation and up-regulated anabolic gene expression. These findings were all consistent with rapamycin administration. Additional disc-tissue analysis detected expression and phosphorylation of mTOR-signaling molecules in varying ages. CONCLUSION: Selective interference of mTORC1/RAPTOR protects against inflammation-induced apoptosis, senescence, and matrix catabolism possibly through Akt and autophagy induction in human disc cells.

A phase I/II trial of irinotecan plus amrubicin supported with G-CSF for extended small-cell lung cancer.

OBJECTIVE: This study reports the findings of a Phase I/II, cohort, dose-escalation trial of amrubicin and irinotecan with the support of granulocyte colony-stimulation factor. This study aimed to determine the dose-limiting toxicity of the combination and to define the maximum-tolerated dose, as a recommended dose for Phase II trials. We also sought to obtain preliminary data on the efficacy of this combination as a frontline therapy for extensive-disease small-cell lung cancer. METHODS: We included 23 chemo-naïve patients with extensive-disease small-cell lung cancer in the trial. The amrubicin dose was escalated from 35 to 40 mg/m(2) (Levels 1 and 2, respectively) to determine the dose-limiting toxicity, with an unchanged dose of irinotecan at 50 mg/m(2). RESULTS: Of nine patients, three experienced dose-limiting toxicities at Level 1 of prolonged Grade 4 neutropenia, Grade 3 febrile neutropenia and Grade 3 febrile neutropenia with Grade 3 diarrhea. At Level 2, two patients experienced dose-limiting toxicities of Grade 4 neutropenia and Grade 3 neutropenia with Grade 4 diarrhea. The maximum-tolerated doses and recommended doses for amrubicin and irinotecan were therefore determined to be 35 and 50 mg/m(2), respectively. The Level 1 trial was then expanded to 21 patients, 14 (70%) of whom showed partial responses to the recommended dose. The median progression-free and overall survival times were 6.37 and 15.21 months, respectively. CONCLUSIONS: The combination of amrubicin and irinotecan with the support of granulocyte colony-stimulation factor produced a potent effect in chemo-naïve extensive-disease small-cell lung cancer patients. The use of biomarkers for this regimen may identify patients who are likely to suffer from treatment-ending severe adverse effects.

Comprehensive validation of early diagnostic algorithms for myocardial infarction in the emergency department.

OBJECTIVE: To comprehensively evaluate diagnostic algorithms for myocardial infarction using a high-sensitivity cardiac troponin I (hs-cTnI) assay. PATIENTS AND METHODS: We prospectively enrolled patients with suspected myocardial infarction without ST-segment elevation from nine emergency departments in Japan. The diagnostic algorithms evaluated: (i) based on hs-cTnI alone, such as the European Society of Cardiology (ESC) 0/1-h or 0/2-h and High-STEACS pathways; or (ii) used medical history and physical findings, such as the ADAPT, EDACS, HEART, and GRACE pathways. We evaluated the negative predictive value (NPV), sensitivity as safety measures, and proportion of patients classified as low or high-risk as an efficiency measure for a primary outcome of type 1 myocardial infarction or cardiac death within 30 days. RESULTS: We included 437 patients, and the hs-cTnI was collected at 0 and 1 hours in 407 patients and at 0 and 2 hours in 394. The primary outcome occurred in 8.1% (33/407) and 6.9% (27/394) of patients, respectively. All the algorithms classified low-risk patients without missing those with the primary outcome, except for the GRACE pathway. The hs-cTnI-based algorithms classified more patients as low-risk: the ESC 0/1-h 45.7%; the ESC 0/2-h 50.5%; the High-STEACS pathway 68.5%, than those using history and physical findings (15-30%). The High-STEACS pathway ruled out more patients (20.5%) by hs-cTnI measurement at 0 hours than the ESC 0/1-h and 0/2-h algorithms (7.4%). CONCLUSIONS: The hs-cTnI algorithms, especially the High-STEACS pathway, had excellent safety performance for the early diagnosis of myocardial infarction and offered the greatest improvement in efficiency.

Altered regulation of c-jun and its involvement in anchorage-independent growth of human lung cancers.

The c-jun oncogene is frequently overexpressed in non-small-cell lung cancers (NSCLC), but its functional involvement in lung cancer development has not been clearly elucidated. In this study, we found that among the immediate-early serum responsible genes, exemplified by c-jun, c-fos and c-myc, induction of c-jun in a human bronchial epithelial cell line, BEAS-2B, was dependent on anchorage, in contrast to clear induction of c-fos and c-myc under both anchorage-dependent and -independent conditions. In fact, forced expression of c-jun in BEAS-2B cells significantly increased cell viability and colony formation in soft agar. Furthermore, we also found that such anchorage-dependent regulation of c-jun was lost in a significant fraction of human lung cancer cell lines. Interestingly, suppressed anchorage-independent but not anchorage-dependent growth was noted by constitutive expression of a dominant-negative c-jun mutant in a lung cancer cell line showing dysregulated and sustained c-jun expression in the absence of anchorage. These findings suggest that dysregulated c-jun expression may be involved in the acquisition of anchorage independence in the process of human lung carcinogenesis.

Nucleotide sequence of the DNA polymerase gene of herpes simplex virus type 2 and comparison with the type 1 counterpart.

The complete nucleotide sequence of the DNA polymerase gene of herpes simplex virus (HSV) type 2 strain 186 has been determined. The gene included a 3720-bp major open reading frame capable of encoding 1240 amino acids. The predicted primary translation product had an Mr of 137,354, which was slightly larger than its HSV-1 counterpart. A comparison of the predicted functional amino acid sequences of the HSV-1 and HSV-2 DNA polymerases revealed 95.5% overall amino acid homology, the value of which was the highest among those of the other known polypeptides encoded by HSV-1 and HSV-2. The functional amino acid changes were spread in the N-terminal one-third of the protein, whereas the C-terminal two-third was almost identical between the two types except a particular hydrophilic region. A highly conserved sequence of 6 aa, YGDTDS, which has been observed in DNA polymerases of HSV-1, Epstein-Barr virus, adenovirus, and vaccinia virus, was also present at positions 889 to 894 in the C-terminal region of HSV-2 DNA polymerase.

Association between the dopamine D2 receptor A2/A2 genotype and smoking behavior in the Japanese.

For the study presented here, we investigated possible links between the dopamine D2 receptor (DRD2) TaqIA genotype (DRD2*A) and smoking behavior in a total of 332 Japanese individuals. For the first time, functional insertion/deletion polymorphism (-141C Ins/Del) in the DRD2 promoter was also examined in relation to smoking behavior. The distribution of the DRD2*A genotype was significantly different among current, former, and never-smokers (P = 0.001; chi(2) test), and smoking appeared to be associated with the DRD2 A2/A2 genotype, showing marked contrast to previous reports for non-Hispanic whites in the United STATES: Multivariate logistic regression analysis incorporating age, sex, genotype, and smoking status as variables revealed that DRD2 A2/A2 genotype was significantly associated with an increased risk of predisposition to smoking behavior in the Japanese (odds ratio, 3.680; 95% confidence interval, 1.499-9.052). In contrast, such an increased risk was not observed in terms of association with the -141C Ins/Del polymorphism. These findings suggest an association of the DRD2*A genotype with an increased risk of being predisposed to smoking behavior in the Japanese and suggest the possible existence of ethnic group-specific differences, which warrant additional studies on the underlying molecular mechanism.

Dopamine D3 and D4 receptor antagonists: synthesis and structure--activity relationships of (S)-(+)-N-(1-Benzyl-3-pyrrolidinyl)-5-chloro-4- [(cyclopropylcarbonyl) amino]-2-methoxybenzamide (YM-43611) and related compounds.

In this study, we synthesized a series of (S)-N-(3-pyrrolidinyl)benzamide derivatives, 1, 2a-d, 5a-1, and 7, and their enantiomers, (R)-1 and (R)-5c-e, and evaluated their binding affinity for cloned dopamine D2, D3, and D4 receptors and their inhibitory activity against apomorphine-induced climbing behavior in mice. The results indicate that D2, D3, and D4 receptors have different bulk tolerance (D4 > D3 > D2) for the substituent of the 4-amino group (R1) on the benzamide nuclei and that cyclopropyl-, cyclobutyl-, and cyclopentylcarbonyl groups likely possess adequate bulkiness with respect to D3 and D4 affinity and selectivity over D2 receptors in this series. The results also suggested that the N-substituent (R2) on the pyrrolidin-3-yl group performs an important role in expressing affinity for D2, D3, and D4 receptors and selectivity among the respective subtypes. One of the compounds, (S)-(+)-N-(1-benzyl-3-pyrrolidinyl)-5-chloro-4-[(cyclopropylcarbonyl+ ++) amino]-2-methoxybenzamide (5c) (YM-43611), showed high affinity for D3 and D4 receptors (Ki values of 21 and 2.1 nM, respectively) with 110-fold D4 selectivity and 10-fold D3 preference over D2 receptors and weak or negligible affinity for representative neurotransmitter receptors. Compound 5c displayed potent antipsychotic activity in inhibiting apomorphine-induced climbing behavior in mice (ED50 value, 0.32 mg/kg sc).

Inhibition of herpes simplex virus type 2 replication in vitro by 1-N-pentadecanoyl-3''-N-trifluoroacetyl kanamycin A.

The in vitro antiviral activity as well as the mechanism of action of a new antiviral agent, a kanamycin analogue, 1-N-pentadecanoyl-3''-N-trifluoroacetyl kanamycin A (PTKA) against herpes simplex virus type 2 (HSV-2) was investigated. The drug showed excellent antiviral action with negligible cytotoxic effect on the culture cells. Based on plaque reduction assays the 50% inhibitory dose (ID50) of the drug was 1 microgram/ml, and at 20 micrograms/ml plaque formation was totally suppressed. The compound inhibited viral protein synthesis in infected cells without affecting RNA and DNA synthesis, when added to the cultures after virus adsorption. Moreover, pretreatment of the cells with PTKA before HSV-2 infection, increased the antiviral activity significantly. Dot-blot hybridization analysis revealed that the drug reduced the level of immediate early viral mRNA if applied before infection. There was no detectable action at the level of virus adsorption, penetration or uncoating. These results indicate that PTKA exerted its antiviral action at the early stage of viral replication as well as at the level of viral protein synthesis.

Anti-herpesvirus activity of citrusinine-I, a new acridone alkaloid, and related compounds.

Citrusinine-I, a new acridone alkaloid isolated from the root bark of the citrus plant (Rutaceae), exhibited potent activity against herpes simplex virus (HSV) type 1 and type 2 at low concentrations relative to their cytotoxicity; 50% effective concentrations (ED50) of citrusinine-I were 0.56 micrograms/ml and 0.74 micrograms/ml against HSV-1 and HSV-2, respectively. Inhibitory action was also demonstrated against cytomegalovirus (CMV) and thymidine kinase-deficient or DNA polymerase mutants of HSV-2. The compound markedly suppressed HSV-2 and CMV DNA synthesis at concentrations which did not inhibit the synthesis of virus-induced early polypeptides. However, citrusinine-I had no inhibitory activity against HSV and CMV DNA polymerases in cell-free extracts. Although the target of this inhibitor remains to be elucidated, the most plausible candidate is a virus-coded ribonucleotide reductase. Citrusinine-1, when combined with acyclovir or ganciclovir, synergistically potentiated the antiherpetic activity of these agents. Based on a comparative study of the antiherpetic activity of citrusinine-1 and 28 related compounds, a structure-activity relationship could be established.

Molecular cloning of herpes simplex virus type 2 DNA.

Restriction enzyme HindIII digestion of the whole genome of herpes simplex virus type 2 strain 186 yielded 10 DNA fragments with molecular weights ranging from approximately 22 X 10(6) to 1.2 X 10(6), which were cloned into the HindIII site of bacterial plasmid pACYC 184. The cloned fragments were identified by hybridization to HSV-2 virus DNA and by double digestion with restriction endonucleases. The recombinant plasmids, even if they carried DNA sequences with molecular weights of more than 10(7), were efficiently replicated in E. coli HB101.

YM-50001: a novel, potent and selective dopamine D4 receptor antagonist.

We investigated some in vitro pharmacological properties of a novel human dopamine D2-like receptor antagonist, YM-50001 [(R)-5-chloro-4-cyclopropylacarbonylamino-2-methoxy-N-[1-(3-methox ybenzyl)- 3-pyrrolidinyl]benzamide monooxalate]. Receptor binding studies revealed that YM-50001 had a potent affinity for human D4 receptors (Ki = 5.62 nM). YM-50001 displayed weak or negligible affinity for other neurotransmitter receptors including human D2 and D3 receptors. YM-50001 shifted the dopamine response curve on each human D2-like receptor subtype-mediated low-Km GTPase activity to the right. YM-50001 also exhibited good D4 selectivity with respect to D2-like receptor antagonism in the functional assay. These results indicate that YM-50001 is a novel, potent and selective D4 receptor antagonist.

Mixed connective tissue disease associated with acute polyradiculoneuropathy.

A rare case of mixed connective tissue disease (MCTD) with acute polyradiculoneuropathy is reported. A 23-year-old woman presented with high body temperature, arthralgia and a headache, and developed gait disturbance two weeks later. She had many clinical features common to patients with MCTD. Her neurological manifestations were diagnosed as acute polyradiculoneuropathy based on the clinical picture, combined with supportive ancillary data, including cerebrospinal fluid (CSF) analysis, electrophysiological evaluation, sural nerve biopsy, peroneus brevis muscle biopsy, and magnetic resonance imaging (MRI). Her neurologic deficits, as well as associated laboratory findings, were improved by corticosteroid therapy.

[Nontuberculous mycobacterial disease in a general hospital].

Annual incidence of nontuberculous mycobacterial (NTM) disease has been gradually increasing in the last 10 years in Japan. It is likely to encounter this disease not only in hospitals specialized in mycobacterial diseases but also in general hospitals. NTM were isolated from 97 cases between January 1990 and June 1996 at our hospital. Out of them, 41 patients were diagnosed as NTM disease. Mycobacterium avium complex (MAC) was the most frequent pathogens (68.3%) and M. kansasii (22%) was the next. Other pathogens were M. chelonae (4.9%), M. fortuitum (2.4%) and M. szulgai (2.4%). Results obtained in our hospital were very similar to the rates which have been reported previously. Patients with MAC infection showed relatively poor prognosis (eight patients were died out of 28 patients with MAC) in this study compared with the cases reported in previous papers, and this result could be explained by the severity of illness when they were admitted to our hospital, the insufficiency of the initial treatment which should be started with the combined use of three to four antibacterial drugs including clarithromycin, and to a low dosage of clarithromycin compared with conventionally adopted dosage. Unlike tuberculosis, human to human transmission is considered to be negligible in the case of NTM disease, and general hospitals are able to provide medical care to the patients with NTM disease. Rather, if general hospitals which are located in the region near to the patients residence can play more active role in the treatment of NTM disease, it would be more beneficial to patients requiring long-term follow-up observation. Based on the result that similar therapeutic results were obtained for infections with other NTM as reported in previous papers, it is indicated that general hospitals are able to provide medical care to patients with NTM disease if therapeutic regimens recommended by specialist are sufficiently understood and applied.

[Bilateral carotid endarterectomy for patients with bilateral carotid artery stenosis].

In a couple of recent randomized trials, the benefits of unilateral carotid endarterectomy (CEA) have been reevaluated in symptomatic patients with severe stenosis. In contrast, the operative indication, procedure, and perioperative management of bilateral CEAs for patients with bilateral carotid artery stenosis are still controversial. In this report, we reviewed 7 patients who underwent bilateral CEAs at out institute during the last 10 years, with regard to the clinical feature, angiographical findings, operative procedure, surgical results and long-term prognosis. The patients ranged from 52 to 73 years in age, and included six males and one female. Clinical symptoms were asymptomatic in 1 patient, transient ischemic attack in 2, reversible ischemic neurological deficits in 2, minor completed stroke in 1, and major completed stroke in 1. The angiographical carotid artery stenosis in the dominant side of symptomatic cases was 50% in 3, 70% in 1, 90% in 2, and ulceration in 4 cases. The stenosis in the non-dominant side of symptomatic cases was 60% in 1, 70% in 3, 90% in 2, and 4 cases with ulceration. One case among the asymptomatic cases had bilateral 80-90% stenosis. We staged bilateral CEAs, in the dominant side first except in one case among the symptomatic cases and on the more severely stenotic side first in the asymptomatic cases. During CEA, an external shunt was placed in 1 case, but no internal shunt was used in any of the cases. Perioperative complications were found in 2 patients, transient bilateral hypoglossal nerve palsy and local hemorrhage in the other case. Totally, all of 7 cases (14 consecutive CEAs) have been performed with satisfactory results. No mortality and no permanent morbidity has resulted. In the follow-up period (mean: 38.3 month), 1 patient was found to have developed cerebral infarction in the ipsilateral carotid artery territory. From our own small experience and from that in the literature, CEAs for bilateral carotid artery stenosis should be performed in the dominant side first. Then, after a certain period, from 2 to 6 weeks, the CEA should be performed in the non-dominant side.

[A case of dural arteriovenous fistula in the transverse and sigmoid sinus which developed over five years].

We report a case of dural arteriovenous fistula (dAVF) of the transverse and sigmoid sinus which developed over five years. The patient was a 64-year-old man, who had a history of congestive heart failure and transient ischemic attack (TIA). No abnormal lesions were detected in the cerebral angiograms five years prior to the time the etiology of his TIA was investigated. He suddenly suffered from left hemiparesis and the CT scan showed right parietal subcortical hemorrhage. Right carotid angiogram demonstrated dAVF of the transverse and sigmoid sinus supplied by the right occipital and ascending pharyngeal arteries. We thought the reason for the subcortical hemorrhage in this patient was due to the disturbance of venous return in the right cerebral hemisphere. We underwent direct embolization of the right transverse sinus by interlocking detachable coils. Postoperative cerebral angiograms demonstrated the disappearance of dAVF and he was discharged. Whether dAVF is a congenital anomaly or not, has been controversial. Since the dAVF in this case had newly developed over five years, it is suggested that dAVF is an acquired lesion.

[Effective hormone therapy of prostatic cancer with lung metastasis: 2 cases].

Many prostatic cancer patients have local symptoms such as dysuria and hematuria, but relatively few are seen with lung metastasis. This time we experienced 2 cases of prostatic cancer with a lung metastasis focus as the first symptom. Administration of diethylstilbestrol 500 mg/day for 20 days produced marked effects; reduction or disappearance of the lung metastasis focus, noticeable reduction of prostatic tumor and the improvement of their total condition. The literature is also reviewed.

[Long-term follow up of transurethral resection of the prostate--a review of 137 patients].

For assessing the long-term outcome of patients after transurethral prostatic resection (TUR-P), telephone interview in terms of the urinary symptom and the sexual function was conducted on 191 cases who underwent TUR-P in Hokkaido University Hospital from 1982 to 1988. Adequate replies were obtained from 137 patients (71.7%), whose mean age was 70.2 years old and mean follow up period was 4.8 years. Subjective urinary symptoms, which are mainly classified as dysuria, frequency and incontinence, were improved in 114/120 (95.0%), 99/108 (91.7%), and 20/21 (95.2%) respectively. Overall symptom-free rates of dysuria, frequency, and incontinence were 85.1% (114/134), 86.6% (116/134), and 90.3% (121/134). Morbidity of incontinence following TUR-P was only 6/134 (4.5%). There was one deaths (0.7%) at 2 weeks after TUR-P, but was not attributable to the operative procedure itself. Although 82 cases (59.9%) had risk factors such as the cardiovascular disease, malignancy or other systemic disorders, they did not jeopardize the postoperative course nor were attributed to the mortality. Uninhibited contraction and/or vesical denervation supersensitivity on perioperative cystometrogram were found in 53/84 (63%). These urodynamic abnormalities were not considered to be postoperative urinary symptoms. Postoperatively, the decrease in libido was noted in 12/63 (19%), but its causal relation to the procedure was obscure in most of the patients. We believe TUR-P can offer a satisfactory outcome in the majority of the patients with minimum risk.

[DNA ploidy of testicular germ cell tumors in childhood; difference from adult testicular tumors].

It is well known that there are various differences in the biological characteristics and clinical behavior between prepubertal testicular germ cell tumors and adult ones. We analyzed the nuclear DNA ploidy of testicular tumors in childhood using DNA flow cytometry for clarifying those biological features and shedding some insights in the pathogenesis of testicular germ cell tumors. Formalin-fixed, paraffin-embedded specimens of primary tumors taken from 9 boys with histological evidence of yolk sac tumors and 8 with prepubertal teratoma treated in our clinic were used for flow cytometry analysis with some modification of the Hedley's technique. The results were compared with those of adult testicular tumors which we previously reported. All specimens in children showed "DNA euploid"; DNA diploid in all teratomas and 6 yolk sac tumors, DNA tetraploid in other 3 yolk sac tumors. Neither distinct DNA aneuploidy nor DNA heterogeneity were detected in children. Our previous study proved that the vast majority of adult testicular tumors contain DNA aneuploid stemlines. Although prepubertal yolk sac tumor and teratoma are histologically identical with those in adults, this study apparently reveal the different DNA stemline ploidy in prepubertal testicular tumors compared with that in adult ones. It has been known that carcinoma in situ (CIS) of the testis is a precursor of adult testicular germ cell tumors and the CIS cells in precancerous state already shows aneuploid DNA histogram patterns. Moreover, CIS has never been observed in children. The current results are in agreement with the hypothesis that the pathogenesis of prepubertal testicular tumor is different from that of adult ones.(ABSTRACT TRUNCATED AT 250 WORDS)

[Early experience with an ileocolic bladder substitution (Mainz pouch) in 11 cases].

In the last decade, many continent urinary diversions have been developed for the cystectomy patients. Mainz pouch, which seems to be a sophisticated one without using an alloplastic prosthesis, was adopted in our clinic. We preliminarily report our result in 11 patients who underwent a Mainz pouch procedure in the last 2 years: 1 for bladder augmentation, 5 for total bladder substitution after cystoprostatectomy and 5 (including 2 females) for continent urinary diversion. The mean age of them was 54 years old and the follow up periods ranged from 6 to 24 months. The antimesenteric longitudinal incision of the ileum and cecum and their sutures were performed similarly to the usual detubularized intestinal pouch. The ureteral reimplantation to the colonic segment was accomplished by the submucosal tunnel method. Although the ureteral hiatus was initially positioned at the anal edge of the colon, a new hiatal creation by stabbing the more oral portion of the colon according to the Goodwin's ureterocolic anastomosis was subsequently employed to avoid the trouble of closure of this portion. When the urethral anastomosis was achieved by 4-5 interrupted sutures between the most dependent portion of the cecum and the urethral stump after cystoprostatectomy, the mucosa was everted to the colonic serosa to prevent the stricture. The continent stoma was created by an intussusception of the proximal ileum, which was stabilized by the seromuscular stripping and 2-3 rows of external metal staples. Complication of the alimentary system occurred in 6 of 11 cases (55%), though they were successfully treated by an appropriate conservative management except one who suffered an ileostomy and nephrostomy because of severe panperitonitis.(ABSTRACT TRUNCATED AT 250 WORDS)