Transanal endoscopic microsurgery: a new technique for completion proctectomy.

AIM: Following subtotal colectomy, the retained rectal stump is a potential source of morbidity. Although restorative ileal pouch-anal anastomosis is the gold standard for ulcerative colitis, up to 14% of patients will opt for a permanent ileostomy and undergo completion proctectomy, traditionally by an abdomino-perineal approach, which itself carries significant morbidity. We describe a new technique of perineal proctectomy using transanal endoscopic microsurgery (TEMS) equipment. To our knowledge, this technique has not previously been described in the literature. METHOD: Twelve patients, mean (SD) age 66 (±13) years, underwent TEMS proctectomy, performed by a single surgeon between January 2007 and October 2011. Excision began with an intersphincteric dissection following which the TEMS (WOLF) proctoscope was inserted and close rectal dissection was performed, entering the peritoneal cavity (if the top of the stump was intraperitoneal). Following perineal extraction of the specimen, the external sphincter and skin were closed with an absorbable suture. RESULTS: Nine patients had inflammatory bowel disease, two had neoplasia and one had intractable radiation proctitis. The mean (SD) rectal stump length was 17.8 (±6.1) cm and the peritoneal cavity was entered in nine patients, with no small-bowel injury. The median postoperative hospital stay was 5.5 days. In four patients there was delayed healing of the perineal wound. There was no perioperative mortality. CONCLUSION: TEMS perineal proctectomy is a novel, but safe, technique that may avoid the need for a traditional abdominoperineal approach in selected patients.

PTSD in French Adolescent Victims Following the London Attack in March 2017: Data From the First Step of the AVAL Study.

Background: The terrorist attack at Westminster Bridge on March 22nd, 2017 impacted on French high school students on a school trip in London. This terrorist attack was claimed by the Islamic State. The aim of the study was to assess the mental health consequences of the attack on the French adolescents who were directly exposed (criteria A for Post-Traumatic Stress Disorder, PTSD). This involved three dimensions, namely: (1) clinical; (2) epidemiological; and (3) prevention and therapeutic. Material and Method: The investigation was the first observational step of AVAL (Adolescents Victimes de l'Attentat de Londres) study, a cohort monitoring project and it was then a monocentric, cross sectional, non interventional survey, at only one-year post-trauma. The study was carried out utilizing self- and clinician-administered questionnaires. Volunteers from the medico-psychological emergency unit provided support for these victims during the study protocol. Results: From the target population (n = 53), 39 adolescents (73.6%) agreed to participate, with a median age 16.9 years. 12 months after the attack, 25.6% of teenagers suffered from current PTSD (p < 0.0001). Those with, vs. without, PTSD showed several significant differences: (1) heightened levels of major depressive episodes (p = 0.0266) and suicidality (p = 0.0164); (2) increased substance use, including tobacco (p = 0.0284) and cannabis (p = 0.0449); and (3) impaired functioning in school (p = 0.0203), social (p < 0.0001) and family (p < 0.0001) settings. Sixty four percentage of directly exposed teenagers also had a current psychiatric disorder other than PTSD. Discussion: The heightened levels of PTSD, psychiatric disorders, and substance use at 12 months highlight the importance of early intervention in adolescents exposed to terrorist-linked potentially traumatic events.

Percutaneous endoscopic sigmoid colostomy for irrigation in the management of bowel dysfunction of adults with central neurologic disease.

BACKGROUND: Bowel dysfunction results in a major lifestyle disruption for many patients with severe central neurologic disease. Percutaneous endoscopic sigmoid colostomy for irrigation (PESCI) allows antegrade irrigation of the distal large bowel for the management of both incontinence and constipation. This study prospectively assessed the safety and efficacy of PESCI. METHODS: A PESCI tube was placed endoscopically in the sigmoid colon of 25 patients to allow antegrade irrigation. RESULTS: Control of constipation and fecal incontinence was improved for 21 (84%) of the 25 patients. These patients were followed up for 6-83 months (mean, 43 months), with long-term success for 19 (90%) of the patients. No PESCI had to be removed for technical reasons or for PESCI complications. Late removal of the PESCI was necessary for 2 of the 21 patients. A modified St. Marks Fecal Incontinence Score to assess bowel function before and after PESCI showed a highly significant improvement (P < 0.0001). There were no procedure-related deaths. Complications included minor sepsis at the initial PESCI tube site in four patients and bumper migration in two patients, but there were no complications related to the button device. CONCLUSION: This study showed that PESCI is a simple, safe, and effective technique for distal antegrade irrigation in the management bowel dysfunction for selected patients with central neurologic disease. A successful PESCI is very likely to continue functioning satisfactorily for a long time without technical problems or local complications.

Complications of transanal endoscopic microsurgery (TEMS): a prospective audit.

BACKGROUND: The aim of this study was to determine the postoperative complications of Transanal Endoscopic Microsurgery (TEMS) excision of rectal lesions. METHOD: A prospective audit of 262 consecutive TEMS procedures performed by a single surgeon between 1999 and 2008. RESULTS: The mean age of patients was 72 years. The mean area of the lesions excised was 17.5 cm(2) with a mean diameter of 4.5 cm at a mean distance of 7.4 cm from the dentate line. There were 201 full thickness excisions, 51 partial thickness excisions and nine were mixed or unclassified. Thirty-three (13%) patients developed 41 complications. There were two (0.8%) deaths within 30 days. Pelvic sepsis occurred in seven (3%) patients and was significantly more common after excision of low lesions within 2 cm of the dentate line. Postoperative haemorrhage occurred in seven (3%) patients and was significantly less common when dissection was performed with ultrasonic dissection than with diathermy. Fourteen (5%) patients developed acute urinary retention. Four (1.5%) patients developed rectal stenosis and four (1.5%) suffered uncomplicated surgical emphysema that required no treatment. CONCLUSIONS: Transanal endoscopic microsurgery is a safe operation with a low mortality and morbidity. Pelvic sepsis is more common after excision of lesions within 2 cm of the dentate line. Ultrasonic dissection is associated with less postoperative haemorrhage than diathermy.

A predictive model for local recurrence after transanal endoscopic microsurgery for rectal cancer.

BACKGROUND: The outcome of local excision of early rectal cancer using transanal endoscopic microsurgery (TEM) lacks consensus. Screening has substantially increased the early diagnosis of tumours. Patients need local treatments that are oncologically equivalent to radical surgery but safer and functionally superior. METHODS: A national database, collated prospectively from 21 regional centres, detailed TEM treatment in 487 subjects with rectal cancer. Data were used to construct a predictive model of local recurrence after TEM using semiparametric survival analyses. The model was internally validated using measures of calibration and discrimination. RESULTS: Postoperative morbidity and mortality were 14.9 and 1.4 per cent respectively. The Cox regression model predicted local recurrence with a concordance index of 0.76 using age, depth of tumour invasion, tumour diameter, presence of lymphovascular invasion, poor differentiation and conversion to radical surgery after histopathological examination of the TEM specimen. CONCLUSION: Patient selection for TEM is frequently governed by fitness for radical surgery rather than suitable tumour biology. TEM can produce long-term outcomes similar to those published for radical total mesorectal excision surgery if applied to a select group of biologically favourable tumours. Conversion to radical surgery based on adverse TEM histopathology appears safe for p T1 and p T2 lesions.

Ferritin particles in macrophages and in associated mast cells.

In a variety of tissues (lymph node and glandular stroma), mast cells have been found in close and often intimate association with macrophages containing numerous ferritin-like particles in their cytoplasm and within cytoplasmic vacuoles (siderosomes). Phagocytic vacuoles in a given macrophage differed markedly. Some contained abundant Prussian blue-reactive material and others contained periodic acid-Schiff reactive substance at the light microscope level, and ultrastructurally some were filled with ferritin particles and others were not. Ferritin-like particles have also been observed occasionally in the mast cells associated with macrophages and even within the matrix of some of the granules in these mast cells.

The creation of a peritoneal defect in transanal endoscopic microsurgery does not increase complications.

INTRODUCTION: During Transanal Endoscopic Microsurgical (TEMS) full-thickness excision of a rectal lesion above the peritoneal reflection, entrance to the peritoneal cavity is inevitable. This has been regarded as a complication that requires conversion to an open procedure. We describe our experience of full thickness intraperitoneal excision of rectal lesions where the peritoneal defect was sutured endoscopically. METHOD: Data were collected prospectively on 15 patients in whom a peritoneal defect was created intraoperatively during TEMS excision of a rectal lesion. When a defect was recognized, it was closed by endoscopic suture. If there was any doubt regarding security of the closure, a defunctioning loop stoma was fashioned. RESULTS: Between November 1998 and January 2008, a total of 257 patients underwent TEMS during which a peritoneal defect was created in 15 patients. Six patients had a defunctioning stoma formed at the time of TEMS. No patient was defunctioned postoperatively and there were no deaths. The mean hospital stay was 8 days (range 3 to 19 days). A contrast enema showed sub-clinical leaks in two patients for which no treatment was required. No patient developed pelvic or peritoneal sepsis, but one patient had to return to theatre for postoperative bleeding when a single bleeding vessel was coagulated. CONCLUSION: Full thickness excision of lesions in the intraperitoneal rectum with endoscopic suture of the defect is a safe procedure. Lesions in the upper rectum should not be excluded from TEMS excision because of the chance of peritoneal breach.

The BSG/ACPGBI guidelines for colonoscopic screening: what are we missing?

INTRODUCTION: Before publication of the British Society of Gastroenterology and Association of Coloproctology of Great Britain and Ireland guidelines in 2002, screening for people with a family history of colorectal cancer was sporadic and largely dependant on unvalidated local guidelines. Since 1990 we have been screening patients with both high and moderate risk family histories of colorectal cancer using local protocols which were more liberal than the new guidelines. In this study, we have analysed the pathology that would have been missed if we had been using the new guidelines in the period 1990-2002. METHOD: A total of 399 consecutive patients with a positive family history of colorectal malignancy underwent screening endoscopy according to local guidelines. Demographic, endoscopic and pathologic data were prospectively collected. Patients were retrospectively divided into those who would have been screened under the new guidelines (group 1) and those who would not (group 2). The recorded pathology was graded as significant or insignificant and the findings compared between the two groups. RESULTS: A total of 399 patients underwent 557 endoscopies of which 278 (50%) were indicated under the new guidelines (group 1) and 279 (50%) were not indicated (group 2). A significant pathology or carcinoma was found in 15.8% of group 1 endoscopies and 10.0% of group 2 endoscopies. This difference was significant. CONCLUSION: If we had been using the new guidelines in the period 1990-2002, we would not have performed 279 (50%) of the 557 procedures, but would not have discovered significant pathology in 10% of the moderate risk endoscopies representing 39% of the significant pathology, which was actually present in this population.

Transanal endoscopic microsurgery: local recurrence rate following resection of rectal cancer.

OBJECTIVE: Transanal endoscopic microsurgery (TEM) is a safe and effective treatment for the excision of benign rectal adenomas. In recent years it has been used for the excision of malignant lesions, although its use in this context remains controversial. The aim of this study was to investigate the local recurrence of rectal cancers following local excision by TEM. METHOD: Forty-two patients with rectal cancer were treated by TEM between 1998 and 2005. However, six patients went on to have immediate radical surgery and are excluded from the study. Of the remaining 36 the treatment intention was for cure in 16 (38.1%), compromise in 17 patients unfit for radical surgery (40.5%), and palliation in three (7.1%). RESULTS: The mean age of patients was 75 years (range 41-90). The mean lesion area was 15 cm(2) (range 0.8-42) and mean distance from the dentate line was 6.6 cm (range 0-11). The mean follow up was 34 months (range 4-94). During the follow-up period there have been eight local recurrences (22%). The recurrence rates were 26% (6/23) for pT1, 22% (2/9) for pT2 and 0% (0/4) for pT3 lesions. The mean time to recurrence was 18.3 months (range 5-42). CONCLUSION: Transanal endoscopic microsurgery is a safe procedure with obvious advantages over radical procedures. However, in this study the local recurrence rate is high. The recurrence rate may be an acceptable compromise in elderly or medically unfit patients but is hard to justify for curative intent.

Kallikrein-kinin system and blood pressure sensitivity to salt.

We evaluated the blood pressure response to chronic salt loading in a rat strain inbred for low urinary kallikrein excretion. Low-kallikrein rats showed greater systolic blood pressure values (130 +/- 1 versus 114 +/- 2 mm Hg in controls; P < .05) at 9 weeks of age. Systolic blood pressure was increased after 10 days of dietary sodium loading in the low-kallikrein group and remained unchanged in controls (153 +/- 1 versus 112 +/- 2 mm Hg, P < .01). In additional experiments, blood pressure sensitivity to salt was tested in low-kallikrein rats receiving a chronic infusion of rat glandular kallikrein (1.7 micrograms/day per 100 g body weight, IV) or vehicle. Systolic blood pressure of vehicle-treated rats was increased by salt loading (from 138 +/- 1 to 158 +/- 2, 153 +/- 1, and 145 +/- 2 mm Hg at 5, 10, and 15 days, respectively; P < .01), while it remained unchanged in the kallikrein-treated group (from 136 +/- 2 to 146 +/- 5, 140 +/- 2, and 134 +/- 4 mm Hg at 5, 10, and 15 days, respectively; P = NS). Urinary kallikrein excretion was increased by kallikrein infusion (from 13.6 +/- 1.4 to 17.8 +/- 2.1 nanokatals per 24 hours; P < .01). Plasma immunoreactive kallikrein levels were higher in the kallikrein-treated group (66.4 +/- 4.4 versus 57.7 +/- 1.4 ng/mL in vehicle-treated rats; P < .05). On normal sodium diet, the ratio of kidney weight to body weight was lower in low-kallikrein rats (329 +/- 5 versus 370 +/- 8 mg/100 g body weight in controls; P < .01). This difference was associated with a decreased number of glomeruli per unit square area and increased width of Bowman's space. These results indicate that kallikrein replacement prevents the exaggerated blood pressure increase observed in rats with a genetically determined defect in urinary kallikrein excretion. Histological abnormalities are present at different levels in the nephron, and they may be functionally related to the altered cardiovascular and renal phenotype of this strain.

Six-month, double-blind comparison of isoxicam with buffered aspirin in rheumatoid arthritis.

The results of a six-month, double-blind comparison of isoxicam (Maxicam), 200 mg once a day, with buffered aspirin, 3,600 mg per day (900 mg four times a day), showed that isoxicam was statistically significantly better than aspirin in eight of 12 measures of efficacy. The study was carried out in 15 centers around the United States in 191 patients with classic or definite rheumatoid arthritis. The measures for which improvement with isoxicam was significantly better than aspirin were number of tender joints, sum of tenderness scores, number of swollen joints, sum of swelling scores, number of joints involved, grip strength, and overall assessment of the patient's condition by physician and patient. The measures for which the difference favoring isoxicam was not statistically significant were duration of morning stiffness, time to walk 50 feet, and global assessment of change in the patient's condition by physician and patient. The results indicate that 200 mg of isoxicam once daily is effective for treating rheumatoid arthritis. Compared with 3,600 mg of buffered aspirin daily, isoxicam is better in relief of symptoms and at least as effective regarding improvement in function.

The use of lead as an ionic tracer for investigating routes of passive fluid transfer.

Several inorganic ions, including lead, barium, silver, and thallium, have been tested as possible tracers for demonstrating fluid-accessible channels in functional epithelia at the ultrastructural level. The most useful of the ionic tracers examined was the lead (plumbous) ion, administered for short time intervals (less than 2 min) and "captured" with phosphate used as the buffer in the fixative. Passive fluid and ion-accessible channels of rat parotid salivary gland have been examined with this method. At short tracer infusion times (0.5-1.0 min), localization of the tracer was primarily extracellular, although intracellular deposits were observed in the following sites: smooth membrane-delimited endocytic vesicles of both epithelial and connective tissue cells, inner Golgi cisternae, and occasional cisternae of rough endoplastic reticulum. The lead tracer readily penetrated tight junctions between parotid acinar cells but rarely passed through the tight junctions between intercalated duct cells and did not penetrate junctions of striated duct cells. Fat cells observed in the stroma of this gland were the only cells that exhibited lead tracer in the cytosol, suggesting that the plasmalemma of this cell type is more permeable to exogenous ions than the plasmalemma of other cell types present in this gland.

Selective subcellular localization of cations with variants of the potassium (pyro)antimonate technique.

Fixation of rat parotid with an unbuffered osmium tetroxide solution containing nearly saturated potassium (pyro)antimonate resulted in abundant deposition of cation-antimonate precipatates in acinar cells. Altering the antimonate concentration, including buffers or chelators in the solution or changing the primary fixative resulted in an altered intensity and distribution of the precipitates formed in the tissue, apparently reflecting a degree of selectivity in ion localization. Decreasing the concentration of pyroantimonate to about half-saturation preserved predominantly the less soluble antimonate salts (e.g., Na+, Ca++) and resulted in preferential retention of deposits along the plasmalemma and in mitochondrial "dense bodies," with loss of most cytoplasmic and nuclear precipitates. A similar pattern was seen if fixation with the high concentration antimonate-osmium procedure was followed by a prolonged rinse. Adding phosphate or collidine buffers markedly decreased precipitates in the nuclei and on granular reticulum as well. Phosphate buffer or ehtyleneglycoltetraacetate inhibited in vitro precipitation of calcium and sodium and decreased or abolished plasmalemmal deposits. Glutaraldehyde fixation, either in the presence of antimonate or prior to antimonate-containing osmium tetroxide, abolished heterochromatin deposits. Mitochondrial dense bodies were of two types, one containing precipitate and the other inherently osmiophilic. The latter were also observed in pyrophosphate-osmium controls. Results from in vitro titrations of cations with the various antimonate methods and from neutron activation analyses of fixed tissues supported conclusions drawn from fine structural distribution patterns and were interpreted as follows. In rat parotid acinar cells, deposits in heterochromatin and on granular reticulum probably arose from precipitation in sites of high K+ and H+ as well as--NH3+-rich histones. Plasmalemmal antimonate deposits demonstrated sites of sodium and/or calcium accumulation. Some mitochondrial dense bodies contained Ca++ whereas others were inherently osmiophilic. Large, extracellular deposits were probably predominantly sodium precipitates.

Distribution of mitochondrial calcium: pyroantimonate precipitation and atomic absorption spectroscopy.

Mitochondrial function is highly dependent upon the concentrations of cations within the various compartments of this organelle. Utilizing variants of the pyroantimonate precipitation method, we have undertaken to localize cations, particularly calcium, in isolated mitochondria. Precipitated cations were present in two major compartments: 1) within the intracristal space and 2) in the matrix, frequently in association with the matrix face of cristal membranes. Precipitated cations were abundant in mitochondrial samples fixed with most pyroantimonate-containing fixatives, but were usually absent in samples fixed in phosphate-buffered, pyroantimonate-containing fixative solutions. Atomic absorption spectroscopy demonstrated that Ca2+ added to mitochondrial suspensions prior to fixation was retained in the mitochondrial pellet if 0.1 M collidine was present as the fixative buffer. When the same concentration of phosphate-buffered pyroantimonate-osmium fixative was employed, however, much of the added Ca2+ was lost to the supernatant. The suborganellar localization of cations was influenced by the presence of added respiratory substrate. Incubation of mitochondria in an isoosmotic buffered sucrose medium without succinate favored localization of precipitates in the intracristal space of the outer compartment. In the presence of succinate, the localization of precipitates was shifted toward the matrix compartment. This redistribution was particularly obvious in samples to which Ca2+ had been added and was blocked by the addition of antimycin. The observation of precipitated cations in the outer mitochondrial compartment supports previous evidence for a calcium-binding protein in this compartment.

Electron microscopic immunostaining of kallikrein in rat submandibular glands.

The subcellular localization of glandular kallikrein in ducts and tubules of the rat submandibular gland was determined using a postembedding immunostaining (peroxidase--antiperoxidase) technique on thin sections of Eponembedded tissue. Kallikrein was found in large granules of granular convoluted tubule cells and in small, apical granules of striated duct cells. It was also present in patchy aggregates along the surface of striated duct cells and intercalated duct cells, but not in granules of the latter. Basal dense bodies (lysosomes?) of granular tubules also stained for kallikrein. Absorption of kallikrein antiserum with rat urinary kallikrein, but not with rat urinary esterase A, abolished the specific immunostaining in these sites.

Immunocytochemical localization of nerve growth factor: effects of fixation.

The fixation dependence of immunocytochemically demonstrable nerve growth factor (NGF) was investigated. Several commonly used fixation methods have been employed, including buffered formaldehyde, Bouin's fluid, and chloroform-methanol, as well as freezing and cryostat sectioning. The immunostaining technique was an immunoenzyme bridge procedure on either paraffin sections or frozen sections. Of those methods tested, fixation for 1 hr in a buffered formaldehyde appeared to provide optimal preservation and localization of immunoreactive material. Using this method, reaction product was localized in granules of the granular tubule cells of the male mouse submandibular gland. Prolonged fixation in buffered formaldehyde resulted in a diffuse background staining and loss of granule immunoreactivity. In frozen sections and in tissues fixed with either Bouin's solution, chloroform-methanol, or buffered paraformaldehyde-glutaraldehyde increased cytoplasmic background staining and loss of granule immunoreactivity were observed. It was concluded that, for the localization of NGF at the light microscopic level, a brief (1 hr) buffered formaldehyde fixation is optimal.

Comparison of the distribution of tissue kallikrein and esterase A, a kallikrein-like enzyme, in rat kidney using specific monoclonal antibodies.

Tissue kallikrein (E.C. 3.4.21.35) and arginine esterase A, another closely related, kinin-generating serine protease, have been localized by immunocytochemistry in rat kidney, using monoclonal antibodies that do not crossreact with other kallikrein-related enzymes or with tonin. Kallikrein was present primarily in the apical cytoplasm of the connecting tubule and the cortical collecting duct. Esterase A, on the other hand, was present primarily in the basolateral region of both proximal and distal straight tubules in the outer medulla and medullary rays. In addition, esterase A was demonstrable in distal convoluted tubules and, to a lesser extent, in proximal convoluted tubules. The presence of different kinin-generating enzymes at these sites would permit the formation of kinins from appropriate substrates on both the vascular and luminal poles of separate segments of the kidney tubule.

Co-localization of a kallikrein-like serine protease (arginine esterase A) and atrial natriuretic peptide in rat atrium.

Atrial natriuretic peptide (ANP) is stored in atrial granules primarily as a larger molecular weight precursor (pro-ANP), which is believed to be rapidly converted to an active peptide of 28 amino acids during or shortly after secretion. A tissue kallikrein-like serine protease has been suggested as a potential processing enzyme. In the present immunocytochemical study, using specific monoclonal antibodies, we found that esterase A, a kallikrein-like serine protease, was demonstrable in rat atrial myocytes and in ventricular myocytes, and was capable of cleaving pro-ANP to yield a low molecular weight product. Using colloidal gold immunocytochemistry at the electron microscopic level, we have found esterase A in atrial myocytes, both in granules and in another subcellular site that corresponds to sarcoplasmic reticulum. Double-label electron microscopic immunocytochemical results indicated that esterase A can co-localize with ANP in granules of atrial myocytes.

Kallikrein localization in rodent salivary glands and kidney with the immunoglobulin-enzyme bridge technique.

Kallikrein has been localized in rodent kidney and salivary glands by means of an immunoglobulin-enzyme bridge technique. In sections of kidney, anti-kallikrein antibodies bound to the apical region of certain distal tubule segments in the cortex, to reabsorption droplets of proximal convoluted tubules, and to certain duct segments in the papilla. In salivary glands of both male and female rats and mice, and apical rim of most striated duct cells of submandibular, parotid and sublingual glands and granular tubules of submandibular glands exhibited immunoreactivity. Granular intercalated duct cells in female submandibular glands also displayed immunostaining for kallikrein. Phenylephrine administration resulted in loss of immunoreactive granules from the granular convoluted tubule cells of male mouse submandibular gland. This response was paralleled by a biochemically demonstrable decrease in kallikrein-like tosylarginine methyl ester (TAME) esterase activity.

Immunocytochemical localization of tissue kallikrein in brain ventricular epithelium and hypothalamic cell bodies.

A specific monoclonal antibody against rat tissue kallikrein was used as the primary antibody for indirect immunoperoxidase staining of rat hypothalamus. Kallikrein was localized in the epithelial cells (ependyma) lining the third ventricle as well as in cell bodies of arcuate, supraoptic, paraventricular, and ventromedial nuclei.