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The antiviral drug tecovirimat* has been used extensively to treat U.S. mpox cases since the start of a global outbreak in 2022. Mutations in the mpox viral protein target (F13 or VP37) that occur during treatment can result in resistance to tecovirimat † (1,2). CDC and public health partners have conducted genetic surveillance of monkeypox virus (MPXV) for F13 mutations through sequencing and monitoring of public databases. MPXV F13 mutations associated with resistance have been reported since 2022, typically among severely immunocompromised mpox patients who required prolonged courses of tecovirimat (3-5). A majority of patients with infections caused by MPXV with resistant mutations had a history of tecovirimat treatment; however, spread of tecovirimat-resistant MPXV was reported in California during late 2022 to early 2023 among persons with no previous tecovirimat treatment (3). This report describes a second, unrelated cluster of tecovirimat-resistant MPXV among 18 persons with no previous history of tecovirimat treatment in multiple states., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Todd G. Smith reports that SIGA Technologies, the owner of TPOXX, provided the drug used in the study under a material transfer agreement. Nicole M. Green reports serving as president of the Southern California Society for Microbiology. Daisy McGrath reports support from the Oak Ridge Institute for Science and Education. Meilan Bielby reports unpaid membership on the Association of Public Health Laboratories (APHL) Infectious Disease and Public Health Preparedness committees. Danielle Haydel reports institutional support from APHL to attend the APHL conference. No other potential conflicts of interest were disclosed.

The Los Angeles County Department of Public Health established a surveillance system to identify complicated (advanced human immunodeficiency virus [HIV] or hospitalized) mpox cases. From 1 August to 30 November 2022, we identified 1581 mpox cases, of which 134 (8.5%) were complicated. A subset of 8 cases did not recover after either initiating or completing a course of oral tecovirimat. All 8 patients were HIV positive and had advanced HIV (CD4 count <200 cells/μL). We identified 8 distinct mutations previously associated with tecovirimat resistance in specimens collected from 6 patients. Ongoing surveillance of viral evolution requires close coordination between health departments and frontline providers., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Since May 2022, approximately 2,500 mpox cases have been reported in Los Angeles County (LAC), California. Beginning in May 2023, the LAC Department of Public Health observed a consistent increase in mpox cases after a prolonged period of low incidence. A total of 56 cases were identified during May 4-August 17, 2023. A minority of mpox patients were fully vaccinated (29%). One patient was hospitalized; no deaths were reported. Two cases of reinfection occurred, both of which were associated with mild illness. The increasing number of cases during this period was significant, as few other health departments in the United States reported an increase in mpox cases during the same period. The outbreak spread similarly to the 2022 U.S. mpox outbreak, mainly through sexual contact among gay, bisexual, and other men who have sex with men. Vaccination against mpox became available in June 2022 and has been shown to be effective at preventing mpox disease. This outbreak was substantially smaller than the 2022 mpox outbreak in LAC (2,280 cases); possible explanations for the lower case count include increased immunity provided from vaccination against mpox and population immunity from previous infections. Nonetheless, mpox continues to spread within LAC, and preventive measures, such as receipt of JYNNEOS vaccination, are recommended for persons at risk of Monkeypox virus exposure., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Abraar Karan received funding from the National Institutes of Health. Nicole M. Green reports serving as president of the Southern California Branch of the American Society for Microbiology. Mario J. Pérez reports institutional support from the Ryan White Program Parts A, B, MAI, and EHE and leadership in the National Coalition of STD Directors. No other potential conflicts of interest were disclosed.

The 2022 multicountry mpox outbreak concurrent with the ongoing Coronavirus Disease 2019 (COVID-19) pandemic further highlighted the need for genomic surveillance and rapid pathogen whole-genome sequencing. While metagenomic sequencing approaches have been used to sequence many of the early mpox infections, these methods are resource intensive and require samples with high viral DNA concentrations. Given the atypical clinical presentation of cases associated with the outbreak and uncertainty regarding viral load across both the course of infection and anatomical body sites, there was an urgent need for a more sensitive and broadly applicable sequencing approach. Highly multiplexed amplicon-based sequencing (PrimalSeq) was initially developed for sequencing of Zika virus, and later adapted as the main sequencing approach for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Here, we used PrimalScheme to develop a primer scheme for human monkeypox virus that can be used with many sequencing and bioinformatics pipelines implemented in public health laboratories during the COVID-19 pandemic. We sequenced clinical specimens that tested presumptively positive for human monkeypox virus with amplicon-based and metagenomic sequencing approaches. We found notably higher genome coverage across the virus genome, with minimal amplicon drop-outs, in using the amplicon-based sequencing approach, particularly in higher PCR cycle threshold (Ct) (lower DNA titer) samples. Further testing demonstrated that Ct value correlated with the number of sequencing reads and influenced the percent genome coverage. To maximize genome coverage when resources are limited, we recommend selecting samples with a PCR Ct below 31 Ct and generating 1 million sequencing reads per sample. To support national and international public health genomic surveillance efforts, we sent out primer pool aliquots to 10 laboratories across the United States, United Kingdom, Brazil, and Portugal. These public health laboratories successfully implemented the human monkeypox virus primer scheme in various amplicon sequencing workflows and with different sample types across a range of Ct values. Thus, we show that amplicon-based sequencing can provide a rapidly deployable, cost-effective, and flexible approach to pathogen whole-genome sequencing in response to newly emerging pathogens. Importantly, through the implementation of our primer scheme into existing SARS-CoV-2 workflows and across a range of sample types and sequencing platforms, we further demonstrate the potential of this approach for rapid outbreak response., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: NDG is a consultant for Tempus Labs and the National Basketball Association for work related to COVID-19. All other authors have declared that no competing interests exist., (Copyright: © 2023 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Transposable elements are powerful agents of evolution that can diversify transcriptional programs by distributing transcription factor DNA-binding sites throughout genomes. To investigate the extent that transposable elements provide transcription factor-binding motifs in Caenorhabditis elegans, we determined the genomic positions of DNA-binding motifs for 201 different transcription factors. Surprisingly, we found that almost all examined transcription factors have binding motifs that reside within transposable elements, and all types of transposable elements have at least 1 instance of a transcription factor motif, demonstrating that transposable elements provide previously unappreciated numbers of transcription factor-binding motifs to the C. elegans genome. After determining the occurrence of transcription factor motifs in transposable elements relative to the rest of the genome, we identified DNA-binding motifs for 45 different transcription factors that are greater than 20-fold enriched within transposable elements compared to what would be expected by chance. Consistent with potential functional roles for these transposable element-enriched transcription factor-binding sequences, we determined that all transcription factor motif types found in transposable elements have instances of residing within accessible chromatin sites associated with transcription factor binding. The overwhelming majority of transcription factor-binding motifs located within transposable elements associate with their cognate transcription factors, suggesting extensive binding of transcription factors to sequences within transposable elements. In addition, transposable elements with accessible or transcription factor-bound motifs reside in the putative promoter regions of approximately 12% of all protein-coding genes, providing widespread possibilities for influencing gene expression. This work represents the first comprehensive analysis of transposable element-transcription factor interactions in C. elegans and demonstrates that transposable element-provided transcription factor-binding sites are prevalent in this important model organism., (© The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America.)

Heat Shock Factor 1 (HSF-1) is a key regulator of the heat shock response (HSR). Upon heat shock, HSF-1 binds well-conserved motifs, called Heat Shock Elements (HSEs), and drives expression of genes important for cellular protection during this stress. Remarkably, we found that substantial numbers of HSEs in multiple Caenorhabditis species reside within Helitrons, a type of DNA transposon. Consistent with Helitron-embedded HSEs being functional, upon heat shock they display increased HSF-1 and RNA polymerase II occupancy and up-regulation of nearby genes in C. elegans . Interestingly, we found that different genes appear to be incorporated into the HSR by species-specific Helitron insertions in C. elegans and C. briggsae and by strain-specific insertions among different wild isolates of C. elegans . Our studies uncover previously unidentified targets of HSF-1 and show that Helitron insertions are responsible for rewiring and diversifying the Caenorhabditis HSR., Competing Interests: JG, BT, MD, AP No competing interests declared, (© 2019, Garrigues et al.)

Elevated temperatures activate a heat shock response (HSR) to protect cells from the pathological effects of protein mis-folding, cellular mis-organization, organelle dysfunction and altered membrane fluidity. This response includes activation of the conserved transcription factor heat shock factor 1 (HSF-1), which binds heat shock elements (HSEs) in the promoters of genes induced by heat shock (HS). The upregulation of protein-coding genes (PCGs), such as heat shock proteins and cytoskeletal regulators, is critical for cellular survival during elevated temperatures. While the transcriptional response of PCGs to HS has been comprehensively analyzed in a variety of organisms, the effect of this stress on the expression of non-coding RNAs (ncRNAs) has not been systematically examined. Here we show that in Caenorhabditis elegans HS induces up- and downregulation of specific ncRNAs from multiple classes, including miRNA, piRNA, lincRNA, pseudogene and repeat elements. Moreover, some ncRNA genes appear to be direct targets of the HSR, as they contain HSF-1 bound HSEs in their promoters and their expression is regulated by this factor during HS. These results demonstrate that multiple ncRNA genes respond to HS, some as direct HSF-1 targets, providing new candidates that may contribute to organismal survival during this stress., (© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Introduction: Keratoacanthomas (KA) are common cutaneous skin tumors originating from the hair follicles. Unlike squamous cell carcinoma, KA can regress spontaneously and have a benign evolution. Solitary KA is the most common form but familial multiple KA (Ferguson-Smith type), genetically predisposed KA (such as in xeroderma pigmentosum, or Muir-Torre syndrome), or sporadic multiple eruptive KA (Grzybowski type) have been described. Generalized eruptive KA of Grzybowski (GEKA) is a rare condition (around 40 reported cases). The pathophysiology is still unclear. Human papillomavirus (HPV) has been detected in sporadic KA but the presence of HPV39 has never been reported, to our knowledge, in GEKA., Case Report: GEKA in an 80-year-old woman was successfully treated with acitretin (0.5 mg/kg/day) combined with surgical removal of the largest lesions. Treatment was well tolerated and led to decreased pruritus and tumor regression within 6 months. The presence of HPV39 was detected in a lesion by polymerase chain reaction and Sanger sequencing. No genetic alteration was found, in particular in the genes usually altered in squamous cell carcinoma (including NOTCH1, NOTCH2, CDKN2A, TP53)., Conclusion: We report a case of GEKA associated with the presence of HPV39 and the successful use of acitretin combined with surgical removal of the larger lesions.

Repression of germline-promoting genes in somatic cells is critical for somatic development and function. To study how germline genes are repressed in somatic tissues, we analyzed key histone modifications in three Caenorhabditis elegans synMuv B mutants, lin-15B , lin-35 , and lin-37 -all of which display ectopic expression of germline genes in the soma. LIN-35 and LIN-37 are members of the conserved DREAM complex. LIN-15B has been proposed to work with the DREAM complex but has not been shown biochemically to be a member of the complex. We found that, in wild-type worms, synMuv B target genes and germline genes are enriched for the repressive histone modification dimethylation of histone H3 on lysine 9 (H3K9me2) at their promoters. Genes with H3K9me2 promoter localization are evenly distributed across the autosomes, not biased toward autosomal arms, as are the broad H3K9me2 domains. Both synMuv B targets and germline genes display a dramatic reduction of H3K9me2 promoter localization in lin-15B mutants, but much weaker reduction in lin-35 and lin-37 mutants. This difference between lin-15B and DREAM complex mutants likely represents a difference in molecular function for these synMuv B proteins. In support of the pivotal role of H3K9me2 in regulation of germline genes by LIN-15B, global loss of H3K9me2 but not H3K9me3 results in phenotypes similar to synMuv B mutants, high-temperature larval arrest, and ectopic expression of germline genes in the soma. We propose that LIN-15B-driven enrichment of H3K9me2 at promoters of germline genes contributes to repression of those genes in somatic tissues., (Copyright © 2019 by the Genetics Society of America.)

The DREAM (Dp/Retinoblastoma(Rb)-like/E2F/MuvB) transcriptional repressor complex acts as a gatekeeper of the mammalian cell cycle by establishing and maintaining cellular quiescence. How DREAM's three functional components, the E2F-DP heterodimer, the Rb-like pocket protein, and the MuvB subcomplex, form and function at target gene promoters remains unknown. The current model invokes that the pocket protein links E2F-DP and MuvB and is essential for gene repression. We tested this model by assessing how the conserved yet less redundant DREAM system in Caenorhabditis elegans is affected by absence of the sole C. elegans pocket protein LIN-35. Using a LIN-35 protein null mutant, we analyzed the assembly of E2F-DP and MuvB at promoters that are bound by DREAM and the level of expression of those "DREAM target genes" in embryos. We report that LIN-35 indeed mediates the association of E2F-DP and MuvB, a function that stabilizes DREAM subunit occupancy at target genes. In the absence of LIN-35, the occupancy of E2F-DP and MuvB at most DREAM target genes decreases dramatically and many of those genes become upregulated. The retention of E2F-DP and MuvB at some target gene promoters in lin-35 null embryos allowed us to test their contribution to DREAM target gene repression. Depletion of MuvB, but not E2F-DP, in the sensitized lin-35 null background caused further upregulation of DREAM target genes. We conclude that the pocket protein functions primarily to support MuvB-mediated repression of DREAM targets and that transcriptional repression is the innate function of the evolutionarily conserved MuvB complex. Our findings provide important insights into how mammalian DREAM assembly and disassembly may regulate gene expression and the cell cycle.

The DREAM (DP, Retinoblastoma [Rb]-like, E2F, and MuvB) complex controls cellular quiescence by repressing cell cycle genes, but its mechanism of action is poorly understood. Here we show that Caenorhabditis elegans DREAM targets have an unusual pattern of high gene body HTZ-1/H2A.Z. In mutants of lin-35, the sole p130/Rb-like gene in C. elegans, DREAM targets have reduced gene body HTZ-1/H2A.Z and increased expression. Consistent with a repressive role for gene body H2A.Z, many DREAM targets are up-regulated in htz-1/H2A.Z mutants. Our results indicate that the DREAM complex facilitates high gene body HTZ-1/H2A.Z, which plays a role in target gene repression., (© 2015 Latorre et al.; Published by Cold Spring Harbor Laboratory Press.)

Formation of heterochromatin serves a critical role in organizing the genome and regulating gene expression. In most organisms, heterochromatin flanks centromeres and telomeres. To identify heterochromatic regions in the heavily studied model C. elegans, which possesses holocentric chromosomes with dispersed centromeres, we analyzed the genome-wide distribution of the heterochromatin protein 1 (HP1) ortholog HPL-2 and compared its distribution to other features commonly associated with heterochromatin. HPL-2 binding highly correlates with histone H3 mono- and dimethylated at lysine 9 (H3K9me1 and H3K9me2) and forms broad domains on autosomal arms. Although HPL-2, like other HP1 orthologs, binds H3K9me peptides in vitro, the distribution of HPL-2 in vivo appears relatively normal in mutant embryos that lack H3K9me, demonstrating that the chromosomal distribution of HPL-2 can be achieved in an H3K9me-independent manner. Consistent with HPL-2 serving roles independent of H3K9me, hpl-2 mutant worms display more severe defects than mutant worms lacking H3K9me. HPL-2 binding is enriched for repetitive sequences, and on chromosome arms is anticorrelated with centromeres. At the genic level, HPL-2 preferentially associates with well-expressed genes, and loss of HPL-2 results in up-regulation of some binding targets and down-regulation of others. Our work defines heterochromatin in an important model organism and uncovers both shared and distinctive properties of heterochromatin relative to other systems., (© 2015 Garrigues et al.; Published by Cold Spring Harbor Laboratory Press.)

Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms. Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths. To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.

A simple and fast procedure has been developed for the direct determination of sucrose in beet root samples through attenuated total reflectance Fourier transform infrared absorbance measurements (ATR-FTIR) at 1056 cm(-1) with a baseline established between 1187 and 887 cm(-1). The method only requires a previous crushing or liquefaction of samples and it is free from matrix effects and from the interference of minoritary sugars and fermentation molecules. Aqueous solutions of sucrose can be used as standards and recovery values from 101 to 103% were found for spiked concentration levels from 3.5 to 10.5% (w/w). The limit of detection provided by this method corresponds to 0.15% (w/w) of sucrose and the standard deviation of three independent analysis of a sample containing 9.30% (w/w) was 0.03% (w/w).

A new procedure has been developed for the FT-IR determination of caffeine in roasted coffee samples. The method involves wetting the coffee samples with a 0.25 M aqueous NH3 solution, extracting the caffeine with CHCl3, and measuring absorbance at 1,659 cm(-1) using a baseline established between 1,900 and 830 cm(-1). The procedure proposed is fast, only requiring a total extraction time of 16 min for each sample, and provides a drastic reduction of the organic solvent consumed, from the 200 mL diethyl ether and 50 mL CHCl3, required for each sample by the reference chromatographic UV-spectrometric determination to only 5 mL CHCl3. The method provides a limit of detection of the order of 3 mg L(-1) caffeine and a relative standard deviation of 0.4% for 3 independent analyses of a sample containing 18.6%mg/g caffeine. The accuracy of the FT-IR procedure was evaluated from recovery experiments on spiked samples providing values from 94.4 to 100.1% and from the comparison of results found for a series of commercial samples, by both FT-IR and the official reference procedure.

A fully automated procedure is proposed for the Fourier transform infrared (FTIR) determination of nicotine in tobacco. The method is based on the on-line extraction of nicotine with CHCl3. Samples, weighed inside empty extraction cartridges, were humidified with NH3 and the cartridges were installed in a flow manifold in which they were extracted with 2 ml CHCl3 for 2 min, then 400 microliters of the extract were introduced into a micro-flow cell using a carrier of CHCl3 and the IR spectrum was registered continuously. The absorbance, in the wavenumber range 1334-1300 cm-1, was measured, obtaining a peak as a function of time. The area of this peak was interpolated on a calibration line established from standard solutions of nicotine in chloroform treated in the same way as samples. The method provided a limit of detection of 0.1 mg ml-1 nicotine, an RSD lower than 2% and a sampling frequency of the whole procedure of 6 h-1. Results obtained for natural samples of cut tobacco and cigar compared well with those obtained by a batch FTIR procedure, involving an off-line extraction with a total time of 16 min. However, for yellow tobacco cigarette, an on-line extraction time of 10 min was required to obtain a good recovery of nicotine.

Purpose: Functional results of total colectomy (TC) and ileorectal anastomosis for colonic inertia are often impaired by postoperative obstruction and diarrhea. In order to avoid these postoperative complications, we propose a subtotal colectomy (STC) preserving the ileo-caecal junction., Methods: Since 1989, 18 consecutive patients (17 F, 1 M; mean age: 54 years) with intractable constipation underwent TC (n = 6) or STC with caecorectal anastomosis (Deloyers Procedure) (n = 12). Mean preoperative bowel frequency was two movements every month. Colonic inertia was defined as diffuse marker delay during transit study without obstructed defecation on manometry or digitalised rectography. Rectocele (n = 10), rectal (n = 5) and genital prolapse (n = 6) were treated in the same operative time., Results: Postoperative course was uneventful after STC but bowel obstruction, requiring laparotomy, occurred in 3 patients (50%) after TC: enterolysis (n = 2), bowel resection (n = 2). Mean postoperative day stool frequency of TC (4.2 +/- 1.2) was higher than STC (1.2 +/- 0.1). Half of patients after TC needed anti-diarrheal treatment and diet, 33% had rectal evacuation difficulties despite liquid stools, 17% had episodic incontinence, 66% had persistent abdominal pain. Compared to TC, the functional results of STC were significantly better: regular normal transit return without diet or treatment in 75% of cases, 25% had rectal emptying difficulties easily treated by mild laxatives, only 17% had persistent abdominal pain. Postoperative obstruction, diarrhea or fecal incontinence never occurred after STC., Conclusion: Compared to TC, STC with Deloyers procedure seems to reduce significantly the postoperative incidence of bowel obstruction, diarrhea and abdominal pain. Expected regular transit return after STC needs a careful selection of patients and simultaneous treatment of ano-rectal and pelvic floor abnormalities frequently associated with colonic inertia.

The authors studied erythrocyte aggregation in 62 patients suffering from hemorrhoidal disease, distributed on the basis of proctoscopy findings between three groups (recent uncomplicated congestive attack, recent thrombosed hemorrhoid, stage IIb or III chronic prolapse). This hemorheological parameter is a sensitive marker of circulatory stasis. Values measured were compared with those obtained in 21 healthy subjects. Erythrocyte aggregation index was significantly higher in patients than in controls (31.6 +/- 6.8 versus 27.7 +/- 4.4) (p < 0.05). This difference was due essentially to increased values in patients with acute hemorrhoid problems. A parallel increase in blood fibrinogen was found in these same patients. Hemorheological changes could predispose to worsening of venous stasis in the hemorrhoidal circulation and participate in the onset or spread of thrombotic processes.

In line with the literature, the authors consider that solitary ulcer of the rectum, either isolated, multiple or histological, like suspended proctitis, inverted hamartomatous polyp, deep cystic colitis, is a complication of rectal prolapse, which usually shares the same clinical symptoms. Solitary ulcer of the rectum is generally discovered on proctoscopy and is due to the strain exerted on the rectal mucosa by 2 opposing forces:violent effort of defecation against an anal and/or perineal obstruction. The reduction of these pressure and counterpressure forces with age and progressive alteration of the pelvic floor accounts for the progression of acute lesions towards chronic or attenuated lesions or even complete resolution. The therapeutic strategy should therefore decrease trauma by facilitating defecation by a combination of hygiene and dietary advice and biofeedback retraining, and surgical reduction of the anal obstruction and prolapse and correction of any perineal insufficiency.

The difficulties for evaluation of the perineal descent have always been linked to the choice of references and mostly with the incertitude of the measurement of length on the radiographic film. This present study was carried out to evaluate the perineal descent on the choice of an angular measurement: the posterior rectal inclination. The dynamic digitalized rectography was used to investigate the pelvic floor status of 134 women: 115 patients complaining of idiopathic constipation, and 19 healthy volunteers. Results have shown 3 populations with an increasing graduation of perineal impairment and led to propose a radiologic classification of pelvic floor impairment: stage I, or solid perineum, stage II, or descending perineum and stage III or descended perineum. This study has brought up that the first sign of a pelvic floor abnormality may be increased descent during straining, only later followed by perineal descent at rest. The relationship linking abnormal perineal descent and excessive opening of the ano-rectal angle suggested logically that fecal incontinence may be the end complication of the Descending Perineum Syndrom.

We report our experience on 61 anal canal epidermoid carcinoma bearing patients. The patients are divided into three therapeutic groups: a) 14 patients treated with combined surgery and preoperative radiotherapy (37.8 Gy in 18 fractions and 21 days); b) 28 patients treated with 60Co and electrontherapy (total tumor dose of 60 to 65 Gy); c) 19 patients treated with external cobaltherapy (30 Gy/10 fractions/12 or 15 days) followed 1 to 2 months later by interstitial brachytherapy with Iridium 192 (20 Gy). Local control was observed in 41 out of 61 patients (67.2%). Out of the six patients who underwent salvage abdomino-perineal resection, five were locally cured at 5 years. The overall 5-year survival is 78.6%; the corrected 5-year survival is 88.8%. Analysis of prognosis factors shows a direct relation between local control survival and the loco-regional extension. The 5-year survival was 90.9% in the first therapeutic group, 90.9% in the second group, and 94.7% in the third group. The 5-year survival rates according to the stage and to treatment were as follows: Stage T1 N0 100% in the 1st therapeutic group, 85.7% in the 2nd group, 100% in the 3rd group; for Stage T2 N0 80% in the 1st group, 90.9% in the 2nd group, 90% in the 3rd group; for Stage T3 N0 83.3% in the 1st group, 85.7% in the 2nd group, and 66.6% in the 3rd group. The rates of sphincter preservation were 85.7% in the 2nd group and 94.7% in the 3rd group. These results show the incidence of loco-regional extension on the prognosis and the usefulness of conservative treatments.

Rectopexy associated with anterior prolepsectomy was performed for 22 patients (19 females, 3 males), with solitary rectal ulcer syndrome (SRUS) surrounding internal rectal prolapse. The different lesions of SRUS were distributed among 3 main groups (G) according to the macroscopic appearance: G1: solitary ulcer (n = 7); G2: ulcerated proctitis (n = 7); G3: muco-hemorroidal prolapse (n = 3). A significant difference (P less than 0.05) was observed between each group, concerning mean age (G1: 34 years, G2 = 49, G3: 65) and the degree of perineal descent, which was more important in G3 and G2. Posterior intersphincteric rectopexy was performed for 6 patients in G3, with descending perineum and faecal incontinence, treated in the same time by perineoplasty (Parks). Abdominal rectopexy, mainly by the antero-posterior technique (Nicholls), was performed for the other patients (n = 6). Large anterior prolapsectomy reaching the top of the mucosal prolapse (4-7 cm), allowing ulcer resection in 3 cases, was combined with rectopexy. Associated operations were: sphincterotomy (n = 8) for narrow fibrous anal canal, sigmoidectomy (n = 4) for dolichocolon. Mean healing time for the solitary ulcer group (G1) was 2 months, 1 month for lesion of G2 and G3. Failures concerned 1 solitary ulcer after abdominal rectopexy and 1 ulcerative proctitis after rectopexy without prolapsectomy. Anorectal pain (81%), rectal bleeding (76%), faecal incontinence (27%), straining (81%), were cured or improved in 80% of cases. These results tend to confirm the efficacy of rectopexy, specially using the antero-posterior technique, for the treatment of SUSR with internal rectal prolapse. Nevertheless, rectopexy seems to be insufficient to correct the mucosal component of internal rectal prolapse, bearing the ulcerated lesion which needs to be treated by associated anterior prolapsectomy. Similarly all functional or organic disorders involving the perineum, anal canal or colon leading to anorectal dysfunction must also be considered to ensure complete treatment.

In a new statistic concerning 245 cases of primary ano-rectal neuralgia, it can be seen that the schematic classical classification derived from Thaysen, Theile, and Bensaude must be maintained (proctalgia fugax: 45 cases; coccygodynia: 44 cases; ano-rectal neuralgia: 95 cases), partially integrating unusual cases of pruritus ani. Among the 4 principle etiologies, while not underestimating the neuropsychical and intestinal factors (constipation, laxatives), the importance of two other factors must be underlined (the urogenital factor, and particularly, the role of menopause, and important pelvic operations (33 cases) often overestimated; rachidian factors: tendomyositis (Garrigues), pseudoradicular factor. The interest of this study is to show that besides these typical cases (81,7%), a number of atypical cases exist, which have often been under-estimated. These cases can be classified in intermediary (4%), associated (10%), alternating (3,3%) cases, in the course of which the different syndromes replace each other or seem superposed. It must be underlined that the notion of these primitive ano-rectal neuralgias must be inserted in the much larger class of perineal urinary, gynecological or bone and ligament neuralgias. The classification remains opened. An etiopathogenical treatment must be installed, that rejects all regional or surgical aggressive acts when not absolutely necessary, and underlines the importance of massage, internal (levator ani), or external (Maigne's technique, attentive and repeated sessions of rachidian massage).U

We report the results of 30 antero-posterior rectopexies (APR) for rectal kinetic disorders with descending perineum syndrome. All patients were investigated by digital subtraction defecography and ano-rectal manometry. The associated surgical procedures were: sphincterotomy (n = 13) for outlet obstruction demonstrated by anal manometry or balloon expulsion test: hypertonic sphincter (n = 7), narrow fibrous sphincter (n = 6); 10 cases of prolapsectomy with extended anterior mucosectomy to reduce anterior rectal prolapse; 2 sigmoidectomy for dolichosigmoid. Best results (mean follow-up: 12 months, 3-26) were observed for ano-rectal or pelvic pain and rectal bleeding, which were cured in more than 80% of cases. Faecal incontinence (n = 5) was cured in all cases. Although normalisation of bowel movements and easier defecation were observed in 78% of cases, improvement in the dyschezic syndrome was differently perceived by the patients. Postoperative investigation demonstrated the probable cause of surgical failures (23%): impairment of rectal sensitivity (n = 2), anismus (n = 3), motor constipation (n = 4), with dolichosigmoid (n = 3). Severe perineal deficiency was also noted in 4 cases. Solitary ulcer (n = 6), anterior proctitis (n = 8), were cured within 2 months. Postoperative defecography showed correction of rectal intussusception without impairment of anterior rectal motility during defecation. These results confirm the efficacy of ARP for treatment of rectal intussusception or anterior rectocele. This functional rectopexy avoids the rectal "sling effect" of standard rectopexy which usually increases rectal dysfunction. Nevertheless, ARP alone seems to be insufficient when the associated functional or organic disorders implicated in rectal dysfunction are not also corrected, essentially outlet obstruction and dolichosigmoid.

The aim of this study was to compare the prevalence and the size of hemorrhoids with the degree of portal hypertension; 101 patients with intrahepatic portal hypertension documented by measuring wedged and free hepatic venous pressures before performing transjugular liver biopsy and 67 patients free of liver disease were investigated by proctoscopy. Portal hypertension was associated with a higher prevalence of hemorrhoids (93 p. 100 vs 76 p. 100); there was no relation between portal pressure and the size of haemorrhoids; no relation was found between the size of hemorrhoids and the grade of esophageal varices.

We report the results of a procedure aimed at correcting the disorders of rectal and perineal tone responsible for the descending perineum syndrome (DPS). The procedure, carried out by the perineal approach, combines a posterior intersphincteric sacro-rectopexy, an anterior perineoplasty via a pre-anal levator myorraphie, a posterior perineoplasty using a post anal repair technique and a mucosal resection aimed at freeing the anal canal. 22 F and 1 M, mean age 68 years, with DPS were operated on. Digitised rectography demonstrated pathological perineal descent (greater than 3 cm) in all cases and posterior rectal angulation at rest of more than 25 degrees (normal less than 10 degrees) confirming an important deterioration in perineal tone. Results after a mean follow up of 12 months (6 to 30 months) were excellent, with objective improvement in rectal bleeding, pain, mucosal prolapse and anal incontinence. In spite of an almost constant return to normal in the number of stools and their facility of evacuation improvement in the dyschesic syndrome (78% of patients) was subjectively variable. Improvement was judged to be very good in 34%, good in 33%, fair in 11%. Healing of mucosal lesions: solitary ulcer (n = 2), rectal inflammation (n = 2), ulcerated mucosal prolapse (n = 3) occurred in all cases within 1 month. Post operative rectography demonstrated a significant decrease in posterior rectal angulation and ano-coccygeal distance confirming the efficacy of the anatomical correction. No serious complications, in particular, infections, were noted under appropriate prophylactic antibiotic cover (Piperacillin) continued up to D5.(ABSTRACT TRUNCATED AT 250 WORDS)