"Prophylactic" transanal irrigation (TAI) to prevent symptoms of low anterior resection syndrome (LARS) after rectal resection: results at 12-month follow-up of a controlled randomized multicenter trial.

BACKGROUND: Low anterior resection syndrome (LARS) is associated with a severe negative impact on patients' quality of life (QOL). In a recent prospective randomized controlled trial (RCT) by our group, early ("prophylactic") use of transanal irrigation (TAI) following rectal resection for rectal cancer was shown to improve symptoms associated with LARS significantly compared with a group under supportive therapy (ST) within 1 and 3 months following closure of the protective ileostomy. The aim of the present study was to evaluate the outcome after 12 months when patients had the option to choose between the two therapeutic options and/or modify the regimen of TAI (volume and time). METHODS: In the RCT, 18 patients had been allocated to start with TAI following ileostomy closure, while 19 patients remained on ST only. Once the 3-month follow-up had been completed patients could choose between TAI or ST, respectively, and were invited for follow-up after 12 months. The maximum number of bowel movements during the day and the Wexner and LARS score as well as physical (PC) and mental (MC) component of the SF-36 questionnaire were evaluated. Furthermore, in patients who had changed their treatment arm, reasons for this decision were reported. RESULTS: Six patients were lost to follow-up (all in the ST group). One patient from the ST group started with TAI due to problems associated with LARS, bringing the total number of TAI patients to 19. Nine patients from the previous TAI arm changed to ST due to the long duration of the emptying process (n: 8) or pain during TAI (n: 1), respectively. After 12 months, the median volume of water used for irrigation was 600 ml (range 200-1000 ml). The ten patients who continued with TAI patients showed a lower number of defecation episodes per daytime (TAI median 3; 1-6, ST median 5; 2-10, p: 0.018) and per night (TAI median 0; 0-1, ST median 1; 0-5, p: 0.004) compared to the ST group. Although the LARS score was lower in patients who used TAI after 12 months (TAI median 18; 9-32, ST median 30; 3-39), this failed to reach the level of significance (p: 0.063). Evaluation of the Wexner score and the 36-item Short Form Health Survey as well as comparison of patients who remained on TAI (n: 9) versus those who had stopped TAI after 3 months (n: 9) failed to find any statistically significant difference between TAI and ST. CONCLUSIONS: This follow-up study revealed that a considerable number of patients decided to stop TAI within 12 months. However, the number of bowel movements during the day were still lower when TAI was used than when patients had ST only. CATEGORY: Randomized trial. REGISTRATION NUMBER: DRKS00011752, https://apps.who.int/trialsearch/ .

Randomized clinical trial of prophylactic transanal irrigation versus supportive therapy to prevent symptoms of low anterior resection syndrome after rectal resection.

Background: Low anterior resection syndrome (LARS) is a frequent problem after rectal resection. Transanal irrigation (TAI) has been suggested as an effective treatment in patients who have developed LARS. This prospective RCT was undertaken to evaluate the effect of TAI as a prophylactic treatment to prevent symptoms of LARS. Methods: Patients who had undergone ultralow rectal resection were randomized to start TAI on a daily basis, or to serve as a control with supportive therapy only after ileostomy closure. All patients were seen after 1 week, 1 month and 3 months, and the maximum number of defaecation episodes per day and night documented during follow-up. Wexner score, LARS score and Short Form 36 questionnaire responses were evaluated in both groups. Results: Thirty-seven patients could be evaluated according to protocol (TAI 18, control 19). The maximum number of stool episodes per day and per night was significantly lower among patients who underwent TAI at 1 month (median 3 versus 7 episodes/day in TAI versus control group, P = 0·003; 0 versus 3 episodes/night, P = 0·001) and 3 months (3 versus 5 episodes per day, P = 0·006; 0 versus 1 episodes/night, P = 0·002). LARS scores were significantly better in the TAI group after 1 month (median 16 versus 32 in control group; P = 0·044) and 3 months (9 versus 31; P = 0·001). A significantly better result in terms of Wexner score was seen in the TAI group after 3 months (median 2 versus 6 in controls; P = 0·046). Conclusion: Prophylactic TAI led to a significantly better functional outcome compared with supportive therapy for up to 3 months. Registration number: DRKS00011752 ( http://apps.who.int/trialsearch/).

Memory re-differentiation and reduced lymphocyte activation in chronic HCV-infected patients receiving direct-acting antivirals.

Recently, the treatment of HCV has advanced significantly due to the introduction of direct-acting antivirals (DAAs). Studies using interferon (IFN)-containing regimens failed to consistently show restoration of immunologic responses. Therefore, IFN-free DAA formulations provide a unique opportunity to dissect the immunologic effect of HCV cure. This study investigates the restoration of the immune compartment as a consequence of rapid viral clearance in patients successfully treated with DAAs and in the absence of IFN and ribavirin. Here, we evaluate the immunologic changes that occurred following DAA-mediated HCV cure. Peripheral blood from nineteen previously treatment-naïve patients with chronic HCV genotype 1a/1b who received an IFN and ribavirin-free regimen of daclatasvir, asunaprevir and BMS-791325 was evaluated. Immune reconstitution occurs in patients in whom HCV was successfully eradicated via DAA therapy. Restoration of the CD4(+) T-cell compartment in the peripheral blood and a re-differentiation of the T lymphocyte memory compartment resulted in a more effector memory cell population and a reduction in expression in the co-inhibitory molecule TIGIT in bulk T lymphocytes. Furthermore, we observed a partial reversal of the exhausted phenotype in HCV-specific CD8(+) T cells and a dampening of the activation state in peripheral NK cells. Collectively, our data provide the groundwork for dissecting the effect of DAA therapy on the immune system and identifying novel mechanisms by which chronic HCV infection exerts immunosuppressive effects on T cells through the recently described co-inhibitory molecule TIGIT.

Survival benefit of repeat liver transplantation in the United States: a serial MELD analysis by hepatitis C status and donor risk index.

Survival benefit (SB) for first liver transplantation (LT) is favorable at Model for End-Stage Liver Disease (MELD)≥15. Herein, we identify the MELD threshold for SB from repeat liver transplantation (ReLT) by recipient hepatitis C virus (HCV) status and donor risk index (DRI). We analyzed lab MELD scores in new United Network for Organ Sharing registrants for ReLT from March 2002 to January 2010. Risk of ReLT graft failure≤1 year versus waitlist mortality was calculated using Cox regression, adjusting for recipient characteristics. Of 3057 ReLT candidates, 54% had HCV and 606 died while listed. There were 1985 ReLT recipients, 52% had HCV and 567 ReLT graft failures by 1 year. Unadjusted waitlist mortality and post-ReLT graft failure rates were 416 (95% confidence interval [CI] 384-450) and 375 (95% CI 345-407) per 1000 patient-years, respectively. Waitlist mortality was higher with increasing waitlist MELD (p<0.001). The MELD for SB from ReLT overall was 21 (21 in non-HCV and 24 in HCV patients). MELD for SB varied by DRI in HCV patients (MELD 21, 24 and 27 for low, medium and high DRI, respectively) but did not vary for non-HCV patients. Compared to first LT, ReLT requires a higher MELD threshold to achieve an SB resulting in a narrower therapeutic window to optimize the utility of scarce liver grafts.

Ex vivo analysis of resident hepatic pro-inflammatory CD1d-reactive T cells and hepatocyte surface CD1d expression in hepatitis C.

Hepatic CD1d-restricted and natural killer T-cell populations are heterogeneous. Classical 'type 1' α-galactosylceramide-reactive CD1d-restricted T cells express 'invariant' TCRα ('iNKT'). iNKT dominating rodent liver are implicated in inflammation, including in hepatitis models. Low levels of iNKT are detected in human liver, decreased in subjects with chronic hepatitis C (CHC). However, high levels of human hepatic CD161(±) CD56(±) noninvariant pro-inflammatory CD1d-restricted 'type 2' T cells have been identified in vitro. Unlike rodents, healthy human hepatocytes only express trace and intracellular CD1d. Total hepatic CD1d appears to be increased in CHC and primary biliary cirrhosis. Direct ex vivo analysis of human intrahepatic lymphocytes (IHL), including matched ex vivo versus in vitro expanded IHL, demonstrated detectable noninvariant CD1d reactivity in substantial proportions of HCV-positive livers and significant fractions of HCV-negative livers. However, α-galactosylceramide-reactive iNKT were detected only relatively rarely. Liver CD1d-restricted IHL produced IFNγ, variable levels of IL-10 and modest levels of Th2 cytokines IL-4 and IL-13 ex vivo. In a novel FACS assay, a major fraction (10-20%) of hepatic T cells rapidly produced IFNγ and up-regulated activation marker CD69 in response to CD1d. As previously only shown with murine iNKT, noninvariant human CD1d-specific responses were also augmented by IL-12. Interestingly, CD1d was found selectively expressed on the surface of hepatocytes in CHC, but not those CHC subjects with history of alcohol usage or resolved CHC. In contrast to hepatic iNKT, noninvariant IFNγ-producing type 2 CD1d-reactive NKT cells are commonly detected in CHC, together with cognate ligand CD1d, implicating them in CHC liver damage.

Impaired plasmacytoid dendritic cell maturation and differential chemotaxis in chronic hepatitis C virus: associations with antiviral treatment outcomes.

BACKGROUND: Dendritic cell (DC) defects may contribute to chronicity in hepatitis C virus (HCV) infection and determine response to PEG-interferon and ribavirin therapy via poor T cell stimulation. Studies to date have produced inconsistent results regarding DC maturation and function: no large study has examined DCs before and after therapy. AIMS: We examined if DC defects in maturation and chemotaxis are present by comparing therapeutic responders to non-responders. METHODS: We analysed peripheral DCs of 64 HCV genotype 1-infected patients from the Virahep-C study 2 weeks before and 24 weeks after therapy. We used flow cytometry to enumerate plasmacytoid DC (pDC) and myeloid DCs (mDC) and quantify expression of chemokine receptors and maturation markers. Chemotaxis was measured with an in vitro assay. RESULTS: Pre-treatment frequencies of pDCs and mDCs were significantly lower in HCV patients than controls and successful therapy normalised pDCs. Levels of CXCR3 and CXCR4 on pDCs were higher at baseline compared to normal controls and decreased with therapy. Pre-therapy levels of co-stimulatory marker CD40 and the maturation marker CD83 were higher in pDCs of patients chronically infected with HCV compared to normal patients, and levels of both markers dropped significantly with therapy in the SVR+ group only. Other maturation markers (CD86 and CCR7) were not elevated suggesting a partially activated phenotype. Baseline chemotaxis of pDCs to CXCL12 and CXCL10 predicted failure of antiviral response and correlated with the histological activity index inflammation score. CONCLUSIONS: Plasmacytoid DC defects exist in chronic HCV and successful antiviral therapy normalises many phenotypic and functional abnormalities.

Associations between the human MHC and sustained virologic response in the treatment of chronic hepatitis C virus infection.

The human major histocompatability complex (MHC) genes encode the human leukocyte antigens, which are important in antigen presentation and regulation of CD8+ and CD4+ T cells. Response to therapies in hepatitis C virus (HCV) infection is highly variable (30-80%) and lower response rates have been reported among African Americans (AA; approximately 30%) compared to Caucasian Americans (CA; approximately 50%) infected with genotype-1 viruses. We evaluated whether MHC gene variants were associated with response to therapy and racial differences in AA and CA sustained virologic response (SVR) rates. We genotyped alleles at 8 MHC loci: 3 class I (A, B and C) and 5 class II (DRB1, DQA1, DQB1, DPA1 and DPB1) loci in 373 individuals (179 AA and 194 CA) with genotype-1 HCV infections, who were treated with peginterferon-alpha-2a and ribavirin. We observed carriage of A(*)02 (RR=1.33(1.08-1.64); P=0.008), B(*)58 (RR=1.84(1.24-2.73); P=0.002) and DPB1(*)1701 (RR=1.57(1.09-2.26); P=0.015) to be associated with SVR after adjustment for other predictors of response. In analysis of AA and CA subgroups separately, we observed potential, though not statistically significant, differences in these MHC associations. Variation in the immunogenetic background of HCV-infected individuals might account for some observed variation in viral-specific immunity and courses of disease. In this regard, future studies examining broader patient populations are warranted.

Sacral nerve stimulation in patients with severe constipation.

PURPOSE: Constipation is frequently a multifactorial disease. This study was designed to evaluate the potential effects of sacral nerve stimulation for patients suffering from severe chronic constipation. METHODS: Nineteen patients suffering from pathologic colonic transit time or rectal outlet obstruction were included. Only patients with severe rectal outlet obstruction who needed digital manipulation for defecation or patients suffering from pathologic colonic transit constipation with less than two bowel movements per week were regarded as candidates. A temporary stimulation lead was implanted into the sacral foramen that showed the best muscular response. After an evaluation period, the stimulation electrode was removed. An improvement in constipation (more than 2 bowel movements per week or defecation without digital manipulation, respectively) during the test stimulation, as well as a recurrence of prestimulation constipation symptoms during the following surveillance period of three weeks were prerequisites for implanting the permanent sacral nerve stimulating system. RESULTS: All of the patients showed a positive motor response to acute needle stimulation. After the evaluation period, eight patients (42 percent) reported an improvement of constipation, and permanent systems were implanted successfully. During the median follow-up of 11 (range, 2-20) months, a significant improvement in the Wexner constipation score was observed compared with the preoperative baseline level (baseline: median: 23, range, 18-27; 12 months after implantation: median, 8, range, 4-13). After successful sacral nerve stimulation, patients also showed a significant improvement in their quality of life. CONCLUSIONS: Patients suffering from severe constipation are a new challenge for sacral nerve stimulation but further research on pelvic floor function is needed.

Review article: the treatment of hepatitis C virus recurrence after liver transplantation.

BACKGROUND: Recurrent hepatitis C represents a major challenge for the liver transplant community. Given the potentially significant impact that hepatitis C recurrence has on graft and patient survival, several treatment strategies have been utilized to prevent/slow the progression to hepatitis C-related graft failure. AIM: To review the efficacy and applicability of treatment strategies for managing recurrent hepatitis C. METHODS: Search of MEDLINE (1990 to December 2006) and national meeting abstracts. Search terms included hepatitis C, liver transplantation, treatment, sustained virological response (SVR), and end of treatment virological response. An emphasis was placed on randomized trials. RESULTS: The largest study of treatment prior to liver transplantation (n = 124) achieved SVR in 24%. Eight randomized trials (n = 383) examined the efficacy of preemptive therapy with SVR ranging from 0-33%. Eligibility for treatment was low and dose reduction common. Four randomized trials (n = 245; all abstracts) have reported SVR from 33-42% for treating those with histological evidence of recurrent disease. CONCLUSIONS: Therapies for treating hepatitis C recurrence have limited applicability and tolerability, and they have a low SVR. Based on available results, preemptive therapy is not recommended. Pegylated interferon and ribavirin is currently the preferred choice for treating established recurrence. There is an urgent need for safer and more effective anti-viral therapy in this situation.

Sacral nerve stimulation for neurogenic faecal incontinence.

BACKGROUND: Sacral nerve stimulation (SNS) has emerged as a promising technique for the treatment of faecal incontinence. This study assessed the outcome of SNS in a cohort of patients with incontinence of neurological aetiology. METHODS: Thirty-six patients were included in a trial of SNS. Twenty-nine subsequently had a permanent implant. Evaluation consisted of a continence diary, anal manometry, saline retention testing and quality of life assessment. RESULTS: After a median follow-up of 35 (range 3-71) months, 28 patients showed a marked improvement in or complete recovery of continence. Incontinence to solid or liquid stool decreased from a median of 7 (range 4-15) to 2 (range 0-5) episodes in 21 days (P = 0.002). Saline retention time increased from a median of 2 (range 0-5) to 7 (range 2-15) min (P = 0.002). Maximum resting and squeeze anal canal pressures increased compared with preoperative values. Quality of life on all scales among patients who received a permanent implant increased at 12 and 24 months after operation. CONCLUSION: SNS is of value in selected patients with neurogenic faecal incontinence.

Patients' expectations of colorectal surgery for cancer.

OBJECTIVE: The primary objectives of surgery for colorectal cancer are to achieve radical resection of the tumour and to ensure a satisfactory quality of life for the patient. But what is satisfactory quality of life for the patients? What do patients desire? The goal of our exploratory investigation was to evaluate prospectively the patient pre-operative expectations as objectively as possible and to analyse results in relation to age, gender and socio-economic status. METHODS: In the period from 1998 to 2001, 167 patients were given a questionnaire consisting of 15 questions prior to surgery. The questionnaire included various aspects that were thought to influence the patient's quality of life. Moreover the patients were given the opportunity to rate the questions they considered most important. RESULTS: The following five points were considered most important by the total group of patients: Complete cure of the disease was rated most important (95%); it was the prime expectation of the patients. This was followed by the avoidance of a stoma (81%), a reliable control of defaecation (52%), normal digestion (44%) and little pain (26%). CONCLUSION: Age, gender and education influence the pre-operative expectations of patients undergoing surgery for colorectal cancer. In addition to the surgical standard, the care of the individual patient must be given due consideration in the treatment strategy.

Aetiology and surgical management of toxic megacolon.

OBJECTIVE: The purpose of this article is to review the surgical management and outcome of toxic megacolon and to update the aetiology of toxic megacolon. PATIENTS AND METHOD: A retrospective chart review of three academic colorectal surgery units was undertaken. Over a period of 20 years, 70 patients with surgically managed toxic megacolon were identified: 32 men and 38 women, median age 63 years (range, 23-87 years). RESULTS: In 33 (48%) patients the main cause of toxic megacolon was inflammatory bowel disease. Thirty-seven (52%) patients had toxic megacolon of different aetiology. Sixty-three patients underwent colonic resection: 49 (70%) subtotal colectomies and 14 (20%) total colectomies, including 4 (6%) proctocolectomies. Seven (10%) patients had decompression (n=3) or faecal diversion (n=4) only. Forty-four of the resected patients underwent a Hartmann's procedure and an ileostomy; 13 (19%) patients had primary anastomoses, 11 (16%) ileorectal anastomoses (IRA) and 2 (3%) patients had ileal pouch-anal anastomosis (IPAA). Twenty-six (37%) patients subsequently had continuity restored. Total surgical complication rate was 19% (n=13), 8% (n=4) in patients treated with subtotal colectomy, 21% (n=3) in patients treated with total proctocolectomy and 86% (n=6) in patients treated with either decompression or diversion. The total mortality rate was 16% (n=11). CONCLUSIONS: Toxic colitis complicated by toxic megacolon can occur after various diseases of the colon and remains a life-threatening disorder associated with a significant risk of postoperative complications. Subtotal colectomy with ileostomy remains the procedure of choice. Surgical colonic decompression with faecal diversion alone is associated with a high rate of complications.

Improving the safety of laparoscopic cholecystectomy: the routine use of preoperative magnetic resonance cholangiography.

BACKGROUND: The aim of this study was to determine the value of routinely performed preoperative magnetic resonance cholangiography (MRC) in detecting common bile duct (CBD) stones in patients stated to undergo elective laparoscopic cholecystectomy. In addition, we used MRC to investigate possible variants of the cystic duct. METHODS: Magnetic resonance cholangiography was performed preoperatively in 773 patients (311 male and 462 female; median age 55 years, range 16-91) who had no clinical signs of cholestasis prior to undergoing elective laparoscopic cholecystectomy. In cases where the MRC was positive for CBD stones, endoscopic retrograde cholangiopancreatiography (ERCP) was then performed. A total of 532 patients were available for continuous postoperatively follow-up (median 54 months, range 36-85). In 462 patients (247 female, and 215 male), MR images were also reviewed for variants of the cystic duct. RESULTS: In 705 patients (91%), MRC was negative for CBD stones. In 64 patients (9%) MRC was positive. Of these patients, 47 (6%) had CBD stones on ERCP. In 12 patients (2%), MRC was false positive. In five cases (0.6%), ERCP had an inconclusive result postoperative follow-up (532 patients, or 69%) revealed evidence of CBD stones in three patients (10.4%) despite a preoperative negative MRC result. Anatomical variants in the course of the cystic duct and its confluence with the common bile duct were found in 27 of 462 patients (6%). CONCLUSIONS: Magnetic resonance cholangiography proved to be a reliable screening technique in the preoperative evaluation of patients with silent CBD stones. Imaging of the course of the cystic duct is possible in a high percentage of cases. Therefore, MRC can be recommended as a screening technique before laparoscopic cholecystectomy.

[Collateral circulation of the left colon: historic considerations and actual clinical significance]. / Die kollaterale Gefässversorgung des linken Hemikolons. Historische Beobachtungen und aktuelle klinische Bedeutung.

INTRODUCTION: The arterial communication between the superior and inferior mesenteric arteries is important in surgery of the colon and aorta. METHODS: The anastomosis between the median colic artery (ACM) and the superior colic artery (AMS) was studied on 52 cadavers (32 female, 20 male). The length of the artery was measured using a flexible scale, and its diameter was determined at three different locations (origin, middle, end). RESULTS: The median lengths of the arteries were: 6.8 cm (range 3.9-9.7) for ACM, 12.2 cm (range 7-17.4) for ACS, and 23 cm (range 13.6-34.2) for margin artery. The median diameters were: 3.4 mm (range 2.7-4.1) for ACM, 3.1 mm (range 2.1-4.1) for ACS, and 2.7 mm (range 2-3.4) for margin artery. In 9.6% of the cadavers ( n=5), additional anastomoses between the AMS and inferior mesenteric arteries were proven. In 90.4% ( n=47), only margin arteries were found. SUMMARY: The low incidence of an additional communication (Riolan's arch) and possible additional impairment of the blood supply should be taken into account during operation.

Efficacy and tolerance of a new gentamicin collagen fleece (Septocoll) after surgical treatment of a pilonidal sinus.

OBJECTIVE: Pilonidal sinus is common. It causes substantial loss of working hours. The major disadvantage of open wound treatment is the long time required for healing. Primary wound closure is on the other hand often followed by infection. A controlled, multicentre trial was carried out to evaluate the efficacy of a new gentamicin collagen fleece (Septocoll) combined with primary closure. PATIENTS AND METHODS: One hundred and three patients (88 men, 15 women, median age 30 years) were included. Fifty-one were randomised to gentamicin fleece plus primary closure (Genta Group), and 52 patients to open treatment alone (Open Group). RESULTS: The median interval to wound healing was 17 days in the Genta group and 68 days in the Open group (P = 0.0001, log-rank test). Two patients in Group 1 developed infection within the first two weeks, requiring reopening of the wound, with primary wound healing occurring in 73%. Failure of primary healing (27%) was usually due to seroma or spontaneous dehiscence which subsequently healed. CONCLUSION: The combination of gentamicin collagen fleece (Septocoll) with primary closure resulted in a shorter period to healing than the open technique without unwanted effects.

Acute-phase response and immunological markers in morbid obese patients and patients following adjustable gastric banding.

OBJECTIVE: We measured markers of acute-phase response and immunological markers in morbid obese patients and in formerly morbid obese patients after a massive weight loss following adjustable gastric banding (GB). SUBJECTS: A total of 49 morbid obese female patients with a body mass index (BMI) above 40 kg/m(2) were investigated during a study period of 6 months. Of these, 24 patients received a gastric banding (GB) and lost a minimum of 20 kg in 1 y (GB group) and 25 patients maintained their weight (obese group). In sum, 13 normal weight subjects (BMI<24 kg/m(2)) were taken for controls. METHOD: Plasma concentration of the acute-phase proteins, C-reactive protein (CRP), orosomucoid, complement factors C3 and C4 and white blood cell count, lymphocyte subsets and serum immunoglobulins were analyzed. RESULTS: Acute-phase proteins were significantly lower in GB compared to morbid obese patients and remained significantly elevated in GB compared to controls. In addition, leukocytes, polymorphonuclear leukocytes and lymphocytes were significantly lower after GB and reached levels comparable to controls (except PMN). No difference in CD3 counts was observed in the three groups. CD4 increased and CD8 decreased in obese and GB patients when compared to controls whereas no statistical difference was found between obese and GB patients. CONCLUSION: Our results confirm the positive effect of GB followed by a massive weight loss without apparent malnutrition. Subclinical chronical inflammation in morbid obese patients leads to irregularities in leukocyte and lymphocyte subsets. These alterations can be positively influenced by GB.

Modern concepts for the treatment of fecal incontinence.

Anal incontinence is estimated to be present in approximately 2% of the total population. However, the incidence of this disorder increases with age, affecting up to 11% of men and 26% of women after the age of 50 years. In general, the causes of long-standing fecal incontinence may be divided into anorectal or congenital malformations, perineal trauma (due to surgery or accident), pudendal nerve lesions with or without muscular injury, and low-motor neuron lesions. Classical surgical treatment includes direct repair of the circumscribed gap in the anal sphincter, the so-called overlapping sphincteroplasty or anal repair. In the short term, this method was shown to be very effective in improving continence. Surgical repair of a diffuse weakness of the pelvic floor by application of the postanal repair method has led to more controversial results. While the short-term results are frequently beneficial, full continence is rarely achieved in the long run, especially in patients with imparied pudendal nerve function. All currently used surgical methods focus on the direct mechanical approach to the pelvic floor muscles and/or the anal sphincter. Therefore, the response to this kind of therapy is limited by the presence of a simultaneously existing neurogenic lesion (pudendal nerve damage), as well as by the magnitude and intensity of muscular injury. These problems have been addressed by the development of new methods that focus on the replacement of large muscular defects (Dynamic Graciloplasty) and the treatment of neurogenic causes of fecal incontinence (Sacral Nerve Stimulation-SNS).

Long-term results of modified graciloplasty for sphincter replacement after rectal excision.

OBJECTIVE: Restoration of the anal sphincter by means of electrically stimulated (dynamic) graciloplasty is a new therapeutic option for patients with severe faecal incontinence or those having abdomino-perineal resection (APR) of the anorectum. The present study reviews the outcome of total anorectal reconstruction (TAR) after APR for low rectal cancer or recurrent anal cancer. METHODS: From 1992 to 2000, 35 of 64 patients treated with dynamic graciloplasty had a TAR performed either synchronously (n=26) or as a secondary procedure one to five years after rectal excision (n = 9). RESULTS: The most frequent complication was injury or erosion of the neorectum (n = 9) which, was avoided with increasing surgical experience. Defaecation disorders and consequent incontinence were the most common functional problem and had to be treated with periodical enemas. CONCLUSION: Although sphincter replacement by means of TAR after APR led to poorer functional results than those achieved in patients treated with dynamic graciloplasty for faecal incontinence, TAR remains a valid treatment option for patients who do not tolerate a permanent stoma.

Hepatitis B and C in the liver transplant recipient: current understanding and treatment.

1. Liver disease related to chronic viral hepatitis is the leading indication for orthotopic liver transplantation (OLT) worldwide. 2. The natural history of hepatitis B virus infection has been dramatically modified, and outcome has improved substantially in the last decade with the use of hepatitis B immunoglobulin and lamivudine. 3. Hepatitis C virus (HCV) recurrence, defined by histological injury, is almost universal, and a subset of patients (20% to 30%) develops allograft cirrhosis by the fifth year post-OLT. 4. Unfortunately, antiviral therapy for hepatitis C post-OLT, even when initiated preemptively before the development of histological recurrence in the first few weeks post-OLT, has failed to alter the natural history of HCV disease recurrence. 5. HCV-related allograft cirrhosis is associated with a high rate of decompensation and mortality.