LARS is Associated with Lower Anastomoses, but not with the Transanal Approach in Patients Undergoing Rectal Cancer Resection.

BACKGROUND: Low anterior resection syndrome (LARS) is a defecation disorder that frequently occurs after a low anterior resection (LAR) with a total mesorectal excision (TME). The transanal (ta) TME for low rectal pathologies could potentially overcome some of the difficulties encountered with the abdominal approach in a narrow pelvis. However, the impact of the transanal approach on functional outcomes remains unknown. Here, we investigated the effect of the taTME approach on functional outcomes by comparing LARS scores between the LAR and taTME approaches in patients with colorectal cancer. METHODS: We conducted a retrospective cohort study including 80 patients (n = 40 LAR-TME, n = 40 taTME) with rectal adenocarcinoma. We reviewed medical charts to obtain LARS scores 6 months after the rectal resection or a reversal of the protective ileostomy. RESULTS: At the 6-month follow-up, 80% of patients exhibited LARS symptoms (44% minor LARS and 36% major LARS). LARS scores were not significantly associated with the T-stage, N-stage, or neo-adjuvant radiotherapy. The mean distance of the anastomosis from the anal verge was 4.0 ± 2.0 cm. The taTME group had significantly lower anastomoses compared with the LAR-TME group (median 4.0 cm [IQR1.8] vs. median 5.0 cm [IQR 2.0], p < 0.001). Univariable analysis revealed significantly higher LARS scores in the taTME group compared with the LAR-TME group (median LARS scores: 29 vs. 25, p = 0.040). However, multivariable regression analysis, adjusting for neo-adjuvant treatment, anastomosis distance from the anal verge, anastomotic leak rate, and body mass index, revealed no significant effect of taTME on the LARS score (adjusted regression coefficient: - 2.147, 95%CI: - 2.130 to 6.169, p = 0.359). We also found a significant correlation between LARS scores and the distance of the anastomosis from the anal verge (regression coefficient: - 1.145, 95%CI: - 2.149 to - 1.141, p = 0.026). CONCLUSION: Fifty percentage of patients in this cohort exhibited some LARS symptoms after a mid- or low-rectal cancer resection. As previously described, LARS scores were negatively correlated with the distance of the anastomosis from the anal verge. TaTME was after adjustment for the height of the anastomosis not associated with higher LARS at 6 months when compared with LAR-TME.

[Smarter Medicine: From the Diagnosis to the Intervention in General and Visceral Surgery]. / Smarter Medicine in der Viszeralchirurgie.

Smarter Medicine: From the Diagnosis to the Intervention in General and Visceral Surgery Abstract. More is not always a plus. With this slogan, in smarter medicine it is a principle to make a decision together. In general surgery diagnostic or therapeutic interventions have the potential to harm the patient. The admission to the emergency room of a young patient with abdominal pain does not necessarily require a computed tomography. A potential acute appendicitis without typical clinical and laboratory findings could potentially be unmasked by watchful waiting, or even a nonessential operation could be avoided. Possibly, acute cholecystitis or some forms of hollow organ perforation could be treated solely with antibiotics. Is it feasible to treat an acute severe diverticulitis with antibiotics only? In addition, if a colon resection is necessary, could a direct anastomosis be made, and a second operation be avoided? Are there thyroid nodules that do not need removal? The management of diseases in the surgical domain are evaluated with evidence-based medicine in the focus of smarter medicine and newly reconsidered.

[Update: Management of colonic diverticulitis]. / Update zum Management der Divertikulitis.

Update: Management of colonic diverticulitis Abstract. Several classification systems exist for diverticulosis and diverticulitis. We preferably use the "Classification of Diverticular Disease" (CDD) to grade the severity of disease. This classification is based on imaging by CT scan or ultrasound. The CDD system divides patients into categories with a common therapeutic strategy. Acute uncomplicated diverticulitis is treated by oral or intravenous antibiotics. For the majority of patients with uncomplicated diverticulitis, antibiotic therapy might be omitted in favor of a solely symptomatic therapy. Acute diverticulitis complicated by a relevant abscess or a perforation is treated by interventional drainage or surgical therapy. Resection with primary anastomosis replaces more and more resection with end colostomy (Hartmann's procedure). For patients with sepsis, the concept of damage control surgery has been introduced. The indication for elective surgery after conservative treatment of diverticulitis shall be dictated by the degree of the patient's symptoms, rather than the number of conservatively treated episodes of diverticulitis. Persisting complications, as fistulas and stenosis, represent an indication for elective colonic resection.

Oncologic long-term outcomes of emergency versus elective resection for colorectal cancer.

PURPOSE: Long-term outcomes in patients undergoing emergency versus elective resection for colorectal cancer (CRC) are discussed controversially. This study aims to assess long-term outcomes of emergency versus elective CRC surgery. METHODS: Single-center retrospective cohort study. Patients undergoing emergency or elective CRC surgery from July 2002 to January 2013 were included. Primary outcome was 5-year survival, secondary outcomes were in-hospital mortality and local tumor recurrence. RESULTS: Overall, 475 patients were included. Median age was 69.0 (IQR 59.0-77.0) years. A total of 141 patients (30%) were operated for rectal cancer and 334 patients (70%) for colon cancer. Median follow-up was 445 (IQR 67-1409) days. Emergency resection was performed in 105 patients (22%) due to obstruction, perforation, or bleeding. Stage IV tumors and ASA scores≥ 3 were significantly more frequent in the emergency than in the elective resection group (39.0% vs. 33.5%, p < 0.001; 75.5% vs. 61.3%, p = 0.003). The rate of patients with positive lymph nodes was similar in the two groups (46.2% vs. 46.3%, p = 1.000). In-hospital mortality was significantly higher in the emergency CRC versus the elective CRC group (8.4% vs. 3.0%, p = 0.023). Five-year survival (aHR 1.38; 95%CI 0.81-2.37, p = 0.237) or local tumor recurrence (aHR 1.48; 95%CI 0.47-4.66, p = 0.500) were not significantly different in patients undergoing emergency versus elective surgery for CRC. CONCLUSION: In-hospital mortality was increased in emergency versus elective CRC resections. However, 5-year survival and local recurrence after surgery for CRC were determined by the tumor stage, and not by the emergency versus elective setting of surgical resection.

A sustaining rod increases necrosis of loop ileostomies: a randomized controlled trial.

PURPOSE: Defunctioning loop ileostomies (LI) are commonly used in colorectal surgery to reduce the potentially detrimental consequences of anastomotic leakages. However, stoma-related morbidity is high with up to 75% of patients having local complications. The aim of this study was to investigate the effect of a sustaining rod on the local complication rate. METHODS: In this prospective, multi-center, randomized controlled trial, subjects were allocated to either a rod or a rod-less protocol (NCT00959738). The primary outcome was local morbidity as measured by a stoma specific morbidity score (SSMS) during the first 3 months postoperatively. RESULTS: Between August 2008 and July 2014, a total of 122 patients were enrolled in the study, of which 78 (63.8%) completed the study [44 (56.4%) rod, 34 (43.6%) rod-less]. There was no significant difference in the SSMS between the two groups. The incidence of necrosis or partial necrosis, however, was significantly increased in the rod group: 13 (29.5%) vs. 1 (2.9%) in the rod-less group (p < 0.01). The retraction rate did not differ significantly between the groups: two (4.5%) in the rod vs. five (14.7%) in the rod-less group (p = 0.13). High body mass index (BMI > 26) was associated with an odds ratio of 5 (p < 0.01) for severe stoma complications. CONCLUSIONS: A rod-less technique for loop ileostomies reduces the risk of stomal necrosis, with a high BMI being an independent risk factor for stomal complications.

Current aspects and future prospects of total anorectal reconstruction--a critical and comprehensive review of the literature.

PURPOSE: Many rectal cancer patients undergo abdominoperineal excision worldwide every year. Various procedures to restore perineal (pseudo-) continence, referred to as total anorectal reconstruction, have been proposed. The best technique, however, has not yet been defined. In this study, the different reconstruction techniques with regard to morbidity, functional outcome and quality of life were analysed. Technical and timing issues (i.e. whether the definitive procedure should be performed synchronously or be delayed), oncological safety, economical aspects as well as possible future improvements are further discussed. METHODS: A MEDLINE and EMBASE search was conducted to identify the pertinent multilingual literature between 1989 and 2013. All publications meeting the defined inclusion/exclusion criteria were eligible for analysis. RESULTS: Dynamic graciloplasty, artificial bowel sphincter, circular smooth muscle cuff or gluteoplasty result in median resting and squeezing neo-anal pressures that equate to the measurements found in incontinent patients. However, quality of life was generally stated to be good by patients who had undergone the procedures, despite imperfect continence, faecal evacuation problems and a considerable associated morbidity. Many patients developed an alternative perception for the urge to defecate that decisively improved functional outcome. Theoretical calculations suggested cost-effectiveness of total anorectal reconstruction compared well to life with a permanent colostomy. CONCLUSIONS: Many patients would be highly motivated to have their abdominal replaced by a functional perineal colostomy. Given the considerable morbidity and questionable functional outcome of current reconstruction technique improvements are required. Tissue engineering might be an option to design an anatomically and physiologically matured, and customised continence organ.

The impact of smoking on HPV infection and the development of anogenital warts.

PURPOSE: The worldwide prevalence of human papillomavirus (HPV) infection is estimated at 9-13 %. Persistent infection can lead to the development of malignant and nonmalignant diseases. Low-risk HPV types are mostly associated with benign lesions such as anogenital warts. In the present systematic review, we examined the impact of smoking on HPV infection and the development of anogenital warts, respectively. METHODS: A systematic literature search was performed using MEDLINE database for peer-reviewed articles published from January 01, 1985 to November 30, 2013. Pooled rates of HPV prevalence were compared using the χ (2) test. RESULTS: In both genders, smoking is associated with higher incidence and prevalence rates for HPV infection, whereas the latter responds to a dose-effect relationship. The overall HPV prevalence for smoking patients was 48.2 versus 37. 5 % for nonsmoking patients (p < 0.001) (odds ratio (OR) = 1.5, 95 % confidence interval (CI) 1.4-1.7). Smoking does also increase persistence rates for high-risk HPV infection, while this correlation is debatable for low-risk HPV. The incidence and recurrence rates of anogenital warts are significantly increased in smokers. CONCLUSIONS: Most current data demonstrate an association between smoking, increased anogenital HPV infection, and development of anogenital warts. These data add to the long list of reasons for making smoking cessation a keystone of patient health.

A novel animal model for external anal sphincter insufficiency.

PURPOSE: Reliable animal models are essential to evaluate future therapeutic options like cell-based therapies for external anal sphincter insufficiency. The goal of our study was to describe the most reliable model for external sphincter muscle insufficiency by comparing three different methods to create sphincter muscle damage. METHODS: In an experimental animal study, female Lewis rats (200-250 g) were randomly assigned to three treatment groups (n = 5, each group). The external sphincter muscle was weakened in the left dorsal quadrant by microsurgical excision, cryosurgery, or electrocoagulation by diathermy. Functional evaluation included in vivo measurements of resting pressure, spontaneous muscle contraction, and contraction in response to electrical stimulation of the afferent nerve at baseline and at 2, 4, and 6 weeks after sphincter injury. Masson's trichrome staining and immunofluorescence for skeletal muscle markers was performed for morphological analysis. RESULTS: Peak contraction after electrical stimulation was significantly decreased after sphincter injury in all groups. Contraction forces recovered partially after cryosurgery and electrocoagulation but not after microsurgical excision. Morphological analysis revealed an incomplete destruction of the external sphincter muscle in the cryosurgery and electrocoagulation groups compared to the microsurgery group. CONCLUSIONS: For the first time, three different models of external sphincter muscle insufficiency were directly compared. The animal model using microsurgical sphincter destruction offers the highest level of consistency regarding tissue damage and sphincter insufficiency, and therefore represents the most reliable model to evaluate future therapeutic options. In addition, this study represents a novel model to specifically test the external sphincter muscle function.

[Necessary and unnecessary treatment options for hemorrhoids]. / Nötige und unnötige Behandlungen beim Hämorrhoidalleiden: Der Patient bestimmt mit.

Up to one third of the general population suffers from symptoms caused by hemorrhoids. Conservative treatment comes first unless the patient presents with an acute hemorrhoidal prolapse or a thrombosis. A fiber enriched diet is the primary treatment option, recommended in the perioperative period as well as a long-term prophylaxis. A timely limited application of topical ointments or suppositories and/or flavonoids are further treatment options. When symptoms persist interventional procedures for grade I-II hemorrhoids, and surgery for grade III-IV hemorrhoids should be considered. Rubber band ligation is the interventional treatment of choice. A comparable efficacy using sclerosing or infrared therapy has not yet been demonstrated. We therefore do not recommend these treatment options for the cure of hemorrhoids. Self-treatment by anal insertion of bougies is of lowrisk and may be successful, particularly in the setting of an elevated sphincter pressure. Anal dilation, sphincterotomy, cryosurgery, bipolar diathermy, galvanic electrotherapy, and heat therapy should be regarded as obsolete given the poor or missing data reported for these methods. For a long time, the classic excisional hemorrhoidectomy was considered to be the gold standard as far as surgical procedures are concerned. Primary closure (Ferguson) seems to be superior compared to the "open" version (Milligan Morgan) with respect to postoperative pain and wound healing. The more recently proposed stapled hemorrhoidopexy (Longo) is particularly advisable for circular hemorrhoids. Compared to excisional hemorrhoidectomy the Longo-operation is associated with reduced postoperative pain, shorter operation time and hospital stay as well as a faster recovery, with the disadvantage though of a higher recurrence rate. Data from Hemorrhoidal Artery Ligation (HAL)-, if appropriate in combination with a Recto-Anal Repair (HAL/RAR)-, demonstrates a similar trend towards a better tolerance of the procedure at the expense of a higher recurrence rate. These relatively "new" procedures equally qualify for the treatment of grade III and IV hemorrhoids, and, in the case of stapled hemorrhoidopexy, may even be employed in the emergency situation of an acute anal prolapse. While under certain circumstances different treatment options are equivalent, there is a clear specificity with respect to the application of those procedures in other situations. The respective pros and cons need to be discussed separately with every patient. According to their own requirements a treatment strategy has to be defined according to their individual requirements.

[Changes in indications for surgery in the management of diverticulitis]. / Primum et super omnium: nihil nocere Operationsindikation im Wandel bei Divertikulitis.

Diverticulitis is a common disease in western countries and its incidence is increasing especially among young patients. Colonic diverticulosis, incidentally diagnosed by endoscopy or CT-scanning, has no immediate clinical consequences. Progression to diverticulitis develops in only 4 % of cases. In the last decades management of diverticular disease evolved and expectative treatment and less invasive techniques have gained importance. Elective resection has traditionally been advised after a second episode of diverticulitis or after a first episode if the patient was less than 50 years of age or complicated disease occurred. Recent changes in understanding the natural history of diverticular disease have substantially modified treatment paradigms. Elective resection in case of recurrent diverticular disease should be performed on a individual basis and in cases with complications like intestinal obstruction or fistulas. Primary anastomosis is an option even in emergency surgery due to colonic perforation, while diverting operations are indicated for selected patient groups with a high risk profile. Several prospective studies showed good results for laparoscopic drainage and lavage in the setting of perforated diverticulitis with generalized peritonitis, though this concept needs to be controlled with randomized clinical trials before application into the daily practice. This article should provide a short overview of trends in the surgical treatment of diverticulitis, help to understand the natural history of the disease and thereby explain the currently lower frequency of surgical interventions for diverticulitis.

Seamless knockins in Drosophila via CRISPR-triggered single-strand annealing.

CRISPR-Cas greatly facilitated the integration of exogenous sequences into specific loci. However, knockin generation in multicellular animals remains challenging, partially due to the complexity of insertion screening. Here, we describe SEED/Harvest, a method to generate knockins in Drosophila, based on CRISPR-Cas and the single-strand annealing (SSA) repair pathway. In SEED (from "scarless editing by element deletion"), a switchable cassette is first integrated into the target locus. In a subsequent CRISPR-triggered repair event, resolved by SSA, the cassette is seamlessly removed. Germline excision of SEED cassettes allows for fast and robust knockin generation of both fluorescent proteins and short protein tags in tandem. Tissue-specific expression of Cas9 results in somatic cassette excision, conferring spatiotemporal control of protein labeling and the conditional rescue of mutants. Finally, to achieve conditional protein labeling and manipulation of short tag knockins, we developed a genetic toolbox by functionalizing the ALFA nanobody.

Objective hypoesthesia and pain after transabdominal preperitoneal hernioplasty: a prospective, randomized study comparing tissue adhesive versus spiral tacks.

BACKGROUND: Irritation of inguinal nerves with laparoscopic hernia repair may cause chronic neuralgia and hypoesthesia. Hypoesthesia in particular is generally not assessed objectively. We objectively investigated hypoesthesia and chronic pain after transabdominal preperitoneal inguinal hernia repair (TAPP) with titanium spiral tacks (STs) compared with tissue adhesive (TA) for mesh fixation. METHODS: Mesh fixation in 80 TAPP procedures was randomized to fixation with ST (n = 40) or TA (n = 40). The outcome parameters included hypoesthesia assessed with von Frey monofilaments, early postoperative and chronic pain with the visual analog scale (VAS), morbidity (surgical-site infection, hematoma/seroma, relapse of hernia, trocar hernia), and recovery time to normal activity. RESULTS: Median (range) follow-up was 38 (13-56) months. Demographic and baseline parameters were similar in the two groups. Prevalence of hypoesthesia was significantly higher at all postoperative times in the ST group (6 weeks: 32 vs. 6%; 6 months: 38 vs. 14%; 12 months: 34 vs. 13%; 13-56 months: 32 vs. 4%). Mean hypoesthesia scores over all time points were significantly higher in the ST group. The percentages of regions with hypoesthesia (abdominal, inguinal, or genitofemoral) following all procedures were higher in the ST group after 6 weeks (14 vs. 2%), 6 months (15 vs. 5%), and 13-56 months (22 vs. 4%). The intensity of pain decreased significantly in both groups over time. CONCLUSIONS: Postoperative hypoesthesia depends on the method of mesh fixation during TAPP and is significantly reduced with TA compared with stapling.

Pit picking vs. Limberg flap vs. primary open method to treat pilonidal sinus disease - A cohort of 327 consecutive patients.

Background: Minimally invasive methods in pilonidal sinus disease (PSD) surgery are becoming standard. Although long-term results are available for some techniques, long-term outcome data of patients after pit picking is lacking. We aimed at investigating perioperative and long-term outcomes of patients undergoing pit picking, Limberg flap or primary open surgery to treat PSD. Methods: In a single-centre observational study, we evaluated the outcomes of 327 consecutive patients undergoing PSD surgery between 2011 and 2020. Results: PSD had recurred in 22% of Limberg flap patients and 62% of pit picking patients at 5 years (p=0.0078; log rank test). Previous pilonidal surgeries, smoking, body mass index, immunodeficiency, and diabetes did not significantly influence the long-term recurrence rate. Primary open treatment was performed for 72% of female patients presenting with primary disease. Conclusions: Due to its especially dismal long-term results, pit picking should be abandoned, and Limberg flap should be promoted instead, even for primary disease and in females.

Improving outcomes after laparoscopic appendectomy: a population-based, 12-year trend analysis of 7446 patients.

OBJECTIVE: Laparoscopic appendectomy for acute appendicitis has become increasingly used over the past decade. The objective of this trend analysis is to assess whether clinical outcomes after laparoscopic appendectomy have improved over the past 12 years. METHODS: This analysis is based on the prospective database of the Swiss Association of Laparoscopic and Thoracoscopic Surgery. All patients undergoing emergency laparoscopic appendectomy for acute appendicitis from 1995 to 2006 were included. The following outcomes were assessed for each of the 12 years: conversion rates, intraoperative complications, surgical postoperative complications, general postoperative complications, rate of reoperations, and length of hospital stay. Unadjusted and risk-adjusted multivariable analyses were performed. Statistical significance was set at a level of P < 0.05. All statistical tests were 2-sided. RESULTS: Data from 7446 patients undergoing laparoscopic appendectomy for acute appendicitis were prospectively collected. Over the period of observation, the conversion rate decreased significantly from 2.2% to 1.2% (P(trend)< 0.001), as did intraoperative complications (from 3.1% to 0.7%; P(trend)< 0.001), surgical postoperative complications (from 6.1% to 1.9%; P(trend)< 0.001), general postoperative complications (from 4.9% to 1.5%; P(trend)< 0.001), and rates of reoperations (from 3.4% to 0.7%; P(trend)< 0.001). Average postoperative length of hospital stay also significantly decreased from 4.9 to 3.5 days (P(trend)< 0.001). CONCLUSIONS: Our investigation provides compelling evidence that intraoperative complications, surgical and general postoperative complications, conversion rates, rates of reoperations, and average length of hospital stay have significantly decreased over the past decade in patients undergoing surgery for acute appendicitis. The present trend analysis is the first one in the literature encompassing more than a decade and reporting clinical outcomes after laparoscopic appendectomy for acute appendicitis, which represents an important quality control.

Splanchnic vasoregulation after major abdominal surgery in pigs.

BACKGROUND: Unrecognized reduction of blood supply to intestinal organs is associated with significant postoperative morbidity in abdominal surgery. The aim of this study was to determine whether--in the absence of hypovolemia--intestinal hypoperfusion as a result of blood flow redistribution occurs after abdominal surgery. METHODS: Standardized operative trauma was induced in 14 healthy pigs. Systemic, regional, and local blood flow, intestinal and gastric intraluminal-to-end-tidal pCO(2) gradients representing mucosal perfusion, and oxygen transport variables were measured for 10 postoperative hours. Normovolemia was maintained using continuous infusion of Ringer's lactate and additional boluses of colloids in response to blood pressure, pulmonary wedge pressure, and urinary output. RESULTS: Postoperative blood flow was significantly increased in the celiac trunk (76% increase [percentage of baseline flow], p = 0.003) and the hepatic (136% increase, p = 0.002) and splenic (36% increase, p = 0.025) arteries. Blood flow was significantly decreased in the mesenteric artery (25% decrease, p = 0.007) and portal vein (13% decrease, p = 0.028). Carotid and renal artery blood flow remained unchanged. CONCLUSIONS: Maintenance of normovolemia is insufficient to protect from intestinal hypoperfusion after abdominal surgery. Postoperative redistribution of cardiac output results in decreased intestinal and increased hepatic and splenic arterial blood flow.

Validation of the International Tumor Budding Consensus Conference 2016 recommendations on tumor budding in stage I-IV colorectal cancer.

Tumor budding is a robust prognostic parameter in colorectal cancer and can be used as an additional factor to guide patient management. Although backed by large bodies of data, a standardized scoring method is essential for integrating tumor budding in reporting protocols. The International Tumor Budding Consensus Conference (ITBCC) 2016 has proposed such a scoring system. The aim of this study is to validate the ITBCC method of tumor budding assessment on a well-characterized colorectal cancer cohort. Three hundred seventy-nine patients with resected stage I-IV colorectal cancer were entered into the study. Tumor budding was scored by 2 pathologists according to the ITBCC recommendations on hematoxylin and eosin-stained slides and scored as BD1 (low grade), BD2 (intermediate grade), and BD3 (high grade). Analysis was performed using a 3-tier approach, a 2-tier approach (BD1 + 2 versus BD3) and budding as a continuous variable. High-grade tumor budding was associated with adverse clinicopathological features including higher pT, higher pN stage, and higher TNM stage (all P < .001) and poorer overall survival on univariate analysis (P = .0251 for BD1/2/3, P = .0106 for BD1 + 2 versus BD3, and P = .0195 for continuous scores; hazard ratio, 1.023 [95% confidence interval, 1.004-1.043 per bud]). In stage II cancers, BD3 was associated with poorer disease-free survival (P < .01). Tumor budding assessed by the method proposed by the ITBCC is applicable to colorectal cancer resection specimens and can be used for widespread reporting in routine.

Autologous transplantation of adipose-derived stem cells improves functional recovery of skeletal muscle without direct participation in new myofiber formation.

BACKGROUND: Skeletal muscle has a remarkable regenerative capacity. However, extensive damage that exceeds the self-regenerative ability of the muscle can lead to irreversible fibrosis, scarring, and significant loss of function. Adipose-derived stem cells (ADSC) are a highly abundant source of progenitor cells that have been previously reported to support the regeneration of various muscle tissues, including striated muscles. The aim of this study was to evaluate the effect of ADSC transplantation on functional skeletal muscle regeneration in an acute injury model. METHODS: Mouse ADSC were isolated from subcutaneous fat tissue and transplanted with a collagen hydrogel into the crushed tibialis anterior muscle of mice. Recovering muscles were analyzed for gene and protein expression by real-time quantitative polymerase chain reaction and immunohistochemistry. The muscle contractility was assessed by myography in an organ bath system. RESULTS: Intramuscular transplantation of ADSC into crushed tibialis anterior muscle leads to an improved muscle regeneration with ADSC residing in the damaged area. We did not observe ADSC differentiation into new muscle fibers or endothelial cells. However, the ADSC-injected muscles had improved contractility in comparison with the collagen-injected controls 28 days post-transplantation. Additionally, an increase in fiber cross-sectional size and in the number of mature fibers with centralized nuclei was observed. CONCLUSIONS: ADSC transplantation into acute damaged skeletal muscle significantly improves functional muscle tissue regeneration without direct participation in muscle fiber formation. Cellular therapy with ADSC represents a novel approach to promote skeletal muscle regeneration.

Postoperative splanchnic blood flow redistribution in response to fluid challenges in the presence and absence of endotoxemia in a porcine model.

We hypothesized that fluid administration may increase regional splanchnic perfusion after abdominal surgery-even in the absence of a cardiac stroke volume (SV) increase and independent of accompanying endotoxemia. Sixteen anesthetized pigs underwent abdominal surgery with flow probe fitting around splanchnic vessels and carotid arteries. They were randomized to continuous placebo or endotoxin infusion, and when clinical signs of hypovolemia (mean arterial pressure, <60 mmHg; heart rate, >100 beats · min(-1); urine production, <0.5 mL · kg(-1) · h(-1); arterial lactate concentration, >2 mmol · L(-1)) and/or low pulmonary artery occlusion pressure (target 5-8 mmHg) were present, they received repeated boli of colloids (50 mL) as long as SV increased 10% or greater. Stroke volume and regional blood flows were monitored 2 min before and 30 min after fluid challenges. Of 132 fluid challenges, 45 (34%) resulted in an SV increase of 10% or greater, whereas 82 (62%) resulted in an increase of 10% or greater in one or more of the abdominal flows (P < 0.001). During blood flow redistribution, celiac trunk (19% of all measurements) and hepatic artery flow (15%) most often decreased, whereas portal vein (10%) and carotid artery (7%) flow decreased less frequently (P = 0.015, between regions). In control animals, celiac trunk (30% vs. 9%, P = 0.004) and hepatic artery (25% vs. 11%, P = 0.040) flow decreased more often than in endotoxin-infused pigs. Accordingly, blood flow redistribution is a common phenomenon in the postoperative period and is only marginally influenced by endotoxemia. Fluid management based on SV changes may not be useful for improving regional abdominal perfusion.