Antibiotic-treated acute appendicitis-reception in social media.

PURPOSE: Social media, especially Twitter®, is becoming increasingly important for medical topics. Systematic analyses of the content of these tweets are rare. To date, no analysis of the reception of antibiotic/non-operative-treated acute appendicitis on Twitter® has been performed. METHODS: Tweets with the content "appendicitis," "appendix," and "appendectomy" from December 31, 2010, to September 27, 2017, were recorded. Further analysis was performed by secondary search strings related to antibiotic-treated acute appendicitis. Subsequent systematic analysis of content, author groups, and followers was performed. RESULTS: Out of 22,962 analyzed tweets, 3400 were applicable on all search strings, and 349 dealt meaningfully with antibiotic-treated acute appendicitis. 47.9% of the tweets were published by individuals, of which non-surgical consultants comprised the largest group. The tweets published by organizations and institutions were mostly published by publishing platforms. Half of the tweets were neutral, with an overall positive trend for antibiotic-treated acute appendicitis, but significant differences were noted among the authors. The number of followers showed a wide range, with an considerable numeric impact. CONCLUSION: The scientific discussion of antibiotic-treated acute appendicitis is reflected on Twitter®. Overall, antibiotic-treated acute appendicitis is presented in a neutral and differentiated manner on Twitter®, but this picture is exclusively derived from assessment of a variety of tweets. Individual tweets are partially undifferentiated in content and misrepresent antibiotic-treated acute appendicitis. In addition, content and intentions are significantly author dependent. Scientists should therefore use Twitter® to make sound medical information heard. If this policy is not implemented, the importance of inadequate and incorrect information transfer is indirectly increased.

Influence of the recipient body mass index on the outcomes after kidney transplantation.

PURPOSE: The relationship between the body mass index (BMI) of kidney transplant recipients and outcomes after kidney transplantation (KT) is not fully understood and remains controversial. We studied the influence of BMI on clinically relevant outcomes in kidney transplant recipients. METHODS: In this retrospective single-centre study, all patients who underwent kidney transplantation at our institution between January 2007 and December 2012 were included. Demographic data and BMI were correlated with the clinical course of the disease, rejection rates, delayed graft function rates, and graft and patient survival. RESULTS: During the study period, 384 single KTs (130 women and 254 men) were performed. Seventeen percent of the transplants were transplanted within the Eurotransplant Senior Programme (ESP). Most of the transplants were performed using organs that were obtained from donors after brain death (DBD), and living donor kidney transplants were performed in 22.4% of all transplants. The median BMI of the recipients was 25.9 kg/m2. Additionally, 13.5% of the recipients had a BMI of 30-34.9 kg/m2 and 3.9% had a BMI >35 kg/m2. A BMI >30 kg/m2 was significantly associated with primary non-function of the kidney (p = 0.047), delayed graft function (p = 0.008), and a higher rate of loss of graft function (p = 0.015). The glomerular filtration rate 12 months after KT was significantly lower in recipients with a BMI >30 kg/m2. Multivariate analysis revealed that recipient BMI, among other factors, was an independent risk factor for delayed graft function and graft survival. Patients with a BMI >30 kg/m2 had an almost four times higher risk for surgical site infection than did recipients with a lower BMI. CONCLUSIONS: Increased BMI at kidney transplantation is a predictor of adverse outcomes, including delayed graft function. These findings demonstrate the importance of the careful selection of patients and pre-transplant weight reduction, although the role of weight reduction for improving graft function is not clear.

The meteorological influence on seasonal alterations in the course of acute appendicitis.

BACKGROUND: Several diseases, including acute appendicitis (AA), have been known to undergo seasonal variations. Changes in the incidence and course of AA are attributed to seasonal weather differences, but this connection remains unproven. METHODS: In this retrospective, single-center analysis, we analyzed daily meteorological data over an 8-year period. A connection of day-by-day meteorological data with 680 consecutive appendectomies was performed. Patients' characteristics, intraoperative findings, and outcome parameters were analyzed. Seasons were classified meteorologically as 3-month periods (winter, spring, summer, and autumn). RESULTS: Nonambient temperature (unusual warm or cold weather) is correlated with a higher rate of complicated (gangrenous or perforated) AA (P = 0.018). In summer and winter, days with nonambient temperatures were more frequent (P < 0.0001). A higher rate of complicated AA was seen during summer and winter (P = 0.009). In addition, patients operated on in summer and accordingly after warm days suffer more complications (P < 0.0001), especially more superficial surgical site infections (P < 0.048). CONCLUSIONS: The concordant observation of more complicated AA and complications after AA with meteorological data and calendric seasonal variations makes it most likely that temperature is a cofactor in complicated AA and contributes to the seasonal variations in AA. Although an increase in the microbiome of the skin during warm seasons might explain the increase in surgical site infection, the functional connection between warmer temperatures and AA complications remains unclear.

Bad bacteria in acute appendicitis: rare but relevant.

PURPOSE: Bacterial infections are a factor for morbidity in patients with acute appendicitis (AA). The spreading of multidrug-resistant (MDR) bacteria is a significant problem in surgery, and the most relevant MDR pathogens are summarized as Enterobacteriaceae, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterococci (ESKAPE) bacteria. Data regarding the species and distribution of bacteria in AA are available, but information about the resistances and their relevance is deficient. METHODS: In this retrospective study, we analyzed microbiological swabs of patients with AA. The outcome parameters of patients after laparoscopic appendectomy were analyzed against microbiological results, including antibiotic resistance testing. Positive swabs were compared with bacteria cultivated after alternative abdominal emergency surgery (AES). RESULTS: In total, 584 patients with AA were included and had a mean age of 35.5 years. In 216 patients (36.9%), a swab was taken, and in 128 (59.3%) swabs, bacteria could be cultivated. The most frequent organisms were Escherichia coli, Bacteroides species, and Pseudomonas. In 9.4% of the positive AA swabs, MDR germs were cultivated, and all of them were ESKAPE pathogens. Patients with MDR bacteria in AA suffered more infectious complications (p = 0.006) and needed longer hospitalizations (p < 0.009). In AES, aside from appendicitis, a different spectrum containing more MDR bacteria was cultivated (5.9 vs. 20.9%; p < 0.0001). CONCLUSIONS: Although they occur less frequently in appendectomy compared to emergency surgeries for other abdominal diseases, MDR bacteria are traceable in this common disease and contribute to additional morbidity.

Salvage abdominoperineal excisions in recurrent anal cancer--impact of different reconstruction techniques on outcome, morbidity, and complication rates.

BACKGROUND: Squamous cell cancer of the anus (SCCA) is a rare disease of the gastrointestinal tract. Even though chemoradiation therapy is the treatment of choice, a substantial number of patients develop recurrent cancers or present with persisting SCCA. Therefore, abdominoperineal excisions as a salvage therapy are the only chance of cure. PATIENTS AND METHODS: Hospital files of all patients with recurrent squamous cell carcinoma of the anus who underwent abdominoperineal excision performed at the Department of General and Visceral Surgery of the University Hospital Frankfurt between January 2003 and December 2013 were retrospectively reviewed. RESULTS: Fourteen (nine males, five females) patients underwent abdominoperineal resections for recurrent SCCA. In six patients, the pelvic floor was closed by direct suture, four patients underwent reconstruction using a vertical rectus abdominis myocutaneous (VRAM) flap, and four patients received a gluteal myocutaneous flap. Patients receiving flap-mediated closure revealed a median hospital stay of 26 days (range 13-60 days) compared to 11 days (range 9-30 days) in patients with direct closure (p = 0.01). Two patients (14%) suffered from wound infections (Dindo-Clavien II), whereas three patients (21%) underwent up to seven reoperations for breakdown of their wounds and/or laparotomies (Dindo-Clavien IIIb). The calculated 5-year survival rate was 86%. Patients with rpT0/T1 stage had a significantly longer survival compared to patients presenting with rpT2/T3/T4 tumors. CONCLUSION: Abdominoperineal excisions in patients with recurrent SCCA can provide long-term local control and survival. The complication rate is not associated with the closure technique employed, but patients undergoing flap-mediated closure revealed a significantly longer hospital stay.

Education in thyroid surgery: a matched-pair analysis comparing residents and board-certified surgeons.

PURPOSE: Resident participation in operative procedures is mandatory in educational residency programs but remains controversial, especially in the context of patient safety. This study compared the surgical quality and outcomes of thyroidectomies performed by surgical residents (RESs) and board-certified surgeons (BCSs). METHODS: This retrospective matched-pair study included patients undergoing thyroidectomies for multinodular goiter, Grave's disease and early-stage thyroid cancer that were performed by a RES with BCS supervision between 2006 and 2014. The intraoperative and postoperative course, complication rates and handling of the recurrent laryngeal nerve (RLN) and parathyroid glands were analyzed. RESULTS: In total, 112 thyroidectomies that were performed by a RES fulfilled the inclusion criteria and were matched 1:1 with BCS patients. We included 88 hemithyroidectomies, 80 subtotal thyroidectomies and 56 total thyroidectomies. No significant differences in the handling of the RLN or parathyroid glands, the rates of postoperative RLN palsies or the rates of hypocalcaemia were found. No intraoperative complications led to the replacement of the RES as the surgeon-in-charge. Three RES and two BCS patients experienced postoperative haemorrhages (p = 0.205), and three surgical site infections (p = 1.000) occurred in each group. The mean operative time and the length of stay did not differ significantly between the two groups. CONCLUSIONS: Major aspects of patient safety in thyroid surgery are not affected by resident participation. Thyroidectomies performed by RES are not significantly longer and reveal no differences in length of stay or complication rates. The economic burden of resident involvement is modest.

Transanal hybrid colon resection: from laparoscopy to NOTES.

BACKGROUND: Reducing access size and trauma are important issues in natural orifice transluminal endoscopic surgery (NOTES). The combination of experience with laparoscopic colorectal surgery and transanal endoscopic microsurgery has helped in the use of the transanal approach as a realistic option of NOTES techniques to introduce transanal hybrid laparoscopic-assisted colon resection into clinical practice. The purpose of this study was to assess the clinical introduction of transanal hybrid colon resection in terms of feasibility and patient safety. METHODS: Patients with pelvic floor disorders, prolapse, and slow-transit constipation in whom a colon resection was indicated were recruited. Patients were followed prospectively with a postoperative well-being score, a pain score, and a quality-of-life score. All complications were prospectively documented. The essential change was the reduction of the number and size of ports by using the transanal route. A camera and two 5-mm ports for grasping forceps and delivering ultrasonic energy were the laparoscopic components. All tasks requiring a port diameter of >5 mm were applied via the transanal route, such as positioning of the proximal stapler anvil, application of linear stapling for resection, specimen retrieval, stapler anastomosis, and closing the bowel. RESULTS: Fifteen patients with benign colorectal disease underwent transanal hybrid colon resection, and 11 had additional rectopexy. All patients were women with a mean age of 61 (range, 28-86) years and a body mass index of 26 kg/m(2). One patient was converted to full laparoscopy. One complication--bleeding that required no reintervention--was recorded. The procedure lasted a mean of 131 (range, 55-184) min. The Gastrointestinal Quality of Life Index was 96 before surgery and 117 after surgery. CONCLUSIONS: From this initial experience, transanal hybrid colon resection seems a feasible and safe hybrid NOTES procedure that can be usefully introduced into clinical practice.

Robotic operations in urgent general surgery: a systematic review.

Robotically assisted operations are the state of the art in laparoscopic general surgery. They are established predominantly for elective operations. Since laparoscopy is widely used in urgent general surgery, the significance of robotic assistance in urgent operations is of interest. Currently, there are few data on robotic-assisted operations in urgent surgery. The aim of this study was to collect and classify the existing studies. A two-stage, PRISMA-compliant literature search of PubMed and the Cochrane Library was conducted. We analyzed all articles on robotic surgery associated with urgent general surgery resp. acute surgical diseases of the abdomen. Gynecological and urological diseases so as vascular surgery, except mesenterial ischemia, were excluded. Studies and case reports/series published between 1980 and 2021 were eligible for inclusion. In addition to a descriptive synopsis, various outcome parameters were systematically recorded. Fifty-two studies of operations for acute appendicitis and cholecystitis, hernias and acute conditions of the gastrointestinal tract were included. The level of evidence is low. Surgical robots in the narrow sense and robotic camera mounts were used. All narrow-sense robots are nonautonomous systems; in 82%, the Da Vinci® system was used. The most frequently published emergency operations were urgent cholecystectomies (30 studies, 703 patients) followed by incarcerated hernias (9 studies, 199 patients). Feasibility of robotic operations was demonstrated for all indications. Neither robotic-specific problems nor extensive complication rates were reported. Various urgent operations in general surgery can be performed robotically without increased risk. The available data do not allow a final evidence-based assessment.

Frailty in elderly patients with acute appendicitis.

PURPOSE: Acute appendicitis in the elderly is becoming increasingly recognized for its often severe course. For various elective and urgent operations in older patients, frailty is a risk factor for poor outcomes. However, there is a lack of data on frailty in elderly patients with acute appendicitis. METHODS: Patients over 65 years old who underwent surgery for acute appendicitis in three hospitals between January 2015 and September 2020 were assessed with the Hospital Frailty Risk Score (HFRS) and the modified Frailty Index (mFI). Outcomes of interest, including morbidity, mortality, and length of stay, were recorded. RESULTS: While frailty can be measured with both tests, the mFI has better applicability and takes significantly less time to implement compared to the HFRS (21.6 s vs. 80.3 s, p < 0.0001) while providing the same information value. Patients who exhibited frailty according to either assessment had a significantly higher rate of milder (OR 5.85/2.87, p < 0.0001/0.009) and serious (OR 4.92/3.61, p < 0.011/0.029) complications, more admissions to the intensive care unit (OR 5.16/7.36, p < 0.0001), and an almost doubled length of stay (12.7 days vs. 6.6 days, p < 0.005). Up to 31% of these patients required institutional care after discharge, which is significantly more than those without frailty (p < 0.0001). Furthermore, the mortality rate in frail patients was significantly elevated to 17%, compared to less than 1% in non-frail patients (p = 0.018). CONCLUSION: In elderly patients, frailty is a significant risk factor for negative outcomes. Frailty can be assessed more quickly and reliably with the mFI compared to the HFRS.

Experience with flexible stapling techniques in laparoscopic and conventional surgery.

BACKGROUND: Currently, advanced minimal-access surgery cannot be realized without the application of modern stapling devices. The introduction of stapling devices with a flexible shaft and computer-assisted steering abilities was followed by the technical basis to provide just these features. This study aimed to assess the clinical application of stapling devices connected to a flexible shaft supported by a computer-assisted drive for maneuvering the system and to study its feasibility, learning curve problems, and clinical safety criteria regarding morbidity of the patients. METHODS: The experience with laparoscopic and open gastrointestinal and colorectal surgery was evaluated. Patients with esophageal, gastric, and colorectal diseases were selected. The stapling system consisted of a power console connected to a flexible shaft and a remote control unit. On the tip of the flexible shaft stapler, loading units could be attached and operated by the remote control. A circular loading unit, size 29 mm, was used for esophageal, gastric, and rectal anastomoses. The linear stapler (length, 55/75 mm) was applied for the gastric tube after esophageal resection, for the jejunal pouch after total gastrectomy, and for division and closure of small bowel. It also was used during laparoscopic sleeve gastrectomy or laparoscopic fundoplication with COLLIS-gastroplasty. All data from the procedures were prospectively assessed and documented. A literature analysis was performed to compare morbidity data and leak rates with those of the current study. RESULTS: During an 8-year period, 394 patients (253 men and 141 women) were included in this study, and laparoscopic technique was performed in 52% of the cases. The mean age of the patients was 63 years (range, 16-93 years), and 33% of the patients had an American Society of Anesthesia classification of 3 or 4. A total of 1,258 firings were performed. The procedures included 54 esophageal resections, 90 gastric operations, and 197 colorectal resections. In the early experience, computer failures occurred for 2.9% of 173 patients (5 of 144 cartridge firings, 3.5%). Later, the problems and leak rate dropped from the initial 6.6% (11/173) to 3.2% (7/221). The complication and morbidity rates were similar to those in the literature. The flexible system had the advantage of enabling stapler application in special indications such as performance of intraabdominal laparoscopic COLLIS-Plasty by bending the system along the subphrenic area. CONCLUSIONS: Application of the described stapling system was thought to be advantageous, especially for minimal-access surgery and special indications that required a flexible shaft. This advantage allows for introduction of innovative techniques in gastrointestinal and colorectal surgery.

Nonoperative Antibiotic Treatment of Appendicitis in Adults: A Survey among Clinically Active Surgeons.

BACKGROUND: As a result of well-publicized studies, the nonsurgical antibiotic therapy of uncomplicated acute appendicitis has been propagated since 2006. A final assessment regarding efficiency and long-term results is not possible; however, nonoperative therapy of acute appendicitis is actually being discussed more diversely and receives a lot of attention. It is still unknown how far this therapy has found its way into everyday clinical care. METHODS: An online questionnaire was sent to 1,400 randomly selected specialists for general/visceral surgery in Germany. Representativeness was achieved by a preselection according to the geographical origin and the care level of the hospitals. RESULTS: 14% of surgeons stated that they methodically treat appendicitis conservatively. 38.1% do so in exceptional cases, while 48.8% reject this therapy. For methodically use, sonography or computed tomography is demanded beforehand. Nonoperative therapy is performed more often in metropolitan areas and maximum-care/university hospitals. Patients' request for antibiotic therapy is an important factor for conservative treatment. The main argument against this therapy is "medical doubts." 26% of the surgeons would treat their own appendicitis conservatively. There are distinct associations between the application of conservative therapy, satisfaction with it, and expectations about future development. The response rate was 19.9%. CONCLUSION: The nonoperative antibiotic therapy of appendicitis is part of clinical practice in Germany. There are differences in preconditions as well as in the acceptance of this therapeutic option with a high proportion of general rejection.

Deep Vein Thrombosis of the Upper Extremity.

BACKGROUND: Deep venous thrombosis (DVT) arises with an incidence of about 1 per 1000 persons per year; 4-10% of all DVTs are located in an upper extremity (DVT-UE). DVT-UE can lead to complications such as post-thrombotic syndrome and pulmonary embolism and carries a high mortality. METHODS: This review is based on pertinent literature, published from January 1980 to May 2016, that was retrieved by a systematic search, employing the PRISMA criteria, carried out in four databases: PubMed (n = 749), EMBASE (n = 789), SciSearch (n = 0), and the Cochrane Library (n = 12). Guidelines were included in the search. RESULTS: DVT-UE arises mainly in patients with severe underlying diseases, especially cancer (odds ratio [OR] 18.1; 95% confidence interval [9.4; 35.1]). The insertion of venous catheters-particularly central venous catheters-also elevates the risk of DVT-UE. Its clinical manifestations are nonspecific. Diagnostic algorithms are of little use, but ultrasonography is very helpful in diagnosis. DVT-UE is treated by anticoagulation, with heparin at first and then with oral anticoagulants. Direct oral anticoagulants are now being increasingly used. The thrombus is often not totally eradicated. Anticoagulation is generally continued as maintenance treatment for 3-6 months. Interventional techniques can be used for special indications. Patients with DVT-UE have a high mortality, though they often die of their underlying diseases rather than of the DVT-UE or its complications. CONCLUSION: DVT of the upper extremity is becoming increasingly common, though still much less common than DVT of the lower extremity. The treatment of choice is anticoagulation, which is given analogously to that given for DVT of the lower extremity.

A Retrospective, Observational Study of Enteral Nutrition in Patients with Enteroatmospheric Fistulas.

Enteroatmospheric fistulas (EAFs) represent a challenging problem in patients with an open abdomen (OA). A retrospective, descriptive study was conducted to evaluate the effects of enteral alimentation on wound status and management and nutrition. All patients with an EAF in an OA treated between October 2012 and December 2014 at a university hospital in Germany were included without criteria for exclusions. Demographic and morbidity-related data collected included age, gender, surgeries, OA grading, body mass index (BMI), serum albumin, and serum creatinin. Underlying diseases and time between the index operation and the formation of the OA and EAFs were analyzed in relation to the initiation of enteral nutrition (EN), which can aggravate and contaminate the OA due to intestinal secretions necessary for digestion. The OA was described in size and area of the fascia defect and classified according to the Björck Scale. The number and location of the fistulas and the duration of negative pressure wound therapy (NPWT) were documented. Outcome parameters included fistula volume, wound management (eg, dressing change frequency, need for wound revision), feeding tolerance, systemic impact of nutrition, nutrition status at discharge, and mortality. Data were analyzed using primary descriptive statistics. The Mann-Whitney test was used to evaluate changes in fistula volume and BMI; categorical data were compared using Fisher's exact test. A P value less than 0.05 was considered significant. Ten (10) patients (8 women, median age of participants 55.4 [range 44-71] years) were treated during the study time period. Seven (7) patients had the first fistula orifice in the upper jejunum (UJF); 8 had more than 1 fistula. EN was initiated with high caloric liquid nutrition and gradually increased to a 25 kcal/kg/day liquid or solid nutrition. All patients were provided NPWT at 75 mm Hg to 100 mm Hg. EN was not followed by a significant increase of median daily fistula volume (1880 mL versus 2520 mL, P = 0.25) or the need for more frequent changes of NPWT dressings (days between changes 2.6 versus 2.9, P = 0.19). In 9 patients, the severity of wound complications such as inflammation or skin erosion decreased both in frequency and magnitude (eg, affected area). All patients achieved a sufficient oral intake, but only 3 were discharged from the hospital without parenteral nutrition. In this study, EN did not cause additional problems in wound management but did not provide sufficient alimentation in patients with a UJF. Prospective studies are needed to clarify associations between EN, nutrition, and wound management.

Increased replication of human cytomegalovirus in retinal pigment epithelial cells by valproic acid depends on histone deacetylase inhibition.

PURPOSE: Human cytomegalovirus (HCMV) replication depends on different cellular pathways, including histone acetylation and extracellular-signal regulated kinases 1 and 2 (Erk 1/2). In the present study, the influence of therapeutic valproic acid (VPA) concentrations was investigated on HCMV replication in retinal pigment epithelial (RPE) cells. METHODS: HCMV antigen expression and replication were detected by immunostaining, real-time RT-PCR, and determination of virus titers. Histone acetylation and Erk 1/2 phosphorylation were detected by Western blot. RESULTS: Pretreatment with VPA < or =1 mM enhanced HCMV antigen expression and replication by up to ninefold. In addition to histone deacetylase (HDAC) inhibition, VPA stimulated Erk 1/2 phosphorylation in RPE cells. Investigation of six VPA derivatives revealed that S-2-pentyl-4-pentynoic acid was the only derivative that induced histone hyperacetylation, indicating HDAC inhibition, in the observed concentrations < or =1 mM and that increased HCMV antigen expression. Other derivatives did not enhance HCMV replication in the tested concentrations, although some were found to induce Erk 1/2 phosphorylation. The mitogen-activated protein kinase kinase (MEK) inhibitor PD98059 inhibited VPA-induced Erk 1/2 phosphorylation but did not affect VPA-induced increased HCMV replication. In addition, the structurally nonrelated HDACI trichostatin A enhanced HCMV replication but did not affect Erk 1/2 phosphorylation in RPE cells. CONCLUSIONS: The data demonstrate that VPA stimulates HCMV replication by HDAC inhibition independent of Erk 1/2 phosphorylation in therapeutic concentrations in RPE cells. Therefore, patients at risk of HCMV retinitis who are treated with VPA or other HDAC inhibitors should be carefully monitored.

Abdominoperineal Excisions in the Treatment Regimen for Advanced and Recurrent Vulvar Cancers-Analysis of a Single-Centre Experience.

Vulva cancer is the fourth leading gynaecological malignancy, accounting for approximately 4 % of all gynaecological cancers. Surgery represents the treatment of choice, and cases of advanced or recurrent vulvar cancers are to date a major challenge to multidisciplinary teams. Abdominoperineal excision (APE) in combination with vulvectomy and inguinal lymphadenectomy is the only curative treatment option. Patients' files of all women with squamous cell carcinoma of the vulva who underwent abdominoperineal resection were retrospectively reviewed with special regards to technical challenges the general surgeon will face. Seven women were enrolled in this retrospective study with a median age of 71 years (range 56-79 years). In six patients, the pelvic floor after abdominoperineal excision could be closed by direct suture of the levator muscles. One woman underwent abdominoperineal resection with closure of the defect using a vertical rectus abdominis myocutaneous (VRAM) flap. All women underwent radical vulvectomy, in five patients in combination with bilateral inguinal lymph node dissection. Operation time was 377 min (range 130-505 min). The median overall survival after surgery was 27 months (range 4-84 months), with a calculated 5-year survival rate of 42 %. Women with negative lymph nodes revealed a longer survival time after surgery compared to women with lymph node metastases (15.5 vs. 72 months; p = 0.09). Abdominoperineal excisions represent a powerful tool in the multidisciplinary treatment regimen of advanced or recurrent vulvar cancer. Reconstruction of the pelvic floor usually does not require myocutaneous flaps, even when facing large tumours. Despite high complication rates, radical surgery was a feasible treatment with long-term survival potential without mortality.

Increased human cytomegalovirus replication in fibroblasts after treatment with therapeutical plasma concentrations of valproic acid.

Valproic acid (2-propylpentanoic acid, VPA), an effective inhibitor of histone deacetylases (HDAC) is used for the treatment of epilepsia. In this study, structure-activity relationships for the action of structurally modified VPA derivatives on human cytomegalovirus (HCMV) replication and HDAC inhibition were defined. Pretreatment of human foreskin fibroblasts with VPA (0.125-1mM) caused a concentration-dependent increase of HCMV immediate early and antigen late antigen expression. Structure-activity relationships of VPA derivatives for HCMV stimulation were compared to those for teratogenic action and those for HDAC inhibition. Side chain elongation and introduction of a triple bond in 4-position of the other chain caused teratogenicity, stimulated HCMV replication, and increased HDAC inhibition, as demonstrated by enhanced levels of acetylated histones. Teratogenic VPA derivatives with a branched chain in 3-position as well as a non-teratogenic anticonvulsive active VPA derivative did not stimulate HCMV or accumulation of acetylated histones. This demonstrates a strict correlation between inhibition of HDAC and increased HCMV replication.