Well-promising outcomes with vacuum-assisted closure in an infected wound following laparotomy: A case report.

INTRODUCATION: Negative pressure wound therapy (NPWT) represents an alternative method to optimize conditions for wound healing. Delayed wound closure is a significant health problem, which is directly associated with pain and suffering from patient's aspect, as well with social and financial burden. PRESENTATION OF CASE: We report a case of vacuum-assisted wound therapy with hypertonic solution distillation and continuous negative pressure application, in an infected wound after laparotomy for incisional hernia reconstruction with mesh placement. Negative pressure was initiated at the wound margins after failure of conventional treatment with great outcomes, achieving a total closure of the incision within two weeks. DISCUSSION: Each wound has particular characteristics which must be managed. Vacuum assisted closure (VAC) with continuous negative pressure and simultaneous wound instillation and cleanse can provide optimum results, reducing the cavity volume, by newly produced granulated tissue. CONCLUSION: The simultaneous use of instillation and constant pressure seemed to be superior in comparison with NPWT alone. Compared to conventional methods, the use of VAC ends to better outcomes, in cases of infected wounds following laparotomy.

Advanced Mesodermal (Müllerian) Adenosarcoma of the Ovary: Metastases to the Lungs, Mouth, and Brain.

Background. A malignant mixed Müllerian tumor (MMMT) is a malignant neoplasm found in the uterus, the ovaries, the fallopian tubes, and other parts of the body that contains both carcinomatous (epithelial tissue) and sarcomatous (connective tissue) components. Outcome of MMMTs is determined primarily by depth of invasion and stage. The metastatic background of these lesions is controversial and unknown. Case Report. A 75-year-old woman was admitted to the hospital with anorexia, weakness, and persistent coughing. The imaging exams revealed a solid, promiscuous lesion of 16 × 14 cm in dimensions located into the small pelvis, surrounding the uterus and the ovaries. The patient underwent exploratory laparotomy. The mass was removed and the histological examination of the specimen revealed an advanced mesodermal adenocarcinoma of the ovary (MMMT). Nine days after the operation the patient presented with metastatic lesions in the mouth as well as the lungs. Within a month after the discharge from the hospital metastatic lesions of the MMMT were also depicted in the CT brain scan. Conclusion. Despite the fact that sarcomas have a long-term metastatic potential, to our knowledge this is the first case of Müllerian adenosarcoma presenting with such extraperitoneal metastases.

Alagille Syndrome: A New Missense Mutation Detected by Whole-Exome Sequencing in a Case Previously Found to Be Negative by DHPLC and MLPA.

Alagille syndrome (ALGS, MIM 118450) is an autosomal dominant, multisystem disorder with high variability. Two genes have been described: JAG1 and NOTCH2. The population prevalence is 1:70,000 based on the presence of neonatal liver disease. The majority of cases (∼97%) are caused by haploinsufficiency of the JAG1 gene on 20p11.2p12, either due to mutations or deletions at the locus. Less than 1% of cases are caused by mutations in NOTCH2. The most widely used methods for mutational screening include denaturing high-performance liquid chromatography (DHPLC) and multiplex ligation-dependent probe amplification (MLPA). Very recently, whole-exome sequencing (WES) has become technically feasible due to the recent advances in next-generation sequencing technologies, therefore offering new opportunities for mutations/genes identification. A proband and its family, negative for the presence of mutations in JAG1 and NOTCH2 genes by neither DHPLC nor MLPA, were analyzed by WES. A missense mutation, not previously described, in JAG1 gene was identified. This result shows an improvement in the mutation detection rate due to novel sequencing technology suggesting the strong need to reanalyze all negative cases.

Two Novel COH1 Mutations in an Italian Patient with Cohen Syndrome.

Cohen syndrome (CS) is an autosomal recessive disease caused by mutations in the COH1 gene. It is characterized by intellectual disability, hypotonia, joint hyperlaxity, severe myopia, characteristic facial dysmorphisms and, in some cases, intermittent isolated neutropenia. We investigated an Italian patient with CS together with his family. Genetic analysis disclosed 2 novel mutations: the first is an intronic mutation (c.8697-9A>G) creating a new splice site 8 nucleotides upstream, and the second is a duplication of 1 base (c.10156dupA) generating a premature stop codon. The compound heterozygous mutations explain the proband's phenotype and improved the knowledge of genotype-phenotype correlation.

Identification of a New Mutation (L46P) in the Human NOG Gene in an Italian Patient with Symphalangism Syndrome.

Proximal symphalangism (SYM1) is a joint morphogenesis disorder characterized by stapes ankylosis, proximal interphalangeal joint fusion, skeletal anomalies and conductive hearing loss. Noggin is a bone morphogenetic protein (BMP) antagonist essential for normal bone and joint development in humans and mice. Autosomal dominant mutations have been described in the NOG gene, encoding the noggin protein. We analyzed an Italian sporadic patient with SYM1 due to a novel NOG mutation (L46P) based on a c.137T>C transition. A different pathogenic mutation in the same codon (L46D) has been previously described in an in vivo chicken model. An in silico model shows a decreased binding affinity between noggin and BMP7 for both L46D and L46P compared to the wild type. Therefore, this codon should play an important role in BMP7 binding activity of the noggin protein and consequently to the joint morphogenesis.

The factors contributing to the risk of sudden infant death syndrome.

Sudden infant death syndrome (SIDS) is defined as the sudden death of an infant under one year of age which remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene and review of the clinical history. SIDS is one of the leading causes of infant mortality and occurs from the first month, until the first year of life for newborns and infants.The aim of this review was to identify and examine risk factors responsible for causing the sudden infant death and to propose certain measures in order to protect newborns and infants from sudden death. The potential factors that contribute to the occurrence of SIDS include inadequate prenatal care, low birth weight (<2499gr), premature infants, intrauterine growth delay, short interval between pregnancies and maternal substance use (tobacco, alcohol, opiates). Moreover, factors related to infant's sleep environment such as the prone or side sleeping position and thick coverlet increase the risk of sudden death in infants. Also, the combination of risk factors such as that of prone sleeping position and soft bed mattress are linked to a 20-fold increased risk of death. Finally, polymorphisms in the serotonin transporter gene (5-HTT), viral respiratory infections, long Q-T (responsible for the presence of fatal arrhythmia) are related to the SIDS.Literature review indicates that each individual risk factor contributes to the appearance of SIDS and the establishment of certain protective measures for parents and health professionals has reduced its prevalence. But the precise identification of the SIDS causes and how these contribute to the occurrence of sudden death in neonates and infants, remains a challenge for health professionals.

Simple suture or prosthesis hiatal closure in laparoscopic repair of paraesophageal hernia: a retrospective cohort study.

Laparoscopic repair of paraesophageal hernia (PEH) involves removal of the hernia sac, cruroplasty, and fundoplication. Mesh application to cruroplasty seems to reduce hernia recurrence rate, but may be associated with dysphagia. The aim of the study was to review the clinical and laboratory outcomes of a series of patients with PEH after laparoscopic repair. Patients with PEH, who had laparoscopic repair and 1-year postoperative follow-up, were included in the study. Pre- and postoperative testing included symptom questionnaires, barium esophagogram, pH-monitoring, barium swallow testing. In the first half cases, suturing of large hernia gaps was reinforced with prosthesis (PR), whereas in the second half only suture cruroplasty (SC) was performed. Sixty-eight patients (36 male) with PEH were included in the study. There were no conversions to open. Postoperatively, dysphagia grading was significantly correlated to esophageal transit time (P < 0.001). There were seven recurrences; one paraesophageal and six wrap migrations. Also, four cases with stenosis were identified all in the PR group. Dysphagia was more common (P= 0.05) and esophageal transit more delayed (P= 0.034) after PR than after SC. Two revisions, one for esophageal stenosis and one for recurrent PEH, derived from the SC group. Reflux was more common after Toupet fundoplication than after Nissen fundoplication (NF) (P= 0.031) in patients with impaired esophageal motility. Laparoscopic repair of PEH with SC is associated with satisfactory clinical outcomes and low rate of wrap migration, at least similar to PR hiatal repair. NF is effective as an antireflux procedure in all cases.

Analysis of DEFB1 regulatory SNPs in cystic fibrosis patients from North-Eastern Italy.

Cystic fibrosis (CF) transmembrane regulator protein (CFTR) gene is undoubtedly the main genetic factor involved in the modulation of CF phenotype. However, other factors such as human defensins and the genes encoding for these antimicrobial peptides have been hypothesized as possible modifiers influencing airways infection in CF patients, but their role in the pathogenesis of lung disease is still debated. Since DEFB1 gene encoding for human beta-defensin 1 displays features such as antimicrobial or chemotactic activity playing a role in inflammation, it has been considered as a possible candidate CF modifier gene. We analysed three single nucleotide polymorphisms (SNPs) in the 5'-untranslated region of the DEFB1 gene (namely g-52G>A, g-44C>G and g-20G>A) in a group of 62 CF patients from North Eastern Italy, and in 130 healthy controls, with the aim of verifying the possible association of these functional SNPs with the pulmonary phenotype of CF patients. DEFB1 SNPs have been genotyped by using Taqman allele-specific fluorescent probes and a real-time PCR platform. No significant differences were found for allele, genotype and haplotype frequencies of DEFB1 g-52G>A, g-44C>G and g-20G>A SNPs in CF patients stratified for Pseudomonas aeruginosa infection, as well as in patients with a severe and mild clinical phenotype or in patients stratified for CFTR genotypes. DEFB1 allele, genotype and haplotype frequencies of CF patients globally considered were similar to those of healthy controls. Our findings are discordant with respect to another recent study performed on CF patients coming from Southern Italy, probably due to different ethnicity of the patients.

Abdominal and pelvic stop-flow chemotherapy. Effect of chemotherapeutic agents and tissue ischemia on rectoanal pressures.

In hypoxic stop-flow chemoperfusion high doses of chemotherapeutic agents are almost directly administered to locally advanced tumors without risking significant systemic toxicity, although chemotherapy-induced neurotoxicity is still a problem. The aim of the study was to assess rectoanal motility and sensation before, during and after abdominal and pelvic stop-flow chemotherapy using the methods of stationary and ambulatory manometry. Stationary rectoanal manometry was performed within 24 hrs before and repeated 48 hrs after stop-flow chemotherapy in 7 consecutive patients with a history of locally advanced or recurrent abdominal and pelvic tumors. Anal sphincter resting and squeeze pressures, rectal sensitivity, rectoanal inhibitory reflex and rectal volumes at which temporary and permanent urge to defecate were reported were examined. Rectal volume associated with leak of rectal contents and rectal compliance were also assessed. Intraoperatively, changes in rectal and anal resting pressures before, during and after occlusion of the vessels and after administration of chemotherapeutic agent were as well recorded, analyzed and interpreted using ambulatory manometry. Induction of anesthesia reduced distal and proximal anal resting pressures. Vascular occlusion further and dramatically decreased resting pressures at all levels, which were fully recovered after re-establishing local blood circulation and for the rest of the recording period. Intraoperative administration of chemotherapy did not further affect anal resting pressures during or after hypoxia. No significant changes in rectoanal motility and sensation were detected on the 48 hrs postoperative assessment as compared to the preoperative state. Tissue hypoxia induced by vascular occlusion during stop-flow chemotherapy procedure, seems to be the only factor leading to a dramatic drop of anal pressures. Anal pressures fully recover after reperfusion of the isolated area. Furthermore, anorectal motility and sensation are not affected by any direct or indirect toxic action of the chemotherapeutic agents.

Effect of sodium valproate on esophageal motility in healthy subjects and patients with gastroesophageal reflux.

BACKGROUND: There is experimental evidence to show that upper gastrointestinal tract motility is influenced by a GABAergic mechanism. Sodium valproate acts as a GABA agonist, and has been proven to affect the human internal anal sphincter. The aim of this study was to evaluate any possible effect of sodium valproate on esophageal motility in healthy subjects and patients with gastroesophageal reflux disease (GERD). METHODS: Ten healthy volunteers (4 M, 6 F; age range: 20-61 years) and 12 patients (4 M, 8 F; age range: 25-70 years) with GERD were included in the study. Standard esophageal manometry and ambulatory 24-h esophageal pH monitoring were performed before and 5 days after oral administration of sodium valproate (400 mg four times per day). Main measurements included a) lower esophageal sphincter (LES) resting pressure and amplitude and duration of peristalsis at 5, 10 and 15 cm proximal to LES, and b) percentage of time with esophageal pH <4 and number of reflux episodes. RESULTS: Sodium valproate (i) significantly increased LES resting pressure in both groups (P<0.05), without affecting either the LES postdeglutition relaxation or any of the parameters of the esophageal peristaltic activity, (ii) significantly reduced the number of reflux episodes at the postprandial period in both healthy subjects (P=0.02) and reflux patients without hiatal hernia (P=0.04) and (iii) the time percentage with esophageal pH <4 at the postprandial period in reflux patients (P=0.01). CONCLUSIONS: Sodium valproate increases normal and reduced tonic activity of the human LES and reduces the number of reflux episodes in health and GERD. This action could be attributed to a central GABAergic mechanism.

First-line intra-arterial chemotherapy (IAC) with epirubicin and mitoxantrone in locally advanced breast cancer.

BACKGROUND: Approximately 20% of patients with breast cancer present with locally advanced disease without distant metastases. This phase II double-center trial aimed at investigating the activity of epirubicin (Farmorubicin)--mitoxantrone (Onkotrone/Novantrone) combination as first-line intra-arterial chemotherapy (IAC) in locally advanced breast cancer patients. PATIENTS AND METHODS: Thirty-six patients with locally advanced disease and no prior exposure to anthracyclines received the following regimen: epirubicin (Farmorubicin) 30 mg/mq and mitoxantrone (Onkotrone/Novantrone) 10 mg/mq by IAC short infusion on day 1, every 3 weeks for up to six cycles. Prior to IAC an arteriogram of subclavian, internal mammary and lateral thoracic arteries was obtained in all patients, followed by infusion of a blue dye solution into the arteries to determine the most appropriate vessel that supplies the tumor area. RESULTS: Objective responses, confirmed at least 4 weeks after the first documentation, were observed in 25 patients (70%; 95%CI, 62% to 80%): 3 CR, 22 PR. Although three of the patients showed complete tumor regression, operative removal or toilet mastectomy became feasible in 25 patients since tumor shrinkage ranged over 75%. A total of 25 mastectomies were carried out for 36 patients. Four patients had bulky tumors (> 13 cm tumor diameter), while 8 patients had ulcerated tumors, two of which presented with complete infiltration of normal breast tissue. The median time to progression and median overall survival were 11 and 27 months, respectively. The time to local response was 3 weeks and time to mastectomy was 9 weeks. Transient neurological disorders developed in six patients and skin chemical burns with painful inflammatory reactions were encountered in ten patients. No systemic toxicity was observed in terms of bone marrow depression and hair loss. No cardiotoxicity was observed. In all specimens necrosis was reported (complete 3 cases, partial 16 and minimal 6). CONCLUSION: A combination of epirubicin (Farmorubicin) and mitoxantrone (Onkotrone/Novantrone) as IAC appears to be a safe and well tolerated treatment for locally advanced breast cancer without clinical evidence of distant metastases. When combined with surgery it offers interesting results in terms of local control and allows a high rate of mastectomies in otherwise inoperable cases.

Octreotide enhances the accelerating effect of erythromycin on gastric emptying in healthy subjects.

BACKGROUND: Erythromycin exhibits gastrokinetic properties through cholinergic pathways. Reports regarding the action of octreotide on gastric emptying are conflicting. AIM: : To assess: (i) the hypothesis that serotonin receptors are involved in the accelerating effect of erythromycin on gastric emptying; and (ii) any modification of the gastrokinetic action of erythromycin induced by octreotide. SUBJECTS AND METHODS: Gastric emptying of a standard meal was estimated in 20 healthy subjects by scintigraphy on three different occasions in a double-blind, placebo-controlled manner and in random order: (i) after placebo; (ii) after 200 mg of intravenous erythromycin; and (iii) after 200 mg of intravenous erythromycin following pre-treatment with either 4 mg of intravenous ondansetron (10 subjects) or 50 micro g octreotide. RESULTS: Erythromycin significantly accelerated gastric emptying in all subjects by abolishing the lag phase. Pre-treatment with ondansetron abolished the accelerating effect of erythromycin by restoring the emptying times to placebo levels. Octreotide significantly enhanced the accelerating effect of erythromycin by reducing both the lag and post-lag phases of gastric emptying. CONCLUSIONS: Serotonin receptors are involved in the accelerating effect of erythromycin on gastric emptying. This effect seems to be enhanced by pre-treatment with octreotide, possibly as a result of the modification of the gastrointestinal hormonal environment.

Laparoscopic vs open approach for Nissen fundoplication. A comparative study.

BACKGROUND: Several studies, most of them nonrandomized, have shown similar functional results for both laparoscopic and open Nissen fundoplication, the operation of choice for the treatment of gastroesophageal reflux disease (GERD). METHODS: A total of 106 patients with documented GERD were randomized to receive either a laparoscopic or an open Nissen fundoplication. Preoperative and postoperative investigations included clinical assessment, esophagogram, upper gastrointestinal endoscopy, esophageal manometry, and 24-h ambulatory pHmetry. RESULTS: Both approaches were successful in controlling reflux. There was an overall improvement in esophageal peristalsis and an increase in lower esophageal sphincter (LES) pressure in both groups. Open Nissen fundoplication was associated with a significantly increased rate of wound (p <0.001) and respiratory (p <0.05) complications. Hospitalization was also longer after the open technique (p <0.001). At 3-month follow-up, although the rate of postoperative dysphagia was similar for the two approaches, the open approach was associated with a significantly higher incidence of postprandial epigastric fullness (p <0.05) and bloating syndrome (p <0.01). CONCLUSIONS: The open and laparoscopic approaches for the Nissen fundoplication are equally effective in controlling GERD. The open approach is associated with a significantly higher rate of wound and respiratory complications and, at early stages, an increased rate of postprandial epigastric fullness and abdominal bloating. The dysphagia rate is similar with both methods.

Laparoscopic Heller cardiomyotomy and Dor fundoplication for esophageal achalasia: possible factors predicting outcome.

HYPOTHESIS: Laparoscopic Heller myotomy with anterior hemifundoplication is the surgical procedure of choice for the treatment of esophageal achalasia. Specific factors, eg, severity of esophageal body deformity, might affect postoperative outcome. DESIGN: Prospective case-control study. SETTING: Academic referral center for gastrointestinal tract motility disorders. PATIENTS: Twenty-nine patients with esophageal achalasia who underwent 1 to 3 sessions of failed pneumatic dilation each. INTERVENTION: Laparoscopic Heller myotomy with anterior (Dor) hemifundoplication. MAIN OUTCOME MEASURES: Preoperative and postoperative symptomatic evaluation, esophagoscopy, esophagography, stationary and ambulatory esophageal manometry, and pH monitoring. RESULTS: Three patients had stage I disease, 10 had stage II, 12 had stage III, and 4 had stage IV at preoperative radiologic examination. At surgery, there were no conversions to open procedures, and 2 mucosal perforations were immediately identified and sutured. Good or excellent results were seen in 26 patients. All patients with stage I or II disease had excellent functional results. Of patients with stage III disease, results were excellent in 7, good in 4, and bad in 1. Of patients with stage IV disease, 2 had good results and 2 had bad results. After surgery, lower esophageal sphincter pressure was reduced significantly (from 46.1 +/- 12.1 to 5.4 +/- 1.8 mm Hg; P<.001), as was esophageal diameter (from 61 +/- 17 to 35 +/- 19 mm; P<.001) (data are given as mean +/- SD). However, an excellent result occurred only in patients with a postoperative esophageal diameter less than 40 mm. CONCLUSION: Functional outcome of laparoscopic Heller-Dor procedure for achalasia is related to the preoperative stage of the disease on the esophagogram and to the extent of reduction in esophageal width after surgery.

Rectoanal motility in Crohn's disease patients.

PURPOSE: It has been documented that Crohn's disease affects anorectal function when anorectal manifestations of the disease are present. The aim of this study was to investigate whether the presence of histologic lesions in rectal biopsy affected anorectal motility in patients with Crohn's disease but no evidence of macroscopic anorectal involvement. METHODS: Forty-one patients with documented Crohn's disease were included in the study. Twenty-one of them had no endoscopic or histologic lesions in the rectum, and 20 patients had a positive histology for Crohn's disease on rectal biopsy, with or without macroscopic or endoscopic involvement of the anorectum. All patients underwent a standard anorectal manometry, with an eight-channel, water-perfused catheter. RESULTS: Patients with positive rectal biopsy but no evidence of endoscopic rectal involvement had lower anal resting and squeeze pressures (76 +/- 16 standard deviation vs. 86 +/- 19 standard deviation P = 0.002; 152 +/- 56 standard deviation vs. 192 +/- 52 standard deviation P < 0.001, respectively), and a lower sphincter and high-pressure zone length (2.8 +/- 0.8 standard deviation vs. 3.2 +/- 0.8 standard deviation P = 0.006; 1.7 +/- 0.6 standard deviation vs. 2 +/- 0.6 standard deviation P = 0.005, respectively) compared with patients with negative rectal histology. Also, slow and ultra slow wave amplitude and ultra slow wave frequency were significantly lower (10 +/- 6 standard deviation vs. 13 +/- 7 standard deviation P = 0.04; 17 +/- 16 standard deviation vs. 34 +/- 24 SD P = 0.004; 0.9 +/- 0.8 standard deviation vs. 1.3 +/- 0.6 standard deviation P = 0.05, respectively), rectal sensation more affected, and rectal compliance significantly reduced (7.4 +/- 1 standard deviation vs. 11.1 +/- 2.2 standard deviation P<0.001) in the former group of patients. Simultaneous presence of endoscopic and histologic lesions in the rectum was associated with further impairment of the anorectal function. CONCLUSION: Microscopic presence alone of Crohn's disease in the rectum appears to induce anorectal motility disorders. The synchronous presence of endoscopic rectal and macroscopic anal involvement is associated with further deterioration of anorectal function.

Surgical repair of incisional ventral hernias: tension-free technique using prosthetic materials (expanded polytetrafluoroethylene Gore-Tex Dual Mesh).

Repairing an incisional ventral hernia is a major challenge for a surgeon. The high recurrence rates observed during hernia repair by tissue approximation led to development of tension-free procedures by using prosthetic materials. The purpose of this study is to report the results of a tension-free repair technique using expanded polytetrafluoroethylene Gore-Tex Dual Mesh (Gore-Tex Soft Tissue Patch, W.L. Gore and Associates Inc, Flagstaff, AZ) in patients with primary or recurrent incisional ventral hernias. Over 3 years, 52 patients with incisional hernias have undergone this procedure in our clinic. Fourteen of them had recurrent hernias which had been primarily repaired by Mayo hernioplasty. Six of our patients had irreducible hernias preoperatively. Twenty-five patients had hernias on midline incisions, and the rest of them had hernias on transverse abdominal incisions. The median patient age was 65 years, and all were operated on under general anesthesia. The majority of the patients had 4 to 6 days of hospitalization. A subcutaneous seroma developed in eight patients. They all were treated by multiple paracentesis. Four of our patients experienced wound infection and were treated by mesh removal. None of the patients presented with cardiovascular or pulmonary complications. During the follow-up period, no other hernia recurrence, except the cases with mesh removal, has been noticed. The tension-free incisional hernia repair using expanded polytetrafluoroethylene mesh is, to our experience, a safe and easy procedure with no major morbidity or recurrence.

Surgical repair of inguinal hernia: tension free technique with prosthetic materials (Gore-Tex Mycro Mesh expanded polytetrafluoroethylene).

The purpose of this study is to report the results of a tension-free repair technique using expanded polytetrafluoroethylene Gore-Tex Mycro Mesh in patients with inguinal hernias. Over 3 years, 104 patients have undergone the aforementioned procedure for 118 hernias (85 indirect and 33 direct) in our clinic. Ninety-three of the patients were operated for the first time, whereas the remainder of them were operated for hernia recurrence. Fourteen patients had bilateral hernias, and six had incarcerated ones. The median patient's age was 53 years. Eighty-three patients were operated under general and 21 under local or epidural anesthesia. One hundred and two patients were offered a one-day surgery procedure, but three were readmitted with wound infection. Two of these patients were conservatively cured, and the third was submitted to mesh removal. Two patients developed hematoma in the scrotum and were discharged a week later after the absorption of the hematoma. All of the patients except the one who was submitted to mesh removal returned to normal life within a week after the operation. During the follow-up period, none of our patients experienced hernia recurrence. Our results are in accordance with those of the world literature. We perform the tension-free hernia repair by using the expanded polytetrafluoroethylene mesh in our patients because we believe it is a safe procedure without significant postoperative morbidity and with no hernia recurrences.