Intraoperative and postoperative outcome of robot-assisted and traditional laparoscopic Nissen fundoplication.

BACKGROUND: Robotics has been proposed as a tool to improve laparoscopic Nissen fundoplication. However, a clear benefit of this technology for minimally invasive antireflux surgery has not been demonstrated. MATERIALS AND METHODS: A retrospective review of a prospective database was used to compare the intraoperative and postoperative outcome of 137 patients who underwent conventional laparoscopic fundoplication (CLF) and 45 patients who underwent laparoscopic robot-assisted fundoplication (LRF). Intraoperative outcome measures were: operative time, blood loss and complications. Length of hospital stay, functional results and patient satisfaction were used to compare postoperative outcome. RESULTS: Operative time was significantly shorter in the LRF group (65 min) compared to the CLF group (85 min) (p < 0.0001). The overall complication rate was comparable between the two techniques, even though a higher incidence of liver tears was encountered in the CLF group (p < 0.05). Hospital stay, symptom relief and patient satisfaction did not differ between the groups. CONCLUSION: Robotics improves surgeon dexterity and maneuverability during laparoscopic Nissen fundoplication, but this does not correspond to a better postoperative outcome. LRF should be used only for complex cases and training.

PKR is a novel functional direct player that coordinates skeletal muscle differentiation via p38MAPK/AKT pathways.

Myogenic differentiation is a highly orchestrated multistep process controlled by extracellular growth factors that modulate largely unknown signals into the cell affecting the muscle-transcription program. P38MAPK-dependent signalling, as well as PI3K/Akt pathway, has a key role in the control of muscle gene expression at different stages during the myogenic process. P38MAPK affects the activities of transcription factors, such as MyoD and myogenin, and contributes, together with PI3K/Akt pathway, to control the early and late steps of myogenic differentiation. The aim of our work was to better define the role of PKR, a dsRNA-activated protein kinase, as potential component in the differentiation program of C2C12 murine myogenic cells and to correlate its activity with p38MAPK and PI3K/Akt myogenic regulatory pathways. Here, we demonstrate that PKR is an essential component of the muscle development machinery and forms a functional complex with p38MAPK and/or Akt, contributing to muscle differentiation of committed myogenic cells in vitro. Inhibition of endogenous PKR activity by a specific (si)RNA and a PKR dominant-negative interferes with the myogenic program of C2C12 cells, causing a delay in activation of myogenic specific genes and inducing the formation of thinner myofibers. In addition, the construction of three PKR mutants allowed us to demonstrate that both N and C-terminal regions of PKR are critical for the interaction with p38MAPK and Akt. The novel discovered complex permits PKR to timely regulate the inhibition/activation of p38MAPK and Akt, controlling in this way the different steps characterizing skeletal muscle differentiation.

Hepatitis C virus core protein enhances B lymphocyte proliferation.

HCV chronic infection leads to liver diseases and also to a wide range of extrahepatic disorders including benign, but pre-lymphomatous forms (mixed cryoglobulinemia) to frank hematological neoplasia (non-Hodgkin's lymphoma). Recent data showed the involvement of p53 superfamily members in the pathogenesis of different lymphatic malignancies. In fact, tymomas and a subset of non-Hodgkin's lymphomas (NHLs) express high levels of p63. Thus, we analyzed whether alterations in p53 superfamily gene expression are observable in B lymphocytes isolated from HCV-infected patients with and without lymphoproliferative disorders. We showed, by real-time PCR, a significant induction of DNp63 mRNAs in B lymphocytes obtained from HCV-positive low grade non-Hodgkin's lymphoma patients. Since our current understanding of HCV proteins emphasizes the ability of the HCV core protein to deregulate the expression and activity of p53-related proteins, we established different B lymphocyte cell lines (Wil2-ns, Daudi and Ramos) stably expressing HCV core protein, in order to investigate the possible involvement of the viral protein in the upregulation of DNp63 in B lymphocytes. The analysis of p63 family transcripts showed no transcriptional changes for the p63 TA isoforms, whereas an increase (>5 times) of DNp63 mRNA occurred. In all cell lines, this abnormal expression was associated with a significant increase of cell proliferation that was specifically inhibited by silencing DNp63 mRNA. These findings suggest a pathogenetic role of the HCV core in HCV-related lymphomagenesis, through the induction of DNp63's pro-proliferative effects.

[Laparoscopic repair of incisional and umbilical hernias. Our experience]. / Riparazione laparoscopica dei laparoceli e delle ernie ombelicali. Nostra esperienza.

BACKGROUND: Incisional hernia is a frequent complication of abdominal surgery (2-20% of all cases). Recurrence rate after simple repair without mesh is very high. The use of prosthetic materials has reduced the recurrences. Over the past decade, laparoscopic repair of incisional and umbilical hernias has become an interesting alternative to open procedure. PATIENTS AND METHODS: The aim of this retrospective study was to evaluate efficacy, safety and advantages of laparoscopic approach in the treatment of incisional and umbilical hernias. From February 2000 through June 2006, a total of 127 incisional hernias (primary and recurrent), 21 umbilical and 19 epigastric hernias, were treated by laparoscopic approach. The exclusions for laparoscopy were: defect size less than 2 cm or more 20 cm, anesthesiologic problems, hemocoagulative disorders. The females/males ratio was 0/7, with a mean age of 59 years (range 24-83). The abdominal associated disease treated were 26. Three cases were treated as urgencies (strangulated hernias). RESULTS: The conversion rate was 2 cases (1.2%). Mean operative time was 78 min (range 25-170). The mean postoperative hospital stay was 2.1 days (range: 1-5). The intra- and postoperative complication rate was 5% (above all seromas). The recurrence rate was 1.8% (3 cases). CONCLUSIONS: More studies with long-term follow-up are necessary to prove the advantages of laparoscopic technique, but this large experience of more than 5 years, demonstrates that in selected cases the laparoscopic approach may be an interesting and effective alternative to open technique.

The biliopancreatic diversion. A comparison of laparoscopic and laparotomic techniques.

AIM: Morbid obesity has increased its frequency in the last 20 years in association with the increase of a country's richness. Bariatric surgery has developed a role which is becoming more and more important. The aim of this study, after 10 years of experience with the biliopancreatic diversion, is to compare the laparoscopic versus open technique METHODS: From March 1993 to December 2004, 150 patients were operated by biliopancreatic diversion. We divided our experience into 2 groups: laparotomic and laparoscopic techniques. We compared the following variables in the 2 groups: total operating time, intestinal functions, postoperative pain, patient's discharge and recovery time, major postoperative complications, postoperative mortality, late complications, incisional hernia incidence and anastomotic ulceration. RESULTS: We found a significant difference in both the reduction of the postoperative pain and the recanalization time in the laparoscopic group. Equally, we found a reduction in the incidence of abdominal wall complications, especially the reduction of incisional hernia and infections. The mean operative time was longer in the laparoscopic group, in particular due to the hard learning curve. CONCLUSIONS: The laparoscopic biliopancreatic diversion is a feasible and safe operation with good results: less postoperative discomfort, shorter recanalization and ospedalization time, less incidence of abdominal wall morbidity (incisional hernia). However, the procedure may prove difficult and it needs a highly experienced surgeon in laparoscopic technique.

[Laparoscopic colon-sigmoid resection with mesenteric artery preservation for diverticular disease]. / Resezione laparoscopica di colon-sigma con conservazione della mesenterica per malattia diverticolare.

AIM: About 2/3 of the Western population over the age of 80 years are affected by colic diverticulosis; 25% will develop diverticular disease with or without complications: fistula, obstruction, pericolic abscess, free perforation or hemorrhage. Laparoscopic approach for benign diseases of the colon such as diverticulosis, Chrohn's disease, etc. is unanimously considered as a very effective procedure. We have performed a retrospective analysis of 9 years with laparoscopic approach of the diverticular disease. The purpose of this study was to determine the feasibility, safety and benefits of laparoscopic approach. METHODS: From May 1994 to November 2002, 69 patients affected by non-complicated diverticular disease, were treated laparoscopically, at the Mininvasive Surgery Department of Spoleto. In the same period other 213 patients suffering from cancer of the colon-rectum were operated through laparoscopic surgery. A colosigmoid resection with mesenteric inferior artery preservation was performed in 46 cases (67%). RESULTS: We have performed only a laparoscopic colectomy technique (no hand-assisted procedures); the convertion rate was of 7.2%, the mean operative time was 145 min, no intraoperative complications were observed and finally the mean hospital stay was of 7.4 days (6-9). The postoperative complications were 1 case of infection of the umbilical scar and 1 case of pleural effusion with bronchopneumonia. CONCLUSIONS: Elective laparoscopic colectomy for diverticular disease is feasible, safe and gives very good results: minimum postoperative discomfort, rapid recovery, low mobility and postoperative stay, rapid return to normal activities. However, in some cases, this procedure can be extremely difficult because of previous inflammatory complications (adhesions, fistulas or stenosis), therefore, high surgical skills in laparoscopic-colic surgery are required.

[Non palpable lesions of the breast: the Mammotome-biopsy in the preoperative management of breast cancer]. / Lesioni non palpabili della mammella: la Mammotome-biopsy nella gestione preoperatoria del cancro della mammella.

BACKGROUND: Breast tumour takes first place for frequency in women in Western Countries and is in constant increase. The diagnosis of the so-called non palpable lesions is increased remarkably above all due to the diffusion of mammographic screening and to a greater awareness of the problem. Furthermore it is helped by an important development of mininvasive diagnostic methods: the traditonal cytology with fine needle is supported by various trans-skin bioptic procedures (micro-histological examination). This methods almost always replaces the surgical excisional biopsy and frozen intraoperative examination, still used but reserved for particular cases. PATIENTS AND METHODS: In our Department of General and Mininvasive Surgery, from December 1999 to September 2004, we carried out 214 biopsies, with the collaboration of the radiological Service, under echographic guidance using vacuum--assisted biopsy (Mammotome) with 11-Gauge needle. The results are examined and discussed here in this report with regard to diagnostic accuracy, quantity and quality of information, significant for subsequent surgical management. RESULTS: Of 214 biopsies carried out with Mammotome technique, 89.3% of the cases are clinically non palpable lesions, with a average diameter of 8 mm. The average age of patients was 57.6 years (range 31-88). There are 90 cases of positive malignant pathology (42%). In the atypical ductal iperplasia and radial scar cases (6%) surgical removal of lesion was carried out which confirmed the previous bioptic diagnosis in 100% of cases. The 19% of patients submitted to a Mammotome biopsy was subject previously to cytology with fine needle. Comparing the results of both methods the diagnostic reliability of Mammotome was significantly superior (p < 0.05) as also the amount of information obtained (histotype, invasivity, grading, estrogen receptor, etc.); discomfort linked to the procedure, valued as pain (VAS), resulted inferior to the discomfort of biopsy with fine needle. The only complication of Mammotome biopsy is represented by haematoma in the biopsy site (8% of cases). The number of false negatives was one case due to incorrect targeting. CONCLUSION: In the present situation, the choice of method is conditioned by the degree of radiological suspicion, taking into account the information obtained thereby, in order to ensure the appropriate surgise management. Mammotome biopsy of non palpable lesions of the breast, in our experience, is preferable if suspicion of malignancy is high. In this way a correct preoperative strategy can be prepared. Including the sentinel lymphnode method. Consequently a decision regarding the type of surgery can be taken (generally conservative), as well as making easier the intraoperative localisation of lesion by positioning the metallic clips during biopsy.

Thr 446 phosphorylation of PKR by HCV core protein deregulates G2/M phase in HCC cells.

Hepatitis C virus (HCV) is the major causative viral agent of cirrhosis and hepatocarcinoma (HCC). HCV core protein affects cell homeostasis, playing an important role in viral pathogenesis of HCC. We investigate the effects of HCV core protein expression on cell growth in HCC cell lines. Cell cycle distribution analysis of HepG2 polyclonal core positive cells reveals a peculiar accumulation of cells in G2/M phase. Different pathways mediate G2/M arrest: such as p53 and double strand RNA protein kinase (PKR). Flow cytometry in p53-null cells demonstrates that p53 plays only a marginal role in inducing HCV core-dependent G2/M phase accumulation that seems to be significantly affected by the functional inactivation of PKR. HCC core positive cells are characterized by a significant PKR phosphorylation in Thr 446 residue, which leads deregulation of mitosis. Moreover, we observe that the overexpression of the viral protein induces an upregulation of PKR activity, which does not correlate with an increased eIF-2 phosphorylation. This uncommon behavior of PKR suggests that its activation by HCV core protein could involve alternative PKR-dependent pathways, implicated in core-dependent G2/M accumulation. The described biological effects of HCV core protein on cell cycle could be an additional viral mechanism for both HCV resistance to interferon (IFN) and HCC HCV-related pathogenesis.

Survey on giardiosis in shelter dog populations.

Faecal samples from 183 dogs living in three different shelters in the Rome metropolitan area were randomly collected and examined for the prevalence of giardiosis. Giardia infections were detected by a commercially available ELISA test (ProspecT Giardia Microplate Assay). Overall prevalence was 55.2%. Prevalence rates in single shelters were 74.3, 35.5, and 20.9%, respectively. Using multivariate analysis, no association was found between Giardia-positivity and shelter or sex, breed, or diarrhoea. Giardia-positive dogs were more likely to be younger than 5-year-old (odds ratio [OR] = 2.87; 95% confidence interval [95% CI]: 1.07-7.77; p = 0.038), living together (OR = 2.58; 95% CI: 1.12-5.93; p = 0.026), and fed commercial wet food, both alone and combined with dry food (OR = 5.67; 95% CI: 1.59-20.24; p = 0.008). Correlation between Giardia infection and type of food has not been previously reported in dogs. Possible use of the ELISA test for detection of Giardia infection in dogs and zoonotic implications are discussed.

Thyroid hormones regulate DNA-synthesis and cell-cycle proteins by activation of PKCalpha and p42/44 MAPK in chick embryo hepatocytes.

The molecular mechanism by which thyroid hormones exert their effects on cell growth is still unknown. In this study, we used chick embryo hepatocytes at different stages of development as a model to investigate the effect of the two thyroid hormones, T3 and T4, and of their metabolite T2, on the control of cell proliferation. We observed that T2 provokes increase of DNA-synthesis as well as T3 and T4, independently of developmental stage. We found that this stimulatory effect on the S phase is reverted by specific inhibitors of protein kinase C (PKC) and p42/44 mitogen-activated protein kinase (p42/44 MAPK), Ro 31-8220 or PD 98059. Furthermore, the treatment with thyroid hormones induces the activation of PKCalpha and p42/44 MAPK, suggesting their role as possible downstream mediators of cell response mediated by thyroid hormones. The increase of DNA-synthesis is well correlated with the increased levels of cyclin D1 and cdk4 that control the G1 phase, and also with the activities of cell-cycle proteins involved in the G1 to S phase progression, such as cyclin E/A-cdk2 complexes. Interestingly, the activity of cyclin-cdk2 complexes is strongly repressed in the presence of PKC and p42/44 MAPK inhibitors. In conclusion, we demonstrated that the thyroid hormones could modulate different signaling pathways that are able to control cell-cycle progression, mainly during G1/S transition.

[Neoplastic residues in the trocar tract in oncologic laparoscopic surgery]. / Recidive neoplastiche in sede di trocar nella chirurgia oncologica laparoscopica.

AIM: The laparoscopic approach to malignant diseases runs up against both old and new problems: respect for the principles of radicality, operating times, the postoperative course and surgical complications, long-term oncological results in terms of survival and recurrence of the disease. One of the problems which has received most attention regards the onset of a metastasis on a trocar scar or a mini-laparotomy recurrence. Trocar site tumor recurrences have been described in the literature following laparoscopic surgery in almost all abdominal malignant pathologies (colorectal, gynaecological, pancreatic, etc.) and even after thoracoscopy. The real frequency is currently of the order of 1% (0-2%) in colic surgery and of 14% (10-17%) after cholecystectomy for occult gallbladder carcinoma. METHODS: A retrospective survey was carried out of our laparoscopic experience; between 1994 and 2002 213 colic resections were carried out for cancer; we also observed 18 occult carcinomas of the gallbladder in 2386 laparoscopic cholecystectomies for lithiasis. RESULTS: Respectively 2 cases (11%) of trocar site neoplastic recurrences in gallbladder carcinoma and 2 cases (0.9%) from colon carcinoma were observed. CONCLUSIONS: The real extent of the problem would appear to be on a much lesser scale at the moment than was initially thought, especially as regards colic surgery. The multifactorial aetiology of the problem explains the importance of their prevention, on the basis above all of rigorous respect for the rules and protocols of laparoscopic technique.

[Laparoscopic right hemicolectomy with intracorporeal anastomosis. Technical aspects and personal experience]. / Emicolectomia destra laparoscopica con anastomosi intracorporea. Aspetti tecnici e nostra esperienza.

BACKGROUND: Laparoscopic colo-rectal surgery has gained wide acceptance as a treatment in a variety of benign and malignant diseases. The reproducibility and safety of all the principal colo-rectal procedures has been demonstrated, but some indications are still controversial. A great part of surgeons perform right hemicolectomy by laparo-assisted technique and consider it more difficult than left hemicolectomy. METHODS: A retrospective analysis of a series of 180 laparoscopic colon resections performed between 1994 and 2001 is presented. Surgical indications were: 46 cases of benign disorders and 134 colonic malignancy. The right hemicolectomy were 27 (15%): 2 benign and 25 malignant diseases. The technical aspects of completely laparoscopic right hemicolectomy is described in details. A completely mechanical intra-corporeal anastomosis is always performed. To remove the bowel specimen from the abdominal cavity it is put it in a large bag and pull it out of a 3-4 cm enlargement of a trocar-site (in the umbilical scar). RESULTS: Data of the 27 laparoscopic right hemicolectomy were analysed: there was 1 conversion to open surgery; no intra-operative complications were observed; the postoperative period was complicated by 1 anastomotic fistula. The median operative time was of 150 minutes. No case of port-site recurrence was observed. CONCLUSIONS: The laparoscopic colo-rectal surgery can reproduce in selected patients, the techniques performed in open surgery with minimally invasive treatment. It is possible to perform a completely laparoscopic right hemicolectomy after an adequate training in advanced laparoscopy, anyway there are many advantages: less postoperative pain, short-term postoperative ileus, earlier return to daily activity.

[Laparoscopic approach versus laparotomy for suspected acute appendicitis]. / Approccio laparoscopico versus laparotomia per sospetta appendicite acuta.

Acute appendicitis is one of the most common surgical disease but, in spite of the progression diagnostic imaging, a definite diagnosis is frequently difficult and often is based in essentially clinical grounds. The Authors retrospectively analyze the results of conventional laparotomic appendectomy (CLA) and videolaparascopic appendectomy (VLA) as performed by two teams of their Department of Surgery. Between January 2000 and November 2001, 156 patients, age ranging from 3 to 67 yrs, underwent surgery because suspected acute appendicitis; 96 patients underwent VLA and 60 patients underwent CLA; a diagnosis of acute appendicitis was confirmed in 142 cases (91%). The patients who had a confirmed diagnosis of acute appendicitis were grouped according to clinical-pathologic criteria into follicular, gangrenous and complicated appendicitisi; operating time, complications and length of hospital stay were compared among the three groups. VLA resulted superior to CLA in terms of diagnostic performance: among the patients with suspected acute appendicitis, VLA allowed to establish a different diagnosis in 41% as compared to 13% with CLA. In two cases (2.08%) VLA was turned into CLA. There were non differences between VLA and CLA in terms of surgical operating time and hospital stay. A significantly higher incidence of surgical complications, such as wound infections and pelvic abscesses, was observed in the CLA group as compared to VLA. The Authors conclude that VLA allows a complete exploration of the abdomen, a better localization of the appendix and an easier diagnosis of unexpected conditions or pathologic processes associated with the clinical appendicitis; further, VLA is gravated by fewer complications.

Specific cellular unreactivity during cytomegalovirus infection in man.

The specific cellular immune response against Cytomegalovirus (CMV) was studied by the Leucocyte Inhibitory Factor (LIF) production test in three groups of subjects: 7 healthy individuals with no CMV antibodies, 4 with antibodies to CMV but without evidence of active infection, and 2 children with clinical CMV infection. Our results show that LIF production in presence of CMV is high in normal seropositive subjects, while it is strongly deficient in patients with active infection, despite a good humoral response to the virus. In one child with congenital infection, a low number of E rosette forming cells was also revealed. We suggest that CMV infection can induce, at least during infancy, a state of specific cellular unresponsiveness to the virus. When the infection is congenital, a generalized depression of the cellular immune system may develop.