Effect of L-carnitine on oxidative stress and platelet activation after major surgery.

BACKGROUND: The surgical/anesthesia trauma is associated with an increased production of reactive oxygen species (ROS). This enhanced oxidative stress leads to cell damage resulting in various complications such as sepsis, myocardial injury and increased mortality. The aim of this study was to investigate the role of antioxidant treatment with l-carnitine in oxidative stress and platelet activation in patients undergoing major abdominal surgery. METHODS: Forty patients scheduled for abdominal surgery were randomly allocated to l-carnitine, administered with a rapid infusion (0.05 g/kg) diluted in 250 ml of saline solution, vs. placebo treatment just before the surgical intervention. At baseline and after treatment, oxidative stress was evaluated by detection of circulating levels of soluble NOX2-derived peptide (sNOX2-dp), a marker of NADPH oxidase activation, and by analyzing platelet ROS formation. Platelet activation was studied by dosing sCD40L. RESULTS: We observed an increase of soluble sNOX2-dp, sCD40L and ROS production in the placebo group compared with the baseline after the surgical intervention. Conversely, in the l-carnitine-treated group, sNOX2-dp, sCD40L and ROS production did not significantly differ from the baseline. A linear correlation analysis showed that Δ of ROS correlated with Δ of sNOX2 (R(s) =0.817; P<0.001) and Δ of sCD40L (R(s) =0.780; P<0.001). Multiple linear regression analysis showed that the only independent predictive variable associated with Δ of ROS was Δ of serum NOX2 levels (SE=0.05; standardized coefficient ß=1.075; P<0.001). CONCLUSION: Our findings suggest that l-carnitine could be helpful in modulating oxidative stress and platelet activation during major abdominal surgery-dependent oxidative damage.

Perioperative nutritional support or perioperative fasting? A narrative review.

Traditionally, overnight fasting before elective surgery has been Romathe routine in medical practice for risk reduction of pulmonary aspiration of gastric contents. Several original study and international societies recommend a 2h preoperative fast for clear fluids and a 6h fast for solids in most elective patients. We conducted a narrative review of the literature, searching electronic databases (Medline and CINAHL). We used PICO approach. The results of our review suggest that nutrition support in the perioperative period is very important to reduce length of hospital stay and reduced postoperative complication.

Perioperative management in patients undergoing pancreatic surgery: the anesthesiologist's point of view.

BACKGROUND: A high rate of mortality and morbidity has been associated with pancreaticoduodenectomy; the 5-year survival rate is 15% to 25% compared with 1% to 5% among those who did not have any cancer-directed treatment. Systemic rather than surgical complications cause the majority of perioperative deaths, so the anesthesiologist has a crucial role in the management of these patients. This work sought to evaluate an improved approach to perioperative pain management, postsurgical complications as well as outcomes. PATIENTS: From 2002 to 2007, 40 patients underwent pancreaticoduodenectomy for pancreatic or periampullary cancer. The anesthesia protocol was standardized for postoperative pain control. Patients were randomly divided into two groups: 16 patients received an epidural analgesia with local anesthetics combined with opioids (T(9)-T(10); group A) and 24 had IV analgesia with morphine (group B). RESULTS: Postoperative mortality was 2.5%. With regard to complications we observed 4 biliary fistulas, 2 pancreatic fistulas with spontaneous healing in one patient and death in the other as well as wound infections. Patients treated with epidural analgesia experienced better pain relief, compared with subjects receiving IV analgesia, which demonstrated a higher incidence of opioid-related adverse effects such as sedation and respiratory depression. CONCLUSION: Adequate perioperative treatment included suitable nutritional support and pain management using loco-regional techniques, which seem to improve the surgical outcomes among pancreatic cancer patients.

Focus on the prophylaxis, epidemiology and therapy of methicillin-resistant Staphylococcus aureus surgical site infections and a position paper on associated risk factors: the perspective of an Italian group of surgeons.

BACKGROUND: The aim of this research was to study the epidemiology, microbiology, prophylaxis, and antibiotic therapy of surgical site infections (SSIs), especially those caused by methicillin-resistant Staphylococcus aureus (MRSA), and identify the risk factors for these infections. In Italy SSIs occur in about 5 % of all surgical procedures. They are predominantly caused by staphylococci, and 30 % of them are diagnosed after discharge. In every surgical specialty there are specific procedures more associated with SSIs. METHODS: The authors conducted a systematic review of the literature on SSIs, especially MRSA infections, and used the Delphi method to identify risk factors for these resistant infections. RESULTS: Risk factors associated with MRSA SSIs identified by the Delphi method were: patients from long-term care facilities, recent hospitalization (within the preceding 30 days), Charlson score > 5 points, chronic obstructive pulmonary disease and thoracic surgery, antibiotic therapy with beta-lactams (especially cephalosporins and carbapenem) and/or quinolones in the preceding 30 days, age 75 years or older, current duration of hospitalization >16 days, and surgery with prothesis implantation. Protective factors were adequate antibiotic prophylaxis, laparoscopic surgery and the presence of an active, in-hospital surveillance program for the control of infections. MRSA therapy, especially with agents that enable the patient's rapid discharge from hospital is described. CONCLUSION: The prevention, identification and treatment of SSIs, especially those caused by MRSA, should be implemented in surgical units in order to improve clinical and economic outcomes.

Neutropenic enterocolitis in patients with acute leukemia: prognostic significance of bowel wall thickening detected by ultrasonography.

PURPOSE: Neutropenic enterocolitis (NE) is a severe complication of intensive chemotherapy and is barely identifiable by clinical signs alone. Ultrasonography (US) supports the diagnosis of NE by showing pathologic thickening of the bowel wall. The aim of this study was to evaluate the prognostic value of the degree of mural thickening evaluated by US in patients with clinically suspected NE. PATIENTS AND METHODS: Neutropenic patients with fever, diarrhea, and abdominal pain after intensive chemotherapy for hematologic malignancies were studied with abdominal US. We evaluated the degree of bowel wall thickening detected by US and its correlation with the duration of the clinical syndrome as well as NE-related mortality. RESULTS: Eighty-eight (6%) of 1,450 consecutive patients treated for leukemia had clinical signs of NE. In 44 (50%) of 88 patients, US revealed pathologic wall thickening (mean +/- SD, 10.2 +/- 2.9 mm; range, 6 to 18). The mean duration of symptoms was significantly longer in this group (7.9 days) than among patients without mural thickening (3.8 days, P <.0001), and the NE-related mortality rate was higher (29.5% v 0%, P <.001). Patients with bowel wall thickness of more than 10 mm had a significantly higher mortality rate (60%) than did those with bowel wall thickness < or = 10 mm (4.2%, P <.001). CONCLUSION: Symptomatic patients with sonographically detected bowel wall thickening have a poor prognosis compared with patients without this finding. In addition, mural thickness of more than 10 mm is associated with poorer outcome among patients with NE.

Squamous and adenosquamous cell carcinomas of the gallbladder.

Squamous and adenosquamous cell carcinomas (ASC and SCC) are rare subtypes of gallbladder cancer, traditionally considered more aggressive and with a poorer prognosis than adenocarcinoma. We report about two patients affected by an advanced squamous cell carcinoma of the gallbladder. Both had a large tumour in the gallbladder fossa region with infiltration of the liver. Surgical resection was radical in one, but palliative in the other. pTNM was T3 N0 M0, G3, R0 in the former and T3 N0 M0, G2 R1 in the latter. Patients died for local recurrence after 12 and 5 months, respectively. Natural history, clinical findings, prognosis and outcome of this rare gallbladder tumour are discussed on the basis of a review of the English literature. In conclusion, an aggressive and radical surgical treatment of advanced squamous and adenosquamous cell gallbladder carcinomas seems to be indicated for their low proclivity to distant spreading.

The surgical choice in neutropenic patients with hematological disorders and acute abdominal complications.

The clinical course of patients with hematological disease, especially after treatment, is often complicated by gastrointestinal infections. Between 1986 and 1990 a total of 18 patients affected with hematologic disease and presenting with an acute abdomen were admitted to the surgery department at the University of Rome "La Sapienza". Most patients were affected with acute or chronic myeloid leukemia (61%) and lymphoma. Five patients with acute appendicitis, three with necrotizing enterocolitis, three with spontaneous hemoperitoneum, three with cholecystitis, two splenic infarctions and two intestinal occlusions were diagnosed. Symptoms were often vague and non specific and blood counts revealed neutropenia in all but two patients, while anemia was characteristic in spontaneous hemoperitoneum and in neutropenic enterocolitis. Fungemia occurred in only two cases while bacteremia was present in seven. The most critical patients were those affected by neutropenic enterocolitis and acute cholecystitis. Sonography was meaningful in the diagnosis of hemoperitoneum, splenic infarct and acute cholecystitis. All patients underwent surgical procedures within 48 hours of admission to the department. In all cases peritoneal washing was performed and at least one peritoneal drainage was left. In all cases of necrotizing enterocolitis, intestinal resections, either ileal or colonic, were followed by an immediate anastomosis in two layers. Intensive hematological and antibiotic post surgical care was performed in all patients. Seven patients presented minor complications (38.8%), and only one died (5.5%). Emergency surgical treatment may be safely carried out in patients with hematological diseases presenting with an acute abdomen. Intensive postsurgical care is mandatory for the recovery of patients and the patient's critical condition should not be a deterrent to surgical intervention.

Surgery in primary gastric lymphoma: impact on clinical staging and long-term survival.

This study analyzes the value of surgery in the treatment, staging and long-term survival of 17 patients affected with primary gastric lymphoma. In 7 patients the neoplasm was localized to the lower third of the stomach, in three to the middle third, in two to the upper third, while in 5 patients there was involvement of the entire stomach. Patients were classified according to the Ann-Arbor classification. Nine patients were stage Ie, five stage Ile, and three stage IVe. A partial gastrectomy was carried out in ten patients and total gastrectomy in 7. In all cases surgical excision of the gastric lymphoma was performed together with intraoperative staging including bilateral hepatic biopsies, and exploration of all abdominal lymph nodes. Two postoperative deaths occurred among the 7 patients who underwent total gastrectomy but no major complications were observed in the remaining 5 patients. No deaths occurred among the 10 patients who underwent partial gastrectomy, but in one case an acute complication developed. Staging laparotomy permitted the correction of clinical staging, and showed that three cases were understaged and one overstaged. All patients received adjuvant chemio-radiotherapy. All but one patient are currently alive, well and free of disease. Survival was correlated significantly with the stage of the disease and extent of gastric involvement, but there was no correlation between survival, histological grade, and the type of gastrectomy performed.

Gastrointestinal emergencies in patients with acute intestinal graft-versus-host disease.

Acute intestinal graft-versus-host disease (GVHD) develops in about 30-50% of allogeneic bone-marrow transplant recipients: 10-20% have gastrointestinal emergencies (hemorrhage or perforation). Mortality reaches 30-60% in patients with acute, grade 2-4 GVHD. We studied 36 bone marrow recipients in whom acute intestinal GVHD developed. Seven had gastrointestinal emergencies: 4 severe gastrointestinal bleeding and 3 acute peritonitis. Three patients with gastrointestinal bleeding and one patient with peritonitis responded to medical therapy. Three needed surgery: one with bleeding and two with peritonitis, while 1 patient had embolization. Of the 7, two patients died, one after embolization and one after surgery. Two of the three surgically-treated cases are still alive several years after operation. From this experience we feel that surgery for gastrointestinal bleeding in acute GVHD is indicated only when medical treatment fails. Severe neutropenia, thrombocytopenia (<10.000 x mm3) and blood cultures positive for CMV have an unfavorable prognostic value.

Clinical evaluation of subcutaneously administered DDAVP.

1-deamino-8D-arginine vasopressin was given subcutaneously at the dosage of 0.3 micrograms/Kg. b.w. to 24 mild factor VIII deficient patients (16 mild, 2 moderate hemophiliacs and 6 patients with von Willebrand's Disease), to treat bleedings (10 episodes) or to prevent bleeding during and after dental extractions (6 extractions) and surgery (11 interventions). None of the patients who underwent surgery bled. The vasopressin analogue was effective in the early treatment of muscle hematomas and promptly stopped all mucosal hemorrhages. Most of the patients treated for "spontaneous" bleedings performed self-injections at home. The drug was administered in two pharmaceutical forms (4 and 40 micrograms/ml): no differences in the clinical outcome were found. No significant side effects were recorded. The subcutaneous route of DDAVP administration thus seems to be particularly useful (mainly in the concentrated pharmaceutical form) in treating mild factor VIII deficiencies even on self- and home-treatment basis.

Localized stage I-IE aggressive non-Hodgkin's lymphoma (NHL): results of prospective study with multimodality therapeutic approach.

BACKGROUND: A brief course of chemotherapy followed by radiation therapy was considered the best treatment for localized high-grade Non-Hodgkin's Lymphoma (NHL). The purpose of this study was to determine the efficacy and feasibility of a brief-course of anthracycline-based chemotherapy (CHOP) and consolidation radiation therapy (CRT) in a series of 57 consecutive patients with stage I-IE intermediate-high grade NHL. PATIENTS AND METHODS: Between January 1990 and December 1998, 57 consecutive patients, stage I=31 (55%) and stage IE=26 (45%), were treated with 3 cycles of CHOP regimen. Forty-four (77%) received a CRT and thirteen (23%) with primitive gastric and splenic NHL underwent radical surgery. Multivariate analysis was performed to evaluate age, lactate dehydrogenase (LDH), bulky, nodal versus extranodal localization, as prognostic factors of locoregional control and survival. RESULTS: After a median follow-up of 84 months (range 4-128 months) the 5-year overall survival (OS), disease-free survival (DFS) and event-free survival (EFS) rates were 88%, 87.5% and 84%, respectively. Risk factor analysis revealed that the LDH value was the most important adverse prognostic factor for OS and EFS. No differences were found regarding the age and or extranodal localization. The 5-year OS, DFS and EFS was 100% in thirteen patients with primitive gastric or splenic NHL treated with a radical surgical approach followed by chemotherapy without CRT. CONCLUSION: We confirm the efficacy and feasibility of a brief course of CHOP chemotherapy followed by CRT in localized I-IE intermediate-high grade NHL without adverse prognostic factors. Randomized studies are warranted in order to define the dose and the target volume of CRT (involved field or extended field) in this setting of patients.

Functional results of a personal technique of reconstruction after pancreaticoduodenectomy.

The aim of the study is to propose a new technique of reconstruction after pancreaticoduodenectomy with more attention to the functional aspects. From 1995 and 2003, 25 patients underwent pancreaticoduodenectomy for pancreatic or periampullary cancer. The reconstruction was carried out by: end-to-end gastro-jejunal anastomosis (first jejunal loop); a Roux-en-Y T-T pancreatico-jejunal anastomosis leaving a silastic catheter in the Wirsung; hepatico-jejunostomy and jejuno-jejunostomy below the biliary anastomosis; superselective vagotomy. Mortality was 8%. Regarding the complications, we observed 3 biliary fistulas, mean duration 5 days, with spontaneous healing; 8 pleural effusions and 7 wound infections. Postoperative 3 months reevaluation showed weight gain in 14 patients with no other digestive symptoms (vomiting, fullness, dumping). With a scintigraphic meal we observed a good rythmic and regular gastric emptying. No jejunal peptic ulcers were noted in all patients after the gastric protonic pump inhibitors were discontinued. Fecal fats were evaluated in all cases for malabsorption 3 months after operation with low fat fecal levels. The preliminary results of our recent experience seem to be encouraging. This technique may have a useful application in the clinical setting as far as radicality and quality of life of the patients with pancreaticoduodenectomy.

Systematic radical gastrectomy and D2 lymphadenectomy in primary gastric B cell lymphoma: impact on diagnosis, classification and long term results. A prospective study.

The role of surgery in the treatment of primary gastric lymphoma has been recently re-evaluated. We report the results of a series of 37 operated patients for primary gastric lymphoma (PGL). All patients underwent gastrectomy with D2 lymphadenectony and bilateral liver biopsies. Postoperative histopathological classification was compared to preoperative staging data. No mortality and low morbidity were observed in this series of patients. We found a high incidence of mixed grading of tumors and a relatively high incidence of lymph node metastases in low grade lymphoma. Relying on preoperative biopsies and imaging techniques could lead to preoperative staging inaccuracy and therefore to inappropriate treatment planning. For these reasons we advocate systematic primary surgery in PGL. Surgery could be useful for staging purposes and seems to be curative in stage IE.

Correlation between lowered PgE2 levels and alkaline reflux gastritis in patients subjected to Billroth II. Pylorogastrectomy: possible improvement with sulglycotide.

In patients subjected to pylorogastrectomy with anterior gastroenterostomy (Billroth's operation II) the remaining gastric mucosa is exposed to the damaging action of bile with consequent reduction of locally generated prostaglandins. The purpose of the present study was to explore the correlation between PgE2 levels in such postgastrectomy patients before and after treatment with sulglycotide. Twelve patients with clinical, endoscopic and histological evidence of alkaline reflux gastritis were treated with sulglycotide in daily doses of 1600 mg for 30 days. At termination there was a definite clinical, endoscopic and histological improvement with significant (p less than 0.001) increase of PgE2 levels.

[Pirenzepine parenterally administered in high doses in the treatment of upper digestive hemorrhage]. / La pirenzepina per via parenterale ad alto dosaggio nel trattamento delle emorragie digestive alte.

22 patients with moderate and severe haemorrhages of the UAC were given endovenous doses of Pirenzepine (100 mg/48 hrs). The drug was effective in 86% of the cases and its effect on pH values was demonstrated by testing before and after administration (p less than 0.01). Better results were observed in the treatment of patients with moderate and severe DUS.

Videoassisted transhiatal esophagectomy for cancer.

Blunt transhiatal esophagectomy is largely performed in selected cases of esophageal cancer according to the experience of Mark Orringer. We have recently performed eleven consecutive videolaparoscopy assisted transhiatal esophagectomies in order to help esophageal dissection and to avoid injuries to mediastinal structures. In our experience the routine use of laparoscopic assistance during transhiatal esophageal dissection improves the safety of this technique and lowers postoperative complications. The results of neoadjuvant treatments (radio-chemotherapy) recently reported emphasize the role of transhiatal esophagectomy for cancer.

[Video-assisted closed-thorax esophagectomy in cancer. A technical proposal]. / L'esofagectomia a torace chiuso videoassistita per cancro. Una proposta di tecnica.

Blunt transhiatal esophagectomy is largely performed in selected cases of esophageal cancer following the experience of Mark Orringer. We have recently performed five consecutive video-laparoscopy-assisted transhiatal esophagectomies in order to help the esophageal dissection and to avoid injuries to mediastinal structures. In our experience a routine use of laparoscopic assistance during transhiatal esophageal dissection improves the safety of this technique and lowers postoperative complications. The results recently reported from neoadjuvant treatments (radio-chemotherapy) emphasize the role of transhiatal esophagectomy for cancer.

Acute abdomen in a 15-year-old patient with Peutz-Jeghers syndrome. Surgical approach.

The natural history of Peutz-Jeghers syndrome (PJS) is characterized by gastrointestinal complications (occlusion, invagination or bleeding), often the first clinical manifestation in young patients. Surgical treatment consists of treating the complication, exploring the bowel and cleaning out all polyps to prevent further emergency operations at brief intervals. For this purpose both the laparotomic and laparoscopic approaches have been proposed, especially in young patients. A 15-year-old girl was admitted for investigation of colicky abdominal pains. When she was 5 years old, PJS was diagnosed. On admission to our department, the patient underwent emergency esophagogastroduodenoscopy and colonoscopy, both negative. At 24 hours after admission peritonitis developed. Given her clinical history, we rejected the laparoscopic approach proposed at admission and decided for an open laparotomy. Laparotomy disclosed a long jejunoileal invagination that caused irreversible ischemic damage of the bowel. We resected about 130 cm of the ileum and did an end-to-end ileo-ileal anastomosis. Meticulous palpation and transillumination of the residual bowel identified no other polyps. In young patients with acute abdomen and with proven or suspected PJS instead of laparoscopy, open laparotomy is a unique occasion to explore the residual bowel thoroughly, manually and, if possible, endoscopically.

Topographic diagnosis and surgical treatment of insulinoma.

AIM: Controversy continues to reign with regard to the need for preoperative localization of insulinomas and to which are the most sensitive and accurate diagnostic imaging modalities. Our aim was to determine the role of diagnostic procedures and suggest which of them are really useful. METHODS: Over a 12-year period 34 patients underwent several preoperative diagnostic procedures to localize the insulinoma: ultrasonography (US) in 20 cases, computed tomography (CT) in 26, magnetic resonance imaging (MRI) in 28, selective angiography in 8, arterial stimulation venous sampling (ASVS) in 23 and Octreoscan in 26. All patients underwent surgical palpation and in 32 cases intraoperative ultrasonography (IOUS) was performed. Twenty-six cases underwent enucleation, six had distal pancreatic resections and two patients had only exploratory laparotomy with liver biopsies. We compared the findings of the diagnostic procedures and analyzed the surgical treatment chosen according to the pancreatic site of the tumor. RESULTS: In 32 (94.1%) of the 34 patients with clinically suspected pancreatic insulinoma the tumor was found at surgery. Preoperative US achieved 5.2% sensitivity, CT 29.1%, selective angiography 28.5% and MRI 76.9%. ASVS achieved 91.3% sensitivity and diagnostic accuracy whereas Octreoscan achieved only 65.3% diagnostic accuracy. Surgical palpation performed before IOUS identified the tumors in 30/34 patients: in the other four cases, one was a false-positive result (a cyst in the pancreatic head), two were true negatives and one was a false negative. Surgical palpation therefore yielded 88.2% diagnostic accuracy. IOUS was performed in 32 cases and localized the tumors in 29/32 cases (sensitivity: 96.6%) with one false-negative result (diagnostic accuracy: 96.8%). The operative mortality was 2.9% and the morbidity 24.6% (30.7% in patients treated by tumor enucleation). CONCLUSIONS: No single diagnostic imaging modality is reliable for localizing insulinoma. We therefore suggest combined MRI, ASVS and IOUS. ASVS provides particularly useful information for planning manual palpation and intraoperative ultrasonography.