Piero Chirletti

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.

Small intestine contrast ultrasonography (SICUS) for the detection of small bowel complications in crohn's disease: A prospective comparative study versus intraoperative findings

Background: In Crohns disease (CD) patients, small intestine contrast ultrasonography (SICUS) accurately assesses small bowel lesions. Its diagnostic role is not known in the assessment of intraabdominal CD complications. The aim was to assess the value of SICUS to detect intestinal complications in patients with CD. Methods: Forty‐nine CD patients (21 female, mean age 37.7 years; range 12–78 years) underwent resective bowel surgery and were included in this study. The accuracy of SICUS to preoperatively detect number, site, and length of strictures, fistulas, and abscesses was compared with surgical and pathological findings by kappa statistics. Results: SICUS identified at least one stricture in 39/40 and excluded it in 9/9 (97.5% sensitivity, 100% specificity, k = 0.93); two or more strictures in 9/12 (75% sensitivity, 100% specificity, k = 0.78). The agreement by k‐statistics between SICUS and surgery in identifying proximal and distal small intestine site of stricture was 1 and 0.92, respectively. The extension of strictures was 6.8 ± 5.4 cm at surgery, 6.6 ± 5.4 cm at SICUS (NS). Fistulas were correctly identified in 27/28 patients and excluded in 19/21 patients (96% sensitivity, 90.5% specificity, k = 0.88). Intraabdominal abscesses were correctly detected in 10/10 patients and excluded in 37/39 patients (100% sensitivity, 95% specificity, k = 0.89). Conclusions: SICUS is an accurate method for the detection of small intestinal complications in CD. Noninvasive SICUS is valuable as a primary investigative method for evaluating and planning proper treatment in patients with severe CD of the small bowel. (Inflamm Bowel Dis 2011;)

Impaired human gallbladder lipid absorption in cholesterol gallstone disease and its effect on cholesterol solubility in bile

BACKGROUND & AIMS The role of the gallbladder in gallstone pathogenesis is still unclear. We examined the effects of gallbladder mucosal lipid absorption on lipid composition and cholesterol crystallization in bile. METHODS The in vitro-isolated, intra-arterially perfused gallbladder model was used (1) to compare the absorption rates of lipids from standard bile by gallbladders obtained from 7 patients with cholesterol gallstones and 6 controls; and (2) to measure the microscopic cholesterol crystal detection time in cholesterol-enriched pig bile before and after lipid absorption by the pig gallbladder. RESULTS Control gallbladders, but not cholesterol gallstone gallbladders, significantly reduced cholesterol (P < 0.02) and phospholipid (P < 0.01) and increased bile salt (P < 0.01) molar percentages in bile over a 5-hour period by efficient and selective cholesterol and phospholipid absorption. A histomorphometric study of the epithelial cells showed significantly higher values for nuclear density (P < 0.01) and nuclear (P < 0.05) and cytoplasmic (P < 0.05) areas in the cholesterol gallstone than the control group. Sequential microscopy of cholesterol-enriched pig bile showed significantly shorter cholesterol filament (P < 0.01) and typical cholesterol plate (P < 0. 02) detection times before than after exposure of bile to the gallbladder lipid absorption. CONCLUSIONS In cholesterol gallstone disease, the human gallbladder epithelium loses its capacity to selectively and efficiently absorb cholesterol and phospholipids from bile, even if it is hyperplastic and hypertrophic. This epithelial dysfunction eliminates the positive effect that the normal gallbladder exerts on cholesterol solubility in bile and might be a pathogenetic cofactor for cholesterol gallstone formation.

Role of CEA, TPA, and Ca 19-9 in the early detection of localized and diffuse recurrent rectal cancer

Sixty-six consecutive patients who underwent curative resection for rectal cancer were studied prospectively to evaluate the roles of sequential carcinoembryonic antigen (CEA), tissue plasminogen activator (TPA), and carcinomatous antigen 19-9 (Ca 19-9) determinations in the early diagnosis of resectable recurrences. Thirty-three recurrences were detected between 6 and 42 months. CEA, TPA, and Ca 19-9 showed a sensitivity of 72.7 percent, 78.8 percent, and 60.1 percent, respectively, and a specificity of 60.6 percent, 60.6 percent, and 87.9 percent, respectively. In 23 cases the rise in the value of CEA and/or TPA and/or Ca 19-9 was the first sign of recurrences, and the diagnosis was established later by clinical methods. In this group, the lead time was two months for liver metastases and four months for disseminated metastases. As far as the relationship between localization of recurrence and marker level increase is concerned, of 16 hepatic metastases CEA, TPA, and Ca 19-9 showed a sensitivity of 94 percent (P<0.05), 69 percent, and 62 percent, respectively. Of six patients with local recurrences, CEA, TPA, and Ca 19-9 showed a sensitivity of 50 percent, 100 percent (P<0.05), and 83.3 percent, respectively. Of three patients with peritoneal carcinomatosis, CEA, TPA (P<0.05), and Ca 19-9 showed a sensitivity of 0 percent, 100 percent, and 0 percent, respectively. No significant differences were reported among the three markers according to multiple metastases and metachronous polyps. Fourteen patients (42.4 percent) underwent surgical treatment for recurrent disease, and eight of them (57 percent) showed a resectable disease, for a total resectability rate of 24.2 percent. The findings of our study indicate that a followup program based on CEA, TPA, and Ca 19-9 assays is related to an early diagnosis and a good resectability rate for both local and metastatic recurrences from rectal cancer.

Increased HMGB1 expression and release by mononuclear cells following surgical/anesthesia trauma

IntroductionHigh mobility group box 1 (HMGB1) is a key mediator of inflammation that is actively secreted by macrophages and/or passively released from damaged cells. The proinflammatory role of HMGB1 has been demonstrated in both animal models and humans, since the severity of inflammatory response is strictly related to serum HMGB1 levels in patients suffering from traumatic insult, including operative trauma. This study was undertaken to investigate HMGB1 production kinetics in patients undergoing major elective surgery and to address how circulating mononuclear cells are implicated in this setting. Moreover, we explored the possible relationship between HMGB1 and the proinflammatory cytokine interleukin-6 (IL-6).MethodsForty-seven subjects, American Society of Anesthesiologists physical status I and II, scheduled for major abdominal procedures, were enrolled. After intravenous medication with midazolam (0.025 mg/Kg), all patients received a standard general anesthesia protocol, by thiopentone sodium (5 mg/Kg) and fentanyl (1.4 μg/Kg), plus injected Vecuronium (0.08 mg/Kg). Venous peripheral blood was drawn from patients at three different times, t0: before surgery, t1: immediately after surgical procedure; t2: at 24 hours following intervention. Monocytes were purified by incubation with anti-CD14-coated microbeads, followed by sorting with a magnetic device. Cellular localization of HMGB1 was investigated by flow cytometry assay; HMGB1 release in the serum by Western blot. Serum samples were tested for IL-6 levels by ELISA. A one-way repeated-measures analysis ANOVA was performed to assess differences in HMGB1 concentration over time, in monocytes and serum.ResultsWe show that: a) cellular expression of HMGB1 in monocytes at t1 was significantly higher as compared to t0; b) at t2, a significant increase of HMGB1 levels was found in the sera of patients. Such an increase was concomitant to a significant down-regulation of cellular HMGB1, suggesting that the release of HMGB1 might partially derive from mononuclear cells; c) treatment of monocytes with HMGB1 induced in vitro the release of IL-6; d) at t2, high amounts of circulating IL-6 were detected as compared to t0.ConclusionsThis study demonstrates for the first time that surgical/anesthesia trauma is able to induce an early intracellular upregulation of HMGB1 in monocytes of surgical patients, suggesting that HMGB1 derives, at least partially, from monocytes.

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.

Pancreaticojejunostomy with Applicationof Fibrinogen/Thrombin-Coated Collagen Patch (TachoSil®) in Roux-en-Y Reconstruction after Pancreaticoduodenectomy

To the Editor We read with great interest the article by Wellner and colleagues about the comparison between pancreaticogastrostomy (PG) and Roux-en-Y pancreaticojejunostomy (PJ) after pancreaticoduodenectomy (PD) with regard to postoperative pancreatic fistula (POPF) and other complications. The authors concluded that PG was superior to PJ in terms of clinically relevant POPF; although this study is retrospective, the use of a large case number and standardized measures in evaluation of the surgical outcome makes the results not negligible. Instead, the results of our previously described technique of Roux-en-Y reconstruction show that PJ may have a lower prevalence of POPF than that reported by Wellner and colleagues and suggest that outcome after Roux-en-Y reconstruction with regard to POPF can be further improved using fibrinogen/thrombincoated collagen patch (TachoSil®, Nycomed, UK Ltd.) in carrying out PJ. Briefly, we reviewed the clinical records of 54 consecutive patients who underwent PD by one surgeon (P.C.) at “La Sapienza” University (Rome, Italy) from January 1995 to December 2008. The underlying diseases were: pancreatic carcinoma in 31 cases; pancreatic serous cystadenoma in six cases; mucinous cystadenoma in one case; pancreatic endocrine tumor in two cases; ampullar carcinoma in seven cases; distal bile duct carcinoma in six cases; and chronic pancreatitis in one case. In all patients, the surgical procedure comprised PD with suprapyloric gastric resection and Roux -en-Y reconstruction with anastomosis of the isolated Roux limb to the stomach and single Roux limb to both the pancreatic stump and hepatic duct. Small catheters were inserted in the main duct, passed through the anastomosed bowel loop and fixed to the abdominal wall (Fig. 1a, b). A drainage tube was placed near to the pancreaticojejunostomy; external biliary drainage was not used. Pancreaticojejunal end-to-end anastomosis was done by simple invagination of the pancreatic stump into the jejunal loop for 2 cm and sutured all around with a singlelayer interrupted pledget-supported Ticron stitches between the seromuscularis of the jejunum and the pancreatic capsule. From January 2005, TachoSil® has been layered on suture line of pancreaticojejunal anastomosis (Fig. 1c, d). All 27 consecutive patients had pancreaticojejunostomy without TachoSil® (group A) whereas 27 consecutive patients had pancreaticojejunostomy with TachoSil®. All patients in our study received octreotide during the first six postoperative days. The postoperative surgical outcome within 60 postoperative days was assessed. POPF, postoperative hemorrhage J Gastrointest Surg (2009) 13:1396–1398 DOI 10.1007/s11605-009-0894-7

Pancreato-jejunostomy versus hand-sewn closure of the pancreatic stump to prevent pancreatic fistula after distal pancreatectomy: a retrospective analysis

BackgroundDifferent methods of pancreatic stump closure after distal pancreatectomy (DP) have been described to decrease the incidence of pancreatic fistula (PF) which still represents one of the most common complications in pancreatic surgery. We retrospectively compared the pancreato-jejunostomy technique with the hand-sewn closure of the pancreatic stump after DP, and analyzed clinical outcomes between the two groups, focusing on PF rate.MethodsThirty-six patients undergoing open DP at our institution between May 2005 and December 2011 were included. They were divided in two groups depending on pancreatic remnant management: in 24 cases the stump was closed by hand-sewn suture (Group A), while in 12 earlier cases a pancreato-jejunostomy was performed (Group B). We analyzed postoperative data in terms of mortality, morbidity and length of hospital stay between the two groups.ResultsPF occurred in 7 of 24 (29.1%) cases of group A (control group) compared to zero fistula rate in group B (anastomosis group) (p=0.005). Operative time was significantly higher in the anastomosis group (p=0.024). Mortality rate was 0% in both groups. Other postoperative outcomes such as hemorrhages, infections, medical complications and length of hospital stay were not significant between the two groups.ConclusionDespite a higher operative time, the pancreato-jejunostomy after DP seems to be related to a lower incidence of PF compared to the hand-sewn closure of the pancreatic remnant.

Enucleation for gastrointestinal stromal tumors at the esophagogastric junction: Is this an adequate solution?

The authors discussed the proposal by Coccolini and colleagues to treat gastrointestinal stromal tumors (GISTs) at the esophagogastric junction with enucleation and, if indicated, adjuvant therapy, reducing the risks related to esophageal and gastroesophageal resection. They concluded that, because the prognostic impact of a T1 high-mitotic rate on esophageal GIST is worse than that of a T1 high-mitotic rate on gastric GIST, enucleation may not be an adequate surgery for esophagogastric GISTs with a high mitotic rate in which the guarantee of negative resection margins and adjuvant therapies can be the only chance of survival.

Lactobacillus rhamnosus protects human colonic muscle from pathogen lipopolysaccharide-induced damage

Lactobacillus species might positively affect gastrointestinal motility. These Gram‐positive bacteria bind Toll‐like receptor 2 (TLR2) that elicits anti‐inflammatory activity and exerts protective effects on damage induced by lipopolysaccharide (LPS). Whether such effect occurs in gastrointestinal smooth muscle has not been established yet. Aim of this study was to characterize the effects of Lactobacillus rhamnosus GG (LGG) and of supernatants harvested from LGG cultures on human colonic smooth muscle and to explore their protective activity against LPS‐induced myogenic morpho‐functional alterations.