Abdominal inflammatory myofibroblastic tumor a clinicopathologic study with reappraisal of biologic behavior

Background and Purpose

Inflammatory myofibroblastic tumor (IMT) is a proliferative lesion of controversial nosology and uncertain prognosis. In an attempt to acquire further understanding of pathogenesis and biologic behavior, we surveyed abdominal IMTs managed over the last 12 years at a single institution.

Methods

Intra-abdominal IMTs treated between 1995 and 2007 were reviewed concerning demographic, clinical, and pathologic features as well as therapeutic management and outcome. All specimens were reevaluated by histologic examination and immunohistochemistry.

Results

There were 7 patients (4 males; age range, 28 days to 14 years). Five lesions were located in alimentary tract: 1 gastric presenting with bleeding, 1 hepatic presenting with a thoracic wall mass, 1 pancreatic and 2 colonic presenting with obstructive symptoms. One splenic IMT was found incidentally. The remaining case arose from the adrenal gland and presented with a palpable mass. The gastric and adrenal IMTs had evidence of a previous or concomitant infectious setting. Five lesions were excised. The pancreatic IMT underwent a drainage procedure followed by steroid administration, and the hepatic lesion received antibiotics. Histopathology revealed characteristic findings of IMT. Expression of anaplastic lymphoma kinase was negative in all cases. At a median follow-up of 6 years (range, 3-15), all children were asymptomatic with no recurrences. The hepatic and pancreatic IMT displayed complete and near total regression, respectively.

Conclusion

A benign behavior of abdominal IMTs was observed even in patients not undergoing surgical excision. Although IMT remains a surgical disease, a conservative approach may be reasonable in select cases.     

Immunoglobulin deposits in liver tissue from infants with biliary atresia and the correlation to cytomegalovirus infection

Purpose

The aim of this report was to study the amount and distribution of immunoglobulin deposits in liver biopsies from infants with biliary atresia (BA) and correlate the results to the cytomegalovirus (CMV) infection status.

Methods

Stored liver biopsies from 18 patients with BA and from 6 control patients without liver disease were immunohistochemically stained to detect IgG and IgM deposits. The intensity of the immunoglobulin staining was evaluated by a semiquantitative scoring scale. Ongoing CMV infection was defined as the detection of CMV-IgM in serum and/or the isolation of CMV in the urine and was noted in 9 of the patients with BA.

Results

When analyzing the immunoglobulin deposits on the hepatocellular canalicular membrane the intensity score for IgM deposits was significantly higher in biopsies from patients with BA infected with CMV than in those without. No canalicular staining was detected in control biopsies.

Conclusions

The results support the possibility that immunologic mechanisms are of importance in the pathogenesis of BA and that a CMV infection may trigger such mechanisms.     

Inflammatory myofibroblastic tumor in children: clinical review with anaplastic lymphoma kinase, Epstein-Barr virus, and human herpesvirus 8 detection analysis

Background/Purpose

Inflammatory myofibroblastic tumor (IMT) is considered as an intermediate neoplasm that may present malignant features. Differential diagnosis with other tumor processes is sometimes difficult. Similar anaplastic lymphoma kinase (ALK) gene abnormalities as in anaplastic large cell lymphoma have been reported. Human herpesvirus 8 (HHV-8) DNA sequences have been described in adult pulmonary IMTs and Epstein-Barr virus (EBV) has been reported in splenic and hepatic IMTs, suggesting the importance of both viruses in IMT development. This article aims to evaluate ALK, EBV, and HHV-8 expression in children with IMT and to correlate our findings with clinical features.

Methods

Sixteen children (range, 1-15 years) who had surgery for IMT between 1978 and 2003 were evaluated retrospectively. Formalin-fixed, paraffin-embedded archival tissues were stained for HHV-8 and ALK with immunohistochemistry. Epstein-Barr virus was detected by in situ hybridization (EBER probes).

Results

Tumors were located in the pulmonary lobe (n = 4), urinary tract (n = 4), mesentery or bowel (n = 4), hepatic lobe (n = 1), vena cava (n = 1), spinal cord (n = 1), and soft tissue (n = 1). Five children were treated with steroids and/or antibiotics before surgery, with no substantial result. IMT was excised totally in all but 2 cases. Four patients presented aggressive IMT with recurrence or metastasis requiring new surgery. ALK was positive in 3 (18.8%) cases and EBV in 1 pulmonary and 1 bladder tumor, all of them without recurrence or metastasis. None of the cases were positive for HHV-8. All patients are now disease-free with a mean follow-up of 4.2 years.

Conclusions

Considering the present lack of efficient medical treatment, surgery should still be considered as the mainstay therapy in IMT, even in cases of recurrence or metastases. Larger multicentric studies would be necessary to understand the prognostic significance of ALK, EBV, and HHV-8 and their relationships with the origins of the tumor.     

Growth factor release in extra- and intramedullary osteosynthesis following tibial fracture

Introduction

Recent studies indicate alterations of local and systemic growth factor level during fracture healing. As a result, osteogenic and angiogenic growth factors allow us to monitor fracture healing on a molecular level. We hypothesised that closed intramedullary (IM) reaming and nail fixation, in contrast to open reduction and internal plate fixation (ORIF), could exert an effect on the cellular elements present in the intramedullary canal, leading to increased release of mediators. The purpose of the study was to investigate whether different osteosynthesis techniques influence the released quantity of cytokines.

Patients and methods

A total of 34 patients with tibia fractures treated with IM fixation and 19 patients treated with ORIF were included in the study. In addition to clinical and radiological examination, serum concentrations of transforming growth factor beta 1(TGF-β1), macrophage-colony stimulating factor (M-CSF) and vascular endothelial growth factor (VEGF), were analysed at 1, 2, 4, 6, 8, 12, and 24 weeks after surgery.

Results

Expression of TGF-β1 and M-CSF was increased during the first 2 weeks of fracture healing in patients treated with the IM fixation technique compared with those treated by ORIF. After 24 weeks, M-CSF levels in patients with IM fixation were clearly higher. Conversely, VEGF levels were higher during the first 2 weeks of fracture healing in patients treated by ORIF compared with IM fixation. However, these results were not significant.

Conclusion

Our results show that 1 week after surgery neither reamed IM fixation nor ORIF of the tibia could increase the expression of VEGF, M-CSF and TGF-β1 in its favour.     

Different pattern of matrix metalloproteinases expression in alveolar versus embryonal rhabdomyosarcoma

Background/purpose

The matrix metalloproteinases (MMPs), a family of enzymes that degrade the extracellular matrix (ECM), are important in neoplastic cell invasion and metastasis. Data for rhabdomyosarcoma (RMS), the most frequent soft tissue sarcoma of childhood, are lacking. The aim of this study was to assess their expression in this tumor and to evaluate the correlation with clinicopathologic parameters.

Methods

Immunohistochemical expression of MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, TIMP-1, and TIMP-2 was investigated in 33 human RMSs, 12 alveolar, and 21 embryonal histologic subtypes (12 high risk and 9 low/standard risk). Evaluation of the results was based on the percent of positive neoplastic cells and on staining intensity (negative, moderate, and strong). In situ zymography was carried out on 4 frozen RMS samples (2 alveolar and 2 high-risk embryonal).

Results

Alveolar type showed a stronger MMP-1, -2 and -9 expression in comparison with embryonal (P = .006, P <.001, and P <.001, respectively). Intratumoral vessels and perivascular ECM were positive for MMP-9 in the majority of RMSs. Both TIMPs had negative results.

Conclusions

Gelatinases MMP-2 and MMP-9 and collagenase MMP-1 overexpression seem to contribute to the more aggressive phenotype of alveolar rhabdomyoblastic cells. Further characterization of the expression of MMPs and consequent utilization of their inhibitors in aggressive alveolar RMSs might lead to the development of novel anticancer therapies.     

Upper extremity arterial injuries: Factors influencing treatment outcome

Objective

The aim of the study was to identify factors influencing surgical treatment outcome following upper extremity arterial injuries.

Methods

This 15-year study (January 1992 to December 2006) included 167 patients with 189 civilian, iatrogenic or military upper extremity arterial injuries requiring surgical intervention. Patient data were prospectively entered into a vascular trauma database and retrospectively analysed.

Results

The most frequently damaged vessel was the brachial artery (55% of injuries), followed by the axillary (21.7%), antebrachial (21.2%) and subclavian (2.1%) arteries. Three primary amputations (1.8%) were performed because of extensive soft-tissue destruction and signs of irreversible ischaemia on admission. Seven secondary amputations (4.2%) were due to graft failure, infection, anastomotic disruption or the extent of soft-tissue and nerve damage. Fasciotomy was required in 9.6% of cases. Operative mortality was 2.4% (four deaths). Early graft failure, compartment syndrome, associated skeletal and brachial plexus damage and a military mechanism of injury were found to be significant risk factors for limb loss (p < 0.01).

Conclusion

Although careful physical examination should diagnose the majority of upper extremity arterial injuries, angiography is helpful in detailing their site and extent. Prompt reconstruction is essential for optimal results. Nerve trauma is the primary cause of long-term functional disability.     

Increased expression of alpha-1-antitrypsin, glutathione S-transferase π and vascular endothelial growth factor in human pancreatic adenocarcinoma

Background

This study was designed to investigate abnormalities in gene expression in ductal adenocarcinoma of the pancreas using cDNA arrays.

Methods

Gene expression in pancreatic ductal adenocarcinoma was compared with normal pancreatic tissue controls. Specimens from 5 patients with pancreatic adenocarcinoma were taken fresh at operation and analyzed using commercially prepared cDNA arrays evaluating approximately 2,000 genes. Immunohistochemical staining was used to confirm protein expression of selected genes.

Results

Alpha-1-antitrypsin (A1AT) and glutathione S-transferase π (GSTP) were significantly up-regulated in all 5 tumors. Vascular endothelial growth factor (VEGF) was up-regulated in 4 of the 5 patients. Immunohistochemical staining verified the overexpression of each of these genes.

Conclusions

A1AT, GSTP, and VEGF are overexpressed in human pancreatic adenocarcinoma specimens taken fresh at operation. To our knowledge, this is the first study of human pancreatic ductal adenocarcinoma demonstrating the up-regulation of these genes using gene expression arrays.     

Interventions at caesarean section for reducing the risk of aspiration pneumonitis

Background

Various interventions are used as prophylaxis for aspiration pneumonitis in obstetric anaesthesia. This review, based on a Cochrane systematic review currently being updated, examines whether interventions given before caesarean section reduce the risk of aspiration pneumonitis.

Methods

Twenty-two studies, involving 2658 women providing data in a usable format for meta-analysis were identified.

Results

Compared to no treatment or placebo, there was a significant reduction in the risk of intra-gastric pH <2.5 with antacids (risk ratio (RR) 0.17, 95% confidence interval (CI) 0.09-0.32), H2 antagonists (RR 0.09, 95% CI 0.05-0.18) and proton-pump antagonists (RR 0.26, 95% CI 0.14-0.46). H2 antagonists were associated with a reduced risk of intra-gastric pH <2.5 when compared with proton-pump antagonists (RR 0.39, 95% CI 0.16-0.97), but compared with antacids the findings were unclear. Combined use of antacids plus H2 antagonists was associated with a significant reduction in the risk of intra-gastric pH <2.5 when compared with placebo (RR 0.02, 95% CI 0.00-0.15) or compared with antacids alone (RR 0.12, 95% CI 0.02-0.92).

Conclusion

The quality of evidence was weak and may not reflect a reduction in the risk of aspiration pneumonitis since none of the studies assessed substantive clinical outcomes or potential adverse effects. Further work is required to validate the suitability of surrogate markers of pH and gastric volume for clinical outcomes in the context of aspiration pneumonitis.     

Anorectal sleeve micromanometry for the diagnosis of Hirschsprung's disease in newborns

Background/Purpose

An accurate diagnosis is mandatory for surgery in newborns with Hirschsprung's disease (HD). Acetylcholinesterase staining of rectal suction biopsy specimens is widely performed in the diagnosis of HD, but results are sometimes incorrect or atypical in newborns. We report the usefulness of our method of anorectal manometry using a specially designed sleeve microassembly for the diagnosis of neonatal HD.

Methods

Anorectal manometry was conducted without sedation in 41 newborns, aged 2 to 30 days (19 newborns were within the first week of life), with abdominal distension. A silastic assembly with a 2-cm-long sleeve sensor and 5 side holes arrayed along the sleeve was designed to reduce the effects of displacement of pressure sensors relative to the anal sphincter. Rectoanal inhibitory reflex (RAIR) was examined with rectal balloon distension.

Results

Thirty-two subjects who showed falls of anal sphincter pressure fulfilling the criteria for RAIR were diagnosed to be without HD. Nine patients without an appropriate RAIR were subsequently confirmed to have HD based on operative pathologic findings. Parameters of anal sphincter function did not differ significantly between the subjects with and without RAIR.

Conclusions

An anorectal sleeve micromanometric technique is useful in the diagnostic workup of newborns suspected of having HD.     

Thoracoscopic repair for congenital diaphragmatic hernia: lessons from 45 cases

Purpose

To describe the surgical technique, initial results, and overview indications of thoracoscopic repair of congenital diaphragmatic hernia (CDH).

Materials and Methods

A retrospective review was undertaken of patients with CDH who underwent thoracoscopic repair by the same surgeon from January 2001 to January 2005. Patients underwent surgery under general anesthesia. Reduction of the hernia contents was carried out using 1 optical trocar and 2 operating trocars. Pleural insufflation with carbon dioxide was maintained at a pressure of 2 to 4 mm Hg. The hernia defect was repaired using nonabsorbable interrupted sutures with extracorporeal knots.

Results

There were 45 patients, including 29 boys and 16 girls. Among 19 newborn patients, there were 13 patients younger than 7 days. The other 26 patients were infants and elders. The hernia was located in the left side in 37 patients and in the right side in 8 patients. The mean operative time was 54 minutes. Conversion was required in 4 patients. There were no complications. However, there were 2 postoperative deaths.

Conclusions

Thoracoscopic repair is feasible and safe for children with CDH, including selective newborn. The technique causes minimal trauma, results in good respiratory function, and promotes early recovery.     

Three-dimensional imaging improves surgical performance for both novice and experienced operators using the da Vinci Robot System

Background

This study was designed to evaluate the impact of 3-dimensional vision on the performance of resident and experienced surgeons using the da Vinci Robot System (Intuitive Surgical, Sunnyvale, CA).

Methods

Four tasks were performed by 12 surgeons with varying experience. Performance times and errors were recorded using both 2-dimensional and 3-dimensional vision for each task.

Results

Performance time and error rates for all 4 skills confirm a significant advantage using 3-dimensional vision. Performance times were reduced by 34% to 46% using 3-dimensional imaging for all participants with statistical significance. Error rates were reduced by 44% and 66%.

Conclusion

Independent of the biomechanical advantages of the da Vinci Robot System, 3-dimensional vision allows for significant improvement in performance times and error rates for both inexperienced residents and advanced laparoscopic surgeons.     

Expression of Pancreatic Endocrine Markers by Prolactin-Treated Rat Bone Marrow Mesenchymal Stem Cells

Background

Mesenchymal stem cells (MSCs) are an attractive source for generation of cells with β-cell properties. Previous studies have demonstrated the ability of prolactin to induce an increase in β-cell mass and maturation, which suggests beneficial effects of its use in MSC differentiation protocols.

Objective

To evaluate the expression of endocrine differentiation markers in rat MSCs treated in vitro with prolactin.

Methods

Mesenchymal stem cells from bone marrow of Wistar rats were isolated, expanded, and characterized. Differentiation of MSCs was induced in medium containing 23 mmol/L of glucose, and nicotinamide, 2-mercaptoethanol, and exendin-4, in the presence or absence of 500 ng/mL of rat recombinant prolactin. Expression of endocrine markers and prolactin receptor genes was evaluated using real-time polymerase chain reaction, and compared between culture stages and presence vs absence of prolactin in the culture medium. Expression of insulin, somatostatin, glucagon, and pancreatic and duodenal homeobox 1 was also evaluated at immunofluorescence microscopy.

Results

Isolated cells were mostly MSCs, as confirmed at fluorescent-activated cell sorting and cytochemistry. Pax6, Ngn-3, Isl1, NeuroD1, Nkx2.2, and Nkx6.1 exhibited varied expression during culture stages. The long form of the prolactin receptor messenger RNA was induced in prolactin-treated cultures (P < .05). The somatostatin gene was induced in early stages of differentiation (P < .05), and its expression was induced by prolactin, as confirmed using immunofluorescence.

Conclusion

Culture of rat bone marrow MSCs in differentiation medium induces expression of pancreatic endocrine-specific genes, and somatostatin and prolactin receptor expression was also induced by prolactin.     

Protective effects of mutant of acidic fibroblast growth factor against cerebral ischaemia-reperfusion injury in rats

Objective

To investigate the protective effect of a mutant of acidic fibroblast growth factor (MaFGF) against cerebral ischaemia-reperfusion injury in rats.

Methods

Sixty male Sprague-Dawley rats were randomly divided into six groups as follows: sham-operated group, untreated group, 20 μg/kg, 40 μg/kg and 80 μg/kg MaFGF-treated groups and also the positive control group. Cerebral ischaemia-reperfusion injury was induced by middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion for 24 h. Different dose of MaFGF were infused intravenously at 1 h after middle cerebral artery (MCA) occlusion. Nimodipine was used as positive control. The behaviour deficit score, brain-infarcted area, brain oedema degree, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were detected at 24 h after reperfusion.

Results

The results showed that MaFGF at the dose of 20 μg/kg, 40 μg/kg and 80 μg/kg significantly alleviated brain injury. Compared to untreated group, the behaviour deficits were much less severe, the brain oedema alleviated obviously, the MDA contents decreased and SOD activity increased dramatically in MaFGF-treated groups respectively. The efficacy of MaFGF was similar to that of nimodipine.

Conclusion

The results demonstrate that MaFGF has neuroprotective effect against brain injury resulting from focal ischaemia-reperfusion in Sprague-Dawley rats.     

Exclusion of neutropenic children from implanted central venous catheter placement: impact on early catheter removal

Background/Purpose

Based on the known risks of implanted central venous catheter (ICVC) placement in neutropenic children, we instituted a protocol whereby children with hematologic malignancies and an absolute neutrophil count less than 0.5 × 10⁹/L were excluded from an ICVC and had a percutaneously inserted central catheter placed until neutropenia resolved. The impact of this policy on the incidence of ICVC removal within 100 days of placement was evaluated.

Methods

The records of all children with hematologic malignancies who underwent placement of an ICVC (port or cuffed catheter) from 1999 through 2008 were reviewed. The incidence of catheter removal within 100 days was compared between subjects who had ICVC placed before (preprotocol) and after (postprotocol) the absolute neutrophil count-based exclusion protocol.

Results

Implanted central venous catheters were placed in 437 children, 311 in group 1 and 126 in group 2. The incidence of catheter removal within 100 days of placement for infection (4.1% [13/314] versus 0.8% [1/126], P = .07) and all causes combined (9.6% [30/314] versus 2.4% [3/126], P = .01) was substantially lower in the postprotocol group.

Conclusions

We have demonstrated that a protocol whereby neutropenic children were excluded from ICVC placement dramatically diminished complications that necessitated early catheter removal.     

Anatomic relationship between the spinal accessory nerve and internal jugular vein in the upper neck

Objective

The goal of this study was to precisely detail the relationship between the spinal accessory nerve (SAN) and the internal jugular vein (IJV) in the upper neck, specifically at the level of the posterior belly of the digastric muscle.

Study Design

Case series with planned data collection.

Setting

University hospital.

Subjects and Methods

This information was prospectively gathered intraoperatively in patients undergoing a neck dissection. The neck dissections were performed for the treatment or diagnosis of cancer, independent of the research goals. Eighty-six subjects underwent neck dissections, 56 unilateral and 30 bilateral. The position of the SAN was determined to be oriented lateral to the IJV, medial to the IJV, posterior to the IJV, or directly through the IJV at the level of the posterior belly of the digastric muscle.

Results

Of 116 neck dissections, 112 (96%) were oriented lateral to the IJV at the level of the superior border of the posterior belly of the digastric muscle. In three necks (3%), the SAN was positioned medial to the IJV, and one (1%) traveled directly through the IJV.

Conclusion

The SAN has an intimate anatomic relationship with the IJV as it travels through the neck. The SAN is nearly always oriented lateral to the IJV, and the IJV and SAN are likely at some increased risk of injury during neck dissection in cases where the nerve travels medial to or through the IJV.     

There are no estrogen and progesterone receptors in cerebral cavernomas: A preliminary immunohistochemical study

Background

Literature consistently mentions that pregnancy and hormonal therapy probably increase the bleeding rate and seizure expression of cerebral cavernomas. Either increased hormonal activity or embryogenesis related abundant expression of some growth factors such as VEGF, bFGF, and placental growth factor during pregnancy were proposed to initiate angiogenic process and vascular proliferation in cavernomas, thereby increasing their bleeding rate and seizure expression.

Methods

To reveal whether estrogen and/or progesterone have direct effect on cerebral cavernomas, their receptor expressions were studied immunohistochemically in recently excised 12 cerebral cavernomas.

Results

Study showed no expression of either estrogen or progesterone receptors in cerebral cavernomas even the staining worked well in positive control tissues of infiltrative ductal carcinoma.

Conclusions

Aggressive behavior of cerebral cavernomas during pregnancy is a commonly proven observation and attributed to some hormonal effects. However, this effect seems not related to effect of estrogen or progesterone on cavernoma tissue via receptor binding.     

Do sentinel node micrometastases predict recurrence risk in ductal carcinoma in situ and ductal carcinoma in situ with microinvasion?

Background

Because the implications of micrometastases found on sentinel node biopsy (SNB) for ductal carcinoma in situ (DCIS) or ductal carcinoma in situ with microinvasion (DCISM) are largely unknown, we wished to determine if SNB pathology predicted recurrence risk in DCIS/DCISM.

Methods

Retrospective chart review identified patients with DCIS/DCISM who underwent SNB. SNB findings and all local and distant recurrences were determined.

Results

A total of 322 patients underwent SNB for DCIS/DCISM. There were 13 local recurrences (4.0%) and 1 (.03%) distant recurrence at a median follow-up of 47.9 months (range 0 to 110.6), 12 in patients with negative SNBs; 1 patient had a positive SNB. There were 4 recurrences after mastectomy and 9 after lumpectomy. In 29 patients with positive SNBs, there was only 1 recurrence (3.4%).

Conclusions

Positive SNBs in patients with DCIS or DCISM are not associated with higher risk of local or distant recurrence. Other features of DCIS and DCISM may be important in predicting recurrence risk.