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1.  Pictorial review of normal postoperative cross-sectional imaging findings and infectious complications following laparoscopic appendectomy 
Insights into Imaging  2014;6(1):65-72.
Laparoscopic appendectomy is increasingly accepted as the preferred surgical treatment for acute appendicitis and represents one of the most common emergency operations performed in both adult and paediatric populations. However, in patients with perforated appendicitis laparoscopy is associated with an increased incidence of postoperative intraabdominal infections compared to open appendectomy. Nowadays urgent imaging is commonly requested by surgeons when postoperative complications are suspected. Due to the widespread use of laparoscopy, in hospitals with active surgical practices clinicians and radiologists are increasingly faced with suspected postappendectomy complications. This pictorial essay illustrates the normal cross-sectional imaging findings observed shortly after laparoscopic appendectomy and the spectrum of appearances of iatrogenic intraabdominal infections observed in adults and adolescents, aiming to provide radiologists with an increased familiarity with early postoperative imaging. Emphasis is placed on the role of multidetector CT, which according to the most recent World Society of Emergency Surgery (WSES) guidelines is the preferred and most accurate modality to promptly investigate suspected intraabdominal infections and highly helpful for correct therapeutic choice, particularly to identify those occurrences that require in-hospital treatment, drainage or surgical reintervention. In teenagers and young adults MRI represents an attractive alternative modality to detect or exclude iatrogenic abscesses without ionising radiation.
Teaching points
• Laparoscopic appendectomy is the preferred surgical treatment for uncomplicated acute appendicitis
• In perforated appendicitis laparoscopy results in increased incidence of intraabdominal infections
• Multidetector CT promptly assesses suspected iatrogenic intraabdominal infections
• Interpretation of early postoperative CT requires knowledge of normal postsurgical imaging findings
• Postsurgical infections include right-sided peritonitis, intraabdominal, pelvic or liver abscesses
doi:10.1007/s13244-014-0369-6
PMCID: PMC4330234  PMID: 25431189
Appendectomy; Laparoscopic surgery; Acute appendicitis; Infectious complications; Abscess; Computed tomography (CT); Magnetic resonance imaging (MRI)
2.  High mobility group A1 protein expression reduces the sensitivity of colon and thyroid cancer cells to antineoplastic drugs 
BMC Cancer  2014;14(1):851.
Background
Development of resistance to conventional drugs and novel biological agents often impair long-term chemotherapy. HMGA gene overexpression is often associated with antineoplastic drug resistance and reduced survival. Inhibition of HMGA expression in thyroid cancer cells reduces levels of ATM protein, the main cellular sensor of DNA damage, and enhances cellular sensitivity to DNA-damaging agents. HMGA1 overexpression promotes chemoresistance to gemcitabine in pancreatic adenocarcinoma cells through an Akt-dependent mechanism.
Methods
To elucidate the role of HMGA1 proteins in chemoresistance we analyzed resistance to conventional drugs and targeted therapies of human colon carcinoma cells (GEO) that are sensitive to the epidermal growth factor receptor inhibitor cetuximab, and express minimal levels of HMGA1 and cetuximab-resistant (GEO CR) cells expressing high HMGA1 protein levels.
Results
GEO CR cells were less sensitive than GEO cells to cetuximab and 5-fluorouracil. GEO CR cells silenced for HMGA1 expression were more susceptible than empty vector-transfected cells to the drugs’ cytotoxicity. Similar results were obtained with anaplastic thyroid carcinoma cells expressing or not HMGA1 proteins, treated with doxorubicin or the HDAC inhibitor LBH589. Finally, HMGA1 overexpression promoted the DNA-damage response and stimulated Akt phosphorylation and prosurvival signaling.
Conclusions
Our findings suggest that the blockage of HMGA1 expression is a promising approach to enhance cancer cell chemosensitivity, since it could increase the sensitivity of cancer cells to antineoplastic drugs by inhibiting the survival signal and DNA damage repair pathways.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2407-14-851) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2407-14-851
PMCID: PMC4247615  PMID: 25409711
HMGA1; Chemoresistance; Colon cancer; Thyroid cancer
4.  Hemorrhage and thrombosis with different LVAD technologies: a matter of flow? 
Annals of Cardiothoracic Surgery  2014;3(6):582-584.
Background
Much of the morbidity and mortality associated with ventricular assist devices (VADs) is due to haemorrhagic and thrombotic complications. To manage antithrombotic therapy, interactions between the patient and pump should be better understood.
Methods
We have compared the Jarvik 2000, an axial flow left ventricular assist device (LVAD), with the HeartWare ventricular assist device (HVAD) centrifugal pump, regarding conventional laboratory findings, thromboelastometric and aggregometric tests.
Results
Patients with the Jarvik 2000 experienced a significant reduction in platelet count following implantation, a phenomenon not seen with the HeartWare model. Conversely, we observed that levels of platelet activation, as assessed by a platelet function analyzer, and activation of the coagulation system, as assessed by thromboelastometry, were significantly greater in the HeartWare group.
Conclusions
It seems that axial flow pumps, being more destructive on blood cells, tend to reduce platelet numbers. On the other hand, centrifugal flow is associated with a hypercoagulable state, possibly resulting from the activation of the coagulation system in the absence of platelet destruction.
doi:10.3978/j.issn.2225-319X.2014.08.21
PMCID: PMC4250552  PMID: 25512898
Ventricular assist device (VAD); bleeding; thrombosis; axial flow; centrifugal flow
5.  Cross-sectional imaging of iatrogenic complications after extracorporeal and endourological treatment of urolithiasis 
Insights into Imaging  2014;5(6):677-689.
Extracorporeal shock wave lithotripsy (ESWL), percutaneous nephrolithotomy (PCNL) and ureteroscopy (URS) currently represent the mainstay treatment options for the vast majority of patients with urolithiasis, with limited contraindications and high success rates. However, minimally invasive extracorporeal and endourological treatments are associated with a non-negligible morbidity including occasional life-threatening occurrences. These complications represent a source of concern for urologists since they may result in prolonged hospitalisation, need for surgical, endoscopic or interventional treatment, long-term renal impairment, and sometimes even medical malpractice claims. Due to the increasing prevalence of urolithiasis and the large number of therapeutic procedures performed, in hospitals with active urologic practices radiologists are increasingly requested to investigate suspected post-procedural complications following ESWL, PCNL or ureteroscopic stone removal. Based upon our experience, this pictorial essay provides an overview of current extracorporeal and endourological treatment modalities for urolithiasis, including indications and possible complications according to the most recent guidelines from the European Association of Urology (EAU). Afterwards, we review the clinical features and cross-sectional imaging appearances of common and unusual complications with case examples, including steinstrasse, subcapsular, perirenal and suburothelial haemorrhages, severe urinary tract infections (such as pyeloureteritis, pyelonephritis, renal abscesses and pyonephrosis), ureteral injuries and delayed strictures.
Teaching points
• Extracorporeal lithotripsy, percutaneous nephrolitotomy and ureteroscopy allow treating urolithiasis.
• Minimally invasive extracorporeal and endourological treatment have non-negligible morbidity.
• Multidetector CT allows confident assessment of stone-free status and postprocedural complications.
• Main complications include steinstrasse, bleeding, severe infections, ureteral injuries and strictures.
• Imaging triage allows the choice among conservative, surgical, endoscopic or interventive treatment.
doi:10.1007/s13244-014-0355-z
PMCID: PMC4263803  PMID: 25256564
Urolithiasis; Lithotripsy; Ureteroscopy; Complications; Computed Tomography (CT)
8.  Decellularized Allogeneic Heart Valves Demonstrate Self-Regeneration Potential after a Long-Term Preclinical Evaluation 
PLoS ONE  2014;9(6):e99593.
Tissue-engineered heart valves are proposed as novel viable replacements granting longer durability and growth potential. However, they require extensive in vitro cell-conditioning in bioreactor before implantation. Here, the propensity of non-preconditioned decellularized heart valves to spontaneous in body self-regeneration was investigated in a large animal model. Decellularized porcine aortic valves were evaluated for right ventricular outflow tract (RVOT) reconstruction in Vietnamese Pigs (n = 11) with 6 (n = 5) and 15 (n = 6) follow-up months. Repositioned native valves (n = 2 for each time) were considered as control. Tissue and cell components from explanted valves were investigated by histology, immunohistochemistry, electron microscopy, and gene expression. Most substitutes constantly demonstrated in vivo adequate hemodynamic performances and ex vivo progressive repopulation during the 15 implantation months without signs of calcifications, fibrosis and/or thrombosis, as revealed by histological, immunohistochemical, ultrastructural, metabolic and transcriptomic profiles. Colonizing cells displayed native-like phenotypes and actively synthesized novel extracellular matrix elements, as collagen and elastin fibers. New mature blood vessels, i.e. capillaries and vasa vasorum, were identified in repopulated valves especially in the medial and adventitial tunicae of regenerated arterial walls. Such findings correlated to the up-regulated vascular gene transcription. Neoinnervation hallmarks were appreciated at histological and ultrastructural levels. Macrophage populations with reparative M2 phenotype were highly represented in repopulated valves. Indeed, no aspects of adverse/immune reaction were revealed in immunohistochemical and transcriptomic patterns. Among differentiated elements, several cells were identified expressing typical stem cell markers of embryonic, hematopoietic, neural and mesenchymal lineages in significantly higher number and specific topographic distribution in respect to control valves. Following the longest follow-up ever realized in preclinical models, non-preconditioned decellularized allogeneic valves offer suitable microenvironment for in vivo cell homing and tissue remodeling. Manufactured with simple, timesaving and cost-effective procedures, these promising valve replacements hold promise to become an effective alternative, especially for pediatric patients.
doi:10.1371/journal.pone.0099593
PMCID: PMC4062459  PMID: 24940754
9.  Epidermal growth factor-receptor activation modulates Src-dependent resistance to lapatinib in breast cancer models 
Introduction
Src tyrosine kinase overactivation has been correlated with a poor response to human epidermal growth factor receptor 2 (HER2) inhibitors in breast cancer. To identify the mechanism by which Src overexpression sustains this resistance, we tested a panel of breast cancer cell lines either sensitive or resistant to lapatinib.
Methods
To determine the role of Src in lapatinib resistance, we evaluated the effects of Src inhibition/silencing in vitro on survival, migration, and invasion of lapatinib-resistant cells. In vivo experiments were performed in JIMT-1 lapatinib-resistant cells orthotopically implanted in nude mice. We used artificial metastasis assays to evaluate the effect of Src inhibition on the invasiveness of lapatinib-resistant cells. Src-dependent signal transduction was investigated with Western blot and ELISA analyses.
Results
Src activation was higher in lapatinib-resistant than in lapatinib-sensitive cells. The selective small-molecule Src inhibitor saracatinib combined with lapatinib synergistically inhibited the proliferation, migration, and invasion of lapatinib-resistant cells. Saracatinib combined with lapatinib significantly prolonged survival of JIMT-1-xenografted mice compared with saracatinib alone, and impaired the formation of lung metastases. Unexpectedly, in lapatinib-resistant cells, Src preferentially interacted with epidermal growth factor receptor (EGFR) rather than with HER2. Moreover, EGFR targeting and lapatinib synergistically inhibited survival, migration, and invasion of resistant cells, thereby counteracting Src-mediated resistance. These findings demonstrate that Src activation in lapatinib-resistant cells depends on EGFR-dependent rather than on HER2-dependent signaling.
Conclusions
Complete pharmacologic EGFR/HER2 inhibition is required to reverse Src-dependent resistance to lapatinib in breast cancer.
doi:10.1186/bcr3650
PMCID: PMC4076622  PMID: 24887236
10.  Multidetector CT imaging of post-robot-assisted laparoscopic radical prostatectomy complications 
Insights into Imaging  2013;4(5):711-721.
Background
Robot-assisted laparoscopic radical prostatectomy (RALRP) is currently accepted as the preferred minimally invasive surgical treatment for localised prostate cancer, with optimal oncologic and functional results. Despite growing surgical experience, reduced postoperative morbidity and hospital stays, RALRP-related complications may occur, which are severe in 5–7 % of patients and sometimes require reoperation. Therefore, in hospitals with an active urologic surgery, urgent diagnostic imaging is increasingly requested to assess suspected early complications following RALRP surgery.
Methods
Based upon our experience, this pictorial review discusses basic principles of the surgical technique, the optimal multidetector CT (MDCT) techniques to be used in the postoperative urologic setting, the normal postoperative anatomy and imaging appearances.
Results
Afterwards, we review and illustrate the varied spectrum of RALRP-related complications including haemorrhage, urinary leaks, anorectal injuries, peritoneal changes, surgical site infections, abscess collections and lymphoceles, venous thrombosis and port site hernias.
Conclusion
Knowledge of surgical procedure details, appropriate MDCT acquisition techniques, and familiarity with normal postoperative imaging appearances and possible complications are needed to correctly perform and interpret early post-surgical imaging studies, particularly to identify those occurrences that require prolonged in-hospital treatment or surgical reintervention.
Teaching points
• Robot-assisted laparoscopic radical prostatectomy allows minimally invasive surgery of localised cancer
• Urologic surgeons may request urgent imaging to assess suspected postoperative complications
• Main complications include haemorrhage, urine leaks, anorectal injuries, infections and lymphoceles
• Correct multidetector CT techniques allow identifying haematomas, active bleeding and extravasated urine
• Imaging postoperative complications is crucial to assess the need for surgical reoperation
doi:10.1007/s13244-013-0280-6
PMCID: PMC3781251  PMID: 24018752
Prostatectomy; Robotic surgery; Laparoscopic surgery; Complications; Haemorrhage; Anastomotic leak; Urine leak; Computed tomography (CT); Cystography
11.  Combination of a Toll-like receptor 9 agonist with everolimus interferes with the growth and angiogenic activity of renal cell carcinoma 
Oncoimmunology  2013;2(8):e25123.
The mTOR inhibitor everolimus is currently approved for the treatment of renal cell carcinoma (RCC) and several Toll-like receptor 9 (TLR9) agonists, including immunomodulatory oligonucleotides (IMOs), have been tested for their therapeutic potential against advanced RCC. However, no clinical trials investigating the combination of mTOR inhibitors with TLR9 agonists in RCC patients have been performed to date. Our results may pave the way to translate this combinatorial approach to the clinical setting.
doi:10.4161/onci.25123
PMCID: PMC3782521  PMID: 24083076
mTOR; TLR9; everolimus; renal cell carcinoma; microenvironment
12.  Early non-aneurysmal infectious aortitis: Cross-sectional imaging diagnosis 
In patients without history of vascular surgery, infectious aortitis is a very uncommon, life-threatening condition with nonspecific clinical manifestations, which exposes the patient to uncontrolled sepsis and to the risk of retroperitoneal rupture. State-of-the-art cross-sectional imaging with contrast-enhanced multidetector computed tomography and magnetic resonance imaging allows confident diagnosis and characterization of unsuspected aortitis in septic patients at an early stage before the development of aneurysmal dilatation. The asymmetric distribution of periaortic inflammatory tissue is helpful for the differentiation of this exceptional disorder from other periaortic abnormalities such as retroperitoneal fibrosis or lymphoma.
doi:10.4103/0974-2700.110811
PMCID: PMC3665067  PMID: 23723629
Aortitis; computed tomography; magnetic resonance imaging; sepsis; Staphylococcus aureus
13.  Water enema multidetector CT technique and imaging of diverticulitis and chronic inflammatory bowel diseases 
Insights into Imaging  2013;4(3):309-320.
Background
Water enema multidetector computed tomography (WE-MDCT) is currently considered the most accurate imaging modality to provide high-resolution multiplanar visualisation of the colonic wall and surrounding structures.
Methods
This pictorial review presents our experience with WE-MDCT applications outside colorectal tumour staging, particularly for investigating diverticular disease and chronic inflammatory bowel diseases. A detailed explanation of the technique is provided, including patient preparation, the acquisition protocol, and study interpretation.
Results
WE-MDCT allows accurate preoperative visualisation of diverticular disease, acute and complicated diverticulitis. Ulcerative, indeterminate, or Crohn’s colitis can be assessed including longitudinal distribution, mural thickening and enhancement patterns, pseudopolyps, associated perivisceral changes, adjacent organ involvement, and features suggesting carcinoma. Elective WE-MDCT represents a useful complementary technique in patients with impossible, incomplete, or inconclusive endoscopy, can allow study of a stricture’s features and the upstream bowel, and helps planning medical, endoscopic, or surgical treatments.
Conclusion
Urgent WE-MDCT with limited or no bowel preparation may prove useful in acutely symptomatic patients, as it may obviate a risky or contraindicated endoscopy, can determine disease severity, and allows making correct therapeutic choices.
Teaching Points
• Water enema multidetector CT provides high-resolution multiplanar visualisation of the colonic wall.
• WE-MDCT allows accurate visualisation of diverticular disease, acute and complicated diverticulitis.
• In chronic inflammatory bowel diseases WE-MDCT depicts the distribution, mural and perivisceral changes.
• Elective WE-MDCT usefully complements incomplete endoscopy to assess strictures and upstream colon.
• Urgent WE-MDCT with limited or no bowel preparation in acute diseases may obviate endoscopy.
doi:10.1007/s13244-013-0239-7
PMCID: PMC3675246  PMID: 23508934
Contrast enema; Computed tomography (CT); Colonoscopy; Diverticular disease; Acute diverticulitis; Chronic inflammatory bowel diseases; Ulcerative colitis; Crohn’s disease; Indeterminate colitis
14.  Erratum to: MRI and CT of anal carcinoma: a pictorial review 
Insights into Imaging  2013;4(1):63.
doi:10.1007/s13244-013-0221-4
PMCID: PMC3579988  PMID: 23361151
15.  Spontaneous esophageal perforation (Boerhaave syndrome): Diagnosis with CT-esophagography 
Spontaneous esophageal perforation (Boerhaave syndrome) is a very uncommon, life-threatening surgical emergency that should be suspected in all patients presenting with lower thoracic-epigastric pain and a combination of gastrointestinal and respiratory symptoms. Variable clinical manifestations and subtle or unspecific radiographic findings often result in critical diagnostic delays. Multidetector computed tomography complemented with CT-esophagography represents the ideal “one-stop shop” investigation technique to allow a rapid, comprehensive diagnosis of BS, including identification of suggestive periesophageal abnormalities, direct visualization of esophageal perforation and quantification of mediastinitis.
doi:10.4103/0974-2700.106329
PMCID: PMC3589863  PMID: 23493470
Computed tomography; contrast medium; esophagography; esophageal perforation; esophagus
16.  MRI and CT of anal carcinoma: a pictorial review 
Insights into Imaging  2012;4(1):53-62.
Background
Squamocellular anal carcinoma is increasingly diagnosed in patients with risk factors.
Methods
State-of-the-art imaging with magnetic resonance imaging (MRI) using phased-array coils and volumetric multidetector computed tomography (CT) provides detailed visualisation of anal disorders, identification and extent assessment of neoplastic tissue, detection and characterisation of nodal and visceral metastases. MRI has been recommended by the European Society for Medical Oncology (ESMO) as the preferred modality of choice to stage anal cancer, taking into account the maximum tumour diameter, invasion of adjacent structures and regional lymph node involvement.
Results
Cross-sectional imaging techniques allow the identification of coexisting complications, and differentiation from other perineal abnormalities.
Conclusion
Cross-sectional imaging is useful for planning radiotherapy, surgical drainage or salvage abdomino-perineal resection. After chemo-radiotherapy, MRI follow-up provides confident reassessment of therapeutic response, persistent or recurrent disease.
Teaching Points
• Anal carcinoma is increasingly diagnosed in patients with human immunodeficiency virus (HIV), anoreceptive intercourse, chronic inflammatory bowel disease.
• An established association exists with human papillomavirus (HPV) infection and premalignant intra-epithelial dysplasia.
• Phased-array MRI is recommended as the preferred imaging modality for regional staging.
• Imaging allows detection of infectious complications, planning of radiotherapy or salvage surgery.
• Follow-up MRI allows reliable assessment of therapeutic response after chemo-radiotherapy.
doi:10.1007/s13244-012-0199-3
PMCID: PMC3579995  PMID: 23208584
Anal carcinoma; Anus; Human immunodeficiency virus; Chronic inflammatory bowel diseases; Computed Tomography (CT); Magnetic Resonance Imaging (MRI)
17.  Pulmonary cement embolism after pedicle screw vertebral stabilization 
Pulmonary arterial embolization of polymethylmethacrylate cement, most usually occurring after vertebroplasty or kyphoplasty, is very uncommon following vertebral stabilization procedures. Unenhanced CT scans viewed at lung window settings allow confident identification of cement emboli in the pulmonary circulation along with possible associate parenchymal changes, whereas hyperdense emboli may be less conspicuous on CT-angiographic studies with high-flow contrast medium injection. Although clinical manifestations are largely variable from asymptomatic cases to severe respiratory distress, most cases are treated with anticoagulation.
doi:10.4103/0974-2700.99710
PMCID: PMC3440899  PMID: 22988411
Vertebral stabilization; vertebroplasty; pulmonary embolism; polymethylmethacrylate bone cement
18.  Septic thrombophlebitis in a HIV-positive intravenous drug user 
Septic thrombophlebitis of the pelvic veins may occur secondary to non-sterile intravenous drug injection and represents an uncommon yet life-threatening condition, most usually manifesting with persistent spiking fever and limb edema. Risk is further increased in HIV-infected people. High clinical suspicion and prompt imaging assessment with contrast-enhanced multidetector CT are necessary for correct diagnosis and staging, since early treatment prevents further complications such as systemic embolization.
doi:10.4103/0974-2700.99711
PMCID: PMC3440900  PMID: 22988412
Computed tomography; human immunodeficiency virus infection; intravenous drug abuse; sepsis; thrombophlebitis
19.  Mycotic visceral aneurysm complicating infectious endocarditis: Imaging diagnosis and follow-up 
One of the rarest complications of endocarditis, infected (mycotic) aneurysms result from haematogenous dissemination of septic emboli and occur more frequently in patients with cardiac valvular abnormalities or prosthetic valves, intravenous drug abuse, diabetes and immunosuppression conditions such as HIV infection. Although often clinically unsuspected, mycotic aneurysms are potentially life-threatening because of disseminated sepsis and propensity to rupture. Contrast-enhanced multidetector CT provides prompt detection, characterization and vascular mapping of these lesions, allowing correct planning of surgical or interventional therapies and reproducible follow-up. Because of their characteristically unpredictable behaviour, mycotic aneurysms may undergo spontaneous thrombosis, size reduction, rapid enlargement or rupture, therefore strict imaging surveillance with CT and/or color Doppler ultrasound is necessary.
doi:10.4103/0974-2700.96501
PMCID: PMC3391851  PMID: 22787357
Endocarditis; mesenteric artery; mycotic aneurysm; sepsis; visceral aneurysm
20.  Multidetector CT cystography for imaging colovesical fistulas and iatrogenic bladder leaks 
Insights into Imaging  2012;3(2):181-187.
Multidetector computed tomography (MDCT) cystography currently represents the modality of choice to image the urinary bladder in traumatized patients. In this review we present our experience with MDCT cystography applications outside the trauma setting, particularly for diagnosing bladder fistulas and leaks. A detailed explanation is provided concerning exam preparation, acquisition technique, image reconstruction and interpretation. Colovesical fistulas most commonly occur as a complication of sigmoid diverticular disease, and often remain occult after extensive diagnostic work-up including cystoscopy and contrast-enhanced CT. We consistently achieved accurate preoperative visualization of colovesical fistulas using MDCT cystography. Urinary leaks and injuries represent a non-negligible occurrence after pelvic surgery, particularly obstetric and gynaecological procedures: in our experience MDCT cystography is useful to investigate iatrogenic bladder leaks or fistulas. In our opinion, MDCT cystography should be recommended as the first line modality for direct visualization or otherwise confident exclusion of both spontaneous enterovesical fistulas and bladder injuries following instrumentation procedures, obstetric or surgical interventions.
Main Messages
• Explanation of exam preparation, acquisition technique, image reconstruction and interpretation.
• Preoperative visualization of colovesical fistulas, usually secondary to sigmoid diverticulitis.
• Visualization or exclusion of iatrogenic bladder injuries following instrumentation or surgery.
doi:10.1007/s13244-011-0145-9
PMCID: PMC3314733  PMID: 22696044
Computed tomography (CT); Urinary bladder; Urinary bladder fistula; Colonic diverticulitis; Postoperative complications
21.  Multidetector CT cystography for imaging colovesical fistulas and iatrogenic bladder leaks 
Insights into Imaging  2012;3(2):181-187.
Multidetector computed tomography (MDCT) cystography currently represents the modality of choice to image the urinary bladder in traumatized patients. In this review we present our experience with MDCT cystography applications outside the trauma setting, particularly for diagnosing bladder fistulas and leaks. A detailed explanation is provided concerning exam preparation, acquisition technique, image reconstruction and interpretation. Colovesical fistulas most commonly occur as a complication of sigmoid diverticular disease, and often remain occult after extensive diagnostic work-up including cystoscopy and contrast-enhanced CT. We consistently achieved accurate preoperative visualization of colovesical fistulas using MDCT cystography. Urinary leaks and injuries represent a non-negligible occurrence after pelvic surgery, particularly obstetric and gynaecological procedures: in our experience MDCT cystography is useful to investigate iatrogenic bladder leaks or fistulas. In our opinion, MDCT cystography should be recommended as the first line modality for direct visualization or otherwise confident exclusion of both spontaneous enterovesical fistulas and bladder injuries following instrumentation procedures, obstetric or surgical interventions.
Main Messages
• Explanation of exam preparation, acquisition technique, image reconstruction and interpretation.
• Preoperative visualization of colovesical fistulas, usually secondary to sigmoid diverticulitis.
• Visualization or exclusion of iatrogenic bladder injuries following instrumentation or surgery.
doi:10.1007/s13244-011-0145-9
PMCID: PMC3314733  PMID: 22696044
Computed tomography (CT); Urinary bladder; Urinary bladder fistula; Colonic diverticulitis; Postoperative complications
22.  Hemoperitoneum from splenic rupture in an expatriate 
Splenic rupture with hemoperitoneum represents a life-threatening surgical emergency. Malaria should be highly suspected as the probable underlying disease in returning travellers, expatriates, or recent immigrants from endemic countries. Malarial complications involving the spleen occur even with appropriate prophylaxis or during antimalarial therapy. Among them, splenic infarction has a favourable course and is treated conservatively, whereas life-threatening rupture requires immediate or delayed splenectomy. Computed tomography (CT) allows confident differentiation between these two complications by identifying ruptured spleen with clotted hematoma and associated high-density peritoneal effusion; furthermore, CT allows differential diagnosis from other causes of spontaneous hemoperitoneum.
doi:10.4103/0974-2700.93100
PMCID: PMC3299142  PMID: 22416169
Malaria; plasmodium falciparum; splenic rupture; hemoperitoneum
23.  Addition of erlotinib to fluoropyrimidine-oxaliplatin-based chemotherapy with or without bevacizumab: Two sequential phase I trials 
The combination of EGFR inhibitors and anti-angiogenic drugs has a strong pre-clinical rationale, yet its use has produced controversial clinical results. We conducted two sequential phase I trials to evaluate the feasibility and the recommended dose of erlotinib when combined with fluoropyrimidine-oxaliplatin-based chemotherapy with or without bevacizumab. A total of 21 metastatic colorectal cancer (mCRC) patients were treated in two sequential phase I trials. In the first trial, 12 patients were treated with escalating doses of erlotinib plus FOLFOX. In the second, 9 patients were treated with escalating doses of erlotinib combined with oxaliplatin, capecitabine and bevacizumab. No MTD was reached in either of the trials. The only dose-limiting toxicities observed were neutropenia and diarrhea. No unexpected toxicities were noted. Hematological toxicity was the most frequently noted adverse event with infusional 5FU therapy, while gastrointestinal toxicity was the most common adverse event. In the second trial most patients withdrew from treatment due to toxicity, and less than half completed the therapeutic program as per protocol, mostly due to toxicity. In conclusion, the present study confirms the disappointing results of the double combination of EGFR inhibitors and anti-angiogenic drugs in mCRC patients.
doi:10.3892/etm.2011.218
PMCID: PMC3440709  PMID: 22977524
phase I trial; colorectal cancer; bevacizumab; erlotinib; capecitabine; FOLFOX
24.  Adjuvant FOLFOX-4 in patients with radically resected gastric cancer: Tolerability and prognostic factors 
The aim of the present study was to evaluate the toxicity and efficacy of the FOLFOX-4 regimen as adjuvant chemotherapy in patients with gastric cancer after radical surgery. Fifty-four patients (1 stage Ib, 6 stage II, 22 stage IIIa, 14 stage IIIb and 11 stage IV) received 8-12 cycles of FOLFOX-4 (oxaliplatin 85 mg/m2, Day 1; leucovorin 100 mg/m2 i.v., Days 1 and 2; 5-fluorouracil 400 mg/m2 i.v. bolus, Days 1 and 2 and 600 mg/m2 in 22 h i.v. continuous infusion, Days 1 and 2; every 14 days). Toxicity was recorded at each cycle according to the National Cancer Institute Common Toxicity Criteria. Disease-free (DFS) and overall survival (OS) were calculated according to the Kaplan-Meier method. Thirty-eight patients (70.4%) completed the prescribed number of cycles of chemotherapy. The toxicity was mild. Grade 3–4 neutropenia occurred in 57% of patients, thrombocytopenia and anemia in 2% of cases. Peripheral neuropathy was experienced by 46% of the patients (grade 4 in 2% of cases). Five patients experienced grade 3 gastrointestinal toxicity. After a median follow-up of 33.1 months, 17 patients relapsed and 17 succumbed to the disease. The mean observed DFS and OS were 49.7 months (range 40.7–58.8) and 57.9 months (range 49.6–66.2), respectively. At univariate analysis, females and patients who had received <8 cycles of chemotherapy had a significantly worse probability of DFS and OS. The Cox model showed gender to be independent of the factors affecting DFS. Adjuvant FOLFOX-4 is feasible and well-tolerated in patients radically resected for gastric cancer. Receiving <4 months of adjuvant FOLFOX-4 could be detrimental to prognosis.
doi:10.3892/etm_00000096
PMCID: PMC3445918  PMID: 22993584
gastric cancer; oxaliplatin; adjuvant
25.  Overcoming resistance to molecularly targeted anticancer therapies: rational drug combinations based on EGFR and MAPK inhibition for solid tumours and haematologic malignancies 
Accumulating evidence suggests that cancer can be envisioned as a “signaling disease”, in which alterations in the cellular genome affect the expression and/or function of oncogenes and tumour suppressor genes. This ultimately disrupts the physiologic transmission of biochemical signals that normally regulate cell growth, differentiation and programmed cell death (apoptosis). From a clinical standpoint, signal transduction inhibition as a therapeutic strategy for human malignancies has recently achieved remarkable success. However, as additional drugs move forward into the clinical arena, intrinsic and acquired resistance to “targeted” agents becomes an issue for their clinical utility. One way to overcome resistance to targeted agents is to identify genetic and epigenetic aberrations underlying sensitivity/resistance, thus enabling the selection of patients that will most likely benefit from a specific therapy. Since resistance often ensues as a result of the concomitant activation of multiple, often overlapping, signaling pathways, another possibility is to interfere with multiple, cross-talking pathways involved in growth and survival control in a rational, mechanism-based, fashion. These concepts may be usefully applied, among others, to agents that target two major signal transduction pathways: the one initiated by epidermal growth factor receptor (EGFR) signaling and the one converging on mitogen-activated protein kinase (MAPK) activation. Here we review the molecular mechanisms of sensitivity/resistance to EGFR inhibitors, as well as the rationale for combining them with other targeted agents, in an attempt to overcome resistance. In the second part of the paper, we review MAPK-targeted agents, focusing on their therapeutic potential in hematologic malignancies, and examine the prospects for combinations of MAPK inhibitors with cytotoxic agents or other signal transduction-targeted agents to obtain synergistic anti-tumour effects.
doi:10.1016/j.drup.2007.03.003
PMCID: PMC2548422  PMID: 17482503
Targeted therapy; drug resistance; combination therapy; molecular markers; EGFR; IGFR1; MAPK; MEK inhibitors; AML

Results 1-25 (26)