Combined hepatocellular-cholangiocarcinoma: which preoperative clinical data and conventional MRI characteristics have value for the prediction of microvascular invasion and clinical significance?

OBJECTIVES: To explore which preoperative clinical data and conventional MRI findings may indicate microvascular invasion (MVI) of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and have clinical significance. METHODS: The study enrolled 113 patients with histopathologically confirmed cHCC-CCA (MVI-positive group [n = 56], MVI-negative group [n = 57]). Two radiologists retrospectively assessed the preoperative MRI features (qualitative analysis of morphology and dynamic enhancement features), and each lesion was assigned according to the LI-RADS. Preoperative clinical data were also evaluated. Logistic regression analyses were used to assess the relative value of these parameters as potential predictors of MVI. Recurrence-free survival (RFS) rates after hepatectomy in the two groups were estimated using Kaplan-Meier survival curves and compared using the log-rank test. RESULTS: The majority of cHCC-CCAs were categorized as LR-M. On multivariate analysis, a higher serum AFP level (OR, 0.523; 95% CI, 0.282-0.971; p = 0.040), intratumoral fat deposition (OR, 14.368; 95% CI, 2.749-75.098; p = 0.002), and irregular arterial peritumoral enhancement (OR, 0.322; 95% CI, 0.164-0.631; p = 0.001) were independent variables associated with the MVI of cHCC-CCA. After hepatectomy, patients with MVI of cHCC-CCA showed earlier recurrence than those without MVI (hazard ratio [HR], 0.402; 95% CI, 0.189-0.854, p = 0.013). CONCLUSION: A higher serum AFP level and irregular arterial peritumoral enhancement are potential predictive biomarkers for the MVI of cHCC-CCA, while intratumoral fat detected on MRI suggests a low risk of MVI. Furthermore, cHCC-CCAs with MVI may have worse surgical outcomes with regard to early recurrence than those without MVI. KEY POINTS: • Higher serum levels of AFP combined with irregular arterial peritumoral enhancement are independent risk factors for the MVI of cHCC-CCA, while fat deposition might be a protective factor. • cHCC-CCA with MVI may have a higher risk of early recurrence after surgery. • Most cHCC-CCAs were categorized as LR-M in this study, and no significant difference was found in MVI based on LI-RADS category.

Use of Intraoperative Indocyanine Green Angiography for Feeder Vessel Ligation and En Bloc Resection of Intramedullary Hemangioblastoma.

BACKGROUND: As vascular tumors, intramedullary hemangioblastomas are associated with significant intraoperative blood loss, making them particularly challenging clinical entities. The use of intraoperative indocyanine green or other fluorescent dyes has previously been described to avoid breaching the tumor capsule, but improved surgical outcomes may result from identifying and ligating the feeder arteries and arterialized draining veins. OBJECTIVE: To describe the use of combined preoperative angiography and intraoperative indocyanine green use for the identification of feeder arteries and arterialized draining veins to decrease blood loss in the resection of intramedullary hemangioblastomas. METHODS: A patient with cervical myelopathy secondary to a large C3 hemangioblastoma and cervicothoracic syrinx underwent a C2-3 laminoplasty with resection of the lesion. To reduce intraoperative blood loss and facilitate safe lesion resection, the vascular architecture of the lesion was defined via preoperative digital subtraction angiography and intraoperative use of indocyanine green. The latter permitted ligation of the major and minor feeding arteries and arterialized veins prior to tumor breach, allowing for facile en bloc resection of the lesion. RESULTS: The lesion was resected en bloc with minimal blood loss (approximately 100 mL) and without intraoperative neuromonitoring signal changes. The patient remained at neurological baseline throughout their stay. CONCLUSION: We present a written and media illustration of a technique for intraoperative indocyanine green use in the en bloc resection of intramedullary hemangioblastoma.

Double-Balloon-Assisted n-Butyl-2-Cyanoacrylate Embolization of Intrahepatic Arterioportal Shunt Prior to Chemoembolization of Hepatocellular Carcinoma.

A case of multiple hepatocellular carcinomas with a severe intrahepatic arterioportal shunt that was successfully embolized with n-butyl-2-cyanoacrylate with coaxial double-balloon occlusion prior to transcatheter arterial chemoembolization is presented. A proximal balloon positioned at the proper hepatic artery was used for flow control, and a coaxial microballoon, positioned in the closest of three arterial feeding branches to the arterioportal shunt, was used to control the delivery of n-butyl-2-cyanoacrylate. This coaxial double-balloon technique can prevent proximal embolization and distal migration of n-butyl-2-cyanoacrylate and enable precise control of the distribution of n-butyl-2-cyanoacrylate. It could also be applicable to n-butyl-2-cyanoacrylate embolization for other than intrahepatic arterioportal shunt.

[Open coloproctectomy with ileoanal J-pouch reconstruction]. / Offene Koloproktektomie mit ileoanaler J-Pouch-Rekonstruktion.

Coloproctectomy is a visceral surgical intervention where the complete colon and rectum are removed up to the level of the pelvic floor or pectinate line and the anal canal. As a rule the anal canal and pelvic floor musculature including the anal sphincter muscle remain intact. The ileoanal J-pouch construction has become established as treatment of choice for reconstruction of the small intestine. This article presents the approach for open coloproctectomy with ileoanal J-pouch reconstruction by means of an operation video which is available on-line.

Intra-arterial chemotherapy for group C retinoblastoma with adjacent high-flow infantile hemangioma.

Intra-arterial chemotherapy for retinoblastoma is an emerging technique that is being adopted at various centers worldwide. The authors report the first case of an infantile hemangioma that shunted flow during intra-arterial chemotherapy in a 4-month-old girl who presented with macular group C retinoblastoma. Excellent tumor response was noted despite only a fraction of the dose entering the central retinal artery. Further studies to examine intra-arterial chemotherapy's pharmacokinetics and dose-response relations are warranted in order to minimize the necessary exposure to chemotherapy.

Multifocal capillary hemangioma-like vascular proliferation of the kidney associated with clear cell renal cell carcinoma: a case report and review of the literature.

We report the case of a 69-year-old man who underwent a radical left nephrectomy for a renal mass. Microscopically, the features were those of a clear cell-type renal cell carcinoma associated with 2 foci of capillary hemangioma-like vascular proliferation in the adjacent renal parenchyma. The main differential diagnosis and the possible pathogenesis of this vascular lesion are discussed.

Prognostic value of the number and volume of liver tumours on portal vein embolization outcomes.

BACKGROUND/AIMS: Portal vein embolization (PVE) extends the resecability of liver tumours.The issue of PVE is an insufficient growth of the liver parenchyma or a tumour progression in some patients. We evaluated the effect of the volume and the number of liver tumours on the effect of PVE. METHODOLOGY: PVE was performed in 40 patients with liver tumours due to an insufficient future remnant liver volume. The number and the volume of the tumours were evaluated and compared with the final PVE effect. RESULTS: In patients without any increase of the liver volume after PVE (n=3) the number and the volume of the tumours before PVE were 2.7±2.1 and 2205.1±2432.7mm3, respectively. In patients with sufficient growth of the liver (n=22) it was 3.8±2.2 (NS) and 1164.9±1392.1mm3 (NS), respectively. In patients with tumour progression (n=11) it was 5.6±2.2 and 6971.4±5189.5mm3, respectively (p<0.04 and p<0.005, respectively). Four patients were treated by radiofrequency ablation only due to worsening of their health state. Patients with >4 foci (OR 4.7) and a tumour volume >400mm3 (OR=13.0) had a higher probability of cancer progression or insufficient growth of the liver tissue. Patients with <6 foci and a tumour volume <3100mm3 had an 87.5% probability of a successful liver hypertrophy after PVE. CONCLUSIONS: The tumour number and volume were crucial for progression of a malignant disease and growth of the liver parenchyma after PVE.

Pelvic angiomyolipoma.

Angiomyolipoma is a rare benign tumor most commonly found in the kidney and, infrequently, extrarenally. We report a case of pelvic angiomyolipoma in a male patient without stigmata of tuberous sclerosis. The patient presented with right retroperitoneal bleeding and was found to have bilateral renal angiomyolipomas as well as a pelvic mass with similar appearance as the other lesions. He underwent urgent embolization of the large right angiomyolipoma and subsequent robot-assisted left laparoscopic partial nephrectomy with simultaneous resection of the pelvic mass, which was well-tolerated. Pathology confirmed what is, to our knowledge, the only reported case of pelvic angiomyolipoma.

Angiogenesis in synchronous and metachronous colorectal liver metastases: the liver as a permissive soil.

OBJECTIVE: Resection of a primary colorectal carcinoma (CRC) can be accompanied by rapid outgrowth of liver metastases, suggesting a role for angiogenesis. The aim of this study is to investigate whether the presence of a primary CRC is associated with changes in angiogenic status and proliferation/apoptotic rate in synchronous liver metastases and/or adjacent liver parenchyma. METHODS: Gene expression and localization of CD31, HIF-1α, members of the vascular endothelial growth factor (VEGF) and Angiopoietin (Ang) system were studied using qRT-PCR and immunohistochemistry in colorectal liver metastases and nontumorous-adjacent liver parenchyma. Proliferation and apoptotic rate were quantified. Three groups of patients were included: (1) simultaneous resection of synchronous liver metastases and primary tumor (SS-group), (2) resection of synchronous liver metastases 3 to 12 months after resection of the primary tumor [late synchronous (LS-group)], and (3) resection of metachronous metastases >14 months after resection of the primary tumor (M-group). RESULTS: In all 3 groups a higher expression of the angiogenic factors was encountered in adjacent liver parenchyma as compared to the metastases. VEGFR-2 gene expression was abundant in adjacent liver parenchyma in all 3 groups. VEGF-A and VEGFR-1 were prominent in adjacent parenchyma in the SS-group. The SS-group showed the highest Ang-2/Ang-1 ratio both in the metastases and the adjacent liver. This was accompanied by a high turnover of tumor cells. CONCLUSION: In the presence of the primary tumor, the liver parenchyma adjacent to the synchronous liver metastases provides an angiogenic prosperous environment for metastatic tumor growth.

[A case of coexisting malignant mesothelioma and squamous cell carcinoma of the lung].

We experienced a case of malignant mesothelioma with squamous cell carcinoma of the lung concurrently. A 40-year-old man presented with dyspnea. A massive pleural effusion was found by X-ray in the right side of his chest. Transcutaneous pleural biopsy yielded a diagnosis of malignant mesothelioma(IMIG cT4N0M0, Stage IV ). At the same time, his chest CT revealed tumor in the right hilar lesion. Transbronchial lung biopsy yielded a diagnosis of squamous cell carcinoma of the lung (cT3N0M0, Stage III B). Our diagnosis was double cancer, malignant mesothelioma and lung cancer. Chemotherapy with carboplatin, gemcitabine and radiation therapy was performed, but the patient died from deterioration of his systemic condition. We encountered a rare case of double cancer. More attention must be paid in making a diagnosis of malignant mesothelioma and lung cancer.

Emerging therapeutics for primary peritoneal cancer.

INTRODUCTION: Primary peritoneal cancer describes a malignancy that originates from the peritoneal lining of the abdomen. The diagnosis is clearest when the ovaries are uninvolved; however, this is rarely the case and, as such, the declaration is often made pathologically by extrinsic or secondary involvement of the ovaries. The disease shares nearly all of the clinicopathologic features of primary ovarian cancer, most importantly, a molecular homology, which has made it unfruitful for considering it a different entity. Because of this, both standard of care treatment algorithms and contemporary drug development protocols nearly uniformly consider these cancers as primary ovarian cancers. AREAS COVERED: A Medline search was performed as well as a review of trials presented in the National Cancer Institute clinical trials website (http://www.Clinicaltrials.gov). We also reviewed abstracts presented at recent oncology congresses, such as the 2010 Annual meetings of the Society of Gynecologic Oncologists and the American Society of Clinical Oncology. The purpose of this review is to highlight areas of current drug development for patients with primary peritoneal carcinoma. While there are numerous investigational agents being evaluated which follow patients with this disease, our review focuses on the most promising agents that are in mature clinical development. In addition, given the recent positive Phase III data of bevacizumab in the first-line setting for patients with this disease, we consider changes that we can anticipate in this field. EXPERT OPINION: Numerous novel agents are being explored in this disease with the majority focusing on direct and indirect perturbations of tumor angiogenesis. Based on ongoing and recently completed investigations, targeted therapies are likely to become part of the armamentarium of first-line and recurrent treatment for patients with peritoneal cancers. Future studies of pathway-specific targeting will probably include pretreatment biomarker selection or eligibility criteria as well as combinatorial strategies.

Value of preoperative superselective embolization of the isthmus in a patient with upper urinary tract urothelial carcinoma and horseshoe kidney.

Standard treatment for upper urinary tract urothelial carcinoma (UUTUC) implies the radical removal of all urothelium-lined tissue, which requires nephroureterectomy with bladder cuff removal. We report on a patient with a rare coincidence of UUTUC and horseshoe kidney in whom a preoperative angiography helped to identify and subsequently embolize an abberant isthmic feeding artery, which was located in between both collecting systems. Ischemic discoloration of the isthmus area facilitated resection and no major blood loss occurred. Preoperative superselective embolization of the isthmus as the renal split area can be an effective tool to facilitate nephroureterectomy in the case of a horseshoe kidney.

Multiple vascular eccrine spiradenomas: a case report and published work review of multiple eccrine spiradenomas.

Eccrine spiradenoma (ES) usually occurs as a solitary small nodule. It presents rarely as multifocal or multiple localized tumors arranged in a linear, zosteriform or nevoid distribution. We present a rare case of a 55-year-old woman who had a 48-year history of multiple vascular eccrine spiradenomas (VES) localized on the left side of the submandibular region and neck. All five tumors were skin-colored or pinkish-purple, and ranged in size 1.5-2.5 cm. Histologically, each tumor was composed of two characteristic cell types and many dilated vascular spaces were noted in the stroma. Contrast-enhanced computed tomography showed irregularly shaped, enhanced areas at the center of the tumors. A published work search revealed 35 cases of multiple ES, but multiple VES was extremely rare. We summarized the features of previously reported multiple ES and discuss the clinical and histological classification of ES.

Contrast-enhanced ultrasound for imaging of adrenal masses.

PURPOSE: The number of incidentally discovered adrenal masses is growing due to the increased use of modern high-resolution imaging techniques. However, the characterization and differentiation of benign and malignant adrenal lesions is challenging. This study aimed to evaluate contrast-enhanced ultrasound for the characterization of adrenal masses. MATERIALS AND METHODS: We studied 58 patients with adrenal masses detected with computed tomography, magnetic resonance imaging, or ultrasound. 7 patients had bilateral adrenal lesions. Contrast-enhanced ultrasound was performed using high-resolution ultrasound (3.5 - 7 MHz) and intravenous injection of 2.4 ml SonoVue. The contrast enhancement pattern of all adrenal lesions was documented. RESULTS: The 18 malignant adrenal tumors were significantly larger at the time of diagnosis compared to the 40 benign lesions (p < 0.03). The majority of benign adrenal lesions (37 / 40) had a nonspecific type of contrast enhancement (24 / 40) or a peripheral to central contrast filling (13 / 40) described as the iris phenomenon. Similar findings were observed in malignant adrenal tumors: most malignant lesions also showed nonspecific (6 / 18) or peripheral to central contrast filling (9 / 18). Peripheral to central contrast filling had 50 % sensitivity (26 - 74 %) and 68 % specificity (51 - 81 %) for indicating malignancy. CONCLUSION: Contrast-enhanced ultrasound facilitates the visualization of vascularization even in small adrenal masses, but it does not help to distinguish malignant and benign lesions.

Survival after an antiangiogenetic therapy and surgery in a wide spread growing teratoma originating from a testicular mixed malignant germ cell tumor.

Growing teratoma is still an often unsolved problem especially in male with mixed malignant GCTs of the testis or the mediastinum. This specific situation with progressive tumor growth and simultaneous normalization of tumor markers during or after treatment of malignant GCTs with teratomatous elements is judged as a fatal situation if this situation can not be controlled by extensive surgery, as teratoma are not sensible to chemotherapy or irradiation. Here, we report the case history of a 17-year old male patient with a testicular malignant GCT and wide spread lymph node metastases, who developed a rapidly progressive growing teratoma within the lymph node metastases. Within the molecular profile of the tumor we could find a cytogenetic picture typically found in malignant adult GCTs. In view of the bulky abdominal, thoracic and cervical metastases and the uncontrolled tumor progression, the situation was considered incurable. However, following an individual treatment attempt, this patient was treated with a four-agent combination of drugs with antiangiogenetic potential as well as low-dose cyclic chemotherapy. This approach resulted in a sustained disease stabilization followed by extensive surgical resection of the metastases. We therefore would like to highlight this treatment approach in unresectable growing teratoma and would like to stimulate further research and collaboration to come to an optimized treatment suggestion for this group of poor prognostic patients.

Use of the tyrosine kinase inhibitor sunitinib in a patient with von Hippel-Lindau disease: targeting angiogenic factors in pheochromocytoma and other von Hippel-Lindau disease-related tumors.

CONTEXT: von Hippel-Lindau disease is characterized by highly vascularized tumors of multiple organs. EVIDENCE ACQUISITION: We present a patient with von Hippel-Lindau disease with multiple renal and pancreatic tumors and a malignant pheochromocytoma infiltrative of the sacrum and associated with lymph nodule metastases. The pheochromocytoma expressed high protein level of vascular endothelial growth factor and platelet-derived growth factor-beta receptor. The patient presented with a poor performance status, severe pelvic pain, weight loss, and manifestations of catecholamine excess. EVIDENCE SYNTHESIS: Treatment against malignant pheochromocytoma with surgery, chemotherapy, or participation in clinical trials was not feasible because of the patient's poor performance status, the presence of multiple tumors, and the extension of the pheochromocytoma into the bones. Patient was treated with sunitinib, a potent tyrosine kinase inhibitor of vascular endothelial growth factor, platelet-derived growth factor, RET, c-KIT, and FLT-3 receptors. Six months of treatment with sunitinib was associated with normalization of the patient's performance status and blood pressure, absence of symptoms of catecholamine excess, weight gain, disappearance of pain, shrinkage of each of the tumors (50% in the largest renal tumor, 38% in the largest islet cell tumor, 21% in the pelvic malignant pheochromocytoma), and reduction of plasma normetanephrines and chromogranin A. CONCLUSION: This study provides evidence that targeting tyrosine kinase receptors such as the vascular endothelial growth factor pathway and the platelet-derived growth factor-beta receptor may have value in the treatment of VHL-related tumors including pheochromocytoma.