Major Arterial Involvement Research Articles

Phase II trial of fixed-dose rate gemcitabine, bevacizumab, and concurrent 30 gy radiotherapy as preoperative treatment for potentially resectable pancreatic adenocarcinoma.

258 Background: Effective multimodality treatment for localized pancreatic cancer is elusive. We hypothesized that preoperative fixed-dose rate (FDR) gemcitabine (GEM) combined with short-course radiotherapy (RT) and the angiogenesis inhibitor bevacizumab (BEV) would improve margin negative surgical outcomes and complete pathological response rates. Methods: Multisite phase II trial evaluating all potentially-resectable pancreatic adenocarcinoma without major arterial involvement or portal venous occlusion. Dual primary endpoints included complete pathological response and margin negative resection rates of 10% and 80%. Subjects received FDR GEM on days 1, 15, and 29 combined with BEV (10 mg/kg IV), followed on day 43 by BEV and concurrent 30 Gy RT (3 Gy/fraction) over 10 days. After restaging, subjects underwent laparoscopy and possible resection after day 85. Stopping criteria required continuous monitoring of serious wound complications. Results: 58 subjects enrolled, of which 29 (50%) had suspected venous involvement. 57 completed treatment without dose-limiting toxicity or delays in surgery. Two grade 4 (3.4%) and 17 grade 3 toxicities (28.8%) occurred. Four patients progressed before surgery. 54 subjects underwent laparoscopy; ten had unexpected carcinomatosis, and one was unresectable. 43 subjects were resected (74%; 33 pancreatico-duodenectomy, 8 distal pancreatectomy, 1 total pancreatectomy, 1 Appleby); 19 (44%) required portal vein resection. Margin negative outcome was achieved in 38 (88%, 95% CI: 75%-96%) with one complete pathological response (2.3%; 95% CI: 0.1%- 12%) and seven (6 grade 3; 1 grade 4) wound complications (13%). Median overall survival (OS) was 16.3 months (95% CI: 13.9 -22.1) and 21.3 months (95% CI: 15.0-32.9) after resection. Median progression-free survival (PFS) was 5.7 months (95% CI: 3.9-9.1) and 9.9 months (95% CI: 5.7 to 14.1) after resection, with 7 local and 21 distant recurrences. Conclusions: Combination therapy was well-tolerated and was within statistical design parameters for the primary endpoints despite a significant proportion of borderline tumors.

Laparoscopic common hepatic artery ligation and staging followed by distal pancreatectomy with en bloc resection of celiac artery for advanced pancreatic cancer

Adeno-carcinomas of pancreatic body are usually asymptomatic and progress to advanced stage with involvement of major arteries. Resection of advanced cancer along with en bloc resection of a common hepatic artery and celiac trunk enables a "curative" resections and only possible treatment. However, the celiac axis resection always has a risk of compromising blood supply to liver, resulting in the hepatic insufficiency. We evaluated practicability of a two-stage procedure for the advanced pancreases body cancer, laparoscopic clamping of a common hepatic artery followed by open distal pancreatectomy with en bloc celiac arterial resection to prevent the hepatic insufficiency. Seventy-five-year-old woman diagnosed with a 50-mm pancreatic body mass, invading splenic artery, common hepatic artery, splenic vein, and portal vein at the confluence. STAGE-1: At laparoscopy, after confirming absence of the peritoneal, superficial liver metastases and negative peritoneal cytology; we approached the common hepatic artery through the lesser sac and ligated. STAGE-2: Her liver function tests were normal after 2 weeks, and CT angiography showed complete blockage of the common hepatic artery with sufficient collateral circulation to the liver through inferior pancreatico-duodenal artery and gastro-duodenal artery. We performed an open distal pancreatectomy with en bloc resection of celiac artery. Histopathology examination confirmed R0 resection. The celiac axis resection with distal pancreatectomy improves the chance of R0 resection and potentially, survival of the patient. Preoperative laparoscopic ligation of the common hepatic artery is a safe, effective, and in-expensive technique to prevent postoperative hepatic insufficiency and improves the safety of en bloc celiac artery resection with a distal pancreatectomy. Also these patients have high risk of peritoneal dissemination. Diagnostic laparoscopy is useful to detect occult metastasis, which are missed by per-operative CT scan.

Current Advancements in the Management of Giant Cell Arteritis

Giant cell arteritis (GCA) is a vasculitis of large and medium-sized vessels that predominantly affects the elderly. GCA should be recognized as a medical emergency owing to its associated critical ischemia, which frequently causes neuro-ophthalmic complications. The pathogenesis of GCA is unclear, but it is speculated that the disease process is triggered by an infectious agent or an autoantigen (through molecular mimicry) being sensed by Toll-like receptors on immature dendritic cells in the tunica adventitia of arteries. Dendritic cells then present antigen to CD4+ T cells leading to T-cell proliferation and cytokine release, activation of macrophages and formation of granulomata-containing giant cells, with injury to the arterial wall by matrix metalloproteinases, reactive oxygen and nitrogen intermediates. Reparative processes then cause revascularization and intimal hyperplasia. This results in vascular occlusion and consequent tissue ischemia. Features predictive of visual loss in GCA include jaw claudication, diplopia and temporal artery abnormalities on physical examination. Modern imaging with duplex ultrasonography and fluorodeoxyglucose positron emission tomography shows promise for early diagnosis and detection of major artery involvement in GCA. However, temporal artery biopsy remains the gold-standard investigation. Early recognition and urgent institution of high-dose corticosteroids is the mainstay of treatment. Studies have found mixed experiences of using conventional disease-modifying drugs and biological therapies. Furthermore, evaluation of their steroid-sparing potential is required with well-constructed, randomized, controlled trials.

Treatment and outcomes of large vessel arteritis

Giant cell arteritis (GCA) and Takayasu's arteritis (TA) are characterised by systemic inflammation and critical ischaemia. GCA is a medical emergency. Neuro-ophthalmic complications occur early, with permanent vision loss in up to a fifth of patients, resulting mainly from failure of prompt recognition and treatment. Diagnosis of large vessel vasculitis is often delayed due to poor recognition of early, often non-specific symptoms. Laboratory inflammatory markers are often discordant with disease activity. Modern imaging techniques show promise in diagnosis and disease monitoring, improving our understanding of major artery involvement in large vessel vasculitis. However, in practice, their role is still unclear. The mainstay of therapy remains corticosteroids. Experience using conventional disease-modifying drugs is mixed, and biological therapies require further evaluation for their steroid-sparing potential.

Neuro-ophthalmic complications in giant cell arteritis

Giant cell arteritis (GCA) is a medical emergency characterized by systemic inflammation and critical ischemia. Neuro-ophthalmic complications occur early, with permanent vision loss in up to one fifth of patients. This mainly results from failure of prompt recognition and treatment. Diagnosis of GCA is often preceded by unrecognized symptoms, including constitutional upset and jaw claudication. Features predictive of permanent visual loss include jaw claudication and temporal artery abnormalities on physical examination. These patients often do not mount high inflammatory responses. Modern imaging techniques show diagnostic promise, and have led to an increased recognition of major artery involvement in GCA. However, temporal artery biopsy remains the gold standard for investigation. Intimal hyperplasia on histologic examination is associated with neuro-ophthalmic complications. The mainstay of therapy remains corticosteroids. Experience using conventional disease-modifying drugs has been mixed, and biologic therapies require further evaluation for their steroid-sparing potential.

Survival After Pancreatectomy With Major Arterial Resection and Reconstruction

Absence of major arterial tumor involvement has generally been regarded as a major criterion for resectability of pancreatic tumors. We hypothesize that resection of a tumor-involved hepatic artery (HA) or celiac artery (CA) with reconstruction may offer a survival benefit to patients whose tumors were traditionally regarded as unresectable. All patients with pancreatic adenocarcinoma treated between 1996 and 2007 were reviewed. Patients were included if they underwent resection of the HA or CA during pancreatectomy. Survival was analyzed by Kaplan-Meier survivor functions, Cox proportional hazard models, and the log rank test. Twelve patients (six men and six women) with adenocarcinoma underwent pancreatectomy with resection of a tumor-involved HA (n = 2) and/or CA (n = 10). Median age at diagnosis was 62 years (range, 53-73 years). All patients completed neoadjuvant chemoradiotherapy with or without full dose chemotherapy before resection. Procedures performed were six extended pancreaticoduodenectomies, two proximal subtotal pancreatectomies, two distal pancreatectomies, and two total pancreatectomies. Ten cases involved celiac resections, and two had isolated HA resections. The 60-day mortality was 17% (2 of 12). Median survival after diagnosis was 20 months (range, 6-41 months). Median survival after resection was 17 months (range, 1-36 months). Survival was not statistically significantly related to age, sex, margin status, or preoperative CA19-9 level. The 3-year survival was 17%. There were no 5-year survivors. Resection of the HA or CA with reconstruction may prolong survival for selected patients who undergo pancreatic resection after neoadjuvant therapy. However, this aggressive approach did not result in any long-term survivors in our series.

Role of Endoscopic Ultrasound in the Diagnosis of Intraductal Papillary Mucinous Neoplasms: Correlation With Surgical Histopathology

Intraductal papillary mucinous neoplasms (IPMNs) are precancerous tumors characterized by dilation of the main pancreatic duct, its side branches, or both. The purpose of this study was to evaluate the role of endoscopic ultrasound (EUS) in differentiating benign and malignant IPMNs. We identified all patients between July 1996-November 2005 who underwent preoperative EUS for IPMNs. Malignancy was defined as the presence of invasive carcinoma; all other neoplasms were considered benign. The results of EUS and EUS-guided fine-needle aspiration (EUS-FNA) were compared with corresponding histopathology. Seventy-four patients (38 male; mean age, 65 years) with 21 (28%) malignant and 53 (72%) benign IPMNs were identified. Sixty-five (88%) underwent EUS-FNA. Compared with benign tumors, patients with malignant IPMNs were more likely to be older (P = .011), present with jaundice (P = .03) or weight loss (P = .03), and have EUS features of a dilated main pancreatic duct (P = .0001), solid lesion (P = .0001), pancreatic ductal filling defects (P = .03), or thickened septa within any cyst (P = .02). The sensitivity, specificity, and accuracy of EUS-FNA for the diagnosis of malignancy were 75% (95% confidence interval [CI], 53%-89%), 91% (95% CI, 79%-97%), and 86% (95% CI, 76%-93%), respectively. Cyst or pancreatic duct fluid carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 did not differ between groups. Older age, jaundice and weight loss, and EUS features of a solid lesion, dilated main pancreatic duct, ductal filling defects, and thickened septa are predictive of malignancy in patients with IPMNs. EUS-FNA cytology is helpful, but cyst fluid CEA and CA 19-9 are of limited value to differentiate malignant from benign IPMNs.

Major Arterial Involvement and Review of Behcet's Disease

Behcet's disease was first defined by Hulusi Behcetin 1937 as a multisystemic disorder with characteristic pathologic findings including recurrent orogenitalulcers, vascular disorders, and ocular and cutaneous lesions. The disease is mostly encountered at the third and fourth decades of life and especially prevalent in Mediterranean and Far East Asia.Behcet's disease may have both venous and arterial manifestations. The arterial form is rare but it is bore with its manner and to consider recurrent surgical treatments. In this retrospective study, we reviewed the literature related to Behcet's disease and discussed in respect to vascular involvement and the prognosis of surgical treatment.Thirty-one consecutive patients with vasculo-Behcet's disease visiting the departments of cardiovascular surgery, dermatology, and internal medicine in Medical Faculty of Istanbul have been reviewed retrospectively. All available clinical,pathologic, and postoperative data were reviewed and analyzed. Venous system pathologies were present in 15 patients. The pathologies in the remaining patients were related to the arterial tree. Ten patients with aneurysms and/or pseudoaneurysms and six patients with occlusive lesions have undergone surgical treatment. Pseudoaneurysms occurred in six patients at least twice or more. Vascular manifestations are the main predictors of mortality and morbidity in Behcet's disease. Arterial complications may lead to difficult surgical problems.Any invasive methods to arterial system may cause pseudoaneurysms. Repairs by using autogenous veins or synthetic grafts may lead to anastomotic false aneurysms. Surgical treatment should not to be applied in the acute phase of the disease and systemic therapy including colchicine, aspirin,and corticosteroids should be considered for all patients.

Giant cell arteritis and polymyalgia rheumatica: usefulness of vascular magnetic resonance imaging studies in the diagnosis of aortitis

One of the unresolved challenges posed in giant cell (temporal) arteritis (GCA) is the detection and monitoring of large-artery complications, particularly aortitis. Recent investigations support vascular magnetic resonance imaging (MRI) studies in this issue. We report our preliminary experience with this imaging technique in the study of the aorta and its proximal branches in patients with GCA and/or polymyalgia rheumatica (PMR). Between 2000 and 2003, six patients with GCA and/or PMR seen in our department were diagnosed with aortitis using vascular MRI studies. In all cases, the study was performed according to a specifically designed protocol that included MRI and MR angiography (MRA). MRI was a hepful non-invasive method for diagnosis of aortitis in all cases, providing accurate information about its extent. In particular, MRI had a higher ability to detect earlier stages of vasculitis disclosing subclinical aortitis in five of the six patients. The main signs of early vascular inflammation observed were vessel wall thickness and oedema (six cases) and increased mural enhancement on postcontrast T1-weighted images (four cases). MRA disclosed lumen changes (stenosis) in two patients. On follow-up studies, whereas vascular stenosis and vessel wall thickness remained invariable, vascular wall oedema and contrast enhancement improved significantly when disease activity decreased. MRI may be a useful technique for diagnosing patients with occult major artery involvement in GCA, whether presenting with classic symptoms of temporal arteritis or PMR. Its utility for monitoring the course of the disease and response to treatment requires further confirmation.

Major resection for chronic pancreatitis in patients with vascular involvement is associated with increased postoperative mortality.

The aim was to evaluate the outcome of major resection for chronic pancreatitis in patients with and without vascular involvement. Of 250 patients with severe chronic pancreatitis referred between 1996 and 2003, 112 underwent pancreatic resection. The outcome of 17 patients (15.2 per cent) who had major vascular involvement was compared with that of patients without vascular involvement. The 95 patients without vascular involvement had resections comprising Beger's operation (39 patients), Kausch-Whipple pancreatoduodenectomy (28), total pancreatectomy (25) and left pancreatectomy (three). Twenty-five major vessels were involved in the remaining 17 patients. One or more major veins were occluded and/or compressed producing generalized or segmental portal hypertension, and three patients also had major arterial involvement. Surgery in these patients comprised Beger's operation (eight), total pancreatectomy (five), Kausch-Whipple pancreatoduodenectomy (two) and left pancreatectomy (two). Perioperative mortality rates were significantly different between the groups (two of 95 versus three of 17 respectively; P = 0.024). There were similar and significant improvements in long-term outcomes in both groups. Resection for severe chronic pancreatitis in patients with vascular complications is hazardous and is associated with an increased mortality rate. Vascular assessment should be included in the routine follow-up of patients with chronic pancreatitis, to enable early identification of those likely to develop vascular involvement and prompt surgical intervention.

Surgical Management of Posterior Fossa Meningioma

A series of 54 posterior fossa meningiomas treated from January 1971 to December 1996 is reported. The patients were 42 women and 12 men ranging in age from 35 to 83 years (mean 55.6 years). Grouped by the site of tumor attachment, these tumors were divided into six categories: tentorial, petroclival, cerebellopontine angle, falcotentorial, cerebellar convexity, and foramen magnum meningiomas. Surgical approaches were selected on the basis of the tumor attachment and extension, the involvement of major cerebral arteries and the venous system, and the involvement of the cranium and brain stem on preoperative neuroimaging. Of 54 patients, 50 underwent operation. Total removal (Simpson I, 8 cases; Simpson II, 27 cases) was achieved in 35 patients (70%), subtotal removal (Simpson III) in 5 patients (10%), and partial removal (Simpson IV) in 10 patients. Eight patients had immediate surgical complications, and the morbidity rate was 16%. One patient died; thus, the mortality rate was 2%. All patients were followed over a mean of 8.1 years (range 3 months to 22 years) after surgery. Recurrence occurred in three patients, two with tentorial meningioma and one with petroclival meningioma. With advances in neuroradiology and micro-surgical techniques, the surgical outcome of meningiomas has markedly improved. The present surgical approach, including skull base operative techniques and intraoperative monitoring and navigation, has resulted in successful removal of posterior fossa meningiomas more safely with acceptable mortality and morbidity rates.

Cerebrovascular complications of bacterial meningitis in adults.

We performed a prospective study of the type, frequency, temporal profile, and prognostic role of cerebrovascular complications in 86 adults with bacterial meningitis. Cerebral angiography was performed in 27 patients (31.4%) who had focal deficits either clinically, on cranial CT, or both, and in patients who had persistent coma without explained cause despite 3 days of antibiotic therapy. Alterations of the vessel systems, including involvement of major arteries at the base of the brain, medium-sized arteries, small vessels, and major sinuses and cortical veins, were present in 13 of the 27 patients who had angiography. Typical cerebrovascular complications were arterial narrowing of the supraclinoid portion of the internal carotid artery; vessel wall irregularities, focal dilatations, and occlusions of distal branches of the middle cerebral artery; focal abnormal parenchymal blush; and thrombosis of the sagittal superior sinus and cortical veins. Prognosis for those patients with cerebrovascular complications was unfavorable. Six patients died, one remained in a vegetative state, four were moderately or slightly disabled, and only two recovered completely. The study showed that angiographically documented cerebrovascular complications are the most frequent intracranial complications in bacterial meningitis of the adult (37.1%) and are major determinants in the prognosis of this disease.

Amputation risk factors in concomitant superficial femoral artery and vein injuries.

Only a small subset of patients with combined superficial femoral artery and vein injuries results in amputation. The importance of the venous component as a risk factor for amputation is uncertain. Ligation vs. reconstruction of venous injuries is controversial. For clarification of these issues, we analyzed retrospectively multiple risk factors for amputation in combined superficial femoral artery and vein injuries in a civilian population. There were 25 patients treated in a 20-year period. Sixteen injuries were caused by small caliber missiles, six by shotgun blasts, and three by knife wounds. Three patients (12%) ultimately underwent amputation. The major risk factor for amputation was method of vascular reconstruction. All three amputations underwent ligation of the superficial femoral vein with arterial reconstruction by placement of a reversed interposition saphenous vein graft (p = 0.0009). None of the remaining 22 patients with salvaged limbs underwent reconstruction by this combination of techniques. Consequently, the authors emphasize the importance of venous reconstruction, particularly in combined injuries with major arterial involvement requiring interposed grafts.

An evaluation of angiocardiography in pulmonary carcinoma with particular emphasis on prognosis.

The cure of cancer of the lung is primarily a surgical problem, virtually all long-term survivals having had surgically resectable disease. Unfortunately, resection can be undertaken in only about half of those patients (3) who come to thoracotomy; the remainder are incurable because of metastatic or unresectable lesions. During the last decade, a variety of diagnostic tests, including angiography, have been employed to help in the selection of those patients with lung cancer who present no other contraindications for surgery but are incurable by present surgical maneuvers. The use of angiocardiography in the study of pulmonary and mediastinal cancer has been attempted from both the point of view of diagnosis (7, 9) and of prognosis (4). The latter point has been investigated with particular respect to the prediction of resectability (1, 4, 10, 11, 14) of a lesion. It is the purpose of the present report to evaluate the efficacy of angiocardiography in the study of pulmonary cancer. Method The method used is venous angiocardiography, with the introduction of contrast medium into an arm or upper thoracic vein by way of a catheter inserted by a venous cut-down. The injection is made on the same side as the lesion and serves to evaluate the adjacent venous structures. It is performed either manually or with a mechanical injector. Rapid serial exposures record the passage of the medium through the pulmonary circulation, the left heart, and aorta. We have largely used the Elema biplane serialograph. Angiocardiographic Changes The vascular pattern of the lung and mediastinum is frequently altered by malignant intrathoracic disease. In 84 per cent of 250 consecutive proved cases of pulmonary and mediastinal cancer, Steinberg and Finby (12) found variations from normal. With lesions in close proximity to the hilar regions of the lung, this figure approaches 100 per cent, and in this location the problem of resectability is greatest. Angiocardiographic changes suggestive of cancer are mimicked by a sufficient number of nonmalignant conditions that the definitive diagnosis must be established by histologic study. Patterns of alteration will also differ with right and left hilar lesions. Angiocardiographic Criteria of Unresectability: The criteria of inoperability were first defined by Dotter, Steinberg, and Holman (4). We have found them to be of value in the following order: 1. Involvement of the great venous structures of the mediastinum (Fig. 1), the superior vena cava or the innominate veins. 2. Mediastinal mass lesions. Metastatic lymph-node involvement in the right paratracheal region (Fig. 2) means extensive mediastinal disease. 3. Major pulmonary artery involvement close to the hilus (Fig. 2). For the left pulmonary artery, the margin is 1.5 cm., and on the right is at the point of bifurcation of the right pulmonary artery. 4. Involvement of left atrium or of the major pulmonary veins (Fig. 3).

Use of Testosterone Propionate and Estrogenic Substance in Treatment of Essential Hypertension, Angina Pectoris and Peripheral Vascular Disease

The effect of the sex hormones in cardiovascular disease has been the subject of relatively few clinical investigations. In recent medical literature, however, several reports have been published indicating that these substances may find a useful place in the management of certain vascular disorders. In 1939, Edwards, Hamilton and Duntley (1) observed objective and subjective improvement in 7 male patients with organic peripheral vascular disease following treatment with testosterone propionate. All patients presented evidence of major arterial involvement with loss of the popliteal, femoral, and in one case, the iliac pulsations. In 1940, I presented data (2), indicating that the sex hormones gave promise of being effective in the treatment of vascular insufficiency of the coronary, cerebral, and peripheral circulatory systems. Such salutary results were manifested among patients with angina pectoris in an increase of emotional and exercise tolerance, a decrease in the severity of pain, and a general inc...