Phase I Dose-Escalation Study of Tirapazamine Chemoembolization for Unresectable Early- and Intermediate-Stage Hepatocellular Carcinoma.

PURPOSE: To investigate the safety of replacing doxorubicin with tirapazamine in conventional transarterial chemoembolization (TACE) in an Asian population with hepatocellular carcinoma (HCC), and to determine the optimal tirapazamine dose for phase II studies. MATERIALS AND METHODS: This was a phase I, 3 + 3 dose-escalation study for patients with unresectable early- and intermediate-stage HCC who received 5, 10, or 20 mg/m2 of intra-arterial (IA) tirapazamine followed by ethiodized oil/gelatin sponge-based embolization. Key eligibilities included HCCs no more than 10 cm in diameter, prior embolization allowed, Eastern Cooperative Oncology Group performance status of 0 or 1, Child-Pugh score of 5-7, and platelet count of ≥60,000 µL. Dose-limiting toxicity (DLT) was defined as any grade 3 nonhematological or grade 4 hematological toxicity, with the exception of transient elevation of aminotransferase levels after the procedure. RESULTS: Seventeen patients were enrolled, 59% of whom had progression from a prior HCC therapy and 35% of whom had progression or recurrence after TACE. All patients tolerated the tirapazamine TACE well without any DLT or serious adverse event. Using the modified Response Evaluation Criteria in Solid Tumors, the complete response (CR) rate was 47%, and the CR + partial response rate was 65%. The median duration of response was not reached. The median time to progression was 12.6 months (95% confidence interval, 5.1-not reached). The median overall survival was 29.3 months. The selected phase II dose was set at a fixed dose of 35 mg of IA tirapazamine. CONCLUSIONS: IA tirapazamine with transarterial embolization was well tolerated and showed promising efficacy signals in intermediate-stage HCC, justifying pursuit of a phase II study.

A rat toxicological study of intra-arterial injection of Tirapazamine, a hypoxia-activating Cancer therapeutic agent, followed by hepatic artery ligation.

Background Tirapazamine's (TPZ) tolerability after an intra-arterial (IA) injection remains unclear. We investigated TPZ's safety and tolerability in rats by first injecting into the left hepatic artery and then performing a hepatic artery ligation, which recapitulates the transarterial embolization used clinically. Research design and methods: Forty-six rats in five groups were respectively injected with 0, 0.25, 0.50, 1.0, or more than 1.5 mL IA of TPZ (0.7 mg/mL) into the left hepatic artery and then subjected to hepatic artery ligation under laparotomy. Blood samples were collected four times daily up to day 15 after which the rats were euthanized and necropsied. The toxicity profile of IA injection of TPZ followed by hepatic artery ligation was then assessed. Results No significant changes to the rats' body weight and serum total bilirubin were observed. Serum alanine aminotransferase (ALT) levels increased slightly but remained below 100 U/L one day after treatment for most rats. Three rats in Groups 3 and 4 exhibited an over two-fold transient elevation of ALT. All ALT recovered to the baseline at day 14. Liver tissues were collected on day 15 using H&E staining. One rat in Group 3 showed ischemic coagulative necrosis in its liver tissue. Other sporadic pathological changes not related to TPZ doses were observed in Groups 2, 3, 4, and 5. Conclusion TPZ by IA injection followed by embolization is tolerated up to 7 mg/kg. This finding supports the strategy of administering an IA injection of TPZ followed by trans-arterial embolization to the liver.

Computed tomographic-guided percutaneous radiofrequency ablation with hydrodissection of hepatic malignancies in the subcapsular location: Evaluation of safety and technical efficacy.

BACKGROUND: Image-guided percutaneous radiofrequency ablation (RFA) has been the most commonly used modality in the treatment of nonresectable hepatic malignancies. However, tumors in the subcapsular location are still technically challenging. This study was undertaken to evaluate the feasibility, safety, and efficacy of computed tomographic-guided percutaneous RFA with hydrodissection for hepatic malignancies in the subcapsular location. METHODS: A total of 103 patients with 253 hepatic lesions were treated with computed tomographic-guided percutaneous RFA. Computed tomographic-guided percutaneous RFA with hydrodissection was performed in 15 patients with 15 hepatic nodules. All tumors located in the hepatic subcapsular location were considered difficult to treat on planning sonography. Hydrodissection was performed with 5% dextrose in water or saline solution in displacing adjacent structures ≥ 10 mm away from the liver capsule. Two RFA systems with multitined expandable electrodes or straight internally cooled single electrodes were used for treatment of hepatic malignancies. The feasibility, safety, and efficacy of this technique were analyzed on follow-up contrast-enhanced computed tomography or magnetic resonance imaging. RESULTS: Hydrodissection was successfully achieved in 15 (100%) patients, displacing the adjacent structures ≥ 10 mm that were originally < 10 mm away from the liver capsule with administration of a mean of 376 mL of dextrose in water or saline solution. The average distance between an adjacent structure and the liver capsule after hydrodissection was 1.50 ± 0.40 cm and 0.11 ± 0.15 cm prior to hydrodissection, which was statistically significant (p < 0.001). No complication related to hydrodissection occurred during the follow-up period. The primary technical success rate of percutaneous RFA for tumor was 100% (15/15) at 1-month follow-up imaging. There were three minor complications (20%, 3/15) related to the RFA procedure. CONCLUSION: Computed tomographic-guided percutaneous RFA with hydrodissection is a feasible, safe, and effective technique in the treatment of hepatic malignancies in the subcapsular location.

Clinical features and computed tomography characteristics of non-Klebsiella pneumoniae liver abscesses in elderly (>65 years) and nonelderly patients.

PURPOSE: To compare the clinical and computed tomography (CT) appearances of liver abscesses caused by non-Klebsiella pneumoniae bacterial pathogens in elderly and nonelderly patients. MATERIALS AND METHODS: Eighty patients with confirmed non-Klebsiella pneumoniae liver abscesses (non-KPLAs) were enrolled and divided into two age groups: elderly (age ≥65 years, n=42) and nonelderly (age <65 years, n=38). Diagnosis of non-KPLA was established by pus and/or blood culture. We compared clinical presentations, outcomes, and CT characteristics of the two groups, and performed multivariate analysis for significant variables and receiver-operating-characteristic analysis to determine the cutoff value of abscess diameter for predicting non-KPLA. RESULTS: Elderly patients with non-KPLA were associated with a longer hospital stay (p<0.01). Regarding etiology, biliary sources had a strong association in the elderly group (p<0.01), and chronic liver diseases were related to the nonelderly group (p<0.01). Non-KPLAs (52.5%) tended to show a large, multiloculated appearance in the elderly group and were associated with bile duct dilatation (p<0.01), compared with the nonelderly group. The abscess diameter (cutoff value, 5.2 cm; area under the curve, 0.78) between the two groups was predicted. In multivariate analysis, underlying biliary tract disease [odds ratio (OR), 3.58, p<0.05], abscess diameter (OR, 2.40, p<0.05), and multiloculated abscess (OR, 1.19, p<0.01) independently predicted elderly patients with non-KPLA. CONCLUSION: In the elderly patients with non-KPLA, a large, multiloculated abscess with a diameter greater than 5.2 cm was the predominant imaging feature.

Imaging differentiation of phytobezoar and small-bowel faeces: CT characteristics with quantitative analysis in patients with small- bowel obstruction.

OBJECTIVE: The objective is to use multidetector computed tomography (MDCT) to differentiate phytobezoar impaction and small-bowel faeces in patients with small-bowel obstruction (SBO). METHODS: We retrospectively reviewed 91 consecutive SBO patients with surgically proven phytobezoars (n = 31) or adhesion with small-bowel faeces (n = 60). Two readers blinded to the diagnosis recorded the following MDCT features: degree of obstruction, transition point, mesenteric fatty stranding, intraperitoneal fluid, air-fluid level, pneumatosis intestinalis, and portal venous gas. MDCT measurements of the food debris length, attenuation, luminal diameter, and wall thickness of the obstructed bowel were also compared. RESULTS: A higher grade of obstruction with an absence of mesenteric fatty stranding and intraperitoneal fluid was more commonly seen in the phytobezoar group than in the small-bowel faeces group (p < 0.01). The food debris length (phytobezoar, 5.7 ± 2.8 cm; small-bowel feces, 20.3 ± 7.9 cm, p < 0.01) and mean attenuation (phytobezoar, -59.6 ± 43.3 Hounsfield units (HU); small-bowel faeces, 8.5 ± 7.7 HU, p <0.01) were significantly different between the two groups. The ROC curve showed that food debris length <9.5 cm and mean attenuation value < -11.75 HU predicted phytobezoar impaction. CONCLUSIONS: MDCT features with measurements of the food debris length and mean attenuation assist the differentiation of phytobezoar impaction and small-bowel faeces. KEY POINTS: • MDCT examination helps to differentiate phytobezoar and small-bowel faeces. • A higher grade of obstruction is commonly associated with phytobezoar impaction. • Mesenteric fatty stranding and intraperitoneal fluid are frequently associated with small-bowel faeces. • Quantitative measurement of the obstructed bowel adds the diagnostic accuracy.

Intra-arterial calcium stimulation test with hepatic venous sampling for preoperative diagnosis of a large insulinoma in an obese young man.

Herein, we report the case of a large benign insulinoma in an obese young man with a three-year history of asymptomatic hypoglycaemia. He presented to our outpatient department with a two-week history of dizziness and morning cold sweats. A random serum glucose test revealed hypoglycaemia. Upon admission, computed tomography and magnetic resonance imaging of the abdomen with intravenous contrast media showed an enhancing mass lesion in the uncinate process of the pancreas. To confirm the diagnosis, an intra-arterial calcium stimulation test with hepatic venous sampling was performed for preoperative localisation and to exclude the presence of occult insulinomas. The patient underwent an exploratory laparotomy, with successful resection of the pancreatic head tumour. Histology confirmed the diagnosis of insulinoma. The patient's postoperative recovery was uneventful, and he has not developed further episodes of hypoglycaemia three years post surgery.

Histological grade of hepatocellular carcinoma correlates with arterial enhancement on gadoxetic acid-enhanced and diffusion-weighted MR images.

PURPOSE: To retrospectively determine the correlation between heptic tumor signal intensity on gadoxetic acid-enhanced and diffusion-weighted MR images and histopathological grading of hepatocellular carcinoma (HCC). METHODS: We retrospectively reviewed the MR images of 79 patients with 141 surgically resected HCCs. The signal intensity and its relationship with histopathological grade were assessed. We measured the apparent diffusion correlation (ADC) values and calculated arterial enhancement ratios, washout ratios, and relative intensity ratios of HCCs relative to the surrounding liver parenchyma in gadoxetic-enhanced MR images in order to determine their relationship to the histological grade. RESULTS: Morphological evaluation showed that larger tumor size and extrahepatic extension were associated with higher histologic grade (p < 0.01). Multivariate logistic regression showed that low ADC value and low relative intensity ratio in the arterial phase (RIRa) predict high histological grade. ADC value (cut-off 1.7 × 10(-3) mm(2)/s, sensitivity 82.4%, specificity 83.2%) was the best predictor of well-differentiated HCC, and RIRa (cut-off 0.93, sensitivity 81.4%, specificity 93.9%) was superior to ADC for predicting poorly differentiated HCC. CONCLUSION: Relative low arterial enhancement on gadoxetic acid-enhanced MR images and low ADC are predictive of worse histological grades of HCC.

Radiofrequency ablation of hepatic metastases: factors influencing local tumor progression.

BACKGROUND: Although radiofrequency ablation (RFA) of nonresectable hepatic metastases has gained wide acceptance by showing survival benefit in selected patients, scattered reports are available regarding risk factors of local control of percutaneous RFA. The purpose of this study was to prospectively evaluate the factors influencing local tumor progression after percutaneous RFA of hepatic metastases. METHODS: Sixty-nine hepatic metastatic lesions in 54 patients were treated by percutaneous RFA. Efficacy was evaluated by contrast-enhanced computed tomography or magnetic resonance imaging at 1 month after ablation, then at 3-month intervals for the first year and biannually thereafter. RESULTS: The results of the log-rank test showed that tumor size of <3 cm (p = 0.024) and the absence of tumor contiguous with large vessels (p = 0.002) significantly correlated with local control for hepatic metastases. Cox regression analysis showed that the tumor size <3 cm and the absence of tumor contiguous with large vessels were independent factors (p = 0.055 and 0.009, respectively). The results of the log-rank test showed that neither the threshold post-ablation margin of 1.8 cm (p = 0.064) nor the presence of a tumor with subcapsular location (p = 0.134) correlated with the success of local control. CONCLUSIONS: Percutaneous RFA is more effective in achieving local control in patients with hepatic metastases when the tumor size is <3 cm and not contiguous with large vessels.

The association of haemoglobin A1C levels with the clinical and CT characteristics of Klebsiella pneumoniae liver abscesses in patients with diabetes mellitus.

OBJECTIVES: To compare the characteristics of Klebsiella pneumoniae liver abscesses (KPLA) in diabetic patients with different levels of glycaemic control. METHODS: The institutional review board approved this retrospective study. A total of 221 patients with KPLA were included. Clinical features of KPLA were compared. We divided the 120 diabetic patients with KPLA into three subgroups based on haemoglobin A1C (HbA1C) concentration (good, HbA1C ≤ 7.0 %; suboptimal, 7.0 % < HbA1C ≤ 9.0 %; poor, HbA1C > 9.0 %). In this study, we used a semiautomated quantitative method to assess the gas and total abscess volumes in KPLA. Statistical analysis was performed with the chi-squared test and one-way analysis of variance. RESULTS: The mortality rate did not significantly differ between the nondiabetic and diabetic groups. However, patients with poor glycaemic control had significantly more complications and therefore a longer hospital stay (P < 0.05). In our study, CT and quantitative analyses found that patients in the group with poor glycaemic control had a significantly higher incidence of gas formation and hepatic venous thrombophlebitis and a higher gas-to-abscess volume ratio than patients with suboptimal and good glycaemic control (P < 0.05). CONCLUSIONS: Diabetic patients with a high HbA1C concentration (>9.0 %) have an association with hepatic venous thrombophlebitis, gas formation and metastatic infection complications associated with KPLA. KEY POINTS: • Poorly controlled diabetes is associated with complications in Klebsiella pneumoniae liver abscesses. • Hepatic venous thrombosis and gas are important signs of metastatic infection. • Hepatic venous thrombophlebitis is associated with 72.7 % of metastatic infections.

Amyand's hernia with scrotal abscess presenting as acute scrotum.

Amyand's hernia is a rare form of inguinal hernia in which an inflamed appendix is incarcerated in a hernial sac. The clinical presentation of Amyand's hernia varies, depending on the extent of inflammation involved in the hernial sac and the presence or absence of a scrotal abscess. If a scrotal abscess is present, this usually indicates that the appendix in the hernial sac is perforated. However, without the availability of computed tomography (CT) scans, the condition is often preoperatively misdiagnosed as a strangulated inguinal hernia. We describe a rare case of a 64-year-old man who presented at our emergency room complaining of scrotal swelling and pain. Diagnosis of Amyand's hernia with a scrotal abscess was confirmed preoperatively by CT scan.

Transarterial treatment of acute gastrointestinal bleeding: prediction of treatment failure by clinical and angiographic parameters.

BACKGROUND: Acute gastrointestinal bleeding (GIB) is a life-threatening abdominal emergency and can be treated by transarterial embolization (TAE). Rehemorrhage and poor outcome are associated with several clinical factors. This study investigated the clinical and angiographic parameters associated with treatment failure for patients with acute GIB undergoing TAE. METHODS: Sixty-seven patients who had angiographic evidence of contrast extravasation and who received subsequent TAE were included in this study. Treatment failure was defined as continuous or recurrent bleeding that required surgery within 7 days after the bleeding episode and/or death within 1 month. Univariate and multivariate logistic regression was applied to analyze the clinical and angiographic parameters affecting treatment failure. RESULTS: Patients were divided into two groups: success (n = 35, 52.3%) and failure (n = 32, 47.7%). In the failure group, 22 patients (68.9%) re-bled and then received surgery. With the aid of angiographic localization, 68.2% (15 of 22 patients) survived after surgery. The other 10 patients who did not receive surgery died within 30 days. Several clinical and angiographic parameters analyzed by multivariate analysis were associated with treatment failure (p < 0.05), including presence of coagulopathy [odds ratio (OR), 14.7], number of supplying arteries >1 (OR, 13.2), and a distance of >5 cm (OR, 6.3) during TAE. CONCLUSION: Angiographic parameters associated with treatment failure in patients undergoing TAE are established when the number of supplying arteries is >1, and a distance of >5 cm. Patients with these risk factors should be watched carefully for recurrence in the post-procedural period.

Intra-arterial treatment in patients with acute massive gastrointestinal bleeding after endoscopic failure: comparisons between positive versus negative contrast extravasation groups.

OBJECTIVE: To determine whether treatment outcome is associated with visualization of contrast extravasation in patients with acute massive gastrointestinal bleeding after endoscopic failure. MATERIALS AND METHODS: From January 2007 to December 2009, patients that experienced a first attack of acute gastrointestinal bleeding after failure of initial endoscopy were referred to our interventional department for intra-arterial treatment. We enrolled 79 patients and divided them into two groups: positive and negative extravasation. For positive extravasation, patients were treated by coil embolization; and in negative extravasation, patients were treated with intra-arterial vasopressin infusion. The two groups were compared for clinical parameters, hemodynamics, laboratory findings, endoscopic characteristics, and mortality rates. RESULTS: Forty-eight patients had detectable contrast extravasation (positive extravasation), while 31 patients did not (negative extravasation). Fifty-six patients survived from this bleeding episode (overall clinical success rate, 71%). An elevation of hemoglobin level was observed in the both two groups; significantly greater in the positive extravasation group compared to the negative extravasation group. Although these patients were all at high risk of dying, the 90-day mortality rate was significantly lower in the positive extravasation than in the negative extravasation (20% versus 42%, p < 0.05). A multivariate analysis suggested that successful hemostasis (odds ratio [OR] = 28.66) is the most important predictor affecting the mortality in the two groups of patients. CONCLUSION: Visualization of contrast extravasation on angiography usually can target the bleeding artery directly, resulting in a higher success rate to control of hemorrhage.

Using multidetector-row CT for the diagnosis of afferent loop syndrome following gastroenterostomy reconstruction.

PURPOSE: To assess the clinical manifestations and multidetector-row computed tomography (MDCT) findings of afferent loop syndrome (ALS) and to determine the role of MDCT on treatment decisions. MATERIALS AND METHODS: From January 2004 to December 2008, 1,100 patients had undergone gastroenterostomy reconstruction in our institution. Of these, 22 (2%) patients were diagnosed as ALS after surgery that included Roux-en-Y gastroenterotomy (n=9), Billroth-II gastrojejunostomy (n=7), and Whipple's operation (n=6). Clinical manifestations and MDCT features of these patients were recorded and statistically analyzed. The presumed etiologies of obstruction shown on the MDCT were correlated with clinical information and confirmed by surgery or endoscopic biopsy. RESULTS: The most common clinical symptom was acute abdominal pain, presenting in 18 patients (82%). We found that a fluid-filled C-shaped afferent loop in combination with valvulae conniventes projecting into the lumen was the most common MDCT features of ALS. Malignant causes of ALS, such as local recurrence and carcinomatosis, are the most common etiologies of obstruction. These etiologies and associated complications can be predicted 100% by MDCT. CONCLUSION: Our results suggest that MDCT is a reliable modality for assessing the etiologies of ALS and guiding treatment decisions.

Cecorectal intussusception induced by a cecal hamartoma.

Cecorectal intussusception, a variant form of intussusception, occurs when the cecum enters through the entire course of colon and reaches to the rectum. This condition is rare but often associated with a pathologic lead point. Here, we report a 13-year-old boy, featuring insidious abdominal discomfort and constipation for 1 month, who developed cecorectal intussusception. Before surgical intervention, multi-detector row computed tomography with reconstructed images demonstrated the route of cecorectal intussusception and identified a cecal fat-containing tumor as the lead point. The patient received surgical reduction with resection of the cecal tumor. Final pathological diagnosis was a hamartoma of the cecum. The relevant literature pertaining to this condition is reviewed, and the possible pathophysiology of the condition discussed.

The value of multidetector-row computed tomography for localization of obscure acute gastrointestinal bleeding.

PURPOSE: There are no simple guidelines on when to perform multidetector-row computed tomography (MDCT) for diagnosis of obscure acute gastrointestinal bleeding (AGIB). We used a risk scoring system to evaluate the diagnostic power of MDCT for patients with obscure AGIB. MATERIALS AND METHODS: Ninety-two patients with obscure AGIB who were referred for an MDCT scan after unsuccessful endoscopic treatment at presentation were studied. We recorded clinical data and calculated Blatchford score for each patient. Patients who required transfusion more than 500mL of blood to maintain the vital signs were classified as high-risk patients. Two radiologists independently reviewed and categorized MDCT signs of obscure AGIB. Discordant findings were resolved by consensus. One-way ANOVA was used to compare clinical data between two groups; kappa statistics were used to estimate agreement on MDCT findings between radiologists. RESULTS: Of the 92 patients, 62 (67.4%) were classified as high-risk patients. Blatchford scores of high-risk patients were significantly greater than those of low-risk patients. Sensitivity for MDCT diagnosing obscure AGIB was 81% in high-risk patients, as compared with 50% in the low-risk. When used in conjunction with selection of the cut-off value of 13 in Blatchford scoring system, the sensitivity and specificity of MDCT were 70.9% and 73.7%, respectively. Contrast extravasation was the most specific sign of AGIB (k=.87), recognition of which would have improved diagnostic accuracy. CONCLUSIONS: With the aid of Blatchford scoring system for evaluating the disease severity, MDCT can localize the bleeders of obscure AGIB more efficiently.