Incidence and Risk Factors of Immediate Hypersensitivity Reactions and Immunization Stress-Related Responses With COVID-19 mRNA Vaccine.

BACKGROUND: With the implementation of mass vaccination campaigns against COVID-19, the safety of vaccine needs to be evaluated. OBJECTIVE: We aimed to assess the incidence and risk factors for immediate hypersensitivity reactions (IHSR) and immunization stress-related responses (ISRR) with the Moderna COVID-19 vaccine. METHODS: This nested case-control study included recipients who received the Moderna vaccine at a mass vaccination center, Japan. Recipients with IHSR and ISRR were designated as cases 1 and 2, respectively. Controls 1 and 2 were selected from recipients without IHSR or ISRR and matched (1 case: 4 controls) with cases 1 and cases 2, respectively. Conditional logistic regression analysis was used to identify risk factors associated with IHSR and ISRR. RESULTS: Of the 614,151 vaccine recipients who received 1,201,688 vaccine doses, 306 recipients (cases 1) and 2478 recipients (cases 2) showed 318 events of IHSR and 2558 events of ISRR, respectively. The incidence rates per million doses were estimated as IHSR: 266 cases, ISRR: 2129 cases, anaphylaxis: 2 cases, and vasovagal syncope: 72 cases. Risk factors associated with IHSR included female, asthma, atopic dermatitis, thyroid diseases, and a history of allergy; for ISRR, the risk factors were younger age, female, asthma, thyroid diseases, mental disorders, and a history of allergy and vasovagal reflex. CONCLUSION: In the mass vaccination settings, the Moderna vaccine can be used safely owing to the low incidence rates of IHSR and anaphylaxis. However, providers should be aware of the occurrence of ISRR. Although recipients with risk factors are associated with slightly increased risks of IHSR and ISRR, this is not of sufficient magnitude to warrant special measures regarding their vaccination.

Early venous return in hepatic angiomyolipoma due to an intratumoral structure resembling an arteriovenous fistula.

Early venous return (EVR) is an important radiological feature of hepatic angiomyolipoma (HAML) that can aid in differential diagnosis, but the pathogenic mechanisms of EVR have yet to be elucidated. We present the first HAML case for which a probable mechanism for EVR is described. The patient was a 46-year-old woman, who had a growing 6-cm tumor with EVR in segment 3 of the liver as revealed by dynamic contrast-enhanced computed tomography. Left hepatic lobectomy was performed to prevent tumor rupture. Histopathological and immunohistochemical analyses of the excised tumor indicated HAML. Successive microsections of the tumor were stained with hematoxylin-eosin and Victoria blue to visualize the vascular structure within and around the tumor. These analyses led to three major findings. First, many well-defined thick-walled vessels, such as arteries, were found entering the tumor. Second, many thick-walled vessels within the tumor were connected directly to thin-walled vessels, resembling arteriovenous fistulae. Finally, thin-walled intratumoral vessels were connected directly to the hepatic vein. These histological findings suggested that the rich arterial flow into the tumor was being rapidly drained into the hepatic vein through intratumoral arteriovenous connections. We also detected these same anomalous circulatory pathways in tissue sections from three of four additional HAML cases with EVR. Aberrant arteriovenous fistulae within the tumor may account for many cases of EVR in HAML patients.

Mucin-producing carcinoma of the gallbladder: evaluation by magnetic resonance cholangiopancreatography in three cases.

We report three cases of mucin-producing carcinoma of the gallbladder, along with the magnetic resonance (MR) findings, especially the findings on a MR cholangiopancreatography. In our cases, linear or curvilinear streaks were detected running along the long axis of an enlarged gallbladder (mucus thread sign). When such findings were seen, a mucin-producing carcinoma of the gallbladder should be included as a differential diagnosis. Thus, gadolinium-enhanced MR imaging is mandatory for the precise diagnosis of the mucin-producing carcinoma of the gallbladder.

CXCL17 and ICAM2 are associated with a potential anti-tumor immune response in early intraepithelial stages of human pancreatic carcinogenesis.

BACKGROUND & AIMS: Anti-tumor immunity changes over the course of tumor progression; it is not clear how or when the developing tumor overcomes immune surveillance. Intraductal papillary mucinous neoplasm (IPMN) is an intraepithelial precursor lesion of pancreatic cancer that progresses from adenoma to carcinoma. We investigated when and how the human anti-tumor immune reaction changes during pancreatic tumor development. METHODS: Using immunohistochemical analysis of cells isolated from patients with IPMN, the numbers of tumor-infiltrating lymphocytes and dendritic cells and the maturation state of dendritic cells in the regional lymph nodes were investigated during tumor progression. Gene expression profiles were compared among epithelial neoplastic cells at each stage of tumor development. Biological functions of the selected gene products were analyzed using syngeneic mouse models. RESULTS: The anti-tumor immune reaction changed from an immune response to immune tolerance between the stages of intraductal papillary mucinous adenoma (IPMA) and intraductal papillary mucinous carcinoma (IPMC). Chemokine (C-X-C motif) ligand 17 (CXCL17) and intercellular adhesion molecule 2 (ICAM2) were involved in immune surveillance during tumor development-their expression levels were up-regulated exclusively in IPMA and disappeared from IPMC. CXCL17 and ICAM2 induced infiltration and accumulation of the tumor epithelial layer by immature myeloid dendritic cells. This was followed by a cellular immune reaction and ICAM2 simultaneously promoted the susceptibility of the tumor cells to cytotoxic T-cell-mediated cytolysis. These processes had a synergistic effect to increase the anti-tumor immune response. CONCLUSIONS: Immune surveillance occurs during the early intraepithelial stages of human pancreatic carcinogenesis and is mediated by expression of CXCL17 and ICAM2.

Solitary hepatic lymphangioma: report of a case.

A 52-year-old woman presented with upper abdominal pain. Abdominal ultrasonography showed a 4-cm well-defined mass containing solid and cystic components in segment IV of the liver, and contrast-enhanced T1-weighted magnetic resonance imaging revealed heterogeneous enhancement within the tumor, indicating a solid or fibrous component. There were no cystic lesions in any other organs. A partial hepatectomy was performed, based on a preoperative diagnosis of sclerosing hemangioma and biliary cystadenoma or cystadenocarcinoma. Pathologically, the tumor appeared to be a multilocular and cystic lesion lined by attenuated endothelial- like cells with no atypia. Immunohistochemistry demonstrated the endothelial-like cells to be positive for the lymphatic-specific markers D2-40, LYVE-1, and Prox-1, which proved helpful for confirming the diagnosis as solitary hepatic lymphangioma. This case is presented with details of the pathologic and radiologic findings, because solitary hepatic lymphangioma is an extremely rare tumor and no previous reports have provided details of the immunohistochemical characteristics.

Adrenomedullin increases renal nitric oxide production and ameliorates renal injury in mice with unilateral ureteral obstruction.

PURPOSE: We evaluated the effects of adrenomedullin (Peptide Institute, Minoh-shi, Osaka, Japan) on mediators, including nitric oxide and transforming growth factor-beta, and parameters of renal injury in a murine unilateral ureteral obstruction model. MATERIALS AND METHODS: Three study groups of control, adrenomedullin treated and adrenomedullin plus L-NAME treated BALB/C mice, respectively, underwent left unilateral ureteral obstruction. A 24-hour urine sample was collected to measure urinary NO(2)/NO(3) 1 day before unilateral ureteral obstruction and kidneys were harvested on postoperative day 14. Tubulointerstitial damage markers were evaluated by immunohistochemistry. Tissue transforming growth factor-beta was determined by enzyme-linked immunosorbent assay. Endothelial and inducible nitric oxide synthase immunolocalization was also determined. RESULTS: Urinary NO(2)/NO(3) was significantly higher in the adrenomedullin group than in controls, confirming increased renal nitric oxide production. Immunohistochemistry showed increased endothelial nitric oxide synthase in vascular endothelial cells in the adrenomedullin group but tissue transforming growth factor-beta did not significantly differ in controls vs the adrenomedullin group. Interstitial collagen deposition and fibroblasts in the obstructed kidney were significantly decreased in the adrenomedullin group. The number of leukocytes and apoptotic cells in the obstructed kidney were significantly decreased by adrenomedullin. Renal injury amelioration resulting from adrenomedullin was blunted by the nitric oxide synthase inhibitor L-NAME. CONCLUSIONS: Adrenomedullin increased renal nitric oxide, and suppressed tubular apoptosis, interstitial fibrosis and inflammatory cell infiltration in mice with unilateral ureteral obstruction. The renoprotective peptide adrenomedullin may be useful for that condition.

Long-term recurrence-free survival in a patient with primary hepatic carcinosarcoma: case report with a literature review.

A 72-year-old man was found to have a 40 mm mass in liver segment VIII during follow-up abdominal ultrasonography for type C viral hepatitis. Abdominal ultrasound showed a well-defined mass containing a cystic component, and computed tomographic hepatic arteriography showed heterogeneous enhancement except for cystic necrosis. Under a pre-operative diagnosis of atypical hepatocellular carcinoma (HCC), partial resection of liver segment VIII was performed. The encapsulated tumor consisted of a peripheral solid component with a central necrotic area. Histologically, the solid component had a two-layer structure, an HCC component in the external area and a sarcomatous component with neoplastic osteoid formation in the internal area, showing histological transition. Immunohistochemically, the HCC component was positive for hepatocyte antigen and negative for vimentin. The Ki-67 labeling index was found to increase from 5% to 58% with increasing histologic atypia. The sarcomatous component was positive for vimentin and negative for pan-keratin and hepatocyte antigen, with a Ki-67 labeling index of >90%. These findings led to a diagnosis of primary hepatic carcinosarcoma. Although previously reported patients with hepatic carcinosarcoma showed early metastasis with a very poor outcome, this patient has remained free of recurrence for 30 months, which is the longest recurrence-free survival time recorded for this type of cancer. Since relatively early-stage hepatic carcinosarcoma rarely seems to present as a small tumor showing a concentric growth pattern, we report this case with a review of the literature.

A novel cell-permeable antioxidant peptide decreases renal tubular apoptosis and damage in unilateral ureteral obstruction.

Unilateral ureteral obstruction (UUO) is characterized by decreases in renal function, increased interstitial fibrosis, tubular apoptosis, and cellular infiltration. It has been suggested that inhibition of tubular apoptosis may protect against renal damage in obstruction. We have recently developed a series of peptides which are concentrated in the inner mitochondrial membrane and prevent cell death. These peptides are also active in vivo, in myocardial infraction, ischemic brain injury, and amyotrophic lateral sclerosis models. We therefore used SS-31, a prototype of these peptides, and assessed its effects on renal damage and oxidative stress in a 14-day obstruction model. SS-31 (1 or 3 mg/kg) or saline was given 1 day before and throughout the 14 days of obstruction. Kidneys were harvested and assessed for apoptosis (terminal transferase-dUTP-nick-end labeling, caspase 3 expression), fibrosis (trichrome staining), macrophage infiltration, fibroblast expression (immunoperoxidase), and oxidative damage (8-OH deoxyguanosine and heme oxygenase-1 expression), cytokines, and signaling pathways (transforming growth factor-beta, CCR-1, p38-MAPK, NF-kappaB). SS-31 significantly attenuated the effects of obstruction on all aspects of renal damage which were examined, with both the 1 and 3 mg/kg doses showing efficacy. We noted increased oxidative stress in obstruction, which was also attenuated by SS-31 treatment. Signaling via NF-kappaB and p38 MAPK pathways were both affected by SS-31 treatment. This study provides a proof of concept that peptides which protect mitochondria in vitro can provide protection from renal damage in a UUO model. The mechanism by which protection is afforded requires further studies both in vitro and in vivo.

[Clinical evaluation for adrenal metastasis of renal cell carcinoma in a single institute].

OBJECTIVE: Clinicopathogical features and prognosis of patients with renal cell carcinoma (RCC) concomitant with adrenal involvement (metastasis or invasion) were evaluated in a single institute. METHODS: In 380 patients with RCC who underwent radical nephrectomy 18 patients had adrenal involvement (13 ipsilateral adrenal involvement). Clinicopathological factors were compared between patients with ipsilateral adrnal involvement and control patients. Cause-spesific survival was calculated by Kaplan-Meier Method. RESULTS: Patients with ipsilateral adrenal involvement had significantly higher percentage of tumor>5.5 cm, upper pole tumor, pathological stage (pT) 3< or =, lymph node metastasis, distant metastasis outside ipsilateral adrenal gland, histological grade 3 and microvascular invasion than control patients (p<0.05). Therefore, large tumor (especially 5.5 cm<), upper pole tumor, clinical T3 (especially patients with tumor thrombus), lymph node metastasis and distant metastasis were candidates for risk factors of ipsilateral adrenal involvement. 76.9% of ipsilateral adrenal metastasis could be diagnosed by computed tomography (CT). Thus, preoperative adrenal finding by CT is very important to determine the indication of ipsilateral adrenalectomy. All 3 patients with small ipsilateral adrenal metastasis that could not be detected preoperative CT died within one and half year postoperatively. Patients with solitary adrenal metastasis appeared to have better prognosis compared to those with both adrenal and other metastases. In 4 patients who survived more than 2 years after the presentation of adrenal metastasis, 3 patients had solitary adrenal metastasis and underwent adrenalectomy. CONCLUSION: From the results in a single institute, radiological finding of adrenal grand, tumor size, tumor location, T stage, lymph node metastasis and distant metastasis outside ipsilateral adrenal gland are possible important factors to determine the indication of ipsilateral adrenalectomy preoperatively.

CT Imaging of early hepatocellular carcinoma and the natural outcome of hypoattenuating nodular lesions in chronic liver disease.

BACKGROUND: The Liver Cancer Study Group of Japan has designated early hepatocellular carcinoma (HCC) a clinically early-stage HCC corresponding to a high-grade dysplastic nodule as proposed by the International Working Party. METHODS: The majority of resected early HCCs were demonstrated as having hypo- or isoattenuation in the arterial and delayed phases of dynamic CT. RESULTS: Only 5% of early HCCs were hyperattenuated on dynamic CT, whereas 94% of advanced small HCC were hyperattenuated. CT arterial portography (CTAP) showed that 66% of early HCCs were hypo- and 34% were isoattenuated. CT hepatic arteriography (CTHA) demonstrated that 55% of them were hypo-, 30% were iso- and the remaining 15% were hyperattenuated. CONCLUSIONS: These findings suggest that most early HCCs receive equal or decreased blood supply from both portal and arterial blood flow compared with surrounding hepatic parenchyma. In contrast, 97% of small advanced HCCs were hypoattenuated on CTAP, and 93% were hyperattenuated on CTHA. For nodule-in-nodule type HCC, the central portion of the lesion was hyperattenuating and the peripheral portion was hypoattenuating in the arterial phase of dynamic CT, and both areas became hypoattenuated in the delayed phase. Sixty hypoattenuating nodular lesions in chronic liver disease were followed periodically with helical CT. Thirty-six (60%) of them developed to the hyperattenuating type (attenuation conversion), 21 were unchanged, and 3 disappeared spontaneously. The hyper-in-hypo-attenuating lesions showed rapid progression to entirely enhanced lesions, i.e. overt HCC. Dynamic CT is recommended as one of the low-invasive imaging modalities to follow the hypoattenuating nodules and to determine the optimal treatment with careful attention being given to intratumoral attenuation conversion.

Retroperitoneoscopic partial nephrectomy using radiofrequency coagulation for small renal tumors.

OBJECTIVES: Adoption of laparoscopic partial nephrectomy (LPN) has been limited by lack of reliable hemostatic techniques. We evaluated radiofrequency coagulation (RFC) in obtaining hemostasis during LPN for small renal masses. METHODS: Over 4 years LPN was performed by a retroperitoneal approach in 11 patients with solitary, predominantly exophytic renal tumors. A retroperitoneal approach was used in all patients. The renal hilum was not exposed. RF energy was delivered to coagulate the lesion and a margin of normal parenchyma. Tumors were excised together with at least a 0.5-cm margin of normal parenchyma, with the use of ultrasonic shears. RESULTS: Mean tumor size was 2.2 cm (range, 1.5 to 3.0). Mean operative time was 222 minutes (range, 130 to 305 minutes) and mean blood loss was 51 mL (range, 10 to 200 mL). During excision bleeding from the cut renal surface was minimal, and structure of the cortex and medulla still could be clearly distinguished after coagulation. No serious complications such as uncontrolled bleeding or urine leakage occurred. One patient had a thermal burn develop at the site of needle electrode insertion and hydronephrosis caused by pyeloureteral junction (PUJ) stricture. In follow-up, ranging from 8 to 53 months, no local recurrence or distant metastasis was detected by computed tomography. CONCLUSIONS: Hemostatic capability of RFC is excellent, improving visibility and ease of operation during LPN, and eliminating need for hilar clamping. Further experience and advancement of RF technology will be needed for the application of this method to larger, centrally located tumors.

CT Evaluation of the progression of hypoattenuating nodular lesions in virus-related chronic liver disease.

OBJECTIVE: The purpose of this study was to clarify the natural outcomes of hypoattenuating nodular lesions in patients with virus-related chronic liver disease depicted on dynamic CT. MATERIALS AND METHODS: Sixty lesions (mean size, 1.3 cm) exhibiting hypoattenuation or isoattenuation in the arterial and delayed phases of dynamic CT were retrospectively evaluated with additional CT (mean, six examinations) for a mean period of 838 days. The primary end point was emergence of hyperattenuating areas within hypoattenuating lesions, a phenomenon called attenuation conversion. Cumulative attenuation conversion rates suggesting rates of malignant transformation were calculated with the Kaplan-Meier method, and factors affecting attenuation conversion rate were analyzed with the Cox proportional hazard model. RESULTS: Thirty-six (60%) of 60 hypoattenuating lesions developed to hyperattenuating lesions, 21 were unchanged, and three disappeared spontaneously. The 36 lesions that became hyperattenuating were divided into two subgroups according to lesion enhancement pattern: hyper-in-hypoattenuating (n = 25) and entirely hyperattenuating (n = 11). The cumulative attenuation conversion rates for the 60 hypoattenuating lesions were 15.8%, 44.3%, and 58.7% at 1, 2, and 3 years. The hyper-in-hypoattenuating lesions showed more rapid progression to entirely enhanced lesions. Positive results for hepatitis C viral antibody (p = 0.028) and initial lesion size (p = 0.007) showed a positive correlation with attenuation conversion rate. CONCLUSION: Hypoattenuating hepatic nodular lesions in chronic liver disease depicted on dynamic CT have high malignant potential and should be followed with special attention to conversion from hypoattenuation to hyperattenuation to determine the optimal timing of treatment.

Multiple non-tumorous arterioportal shunts due to chronic liver disease mimicking hepatocellular carcinoma: outcomes and the associated elevation of alpha-fetoprotein.

PURPOSE: To elucidate the morphologic appearance of small non-tumorous arterioportal (AP) shunts mimicking hepatocellular carcinoma on helical computed tomography (CT), their associated outcomes, and their relationship with alpha-fetoprotein levels in patients with chronic liver disease. MATERIALS AND METHODS: Ten patients with multiple AP shunts on dynamic helical CT were evaluated. A non-tumorous AP shunt was defined as no increase or spontaneous regression in size on follow-up CT scans. The number and shape of shunts more than 5 mm in diameter were studied on a segment-by-segment basis on the initial CT scan, and compared with those on follow-up CT scans. Alpha-fetoprotein levels were measured at the same time as CT scanning was performed. RESULTS: Ten patients with 86 AP shunts (range 0.5-3.8 cm; mean 1.2 cm) underwent arterial, portal and delayed phase imaging of the entire liver. The AP shunts were geographic (44%), round (33%) or wedge-like (23%) in shape. All shunts changed from high- to iso-attenuation on the delayed phase CT. A follow-up CT (mean 73 days) revealed spontaneous disappearance in all but three (97%) of the 86 AP shunts. Furthermore, 16 new shunts appeared in different segments from the primary ones in four patients. The rapid elevation of alpha-fetoprotein levels to 5-10-fold higher than the baseline level was recognized at the same time as the initial appearance of AP shunts in three patients (30%). Further follow-up CT scans detected solitary hepatocellular carcinomas in four patients at a mean 1283 days after the initial CT. The location of the hepatocellular carcinomas was quite different from those of the initially recognized AP shunts. CONCLUSIONS: Non-tumorous AP shunts varied in CT appearance and demonstrated iso-attenuation in the delayed phase, most of which disappeared within 4 months. For these multiple small stains in chronic liver disease, periodic follow-up CT is recommended rather than alternative invasive interventions, even though there was an association with rapid elevation of alpha-fetoprotein levels.

[Clinical experience of laparoscopic adrenalectomy: the National Defense Medical College experience].

Twenty-seven laparoscopic adrenalectomies (LapAdx) were performed at the National Defense Medical College between 1999 and 2004. We evaluated the results of LapAdx (group L) compared to the results of open adrenalectomy (group O). Twenty-six of the 27 LapAdx were successfully performed, but one patient with a large pheochromocytoma required open surgey because of arterial bleeding in the renal hilus. The mean operating time in group L (185 +/- 19 min) was not significantly different from that in group O (206 +/- 13 min). The mean estimated blood loss in group L (111 +/- 61 g) was significantly lower than that in group O (308 +/- 67 g). The starting time for oral feeding and for ambulation was significantly earlier in group L than in group O. There was a major complication (intraoperative bleeding) in which a group L patient required a blood transfusion. We also compared the surgical results of 26 patients in LapAdx divided chronologically into the first half and the last half to determine the surgical skill acquired. The operating time was significantly shorter and blood loss significantly less for patients in the last half. In addition, the operating time and blood loss for the first-time LapAdx operators were comparable with those of experienced surgeons. Our results support the efficacy and the minimal invasiveness of LapAdx. The accumulated experience and knowledge regarding laparoscopic surgery in our institute were important in improving surgical procedures and results.

Atorvastatin ameliorates renal tissue damage in unilateral ureteral obstruction.

PURPOSE: The current study was done to determine whether atorvastatin, the HMGCoA (3-hydroxy-3-methylglutaryl CoA) reductase inhibitor, could decrease renal transforming growth factor-beta (TGF-beta) levels in unilateral ureteral obstruction (UUO) and concomitantly affect renal tissue damage in UUO. MATERIALS AND METHODS: Atorvastatin (20 mg/kg) was administered to rats 1 day prior to UUO and every day thereafter. Kidneys were harvested at day 14 after UUO. Tissue TGF-beta was measured by bioassay using mink lung epithelial cells. Renal tubular proliferation and apoptosis were detected by immunostaining proliferating cell nuclear antigen and polyclonal antisingle strand DNA antibody, respectively. Fibrosis was assessed by measuring collagen deposition with trichrome stained slides. Interstitial leukocyte was detected by immunostaining CD45. RESULTS: TGF-beta bioassay showed that the obstructed kidney in the control group contained significantly higher TGF-beta than the unobstructed kidney in the control group (mean +/- SD 79.1 +/- 48.5 vs 28.7 +/- 13.7 pg/mg tissue) and atorvastatin significantly decrease tissue TGF-beta in the obstructed kidney (53.4 +/- 37.0 pg/mg tissue). Immunostaining polyclonal antisingle strand DNA antibody demonstrated that the obstructed kidney in the control group has significantly more tubular apoptosis than the unobstructed counterpart (4.8 +/- 2.8 vs 2.1 +/- 1.2 nuclei per high power field) and atorvastatin significantly decreased renal tubular apoptosis in the obstructed kidney (1.1 +/- 0.7 nuclei per high power field). In addition, immunostaining proliferating cell nuclear antigen showed that the obstructed kidney in the atorvastatin group had significantly more renal tubular proliferation than the obstructed kidney in the control group (48.7 +/- 20.8 vs 17.3 +/- 10.6 per high power field). Control obstructed kidney showed significantly more fibrosis, which was also blunted by atorvastatin. CONCLUSIONS: Atorvastatin significantly decreases tissue TGF-beta, resulting in a decrease in tubular damage and interstitial fibrosis. This suggests that atorvastatin is a promising agent for preventing renal tubular damage in UUO.

Imaging of early hepatocellular carcinoma and adenomatous hyperplasia (dysplastic nodules) with dynamic ct and a combination of CT and angiography: experience with resected liver specimens.

Early hepatocellular carcinoma (HCC) as defined by the Liver Cancer Study Group of Japan would correspond to high-grade dysplastic nodules with small foci of HCC in the majority of cases, using the classification system proposed by the International Working Party. A large number of early HCCs were revealed to be hypo- or isovascular in the arterial phase of dynamic CT. Only 5% of the lesions evaluated were hypervascular, which contrasted with advanced small HCCs, of which 94% were hypervascular. CT arterial portography (CTAP) showed hypoattenuation in 66% of early HCCs and isoattenuation in 34%. CT hepatic arteriography (CTHA) demonstrated hypoattenuation in 55% of early HCC, isoattenuation in 30% and hyperattenuation in 15%. These findings suggest that most early HCCs receive equal or reduced blood supply from both portal and arterial flow compared with surrounding noncancerous parenchyma. In contrast, 97% of small HCCs are hypoattenuated on CTAP, and 93% are hyperattenuated on CTHA. For nodule-in-nodule type HCC (advanced HCC within early HCC), the CT attenuation of the central and peripheral portions revealed areas of isolated advanced HCC and isolated early HCC, respectively. Adenomatous hyperplasia (low-grade dysplastic nodules) was not readily differentiated using the various imaging modalities, mainly due to the smaller size of these lesions compared to early HCC and/or a portal and arterial blood supply very similar to that of the surrounding parenchyma. Hemodynamic changes in cirrhotic liver were similarly evaluated using CTAP and CTHA, and the treatment of early HCC is briefly discussed herein.

Suppression of lung metastasis of renal cell carcinoma by the intramuscular gene transfer of a soluble form of vascular endothelial growth factor receptor I.

PURPOSE: We clarified whether adenovirus mediated intramuscular gene transfer of soluble vascular endothelial growth factor receptor 1 (sFlt-1) can inhibit lung metastasis of renal cell carcinoma. MATERIALS AND METHODS: We constructed the adenovirus vector AdsFlt-1, which expresses soluble Flt-1 protein. Functional validation of the vector was determined by HUVEC (in vitro human umbilical vein endothelial cell) proliferation inhibition assay. The efficacy of AdsFlt-1 was tested in a Renca murine renal cell carcinoma lung metastasis model. BALB/c mice were injected with Renca cells, followed by the intramuscular administration of AdsFlt-1 24 hours later. Lung specimens were harvested 17 days later and the number of lung metastases was counted. Immunohistochemical analysis of the specimen for angiogenesis and apoptosis was done. RESULTS: Treatment with adenovirus expressed sFlt-1 inhibited HUVEC proliferation. The intramuscular administration of AdsFlt-1 significantly inhibited lung metastasis of Renca cells. Immunohistochemical analysis of the lung specimen showed fewer neovessel formations and more apoptotic cells in AdsFlt-1 treated tumors in mice. CONCLUSIONS: The intramuscular administration of AdsFlt-1 effectively inhibited lung metastasis in a murine model of renal cell carcinoma. Because of the simplicity of this therapy, it may well be useful as an effective adjuvant therapy for renal cell carcinoma.

Dynamic computed tomography and color Doppler ultrasound of renal parenchymal neoplasms: correlations with histopathological findings.

BACKGROUND: We evaluated whether color Doppler ultrasound (US) had diagnostic accuracy equal to dynamic computed tomography (CT) and whether performing dynamic CT and Doppler US together would be more informative in preoperative diagnosis of renal solid tumors. METHODS: A total of 110 renal solid tumors smaller than 7 cm were evaluated with dynamic CT and Doppler US. We compared the enhancement and the color flow patterns with the histopathological subtypes. RESULTS: Eighty-seven (95.6%) of 91 clear cell carcinomas showed rich enhancement in the cortical nephrographic phase (CNP) and 82 (90.1%) of them had color flow in the Doppler US. Of the total of 110 tumors, nine (8.1%) did not show color flow in spite of rich enhancement in the CNP. Conversely, eight (7.2%) of the 110 tumors showed color flow in spite of poor enhancement, including two chromophobe cell carcinomas and two metastatic renal tumors. CONCLUSIONS: The enhancement pattern in dynamic CT and the color flow pattern in Doppler US were different among the subtypes of RCC. Color Doppler US had diagnostic accuracy equal to dynamic CT in most patients with renal solid tumors. Although Doppler US may play a unique role in the diagnosis of some renal parenchymal solid tumors, it is sufficient to perform dynamic CT alone for diagnosis of clear cell carcinoma.