Whole cancer-region enhancement using meglumine-gadopentetate-glucose solution and 7.0-T magnetic resonance imaging.

To visualize whole cancerous region including hypoxic cancer without radiation exposure, we developed meglumine-gadopentetate-glucose solution for 7.0-T magnetic resonance imaging. The infusion solution consists of meglumine-gadopentetate and glucose solutions, and these solutions are mixed before the vein drip infusion. We used readily available solutions, and the concentrations of the meglumine-gadopentetate and glucose solutions were 37.14 and 5.0%, respectively. In the first and second experiments, vein infusions were conducted from a rabbit ear using meglumine-gadopentetate-saline and meglumine-gadopentetate-glucose solutions, and T1 weighted imaging was performed to visualize cancerous region. Using the meglumine-gadopentetate saline, it was not difficult to image cancer-growth regions with new blood vessels. Using the meglumine-gadopentetate-glucose solution, the signal intensity of whole cancerous region including hypoxic cancer substantially increased. The visualizing duration for the meglumine gadopentetate glucose was beyond 90 min, and the rabbit survived after the infusion. The signal intensity in the hypoxic cancer was increasing until 90 min using the meglumine-gadopentetate-glucose solution, since the meglumine-gadopentetate molecules were absorbed into almost the whole cancerous region along with glucose-molecule flows.

High-grade PanIN presenting with localised stricture of the main pancreatic duct: A clinicopathological and molecular study of 10 cases suggests a clue for the early detection of pancreatic cancer.

AIMS: This study aimed to identify the pathological features of high-grade PanIN that presents with imaging-detectable abnormalities. METHODS AND RESULTS: Ten cases of isolated, main-duct, high-grade PanIN as the primary clinical presentation were identified. All patients presented with stenosis of the main pancreatic duct, with two being associated with extensive upstream duct dilatation (>5 mm in diameter). Pancreatic juice cytology suggested adenocarcinoma in all seven cases examined. In resected specimens, high-grade PanIN was present chiefly in the main pancreatic duct, with longitudinal extension ranging between 3 and 40 mm in length (median = 18 mm). In four cases, in which hypoechoic or hypovascular masses were observed on imaging, radiopathology correlations suggested that they represented parenchymal atrophy and subsequent fibrosis around affected ducts, but not invasive malignancy. On immunohistochemistry, the loss of p16 expression was found in five (50%), p53 overexpression in two (20%) and loss of SMAD4 expression in none (0%). KRAS mutations were detected in nine cases, with two dominant clones being found in three by ultrasensitive droplet digital polymerase chain reaction, suggesting the genetic heterogeneity of dysplastic cells composing individual lesions. Mutant GNAS was also observed in one case. CONCLUSIONS: Isolated high-grade PanIN may present with pancreatic duct stenosis. Therefore, intensive investigations including pancreatic juice cytology will be required for patients with unexplained pancreatic duct stenosis. The abnormal expression of p53 and SMAD4 is infrequent, while GNAS may be mutated in premalignant lesions mainly affecting the main pancreatic duct, similar to KRAS.

Investigation of quad-energy high-rate photon counting for X-ray computed tomography using a cadmium telluride detector.

To obtain four kinds of tomograms at four different X-ray energy ranges simultaneously, we have constructed a quad-energy (QE) X-ray photon counter with a cadmium telluride (CdTe) detector and four sets of comparators and microcomputers (MCs). X-ray photons are detected using the CdTe detector, and the event pulses produced using amplifiers are sent to four comparators simultaneously to regulate four threshold energies of 20, 33, 50 and 65keV. Using this counter, the energy ranges are 20-33, 33-50, 50-65 and 65-100keV; the maximum energy corresponds to the tube voltage. We performed QE computed tomography (QE-CT) at a tube voltage of 100kV. Using a 0.5-mm-diam lead pinhole, four tomograms were obtained simultaneously at four energy ranges. K-edge CT using iodine and gadolinium media was carried out utilizing two energy ranges of 33-50 and 50-65keV, respectively. At a tube voltage of 100kV and a current of 60 µA, the count rate was 15.2 kilocounts per second (kcps), and the minimum count rates after penetrating objects in QE-CT were regulated to approximately 2 kcps by the tube current.

Comprehensive Diagnosis of Bacterial Infection Associated with Acute Cholecystitis Using Metagenomic Approach.

Acute cholecystitis (AC), which is strongly associated with retrograde bacterial infection, is an inflammatory disease that can be fatal if inappropriately treated. Currently, bacterial culture testing, which is basically recommended to detect the etiological agent, is a time-consuming (4-6 days), non-comprehensive approach. To rapidly detect a potential pathogen and predict its antimicrobial susceptibility, we undertook a metagenomic approach to characterize the bacterial infection associated with AC. Six patients (P1-P6) who underwent cholecystectomy for AC were enrolled in this study. Metagenome analysis demonstrated possible single or multiple bacterial infections in four patients (P1, P2, P3, and P4) with 24-h experimental procedures; in addition, the CTX-M extended-spectrum ß-lactamase (ESBL) gene was identified in two bile samples (P1 and P4). Further whole genome sequencing of Escherichia coli isolates suggested that CTX-M-27-producing ST131 and CTX-M-14-producing novel-ST were identified in P1 and P4, respectively. Metagenome analysis of feces and saliva also suggested some imbalance in the microbiota for more comprehensive assessment of patients with AC. In conclusion, metagenome analysis was useful for rapid bacterial diagnostics, including assessing potential antimicrobial susceptibility, in patients with AC.

Evaluating the timing of laparoscopic cholecystectomy for acute cholecystitis in an experienced center based on propensity score matching.

INTRODUCTION: This study evaluates the therapeutic outcomes for laparoscopic cholecystectomy for acute cholecystitis based on the time from symptom onset to surgery. METHODS: This study enrolled 224 patients. Patients' characteristics and operative outcomes were compared between patient groups based on the timing of laparoscopic cholecystectomy from symptom onset: ≤72 h versus >72 h, and ≤7 days versus ≥8 days. Then, we performed propensity score matching of 13 relevant variables, including patient demographics, examination findings, and therapeutic factors. RESULTS: The early surgery groups (≤72 h and ≤7 days) had significantly younger patients with fewer comorbidities and a shorter duration from symptom onset to presentation before performed propensity score matching. These groups also had shorter surgery, postoperative hospital stay, and total length of stay. Other operative outcomes, including blood loss, conversion to open surgery, bile duct injury, and postoperative complications, did not significantly differ among the groups. After propensity score matching, all therapeutic outcomes, including duration of surgery, showed no significant differences in either analysis. CONCLUSIONS: In a center with sufficient experience, performing laparoscopic cholecystectomy at the earliest possible time after presentation was a safe therapeutic strategy for each patient with acute cholecystitis, regardless of the time from symptom onset.

Risk factors for conversion of laparoscopic cholecystectomy to open surgery associated with the severity characteristics according to the Tokyo guidelines.

PURPOSE: The aim of this retrospective study was to identify the risk factors associated with the severity characteristics in the Tokyo guidelines for conversion to open surgery in patients with acute cholecystitis (AC) who underwent laparoscopic cholecystectomy. METHODS: A total of 225 patients were enrolled in the study. The patients were classified into two groups: a conversion group and a no-conversion group. The preoperative characteristics and therapeutic strategy were analyzed as risk factors for conversion to open surgery. The postoperative outcomes were also analyzed. RESULTS: Conversion to open surgery occurred in 29 patients (12.9%), including seven patients (6.7%) with mild AC and 22 patients (18.5%) with moderate AC. A univariate analysis showed that the risk factors for conversion to open surgery included a duration of symptoms longer than 72 h, an elevated C-reactive protein (CRP) value and the Tokyo guidelines 2013 (TG 13) severity classification. The multivariate analysis showed that the risk factors for conversion to open surgery included a duration of symptoms longer than 72 h and a CRP value >11.5 mg/dl. CONCLUSIONS: A duration of symptoms longer than 72 h, which is included in the criterion for moderate AC severity in the TG 13, was an independent risk factor for conversion to open surgery. In addition, adoption of a high CRP value as an additional criterion for moderate AC may increase the utility of the TG 13.

Successful treatment of a common hepatic artery pseudoaneurysm using a coronary covered stent following pancreatoduodenectomy: report of a case.

This report presents the case of a common hepatic artery (CHA) pseudoaneurysm secondary to postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD), which was successfully treated using a coronary covered stent. A 70-year-old female underwent subtotal stomach-preserving PD for middle cholangiocarcinoma. POPF was identified on postoperative day (POD) 7, and the patient suddenly lost 500 ml of blood via the abdominal drain on POD 19. Urgent celiac arteriography revealed a CHA pseudoaneurysm. A coronary covered stent was placed to prevent rupture of the pseudoaneurysm and to maintain hepatic arterial flow, instead of performing transarterial embolization. No vascular adverse events were encountered during or after the procedure. Computed tomography and angiography showed a patent stent graft and good hepatic arterial flow 9 months after placement of the stent. Endovascular stent-graft placement not only treated the pseudoaneurysm, but also preserved the arterial blood flow. This report describes the placement of a covered stent graft for delayed hemorrhage after PD.

Changes in the therapeutic strategy for acute cholecystitis after the Tokyo guidelines were published.

BACKGROUND: This study examined the feasibility of early laparoscopic cholecystectomy (ELC) for acute cholecystitis (AC) according to the Tokyo guidelines severity grade, and analyzed the changes in the therapeutic strategy for AC after the Tokyo guidelines were published. METHODS: A total of 225 patients were enrolled in this study. The therapeutic period was divided into two periods: before and after the publication of the Tokyo guidelines (prior to and including 2007, and from 2008, respectively). RESULTS: Comparing the surgical strategy between ELC and delayed laparoscopic cholecystectomy (DLC), significant differences were found in the length of preoperative hospital stay and total hospital stay for cases of mild AC compared with moderate AC. With conversion to open surgery, postoperative complications including postoperative bile leak were not significantly different. Since ELC was performed significantly more often after publication of the guidelines, preoperative, postoperative, and total hospital stays were significantly shorter in the later period. CONCLUSION: ELC is a safe and effective therapeutic strategy for both mild and moderate AC. The Tokyo guidelines resulted in a significant increase in the performance of ELC and significantly reduced preoperative and total hospital stays without increasing intra- and postoperative complications.

Demonstration of enhanced iodine K-edge imaging using an energy-dispersive X-ray computed tomography system with a 25 mm/s-scan linear cadmium telluride detector and a single comparator.

An energy-dispersive (ED) X-ray computed tomography (CT) system is useful for carrying out monochromatic imaging. To perform enhanced iodine K-edge CT, we developed an oscillation linear cadmium telluride (CdTe) detector with a scan velocity of 25 mm/s and an energy resolution of 1.2 keV. CT is performed by repeated linear scans and rotations of an object. Penetrating X-ray photons from the object are detected by the CdTe detector, and event signals of X-ray photons are produced using charge-sensitive and shaping amplifiers. The lower photon energy is determined by a comparator device, and the maximum photon energy of 60 keV corresponds to the tube voltage. Rectangular-shaped comparator outputs are counted by a counter card. In the ED-CT, tube voltage and current were 60 kV and 0.30 mA, respectively, and X-ray intensity was 14.8 µGy/s at 1.0m from the source at a tube voltage of 60 kV. Demonstration of enhanced iodine K-edge X-ray CT for cancer diagnosis was carried out by selecting photons with energies ranging from 34 to 60 keV.

15Mcps photon-counting X-ray computed tomography system using a ZnO-MPPC detector and its application to gadolinium imaging.

15Mcps photon-counting X-ray computed tomography (CT) system is a first-generation type and consists of an X-ray generator, a turntable, a translation stage, a two-stage controller, a detector consisting of a 2mm-thick zinc-oxide (ZnO) single-crystal scintillator and an MPPC (multipixel photon counter) module, a counter card (CC), and a personal computer (PC). High-speed photon counting was carried out using the detector in the X-ray CT system. The maximum count rate was 15Mcps (mega counts per second) at a tube voltage of 100kV and a tube current of 1.95mA. Tomography is accomplished by repeated translations and rotations of an object, and projection curves of the object are obtained by the translation. The pulses of the event signal from the module are counted by the CC in conjunction with the PC. The minimum exposure time for obtaining a tomogram was 15min, and photon-counting CT was accomplished using gadolinium-based contrast media.

Bacteriological analysis of bile in acute cholecystitis according to the Tokyo guidelines.

BACKGROUND: We performed bacteriological analysis of bile in acute cholecystitis (AC) patients graded in severity according to the Tokyo guidelines. METHODS: We enrolled 163 AC patients in whom bacteriological analysis of bile was performed. RESULTS: Significant differences in age (60 vs. 67 years), body temperature (BT) (37.2 vs. 37.6°C), white blood cell count (13,033 vs. 15,177/mm(3)), and serum C-reactive protein (CRP) (8.9 vs. 16.9 mg/dL) were found between the Mild and Moderate severity groups. The prevalence of bactibilia differed significantly between Mild and Moderate patients (45.3 vs. 67.0%, P = 0.0107); however, there were no significant differences in the bacterial strains, prevalence of antimicrobial resistance, or polymicrobial isolation frequency between the 2 groups. Our local antibiogram revealed that several microorganisms showed higher resistance rates; these were also isolated even in Mild cases. Advanced age, high BT, high serum CRP, and presence of marked local infection were identified as being significantly associated with high risk of bactibilia. Receiver operating characteristic curve analysis indicated the optimal cutoff value of age to be 65 years, of BT to be 37.5°C, and of serum CRP to be 13.4 mg/dL. CONCLUSION: Adequate broad-spectrum antimicrobial therapy should be administered perioperatively even for Mild patients classified according to the current Tokyo guidelines. These results suggest that more precise severity grades may need to be established, including age and CRP as additional parameters.

100 µA-100 kV Photon-counting X-ray Computed Tomography System Using an LSO-MPPC Detector and a High-Speed Comparator and its Application to Gadolinium Imaging.

A high-sensitive x-ray computed tomography (CT) system is useful for decreasing absorbed dose for patients, and we performed preliminary experiments for first-generation photon-counting CT using a high-sensitive single detector. X-ray photons are detected using an LSO [Lu2(SiO4)O] single crystal scintillator and a multipixel photon counter (MPPC). The photocurrent from the MPPC is amplified by a current-voltage amplifier and an integrator, and the event pulse is sent to a high-speed comparator. Logical pulses are then produced by the comparator and are counted by a counter card. Tomography is accomplished by repeated linear scans and rotations of an object, and projection curves of the object are obtained by the linear scan. The count rate decreased with increase in lower level voltage of the comparator Vl, and the maximum count rate was 265 kcps at a Vl of 0.4 V. The exposure time for obtaining a tomogram was 10 minutes at a scan step of 0.5 mm and a rotation step of 1.0°. The image contrast of gadolinium medium slightly varied with change in Vl. We carried out low-dose-rate photon-counting CT at a tube current of 100 µA and a tube voltage of 100 kV. The energy-dispersive effect of the CT image was confirmed by selecting Vl. The absorbed dose for objects can be reduced using the linear detector consisting of plural LSO-MPPC detectors.

Combined hepatic resection with the inferior vena cava and diaphragm and reconstruction using an equine pericardial patch: report of a case.

We herein report a case of combined hepatic resection with inferior vena cava (IVC) and diaphragm resection, and reconstruction using an equine pericardial patch. A 54-year-old woman showed hepatic cancer recurrence on radiological imaging, with invasion to the caudate lobe of the liver, IVC, diaphragm, and adrenal gland. We resected 10 × 5 cm of the diaphragm. After dissecting the hepatic parenchyma, the caudate lobe was connected only to the IVC. Clamping of the IVC was performed between the IVC below the confluence of the hepatic vein and the suprarenal IVC. A 6 × 3-cm segment of the IVC was then resected. The IVC and diaphragm were reconstructed using an equine pericardial patch, as both defects were too large to repair without a patch. The equine pericardium represents a suitable graft material for repairing both the IVC and diaphragm. Further investigation is needed to determine the durability and anti-infection properties of equine pericardial grafts.

Pancreatic adenosquamous carcinoma presenting as splenic rupture: report of a case.

A 58-year-old female patient presented with the sudden onset of left upper quadrant pain. The physical examination revealed the presence of shock status. Abdominal computed tomography revealed splenomegaly with a huge mass inside the spleen, and massive fluid collection in the abdominal cavity. After splenic artery embolization, laparotomy was performed. The operative findings revealed intra-abdominal hemorrhage and rupture of the lower pole of the spleen. Furthermore, a palpable solid mass was observed at the splenic hilum, and distal pancreatectomy with splenectomy was performed. The macroscopic findings revealed a pancreatic tail tumor at the splenic hilum directly invading the splenic parenchyma. Microscopic examinations showed the tumor to consist of squamous cell carcinoma. Furthermore, old and new thrombi were observed inside small splenic arteries. These findings were considered to represent invasion of pancreatic adenosquamous carcinoma to the spleen, and rupture of the spleen was attributed to splenic ischemia resulting from cancer invasion and splenic vein obstruction.

[Three cases of biliary tract cancer with positive surgical margin obtained a long-term survival after multimodality therapy].

We report three cases of biliary tract cancer with positive surgical margin obtained a long-term survival after multimodality therapy. Case 1: A 58-year-old man had operated PPPD for middle part of biliary tract cancer. Final pathological findings revealed HM2. Hepatic metastasis and anastomotic recurrence were observed, postoperatively. RFA and chemoradiation therapy were performed against these lesions. Nevertheless, the patient died of sepsis associated with hepatic abscess caused by cholangitis 5 years and 10 months after surgery. Case 2: A 72-year-old man had operated for upper part of biliary tract cancer. Intra-operative pathological findings revealed HM 2 and DM 2, extra-bile duct resection was performed for this lesion. After surgery, radiation therapy, systemic chemotherapy and hepatic arterial chemotherapy were performed, nevertheless the patient died of cancer 2 years and 6 months after surgery. Case 3: A 75-year-old man had operated for upper part of biliary tract cancer. Intra-operative pathological findings revealed HM 2 and DM 2, an extra-bile duct resection was performed for this lesion. After surgery, chemoradiation therapy, hepatic arterial chemotherapy and systemic chemotherapy were performed, nevertheless the patient died of cancer 3 years and 6 months after surgery.

Embossed radiography utilizing energy subtraction.

Currently, it is difficult to carry out refraction-contrast radiography by using a conventional X-ray generator. Thus, we developed an embossed radiography system utilizing dual-energy subtraction for decreasing the absorption contrast in unnecessary regions, and the contrast resolution of a target region was increased by use of image-shifting subtraction and a linear-contrast system in a flat panel detector (FPD). The X-ray generator had a 100-microm-focus tube. Energy subtraction was performed at tube voltages of 45 and 65 kV, a tube current of 0.50 mA, and an X-ray exposure time of 5.0 s. A 1.0-mm-thick aluminum filter was used for absorbing low-photon-energy bremsstrahlung X-rays. Embossed radiography was achieved with cohesion imaging by use of the FPD with pixel sizes of 48 x 48 microm, and the shifting dimension of an object in the horizontal direction ranged from 100 to 200 microm. At a shifting distance of 100 mum, the spatial resolutions in the horizontal and vertical directions measured with a lead test chart were both 83 microm. In embossed radiography of non-living animals, we obtained high-contrast embossed images of fine bones, gadolinium oxide particles in the kidney, and coronary arteries approximately 100 microm in diameter.

X-ray fluorescence camera for imaging of iodine media in vivo.

X-ray fluorescence (XRF) analysis is useful for measuring density distributions of contrast media in vivo. An XRF camera was developed for carrying out mapping for iodine-based contrast media used in medical angiography. Objects are exposed by an X-ray beam from a cerium target. Cerium K-series X-rays are absorbed effectively by iodine media in objects, and iodine fluorescence is produced from the objects. Next, iodine Kalpha fluorescence is selected out by use of a 58-microm-thick stannum filter and is detected by a cadmium telluride (CdTe) detector. The Kalpha rays are discriminated out by a multichannel analyzer, and the number of photons is counted by a counter card. The objects are moved and scanned by an x-y stage in conjunction with a two-stage controller, and X-ray images obtained by iodine mapping are shown on a personal computer monitor. The scan pitch of the x and y axes was 2.5 mm, and the photon counting time per mapping point was 2.0 s. We carried out iodine mapping of non-living animals (phantoms), and iodine Kalpha fluorescence was produced from weakly remaining iodine elements in a rabbit skin cancer.

Multiple necrotic nodules of the liver simulating liver metastasis.

A 70-year-old man was referred to our hospital due to anemia and elevated serum tumor marker levels. He had advanced colon cancer, and hepatic lesions were found incidentally. On ultrasonography (US) and computed tomography (CT), the hepatic lesions had a maximum diameter of 20 mm and were located in Couinaud's segments V, VI, VII, and VIII, which suggested liver metastasis. On early- and late-phase CT during hepatic arteriography (CTHA), all of the lesions had rim enhancement. On early-phase CT during arterioportography (CTAP), all of the lesions were seen as nodules with an irregular perfusion defect, and on late-phase CTAP, all the lesions gradually became iso-dense, and their shape and size changed. Based on the CTAP findings, these lesions were thought to be fibrotic tumors. Partial resection of the liver (including the lesions in Couinaud's segments V and VIII) was done. Histological examination revealed that the lesions were necrotic nodules. Thus, CT angiography (CTHA and CTAP) was useful for identifying necrotic nodules, because their appearance on this modality is different from that of liver metastases.

Single case of renal cell carcinoma and endocrine pancreatic head cancer occurring with von Hippel-Lindau disease.

Von Hippel-Lindau (VHL) disease is an autosomal dominant genetic disease in which various neoplastic lesions occur in multiple organs. Reported here is a case of VHL disease with concurrent renal cell carcinoma and endocrine pancreatic cancer. The patient was a 43-year old woman. On this occasion, the patient had sought treatment from her local physician, complaining chiefly of yellowing of the skin and bulbar conjunctiva. Abdominal ultrasound and computed tomography scans revealed a mass in the right kidney and a mass in the pancreatic head. Peripheral blood genetic analysis revealed an Arg/stop heteroconjugative mutation in codon 113 in exon 1 of the VHL gene on the short arm of chromosome 3 (p25-26). After various tests were performed, the patient was diagnosed with right renal cell carcinoma, malignant tumor of the pancreatic head, and multiple pancreatic cysts accompanying von Hippel-Lindau disease. Right nephrectomy and pancreatoduodenectomy were performed. Based on the histopathological results, the patient was diagnosed with right renal cell carcinoma and highly differentiated endocrine pancreatic cancer. Immunohistologically, a large number of atypical cells were found to be positive for both anti-chromogranin and anti-synaptophysin antibodies in the endocrine tumor. Immunostaining for each type of gut hormone was also performed, but all results were negative. Based on the above findings, nonfunctioning, highly differentiating endocrine cancer was diagnosed. This is the first confirmed case of renal cell carcinoma and endocrine pancreatic cancer occurring concurrently with VHL. This is an important case, so it is presented here along with a short discussion of the literature.

[A case of resectable solitary liver metastasis from breast cancer].

We report a case of resectable solitary liver metastasis from breast cancer. A 53-year-old woman underwent a pectoral muscle-preserving mastectomy for T1 N0M0 (Stage I) left breast cancer in May 2000. Histopathologic diagnosis was medullary carcinoma. Thereafter, the patient was followed up with adjuvant chemotherapy. A solitary tumor in the right lobe of the liver at S6 was found 10 months after mastectomy by ultrasonography. With a diagnosis of liver metastasis from breast cancer, right hepatectomy was performed in May 2001. At present, she remains disease free for 4 years after hepatectomy. We think that a surgical procedure for liver metastasis from breast cancer, if possible, is beneficial in prolonged survival.