Successful R0 resection after chemotherapy, including nivolumab, for gastric cancer with liver metastases: three case reports.

BACKGROUND: Advances in chemotherapy have increased clinical experience with conversion surgery for inoperable advanced gastric cancer. This report describes three patients with unresectable gastric cancer accompanied by multiple liver metastases. In all three patients, nivolumab resolved the liver metastases and subsequent conversion surgery achieved a pathological complete response. CASE PRESENTATION: In Case 1, a 68-year-old man with clinical Stage IVB gastric cancer and multiple liver metastases initiated first-line therapy with SOX plus nivolumab. The patient completed 13 cycles; however, only nivolumab was continued for 3 cycles because of adverse events. Distal gastrectomy and partial hepatic resection were performed because of a significant reduction in the size of the liver metastases as observed on magnetic resonance imaging (MRI). In Case 2, a 72-year-old man with clinical Stage IVB gastric cancer and multiple liver metastases initiated first-line therapy with SOX. Because of the subsequent emergence of new liver metastases, the patient transitioned to ramucirumab plus paclitaxel as second-line therapy. Third-line therapy with nivolumab was initiated because of side effects. MRI revealed necrosis within the liver metastasis, and the patient underwent proximal gastrectomy and partial hepatectomy. In Case 3, a 51-year-old woman with clinical Stage IVB gastric cancer accompanied by multiple metastases of the liver and para-aortic lymph nodes began first-line therapy with SOX plus nivolumab. The patient completed 10 cycles; however, only nivolumab was continued for 5 cycles because of adverse events. Computed tomography showed a significant decrease in the size of the para-aortic lymph nodes, while MRI indicated the presence of a singular liver metastasis. Distal gastrectomy and partial hepatic resection were subsequently performed. In all three cases, MRI revealed the presence of liver metastases; however, pathological examination showed no viable tumor cells. CONCLUSIONS: We herein present three cases in which chemotherapy, including nivolumab, elicited a response in patients with multiple unresectable liver metastases, ultimately culminating in R0 resection through conversion surgery. Although MRI showed liver metastases, pathological analysis revealed no cancer, underscoring the beneficial impact of chemotherapy.

Brachiocephalic to left brachial vein thrombotic vasculitis accompanying mediastinal pancreatic fistula: A case report.

BACKGROUND: Pancreatitis is a severe inflammatory pancreatic disease commonly due to bile duct stones or excessive alcohol usage, with clinical manifestations of abdominal pain, nausea, fever, and fluid collections. Healthy persons with less symptomatic pancreatitis are quite rare. Herein, we report a case of a patient with an undetermined onset of pancreatitis mimicking left arm cellulitis due to thrombotic vasculitis of the brachiocephalic vein. CASE SUMMARY: A 50-year-old woman visited our hospital for tenderness in the left arm over several recent days. She was diagnosed with cellulitis on the left arm due to left elbow tenderness. Intravenous antibiotics administration did not improve symptoms and laboratory data worsened; thus, chest and abdominal computed tomography (CT) was performed. CT demonstrated pancreatitis with pseudocyst around the pancreas extending to the mediastinum. Thrombotic vasculitis of the brachiocephalic to left brachial vein was observed, which could be the cause of left elbow pain. A pancreatic fistula was found in the head of the pancreas by endoscopic retrograde cholangiopancreatography, so a pancreatic cyst drainage tube via the duodenum was placed in the pseudocyst. Cyst content culture was positive for Escherichia coli infection. Clinical symptoms, imaging findings, and inflammatory reactions resolved gradually after starting therapeutic intervention. The mediastinal pancreatic pseudocysts shrunk, and the venous thrombi remained but shrunk. CONCLUSION: The case of a patient with pancreatitis with an undetermined onset that mimics left arm cellulitis is reported. Deep vein thrombosis should be kept in mind when treating patients with severe inflammatory disease.

The feasibility of superparamagnetic iron oxide-enhanced magnetic resonance imaging for assessing liver lesions in patients with contraindications for iodine CT contrast media or gadolinium-based MR contrast media: a retrospective case-control study.

Background: The detection and characterization of liver lesions are problematic in patients with bronchial asthma, renal dysfunction, or a history of allergy to gadolinium-based magnetic resonance contrast media or iodine-computed tomography contrast media because these contrast media cannot be used. Hence, the information on the lesion vascularity cannot be obtained. Therefore, this retrospective case-control study evaluated the feasibility of superparamagnetic iron oxide (SPIO) in patients with one or more of these contraindications who underwent SPIO-enhanced magnetic resonance imaging for the assessment of liver lesions. Methods: Twenty-six patients with a total of 48 lesions were analyzed. SPIO was used in the case of all patients because each patient had at least one reason not to use iodine contrast or gadolinium-based contrast media. Additionally, all patients were subjected to the perfusion study. A total volume of 1.3 mL of SPIO was injected via the cubital vein at a rate of 3 mL per second, followed by 40 mL saline at the same speed. The scanning of the perfusion study was started 4 s after the beginning of superparamagnetic iron oxide injection and scanning took 50 s. Two radiologists independently evaluated whether the lesion was malignant or benign. Receiver operating characteristic analysis (ROC) was performed to determine the additional benefit of the perfusion study. Results: There were no adverse effects associated with SPIO. The area under the curve (AUC) value without perfusion study for observers 1 and 2 were 0.473 (P=0.794, 95% CI: 0.275-0.672) and 0.602 (P=0.305, 95% CI: 0.407-0.798), respectively, whereas the Az values with perfusion study for observers 1 and 2 were 0.782 (P=0.011, 95% CI: 0.565-0.998) and 0.784 (P=0.004, 95% CI: 0.591-0.977), respectively. Az value became significantly better when the perfusion study has added (P=0.001 and 0.012 by observers 1 and 2). Conclusions: SPIO can be used safely in patients with bronchial asthma, renal dysfunction, or a history of contrast media allergy. Furthermore, the diagnostic accuracy of SPIO was acceptable.

Evaluation of liver tumor identification rate of volumetric-interpolated breath-hold images using the compressed sensing method and qualitative evaluation of tumor contrast effect via visual evaluation.

Background: To evaluate the possible clinical use of the compressed sensing-volumetric-interpolated breath-hold examination (CS-VIBE) in patients with liver tumors by evaluating tumor contrast enhancement effect by radiologists. Methods: We examined 22 patients with pathologically confirmed neoplastic lesions in the liver and 62 patients with lesions confirmed by imaging and clinical observation. To evaluate image quality, dynamic contrast-enhanced multiphase breath-hold magnetic resonance imaging was performed. The contrast agent used in this study was gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid. Image quality was assessed by three radiologists experienced in this field. Using a four-point scale, we evaluated the gradual contrast enhancement effect of the portal vein to determine whether a decent arterial phase could be obtained. We assessed interobserver agreement using the Fleiss kappa to evaluate image quality between readers. The detection and evaluation of the tumor itself by its enhancement effects are very important in contrast studies. Thus, we evaluated the contrast enhancement effect of the tumors on a three-point scale in 26 patients already known to have hypervascularized tumors using ultrasound or computed tomography as assessed by experienced radiologists. Results: In terms of contrast enhancement effects of the portal vein, the mean value of the readers was 1.85 in the first phase, 2.07 in the second phase, 2.66 in the third phase, 3.05 in the fourth phase, and 3.24 in the fifth phase. Moreover, the interreader agreement was moderate (kappa 0.400-0.502) for all evaluated scores. In the signal of the portal vein, the score of the second arterial phase increased gradually, and in the third arterial phase, the mean score varied from 2 to 3. Compared with ultrasound or computed tomography, CS-VIBE identified 92.3% tumors with hypervascularized tumors (24 of 26 patients with findings hypervascularized tumors). In the results, the interreader agreement was fair to moderate (kappa 0.414-0.521). Conclusions: We obtained multiphase images, including at least one phase, which are useful for the evaluation of liver tumors. Furthermore, the radiologist was able to detect the tumor as before. Therefore, compressed sensing-volumetric-interpolated breath-hold examination is clinically useful in Ethoxybenzyl liver studies.

Effects of Β‒Blocker Administration on Cardiac Function: A Coronary Computed Tomography Angiography Study.

BACKGROUND: ß-blockers are widely used for lowering heart rate (HR) during coronary computed tomography angiography (CCTA); however, they should be used with caution for patients with heart failure as they may have a negative inotropic effect. OBJECTIVE: To clarify the effects of ß-blockers (oral and intravenous injection) on cardiac function using CCTA. METHODS: A total of 244 patients (men: women = 166: 78; mean age, 64.4 years old) suspected of having ischemic cardiac disease and had undergone echocardiography within 3 months before and after CCTA were included in the study. Systematic errors in ejection fraction (EF) were corrected by calculating ΔEF from the EF difference between echocardiography and CCTA in patients not using ß- blockers. Univariate and multivariate analyses were performed for factors affecting ΔEF. In addition, HR between, before, and during CCTA were compared by Wilcoxon's test. RESULTS: Temporary oral or intravenous administration of ß-blockers at the CCTA had no significant effects on EF (p = 0.70), whereas HR was significantly decreased (p < 0.001). However, regular administration of ß-blockers increases the EF on CCTA. CONCLUSION: The administration of ß-blockers immediately before CCTA affects HR but not EF. Premedication with ß-blockers can be safely used for patients who undergo CCTA, and CCTA is useful for EF evaluation, independent of the use of ß-blockers.

Comparison of Liver Fibrosis and Function Indices with Extracellular Volume Using Dual-energy CT: A Retrospective Study.

BACKGROUND: Dual-Energy Computed Tomography (DECT) enables the direct measurement of iodine accumulation in the extracellular space. OBJECTIVE: To compare measures of liver fibrosis and function with Extracellular Volume (ECV) from iodine/water images using DECT. METHODS: Data was obtained from 119 consecutive patients who underwent abdominal DECT. A region of interest was set in the right lobe of the liver, pancreas, spleen, and aorta on iodine density images. ECV was calculated using the following formula: ECV = (1 - hematocrit) × [iodine concentration in the liver (or pancreas, spleen) / iodine concentration in the aorta]. The severity of liver fibrosis was estimated using the aminotransferase/platelet ratio index (APRI) and the Fibrosis-4 (FIB-4) index. Liver function was assessed by the Child-Pugh classification and albumin-bilirubin (ALBI) grade. Data were analyzed by the Spearman rank correlation coefficient, one-way analysis of variance, and post hoc analysis. RESULTS: The correlation between ECV and fibrosis indices (APRI and FIB-4) was only significant, with a weak magnitude for liver ECV quantification at the equilibrium phase (r=0.25 and r=0.20, respectively). The correlations between liver function index and ECV quantification were more robust than with fibrosis index. The highest correlations (r=0.50) were found between ALBI grade and liver ECV at the equilibrium phase. Liver ECV values at the equilibrium phase had a significant difference between ALBI grade 1 vs. 2 and grade 1 vs. 3. CONCLUSION: Liver ECV quantification by DECT is more suitable for evaluating liver function than liver fibrosis severity.

Giant esophageal hemangioma diagnosed by 99mTc-HSA-D scintigraphy following equivocal CT, MRI, and endoscopy.

Mediastinal cavernous hemangioma is a rare lesion requiring diagnosis without invasive procedure due to the risk of hemorrhage, which can be massive and even fatal. Here we describe the successful diagnosis of such a lesion using technetium-99m diethylenetriamine penta-acetic acid human serum albumin (99mTc-HSA-D) scintigraphy. A 36-year-old female with a 3-week back pain underwent endoscopic ultrasonography, contrast-enhanced CT, and MRI dynamic study which together revealed a submucosal tumor of the esophagus; likely to be either hemangioma or lymphangioma. Because of poor or no enhancement, it was impossible to distinguish the nature of the lesion. However, using delayed blood-pool imaging of 99mTc-HSA-D (at 40 minutes postinjection), and the characteristic accumulation, the tumor was clearly identifiable as an esophageal hemangioma. This case shows 99mTc-HSA-D scintigraphy to be an effective noninvasive imaging method to capture the characteristic hemodynamics of hemangioma.

Evaluation of abdominal hemodynamics through compressed sensing accelerated functional imaging.

PURPOSE: To compare the imaging characteristics of the volumetric-interpolated breath-hold examination (VIBE) using compressed-sensing (CS) acceleration (CS-VIBE) with the conventional sequence relying on parallel imaging to assess the potential use of CS-VIBE as a functional imaging technique for upper abdominal haemodynamics. MATERIALS AND METHODS: Patients (30 men, 27 women) suspected of having a hepatic disease underwent magnetic resonance imaging (MRI) of the liver, including a dynamic contrast-enhanced study. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid was used as the contrast agent. MRI data of two multi-phase breath-hold exams were used for intra-individual comparisons. The VIBE and CS-VIBE were performed on different days. Image quality in both sequences was qualitatively assessed by three experienced radiologists. Moreover, the contrast ratio (CR) of the aorta, portal vein, liver and pancreas to muscle tissue were measured as a quantitative assessment. For the CS-VIBE, a five-phase time-intensity curve (TIC) was created to evaluate haemodynamics. The measurement area included the pancreas, common hepatic artery, portal vein and superior mesenteric vein. The ratio of that area to the muscle tissue in the same cross section was used to create the TICs. RESULTS: The qualitative assessment showed that artefacts were significantly different between the VIBE and CS-VIBE sequences. This finding indicated that the conventional VIBE had fewer artefacts. The CR was significantly higher for the CS-VIBE than for the VIBE images in all phases (p < 0.001). An evaluation of haemodynamics compared with those obtained by CT angiography showed almost the same temporal characteristics in the common hepatic artery, portal vein and superior mesenteric vein signals as those in a previous study. CONCLUSION: Compared with the conventional VIBE, the CS-VIBE had significantly higher temporal resolution and higher image contrast. The temporal resolution of the CS-VIBE was sufficient for viewing abdominal haemodynamics. If the remaining limitation of acquisition speed for dynamic MRI can be adequately addressed, we believe that CS-VIBE functional images with high-contrast haemodynamics will be very useful in clinical practise.

Multiple Life-threatening Coronary Artery Spasms after Percutaneous Coronary Intervention for Acute Coronary Syndrome.

A 69-year-old man who had been hospitalized with acute coronary syndrome (ACS), underwent urgent percutaneous coronary intervention. In the subacute phase, he developed sudden chest pain and hemodynamic deterioration, and urgent coronary angiogram showed multiple coronary artery spasms. The discontinuation of beta-blocker treatment and the administration of a calcium antagonist helped prevent angina attacks. In Japanese patients who tend to have coronary artery spasm, the routine administration of beta-blockers for post-ACS patients with a preserved left ventricular systolic function should be considered carefully.

3D analysis of apparent diffusion coefficient histograms in hepatocellular carcinoma: correlation with histological grade.

BACKGROUND: To evaluate the usefulness of differentiation of histological grade in hepatocellular carcinoma (HCC) using three-dimensional (3D) analysis of apparent diffusion coefficient (ADC) histograms retrospectively. METHODS: The subjects consisted of 53 patients with 56 HCCs. The subjects included 12 well-differentiated, 35 moderately differentiated, and nine poorly differentiated HCCs. Diffusion-weighted imaging (b-values of 100 and 800 s/mm2) were obtained within 3 months before surgery. Regions of interest (ROIs) covered the entire tumor. The data acquired from each slice were summated to derive voxel-by-voxel ADCs for the entire tumor. The following parameters were derived from the ADC histogram: mean, standard deviation, minimum, maximum, mode, percentiles (5th, 10th, 25th, 50th, 75th, and 90th), skew, and kurtosis. These parameters were analyzed according to histological grade. After eliminating steatosis lesions, these parameters were re-analyzed. RESULTS: A weak correlation was observed in minimum ADC and 5th percentile for each histological grade (r = -0.340 and r = -0.268, respectively). The minimum ADCs of well, moderately, and poorly differentiated HCC were 585 ± 388, 411 ± 278, and 235 ± 102 × 10-6 mm2/s, respectively. Minimum ADC showed significant differences among tumor histological grades (P = 0.009). The minimum ADC of poorly differentiated HCC and that of combined well and moderately differentiated HCC were 236 ± 102 and 437 ± 299 × 10-6 mm2/s. The minimum ADC of poorly differentiated HCC was significantly lower than that of combined well and moderately differentiated HCC (P = 0.001). The sensitivity and specificity, when a minimum ADC of 400 × 10-6 mm2/s or lower was considered to be poorly differentiated HCC, were 100 and 54%, respectively. After exclusion of the effect of steatosis, the sensitivity and specificity did not change, although the statistical differences became strong (P < 0.0001). CONCLUSION: Minimum ADC was most useful to differentiate poorly differentiated HCC in 3D analysis of ADC histograms.

Diffusion-weighted imaging of the liver: Current applications.

Diffusion-weighted imaging (DWI) of the liver can be performed using most commercially available machines and is currently accepted in routine sequence. This sequence has some potential as an imaging biomarker for fibrosis, tumor detection/characterization, and following/predicting therapy. To improve reliability including accuracy and reproducibility, researchers have validated this new technique in terms of image acquisition, data sampling, and analysis. The added value of DWI in contrast-enhanced magnetic resonance imaging was established in the detection of malignant liver lesions. However, some limitations remain in terms of lesion characterization and fibrosis detection. Furthermore, the methodologies of image acquisition and data analysis have been inconsistent. Therefore, researchers should make every effort to not only improve accuracy and reproducibility but also standardize imaging parameters.

Radiotherapy in patients with extramammary Paget's disease--our own experience and review of the literature.

BACKGROUND: There are few reports on radiotherapy methods for treating extramammary Paget's disease (EMPD). The aim of this study was to explore the outcome of radiotherapy for EMPD. PATIENTS AND METHODS: Between June 1995 and October 2010, 14 patients with EMPD (7 male and 7 female; median age 77 years) underwent radiotherapy at the Tokyo Medical University Hospital. The median total irradiation dose was 50 Gy, delivered in 20-33 fractions. Case reports of patients with EMPD were obtained from the PubMed database for the period of 1991-2012. 66 patients (median age 73 years) were identified. Radiotherapy outcomes were analyzed. RESULTS: All patients achieved complete response within the irradiated volume during a median observation period of 71.4 months. The 5-year locoregional progression-free survival and overall survival were 91.7% (95% confidence interval (CI) 53.9-98.8%) and 84.3% (95% CI 50.3-95.8%), respectively. From the PubMed database, the 5-year local progression-free survival and locoregional progression-free survival were 84.5% (95% CI 65.3-93.6%) and 77.5% (95% CI 57.3-89.0%), respectively. 12 (18%) patients had a recurrence in the inguinal lymph nodes. CONCLUSION: Radiotherapy yielded good local control and survival, which suggests that it was effective for patients with EMPD and in particular medically inoperable EMPD.

Cryptogenic organizing pneumonia associated with radiation: A report of two cases.

Cryptogenic organizing pneumonia (COP) following radiotherapy is occasionally diagnosed as radiation pneumonitis or bacterial pneumonia. The current study presents two cases of COP following radiotherapy: A 48-year-old premenopausal female with breast cancer and an 84-year-old male with non-small cell lung cancer. In the cases of breast cancer and lung cancer, patients were first diagnosed with bacterial pneumonia and radiation pneumonitis, respectively. In the two cases, computed tomography disclosed the migration of ground glass shadows, which were finally resolved without any fibrotic changes. The two cases were finally diagnosed as COP associated with radiotherapy. When an infiltrating shadow is present outside of the irradiated field, COP must be included in the differential diagnosis.

Tumor response after low-dose preoperative radiotherapy combined with chemotherapy for squamous cell esophageal carcinoma.

AIM: Patients with T3 or more squamous cell esophageal cancer underwent low-dose preoperative radiotherapy with chemotherapy, to reduce local recurrence, followed by surgery. The aim was to ascertain tumor response and assess prognostic factors. PATIENTS AND METHODS: Between May 2002 and June 2011, 37 consecutive patients with esophageal cancer underwent chemoradiotherapy followed by surgery. The numbers of patients in clinical stages IIA/IIIA/IIIB/IIIC were 2/24/7/4, respectively. All were given a dose of 30 Gy in 15 fractions, with concurrent chemotherapy using cisplatin and fluorouracil. Curative surgery was performed a median of 1.2 months after completion of chemoradiotherapy. RESULTS: Based on the findings from surgery, 26 patients (70%) achieved a stage reduction and six patients (16%) had a complete pathological response. The numbers of patients undergoing resections microscopically complete, with microscopically positive margins, and macroscopically positive margins were 33, 3, and 1, respectively. During a median follow-up period of 22.5 months, the two-year progression-free survival and overall survival were 62.1% [95% confidence interval (CI)=45.8 to 78.4%] and 71.9% [95% CI=55.1 to 88.7%], respectively. Statistically significant prognostic factors for overall survival were age [hazard ratio=6.6; 95% CI=1.1 to 38; p=0.04] and pathological T factor [hazard ratio=10.2; 95% CI=1.4 to 77; p=0.02]. No patients died as a result of surgery. CONCLUSION: Seventy percent of patients with esophageal cancer who received radiotherapy dose of 30 Gy in 15 fractions combined with chemotherapy achieved a stage reduction with low toxicity.

Preliminary results of radiotherapy for primary intraocular non-Hodgkin lymphoma.

This study aimed to retrospectively evaluate the efficacy of radiotherapy for primary intraocular non-Hodgkin lymphoma (PIOL). Between May 1998 and October 2010, 22 immunocompetent patients (four men, 18 women; median age 70 years, range 53-79 years) were diagnosed with PIOL. Magnetic resonance imaging showed no intracranial involvement in any patient. Patients received radiotherapy at a median total dose of 30 Gy (range 30-40 Gy). Three-year overall survival, progression-free survival and local control rates were 89% (95% confidence interval [CI]: 75, 103), 49% (95% CI: 24, 73) and 95% (95% CI: 86, 105) over a median of 36 months of observation, respectively. Twelve patients (55%) had intracranial relapse at a median of 28 months after initiation of radiotherapy. Visual acuity improved or was stable in 81% of treated eyes. The only grade ≥ 3 toxicity was cataract formation (five patients). Radiotherapy without chemotherapy for PIOL achieved high local control rates with acceptable toxicities.

Significance of the number of brain metastases for identifying patients who don't need whole brain radiotherapy: implication as oligometastases of the brain.

BACKGROUND AND PURPOSE: To investigate the significance of the number of brain metastases in the treatment with stereotactic radiotherapy (SRT) with or without whole brain radiotherapy (WBRT). MATERIAL AND METHODS: Between February 2003 and October 2010, 218 consecutive patients with brain metastases who underwent SRT alone or WBRT plus SRT were investigated. The prognostic factors affecting overall survival and brain progression-free survival were analyzed by multivariate and univariate analysis. By logistic regression analysis, factors associated with the number recurrences of brain metastasis after SRT were also investigated. RESULTS: The median overall and brain progression-free survivals were 7.2 months and 4.3 months, respectively. Significant prognostic factors for overall survival in multivariate analyses were performance status (hazard ratio [HR] = 1.71, 95% confidence interval [CI] 1.13-2.57, p = 0.01) and the number of brain metastases (HR = 1.75, 95% CI 1.08-2.83, p = 0.02). Cut-off line of the number of brain metastases was between 3 and 4, and 3 or fewer brain metastases were significantly better than 4 or more in prognosis by univariate and multivariate analysis (p < 0.01, p = 0.02). CONCLUSIONS: The patients with 3 or fewer brain metastases were associated with brain progression free survival and 3 or fewer brain relapse. Repeated SRT without WBRT may be effective for patients with 3 or fewer brain metastases.

Preliminary results of fractionated stereotactic radiotherapy after cyst drainage for craniopharyngioma in adults.

PURPOSE: To retrospectively evaluate the effectiveness of fractionated stereotactic radiotherapy (FSRT) for craniopharyngioma. METHODS AND MATERIALS: Between 1999 and 2005, 16 patients with craniopharyngioma were referred to Tokyo Medical University Hospital. They received FSRT alone after histologic confirmation by needle biopsy and underwent cyst drainage via endoscopy. The median prescription dose fraction was 30 Gy in six fractions. All patients except 1 were followed up until December 2009 or death. RESULTS: The median follow-up period was 52 months (range, 4-117 months). Of the 17 patients, 3 experienced recurrence 4 to 71 months after FSRT. The 3-year local control rate was 82.4%. One patient died of thyroid cancer, and the 3-year survival rate was 94.1%. Eight patients had improved visual fields at a median of 2.5 months after FSRT, but hormonal functions did not improve in any patient. CONCLUSIONS: FSRT after cyst drainage seems to be safe and effective for patients with craniopharyngiomas, and it may be a safe alternative to surgery.