Prognostic prediction using maximum standardized uptake value ratio of lymph node-to-primary tumor in preoperative PET-CT for oral squamous cell carcinoma.

This study aimed to calculate the ratio of maximum standardized uptake values of cervical lymph nodes to maximum standardized uptake values of primary tumors measured by preoperative fluorodeoxyglucose positron-emission tomography in oral cancer patients, and to retrospectively examine the prognostic association and evaluate whether it could be a prognostic factor. We retrospectively examined consecutive Japanese patients diagnosed with oral squamous cell carcinoma who underwent oral cancer resection and cervical dissection between January 2014 and December 2018. The study included 52 patients aged 39-89 years (median age 66.5 years), excluding non-cervical dissection surgery and/or non-underwent preoperative positron-emission tomography. The maximum standardized uptake value of the cervical lymph nodes and primary tumor was measured, and the ratio of maximum standardized uptake values of the lymph nodes to that of the primary tumor was calculated. The median follow-up of 52 patients was 1,465 days (198-2,553 days), and overall survival was significantly worse in patients with a high lymph node-to-tumor standardized uptake values ratio (>0.4739) (5 years, 58.8% vs. 88.2%; P<0.05). Pretreatment lymph node-to-tumor standardized uptake values ratio can be easily calculated, and as a predictor of prognosis, it may be of assistance when considering the treatment strategy for oral cancer.

[False-Positive ¹²³I-Metaiodobenzylguanidine Scan in a Patient with Adrenocortical Cancer].

A 59-year-old woman presented with a left adrenal tumor 4 cm in diameter. The ¹²³I-metaiodobenzylguanidine (MIBG) scintigraphy showed apparent accumulation in the left adrenal tumor. However, the patient had no sign or symptoms suggesting pheochromocytoma. No biochemical evidence of catecholamine excess was noticed. Computed tomography (CT) revealed relatively strong enhancement in the arterial phase, which persisted until the portal phase. The computed tomography (CT) and magnetic resonance imaging showed 2 liver nodule suspected to be metastatic tumors. No ¹²³I-MIBG accumulation was seen in these nodules. CT also showed thyroid nodules with calcification, which suggested papillary thyroid cancer. Based on the findings, open left adrenalectomy, partial hepatectomy and segmentectomy were performed under the clinical diagnosis of pheochromocytoma and metastatic liver tumors. Histopathological diagnosis was adrenocortical cancer. There was only lymphocyte infiltration in the liver nodules. Postoperative recovery was uneventful, and the patient underwent partial thyroidectomy 6 months later. The pathological diagnosis was papillary thyroid cancer. She has been without recurrence or metastases for 18 months after adrenalectomy. We found only 6 cases of MIBG scintigraphy-positive adrenocortical cancer in the literature. The mechanisms for MIBG uptake in adrenocortical cancer are discussed with a review of the literature.

Ovarian and non-ovarian teratomas: a wide spectrum of features.

Teratoma is a germ cell tumor (GCT) derived from stem cells of the early embryo and the germ line. Teratoma is the most common neoplasm of the ovaries and is usually diagnosed easily using imagings by detecting fat components. However, there are various histopathological types and the imaging findings differ according to the type. Teratoma usually occurs in the gonads or in the midline due to migration of primordial germ cells during development. The clinical course of teratomas depends on the age of the patient, histological type, and anatomical site. Sometimes teratomas show unusual manifestations, such as mature teratoma without demonstrable fat components, torsion, rupture, growing teratoma syndrome, anti-N-methyl-D-aspartate receptor encephalitis, and autoimmune hemolytic anemia. For all of these reasons, teratomas demonstrate a wide spectrum of imaging features and radiologists should be familiar with these variabilities. The present article aims to introduce a model encompassing types of GCTs based on their developmental potential, and to review several histopathological types in various anatomical sites and unusual manifestations of teratomas, with representative imaging findings.

FDG-PET/CT Demonstrates Splenic Angiosarcoma Bone Marrow Metastasis.

Some patients with splenic angiosarcoma initially manifest thrombocytopenia owing to hypersplenism or tumor-related bone marrow fibrosis. The diagnosis of bone marrow metastasis in patients with splenic angiosarcoma is challenging, as the presentation mimics idiopathic thrombocytopenic purpura or primary myelofibrosis. Our case showed diffuse FDG uptake in the vertebral bodies, sacroiliac bone, humerus, femur, and clavicles. It was pathologically diagnosed as bone marrow metastasis of splenic angiosarcoma. We believe that the heterogeneous FDG accumulation in the bone marrow, although nonspecific, can be useful for the diagnosis of the bone marrow metastasis in patients with splenic angiosarcoma.

Clinical usefulness of temporal subtraction CT in detecting vertebral bone metastases.

PURPOSE: The purpose of this study was to determine whether temporal subtraction (TS) computed tomography (CT) contributes to the detection of vertebral bone metastases. METHOD: The calculation of TS CT was composed of bony landmark detection, bone segmentation with a multiatlas-based method, and spatial registration. Temporal increase and decrease of the CT values were visualized in blue and red, respectively. Paired CT images of 20 patients with cancer and newly-developed vertebral metastases were analyzed. Control CT examinations of 20 different patients were also included. The presence of vertebral metastases on the TS CT was evaluated by two board-certified radiologists. Five additional board-certified radiologists and five radiology residents independently interpreted the 40 paired CT images with and without TS CT. RESULTS: In the lesion conspicuity evaluation, 96% of vertebral metastases were scored as excellent or good. In the image interpretation examination, according to free-response receiver operating characteristics analysis, the overall figure of merit (FOM) of the board-certified radiologist group was 0.892 and 0.898 with and without TS CT, respectively. The FOM of the resident group improved from 0.849 to 0.902 with viewing TS CT. In the sub-analysis focusing on the location of the lesion, the FOM of the resident group significantly improved from 0.75 to 0.92 in vertebral arch lesions (p = 0.001). CONCLUSIONS: The TS CT may be useful to detect vertebral metastases because almost all the vertebral metastases were shown to be favorable visualization. The TS CT was proven to be especially helpful for radiology residents in detecting vertebral arch metastases.

Phase I/IIa PET imaging study with 89zirconium labeled anti-PSMA minibody for urological malignancies.

OBJECTIVE: We conducted the present phase I/IIa positron emission tomography (PET) imaging study with 89Zr conjugated with desferroxamine-IAB2M (89Zr-Df-IAB2M), an anti-prostate-specific membrane-antigen minibody, to assess its safety and feasibility in patients with urological cancer. METHODS: 89Zr-Df-IAB2M was synthetized by IBA Molecular (Somerset, NJ, USA) and transported by air to Tsukuba Molecular Imaging Center (Tsukuba, Ibaraki, Japan).17 patients received 74 MBq (2 mCi) of 89Zr-Df-IAB2M at total mass doses of 10 mg. Whole-body and plasma clearance, normal-organ and lesion uptake, and radiation absorbed dose were estimated. We also preliminarily tested the performance of 89Zr-immuno-PET imaging for 13 patients with prostate cancer and 4 patients with other urological cancer. RESULTS: The administration of 89Zr-Df-IAB2M was well-tolerated, and no infusion-related reactions were observed in any patient. No adverse events were noted in the laboratory parameters, vital signs, or other parameters. The plasma clearance was biphasic, with an initial rapid phase (t 1/2 fast: 10.1 ± 3.4 h) followed by a slow phase (t 1/2 slow: 49.0 ± 22.7 h). The half-life of radioactivity in the whole body (WB t1/2) was 237 ± 9 h. The highest absorbed radiation dose was 1.67 mGy/MBq, observed in the liver and kidney. The effective dose was 0.68 ± 0.08 mSv/MBq. The radiation dose rate at 0.5 m distance from the patient was 8.67 µSv/h on day 1, and decreased to 2.26 µSv/h at 5 days after injection. Both bone and lymph node metastases were detected with 89Zr-Df-IAB2M by 24 or 48 h imaging. CONCLUSIONS: Administration of 89Zr-Df-IAB2M was well-tolerated and safe in terms of adverse events and radiation exposure and protection. 89Zr-Df-IAB2M is feasible for usage by long-distance transportation. Further studies are warranted for analysis of its use for tumor lesion detection (UMIN000015356).

Pharmacokinetic Analysis of Intraocular Penetration of Latanoprost Solutions with Different Preservatives in Human Eyes.

PURPOSE: To investigate the effect of excipients on latanoprost penetration into the aqueous humor with clinically available 6 products with different solutions mainly in the types and concentrations of preservatives. METHODS: In 363 patients with cataracts, we instilled 1 latanoprost drop in 1 eye before surgery. The drop was randomly selected by brand name product (A) and 5 generic products (B-F) composed with different excipients. B contains similar excipients to A. C and D contain lower concentrations of benzalkonium chloride than A. E includes sodium benzoate, and F contains no preservatives. At 0.5-1, 3, and 6 h after instillation, samples of aqueous humor were collected to determine the latanoprost free acid by mass spectrometry. The time course of intraocular concentration and the areas under the aqueous humor latanoprost free acid concentration-time curves (AUCs) were calculated. RESULTS: At 0.5-1 h, the aqueous humor concentration of latanoprost free acid was 8.5 ± 1.0 ng/mL for C, which was significantly higher (P < 0.01) than that of A (3.4 ± 0.5 ng/mL). At 3 and 6 h, however, no significant difference was noted in the concentrations of latanoprost free acid between the brand name and generic products. For each of the generic products, the peak free acid concentration was above the known threshold concentration for biological activity. At 6 h postdose, however, the levels of latanoprost free acid were below the threshold for Products C, E, and F. Comparisons of AUC0-6h and AUC0-24h values showed that these parameters were the greatest with A, and E was significantly inferior to A (P < 0.05). CONCLUSIONS: Currently available latanoprost solutions with different preservatives showed sufficient intraocular concentration to activate the FP receptor, but different pharmacokinetic profiles of absorption or elimination.

The association between structure-function relationships and cognitive impairment in elderly glaucoma patients.

Accurate measurement of visual field (VF) is important in accessing glaucoma, however this may not be achieved in patients with dementia or mild cognitive impairment (CI). We investigated the association between CI and structure-function relationships in elderly glaucoma patients. The study included 94 eyes of 51 glaucoma patients aged ≥75 years with no diagnoses of dementia. CI was assessed using the Mini Mental State Examination (MMSE). Using the leave-one-out cross-validation, the mean deviation (MD) of the Humphrey 30-2 VF was predicted from measurements of optical coherence tomography, and the relationship between the squared prediction error and the MMSE score, together with age, fixation loss (FL), false positive (FP), and false negative (FN) percentages that were analyzed using the linear mixed model. A high prevalence of MCI or dementia was observed in the elderly population. The squared prediction error value of the MD was 17.0 ± 21.1 (mean ± standard deviation). The squared prediction error increased with decreasing MMSE total score, but age, FL, FP, and FN were not related. Careful consideration is needed when interpreting the VF results of these patients, because VF can be over- or underestimated, as suggested by the decreased structure-function relationships.

Enlargement of the brachial plexus on magnetic resonance imaging: a novel finding in adult-onset Krabbe disease.

Adult-onset Krabbe disease is an autosomal recessive degenerative leukodystrophy that presents with bilateral corticospinal tract involvement on MRI. Although peripheral nerve involvement is a known manifestation of Krabbe disease, MRI findings of peripheral nerve abnormalities are limited to the cranial nerves and spinal nerve roots. In this case report, we discuss two cases of adult-onset Krabbe disease with brachial plexus enlargement on MRI. Adult-onset Krabbe disease should be included in the differential diagnoses when brachial plexus enlargement and white matter lesions involving corticospinal tracts present simultaneously.

Small Cell Type of Esophageal Neuroendocrine Carcinoma Resembling a Submucosal Tumor.

We report a rare case of primary small cell type esophageal neuroendocrine carcinoma with a unusual endoscopic form similar to a submucosal tumor with the results of the histological and immunohistochemical analyses. A 57-year-old woman with dysphagia was referred to our hospital for further examination and treatment, and was diagnosed as type 1s esophageal carcinoma in the middle thoracic esophagus. Endoscopy revealed a protruding esophageal carcinoma resembling a submucosal tumor with an irregular and nodular surface covered by non-neoplastic epithelium stained with iodine. Analysis of the esophageal biopsy specimen revealed poorly differentiated squamous cell carcinoma. Based on a diagnosis of type 1s carcinoma in the middle thoracic esophagus that was 5 cm in size longitudinally, a radical esophagectomy with three-field lymph node dissection was performed. The pathological examination with histological and immunohistochemical analysis of the resected specimen revealed a small cell type neuroendocrine carcinoma overlaid by a non-neoplastic epithelium, extending into the adventitia without lymph node metastasis (T3, N0, M0, Stage II). However, multiple metastases in the brain and lung developed 3 months postoperatively, and the patient died of the cancer 7 months after the operation. This was a rare case of a highly malignant primary small cell type esophageal neuroendocrine carcinoma showing extremely rare form.

Small Intestinal Metastasis from Esophageal Squamous Cell Carcinoma Presenting with Perforated Peritonitis.

Metastatic tumors of the small intestinal tract from extra-abdominal sites are rare. We report herein a rare case of small intestinal metastasis from esophageal carcinoma that presented with perforated peritonitis. A 71-year-old man with dysphagia was referred to our hospital for further examination and treatment, and was diagnosed with type 3 advanced esophageal squamous cell carcinoma of the lower thoracic esophagus. Based on a diagnosis of Stage II cancer, a radical esophagectomy with three-field lymph node dissection was performed after neoadjuvant chemotherapy composed of 5-fluorouracil plus cisplatin. Pathological examination of the resected specimen revealed a moderately differentiated squamous cell carcinoma, extending into the adventitia with lymph node metastasis (T3, N2, M0, Stage III). During postoperative adjuvant chemotherapy, the patient complained of abdominal pain and was found to have perforated peritonitis. Emergency laparotomy was performed. A jejunal perforation with a submucosal nodule approximately 80 cm distal from the ligament of Treitz was detected, and completely resected by jejunal partial resection. Histopathology of the specimen showed a perforation of the small intestine due to metastasis of esophageal squamous cell carcinoma with mesenteric lymph node metastasis. The patient died of cancer 9 months after surgery. An extremely rare case of small intestinal metastasis from esophageal carcinoma presenting with perforated peritonitis was described.

[The Development of a Normal Database of Elderly People for Use with the Statistical Analysis Software Easy Z-score Imaging System with 99mTc-ECD SPECT].

We created a new normal database of elderly individuals (Tsukuba-NDB) for easy Z-score Imaging System (eZIS), a statistical imaging analysis software, comprised of 44 healthy individuals aged 75 to 89 years. The Tsukuba-NDB was compared with a conventional NDB (Musashi-NDB) using Statistical Parametric Mapping (SPM8), eZIS analysis, mean images, standard deviation (SD) images, SD values, specific volume of interest analysis (SVA). Furthermore, the association of the mean cerebral blood flow (mCBF) with various clinical indicators was statistically analyzed. A group comparison using SPM8 indicated that the t-value of the Tsukuba-NDB was lower in the frontoparietal region but tended to be higher in the bilateral temporal lobes and the base of the brain than that of the Musashi-NDB. The results of eZIS analysis by Musashi-NDB in 48 subjects indicated the presence of mild decreases in cerebral blood flow in the bilateral frontoparietal lobes of 9 subjects, precuneus and posterior cingulate gyrus of 5 subjects, lingual gyrus of 4 subjects, and near the left frontal gyrus, temporal lobe, superior temporal gyrus, and lenticular nucleus of 12 subjects. The mean images showed that there were no visual differences between both NDBs. The SD images intensities and SD values were lower in Tsukuba-NDB. Clinical case comparison and visual evaluation demonstrated that the sites of decrease in blood flow were more clearly indicated by the Tsukuba-NDB. Furthermore, mCBF was 40.87 ± 0.52 ml/100 g/min (mean ± SE), and tended to decrease with age. The tendency was stronger in male subjects than female subjects. Among various clinical indicators, the platelet count was statistically significantly correlated with CBF. In conclusion, our results suggest that Tsukuba-NDB, which is incorporated into a statistical imaging analysis software, eZIS, is sensitive to changes in cerebral blood flow caused by Cranial nerve disease, dementia and cerebrovascular accidents, and can provide precise diagnosis of these brain diseases in the rapidly aging Japanese population.

[Predisposition to latex allergy undetected on preoperative evaluation: a case report].

A 70-year-old man was scheduled to undergo laparoscopic total gastrectomy for stomach cancer. He had no history of atopy, fruit allergies, or frequent exposure to natural rubber. Preoperative latex-specific IgE antibodies were negative. Anesthesia was induced, and the surgery was started uneventfully. Soon after the surgeon had begun to manipulate the intestine, the blood pressure suddenly dropped to 27/21 mmHg. Facial flushing was also observed. Anaphylactic shock caused by latex was strongly suspected, and surgery was immediately halted. The surgical gloves were changed to latex-free ones, and adrenaline was administered. The blood pressure was gradually normalized within 30 min, and the facial flushing mostly disappeared. Postoperative laboratory examination revealed that serum tryptase had increased to 34.4 microg l-1, 40 minutes after the onset of anaphylaxis, and decreased to 19.4 microg l-1, 24 hours than later. Latex-specific IgE antibodies and a prick test with latex were both positive. Consequently, the diagnosis of latex-induced anaphylactic reaction was confirmed. Because even detailed questioning and examination does not always identify such a predisposition, avoiding contactwith latex products is more rational exhaustively checking every preoperative patient for latex allergy

[Suspected diltiazem intoxication resulting in repeated asystole after the induction of anesthesia].

We present a case of diltiazem intoxication resulting in repeated asystole after the induction of anesthesia. A 39-year-old man was diagnosed as subarachnoid hemorrhage, and cerebral aneurysm clipping was scheduled on the next day. Electrocardiogram revealed normal sinus rhythm with complete right bundle branch block. Continuous intravenous administration of diltiazem, nicardipine and midazolam were started for intractable hypertension and tachycardia. In the operating room, electrocardiogram showed atrioventricular nodal rhythm. Nicardipine and midazolam were stopped and anesthesia was induced with thiamylal, fentanyl and vecuronium, and was maintained with sevoflurane. After tracheal intubation, the patient developed asystole, and cardiopulmonary resuscitation was provided immediately. Diltiazem was stopped. Cardiac rhythm was restored 8 min afterwards; however, asystole recurred six times. Temporary cardiac pacing was effective, and percutaneous cardiopulmonary support (PCPS), intraaortic balloon pumping (IABP), and continuous hemodiafiltration (CHDF) were initiated. The operation was canceled. On the next day, normal sinus rhythm was restored and the temporary pacing, PCPS, IABP, and CHDF were discontinued. Cerebral aneurysm was treated by endovascular coiling and the patient was discharged from the hospital without sequelae. This case illustrates asystole associated with diltiazem intoxication. It is necessary to consider this potential complication when diltiazem is used.

Clinical value of FDG-PET for preoperative evaluation of endometrial cancer.

OBJECTIVE: Whole body positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) has been widely used in various malignancies, but the clinical value of FDG-PET for endometrial cancer has not been fully investigated. The purpose of this study was to evaluate the usefulness of FDG-PET for preoperative evaluation of endometrial cancer. METHODS: Forty female patients suspected of having endometrial cancer were included in this study. All patients underwent an FDG-PET or PET/CT scan, and images were interpreted visually. The diagnostic performance in detecting the primary tumor, regional nodal status, and distant metastasis was determined. In addition, the usefulness of PET was assessed in terms of additional information and clinical impact for therapeutic management. RESULTS: Of 40 patients, 30 were histologically confirmed to have endometrial cancer. The patient-based sensitivity and specificity of FDG-PET for primary tumors were 83 and 100%, respectively, and 100 and 100%, respectively, for nodal metastases. There were 12 distant metastases in 6 patients and two second primary cancers in two patients, which were all accurately diagnosed by PET on a patient-basis. PET yielded 12 additional findings in 10 patients, and had a bearing on the therapeutic management of four patients, including one patient with recurrent breast cancer. CONCLUSIONS: FDG-PET had a reasonably high diagnostic accuracy in endometrial cancer. Although the number of cases with clinical impact was limited, additional information by PET was obtained in one-third of the cases.

The contribution of peripheral stem-loops to the catalytic activity of archaeal RNase P RNA from Pyrococcus horikoshii OT3.

We investigated the contribution of peripheral stem-loops to the catalytic activity of an archaeal RNase P RNA, PhopRNA, from Pyrococcus horikoshii OT3. PhopRNA mutants, in which the stem-loops were individually deleted, were prepared and characterized with respect to precursor tRNA (pre-tRNA) cleavage activity in the presence of five RNase P proteins. All the mutants retained the activity to some extent, indicating that they are moderately implicated in catalysis. Further characterization suggested that the stem-loops serve largely as binding sites for the proteins, and that their interactions are predominantly involved in stabilization of the active conformation of PhopRNA.

Prevalence of positive FDG-PET findings in patients with high CEA levels.

OBJECTIVE: The purpose of this study was to evaluate the prevalence of positive findings of positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose (FDG) in patients with high serum CEA levels. METHODS: A total of 303 patients who had undergone an FDG-PET scan in our institution with high serum CEA levels were analyzed. The prevalence of positive PET findings was evaluated with regard to a previous history of malignancy, absolute value of CEA levels, and the time course of CEA levels (an increasing or decreasing pattern, a change divided by time (DeltaCEA) and doubling time of CEA). RESULTS: Of 303 patients, 232 were confirmed to have malignancy, and the patient-based sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of PET were 87, 86, 95, 66, and 86%, respectively. There was no statistically significant difference in positive rates according to the history of previous malignancy. The prevalence of PET-positive cases was higher with an increase in absolute CEA levels, and more than 90% of the patients were positive when CEA levels were more than 20 ng/ml. The DeltaCEA was significantly higher and the doubling time was significantly shorter in patients with positive results than those with negative results. CONCLUSIONS: A high value of serum CEA levels was correlated with a higher prevalence of positive PET findings. FDG-PET scans would be justified in patients with high serum CEA levels, regardless of whether there was or was not a previous history of malignancy.

Archaeal homologs of human RNase P protein pairs Pop5 with Rpp30 and Rpp21 with Rpp29 work on distinct functional domains of the RNA subunit.

We examined the functional equivalency between Escherichia coli RNase P protein (C5) and Pyrococcus horikoshii RNase P proteins (PhoPop5, PhoRpp21, PhoRpp29, PhoRpp30, and PhoRpp38) for RNase P activity. The C5 protein and P. horikoshii RNase P proteins were unable to activate non-congnate RNase P RNAs, P. horikoshii RNase P RNA (PhopRNA) and E. coli RNase P RNA (M1 RNA) respectively. Two chimeric RNAs, in which functional C- and S-domains of M1 RNA and PhopRNA were exchanged, were prepared and characterized with respect to the cleavage of P. horikoshii pre-tRNA(Tyr) in the presence of C5 or P. horikoshii proteins. The results suggest that PhoPop5 and PhoRpp30 function equivalently to the C5 protein in the E. coli RNase P, being involved in activation of the PhopRNA C-domain. On the other hand, PhoRpp21 and PhoRpp29 are implicated in stabilization of the PhopRNA S-domain.

Inhomogeneous bone marrow uptake caused by G-CSF mimics multiple bone metastases on FDG-PET.

Administration of granulocyte colony stimulating factor can cause homogeneous hypermetabolic activity of bone marrow in positron emission tomography using F-18-fluorodeoxyglucose. We report a case in which positron emission tomography demonstrated multiple foci of hypermetabolic activity in the bone marrow, which was considered an early effect of granulocyte colony stimulating factor, and not multiple osseous metastases.