A rare case of Helicobacter pylori-uninfected intramucosal poorly differentiated adenocarcinoma that occurred in the gastric fornix.

We report a rare case of undifferentiated-type intramucosal gastric cancer that occurred in the fornix of the stomach without Helicobacter pylori infection, which consisted mainly of poorly differentiated adenocarcinoma. A 49-year-old man visited our hospital for a follow-up endoscopic examination of a small depressed lesion of the gastric fornix detected by surveillance esophagogastroduodenoscopy. On magnifying endoscopy with blue laser imaging, the depressed lesion (approximately 10 mm in diameter) was regarded as undifferentiated-type early gastric cancer that proved to be a poorly differentiated adenocarcinoma by histological examination of biopsied specimens. The cancerous lesion was successfully treated with endoscopic submucosal dissection and microscopically showed an intramucosal cancer that invaded the whole mucosal layer with predominant growth of a poorly differentiated adenocarcinoma component. The patient status was verified as Helicobacter pylori-naïve according to the strict diagnostic criteria, thereby confirming this case as an undifferentiated-type Helicobacter pylori-uninfected gastric cancer. Helicobacter pylori-uninfected intramucosal poorly differentiated adenocarcinoma occurring in the gastric fornix has not been previously reported.

Evaluation and treatment results of trimodality therapy for advanced esophageal squamous cell carcinoma.

OBJECTIVES: The prognosis for highly advanced esophageal squamous cell carcinoma (ESCC) remains poor, and there is currently no standard treatment. The purpose of this study was to examine the benefits of trimodality therapy [chemoradiation plus surgery, (CRT + S)] by evaluating the surgical outcomes of patients with ESCC in Keiyukai Sapporo Hospital, Japan. We assessed the preoperative and postoperative adverse events, treatment effects of preoperative CRT, metastatic diagnosis of the dissected lymph nodes, and survival. PATIENTS AND METHODS: Between 2012 and 2018, 148 patients with highly advanced ESCC who underwent preoperative CRT + S were analyzed for diagnosis and staging, preoperative complications, clinical and histopathological effects of CRT in the resected specimens, survival rates, and recurrences. RESULTS: The grade 3 and higher complications of preoperative CRT were neutropenia in 3 cases and thrombocytopenia in 1 case. Among the postoperative complications, there were 2 cases (1.4%) of direct surgical death, only tracheobronchial bleeding and liver failure. Using the 11th edition of the classification of esophageal cancer by the Japanese Esophageal Society, 60 patients (40.5%) were classified as grade 3 (negative for cancer cells, pathological complete response). However, 20 of them (33.3%) had metastatic tumor cells in the lymph nodes. The overall 5-year survival rate was 58.5%. Including references to the pathological findings and recurrence patterns, there is no effective diagnostic method for selecting the subsequent approach based on the effectiveness of CRT. CONCLUSION: Planned surgery following CRT was the only solution for achieving better treatment results. CRT + S is a promising treatment with low direct surgical mortality.

Prognosis and prognostic factors of esophageal spindle cell carcinoma treated by esophagectomy: a retrospective single-institution analysis.

BACKGROUND: Esophageal spindle cell carcinoma (ESpCC) is a malignant tumor composed of sarcomatous components. ESpCC is treated as a squamous cell carcinoma. However, because ESpCC is a rare tumor, little is known regarding its prognosis. This study aimed to analyze patients with ESpCC who were surgically treated at our hospital, determine the validity of surgery, and identify factors that indicate a prognosis. METHODS: Treatment characteristics, overall survival (OS), and recurrence-free survival (RFS) of 28 patients with ESpCC who underwent surgery at our hospital between 1990 and 2016 were assessed. Furthermore, factors associated with OS and RFS were analyzed. RESULTS: Subtotal esophagectomy with 3-field lymph node dissection and lower esophagectomy with 2-field lymph node dissection were performed in 25 and 3 patients, respectively. Chemotherapy was administered as preoperative therapy to two patients. Postoperative therapy, comprising radiotherapy and chemotherapy, was administered to three and nine patients, respectively. The 3- and 5-year RFS were 66.4% and 61.6% and the 3- and 5-year OS were 73% and 61.9%, respectively. Macroscopic type was identified as a prognostic factor. In terms of OS, prognosis was significantly worse in ulcerative-type ESpCC than in the polypoid type. CONCLUSION: The 5-year OS of ESpCC mainly treated with surgical therapy was 61.9%. However, prognosis was poor in some patients with ulcerative-type ESpCC according to macroscopic type. In the future, it will be necessary to accumulate more cases and investigate therapeutic strategies added to surgery to improve prognosis.

Prognostic factors of adenoid cystic carcinoma of the head and neck in carbon-ion radiotherapy: The impact of histological subtypes.

PURPOSE: The aim of this study was to evaluate the effect of histological subtypes of head and neck adenoid cystic carcinoma (ACC) on the results of carbon-ion radiotherapy (CIRT). MATERIAL AND METHODS: Of the 113 patients with ACC who were treated with CIRT between December 2006 and July 2013, 100 patients with identified histological subtypes were enrolled in this study. CIRT at a total dose of 57.6 or 64.0Gy (RBE) was administered in 16 fractions. Histological grading was defined as the presence or absence of a solid growth pattern. RESULTS: Median follow-up was 60 months. 5-Year local control (LC), overall survival (OS) and distant metastasis free survival (DMFS) of all patients were 68.6%, 74.8% and 65.7%, respectively. On multivariate analysis, the prescribed dose (p=0.001) and gross tumor volume (p=0.002) were significant independent risk factors for LC. No significant difference for local control of solid/non-solid growth patterns was found (p=0.093). Solid growth pattern was an independent risk factor for both OS (p=0.033) and DMFS (p=0.024). CONCLUSIONS: CIRT appears able to locally control solid growth pattern ACC in the head and neck. Improved intervention is needed to extend DMFS and OS.

Association of Fusobacterium nucleatum with clinical and molecular features in colorectal serrated pathway.

Human gut microbiota is being increasingly recognized as a player in colorectal cancers (CRCs). Evidence suggests that Fusobacterium nucleatum (F. nucleatum) may contribute to disease progression and is associated with CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) in CRCs; however, to date, there are no reports about the relationship between F. nucleatum and molecular features in the early stage of colorectal tumorigenesis. Therefore, we investigated the presence of F. nucleatum in premalignant colorectal lesions. In total, 465 premalignant lesions (343 serrated lesions and 122 non-serrated adenomas) and 511 CRCs were studied. We determined the presence of F. nucleatum and analyzed its association with molecular features including CIMP, MSI and microRNA-31 status. F. nucleatum was detected in 24% of hyperplastic polyps, 35% of sessile serrated adenomas (SSAs), 30% of traditional serrated adenomas (TSAs) and 33% of non-serrated adenomas. F. nucleatum was more frequently detected in CIMP-high premalignant lesions than in CIMP-low/zero lesions (p = 0.0023). In SSAs, F. nucleatum positivity increased gradually from sigmoid colon to cecum (p = 0.042). F. nucleatum positivity was significantly higher in CRCs (56%) than in premalignant lesions of any histological type (p < 0.0001). In conclusion, F. nucleatum was identified in premalignant colorectal lesions regardless of histopathology but was more frequently associated with CIMP-high lesions. Moreover, F. nucleatum positivity increased according to histological grade, suggesting that it may contribute to the progression of colorectal neoplasia. Our data also indicate that F. nucleatum positivity in SSAs may support the "colorectal continuum" concept.

IGF2 differentially methylated region hypomethylation in relation to pathological and molecular features of serrated lesions.

AIM: To investigate insulin-like growth factor 2 (IGF2) differentially methylated region (DMR)0 hypomethylation in relation to clinicopathological and molecular features in colorectal serrated lesions. METHODS: To accurately analyze the association between the histological types and molecular features of each type of serrated lesion, we consecutively collected 1386 formalin-fixed paraffin-embedded tissue specimens that comprised all histological types [hyperplastic polyps (HPs, n = 121), sessile serrated adenomas (SSAs, n = 132), traditional serrated adenomas (TSAs, n = 111), non-serrated adenomas (n = 195), and colorectal cancers (CRCs, n = 827)]. We evaluated the methylation levels of IGF2 DMR0 and long interspersed nucleotide element-1 (LINE-1) in HPs (n = 115), SSAs (n = 120), SSAs with cytological dysplasia (n = 10), TSAs (n = 91), TSAs with high-grade dysplasia (HGD) (n = 15), non-serrated adenomas (n = 80), non-serrated adenomas with HGD (n = 105), and CRCs (n = 794). For the accurate quantification of the relative methylation levels (scale 0%-100%) of IGF2 DMR0 and LINE-1, we used bisulfite pyrosequencing method. Tumor specimens were analyzed for microsatellite instability, KRAS (codons 12 and 13), BRAF (V600E), and PIK3CA (exons 9 and 20) mutations; MLH1 and MGMT methylation; and IGF2 expression by immunohistochemistry. RESULTS: The distribution of the IGF2 DMR0 methylation level in 351 serrated lesions and 185 non-serrated adenomas (with or without HGD) was as follows: mean 61.7, median 62.5, SD 18.0, range 5.0-99.0, interquartile range 49.5-74.4. The IGF2 DMR0 methylation level was divided into quartiles (Q1 ≥ 74.5, Q2 62.6-74.4, Q3 49.6-62.5, Q4 ≤ 49.5) for further analysis. With regard to the histological type, the IGF2 DMR0 methylation levels of SSAs (mean ± SD, 73.1 ± 12.3) were significantly higher than those of HPs (61.9 ± 20.5), TSAs (61.6 ± 19.6), and non-serrated adenomas (59.0 ± 15.8) (P < 0.0001). The IGF2 DMR0 methylation level was inversely correlated with the IGF2 expression level (r = -0.21, P = 0.0051). IGF2 DMR0 hypomethylation was less frequently detected in SSAs compared with HPs, TSAs, and non-serrated adenomas (P < 0.0001). Multivariate logistic regression analysis also showed that IGF2 DMR0 hypomethylation was inversely associated with SSAs (P < 0.0001). The methylation levels of IGF2 DMR0 and LINE-1 in TSAs with HGD (50.2 ± 18.7 and 55.7 ± 5.4, respectively) were significantly lower than those in TSAs (61.6 ± 19.6 and 58.8 ± 4.7, respectively) (IGF2 DMR0, P = 0.038; LINE-1, P = 0.024). CONCLUSION: IGF2 DMR0 hypomethylation may be an infrequent epigenetic alteration in the SSA pathway. Hypomethylation of IGF2 DMR0 and LINE-1 may play a role in TSA pathway progression.

Diagnostic value of ¹8F-FDG PET/CT for lymph node metastasis of esophageal squamous cell carcinoma.

PURPOSE: This study investigated the diagnostic accuracy of hybrid positron-emission tomography/computed tomography (PET/CT) for lymph node (LN) metastasis of esophageal cancer. We also investigated the correlation between the size of metastatic nests and the detection by PET/CT. METHODS: Two hundred and fifty-eight patients with esophageal squamous cell carcinoma who underwent esophagectomy with two- or three-field radical lymphadenectomy were analyzed retrospectively. We compared the diagnosis of preoperative PET/CT to the postoperative histopathological examination by each anatomical field (n = 1,231) in all 258 patients. The metastatic LNs resected from PET/CT positive fields were classified as belonging to the PET/CT-N-positive group (n = 229) and those from negative fields as belonging to the PET/CT-N-negative group (n = 352). The cross-sectional areas of metastatic nests were measured in each metastatic LN. RESULTS: Of the 1,231 fields, 275 (22 %) were positive for metastasis, including 581 LNs from 408 regional LN stations. The sensitivity and specificity of PET/CT examined by each anatomical field were 25.8 and 97.8 %, respectively. The median area of metastatic nests was 17.7 mm2 in the PET/CT-N-positive group, and 7.7 mm2 in the PET/CT-N-negative group (p < 0.001). CONCLUSIONS: A significant correlation was suggested between the nest size and detection by PET/CT. Because of its low sensitivity, PET/CT alone is insufficient to determine the surgical procedures, especially when considering reduction surgery.

Expression of angiotensin II receptor-like 1 in the placentas of pregnancy-induced hypertension.

Angiotensin II receptor-like 1 (APJ), a G protein-coupled receptor that was identified as a homologue of angiotensin II type 1 (AT1) receptor, exerts antagonistic effects on AT1-mediated vasoconstriction. Studies on pregnancy-induced hypertension (PIH) revealed aberrant activation of AT1 downstream signaling. In contrast, little is known about APJ in the pathophysiology of human pregnancy. In this study, we investigated APJ expression in normal human and PIH placentas. mRNAs were extracted from 50 placental villous tissues of 18 cases with severe PIH (8 late-onset, 4 early-onset, and 6 superimposed PIH) and 32 control pregnancies (including 6 preterm cases). Histopathologic studies were conducted using paraffin-embedded placental tissues from 12 control placentas (from 23 to 39 wk) and 23 PIH placentas (from 24 to 41 wk). Reverse transcriptase-polymerase chain reaction showed that APJ was cooperatively expressed with its ligand apelin and AT1 in controls and in late-onset PIH placentas but was significantly downregulated in early-onset PIH placentas with poor fetal growth. Quantitative reverse transcriptase-polymerase chain reaction analysis revealed upregulated APJ in late-onset PIH placentas but significantly downregulated APJ in early-onset PIH. In immunohistochemical staining, APJ was detected strongly in villous capillary endothelial cells and trophoblasts of late-onset PIH placentas. In contrast, APJ was poorly stained in endothelial cells of hypoplastic villi of early-onset PIH placentas. Collective data indicate that the apelin-APJ system is involved in fetoplacental circulation during human pregnancy. Impaired APJ expression in early-onset PIH placentas may reflect an aggravated placental condition with poor fetal growth.

Successful rescue of late-onset acute T-cell mediated rejection with anti-CD25 antibody: a case report.

Japan A 56-yr-old Japanese male with a history of diabetic nephropathy underwent a HLA 5/6 mismatch and ABO-compatible living-related kidney transplantation (donor: his 49-yr-old wife). A pre-transplant standard NIH complement-dependent cytotoxicity cross-match (Xm) test, a flow-cytometric T-cell Xm, and a FlowPRA test were totally negative. Inductionimmunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil, methylprednisolone, and basiliximab (BAS). The patient's post-operative course was almost uneventful, and the graft was functioning well (sCr 1.1 mg/dL). He developed general fatigue, and his sCr was elevated to 2.2 mg/dL 792 d after transplant. A graft biopsy showed acute T-cell mediated rejection Banff grade IB (i3, t3, g0, v0, ptc0, C4d staining negative). The conventional anti-rejection therapy could not improve his graft function; therefore, we added BAS to eliminate activated graft-infiltrating T-cells. He responded to the rescue therapy, and the improvement in graft function was confirmed by a subsequent graft biopsy. He enjoyed his health without any opportunistic infections.

[A case of thrombotic thrombocytopenic purpura with systemic lupus erythematosus].

We described a case of thrombotic thrombocytopenic purpura (TTP) with systemic lupus erythematosus (SLE). A-60-year old woman was admitted to our hospital because of fever, disconsciousness, and general fatigue. 32 years ago, she was diagnosed as SLE with Raynaud's phenomenon, rash, photosensitivity, arthritis, lymphocytopenia, and ANA. Her SLE was well controlled with 10 mg predonisolone as a maintance dose until several weeks ago. On admission, severe thrombocytopenia (0.7x10(4)/microl) and other laboratory data revealed microangiopathic hemolytic anemia and renal dysfunction, Immediately after diagnosed as TTP, plasma exchange and corticosteroid therapy started. In spite of the treatment, disconsciousness progressed and systemic convulsion occurred and died 4 days after admission. Autopsied examination revealed diffuse microvascular hyalinized thrombi in heart, kidney, liver, spleen, and pancreas. Some microvascular thrombi were detected in lymph nodes, bone marrow, intestine. Pathological diagnosis of TTP was made on microvascular hyalinized platelet thrombi in organs. Von Willebrand factor-cleaving protease (VWF-CP) activity in plasma on set is less than 0.5 percent of normal and inhibitor for VWF-CP was detected. We here report a valuable case for analysis of pathogenesis in SLE-TTP.

Late corticosteroid withdrawal can be safely performed for kidney recipients with stable graft function under pathological confirmation.

Corticosteroid withdrawal (CSWD) protocols to minimize the risk of cardiovascular events after kidney transplantation have been reported. However, most of them were within one year post-transplant, and the pathological survey after CSWD was poorly done. We conducted the present retrospective study to elucidate the usefulness and safety of late-steroid withdrawal more than one year after transplantation in kidney recipients with pathological evaluation. Twenty kidney recipients with stable graft function more than one year post-transplant, and whose corticosteroid (CS) was withdrawn were enrolled in this study. The change in their clinical parameters of graft function (sCr and uP/Cr), metabolic profiles, and histological graft status (Banff 97 scoring system) were studied pre- and post-CSWD, and compared with a control cohort taking continuous CS. The dose of CS was tapered gradually and has been maintained with the minimal dose of CS (1.25-5 mg of prednisone) by three months after transplant. CS was furthermore reduced thereafter, if graft function had been stable more than one year and a patient wanted CS to be withdrawn, then a graft biopsy was undertaken. CSWD was accomplished between 16 and 195 (median 41.5) months post-transplant, if there was no significant histological graft damage or on-going acute rejection. A repeat biopsy was carried out two to 21 months after CSWD. In contrast, the observation point of the control cohort was 24 to 49 (median 36.5) months after transplant, and the second biopsy was done five to 30 months after the initial biopsy. The control cohort took 2.5 to 5 (median 2.5) mg of prednisone daily. There were no significant alterations of graft function between pre- and post-CSWD (sCr: 1.14 +/- 0.1 and 1.17 +/- 0.1 mg/dL, respectively, p = 0.3299, uP/Cr: 0.12 +/- 0.01 and 0.21 +/- 0.06, respectively, p = 0.0574). The hypertension rate between both groups was not different between double biopsy points. In addition the rates of glucose intolerance and hyperlipidemia were comparable between two points in both cohorts. There was no significant change in the acute/active lesion scoring (2 t1 and 3 i1 were only positive factors before CSWD and they all returned to t0 and i0 after CSWD). Moreover, chronic/sclerosing allograft nephropathy scorings were minimal and similar between pre- and post-CSWD compared with the control. CSWD for more than one year is safe for patients whose graft functions are stable with pathological confirmation; however, a longer follow-up study is warranted.

Two cases of adenoid cystic carcinoma: preoperative cytological findings were useful in determining treatment strategy.

Adenoid cystic carcinoma (ACC) of the breast is a rare variant of breast malignancy and is known to have an excellent prognosis. We report two cases of ACC diagnosed by preoperative fine-needle aspiration cytology (FNAC), which proved to be very useful in determining the appropriate treatment. The patients were a 57-year-old woman (case 1) and a 71-year-old woman (case 2). On physical examinations and imaging studies both tumors were recognized as lobulated tumors that measured 3.0 x 2.3 cm (case 1) and 3.9 x 3.4 cm (case 2) respectively. FNAC materials showed clusters of malignant cells surrounding globules of mucus, therefore, ACC was diagnosed. Considering the characteristics of ACC, breast-conserving surgeries with axillary dissection and adjuvant radiotherapy were performed instead of primary chemotherapy or mastectomy. Histologically, a distinctive biphasic pattern was observed that consisted of true laminae and pseudocystic spaces. Tumor sizes were 4.0 x 3.3 cm (case 1) and 4.6 x 3.8 cm (case 2), respectively, and surgical margins were negative on microscopic examination. Lymph node metastasis was not present in either case. Even though ACC is very rare, preoperative diagnosis can be made based on its characteristic features. Preoperative diagnosis is extremely useful for determining appropriate treatment.

Strong HLA-DR antigen expression on cancer cells relates to better prognosis of colorectal cancer patients: Possible involvement of c-myc suppression by interferon-gamma in situ.

Strong HLA-DR antigen expression on cancer cells relates to better prognosis of colorectal cancer patients, although the precise mechanism is controversial. From an immunological point of view, HLA-DR antigen, induced by interferon (IFN)-gamma, is required for tumor-associated antigen recognition by CD4(+) T cells. For instance, as reported previously, the expression of HLA-DR antigen in normal colorectal epithelium immediately adjacent to cancer coincided significantly with the existence of IFN-gamma mRNA in the tissue. From another aspect, IFN-gamma has been revealed to suppress c-myc expression in vivo through a stat1-dependent mechanism, which is important for cell growth, cell cycle and chromosome instability. In the present study, strong HLA-DR-positive expression on cancer cells was significantly related to better prognosis for colorectal cancer patients. High IFN-gamma mRNA expression in situ indicated significantly less activation of c-myc mRNA expression. Further, HLA-DR antigen expression in cancer cells, as well as Dukes stages, was an independent factor for better long-term survival by multivariate analysis. Taken together, IFN-gamma, which induces HLA-DR antigens on the cell surface, also suppresses c-myc expression in situ, and is a possible non-immunological mechanism involved in the better long-term survival of colorectal cancer patients.

Transperineal ultrasound-guided 12-core systematic biopsy of the prostate for patients with a prostate-specific antigen level of 2.5-20 ng/ml in Japan.

BACKGROUND: The aim of this study was to investigate the cancer detection rate in patients with a prostate-specific antigen (PSA) level of 2.5 to 20 ng/ml, using transperineal ultrasound-guided systematic biopsy of the prostate. METHODS: Three hundred consecutive patients with PSA levels of 2.5 to 20 ng/ml underwent transperineal ultrasound-guided 12-core systematic biopsy of the prostate. RESULTS: Prostate cancer was detected in 108 of the 300 patients (36.0%). The cancer detection rates in patients with total PSA levels of 2.5-4.0, 4.01-10.0 and 10.01-20.0 ng/ml were 18.2%, 31.0%, and 50.0%, respectively. The cancer detection rates in patients with prostate volumes of less than 30 cc and over 50 cc were almost 50%, and 13.3%, respectively. The cancer detection rate in patients with a PSA density (PSAD) of less than 0.10 ng/ml per cc was only 5.6%, and no prostate cancer was detected in patients with a free-to-total PSA ratio (% f PSA) over 40%. CONCLUSION: We demonstrated a high prostate cancer detection rate by the transperineal ultrasound-guided 12-core systematic biopsy method in patients with PSA levels of 2.5 to 20 ng/ml. Accordingly, if the number of core biopsies is further increased overall, except in patients with a large prostate volume, and if the indication for biopsy is decided based on the PSAD and %f PSA, then the cancer detection rate by the present method may be further improved, with fewer unnecessary biopsies.

Correlation between angiogenesis and reduction ratio measured using 201Tl chloride single photon emission computed tomography in patients with oral cavity squamous cell carcinoma.

OBJECTIVE: The aim of this study is to examine the correlation between tumor angiogenesis and response to preoperative radiotherapy evaluated using 201Tl single photon emission computed tomography (Tl SPECT) in oral cavity squamous cell carcinoma (SCC). METHODS: Tl SPECTs before and after preoperative radiotherapy were obtained from 11 patients diagnosed with SCC in oral cavity. Regions of interest were set around the tumor and scalp respectively, and the ratio of mean counts in the tumor to those in the scalp was calculated (T/N). Immunohistochemical staining for investigating microvessel density of pre-treatment biopsy specimen was performed using CD31 monoclonal antibody. We compared microvessel density with semi-quantitative parameters obtained using Tl SPECT (T/N at pre- an post-treatment, reduction ratio) and prognosis. RESULTS: The subgroup with higher microvessel density showed a significantly higher reduction ratio than the one with lower microvessel density. Regarding prognosis, the subgroup with locoregional recurrent disease exhibited a significantly higher microvessel density than the one without recurrence. CONCLUSIONS: In SCC of the oral cavity, there was a significant correlation between microvessel density and response to preoperative radiotherapy. Namely, it was revealed that change of 201Tl uptake after preoperative radiotherapy correlated with tumor angiogenesis of oral cavity SCC.

Evaluation of mandibular invasion by head and neck cancers using 99mTc-methylene diphosphonate or 99mTc-hydroxymethylene diphosphonate and 201Tl chloride dual isotope single photon emission computed tomography.

Whether a patient with head and neck cancer has mandibular invasion or not is important in determining the method of resection surgery. But, no modality is adequately reliable when used alone in the evaluation of mandibular invasion. Therefore, to more accurately diagnose mandibular invasion in head and neck cancer, we used a new modality, namely, 99mTc methylene diphosphonate (MDP) or 99mTc hydroxymethylene diphosphonate (HMDP) and 201Tl chloride dual isotope single photon emission computed tomography (Tc/Tl SPECT). The aim of this study is to disclose the usefulness of Tc/Tl SPECT in the assessment of mandibular invasion by head and neck cancers. 99mTc-MDP or -HMDP SPECT (Tc SPECT)s and 201Tl chloride SPECT (Tl SPECT)s were performed in 34 patients with suspected mandibular involvement of head and neck cancer. Thirty of 34 cases underwent both TcMTl SPECT and CT examination. Tc/Tl SPECT fusion images were obtained using the Automatic Registration Tool (ART, TOSHIBA, Japan) system. In the diagnosis of mandibular invasion on Tc/Tl SPECT fusion images, a problem was that the range of Tc and Tl uptake was changed by the condition of display used in the reconstruction and expression of the images. Then, prior to clinical evaluation, to reveal the most appropriate upper window level for display, a phantom study was performed. In a clinical study, the upper window level was set at 40 or 50%, which were verified to be the proper values in the preliminary study. The diagnostic accuracy obtained using Tc SPECT, TcMTl SPECT and CT was compared with the histopathological findings. Tc/Tl SPECT at 40 and 50% upper window level had higher specificity, accuracy, and positive predictive value (73.3%, 85.3%, 81.8%) than Tc SPECT alone (21.4%, 67.6%, 64.5%) and higher sensitivity and negative predictive value (94.7%, 91.7%) than CT (70.6%, 72.2%) for detecting mandibular invasion. Tc/Tl SPECT was a useful diagnostic procedure for the assessment of mandibular invasion by head and neck cancers.

Semi-quantitative assessment of oral cavity squamous cell carcinoma using 201Tl SPECT for evaluating effectiveness of preoperative radiotherapy.

The aim of this study is to reveal the usefulness of semi-quantitative assessment using 201Tl chloride (Tl) single photon emission computed tomography (SPECT) (Tl SPECT) to evaluate the effectiveness of radiotherapy in 15 patients with oral cavity squamous cell carcinma (SCC). Fifteen patients were diagnosed with SCC by biopsy. All 15 patients enrolled in this study were planned to undergo preoperative radiotherapy with or without chemotherapy using carboplatin (CBDCA) and received reduction operation. Tl SPECTs were performed 15 minutes after intravenous administration of 111 MBq 201Tl chloride. Regions of Interest (ROI) were set up around tumor (T), and non-lesion (N) at the part of contralateral scalp at the height of the cerebellum. The ratios of mean counts in ROI of the tumor to those in non-lesion were measured as pre- and post-treatment T/N ratios (pre T/N, post T/N). Furthermore, reduction rate (RR) was obtained by calculating [(pre T/N - post T/N)/(pre T/ N)] x 100%. Each parameter (pre T/N, post T/N, and RR) was compared to histopathological grade of surgical specimen based on the Oboshi and Shimosato classification (grade I-IV). RR showed significantly higher values in grade III and IV than in grade I and II (p = 0.0008). In conclusion, semi-quantitative assessment using Tl SPECT, especially calculating RR, is useful to evaluate the effectiveness of preoperative radiotherapy.

PIVKA-II-producing advanced gastric cancer.

We describe the case of a 68-year-old man with primary advanced adenocarcinoma of the stomach, who displayed extremely high plasma levels of protein induced by vitamin K antagonist (PIVKA)-II (15 600 mAU/ml) and normal levels of alphafetoprotein (AFP) (4 ng/ml). Ultrasonography and dynamic computed tomography ruled out hepatocellular carcinoma (HCC) or liver metastasis. After preoperative chemotherapy, pancreatico-spleno total gastrectomy with D2 lymphadenectomy was performed. Postoperatively, plasma levels of PIVKA-II returned to within the normal range (29 mAU/ml). Microscopic examination revealed stomach adenocarcinoma showing various histological types, such as moderately to poorly differentiated mucinous adenocarcinoma, but hepatoid differentiation of gastric adenocarcinoma was not detected. Localization of PIVKA-II and AFP within tumor cells was demonstrated by immunohistochemical staining using monoclonal antibodies. These results indicate that tumor cells from gastric cancer may produce PIVKA-II. Some cases of PIVKA-II- and AFP-producing advanced gastric cancer with liver metastasis have been reported, but this is the first report of gastric cancer without liver metastasis producing PIVKA-II alone.

Longterm survival after surgical removal of solitary brain metastasis from osteosarcoma.

The prognosis of osteosarcoma with brain metastasis is very poor. We report a 14-year-old girl with osteosarcoma of the right distal femur who is alive and free of disease 6 years after the craniotomy and irradiation for brain metastasis. This longterm survival is attributed to the absence of active pulmonary metastasis at the onset of brain metastasis and the complete removal of the brain metastasis by craniotomy. Patients without active pulmonary metastasis at the onset of brain metastasis may achieve longterm survival. In such patients, it would be worthwhile to perform craniotomy aggressively.