Hysteroscopic resection of retained products of conception combined with uterine artery balloon occlusion: A novel case report.

Retained products of conception can cause massive bleeding that can be prevented by uterine artery embolization before resection; however, uterine artery balloon occlusion is less invasive. While scattered reports of its use for postpartum hemorrhage exist, no indications have been described. We report a case of hysteroscopic resection of retained products of conception using uterine artery balloon occlusion instead of uterine artery embolization. A 29-year-old woman, gravida 2 para 0, noted an intrauterine mass after an abortion at 7 weeks' gestation. Follow-up visits showed insufficient lowering of human chorionic gonadotropin levels, necessitating surgical treatment. Considering the patient's desire to conceive, we performed uterine artery balloon occlusion to reduce the risk of perinatal complications associated with uterine artery embolization. The operation was completed without complications. The patient conceived spontaneously and had a live baby 7 months after surgery, thus proving the benefits of uterine artery balloon occlusion before hysteroscopic resection.

A vector correlation study using a hexapole-oriented molecular beam: photodissociation dynamics of oriented isohaloethane.

The photodissociation dynamics of isohaloethane (1-bromo-2-chloro-1,1,2-trifluoroethane) at 234 nm was studied by a sliced imaging technique combined with an oriented molecular beam. The speed and angular distributions of the competitive products of spin-orbit selected Br and Cl atoms were determined by analysis of the obtained images. The anisotropic parameter, ß, was found to be 2.0 ± 0.2 for the excited state of Br(2P1/2) (Br*) and 1.2 ± 0.3 for the ground state of Br(2P3/2) (Br). The speed distributions for both Br and Br* exhibited Gaussian-like characteristics. These results indicate that Br atoms were generated by direct formation after excitation through the nσ*(C-Br) potential energy surfaces. In contrast, the angular distributions for the Cl fragments were almost isotropic, while the speed distributions displayed Boltzmann-like characteristics. This suggests that the Cl atoms may form through long-lived parent molecules after photoexcitation. The branching ratio for Br and Cl atom formation was found to be approximately 1.2, that is, Br atom formation occurred preferentially, in contrast to the case of halothane photodissociation reported in our previous work [Che et al., J. Phys. Chem. A, 2020, 124, 5288]. A vector correlation study between the laser polarization axis and the direction of the dipole moment revealed a similar tendency for all photofragments, suggesting that the fragments were formed through a common excited state of isohaloethane. The vector correlation was also studied theoretically for comparison with the experimental results. The angle between the transition dipole moment in photodissociation and the permanent dipole moment was found to be 42 ± 15°. The obtained results indicate that this vector correlation approach combined with an oriented molecular beam is a powerful tool for determining the transition dipole moments in photodissociation.

Photodissociation Dynamics of CF2ClCHFI Using Slice Imaging Combined with a Hexapole-Oriented Molecular Beam.

Photodissociation dynamics of 1-chloro-2-iodo-1,1,2-trifluoroethane (CF2ClCHFI) were investigated at 267 nm by a slice imaging technique combined with an oriented molecular beam. The speed and angular distributions of the spin-orbit-selected I atoms were determined by analyzing the images. The anisotropic parameter was 1.67 ± 0.04 for the ground state of I(2P3/2) and 1.94 ± 0.04 for the excited state of I(2P1/2). A vector correlation study between the laser polarization and the dipole moment of the molecule revealed that the transition dipole moment in photoabsorption was found to be at 90° ± 15 to the molecular dipole moment, suggesting the transition dipole moment was nearly parallel to the C-I bond axis. The quantum yield for the excited state obtained from the observed signal intensities was estimated to more than 0.9 at this wavelength. The analysis of the kinetic energy release for both fragments indicated that a large amount of energy was distributed into the internal energy of the CF2ClCHF· radical, which led to the secondary reaction of the C-Cl bond rupture. The study of the ground state of Cl atom formation via photolysis at 235 nm supported the existence of the secondary reaction. The results of the kinetic energy release of the I photofragments and the analysis of the image for the photofragment of the Cl atom suggested that the ground state of I atom formation mainly led to the secondary reaction of the C-Cl bond rupture through the short-lived CF2ClCHF· radical. However, only part of the excited state of I atom formation involved the Cl atom formation through the long-lived CF2ClCHF· radical.

[Conversion Surgery for Initially Unresectable Locally Advanced Pancreatic Cancer Following Gemcitabine plus Nab-Paclitaxel - A Case Report].

We report a case of unresectable locally advanced pancreatic cancer successfully resected after gemcitabine(GEM)plus nab-paclitaxel(PTX)treatment. A 68-year-old man was referred to our institution with jaundice. We diagnosed pancreatic head cancer using computed tomography(CT)and endoscopic retrograde cholangiopancreatography. We initially diagnosed it as locally advanced unresectable pancreatic cancer because of extensive invasion to the portal vein. GEM plus nab- PTX was administered to the patient as systemic chemotherapy. After 9 courses of chemotherapy, a CT scan revealed that the tumor had significantly reduced in size and range of portal vein invasion. Therefore, we performed pancreaticoduodenectomy with resection of the portal vein and achieved R0 resection. Currently, the patient is alive without recurrence. Therefore, conversion surgery after treatment with GEM plus nab-PTX chemotherapy for unresectable pancreatic cancer should be considered.

Discrepancies between the K-ras mutational status of primary colorectal cancers and corresponding liver metastases are found in codon 13.

K-ras mutation status has remained elusive in the metastatic liver tumors of colorectal cancer (CRC) in contrast to the primary CRC tumors. In this study, K-ras mutational status of the primary and corresponding liver metastatic tumors was investigated in the 43 CRC patients. Codons 12 and 13 of K-ras were directly sequenced, and a K-ras mutation was evident in 17 cases (39.5%). In 6 cases, the K-ras mutation was evident only in the liver metastasis, but not in the primary CRC, where the mutation was found in codon 13. This discrepancy between primary and metastatic lesions with regard to codon 13 of the K-ras gene may explain the clinical discrepancy of EGFR antibody therapy. In conclusion, the current data may lead to the development of personalized medicine for recurrent CRC, although further validation study is still required.

Segmental low-density area on contrast-enhanced CT is a possible clue to diagnosing branch artery fibromuscular dysplasia.

Summary: Fibromuscular dysplasia can cause renovascular hypertension. Since fibromuscular dysplasia may be underdiagnosed, precise diagnosis and management are crucial, especially for young women. A 20-year-old woman with hypertension and hypokalemia was referred to our hospital for further evaluation of secondary hypertension. At the previous hospital, her blood pressure was 160/110 mmHg and the serum potassium level was 2.9 mEq/L. The equilibrium phase on contrast-enhanced computed tomography revealed a low-density area in the upper median portion of the right kidney. On admission to our hospital, her blood pressure was 141/96 mmHg under 5 mg of amlodipine. Laboratory tests revealed plasma renin activity of 11.3 ng/mL/h and plasma aldosterone concentration of 117.1 pg/mL. Renal venous sampling of active renin concentration showed a right-to-left renin ratio of 3.13, confirming a significant increase in renin secretion from the right kidney. Selective reno-angiography detected focal stenosis with adjacent aneurysmal dilation and tortuosity in the proximal branch of the right renal artery. She was diagnosed with branch artery fibromuscular dysplasia and successfully treated with percutaneous transluminal angioplasty. After the treatment, she was free from hypertension and hypokalemia without any medications. Since branch artery fibromuscular dysplasia is sometimes difficult to diagnose, contrast-enhanced computed tomography can be a promising diagnostic tool as shown in this case. Concerning treatment, our patient was treated with percutaneous transluminal angioplasty, which should be considered for women of reproductive age because recommended antihypertensive medications can be teratogenic even in the first trimester of pregnancy. Learning points: Although branch artery fibromuscular dysplasia (FMD) is sometimes difficult to diagnose, it should be considered in patients with high-renin, high-aldosterone hypertension. Branch artery FMD can present with a low-density area of the kidney on contrast-enhanced computed tomography, as shown in this case. Percutaneous transluminal angioplasty (PTA) can be an appropriate treatment for branch artery FMD, especially in young female patients. PTA may immediately improve hypertension and hypokalemia without the need for medications.

Development of an ultra-widely tunable DFG-THz source with switching between organic nonlinear crystals pumped with a dual-wavelength BBO optical parametric oscillator.

We developed a difference frequency generation (DFG) source with an organic nonlinear optical crystal of DAST or BNA selectively excited by a dual-wavelength ß-BaB(2)O(4) optical parametric oscillator (BBO-OPO). The dual-wavelength BBO-OPO can independently oscillate two lights with different wavelengths from 800 to 1800 nm in a cavity. THz-wave generation by using each organic crystal covers ultrawide range from 1 to 30 THz with inherent intensity dips by crystal absorption modes. The reduced outputs can be improved by switching over the crystals with adequately tuned pump wavelengths of the BBO-OPO.

Cancer specific promoter CpG Islands hypermethylation of HOP homeobox (HOPX) gene and its potential tumor suppressive role in pancreatic carcinogenesis.

BACKGROUND: We have recently identified HOP hoemobox (HOPX) as a tumor suppressor gene candidate, characterized by tumor-specific promoter DNA hypermethylation in human cancers, and it can remarkably inhibit tumors' aggressive phenotypes. In this current study, we for the first time examined methylation level of HOPX and tested the functional relevance in pancreatic cancer (PC). METHODS: Clinical features of HOPX promoter hypermethylation was investigated in 89 PC tissues, and immunohistochemistry was added. We also examined its functional relevance in phenotype assays such as soft agar, proliferation, invasion, and cell cycle analysis. RESULTS: PC tissues had HOPX gene hypermethylation as compared to the corresponding normal pancreas tissues, and its uniqueness was robust to discriminate tumor from normal tissues (AUC = 0.85, P < 0.0001). Unexpectedly, HOPX was increased in expression in tumor tissues, and immunohistochemistry revealed its predominant expression in the Langerhans islet cells, where HOPX was reduced in expression for PC cells with promoter hypermethylation. HOPX transfectants exhibited G1 arrest with subG1 accumulation, and inhibited tumor forming and invasive ability. CONCLUSION: Defective expression of HOPX which is consistent with promoter DNA hypermethylation may explain aggressive phenotype of pancreatic cancer, and intense expression of HOPX in the Langerhans cells may in turn uniquely contribute to pancreatic carcinogenesis.

Elective Endovascular Stent-Graft Implantation for External Iliac Artery Injury after Blunt Pelvic Trauma.

External iliac artery (EIA) injuries caused by blunt trauma are rare. Here, we describe a blunt EIA injury after a motorbike accident suffered by a 16-year-old male. Despite conservative treatment, intermittent claudication persisted. He was successfully treated by elective endovascular stent-graft implantation on day 59 after the injury. Ankle-brachial index (ABI) improved, as did his symptoms. A contrast-enhanced computed tomography scan on postoperative day 90 showed no residual stenosis and favorable peripheral blood flow. This report suggests that elective endovascular stent-graft implantation might be a viable treatment option for blunt EIA injuries.

Endovascular treatment with Viabahn stent-grafts for arterial injury and bleeding at the visceral arteries: initial and midterm results.

PURPOSE: The purpose of the study is to evaluate the initial and midterm efficacy and safety of endovascular treatment (EVT) using Viabahn stent-graft (SG) for arterial injury and bleeding (AIB) at the visceral arteries. MATERIALS AND METHODS: Consecutive patients with visceral AIB who underwent EVT using Viabahn between January 2017 and February 2021 were retrospectively reviewed. Technical success, clinical success, peripheral organ ischemia, peri-procedural complications, bleeding-related mortality, 30-day mortality, neck length, re-bleeding, endoleaks, and patency of the SGs at 1, 3, 6, and 12 months were evaluated. RESULTS: EVT using Viabahn was performed in 14 patients (mean age: 68.6 years; 12 males) and 15 arteries. The technical and clinical success rates were 100%. The rates of peripheral organ ischemia, peri-procedural complications, bleeding-related mortality, and 30-day mortality were all 0%. The mean neck length was 9.9 mm. No endoleaks or re-bleeding occurred during the follow-up (mean: 732 days). The SG patency was confirmed after 1, 3, 6, and 12 months in 78.6%, 78.6%, 78.6%, and 56.1% of the patients, respectively. CONCLUSION: EVT using Viabahn for AIB at the visceral arteries was safe and effective. SG occlusions without ischemia often occurred after 12 months.

Therapeutic potential of PRL-3 targeting and clinical significance of PRL-3 genomic amplification in gastric cancer.

BACKGROUND: Phosphatase of regenerating liver-3 (PRL-3) has deserved attention as a crucial molecule in the multiple steps of metastasis. In the present study, we examined the mechanisms regulating PRL-3 expression, and assessed the clinical potential of PRL-3-targeted therapy in gastric cancer. METHODS: PRL-3 genomic amplification was analyzed using quantitative-polymerase chain reaction and/or fluorescence in situ hybridization in 77 primary gastric tumors. The anticancer activity of PRL-3 inhibitor (1-4-bromo-2-benzylidene rhodanine) treatment was evaluated against cancer cells with different genetic and expression status. RESULTS: PRL-3 genomic amplification was closely concordant with high level of its protein expression in cell lines, and was found in 20% (8/40) among human primary tumors with its expression, which were all stage III/IV disease (40%, 8/20), but in none (0/37) among those without expression. Additionally, PRL-3 genomic amplification was associated with metastatic lymph node status, leading to advanced stage and thereby poor outcomes in patients with lymph node metastasis (P = 0.021). PRL-3 small interfering RNA robustly repressed metastatic properties, including cell proliferation, invasion, and anchorage-independent colony formation. Although neither PRL-3 genomic amplification nor expression level was responsible for the sensitivity to PRL-3 inhibitor treatment, the inhibitor showed dose-dependent anticancer efficacy, and remarkably induced apoptosis on all the tested cell lines with PRL-3 expression. CONCLUSIONS: We have for the first time, demonstrated that PRL-3 genomic amplification is one of the predominant mechanisms inducing its expression, especially in more advanced stage, and that PRL-3-targeted therapy may have a great potential against gastric cancer with its expression.

Emergency endovascular treatment using a Viabahn stent graft for upper and lower extremity arterial bleeding: a retrospective study.

BACKGROUND: A Viabahn stent graft (SG) is a heparin-coated self-expandable SG for lower extremity arterial disease that exhibits high flexibility and accuracy in the delivery system. This study aimed to evaluate the short-term efficacy and safety of emergency endovascular treatment (EVT) using a Viabahn SG for upper and lower extremity arterial bleeding (ULEAB). METHODS: Consecutive patients with ULEAB who underwent emergency EVT using the Viabahn SG between January 2017 and August 2021 were retrospectively reviewed. The indications for EVT, location of artery, technical success, clinical success, limb ischemia, periprocedural complications, bleeding-related mortality, 30-day mortality, diameter of the target artery, diameter of the SG, neck length, rebleeding, endoleaks, and patency of the SGs at 1, 3, 6, and 12 months were evaluated. RESULTS: EVT using the Viabahn SG was performed in 22 patients (mean age, 72.0 ± 13.0 years; 11 men) and 23 arteries (upper, 6; lower, 17). The indications for EVT were pseudoaneurysm (n = 13, 59.1%), extravasation (n = 9, 39.1%), and inadvertent arterial cannulation (n = 1, 4.3%). The anatomical locations of the 23 ULEAB injuries were the brachiocephalic (1 [4.3%]), subclavian (3 [13.0%]), axillary (1 [4.3%]), brachial (1 [4.3%]), common iliac (4 [17.4%]), external iliac (8 [34.8%]), common femoral (2 [8.7%]), superficial femoral (2 [8.7%]), and popliteal (1 [4.3%]) arteries. The technical and clinical success rates were 100%. The rates of limb ischemia, periprocedural complications, and bleeding-related mortality were 0%, whereas the 30-day mortality rate was 22.7%. The mean diameters of the arteries and SGs were 7.7 ± 2.2 and 8.9 ± 2.3 mm, respectively. The mean neck length was 20.4 ± 11.3 mm. No endoleaks or rebleeding occurred during the follow-up period (mean, 169 ± 177 days). Two SG occlusions without limb ischemia occurred in the external iliac and brachial arteries after 1 and 4 months, respectively. Subsequently, cumulative SG patency was confirmed after 1, 3, 6, and 12 months in 91.7%, 91.7%, 81.5%, and 81.5% of patients, respectively. CONCLUSIONS: Emergency EVT using the Viabahn SG for ULEAB was effective and safe according to short-term outcomes. Appropriate size selection and neck length are important for successful treatment. SG patency was good after 1, 3, 6, and 12 months.

Imaging the nature of the mode-specific chemistry in the reaction of Cl atom with antisymmetric stretch-excited CH4.

Following up our preliminary communication [Kawamata et al., Phys. Chem. Chem. Phys. 10, 4378 (2008)], the effects of the antisymmetric-stretching excitation of methane on the Cl((2)P(3/2))+CH(4) reaction are examined here over a wide range of initial collision energy in a crossed molecular beam imaging experiment. The antisymmetric stretch of CH(4) is prepared in a single rovibrational state of (v(3)=1, j=2) by direct infrared absorption, and the major product states of CH(3)(v=0) are probed by a time-sliced velocity-map imaging method. We find that at fixed collision energies, the stretching excitation promotes reaction rate. Compared to the ground-state reaction, this vibrational enhancement factor is, however, no more effective than the translational enhancement. The correlated HCl(v'=1) vibrational branching fraction shows a striking dependence on collision energies, varying from 0.7 at E(c)=2 kcal mol(-1) to about 0.2 at 13 kcal mol(-1). This behavior resembles the previously studied Cl+CH(2)D(2)(v(6)=1), but is in sharp contrast to the Cl+CHD(3)(v(1)=1) and CH(2)D(2)(v(1)=1) reactions. Dependences of experimental results on the probed rotational states of CH(3)(v=0) are also elucidated. We qualitatively interpret those experimental observations based on a conceptual framework proposed recently.

Heterochronous Suture Line Recurrences in the Jejunal Pouch following Total Gastrectomy for Stage II Gastric Cancer: A Case Report and Literature Review.

We report the case of a 65-year-old male who developed heterochronous local recurrences of gastric cancer in the jejunal pouch (J-pouch) four times after total gastrectomy. He underwent total gastrectomy, J-pouch, and Roux-en-Y reconstruction for stage II gastric cancer in 2005. Four local recurrences appeared on the esophago-jejunal anastomosis, the suture line within the pouch, the esophago-jejunal anastomosis, and the anastomosis between the jejunum and Y-loop, which were resected by partial excision or endoscopic submucosal dissection. Suture line recurrence of gastric cancer is rare. The common features for each recurrence included the surgically negative resection margins, observation of the same histopathological subtype, absence of remote metastasis or peritoneal seeding, and the recurrence on the anastomotic suture line, suggesting that the cause of recurrence was the implantation of exfoliated cancer cells probably in the suture line. However, there is no established procedure for preventing implantation recurrence currently, the effectiveness of lumen lavage is suggested.

Long-term outcomes of endovascular aortic aneurysm repair with the Zenith AAA endovascular graft: a single-center study.

PURPOSE: To present long-term results obtained with endovascular abdominal aortic aneurysm (AAA) repair (EVAR) using the Zenith AAA endovascular graft from a single institution. MATERIALS AND METHODS: Between 2007 and 2013, 95 consecutive patients (median age 77 years) underwent EVAR using Zenith. Data were prospectively collected and retrospectively analyzed until 2019. Primary outcomes were overall survival, freedom from AAA rupture, and freedom from AAA-related death. Secondary outcomes were freedom from late (> 30 days) re-intervention and surgical conversion, and freedom from aneurysm sac growth (> 5 mm). RESULTS: The initial technical success rate was 96.8%. There were no deaths or intraoperative conversions. Overall survival at 1, 3, 5, and 10 years was 90.8%, 81.7%. 74.3%, and 57.2%, respectively. AAA rupture occurred in one patient (1.1%). Freedom from AAA-related death was 100% during the follow-up period. Freedom from aneurysm sac growth at 1, 3, 5, and 10 years was 98.8%, 86.4%, 76.9%, 53.0%, respectively. Freedom from late re-intervention and open surgical conversion at 1, 3, 5, and 10 years was 98.9%, 88.9%, 86.7, and 57.9%, respectively. CONCLUSION: EVAR with Zenith endografts represents a safe and durable means of AAA repair, and risk of rupture and aneurysm-related death are low.

IR-UV double-resonance of methyl radicals and a determination of the detection sensitivity of REMPI bands.

A novel method is exploited in this report to directly determine the relative detection sensitivity of the (2+1) resonance-enhanced multiphoton ionization (REMPI) bands of CH(3) and CHD(2) radicals. The basic idea is based on the simple fact that in an infrared (IR) absorption process the number of molecules being pumped from the lower state must be the same as the number of molecules in the excited upper state. Hence, the measured intensities of the respective REMPI bands should directly reflect their relative detection sensitivities. In order to ensure the processes involved and better quantify the measurements, extensive IR-UV double resonance spectroscopy was also performed. Using the REMPI-IR scheme, the IR spectrum of the v(1) fundamental (CH stretch) of CHD(2) was obtained and assigned for the first time. Using the IR-REMPI approach, high-resolution (2+1) REMPI spectra via the Rydberg 3p states of both radicals were demonstrated in a rotationally specific manner for both the origin and vibronic-excited bands, from which the predissociation rates of the Rydberg 3p states were deduced.

Critical relevance of genomic gains of PRL-3/EGFR/c-myc pathway genes in liver metastasis of colorectal cancer.

The PRL-3 gene is involved in the liver metastasis of colorectal cancer (CRC) and oncogene addiction to anticancer therapy. In the present study genomic gains in PRL-3 and its pathway genes, c-myc and EGFR, were investigated in order to determine their clinical relevance during metastatic formation in primary CRC and corresponding liver metastases. The genomic gain statuses of PRL-3, EGFR, and c-myc were investigated using quantitative polymerase chain reaction (qPCR) analysis in 35 samples of CRC and corresponding liver metastases. In the primary CRC specimens, genomic gains in PRL-3, c-myc, and EGFR were observed in 4, 4, and 13 cases, respectively. A genomic gain in one gene was observed in 18 cases, and these genomic gains were mutually exclusive. In the liver metastasis specimens, genomic gains were observed in 14, 8, and 13 cases, respectively. The copy numbers of PRL-3 and c-myc were significantly higher in the liver metastases than in the primary CRC specimens (P=0.03, P=0.009, respectively). A genomic gain in PRL-3 was the most frequent gain in the liver metastases (P=0.004) and was partially redundant with a c-myc genomic gain. EGFR genomic gains were consistent between the primary CRC and the liver metastases (P=0.0000008). In addition, a genomic gain in any of the 3 genes was observed in 23 cases (66%). Among the clinicopathological factors that were assessed, an EGFR genomic gain was significantly associated with tumour size in the primary CRC and the liver metastases (P=0.04). A c-myc genomic gain was also significantly associated with the v factor of the primary tumours in the liver metastases (P<0.01). In conclusion, the genomic copy numbers of PRL-3, c-myc and EGFR were frequently characterised by aberrations in genomic gain in liver metastases from CRC; thus, these gene statuses exhibit potential for the identification of patients who are likely to respond positively to anticancer therapies.

A simple yet effective multipass reflector for vibrational excitation in molecular beams.

The fraction of molecules that can be vibrationally excited is often the limiting factor in many infrared laser excitation experiments, in particular, when using weak absorption bands. Reported here is a simple multipass reflector designed to overcome that obstacle. Its enhancement in pumping efficiency is demonstrated in a crossed-beam scattering experiment on the Cl+CH2D2(v1 or v6=1) reactions. Compared to a double-pass arrangement, the effective laser fluence for excitation is also characterized.

Prognostic significance of promoter DNA hypermethylation of the cysteine dioxygenase 1 (CDO1) gene in primary gallbladder cancer and gallbladder disease.

BACKGROUND: Aberrant promoter DNA methylation of the cysteine dioxygenase 1 (CDO1) gene is found in various human cancers and is associated with clinical outcome. In this study, we assessed for the first time the clinicopathological significance of CDO1 methylation in primary gallbladder cancer (GBC) in comparison with non-malignant gallbladder disease. METHODS: CDO1 DNA methylation was quantified using quantitative TaqMan methylation specific PCR (Q-MSP) in 99 primary GBC patients together with the 78 corresponding non-tumor tissues and 26 benign gallbladder disease (including 7 patients with xanthogranulomatous cholecystitis) who underwent surgical resection between 1986 and 2014. RESULTS: The average CDO1 TaqMeth value of primary GBCs was 23.5±26. These values were significantly higher than those of corresponding non-tumor tissues (average 8±13, p < .0001) and diseased gallbladder tissues from patients with benign gallbladder diseases (average 0.98±1.6, p < .0001). CDO1 hypermethylation is also found in xanthogranulomatous cholecystitis. Using a cut-off value of 17.7, GBC cases with CDO1 hypermethylation (n = 47) showed significantly poorer prognosis than those with CDO1 hypomethylation (n = 52) (p = 0.0023). Multivariate Cox proportional hazards analysis identified that CDO1 hypermethylation was an independent prognostic factor. Notably, CDO1 hypermethylation showed prognostic relevance, especially in stage II GBC, in which it is highly anticipated to work as a predictive marker for candidates of adjuvant therapy. CONCLUSIONS: Promoter NA methylation of CDO1 was demonstrated for the first time to be a cancer-associated methylation in primary GBC, and it has the potential to be a prognostic biomarker of GBC for high-risk patients with stage II GBC.

Homeobox-Only Protein Expression Is a Critical Prognostic Indicator of Pancreatic Neuroendocrine Tumor and Is Regulated by Promoter DNA Hypermethylation.

OBJECTIVES: We have identified homeobox-only protein (HOPX) as a tumor suppressor gene in various human cancer, and its expression was reduced by promoter DNA hypermethylation. Homeobox-only protein is strongly expressed on pancreatic islet cells; however, clinical relevance of HOPX expression has remained elusive in pancreatic neuroendocrine tumor (pNET). METHODS: We investigated 36 patients with pNET who undertook surgical resection between 1988 and 2012 for HOPX expression and DNA methylation to reveal its clinical significance. RESULTS: (1) Homeobox-only protein is strongly expressed on pancreatic islet cells by immunohistochemistry (IHC). Homeobox-only protein expression was recognized on pNET tumor cells for 1+ in 15, for 2+ in 16, and for 3+ in 5. (2) Homeobox-only protein IHC expression was significantly associated with prognosis (P = 0.03), and survival rate was 37.5%, 70.3%, and 100% in HOPX 1+, 2+, and 3+, respectively. (3) Promoter DNA methylation was quantitatively assessed, and HOPX hypermethylation is found in 6.3%, 11.8%, and 66.7% of G1/G2/G3 pNET, respectively (P = 0.02). (4) Multivariate Cox proportional hazards model identified HOPX IHC expression and HOPX promoter DNA hypermethylation as independent prognostic factors in pNET. CONCLUSIONS: Homeobox-only protein expression is a critical prognostic indicator of pNET, and its regulation may be made through promoter DNA methylation.