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Aims: Skin perfusion pressure (SPP) and ankle-brachial index (ABI) are useful in screening for peripheral arterial disease in patients undergoing hemodialysis (HD). We compared the prognostic abilities of the SPP and ABI in predicting the composite outcomes of mortality and atherosclerotic vascular events., Methods: This single-center prospective cohort study enrolled 258 patients undergoing HD. The patients with SPP and ABI measurements were divided into tertiles. Log-rank tests, Cox regression analyses, and discrimination parameters were used for comparisons., Results: Over a median follow-up period of 3.7 (1.4-5.0) years, 119 composite events were recorded. The incidence rates of composite events were 27.5, 13.3, and 9.1 per 100 person years, respectively, across the SPP tertiles (log-rank: p＜0.001), and 23.2, 13.2, and 11.6 per 100 person years across the ABI tertiles (p=0.003). With the 3rd tertiles as references, the 1st tertiles of the SPP and ABI were significantly associated with the composite outcome (adjusted hazard ratio [aHR]: 2.58, 95% confidence interval [CI]: 1.57-4.23 and aHR: 1.70, 95% CI: 1.06-2.73, respectively). Adding the tertiles of the SPP to a predictive model with established risk factors significantly improved the model performance. This improvement was larger than that of the ABI in terms of net reclassification (0.330 vs. 0.275) and integrated discrimination (0.045 vs. 0.012). Furthermore, in patients with a normal ABI, the 1st SPP tertile (＜71 mmHg) was significantly associated with the outcome (aHR, 1.97; 95% CI, 1.13-3.41) when compared to the 3rd tertile., Conclusions: Even patients with a normal ABI have a poor prognosis if their SPP levels are low. SPP outperformed ABI in predicting mortality and cardiovascular outcomes in HD patients.

Background: Pembrolizumab (PEM), an immune checkpoint inhibitor (ICI), is often used for triple-negative breast cancer, but can also be used to treat solid tumors that exhibit high microsatellite instability (MSI-High). However, patients with breast cancer rarely have MSI-High, the use of PEM in such cases in clinical practice is uncertain due to lack of sufficient supporting data. Here, we report the case of a premenopausal woman in who received PEM for MSI-High luminal-type breast cancer., Case Presentation: A 40-year-old premenopausal Asian woman was diagnosed with stage IIA (T2N0M0) breast cancer and had an Oncotype DX recurrence score of 38. After surgery, she received 4 courses of chemotherapy with docetaxel and cyclophosphamide. After 3 months of tamoxifen therapy, the patient complained of abdominal pain due to right iliac metastasis, and biopsy of the metastatic lesion showed of luminal type; she was sequentially treated with fulvestrant, a CDK4/6 inhibitor, and an anticancer drug (TS1), but over the next year, metastasis to the bone and para-aortic lymph nodes increased. Tumor was MSI-High; PEM was started, and after three courses, bone metastases were reduced, para-aortic lymph node metastases resolved, opioids were discontinued, and the patient returned to society; PEM was administered for 1 year with no worsening of bone metastases on imaging. Asymptomatic brain metastasis less than 1 cm was detected and gamma knife was performed. Six months after completion of PEM, the patient is working with no new lesions., Conclusion: We report a case of luminal-type breast cancer with bone metastases and MSI-High, which was treated with PEM and showed a rapid therapeutic response., (© 2024. The Author(s).)

Background: Hyponatremia is associated with worse outcomes among patients with malignancy. However, contemporary cohort data on epidemiology and risk factors are lacking., Methods: In this single-centre, retrospective cohort study, patients who received intravenous antineoplastic agents from 2018 to 2020 at Nagoya City University Hospital were enrolled. Associations of demographics, antineoplastic agents, types of malignancy and concomitant medications with hyponatremia, defined as serum sodium concentration ≤130 mmol/l, were analysed by mixed-effects logistic regression and the machine learning-based LightGBM model artificial intelligence technology., Results: Among 2644 patients, 657 (24.8%) developed at least one episode of hyponatremia. Approximately 80% of hyponatremia was due to sodium wasting from the kidneys. Variables associated with hyponatremia both by mixed-effects logistic regression and the LightGBM model were older age, hypoalbuminemia and higher estimated glomerular filtration rate. Among antineoplastic agents, cisplatin {odds ratio [OR] 1.52 [95% confidence interval (CI) 1.18-1.96]}, pembrolizumab [OR 1.42 (95% CI 1.02-1.97)] and bortezomib [OR 3.04 (95% CI 1.96-4.71)] were associated with hyponatremia and these variables also had a positive impact on predicted hyponatremia in the LightGBM model., Conclusions: Hyponatremia was common among patients with malignancy. In addition to older age and poor nutritional status, novel antineoplastic agents, including immune checkpoint inhibitors and bortezomib, should be recognized as risk factors for hyponatremia., Competing Interests: T.H. has received honoraria from Kissei Pharmaceutical, Otsuka Pharmaceutical, Chugai Pharmaceutical and Kyowa Kirin; research grants from Otsuka Pharmaceutical and Chugai Pharmaceutical and lecture fees from Chugai Pharmaceutical, Sumitomo Pharma, Kyowa Kirin, Kissei Pharmaceutical, Ono Pharmaceutical, Otsuka Pharmaceutical, AstraZeneca KK and Astellas Pharma., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

An aberrant right subclavian artery (ARSA) is an extremely rare congenital anomaly that forms during aortic arch development. Most reports of thoracic endovascular aortic repair (TEVAR) described an ARSA in the right aortic arch, but it is rare in the left aortic arch. We present the case of a 66-year-old man who underwent total arch replacement because of acute type A aortic dissection. An outpatient follow-up examination revealed that the aortic diameter enlargement exceeded 60 mm because of false lumen entry from the ARSA. Therefore, surgical intervention was planned. TEVAR, ARSA embolization, and bilateral axillary bypass surgery were successfully performed for a chronic dissecting aortic aneurysm for which the ARSA was the inflow route. He was discharged 12 days after surgery. Four years later, no enlargement of the aneurysm diameter was observed. TEVAR is a minimally invasive and useful treatment option for chronic type B dissections with an ARSA associated with the left aortic arch; however, patients with an ARSA have fragile blood vessels and require careful follow-up., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor. In this report, we describe the case of a 62-year-old man who presented with pain in the left clavicle and swelling of the left upper limb. Contrast-enhanced computed tomography revealed an intravascular tumor, which was completely resected surgically. Histopathological examination and immunohistochemical staining revealed that it was epithelioid hemangioendothelioma with occurrence in the left brachiocephalic vein. It has been 6 years since the surgery was performed, and no recurrence has been observed. Epithelioid hemangioendothelioma may recur or metastasize and therefore requires careful follow-up., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Aims/introduction: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were reported to increase hemoglobin levels in short-term clinical trials. Whether it is also true in real clinical practice is unknown., Materials and Methods: This is a retrospective cohort study. Inclusion criterion was diabetes patients who visited our outpatient clinic from January 2019 to August 2020. Exposure of interest was the use of SGLT2i. Outcomes were hemoglobin levels. For the cross-sectional analyses, non-linear regression models were fitted with restricted cubic splines to investigate the association between hemoglobin levels and estimated glomerular filtration rate (eGFR) for users and non-users of SGLT2i. For the case-control study, cases (anemia defined as hemoglobin <120 g/L for men, <110 g/L for women or the use of erythropoiesis stimulating agents) and controls were matched by age, sex and eGFR., Results: Among 2,063 diabetes patients, 723 were taking SGLT2i. In the cross-sectional analyses, hemoglobin levels were higher among SGLT2i users compared with non-users at eGFR >15 mL/min/1.73 m 2 . For the case-control study, 197 cases and controls were matched. Conditional logistic regression showed that the use of SGLT2i was associated with significantly lower prevalence of anemia (odd ratio 0.35, 95% confidence interval 0.21-0.58). Adjusted mean differences in hemoglobin levels between users and propensity score-matched non-users of SGLT2i were 7.0 g/L (95% confidence interval 3.0-10.0 g/L) at 6 months. Among SGLT2i users, the odds of an increase in 6-month hemoglobin were similar across eGFR categories, except for eGFR <15 mL/min/1.73 m 2 ., Conclusions: The use of SGLT2i was associated with higher hemoglobin levels and lower prevalence of anemia in real clinical practice., (© 2021 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Previous studies have reported that the expressions of specific proteins may predict the efficacy of chemotherapy agents for non-small cell lung cancer (NSCLC) patients. The present study evaluated the expression of proteins hypothesized to be associated with the effect of chemotherapeutic agents in 38 NSCLC patients with pathological stage II and IIIA. The subjects received carboplatin plus paclitaxel (CP) or S-1 as adjuvant chemotherapy following complete resection. The protein expressions evaluated were those of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phsphoribosyltransferase (OPRT), which were suspected to be associated with the effect of S-1 agents, excision repair cross-complementation group 1 (ERCC1), which was suspected to be associated with the effect of platinum-based agents, and class III β-tubulin (TUBB3), which was suspected to be associated with the effect of taxane-based agents. The positive rate of TS was 55.3% (n=21/38), DPD was 57.9% (n=22/38), OPRT was 42.1% (n=16/38), ERCC1 was 47.4% (n=18/38) and TUBB3 was 44.7% (n=17/38). Among the patients who received S-1 adjuvant chemotherapy, TS-negative cases demonstrated a significantly better disease-free survival than positive cases. Thus, TS protein expression may have been a factor that predicted the effect of S-1 agent as adjuvant chemotherapy.

Nontuberculous mycobacteria (NTM) are rarely isolated from peritoneal dialysis (PD)-associated catheter infections. However, NTM infection is usually difficult to treat and leads to catheter loss. Prompt diagnosis is essential for appropriate treatment. A 70-year-old Japanese man who had been on PD for 2 years and with a medical history of 2 episodes of exit site infections (ESIs) due to methicillin-resistant Staphylococcus aureus was admitted to the hospital due to suspected ESI recurrence. However, Gram staining of the pus revealed no gram-positive cocci. Instead, weakly stained gram-positive rods were observed after 7 days of incubation, which were also positive for acid-fast staining. Rapidly growing NTM Mycobacterium chelonae was isolated on day 14. Despite administering a combination antibiotic therapy, ESI could not be controlled, and catheter removal surgery was performed on day 21. Although PD was discontinued temporarily, the patient did not require hemodialysis, without any uremic symptoms. The catheter was reinserted on day 48, and PD was reinitiated on day 61. The patient was discharged on day 65. Antibiotic therapy was continued for 3 months after discharge, with no indications of recurrent infections observed. It is important to consider the risk of NTM infections in patients on PD. Acid-fast staining could be a key test for prompt diagnosis and provision of an appropriate treatment.

The majority of patients with completely resected stage II or IIIA non-small-cell lung cancer (NSCLC) require adjuvant chemotherapy to improve survival following surgery. In the present trial, the 2-year disease-free survival (DFS), and the feasibility and safety of S-1 as an adjuvant chemotherapy for advanced lung cancer were evaluated. A total of 40 patients with completely resected stage II or IIIA NSCLC were enrolled and randomized to receive postoperative chemotherapy with either up to 4 cycles of paclitaxel plus carboplatin (arm A) or with up to 1 year of S-1 (arm B). The primary endpoint was 2-year DFS. The secondary endpoints were feasibility and toxicity. A total of 40 patients were enrolled, but 3 were excluded in accordance with the exclusion criteria. The remaining 37 patients were analyzed. The 2-year DFS rate was 54.2% in arm A and 84.2% in arm B. Overall, 15/18 (83.3%) patients completed 4 cycles of paclitaxel plus carboplatin and 13/19 (68.4%) completed 1-year of S-1adjuvant chemotherapy. Of the 18 (16.7%) patients in arm A, 3 experienced grade 3 or 4 adverse events, while none in arm B experienced such events. Therefore, S-1 chemotherapy for patients with completely resected stage II or IIIA NSCLC was a feasible and safe regimen, and it may therefore be considered as a potential adjuvant chemotherapy option for advanced NSCLC.

Background: TAFRO (thrombocytopenia, anasarca, fever, reticulin myelofibrosis/renal failure, and organomegaly) syndrome is a systemic inflammatory disorder and unique clinicopathological variant of idiopathic multicentric Castleman disease that was proposed in Japan. Prompt diagnosis is critical because TAFRO syndrome is a progressive and life threating disease. Some cases are refractory to immunosuppressive treatments. Renal impairment is frequently observed in patients with TAFRO syndrome, and some severe cases require hemodialysis. Histological evaluation is important to understand the pathophysiology of TAFRO syndrome. However, systemic histopathological evaluation through autopsy in TAFRO syndrome has been rarely reported previously., Case Presentation: A 46-year-old Japanese man with chief complaints of fever and abdominal distension was diagnosed with TAFRO syndrome through imaging studies, laboratory findings, and pathological findings on cervical lymph node and bone marrow biopsies. Interleukin (IL)-6 and vascular endothelial growth factor (VEGF) levels were remarkably elevated in both blood and ascites. Methylprednisolone (mPSL) pulse therapy was initiated on day 10, followed by combination therapy with PSL and cyclosporine A. However, the amount of ascites did not respond to the treatment. The patient became anuric, and continuous renal replacement therapy was initiated from day 50. However, the patient suddenly experienced cardiac arrest associated with myocardial infarction (MI) on the same day. Although the emergent percutaneous coronary intervention was successfully performed, the patient died on day 52, despite intensive care. Autopsy was performed to ascertain the cause of MI and to identify the histopathological characteristics of TAFRO syndrome., Conclusions: Bacterial peritonitis, systemic cytomegalovirus infection, and Trichosporon asahii infection in the lungs were observed on autopsy. In addition, sepsis-related myocardial calcification was suspected. Management of infectious diseases is critical to reduce mortality in patients with TAFRO syndrome. Although the exact cause of MI could not be identified on autopsy, we considered embolization by fungal hyphae as a possible cause. Endothelial injury possibly caused by excessive secretion of IL-6 and VEGF contributed to renal impairment. Fibrotic changes in anterior mediastinal fat tissue could be a characteristic pathological finding in patients with TAFRO syndrome., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2018.)

BACKGROUND Spontaneous spinal epidural hematoma (SSEH) occurs in the spinal epidural space in the absence of traumatic or iatrogenic causes, and is considered to be a neurological emergency, as spinal cord compression may lead to neurological deficit. Prompt diagnosis of SSEH can be difficult due to the variety of presenting symptoms, which may resemble those of stroke. Patients who undergo hemodialysis (HD) are at risk of bleeding due to anticoagulation during dialysis and uremia. However, SSEH in HD patients undergoing HD has rarely been reported. CASE REPORT A 70-year-old Japanese man, who has been undergoing maintenance HD for the previous three years, was admitted to Kariya Toyota General Hospital, Aichi, Japan, with acute chest and abdominal pain, and with complete paraplegia. The patient denied any recent trauma or medical procedures. Magnetic resonance imaging showed an extensive hematoma in the thoracic and lumbar epidural space, extending from T8 to L5. The patient's symptoms improved within three hours following hospital admission, and after three days without HD treatment, the SSEH decreased in size, and the patient successfully recovered without residual neurological deficits and without requiring surgery. CONCLUSIONS The management of SSEH in patients undergoing HD can be difficult, due to anticoagulation during dialysis and uremia. Prompt diagnosis and close neurological monitoring are important for appropriate management. In patients whose symptoms improve within a short period, conservative management may be considered.

An 89-year-old Japanese man on peritoneal dialysis (PD) was suspected of having a PD-associated catheter infection. He visited the hospital because of the discharge of pus from the exit site of his catheter. Gram staining of the pus showed Gram-positive bacilli, but these were acid-fast bacilli. The rapidly growing nontuberculous mycobacteria, Mycobacterium abscessus, was isolated. PD catheter removal and debridement were immediately performed. The patient received combination antibiotic therapy. His clinical course was good, but he required hemodialysis due to the discontinuation of PD. However, the patient and his family chose not to continue hemodialysis even when the symptoms of uremia appeared. Best supportive care was arranged by his primary care physician. M. abscessus is a rare causative organism for PD-associated catheter infections and is difficult to treat. In our case, a rapid and precise diagnosis was made using acid-fast staining and Mycobacterium culture. The risk of nontuberculous mycobacterial infections should be considered in patients on PD.

A 52-year-old Japanese male professional diver was referred to our hospital for decompression illness (DCI). After 1 h of diving operation at 20 m below sea level, he complained of dyspnea, chest pain, and abdominal pain. He dove again, intending to ease the symptoms, but the symptoms were never relieved. He dove for a total of 4 h. No neurological abnormalities were observed. Computed tomography images revealed portal venous gas and mesenteric venous gas, in addition to bubbles in the femoral veins, pelvis, lumbar canal, intracranial sinuses, and joints. Hyperbaric oxygen therapy (HBOT) was immediately administered. His symptoms improved after the first course of HBOT, however, the patient had anuria for almost 36 h after admission and exhibited acute kidney injury (AKI). Serum creatinine and creatine kinase (CK) levels were increased to maximal values of 6.16 mg/dL and 18,963 U/L, respectively. Blood flow signals were not detected on kidney Doppler ultrasound. We considered that AKI was caused by blood flow impairment and capillary leak syndrome due to DCI in addition to rhabdomyolysis secondary to arterial gas embolism in the skeletal muscles. Temporary dialysis was required to correct the acidemia and electrolyte disturbance. Diuretic phase was initiated, and the patient was put off dialysis on day 3. Serum creatinine and CK levels returned to normal on day 11. He was successfully treated without any complications. Although AKI is a rare manifestation, we should consider AKI risk in patients with severe DCI.

In polyandrous mating systems, sperm competition and cryptic female choice (CFC) are well recognized as postcopulatory evolutionary forces. However, it remains challenging to separate CFC from sperm competition and to estimate how much CFC influences insemination success because those processes usually occur inside the female's body. The Japanese pygmy squid, Idiosepius paradoxus, is an ideal species in which to separate CFC from sperm competition because sperm transfer by the male and sperm displacement by the female can be observed directly at an external location on the female's body. Here, we counted the number of spermatangia transferred to, removed from, and remaining on the female body during single copulation episodes. We measured behavioral and morphological characteristics of the male, such as duration of copulation and body size. Although males with larger body size and longer copulation time were capable of transferring larger amounts of sperm, females preferentially eliminated sperm from males with larger body size and shorter copulation time by spermatangia removal; thus, CFC could attenuate sperm precedence by larger males, whereas it reinforces sperm precedence by males with longer copulation time. Genetic paternity analysis revealed that fertilisation success for each male was correlated with remaining sperm volume that is adjusted by females after copulation., (© 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.)

Introduction: Liposarcoma is one of the most common soft tissue sarcomas; however, early diagnosis is rare as the tumor remains difficult and unpalpable for a prolonged period of time., Presentation of Case: Here we report the first case of retroperitoneal liposarcoma associated with pregnancy and expression of estrogen receptor. A 34-year-old woman experienced persistent abdominal distension after her first delivery. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a large (40cm×35cm), solid, palpable abdominal mass with fat attenuation displacing the ascending colon and the right kidney to the left. Laparotomy and an en-bloc resection of the tumor were performed; further, right nephrectomy and adrenalectomy were required. Histopathology showed a well-differentiated liposarcoma; approximately 10-20% of the tumor cells were ER-positive., Discussion: Retroperitoneal liposarcoma associated with pregnancy is an extremely rare occurrence. Surgical resection is unquestionably the first choice of treatment, but complete resection is sometimes impossible due to the volume and depth of invasion of the tumor. In such cases, additional therapy for liposarcoma is important to improve prognosis. Thus, this report highlights the need for further research into hormone therapy., Conclusion: Retroperitoneal liposarcoma has a high local recurrence rate due to the difficulty in complete surgical resection; therefore, additional hormone therapy is important for improving the prognosis., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We experienced a leiomyosarcoma of the breast in an 18-year-old female. No specific treatment has been established. In order to clarify appropriate therapeutic management methods, the limited data available from our and previous case reports were assessed. A leiomyosarcoma of the breast must be excised with a negative margin. If the tumor size is large and an adequate margin, greater than 3-cm margin around the excised tumor, is not achieved due to anatomical constraints, radiotherapy may be indicated., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

We verified whether telomere length shortens with age in the loggerhead sea turtle (Caretta caretta) by measuring telomere lengths (relative telomere to single copy gene [T/S] ratios) in whole blood and epidermis from 20 captive individuals with a real-time PCR method. There was no significant correlation between age and relative T/S ratios in blood. Although the correlation between age and relative T/S ratios in epidermis was not significant, older turtles had smaller relative T/S ratios in epidermis. It was thus demonstrated that telomere length in epidermis could be a useful age estimator for sea turtles. Relative age information obtained with this simple, rapid, non-invasive technique may help to advance our understanding of the ecology of endangered sea turtles. This is the first publication on age-related changes in telomere length among chelonians.

A 76-year-old Japanese man was admitted to Kosei-Nenkin Hospital (Osaka, Japan) in November 2006; his chief complaint was a 10-kg loss in body weight over 3 months prior to admission. Abdominal computed tomography (CT) and dynamic magnetic resonance imaging (MRI) showed three masses in the retroperitoneum. The patient subsequently underwent surgery. The final histopathological diagnosis of tumors 1 and 2 was malignant fibrous histiocytoma of the retroperitoneum, and tumor 3 was a well-differentiated liposarcoma. By the presence of the liposarcoma, tumor 1 and 2 were thought to be the dedifferentiated areas of liposarcomas. At the age of 16, the patient had been exposed to radiation from the atomic bomb at Hiroshima towards the end of the Second World War. We postulate that in this case, radiation from the atomic bomb may have played an important role in the development of the sarcomas.

Soluble forms of major histocompatibility complex (MHC) class I-related chain A and B (MICA/B) are increased in the sera of patients with malignancy and impair the antitumor immune response by downregulating expression of their cognate immunoreceptor natural killer group 2, member D (NKG2D). Recently, soluble MICA/B were reported to appear even in some premalignant diseases, raising questions about the impact of soluble MICA/B produced from tumors on the expression of NKG2D. The present study examined soluble MICA/B in chronic liver disease and hepatocellular carcinoma (HCC) and their involvement in the immune-cell expression of NKG2D during transcatheter arterial embolization for HCC. The levels of soluble MICA/B were significantly higher in chronic liver disease and HCC patients than in healthy volunteers. The progression of liver disease and that of the tumor were independent determinants for soluble MICA/B levels. Immunohistochemistry revealed that MICA/B were expressed not only in HCC tissue but also on hepatocytes in cirrhotic livers. The transcatheter arterial embolization therapy significantly decreased serum levels of soluble MICA, but not soluble MICB, and increased the NKG2D expression on natural killer cells and CD8-positive T cells; there was an inverse correlation between changes in soluble MICA levels and in NKG2D expression. In conclusion, although soluble MICA/B are produced from both HCC and premalignant cirrhotic livers, therapeutic intervention for HCC can reduce the levels of soluble MICA and thereby upregulate the expression of NKG2D. Cancer therapy may have a beneficial effect on NKG2D-mediated antitumor immunity.

Pancreatic ductal adenocarcinoma (PDAC) shows the worst mortality rate among common malignancies, with a 5-year survival rate of only 4%, and the majority of PDAC patients are diagnosed at an advanced stage in which no effective therapy is available at present. Although the proportion of curable cases is still not so high, surgical resection of early stage PDAC is the only way to cure the disease. Hence, establishment of a screening strategy to detect early stage PDAC by novel serological markers is required urgently, and development of novel molecular therapies for PDAC treatment is also eagerly expected. We here report overexpression of REG4, a new member of the regenerating islet-derived (REG) family, in PDAC cells on the basis of genome-wide cDNA microarray analysis as well as reverse transcription-polymerase chain reaction and immunohistochemical analysis. We also detected significant elevation of REG4 in the serum of some patients with early-stage PDAC using our enzyme-linked immunosorbent assay system, indicating the possibility of REG4 as a new serological marker of PDAC. Furthermore, we found that knockdown of endogenous REG4 expression in PDAC cell lines with small interfering RNA caused a decrease in cell viability. Concordantly, addition of recombinant REG4 to the culture medium enhanced growth of a PDAC cell line in a dose-dependent manner. A monoclonal antibody against REG4 neutralized its growth-promoting effects and attenuated significantly the growth of PDAC cells. These findings indicate that REG4 is a promising tumor marker to screen early-stage PDAC, and also that neutralization of REG4 by the antibody may offer novel potential tools for the treatment of PDAC.

Background: Accelerated partial breast irradiation (APBI) is generally limited to patients at extremely low risk of local recurrence. The significance of the risk factors, however, depends on the extent of surgery, radiation, and systemic therapy. In Japan, wide excision is generally supplemented by intraoperative margin-directed re-excision if the frozen section examination yields positive results. This approach combined with conventional radiotherapy achieved an excellent 10-year local control rate of 93%, and young age and ductal carcinoma in situ were not risk factors for local recurrence. To reduce the treatment duration, high-dose-rate interstitial brachytherapy (HDRIB) was employed. The first APBI phase I / II trial in Japan was conducted to determine if wider indications for early breast cancer patients were appropriate., Methods: The subjects comprised 20 patients including those with extensive intraductal component (n=7), ductal carcinoma in situ (n=2), positive final margins (n=3), and of younger age (< or = 45 years; n=5). Breast-conserving surgery using an intraoperative re-excision approach was followed by intraoperative implantation of applicators. Sole HDRIB of a 36-42 Gy in 6-7 fractions was delivered postoperatively over 3-4 days. Tumors were staged as follows: cT1 (n=12), cT2 (n=8), cN0 (n=20). Systemic therapy was used in 16 patients (80%). The median follow-up period was 52 months (range, 26-86 months)., Results: Te five-year crude local, distant control, and Kaplan-Meier cause-specific survival rates were 95%, 95%, and 89%, respectively. Fat necrosis developed in 1 patient., Conclusions: Sole HDRIB with intraoperative margin-directed re-excision was feasible under wider indications compared to other contemporary APBI series, and achieved acceptable and similar results to these series in terms of the local control rate and complications.

Background: A considerable percentage of gallbladder cancers are accompanied by superficial cancer spread adjacent to the main tumor, therefore cholecystectomy for early gallbladder cancer must be performed carefully to avoid leaving cancer cells at the surgical margins., Methods: Thirty-two patients with gallbladder cancer invading no more than perimuscular connective tissue underwent surgical resection at our medical center. After the operation, resected specimens were investigated macroscopically and microscopically to clarify the clinicopathological features and the risk factors of superficial cancer spread., Results: Sixty-six percent of all cases (21 cases) had superficial cancer spread. Comparison between the cases having superficial cancer spread and the cases without it revealed that the macroscopic morphology of the primary tumor and the depth of cancer invasion in the gallbladder wall were significantly different between the two groups. Furthermore, multivariate analysis indicated that 'superficial raised type' in macroscopic morphology was an independent predictive factor for having superficial cancer spread. Superficial cancer spread from the main tumor located in the neck of the gallbladder grows predominantly in the direction of the fundus. More advanced gallbladder cases were accompanied by more extensive superficial spread., Conclusions: Superficial cancer spread is frequently observed adjacent to the gallbladder cancer, especially in the superficial raised type. A negative margin should be confirmed by intraoperative frozen section histology while performing cholecystectomy.

Background: In the West, the incidence of adenocarcinoma of the cardia or esophagogastric junction (EGJ) is increasing. This carcinoma is variously defined, however, and it contains heterogeneous tumors. In Japan, the frequency of this carcinoma is low, and little is known about it. We studied small esophagogastric junctional adenocarcinoma to determine its characteristics in Japanese patients., Methods: Fifty-four patients with Siewert type II junctional adenocarcinoma (with tumors <<4 cm in maximum diameter) were studied. The carcinomas were classified into two types: tumors straddling the EGJ (EGJ-type) and tumors occurring entirely below the EGJ (bEGJ-type). Characteristics of the tumors and surrounding mucosae were evaluated. Phenotypic expression of mucin, p53 overexpression, and Helicobacter pylori infection were investigated histologically and immunohistochemically., Results: Twenty-three (43%) patients had EGJ-type and 31 (57%) had bEGJ-type carcinomas. The ratio of advanced cancers was significantly higher in EGJ-type. Some between-group similarities and differences existed in histological type, mucin phenotype, and p53 protein overexpression, but they were not statistically significant. In the mucosa surrounding EGJ-type tumors vs bEGJ-type tumors, oxyntic glands were significantly better preserved, gastric intestinal metaplasia occurred significantly less frequently, and the H. pylori infection rate was lower. Barrett's metaplasia was seen in only 2 patients, with the EGJ-type., Conclusion: EGJ-type and bEGJ-type adenocarcinomas have different background mucosa of the stomach. EGJ-type has less atrophy of the oxyntic glands and less intestinal metaplasia in the stomach. This type appears to be the Western-type junctional adenocarcinoma that is still rare in Japan. Many cases of advanced junctional adenocarcinoma in Japan are of subjunctional origin.

Helicobacter pylori (H. pylori) is considered to be a cause of gastric ulcer, gastric cancer and other diseases. The relationship between infection and the hygiene or housing circumstances of such patients in their childhood was explored. The study subjects were those who applied for a H. pylori antibody test, and were asked to fill out a questionnaire enclosed with a test kit, inquiring as to their hygiene and housing conditions when they were 10 years old. Of 5971 applicants, 5854 agreed to participate in the study. Associations between the six factors in the questionnaire and infection were calculated, and adjusted for sex, age and district. Drinking water, type of toilet, residential area, number of people in the house, and birth order showed significant correlations with H. pylori infection. The odds ratios (95% confidence intervals) were 0.73 (0.55-0.96) for tap water, 0.72 (0.63-0.84) for flush toilets, 0.74 (0.66-0.83) for urban location, 1.34 (1.09-1.64) for 7 or more people in the household, 1.19 (1.00-1.41) for 4th or 5th in birth order, and 1.47 (1.17-1.85) for 6th or more in birth order. No significant association with breast feeding was observed. These results suggest that infection with H. pylori may be associated with water-related sanitary factors in childhood, and that the bacillus may be transmitted within a family.

Objective: To evaluate the postoperative cytology of drained fluid from the pancreatic bed as a predictive indicator of local recurrence after curative (R0) resection of pancreatic cancer., Summary Background Data: The pancreatic bed offers a common site of cancer recurrence (local recurrence), even after curative (R0) resection is performed for pancreatic cancer. If local recurrence is thereby predicted precisely, soon after surgery, we have a chance to treat it by adding radiation or some other locoregional therapy before it can grow or spread beyond the pancreatic bed. However, there have been no previous reports of cytology performed on the drained fluid after pancreatectomy., Methods: This study includes 94 patients who had shown negative results in the peritoneal washing cytology before resection and subsequently received pancreatectomies for pancreatic tumors. They consisted of 12 benign tumors, 17 noninvasive or minimally invasive carcinomas and 65 invasive ductal carcinomas (R0 = 58; R1/2 = 7). Postoperatively, the drained fluid from the pancreatic bed was collected for 24 hours and used for cytologic examination. The cytologic results were examined in association with the histopathology of the resected tumor, patient's survival, and mode of cancer recurrence, including local recurrence., Results: Patients with benign tumors or noninvasive/minimally invasive carcinomas had negative result in cytology, and none of them have died of local recurrence (limited to the pancreatic bed) to date. However, patients with invasive ductal carcinoma revealed higher cytology-positive rates: 28% (16/58) in curative (R0) resection; and 71% (5/7) in noncurative (R1/2) resection. Among 58 patients with R0 resection, the 3-year survival rate was 14% in 16 cytology-positive patients and 55% in 42 cytology-negative patients (P < 0.05). The 3-year cumulative rate of local recurrence was 85% and 23%, respectively (P < 0.05). Compared with other histopathologic parameters obtained from the resected specimens, the drain cytology was more specific in predicting the subsequent development of local recurrence., Conclusions: Drain-cytology was a quick examination that enabled us to specifically indicate both minute residual cancer and subsequent development of local recurrence even after R0 resection of pancreatic cancer.

Objective: To determine whether subtumoral injection of radiocolloid is useful for lymphoscintigraphic visualization of the internal mammary node and in sentinel lymph node (SLN) biopsy of the axilla in breast cancer patients., Summary Background Data: The presence of retromammary lymphatics connecting to the axillary and internal mammary basins has been demonstrated by early anatomic studies. Thus, it is hypothesized that some lymph, especially that from the parenchyma under the tumor, may drain into both the axillary and internal mammary basins., Methods: Patients (n = 196) with T1-2, N0 breast cancer underwent preoperative lymphoscintigraphy with radiocolloid (technetium 99m tin colloid) injection into various sites of the breast, followed by SLN biopsy using the combined method with blue dye. Patients were divided into four groups: group A (n = 41), peritumoral injection of both radiocolloid and blue dye; group B (n = 70), periareolar radiocolloid and peritumoral blue dye; group C (n = 45), intradermal radiocolloid and periareolar blue dye; and group D (n = 40), subtumoral radiocolloid and intradermal blue dye. A retrospective analysis of 1,297 breast cancer patients who underwent extended radical mastectomy with internal mammary node dissection was also conducted to determine the relationship between vertical tumor location (superficial or deep) and frequency of axillary and internal mammary node metastases., Results: One patient (2%) in group A, 3 (4%) in group B, 0 (0%) in group C, and 15 (38%) in group D exhibited hot spots in the internal mammary region on lymphoscintigraphy (P <.001, group D vs. the other groups). The concordance rate of radiocolloid and blue dye methods in detection of SLNs in the axillary basin was significantly lower in group D than in the other groups. In contrast, the mismatch rate (some SLNs were identified by radiocolloid and other SLNs were identified by blue dye, but no SLN was identified by both in the same patient) was significantly higher in group D than in the other groups. In patients treated with extended radical mastectomy, positivity of axillary and internal mammary metastases was significantly higher in patients (n = 215) with deep tumors than those (n = 368) with superficial tumors., Conclusions: These results suggest the presence of a retromammary lymphatic pathway from the deep portion of the breast to both axillary and internal mammary basins, which is distinct from the superficial pathway. Therefore, SLN biopsy with a combination of subtumoral and other (peritumoral, dermal, or areolar) injections of radiocolloid will improve both axillary and internal mammary nodal staging.

Recently, there have been a few case reports of invasive ductal adenocarcinoma (IDC) developed in the remnant pancreas after partial pancreatectomy for intraductal papillary-mucinous neoplasm (IPMN). It is necessary to clarify their histogenetic relationships among two sporadic tumors and their surrounding duct epithelium and it would be more reliable if genetic analysis is added to the conventional histology. We report a 76-year-old woman who received pancreaticoduodenectomy for IPMN with a focal in situ carcinoma (IPMC), which was transitional to the surrounding duct epithelium with papillary proliferation and a wide variety of dysplasia. Nine years after the operation, she died of IDC in the remnant pancreatic body and its surrounding duct epithelium consisted of hyperplastic mucous cells with slight-mild dysplasia. Analysis of K-ras mutation at codon 12 (wild-GGT) by direct sequencing after polymerase chain reaction indicated that their transitioning patterns differed from each other: CGT in IPMC; no mutation in the mildly dysplastic duct epithelium around IPMC; GAT in IDC of the remnant pancreas; and AGT in mucous cell hyperplasia with mild dysplasia close to the IDC. This is the first report in which the DNA sequence of K-ras mutation was determined for the two sporadic pancreatic cancers and surrounding duct changes. The following two suggestions are made: (1) the cell-origin might have differed between the two types of cancer (IDC and IPMC); and (2) no precursor lesion toward IDC or IPMC was identified in their surrounding duct epithelium.