A Case of Insulinoma with Hyperprocalcitoninemia and Hypercalcitoninemia Showing Coexpression of Insulin and Calcitonin in Its Tumor Cells.

Neuroendocrine neoplasms can produce multiple hormones that are released into the bloodstream, causing symptoms that vary depending on the type and quantity of hormones involved. We herein report a 63-year-old asymptomatic patient with pancreatic insulinoma who showed marked elevations in circulating calcitonin and procalcitonin levels that returned to normal following surgery. Immunohistochemical analyses confirmed the co-staining of calcitonin and insulin immunoreactivity in the tumor cells, suggesting a calcitonin-producing insulinoma. This insulinoma released calcitonin and a considerable amount of its precursor peptide, procalcitonin, resulting in both hyperprocalcitoninemia and hypercalcitoninemia.

A Comparative Study of Tumor-Specificity and Neurotoxicity between 3-Styrylchromones and Anti-Cancer Drugs.

Background. Many anti-cancer drugs used in clinical practice cause adverse events such as oral mucositis, neurotoxicity, and extravascular leakage. We have reported that two 3-styrylchromone derivatives, 7-methoxy-3-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one (Compound A) and 3-[(1E)-2-(4-hydroxyphenyl)ethenyl]-7-methoxy-4H-1-benzopyran-4-one (Compound B), showed the highest tumor-specificity against human oral squamous cell carcinoma (OSCC) cell lines among 291 related compounds. After confirming their superiority by comparing their tumor specificity with newly synthesized 65 derivatives, we investigated the neurotoxicity of these compounds in comparison with four popular anti-cancer drugs. Methods: Tumor-specificity (TSM, TSE, TSN) was evaluated as the ratio of mean CC50 for human normal oral mesenchymal (gingival fibroblast, pulp cell), oral epithelial cells (gingival epithelial progenitor), and neuronal cells (PC-12, SH-SY5Y, LY-PPB6, differentiated PC-12) to OSCC cells (Ca9-22, HSC-2), respectively. Results: Compounds A and B showed one order of magnitude higher TSM than newly synthesized derivatives, confirming its prominent tumor-specificity. Docetaxel showed one order of magnitude higher TSM, but two orders of magnitude lower TSE than Compounds A and B. Compounds A and B showed higher TSM, TSE, and TSN values than doxorubicin, 5-FU, and cisplatin, damaging OSCC cells at concentrations that do not affect the viability of normal epithelial and neuronal cells. QSAR prediction based on the Tox21 database suggested that Compounds A and B may inhibit the signaling pathway of estrogen-related receptors.

Chronic hyperadiponectinemia induced by transgenic overexpression increases plasma exosomes without significantly improving glucose and lipid metabolism.

The fat-derived factor, adiponectin, is considered a salutary circulating factor. We recently demonstrated that native adiponectin binds T-cadherin and promotes intracellular biogenesis and secretion of the exosome. Exosomes play important roles in various aspects of homeostasis, including glucose and energy metabolism. However, it remains unclear whether and how the promotion of exosome production by adiponectin in vivo is beneficial for glucose and lipid metabolism. In the present study, overexpression of human adiponectin in mice resulted in an increased number of circulating exosomes, but it did not significantly improve glucose metabolism, change body weights, or change triglyceride clearance under a high-fat diet. Multiple small doses of streptozotocin increased blood glucose and decreased triglyceride clearance similarly in both wild-type and transgenic mice. Thus, these results indicated that human adiponectin overexpression in mice increases plasma exosomes but does not significantly influence glucose and lipid metabolism.

Changes in Eating Behaviors and Their Associations with Weight Loss in Japanese Patients Who Underwent Laparoscopic Sleeve Gastrectomy.

BACKGROUND: Metabolic and bariatric surgery (MBS) has been established to provide long-term weight loss in severe obesity. In this study, we investigated the factors that affect post-operative weight loss, with a particular focus on changes in eating behaviors. METHODS: Time-course changes in body weight and eating behaviors were examined in 49 Japanese patients who underwent laparoscopic sleeve gastrectomy from the first visit to 12 months after surgery. Each eating behavior was evaluated via the questionnaire of the Japan Society for the Study of Obesity. RESULTS: Pre-operative weight reduction mediated by dietary and lifestyle interventions showed significant positive correlations with weight loss outcomes at 12 months after surgery. We observed significant decreases in scores for most of the eating behaviors 12 months after surgery. However, "emotional eating behavior" scores declined temporarily in the early post-operative period of one month but thereafter returned to the pre-operative level at 12 months. Furthermore, increases in the scores for "emotional eating behavior" and "sense of hunger" from 1 to 12 months post-operatively were significantly associated with poor weight loss. CONCLUSIONS: Our results demonstrate the beneficial effects of MBS on obesity-related eating behaviors, as well as highlighting "emotional eating behavior" as requiring particular attention.

Prognostic impacts of categorized postoperative complications in surgery for gastric cancer.

BACKGROUND: Postoperative complications generally aggravate postoperative prognosis and are correlated with both cancer-specific death and death from other causes. METHODS: Subjects were 197 patients who underwent gastrectomy at Kyoto Chubu Medical Center. Cancer-specific survival (CSS) and non-CSS (NCSS) were compared between cases with and without complications. Major complications were classified into C-com and N-com groups based on their prognostic impact on CSS and NCSS, respectively. Uni- and multivariate analyses were conducted using clinicopathological factors. RESULTS: During the study period, 30 patients (15.2%) died from gastric cancer and 34 (17.3%) died from other causes. The incidence of postoperative complications was 16.8%. Sixteen patients with anastomosis leakage, pancreatic fistula, or organ/space surgical site infection had significantly poorer CSS, whereas 30 patients with pneumonia or passage obstruction had significantly poorer NCSS. These were defined as C-com and N-com cases, respectively. In the uni- and multivariate analyses, C-com was a significant prognostic factor for CSS (p = 0.002, p = 0.039) and N-com was a significant prognostic factor for NCSS (p < 0.0001, p = 0.004). C-reactive protein levels indicated intermediate and severe inflammation in N-com and C-com cases, respectively. CONCLUSION: In N-com cases, surgical stress caused disruption of essential organ function, whereas damage in C-com cases occurred mostly in the abdominal cavity but was a risk for cancer regrowth. Thus, different postoperative complications worsen patient prognosis after gastrectomy in different ways. To optimize surgical outcomes, improved selection of treatment strategies for different complication types may be important.

Hotspot analysis of COVID-19 infection using mobile-phone location data.

Restrictions on outdoor activities are required to suppress the COVID-19 pandemic. To monitor social risks and control the pandemic through sustainable restrictions, we focus on the relationship between the number of people going out and the effective reproduction number. The novelty of this study is that we have considered influx population instead of staying-population, as the data represent congestion. This enables us to apply our analysis method to all meshes because the influx population may always represent the congestion of specific areas, which include the residential areas as well. In this study, we report the correlation between the influx population in downtown areas and business districts in Tokyo during the pandemic considering the effective reproduction number and associated time delay. Moreover, we validate our method and the influx population data by confirming the consistency of the results with those of the previous research and epidemiological studies. As a result, it is confirmed that the social risk with regard to the spread of COVID-19 infection when people travel to downtown areas and business districts is high, and the risk when people visit only residential areas is low.

Impact of Preoperative Nutritional Indicator on Poor Postoperative Outcomes in Geriatric Patients with Colorectal Cancer.

The present study aimed to analyze the association between preoperative nutritional assessment and poor postoperative outcomes in geriatric patients with colorectal cancer. This retrospective study included 138 patients aged ≥80 years with colorectal cancer who underwent surgery from January 2013 to December 2018. Patients were classified into two groups according to outcomes, poor group and normal group. Clinicopathological factors were compared between the groups, and the relationships of several nutritional indices were examined. There was no significant difference in sex, age, or preoperative comorbidities. There were significant differences in volume of blood loss and proportion of laparoscopic surgery. The group with poor outcomes had significantly higher neutrophil/lymphocyte ratio (NLR) and modified Glasgow prognostic score (mGPS) than the group with normal outcomes. Multivariate analysis revealed that open approach, high NLR, and category D mGPS were independent risk factors of poor postoperative outcomes in elderly patients with colorectal cancer. Our findings indicate that mGPS and NLR could be useful nutritional indicators of short-term outcomes of surgical treatment in geriatric patients with colorectal cancer. They can be evaluated based on albumin and C-reactive protein levels and blood count, which are inexpensive and beneficial to use in routine clinical practice.

[Two Cases of Blind Pouch Syndrome after Total Gastrectomy].

Blind loop syndrome(BLS)is one of the complications that can occur after intestinal anastomosis. Patients with the syndrome present with various clinical features, including nutrient malabsorption caused by the blind end as a result of the anastomotic morphology. On the other hand, blind pouch syndrome(BPS)is a subtype of BLS. While it has a similar underlying mechanism, the clinical symptoms of patients with BPS are significantly different from those of patients with BLS; ie, the symptoms develop almost locally without nutrient malabsorption. There have been some reports that dealt with BPS as a disease that was distinct from BLS. Since conservative treatment cannot be expected to produce a curative effect in patients with BPS, it is necessary to administer surgical treatment in many cases. Previous studies have reported that resection of the blind pouch, which caused the local symptoms, was a curative surgical procedure for BPS. In the present study, we report 2 cases of BPS after Roux-en-Y reconstruction during total gastrectomy for gastric cancer patients, that were cured by surgical treatment by creating a bypass to the blind pouch.

Synthesis and antifungal activity of polycyclic pyridone derivatives with anti-hyphal and biofilm formation activity against Candida albicans.

Thirty-five pyridone derivatives were synthesized, with derivatization conducted on polycyclic pyridone scaffolds, including cis- or trans-oxydecalin and other cyclic structures, by domino-Knoevenagel-electrocyclic reactions. The anti-fungal activities of the synthesized compounds were tested against Candida albicans. Ten compounds inhibited hyphal formation without inhibiting growth. Pyridones with anti-hyphal formation activity (4c, 6d, 12a and 12c) were tested for their ability to inhibit biofilm formation. Compound 6d showed both anti-hyphal and biofilm inhibition activity.

[Comparison between Overall Survival and Disease-Specific Survival after Surgery in Gastric Cancer].

BACKGROUND: It has been reported that we should give consideration to death caused by other disease from comparison between overall survival(OS)and disease specific survival(DSS)in several studies. PATIENTS AND METHODS: Relationships between the clinicopathological features of OS and DSS were examined among 197 patients undergoing surgery for gastric cancer. RESULTS: In OS analysis, the Charlson comorbidity index(CCI), pathological T and postoperative complications with Clavien-Dindo Grade≥Ⅲ were associated significantly in multivariate analyses(p=0.009, 0.022, 0.027). On the other hand, in DSS analysis, CCI was not associated, but gender, DG/TG, pathological N and complication were associated significantly( p=0.0002, 0.016, 0.0003, 0.009). CONCLUSION: The complication is a significant prognostic factor of OS and DSS in gastric cancer patients. It is important to pay attention for comorbidities and to prevent the postoperative complications in order to improve the prognosis in gastric cancer surgical therapy.

[Impact of the Age-Adjusted Charlson Comorbidity Index on Postoperative Complications after Gastric Cancer Surgery].

BACKGROUND: The primary objective of this retrospective study was to examine the association between the age-adjusted Charlson comorbidity index(aCCI)score and postoperative complications after gastric cancer surgery. METHOD: A total of 237 patients who underwent distal/total gastrectomy for gastric cancer between 2012 and 2020 were enrolled in this study. The aCCI and CCI were calculated by weighting individual comorbidities. The correlations between the clinicopathologic features, including CCI or aCCI, and postoperative complications were analyzed statistically. RESULTS: Univariate and multivariate analyses demonstrated that both the CCI- and aCCI- high classifications were significant risk factors for postoperative complications. CONCLUSION: The aCCI exhibits a suitable predictive ability for patients undergoing gastric surgery. Although patients with a CCI≤2 showed little risk, patients with an aCCI≥5 were at a high surgical risk and should receive very careful attention for postoperative complication(s).

[A Case of R0 Resection, with Preservation of Bladder Function, of Advanced Rectal Cancer Infiltrating the Bladder with a Single Metastatic Liver Tumor Due to Preoperative Chemotherapy].

A 75-year-old man was diagnosed with advanced rectal cancer infiltrating the bladder and a single metastatic liver tumor. The patient first underwent colostomy followed by 8 cycles of chemotherapy, using a regimen of cetuximab, calcium levofolinate hydrate, fluorouracil and oxaliplatin(Cmab plus mFOLFOX6). This treatment resulted in a partial response(PR). Five months after the first operation, laparoscopic partial hepatectomy(S4), low anterior resection and ileostomy by laparotomy were performed. The pathological findings were T4b, N1b, M1a, H1, ypStage Ⅳa and all surgical margins were negative, so R0 resection was performed for preservation of bladder function. The patient received adjuvant chemotherapy and has survived without recurrence for 10 months after the second operation. The preoperative chemotherapy permitted combined resection of the bladder and urostomy. This is important because a double stoma commonly reduces quality of life. Thus, Cmab plus mFOLFOX6 may be useful as preoperative chemotherapy to preserve bladder function and quality of life.

Phosphonated mesoporous silica nanoparticles bearing ruthenium complexes used as molecular probes for tracking oxygen levels in cells and tissues.

Molecular oxygen plays an important role in living organisms. Its concentration and fluctuation in cells or tissues are related to many diseases. Therefore, there is a need for molecular systems that can be used to detect and quantify oxygen levels in vitro and in vivo. In this study, we synthesized phosphonated mesoporous silica nanoparticles bearing ruthenium complexes in their pores (pM-Rus) and evaluated their photophysical and biological properties. The pM-Rus were highly soluble in water and showed robust phosphorescence under hypoxic conditions, while the addition of oxygen suppressed this emission. Cellular experiments revealed that pM-Rus with a size of 100 nm showed efficient cellular uptake to emit phosphorescence in hypoxic cells. In addition, pM-Rus have negligible toxicity to cells due to the blockage of direct contact between ruthenium complexes and intracellular biomolecules and the deactivation of singlet oxygen (1O2) generated by photoexcitation of ruthenium complexes before leaking out of the pores. Animal experiments confirmed that pM-Rus showed robust emission at hypoxic regions in mice. Thus, pM-Rus are promising oxygen probes for living systems.

Photoacoustic in vivo 3D imaging of tumor using a highly tumor-targeting probe under high-threshold conditions.

Three-dimensional (3D) representation of a tumor with respect to its size, shape, location, and boundaries is still a challenge in photoacoustic (PA) imaging using artificial contrast agents as probes. We carried out PA imaging of tumors in mice using 800RS-PMPC, which was obtained by coupling of 800RS, a near-infrared cyanine dye, with PMPC, a highly selective tumor-targeting methacrylate polymer having phosphorylcholine side chains, as a probe. The conjugate 800RS-PMPC forms compact nanoparticles (dDLS = 14.3 nm), retains the biocompatibility of the parent polymer (PMPC) and exhibits unprecedented PA performance. When applied to mice bearing a 6 × 3 × 3 mm3 tumor buried 6 mm beneath the skin, the probe 800RS-PMPC selectively accumulates in the tumor and emits PA signals that are strong enough to be unambiguously distinguished from noise signals of endogenous blood/hemoglobin. The PA image thus obtained under high-threshold conditions allows 3D characterization of the tumor in terms of its size, shape, location, and boundaries.

Aggregate Formation of BODIPY-Tethered Oligonucleotides That Led to Efficient Intracellular Penetration and Gene Regulation.

Exogenous nucleic acids showed low efficiency regarding cellular uptake and low stability in biological conditions; therefore, a number of techniques have been developed to improve their basic properties. One of the best solutions is the application of nanosized particles consisting of oligonucleotides that penetrate the cell membrane without any additives and exhibit high stability in cells. In this report, we employed a simple approach to address the basic properties of nanoparticles of oligonucleotides in biological systems. We prepared BODIPY-labeled oligonucleotides that carried an exclusive modification at the strand end. BODIPY shows high hydrophobicity and fluorescent emission; therefore, the oligonucleotides formed nanosized aggregates in aqueous solution and their behaviors in cells or tissues were easily tracked. Detailed experiments revealed that aggregate formation was indispensable for the high cellular uptake of the oligonucleotides via scavenger-receptor-mediated endocytosis. In addition, the aggregates provided an efficient gene regulation in living cells and tumor tissues transplanted into mice.

Biological reduction of nitroimidazole-functionalized gold nanorods for photoacoustic imaging of tumor hypoxia.

Tumor-selective accumulation of gold nanorods (GNR) has been demonstrated for visualization of tumor hypoxia by photoacoustic imaging. We prepared GNRs with hypoxia-targeting nitroimidazole units (G-NI) on their surface. Biological experiments revealed that G-NI produced a strong photoacoustic signal in hypoxic tumor cells and tissues.

[A Distal Bile Duct Carcinoma Patient Who Underwent Surgical Resection for Liver Metastasis].

A 70-year-old man with distal bile duct carcinoma underwent a subtotal stomach-preserving pancreaticoduodenectomy without adjuvant chemotherapy. One and a half years after the surgery, elevated levels of serum SPan-1(38.1 U/mL)were observed and CT scans demonstrated a solitary metastasis, 25mm in size, in segment 8 of the liver. The patient received 2 courses of gemcitabine-cisplatin combination chemotherapy. No new lesions were detected after chemotherapy and the patient underwent a partial liver resection of segment 8. The pathological examination revealed a metachronous distant metastasis originating from the bile duct carcinoma. Subsequently, the patient received S-1 adjuvant chemotherapy for 6 months. Following completion of all therapies, the patient survived without tumor recurrence for 3 years and 10 months after the initial operation. Thus, surgical interventions might be effective in improving prognosis among selected patients with postoperative liver metastasis of bile duct carcinoma.

Homogeneous Sc(OTf)3-Catalyzed Direct Allylation Reactions of General Alcohols with Allylsilanes.

Homogeneous Sc(OTf)3 used in nitromethane showed excellent catalytic activity for the direct allylation reactions of general alcohols including benzylic, propargylic, allylic, and some aliphatic alcohols with allyltrimethylsilane under mild and neutral reaction conditions. Metal-free ß-silyl-substituted carbocations are intermediates generated by the highly oxophilic Sc(OTf)3-assisted rapid removal of a hydroxyl group in alcohols, which is supported by the result that allylation of (R)-1-(naphthalen-2-yl)ethan-1-ol with allytrimethylsilanes using the Sc(OTf)3 catalyst combined with (R)- or (S)-[1,1'-binaphthalene]-2,2'-diol ligands gave only racemic 2-(pent-4-en-2-yl)naphthalene in quantitative yield. The present study resolves the argument about the uncertain catalytic activity of Sc(OTf)3.

Polymeric 1 H MRI Probes for Visualizing Tumor In Vivo.

Magnetic resonance imaging (MRI) has become a prominent non- or low-invasive imaging technique, providing high-resolution, three-dimensional images as well as physiological information about tissues. Low-molecular-weight Gd-MRI contrast agents (CAs), such as Gd-DTPA (DTPA: diethylenetriaminepentaacetic acid), are commonly used in the clinical diagnosis, while macromolecular Gd-MRI CAs have several advantages over low-molecular-weight Gd-MRI CAs, which help minimize the dose of CAs and the risk of side effects. Accordingly, we developed chiral dendrimer Gd-MRI CAs, which showed high r1 values. The association constant values (Ka ) of S-isomeric dendrimer CAs to bovine serum albumin (BSA) were higher than those of R-isomeric dendrimer CAs. Besides, based on a totally new concept, we developed 13 C/15 N-enriched multiple-resonance NMR/MRI probes, which realized highly selective observation of the probes and analysis of metabolic reactions of interest. This account summarizes our recent study on developing both chiral dendrimer Gd-MRI CAs, and self-traceable 13 C/15 N-enriched phosphorylcholine polymer probes for early detection of tumors.

[A Case of Recurrent Rectal Cancer with Adrenal and Lung Metastasis with More than Ten-Year Survival after Surgery].

A 60-year-old man underwent low anterior resection for rectal cancer. Histological findings indicated well-differentiated adenocarcinoma(T3[SS]N1M0, ly3, v2, Stage III a). Two years and 1 month later, right adrenalectomy was performed for solitary adrenal metastasis. Three months thereafter, left partial pulmonary resection was performed for a metastatic lung tumor. All resected specimens showed metastatic adenocarcinoma derived from the rectal cancer. The patient is alive and well without recurrence for more than 10years after lung resection. Given that adrenal metastasis is usually found as widespread metastasis, aggressive resection of well-controlled metastatic lesions including those in the adrenal glands is recommended.