Autotuning of Vibrational Strong Coupling for Site-Selective Reactions.

Site-selective chemistry opens new paths for the synthesis of technologically important molecules. When a reactant is placed inside a Fabry-Perot (FP) cavity, energy exchange between molecular vibrations and resonant cavity photons results in vibrational strong coupling (VSC). VSC has recently been implicated in modified chemical reactivity at specific reactive sites. However, as a reaction proceeds inside an FP cavity, the refractive index of the reaction solution changes, detuning the cavity mode away from the vibrational mode and weakening the VSC effect. Here we overcome this issue, developing actuatable FP cavities to allow automated tuning of cavity mode energy to maintain maximized VSC during a reaction. As an example, the site-selective reaction of the aldehyde over the ketone in 4-acetylbenzaldehyde is achieved by automated cavity tuning to maintain optimal VSC of the ketone carbonyl stretch during the reaction. A nearly 50 % improvement in site-selective reactivity is observed compared to an FP cavity with static mirrors, demonstrating the utility of actuatable FP cavities as microreactors for organic chemistry.

Effects of cataract surgery in Japanese patients with neovascular age-related macular degeneration.

PURPOSE: To investigate the effects of cataract surgery in Japanese patients with neovascular age-related macular degeneration (nAMD). METHODS: The primary endpoint in this prospective, observational study was patient satisfaction at 6 months after cataract surgery in patients with nAMD. Secondary endpoints comprised changes in best-corrected visual acuity (BCVA), M-chart score, central retinal thickness (CRT), AMD status, and number of AMD treatments. All examinations were performed before surgery, and at 1, 3, and 6 months postoperatively. RESULTS: Fifty patients (52 eyes) were included in this study (32 men; mean age, 76.1 ± 7.1 years). Thirty-nine patients (75.0%) reported satisfaction with cataract surgery. BCVA significantly improved at all postoperative timepoints (all p < 0.0001), whereas differences in M-chart scores were not statistically significant. The number of eyes with BCVA ≤ 0.3 logarithm of the minimum angle of resolution (logMAR) increased from 21 to 38; however, CRT did not change. The number of AMD treatments did not change during follow-up. All questionnaire scores showed postoperative improvement. Univariate and multivariate analyses revealed that final BCVA ≤ 0.3 logMAR was significantly associated with patient satisfaction. CONCLUSION: Cataract surgery significantly improved vision in Japanese patients with nAMD, without affecting AMD status. Patients were satisfied with cataract surgery, especially with respect to improvement of distance vision.

Ten-year changes in visual acuity at baseline and at 2 years after treatment in a Japanese population with age-related macular degeneration.

PURPOSE: We investigated 10-year changes in baseline best-corrected visual acuity (BCVA), as well as functional and anatomical changes at 1 and 2 years after initial treatment, in eyes with treatment-naïve neovascular age-related macular degeneration (nAMD). METHODS: This retrospective, multicenter, case series reviewed patients with treatment-naïve nAMD who underwent initial treatment from 2006 to 2015, using photodynamic therapy (PDT), anti-vascular endothelial growth factor (VEGF), or a combination of PDT and anti-VEGF. BCVA and central retinal subfield thickness (CRST), were measured at baseline and at 1 or 2 years of follow-up. RESULTS: In total, 3096 eyes of 3096 patients were included from 14 hospitals. Mean BCVA at baseline became significantly better over the 10-year study period (P < 0.001). BCVA at 1 year significantly improved from baseline in patients who underwent initial treatment from 2009 to 2015 (P = 0.001, 2009; P = 0.004, 2010; P = 0.01, 2011; P < 0.001, 2012-2015). BCVA at 2 years significantly improved from baseline in patients who underwent initial treatment from 2012 to 2015 (P < 0.001, 2012; P < 0.001, 2013-2015). CRST at 1 year decreased significantly from CRST at baseline, each year from 2006 to 2015 (P < 0.001, 2006-2015). CRST at 2 years decreased significantly from CRST at baseline, each year from 2006 to 2015 (P = 0.03, 2006; P < 0.001, 2007-2015). CONCLUSION: Baseline BCVA with treatment-naïve nAMD tended to become better during the study period. BCVA at 1 year improved in the era of anti-VEGF; BCVA at 2 years improved in patients who underwent initial treatment in 2012 or later; and CRST decreased in each year during the study period.

Neoadjuvant Hyperthermia and Chemoradiotherapy for Borderline Resectable Pancreatic Cancer.

Pancreatic cancer(PC)is associated with poor prognosis and low resectability rates. Currently, only 15-20% of all patients are candidates for upfront surgery at the time of diagnosis, which offers the chance of long-term survival. In recent years, patients with borderline resectable PC(BR-PC)have been treated with surgery following neoadjuvant chemoradiotherapy or intensive multi-agent chemotherapy. In PC, which is therapy resistant due to its hypoxic microenvironment, hyperthermia may enhance the effect of chemo(radio)therapy. An 84-year-old man with fatty stool was diagnosed with pancreatic head cancer according to the result of contrast computed tomography(CT), which showed a 37 mm irregular low-density area at the pancreatic head infiltrating nearly half of the superior mesenteric artery(SMA)plexus. There were no findings of lymph node metastasis or distant metastasis. The pretreatment diagnosis was BR-PC, cT3, N0, M0, cStage Ⅱ A. The patient was treated with hyperthermia plus S-1 and radiotherapy. The size of the tumor had reduced from 37 mm to 15 mm after the neoadjuvant therapy, and the infiltration into the SMA plexus had also reduced. Therefore, the patient underwent subtotal stomach-preserving pancreaticoduodenectomy(SSPPD)concomitant resection of the PV, SMV, SV confluence. The histopathological findings were invasive ductal carcinoma with R0 radical resection. There has been no recurrence 18 months after the surgery. Based on the above-mentioned findings, hyperthermia and chemoradiotherapy can be an effective option of neoadjuvant treatment for BR-PC.

[A Case of Lipoma Arising from the Mesentery Proper That Had Difficulty in Differential Diagnosis with Well-Differentiated Liposarcoma].

A 54-year-old male patient with a chief complaint of right lower abdominal pain and nausea visited the reporting hospital. Abdominal computed tomography was performed, which showed findings of a membrane-covered internally heterogeneous solid mass associated with a 11×10 cm well-circumscribed calcification, as well as ileus in the right lower abdomen. Based on the imaging findings, it was diagnosed with liposarcoma, and surgery was performed for both diagnosis and treatment. The mass was located in the mesentery of the terminal ileitis and could be removed without gross residue. Histopathological examination showed altered fat cells and fibrous partition, most of which were lipoma, but well-differentiated liposarcoma could also not be ruled out. It was diagnosed with lipoma mixed with well-differentiated liposarcoma. In particular, lipoma and liposarcoma from the mesentery proper is extremely rare. We encountered a case of lipoma arising from the mesentery proper that had difficulty in differential diagnosis with well-differentiated liposarcoma and here in report it with the addition of some literature consideration.

[A Case Report of Duodenal Ampullary Carcinoma with Annular Pancreas].

Annular pancreas is a rare congenital anomaly that rarely occurs in parallel with malignancy. We herein report a case of annular pancreas with carcinoma of the papilla of Vater. A 76-year-old woman presented with abdominal pain and was referred to us after gastroduodenal endoscopy showed a tumor of the papilla. Preoperative computed tomography confirmed the presence of an ampullary tumor. During surgery, we found an anomaly consisting of a ring-like band of pancreatic tissue encircling the second part of the duodenum. Transduodenal papillectomy with preservation of the annular pancreas was subsequently performed. The patient was discharged without any postoperative morbidity.

[A Case of Pancreatoduodenectomy for Pancreatic Head Cancer with Invasion to the Hepatic Artery from the Pancreatic Arcade].

This case pertained a 53-year-old man who underwent nab-PTX plus GEM therapy for BR-A pancreatic head cancer. He achieved a partial response and underwent pancreatoduodenectomy. Dynamic CT showed blockage of the original common hepatic artery branching from the celiac artery. Hepatic blood flow was maintained by a pancreatic arcade branching from the superior mesenteric artery which ran along the ventral side of the pancreatic head. The cancer had invaded the same location; therefore, the hepatic artery and portal vein were both resected and reconstructed. The patient had no complications, such as postoperative pancreatic fistula, and was discharged 45 days postoperatively. Currently(5 months postoperatively), postoperative S-1-based adjuvant chemotherapy is being administered, and the patient had a recurrence-free survival.

Comparison of United States and International Ophthalmic Drug Pricing.

PURPOSE: To compare United States and international drug pricing for commonly prescribed intravitreal and topical ophthalmic medications. DESIGN: Cross-sectional observational study. METHODS: For 25 commonly used ophthalmic medications (3 intravitreal, 22 topical), we obtained 2017 third quarter United States average wholesale price (AWP), drug acquisition cost, or consumer pricing through United States government health insurance plans (Veterans Affairs [VA], Medicaid, Medicare Part B, and Medicare Part D) and commercial drug plans (CVS Caremark and Navitus Health Solutions), online pricing without insurance through a large United States warehouse retailer (Costco), and international drug pricing through government-sponsored health plans in Italy, Spain, Turkey, Canada, and Japan. MAIN OUTCOME MEASURES: Drug acquisition costs and consumer pricing of ophthalmic drugs through various payment systems. All prices were converted to United States dollars. RESULTS: For intravitreal medications in the United States, aflibercept and ranibizumab were priced similarly to each other and were more expensive than dexamethasone implants. Pricing of aflibercept and ranibizumab through government health insurance plans in Italy, Spain, Turkey, Canada, and Japan were less expensive by as much as 84.3% compared with the United States. For topical medications in the United States, pricing varied significantly both across different classes of medications and also between nonbranded and branded medications. Drug acquisition costs through the VA and Medicaid were inexpensive on average, but pricing through a hospital-employee drug insurance plan offered the smallest range (between $2.35 and $60.00). In all 5 non-United States countries studied, each topical medication with the exceptions of cyclosporine emulsion and difluprednate was less than $100, and 94.4% of topical medications in these countries had a nonbranded or branded option that was less than $50. CONCLUSIONS: In the United States, for topical more than intravitreal medications, significant price variation exists across both different drug pricing systems and different medications. Price differentials between nonbranded and branded medications can be significant. Internationally, topical medications exhibited a more limited and lower price range compared with drug pricing in the United States.

TRAFFIC ACCIDENT-RELATED OPEN GLOBE INJURIES.

PURPOSE: To evaluate the clinical characteristics and visual outcomes of patients with traffic accident-related open globe injuries, and to examine preoperative factors influencing the visual prognosis after pars plana vitrectomy, as compared with common open globe injuries. METHODS: Patients with open globe injuries, who underwent pars plana vitrectomy, were identified. Patients' demographic and clinical data were entered into a computerized database for review and analysis; data included age, sex, initial visual acuity, duration between onset of injury and surgery, information about the type and cause of injury, wound location and length, presence of ocular complications, and final visual acuity. RESULTS: Of the 355 open globe injuries, 14 were sustained during a traffic-related accident; the average age was 50.4 years (range: 20-85) and most (78.6%) were men. Of these 14 patients, 9 (64.3%) presented with rupture and 5 (35.7%) with laceration. Injuries were caused while driving (6 eyes; 42.9%), riding a bicycle (5 eyes; 35.7%), involved in car accident while walking (2 eyes; 14.3%), and riding a motorbike (1 eye; 7.1%). Initial visual acuity was significantly related to final visual acuity (P = 0.003, R = 0.80). The final visual acuity in patients with traffic accident-related open globe injuries was significantly better than that of the total group (P = 0.01). CONCLUSION: Traffic accident-related open globe injuries had better visual outcomes than common open globe injuries. Visual outcomes in patients with traffic accident-related open globe injuries were related to the initial visual acuity. No eyes developed endophthalmitis in patients with traffic accident-related open globe injuries.

[Long-Term Disease-Free Survival after Chemoradiotherapy for Postoperative Local Recurrence of Rectal Cancer-A Case Report].

We report a case of a 63-year-old man with a perirectal abscess due to rectal cancer referred to us from another clinic. We performed 3 courses of preoperative chemotherapy using mFOLFOX6 and then performed a Miles operation plus D3 dissection followed by reconstruction of an artificial anus using the ileum. The pathological diagnosis was tub2, pAI(prostate), pN0 (0/12), ND(v+), and fStage Ⅲa. Dehiscence of the perineum wound area occurred 4 months after surgery, for which drainage was required. Local recurrence was then discovered by cytology. We administered mild 40 Gy radiation and chemotherapy using Bmab combined with mFOLFOX6. CT scans showed a significant reduction in the tumor and the tumor marker levels returned to within normal ranges. We then converted to Pmab plus FOLFIRI, which has been administered bimonthly for 3 years to date. The overall chemoradiotherapy duration has been about 5 years. Follow-up imaging findings continue to show sustained remission.

[Two Cases of Afferent Loop Obstruction Treated with Percutaneous Bowel Drainage(PBD)].

Here, we report our experiences with 2 cases of afferent loop obstruction with percutaneous bowel drainage(PBD)and present a review of the literature. Case 1 involved a 60-year-old woman. She underwent pancreaticoduodenectomy for pancreatic cancer. Eighteen months postoperatively, a recurrence marked by a jejunal elevation and expansion on the cecal side near the porta hepatic lymph nodes appeared. We performed PBD because intestinal depression via the endoscopic approach was difficult. She was discharged from the hospital 7 days after PBD. Case 2 involved a 51-year-old woman. She underwent total gastrectomy and Roux-en-Y reconstruction for progressive stomach cancer. We detected a local recurrence in the Y anastomosis following a chief complaint of vomiting 10 months postoperatively. Fifteen months postoperatively, she developed acute pancreatitis with afferent loop syndrome. We performed PBD via a trans-liver route. The patient was discharged from the hospital 11 days after PBD. By devising a puncture route, we could safely perform PBD for an afferent loop obstruction.

[Two Cases of Surgery Combined with Intraoperative Radiofrequency Ablation for Colorectal Cancer and Synchronous Liver Metastases].

The therapeutic management of simultaneous liver metastasis of colorectal cancer(SCRLM)remains controversial. Although hepatic metastasectomy is the first choice for resectable liver metastasis of colorectal cancer, radiofrequency ablation (RFA)is one of the least invasive application for patients who refuse more invasive treatment such as hepatectomy and longterm systemic chemotherapy or for whom such treatment is not suitable. We report 2 cases of SCRLM treated by surgery combined with intraoperative RFA and adjuvant chemotherapy, raising the possibility of local control in the liver for selected patients.

[A Case of Recurrent Gallbladder Carcinoma Treated with Resection and Hepatic Arterial Infusion].

A 69-year-old woman underwent extended cholecystectomy for gallbladder cancer[T2N0M0, fStage Ⅱ(UICC 7th edition)]. She was then administered adjuvant S-1 and was treated for drug-induced neutropenia. One year later, recurrent lesions were detected in liver S4 and S5. We treated the patient with hepatectomy and hepatic arterial infusion adjuvant chemotherapy by cisplatin, along with the systemic administration of gemcitabine for 10 months. The patient is now doing well without any sign of recurrence 29 months after the initial operation and 16 months after the secondary liver resection.

[A Case of Laparoscopic Hepatectomy and Combined Resection of Lymph Nodes and Ureter for Liver Metastasis after Colorectal Cancer Surgery, with Local Lymph Node Recurrence and Bilateral Hydronephrosis].

A 65-year-old man with sigmoid colon cancer underwent sigmoidectomy, followed by 8 courses of oral S-1 as postoperative adjuvant chemotherapy. Three years and 3 months after surgery, the patient developed liver metastasis, lymphadenopathy at the root of the inferior mesenteric artery, and bilateral hydronephrosis. The left hydronephrosis was believed to be due to invasion by lymph node metastasis at the root ofthe inferior mesenteric artery. The patient underwent laparoscopic partial resection ofsegment 5 ofthe liver, excision ofthe lymph nodes at the root ofthe inferior mesenteric artery(combined resection ofthe left ureter), bilateral ureteral stent placement, and left ureteral reconstruction. The postoperative course was without complications, and he was discharged 12 days after surgery. Follow-up observation without postoperative adjuvant chemotherapy was planned, according to the patient's wishes.

Clinical characteristics and outcomes of fall-related open globe injuries in Japan.

PURPOSE: To investigate the clinical characteristics and visual outcomes in patients with fall-related open globe injuries and to evaluate differences between fall-related and non-fall-related open globe injuries in Japan. METHODS: A retrospective review of patients with open globe injury who presented to Japan-Clinical Research of Study (J-CREST) hospitals between 2005 and 2015 was enrolled. Clinical information including age, sex, initial visual acuity, final visual acuity, type of injury, status of the crystalline lens, zone of injury, wound length, presence of retinal detachment, proliferative vitreoretinopathy, expulsive hemorrhage, and endophthalmitis was recorded. RESULTS: A total of 374 eyes were enrolled, of which 120 (32.1%) suffered from fall-related injury with average age of 73.7 ± 15.9 years (range, 11-101 years). A majority of patients were female (55.8%). Of 120 patients with fall-related injury, 109 (90.8%) presented with rupture and 11 (9.2%) with laceration. A multiple regression analysis revealed that final visual acuity was significantly associated with initial visual acuity (r = 0.99, P < 0.001). Compared to non-fall-related open globe injuries, fall-related open globe injuries were associated with elderly age, female sex, poorer initial and final visual acuity, rupture, absence of the lens, larger wound size, retinal detachment, expulsive hemorrhage, and absence of endophthalmitis (P < 0.01). CONCLUSIONS: Fall-related open globe injuries were more frequent in elderly female and accompanied by larger wound lengths and severer ocular complications. Visual outcomes in patients with fall-related open globe injuries were related to initial visual acuity.

[Treatment Strategy for Non-Functional Pancreatic Neuroendocrine Tumors (P-NETs) at Kurume University Hospital].

Pancreatic neuroendocrine tumors (P-NETs) are relatively rare. Approximately 50-90% of non-functioning P-NETs are malignant, and the only curative treatment is surgical resection. Liver and lymph node metastases often occur. In Japan, the mTOR inhibitor everolimus is now covered by the national health insurance for treatment of P-NETs, including advanced and unresectable tumors. We present a case of P-NETs with liver metastases seen at our hospital and discuss our treatment strategy for this disease. Patients with tumors≤1 cm receive follow-up observation. For G1 and G2 (other than G3) tumors, if their size is >1 cm when first discovered, resection of the primary lesion along with lymph node dissection (as for pancreatic cancer) is performed. In G1 and G2 tumors with synchronous distant metastases, the primary lesion is first resected, and depending on the pathological findings, chemotherapy (LAR plus everolimus) may be administered. After 4 courses of chemotherapy, the response is assessed, and if further resection is possible, resection is performed. When there are synchronous liver metastases, if partial resection and local treatment (such as RFA) are possible, the primary lesion and synchronous lesions are resected. If a major hepatic resection procedure such as a segmentectomy or lobectomy is possible, the primary lesion is resected, followed by chemotherapy. After 4 courses of chemotherapy, the response is assessed, and if further resection is possible, hepatic resection is performed. G3 tumors are usually highly malignant, advanced, and often associated with metastases at the time of diagnosis. Chemotherapy may be an option for treating patients with G3 tumors.

[A Case of Laparoscopic Resection of Peritoneal Hepatocellular Carcinoma Recurrence after Percutaneous Ethanol Injection Therapy].

Needle tract implantation after percutaneous ethanol injection therapy(PEIT)for hepatocellular carcinoma(HCC)is rare. Surgical treatment of such HCC implants is still controversial. We herein report the case of a patient who underwent laparoscopic resection for peritoneal dissemination after PEIT. An 81-year-old man underwent PEIT for primary HCC at another hospital. Thereafter, percutaneous radiofrequency ablation(RFA)was performed twice for intrahepatic recurrence. After the second RFA, a mass lesion was detected at the subhepatic space on computed tomography(CT). We reevaluated the CT and diagnosed the patient with peritoneal dissemination after PEIT. Laparoscopic resection was performed. However, the patient developed recurrences at the thoracic wall and peritoneum 12 months after laparoscopic surgery. Those 2 tumors were resected, and he remains alive, approximately 30 months after the laparoscopic resection. Laparoscopic extirpation of tract seeding may provide better clinical outcomes in select patients.

Intravenous transplants of human adipose-derived stem cell protect the brain from traumatic brain injury-induced neurodegeneration and motor and cognitive impairments: cell graft biodistribution and soluble factors in young and aged rats.

Traumatic brain injury (TBI) survivors exhibit motor and cognitive symptoms from the primary injury that can become aggravated over time because of secondary cell death. In the present in vivo study, we examined the beneficial effects of human adipose-derived stem cells (hADSCs) in a controlled cortical impact model of mild TBI using young (6 months) and aged (20 months) F344 rats. Animals were transplanted intravenously with 4 × 10(6) hADSCs (Tx), conditioned media (CM), or vehicle (unconditioned media) at 3 h after TBI. Significant amelioration of motor and cognitive functions was revealed in young, but not aged, Tx and CM groups. Fluorescent imaging in vivo and ex vivo revealed 1,1' dioactadecyl-3-3-3',3'-tetramethylindotricarbocyanine iodide-labeled hADSCs in peripheral organs and brain after TBI. Spatiotemporal deposition of hADSCs differed between young and aged rats, most notably reduced migration to the aged spleen. Significant reduction in cortical damage and hippocampal cell loss was observed in both Tx and CM groups in young rats, whereas less neuroprotection was detected in the aged rats and mainly in the Tx group but not the CM group. CM harvested from hADSCs with silencing of either NEAT1 (nuclear enriched abundant transcript 1) or MALAT1 (metastasis associated lung adenocarcinoma transcript 1), long noncoding RNAs (lncRNAs) known to play a role in gene expression, lost the efficacy in our model. Altogether, hADSCs are promising therapeutic cells for TBI, and lncRNAs in the secretome is an important mechanism of cell therapy. Furthermore, hADSCs showed reduced efficacy in aged rats, which may in part result from decreased homing of the cells to the spleen.

[Two Cases of Effective Hepatic Arterial Infusion Chemotherapy for Liver Metastases of Colon Cancer Resistant to Systemic Chemotherapy].

A 69-year-old man underwent right hemicolectomy for ascending colon cancer with liver metastases. Postoperative systemic chemotherapy did not reduce the metastases, and therefore, hepatic arterial infusion chemotherapy (HAI) was administered. The metastases decreased in size after 26 rounds of therapy, and the patient underwent resection. He is recurrence-free 63 months after the primary operation. A 57-year-old man underwent Hartmann's operation for sigmoid colon cancer with liver metastases. He underwent hepatic left lobe resection after metastases reduction by systemic chemotherapy. However, multiple liver metastases were detected 2 months later. Because the disease progressed despite the administration of systemic chemotherapy, HAI was utilized instead. The metastases decreased in size remarkably, and resection was performed. The patient is surviving 52 months after the primary operation while being continuously treated with HAI, resection, and systemic chemotherapy for re-recurrence. HAI is a potential alternative treatment for patients with colorectal liver metastases resistant to systemic chemotherapy.