Efficacy of ramucirumab and subsequent nivolumab therapy in patients with advanced gastric cancer: A retrospective study.

Nivolumab monotherapy is a standard treatment of metastatic gastric cancer, and this type of cancer involves vascular endothelial growth factor (VEGF) signaling in the tumor immunological environment. The subgroup analysis of the ATTRACTION-2 trial revealed that prior treatment with ramucirumab (RAM), a VEGF inhibitor, affected the therapeutic effect of nivolumab. The present retrospective study aimed to review patients with metastatic gastric cancer who were treated with paclitaxel (PTX) and RAM followed by nivolumab. A total of 29 patients with metastatic gastric cancer were treated with PTX + RAM as second-line treatment, followed by nivolumab monotherapy as third-line treatment. The therapeutic efficacy of nivolumab was compared in 13 patients with progression-free survival (PFS) of <5 months and 16 patients with PFS ≥5 months after PTX + RAM therapy. The present study included 22 male and seven female patients, with a median age of 68 years (range, 45-82 years). Human epidermal growth factor receptor 2 positivity was observed in six patients. The disease control rate was 62.1%. The PFS and overall survival (OS) were 4.4 and 11.9 months, respectively. Patients with PFS ≥5 months after PTX + RAM therapy showed better outcome in both PFS (5.3 months vs. 2.8 months, P=0.039) and OS (6.9 months vs. 15.2 months, P=0.066) after nivolumab treatment than patients with PFS of <5 months after PTX + RAM therapy. However, no significant relationship was observed between the outcome of first-line treatment and nivolumab. The therapeutic effect of nivolumab was associated with prior PTX + RAM treatment in advanced gastric cancer.

Recurrence Pattern, Treatment Modalities, and Prognostic Factors After Definitive Chemoradiotherapy for Recurrent Esophageal Cancer.

BACKGROUND: Recurrent esophageal cancer (EC) has a poor prognosis. However, the recurrence patterns and therapeutic outcomes after definitive chemoradiotherapy (CRT) are not fully understood. We analyzed survival and prognostic factors associated with post-definitive CRT recurrent EC. METHODS: We retrospectively reviewed 71 consecutive patients with post-definitive CRT EC recurrence between 2008 and 2021 at our institution. Recurrence was locoregional, distant, and combined in 42 (59%), 18 (25%), and 11 (16%) patients, respectively. The median time from definitive CRT to recurrence was 8.3 months. Treatment modalities included local therapy, systemic therapy, and palliative care. Overall survival (OS) after recurrence was analyzed using the Kaplan-Meier and Cox proportional hazards models. RESULTS: The median follow-up time from recurrence was 7.1 months, and the median survival time (MST) was 12.5 months. In the univariate analysis, longer time to recurrence, earlier stage at initial treatment, surgical tolerance at initial diagnosis, treatment modalities, and oligo-recurrence were associated with a better prognosis. The MST of the local therapy, systemic therapy, and palliative care groups were not reached, 11.8 months and 4.1 months, respectively (P < 0.001). In the multivariate analysis, treatment modalities and oligo-recurrence emerged as independent prognostic factors (P < 0.001 and P = 0.009). CONCLUSIONS: Aggressive local therapy should be considered to improve the prognosis for patients with oligo-recurrence and/or indication of local therapy to treat recurrent EC.

Enhancement of DNA hypomethylation alterations by gastric and bile acids promotes chromosomal instability in Barrett's epithelial cell line.

Gastric and bile acid reflux leads to chronic inflammation, resulting in methylation alterations in Barrett's esophagus (BE) together with chromosomal instability (CIN). We investigated DNA hypomethylation following acid exposure and confirmed its significance in BE-related carcinogenesis by inducing CIN in vitro. OACP4C, an esophageal cancer cell line, and CP-A, a non-dysplastic cell line originating from BE, were exposed to acidic conditions using deoxycholic acid. CP-A exhibited substantially increased DNA hypomethylation of alpha satellite sequences in the centromere region, as well as increased levels of alpha satellite transcripts, but no changes were observed in the long interspersed nucleotide element-1 sequences distributed throughout the entire genome. These changes were not clearly found in OACP4C. Copy number changes at specific chromosomes were identified in CP-A, along with an increased number of cells exhibiting abnormal segregations, whereas these changes were rarely observed in OACP4C. The changes were maintained after several cell divisions. These findings suggest that alpha satellites are likely targets of DNA hypomethylation induced by acid exposure. CP-A was more sensitive to acid exposure than OACP4C, indicating that acid-induced DNA hypomethylation is involved in cancer development rather than progression, which could be involved in the underlying mechanism of esophagogastric junction carcinoma development.

A case of intraocular inflammation after intravitreal brolucizumab injection monitored by laser flare-cell photometer.

Purpose: To report the efficacy of combination therapy using intravitreal injection of brolucizumab (IVbr) and sub-Tenon's injection of triamcinolone acetonide (STTA) and of monitoring with a laser flare-cell photometer (LFP) in a case of polypoidal choroidal vasculopathy (PCV) with intraocular inflammation (IOI). Observations: A 72-year-old Japanese woman with PCV had her treatment switched to IVbr due to being refractory to aflibercept. Two weeks after starting IVbr, her visual acuity (VA) declined to 0.40 from 0.10 logarithm of the minimum angle of resolution (logMAR) VA at baseline. In addition, the LFP flare increased to 51.2 photon count/ms (pc/ms) compared with the baseline of 16.1 pc/ms. We diagnosed her with the onset of IOI and immediately started treatment with sub-Tenon's injection of 20 mg triamcinolone acetonide (STTA). Two weeks after receiving STTA, her VA had recovered to 0.15 logMAR, and the LFP flare had decreased to 17.9 pc/ms with dry macula. Eight weeks after the first IVbr treatment, the logMAR VA had improved to -0.18 with achievement of dry macula and stabilization of the LFP flare at 12.2 pc/ms. We administered combined therapy using IVbr and STTA to our patient, and 12 weeks later, the logMAR VA remained at 0.00 with dry macula and 18.1 pc/ms for LFP flare. We continued combination therapy, and after 8 months, her logMAR VA remained at -0.08, and optical coherence tomography showed dry macula, while the LFP flare had stabilized at 16.6 pc/ms. Conclusions and Importance: Combination therapy of IVbr and STTA stabilized IOI and achieved dry macula. The LFP flare score clearly showed the degree of and changes in inflammation.

Preoperative factors associated with shunt responsiveness in patients with idiopathic normal-pressure hydrocephalus.

OBJECTIVE: We aimed to evaluate a possible association between preoperative factors (disease duration and vascular risk factors) and shunt responsiveness in patients with idiopathic normal-pressure hydrocephalus (iNPH). METHODS: We conducted a retrospective observational study in a high-volume center for iNPH treatment in Japan and reviewed the clinical data of 107 consecutive patients with probable iNPH who underwent shunt surgery between January 1, 2018, and August 31, 2019, and were followed up for at least 12 months after surgery. Preoperatively, these patients underwent the timed up-and-go test (TUG) and Mini-Mental State Examination (MMSE); moreover, follow-up evaluations were performed 12 months postoperatively, at which TUG and MMSE scores were used as metrics for shunt responsiveness assessment. The degree of shunt responsiveness was regressed to several preoperative factors, including preoperative TUG and MMSE scores, vascular risk factors, and duration from iNPH onset to shunt surgery, to evaluate which preoperative factors may be predictive of shunt responsiveness. RESULTS: In multivariate regression analysis, there was no statistically significant association between the presence of preoperative vascular risk factors and the postoperative TUG or MMSE score 12 months after shunt surgery. Meanwhile, preoperative history of ischemic stroke and a longer duration from iNPH onset to surgery were significantly associated with poorer shunt responsiveness in terms of MMSE and TUG scores. CONCLUSIONS: The current study suggested the potential involvement of stroke history and disease duration with the 1-year prognosis of iNPH after shunt surgery, of which validity needs to be corroborated in further studies.

Indications and Outcomes of a Hybrid Method Combining Laparoscopic and Anterior Approaches for Inguinal Hernia Repair.

Introduction Surgery for complex inguinal hernia (IH) (recurrent IH or IH after radical prostatectomy (RP)) may be difficult because of the presumed scar or adhesion in the retropubic space. A hybrid method combining the laparoscopic and anterior approaches (HLAA) in a bidirectional surgical technique may be an option in complex IH cases. Methods Patients at our institution who underwent IH repair for complex IH using HLAA from April 2018 to November 2019 were included. We retrospectively evaluated the patient characteristics, IH diagnosis, intraoperative variables, complications, and hernia recurrence during the follow-up period. Results Twenty patients were involved in this study. Seven patients underwent hLAA for recurrent IH, whereas the remaining 13 underwent hLAA for IH after RP. Five patients had bilateral IH, all of whom had IH after RP. The type of IH was lateral in 21 patients, medial in six patients, and lateral and medial in two patients. Hernia repair was performed using a patch alone in two patients and a plug and patch in 18 patients. Seroma or hematoma was observed in five patients, and one patient experienced chronic pain. No hernia recurrence was observed during the median follow-up period of 24 months. Conclusion hLAA could facilitate precise diagnosis and intraoperative confirmation of repair for recurrent IH and IH after RP. The intraoperative findings and the cause of recurrence can be easily shared among surgeons in hLAA. Further investigations are necessary to determine the long-term efficacy of hLAA in a larger cohort.

Minimally invasive esophagectomy in the semi-prone position for corrosive esophagitis: a case report.

Treatment strategies for corrosive esophagitis include conservative treatment, such as balloon dilatation at the stenosis site, and surgical treatment. Esophagectomy for corrosive esophagitis is usually performed through the transthoracic or transhiatal approaches. Herein, we report a case of corrosive esophagitis treated with thoracoscopic esophagectomy with the patient in the semi-prone position. The patient was a 48-year-old woman who developed corrosive esophagitis due to accidental ingestion of an alkaline agent. Surgical intervention was required for esophageal stenosis. Therefore, thoracoscopic esophagectomy was performed with the patient in the semi-prone position with bilateral pulmonary ventilation. In our hospital, good operative outcomes have been obtained using thoracoscopic esophagectomy for esophageal cancer with the patient in the semi-prone position with bilateral pulmonary ventilation. This technique is also considered effective for the treatment of corrosive esophagitis.

Overexpression of satellite RNAs in heterochromatin induces chromosomal instability and reflects drug sensitivity in mouse cancer cells.

Overexpression of satellite RNAs in heterochromatin induces chromosomal instability (CIN) through the DNA damage response and cell cycle checkpoint activation. Although satellite RNAs may be therapeutic targets, the associated mechanisms underlying drug sensitivity are unknown. Here, we determined whether satellite RNAs reflect drug sensitivity to the topoisomerase I inhibitor camptothecin (CPT) via CIN induction. We constructed retroviral vectors expressing major satellite and control viruses, infected microsatellite stable mouse colon cancer cells (CT26) and MC38 cells harboring microsatellite instability, and assessed drug sensitivity after 48 h. Cells overexpressing satellite RNAs showed clear features of abnormal segregation, including micronuclei and anaphase bridging, and elevated levels of the DNA damage marker γH2AX relative to controls. Additionally, overexpression of satellite RNAs enhanced MC38 cell susceptibility to CPT [half-maximal inhibitory concentration: 0.814 µM (control) vs. 0.332 µM (MC38 cells with a major satellite), p = 0.003] but not that of CT26. These findings imply that MC38 cells, which are unlikely to harbor CIN, are more susceptible to CIN-induced CPT sensitivity than CT26 cells, which are characterized by CIN. Furthermore, CPT administration upregulated p53 levels but not those of p21, indicating that overexpression of major satellite transcripts likely induces CPT-responsive cell death rather than cellular senescence.

Prophylactic use of pegfilgrastim enables the management of severe neutropenia without dose delays in patients with metastatic colorectal cancer treated with TAS-102 plus bevacizumab.

Combined treatment with bevacizumab and trifluridine/tipiracil (TAS-102) leads to an increased chance of survival in patients with refractory metastatic colorectal cancer (mCRC); however, this treatment is associated with an increased frequency of severe neutropenia (number of neutrophils <1,000), which should ideally be managed without dose delays. The present study provided a retrospective review of 35 patients with mCRC, and aimed to elucidate the benefits of prophylactic pegfilgrastim for the treatment of severe neutropenia. Patients received TAS-102 (35 mg/m2) orally twice daily on days 1-5 and 8-12 of each 28-day treatment cycle, along with intravenous bevacizumab (5 mg/kg) on days 1 and 15. Moreover, the patients received 3.6 mg pegfilgrastim on day 15 of each cycle. The incidence of adverse events (AEs), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were assessed. In the first and subsequent cycles, 23 and 12 patients, respectively, received pegfilgrastim. The most common AE experienced was grade 3/4 neutropenia (8 patients; 22.9%). Among these 8 patients, 6 (17.1%) and 3 (8.6%) exhibited neutropenia prior to receiving pegfilgrastim or following discontinuation of pegfilgrastim administration, respectively. Moreover, 1 individual among these 8 patients (2.9%) demonstrated grade 3 neutropenia both prior to receiving pegfilgrastim and following discontinuation of pegfilgrastim. A total of 2 patients (5.7%) exhibited grade 3 bone pain, which prevented sustainable administration of pegfilgrastim and resulted in grade 3 neutropenia. Dose delays and dose reduction of TAS-102 due to neutropenia were required in 5 (14.3%) and 2 (5.7%) patients, respectively, during the treatment period. None of the patients exhibited severe neutropenia during chemotherapy after pegfilgrastim administration, thereby preventing dose delays and dose reduction of TAS-102. The relative dose intensity was 96.8% (65.0-100.0%), and the DCR was 54.3%. The median PFS and median OS were 4.4 and 14.9 months, respectively. In conclusion, prophylactic pegfilgrastim may facilitate the management of severe neutropenia without dose delays in patients with mCRC treated with TAS-102 plus bevacizumab.

Genome­wide DNA hypomethylation drives a more invasive pancreatic cancer phenotype and has predictive occult distant metastasis and prognosis potential.

Genome­wide DNA hypomethylation is the most common molecular feature in human cancers associated with chromosomal instability (CIN), which is involved in the mechanisms that regulate pancreatic cancer (PC) metastasis. It was investigated whether genome­wide DNA hypomethylation affects the phenotype in PC via CIN in vitro, and its significance on the biological behavior of PC was verified. The relative demethylation level (RDL) of long interspersed nucleotide element­1 (LINE­1) in human PC cell lines was used to characterize DNA hypomethylation using methylation­specific quantitative (q)PCR. CIN was estimated by changes in chromosomal copy number using comparative genomic hybridization analysis. Abnormal segregation of chromosomes was assessed by immunocytochemistry, and the DNA damage response was evaluated using the number of anti­Î³H2AX positive cells. Invasion ability was assessed using a Matrigel invasion assay. Clinical specimens from 49 patients with PC who underwent curative surgery were evaluated for a correlation of DNA hypomethylation with clinical outcome. Successful induction of genome­wide DNA hypomethylation in PC cells led to copy number changes in specific chromosomal regions. The number of cells with abnormal segregation of chromosomes significantly increased with the number of anti­Î³H2AX positive cells. The invasive potential of these cells also significantly increased. The occurrence of occult distant metastasis in the clinical specimens and receiver operating characteristic analysis clearly identified those who were and were not likely to have occult distant metastasis, with high LINE­1 RDL significantly correlated with the presence of occult distant metastasis (P=0.035) and poor prognosis (P=0.048). The significance of genome­wide DNA hypomethylation on the biological behavior of PC, which promotes a more invasive phenotype via CIN in vitro and predicts the susceptibility to occult distant metastasis and poor prognosis in patients with PC was revealed.

Progression of age-related macular degeneration in eyes with abnormal fundus autofluorescence in a Japanese population: JFAM study report 3.

PURPOSE: To evaluate the progression of early age-related macular degeneration to neovascular age-related macular degeneration (nAMD), and identify the abnormal fundus autofluorescence (FAF) patterns and markers of choroidal neovascularization (CNV) in fellow eyes of patients with unilateral nAMD. METHODS: Sixty-six patients with unilateral nAMD who developed abnormal FAF in the fellow eyes were enrolled in this multicenter, prospective, observational study, and followed-up for 5 years. FAF images on Heidelberg Retina Angiogram Digital Angiography System (HRA) or HRA2 were classified into eight patterns based on the International Fundus Autofluorescence Classification Group system. The patients in which the fellow eyes progressed to advanced nAMD, including those who did not develop nAMD, were assessed based on the following factors: baseline FAF patterns, age, sex, visual acuity, drusen, retinal pigmentation, baseline retinal sensitivity, family history, smoking, supplement intake, hypertension, body mass index, and hematological parameters. RESULTS: Of the 66 patients, 20 dropped out of the study. Of the remaining 46 patients, 14 (30.42%, male: 9, female: 5) progressed to nAMD during the 5-year follow-up. The most common (50% eyes) FAF pattern in the fellow eyes was the patchy pattern. According to the univariate analysis, CNV development was significantly associated with age, supplement intake, and low-density lipoprotein levels (p<0.05). Multivariable analysis revealed that patients who showed non-compliance with the supplement intake were more likely to develop nAMD (p<0.05). No significant association was found between the patchy pattern and CNV development (p = 0.86). CONCLUSION: The fellow eyes (with abnormal FAF) of patients with unilateral nAMD may progress from early to advanced nAMD. However, no FAF pattern was found that predicted progression in nAMD.

Long-term characteristics of exudative age-related macular degeneration in Japanese patients.

PURPOSE: The present study aimed to evaluate the clinical characteristics of exudative age-related macular degeneration (AMD) in Japanese patients over a 10-year period and to compare the past our report. METHODS: We retrospectively reviewed 1,600 treatment-naïve patients (1,777 eyes) with exudative AMD. The 10 years were divided into 2-year phases I to V. RESULTS: Of the 1,600 patients, 720 (45.0%), 733 (45.8%), 98 (6.1%), and 49 (3.1%) were diagnosed with typical AMD, polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation, and combined subtypes, respectively. The prevalence of PCV decreased from 54.7% in phase I to 46.0% at phase V. Of the 1,777 eyes, the mean baseline logarithm of the minimum angle of resolution best-corrected visual acuities (BCVAs) in phases I, II, III, IV, and V were 0.70, 0.66, 0.55, 0.50, and 0.48, respectively. Phases III, IV, and V had significantly (P = 0.0012, P<0.0001, P<0.0001, respectively) better baseline VAs compared with phase I. The mean lesion sizes in phases I, II, III, IV, and V were 8.6, 6.7, 5.3, 5.7, and 5.7 Macular Photocoagulation Study disc areas, respectively. The sizes were significantly (P<0.0001 for all comparisons) smaller in phases III, IV, and V compared with phase I. CONCLUSIONS: Although the prevalence of PCV decreased from 54.7% in phase I to 46.0% at phase V, PCV has nevertheless been highly prevalent in Japanese patients with AMD compared with Caucasian patients. The annual better baseline VAs and smaller lesion sizes over time might be related to development of treatment and better concerns about AMD.

Optimal value of CA19-9 determined by KRAS-mutated circulating tumor DNA contributes to the prediction of prognosis in pancreatic cancer patients.

Despite the acceptance of carbohydrate antigen 19-9 (CA19-9) as a valuable predictor for the prognosis of pancreatic ductal adenocarcinoma (PDAC), its cutoff value remains controversial. Our previous study showed a significant correlation between CA19-9 levels and the presence of KRAS-mutated ctDNA in the blood of patients with PDAC. Based on this correlation, we investigated the optimal cutoff value of CA19-9 before surgery. Continuous CA19-9 values and KRAS-mutated ctDNAs were monitored in 22 patients with unresectable PDAC who underwent chemotherapy between 2015 and 2017. Receiver operating characteristic curve analysis identified 949.7 U/mL of CA19-9 as the cutoff value corresponding to the presence of KRAS-mutated ctDNA. The median value of CA19-9 was 221.1 U/mL. Subsequently, these values were verified for their prognostic values of recurrence-free survival (RFS) and overall survival (OS) in 60 patients who underwent surgery between 2005 and 2013. Multivariate analysis revealed that 949.7 U/mL of CA19-9 was an independent risk factor for OS and RFS in these patients (P = 0.001 and P = 0.010, respectively), along with lymph node metastasis (P = 0.008 and P = 0.017), unlike the median CA19-9 level (P = 0.150 and P = 0.210). The optimal CA19-9 level contributes to the prediction of prognosis in patients with PDAC before surgery.

Superiority trial comparing intraoperative wound irrigation with aqueous 10% povidone-iodine to saline for the purpose of reducing surgical site infection after elective gastrointestinal surgery: study protocol for a randomised controlled trial.

INTRODUCTION: Surgical site infection (SSI) is one of the most common complications after gastrointestinal surgery, with a reported incidence of approximately 10%-25%, which is higher than the rates after other types of surgery. Intraoperative wound irrigation (IOWI) is a simple intervention for SSI prevention, and recent studies have reported that IOWI with aqueous povidone-iodine (PVP-I) is significantly more effective at reducing the incidence of SSI than saline. However, the evidence level of previous trials evaluating the efficacy of aqueous PVP-I solution for preventing SSI has been low. METHODS AND ANALYSES: We propose a single-institute, prospective, randomised, blinded-endpoint trial to assess the superiority of IOWI with aqueous 10% PVP-I solution compared with normal saline for reducing SSI in clean-contaminated wounds after elective gastrointestinal surgery. In the study group, IOWI with 40 mL of aqueous 10% PVP-I solution is performed for 1 min before skin suture, and in the control group, IOWI with 100 mL of saline is performed for 1 min before skin suture. We hypothesise that IOWI with aqueous 10% PVP-I solution will achieve a 50% reduction in the incidence of SSIs. The target number of cases is set at 950. The primary outcome is the incidence of incisional SSI up to postoperative day 30 and will be analysed in the modified intention-to-treat set. ETHICS AND DISSEMINATION: This trial was designed and is being conducted by Saitama Medical Center, Jichi Medical University, with approval from the Bioethics Committee for Clinical Research, Saitama Medical Center, Jichi Medical University. Participant recruitment began in June 2019. The final results will be reported in international peer-reviewed journals immediately after trial completion. TRIAL REGISTRATION NUMBER: UMIN000036889.

Intestinal perforation secondary to intestinal Burkitt lymphoma.

INTRODUCTION AND IMPORTANCE: Small intestinal perforation in patients with Burkitt lymphoma is extremely rare. We present the first report of such a case. CASE PRESENTATION: A 53-year-old woman was admitted with abdominal pain and vomiting. Abdominal examination revealed rigidity and tenderness in the upper abdomen. Computed tomography scan showed thickening of the wall of the jejunum, intra-abdominal free gas, and ascites; the patient was diagnosed with small intestinal perforation, and underwent emergency surgery on the same day. Laparoscopic findings were a 50 mm jejunal perforation and perforation in the transverse mesocolon. A partial jejunal resection of the perforated area, partial transverse colectomy, temporary colostomy, and intra-abdominal drainage were performed. Histological examination showed diffuse infiltration of medium-sized atypical lymphocytes in the perforated area, exhibiting a "starry sky" appearance. Immunostaining results showed that the atypical lymphocytes were CD20 and virtually 100% Ki-67 positive, and CD56, CD30, and EBER negative. The lesion was identified as Burkitt lymphoma (BL). The postoperative course was favorable. On postoperative day 18 the patient began chemotherapy through the hematology department. Currently, the patient is in remission. CLINICAL DISCUSSION: The majority of the malignant lymphomas occurring in the digestive tract are identified in the stomach; over 90% are B-cell lymphomas and mucosa-associated lymphoid tissue lymphoma Nakamura et al. BL originating from the small intestine accounts for only about 9%. CONCLUSION: The incidence of BL in the small intestine is low. Pretreatment BL can lead to bowel perforation. Prompt involvement of the hemato-oncologist after definitive diagnosis, and commencing chemotherapy as early as possible after surgery, are thought to improve prognosis.

Fundus autofluorescence of retinal angiomatous proliferation.

PURPOSE: The present study aimed to evaluate the characteristics of fundus autofluorescence in Japanese patients with retinal angiomatous proliferation (RAP). METHODS: We retrospectively reviewed 100 eyes from 76 patients (male, n = 45; female, n = 31; age range, 50-94 years; mean ± standard deviation, 81.4 ± 6.4 years) with treatment-naïve RAP, which was diagnosed based on the identification of retinal-retinal anastomosis on early-phase fluorescein angiography or indocyanine green angiography (ICGA) and the identification of a hot spot on late-phase ICGA. RAP was classified into the following three stages: stage 1, proliferation of intraretinal capillaries originating from the deep retinal complex (intraretinal neovascularization); stage 2, growth of the retinal vessels into the subretinal space (subretinal neovascularization); and stage 3, clinically or angiographically observed choroidal neovascularization. In all cases, short-wavelength and near-infrared autofluorescence (SW-AF, NIR-AF) was evaluated using a confocal scanning laser ophthalmoscope. RESULTS: The conditions of the 100 eyes were as follows: stage 1 RAP, n = 6 (6%); stage 2 RAP without retinal pigment epithelial detachment (PED), n = 40 (40%); stage 2 RAP with PED, n = 44 (44%); and stage 3 RAP, 10 (10%). On NIR-AF imaging, the number of abnormalities that were observed to correspond to the RAP lesions on ICGA (87 eyes, 87%) was significantly greater in comparison to SW-AF imaging (27 eyes, 27%). The mean follow-up period in all 76 patients was 39.2 months. In the 76 patients with unilateral disease, 21 (21%) eyes developed RAP in the fellow eye during the follow-up period. Among 18 eyes that were examined by both SW-AF and NIR-AF imaging before the onset of RAP lesions, NIR-AF imaging showed hypoautofluorescence in 15 (83%) eyes before the onset of RAP lesions. CONCLUSIONS: SW-AF and NIR-AF abnormalities may be related to the dysfunction of the photoreceptor/retinal pigment epithelium complex. Hypoautofluorescence on NIR-AF imaging may accurately indicate the presence or onset of RAP lesions.

Efficacy and Safety of Low-Molecular-Weight Heparin on Prevention of Venous Thromboembolism after Laparoscopic Operation for Gastrointestinal Malignancy in Japanese Patients: A Multicenter, Open-Label, Prospective, Randomized Controlled Trial.

BACKGROUND: The risk of venous thromboembolism (VTE) after surgery for malignancy in Japanese patients is unclear; therefore, standard prevention protocols have not been established, especially for minimally invasive procedures. We aimed to investigate the additional effect of low molecular weight heparin (LMWH) on prevention of VTE after laparoscopic surgery for gastrointestinal malignancy. STUDY DESIGN: From February 2013 to January 2017, 400 patients scheduled for laparoscopic surgery were included. Cases were randomly allocated to the physical therapy group (Control group; 201 patients) or to the combination-therapy group (LMWH group; 199 patients), in which enoxaparin sodium (20 mg [= 2000 IU] twice a day) was administered for 1 week postoperatively in addition to the physical therapy. A diagnosis of VTE was made by contrast-enhanced CT or ultrasonography when symptomatic or D-dimer was ≥10 µg/mL. RESULTS: VTE was observed in 1.2% and 4.0% of patients in the LMWH and Control groups, respectively (odds ratio [OR] 0.3, 95% confidence interval [CI] 0.03-1.53). Pulmonary embolism was confirmed only in the Control group (1.7%). No major bleeding occurred in either group. Logistic multiple regression analysis revealed that surgical time extension (OR 1.02, 95% CI 1.00-1.04) was a risk factor of VTE, while administration of LMWH (OR 0.21, 95% CI 0.03-0.99), male sex (OR 0.12, 95% CI 0.01-0.60), and early cancer (OR 0.17, 95% CI 0.02-0.82) reduced the risk of VTE. CONCLUSIONS: Postoperative LMWH administration is safe. The additional effect of LMWH administration on the physical therapy was not statistically proven in this study. However, it could be useful for the patients with risk factors such as female sex, long operation time, and higher cancer stage.

Three-year outcome of aflibercept treatment for Japanese patients with neovascular age-related macular degeneration.

BACKGROUND: To evaluate the three-year outcome after intravitreal aflibercept injection (IAI) for neovascular age-related macular degeneration (nAMD). METHODS: Forty-nine treatment-naïve nAMD patients (50 eyes) were enrolled in this prospective study. The eyes received IAI at two-month intervals in the first year. The treatment regimen was changed to IAI based on a treat-and-extend approach in the second and third years. RESULTS: Twenty-nine eyes of 28 patients were successfully followed up over 36 months. The nAMD subtypes included 15 eyes with typical AMD and 14 eyes with polypoidal choroidal vasculopathy. The number of IAIs performed over the 3 years was 17.2 ± 3.1 (mean ± standard deviation). The mean logMAR, which was 0.42 at baseline, improved to 0.19 (P = 0.001) at 12 months, and 0.26 (P = 0.049) at 36 months. The central retinal thickness (CRT) was 329 ± 120 µm at baseline, 151 ± 38 µm (P < 0.001) at 12 months, and 143 ± 61 µm (P < 0.001) at 36 months. The mean subfoveal choroidal thickness (SFCT) was 288 ± 97 µm at baseline, 243 ± 82 µm (P < 0.001) at 12 months, and 208 ± 63 µm (P < 0.01) at 36 months. The changes in logMAR, CRT, and SFCT over the study period did not differ between typical AMD and PCV. CONCLUSION: Long-term aflibercept injection can achieve visual improvement and reduce the thickness of the retina and choroid in nAMD. Morphological improvement of these tissues may not be sufficient to sustain earlier visual improvement over the long-term.

Ileectomy performed on a case of adult intussusception due to inversion of Meckel's diverticulum.

We report a rare case of adult intussusception caused by an inverted Meckel's diverticulum with ectopic pancreatic tissue. A 43-year-old woman was referred to our hospital with complaints of abdominal distention, intermittent abdominal pain and nausea that she experienced 3 months ago. Abdominal computed tomography scans demonstrated ileo-ileal intussusception that contained a tumor with fat density as the lead point. Laparoscopic-assisted partial resection of the small intestine was performed. The surgical specimen showed an elongated polypoid lesion invaginated into the intestinal tract indicating an inverted Meckel's diverticulum. Pathological findings showed a true diverticulum that ran antimesentrically, with tall columnar epithelium, a mucous gland and an islet of Langerhans. The postoperative period was uneventful, and she was discharged on the ninth postoperative day.

Temporary loss of consciousness during cetuximab treatment of a patient with metastatic colon cancer: a case report.

BACKGROUND: Anti-epidermal growth factor receptor (EGFR) antibody is widely used for the treatment of patients with metastatic colorectal cancer. Hypomagnesemia is a comparatively frequent adverse event of this drug, which is likely overlooked because it occurs later in treatment without symptoms. Furthermore, hypomagnesemia and hypomagnesemia-induced corrected QT (QTc) prolongation may lead to loss of consciousness (LOC), the onset of which is not generally considered associated with the treatment of anti-EGFR antibody because of its rare occurrence. Here, we present a colorectal cancer patient treated with anti-EGFR antibody, who suffered LOC during treatment while severe hypomagnesemia or QTc prolongation was not observed. CASE PRESENTATION: A 69-year-old man with metastatic colon cancer was treated with cetuximab (anti-EGFR antibody) plus irinotecan as third-line chemotherapy. His serum magnesium level gradually decreased, and grade 2 hypomagnesemia (a serum magnesium level of 0.9 mg/dL) was observed at the 12th administration of cetuximab. In light of this development, intravenous supplementation of 20 mEq magnesium sulfate began with careful blood monitoring despite the lack of clinical symptoms. Electrocardiogram (ECG) showed prolonged QT or corrected QT (QTc) intervals (grade 1). His serum magnesium level remained at 0.9 mg/dL, and no hypomagnesemia symptoms were observed by the 17th administration of cetuximab. After the treatment, however, he suddenly lost consciousness without symptoms related to infusion or allergic reactions. Circulatory collapse following dermatological reactions and respiratory events were not evident. Intravenous supplementation of magnesium sulfate was administered again. He awakened 2 min after the onset of temporary LOC without any other symptoms related to hypomagnesemia, such as lethargy, tremor, tetany, and seizures. No other etiology outside of the low level of serum magnesium was confirmed in further examinations. Cetuximab was discontinued, and his serum magnesium level returned to a level within the normal range after 6 weeks. Because of tumor progression, regorafenib and TAS-102 (trifluridine tipiracil hydrochloride) were introduced sequentially for 6 months. Five months after the final treatment of TAS-102, he died of his primary disease, which reflected a survival period of 4 years and 6 months since the beginning of treatment. CONCLUSIONS: This case report reminds clinicians that LOC can be induced without severe hypomagnesemia or QTc prolongation, during anti-EGFR antibody treatment for metastatic colorectal cancer even while under carefully monitored magnesium supplementation.