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.

Subfoveal Choroidal Thickness during Aflibercept Therapy for Neovascular Age-Related Macular Degeneration: Twelve-Month Results.

PURPOSE: To investigate changes in subfoveal choroidal thickness after intravitreal aflibercept injections (IAIs) for neovascular age-related macular degeneration (AMD) at 12 months. DESIGN: Retrospective, consecutive, interventional case series. PARTICIPANTS: One hundred forty-four patients with treatment-naïve neovascular AMD examined at 3 university hospitals. METHODS: After a loading phase of 3 monthly 2.0-mg IAIs, the patients were injected bimonthly with additional rescue injections performed for worsening. Subfoveal choroidal thickness in IAI-treated eyes was evaluated using enhanced depth imaging optical coherence tomography (OCT) or swept-source OCT. MAIN OUTCOME MEASURES: Changes in subfoveal choroidal thickness over a 12-month period. RESULTS: Of the 144 treated eyes, 58 (40.3%) had typical neovascular AMD and 86 (59.7%) had polypoidal choroidal vasculopathy (PCV). The mean subfoveal choroidal thickness of treated eyes decreased from 268.1±101.3 µm at baseline to 233.0±99.7 µm at 3 months and remained unchanged at 232.4±99.6 µm at 12 months (percentage decrease, 13.3% at 12 months compared with baseline; P < 0.0001), although there was some fluctuation in between treatments. This decrease in subfoveal choroidal thickness was associated significantly with gain in visual acuity for PCV eyes (P = 0.0087; R = 0.28), but not for eyes with typical neovascular AMD (P = 0.17; R = 0.18). Eyes without persistent or recurrent retinal fluid after the loading phase showed greater decrease in subfoveal choroidal thickness compared with those with persistent or recurrent retinal fluid, in both typical neovascular AMD (P = 0.042) and PCV (P = 0.038) eyes. CONCLUSIONS: Subfoveal choroidal thickness decreased over 12 months with IAI therapy in eyes with neovascular AMD. Changes in subfoveal choroidal thickness after IAIs seem to be related to visual and anatomic outcomes.

Herpes simplex virus-1 encephalitis induced by chemoradiotherapy and steroids in an esophageal cancer patient: a case report.

BACKGROUND: Systemic chemotherapy combined with steroids used as prophylactic antiemetics have been reported to induce immunosuppression. Further, herpes simplex virus-1 (HSV-1) infection has been reported to occur in patients with small cell carcinomas after chemoradiotherapy that includes brain irradiation. Here, we report a case of HSV-1 encephalitis that occurred in a patient undergoing chemoradiotherapy for advanced esophageal cancer. CASE PRESENTATION: A 77-year-old woman received chemoradiotherapy (5-fluorouracil, 700 mg/m(2); cisplatin, 70 mg/m(2); and radiotherapy, 60 Gy in total) for stage III esophageal cancer. The total radiation dose was administered concurrently with the first two courses of chemotherapy, together with dexamethasone as a prophylactic antiemetic. Two days before completion of the fourth course of chemotherapy, the patient developed acute neurological symptoms of disorientation, clouding of consciousness, and fever. T2-weighted magnetic resonance imaging showed a high intensity area in the bilateral temporal lobes and insular cortex. Furthermore, DNA PCR testing of cerebrospinal fluid showed clear positivity for HSV-1 DNA, and the patient was diagnosed with herpetic encephalitis. Intravenous administration of acyclovir for 3 weeks led to gradual improvement of consciousness, and the patient was able to respond to verbal cues. CONCLUSION: In advanced esophageal cancer patients, standard treatment involves chemoradiotherapy and surgery. However, primary infection with or reactivation of endogenous latent HSV-1 in the brain cortex during chemoradiotherapy combined with administration of a steroid may compromise the benefits of treatment.

Clinical characteristics of synchronous colorectal cancers in Japan.

BACKGROUND: Incidence and clinical characteristics of synchronous colorectal cancer (sCRC) patients significantly vary among studies, likely due to differences in surveillance methodology. If remain undetected, sCRC can progress to more advanced stages seriously aggravating patient prognosis. We studied the incidence and clinicopathological characteristics of Japanese patients with sCRCs who underwent surgery for primary CRC and received exhaustive perioperative surveillance. METHODS: We recruited 1005 patients with surgically resected CRCs between January 2007 and December 2011. The associations of clinical and pathological factors with sCRC development were assessed by univariate and multivariate logistic regression. RESULTS: Eighty-four patients (8.4 %) developed sCRCs, 16 of them (19.0 %) harboring three or more cancers. Companion sCRCs were smaller and earlier stage than the index lesion (P < 0.0001). In multivariate analysis, advanced age (odds ratio (OR) 1.03 per year; P = 0.009) and left colon tumor location (OR 1.78; P = 0.013) are associated with higher risk of sCRCs, particularly in females. Overall survival did not differ between solitary CRC and sCRC (P = 0.62). CONCLUSIONS: Our results highlight the importance of perioperative colonoscopy examination to ensure the absence of sCRCs that, being small and early staged, are more difficult to detect. The incidence of sCRC, and notably of triple or more sCRCs, was higher than previously recognized. Because they are also significantly higher than expected by merely stochastic accumulation of individual cancerous lesions, we suggest that the occurrence of many sCRC reflects a hitherto uncharacterized predisposition condition.

One-Year Results of Intravitreal Aflibercept for Polypoidal Choroidal Vasculopathy.

PURPOSE: To investigate 1-year outcomes of intravitreal aflibercept for polypoidal choroidal vasculopathy (PCV). DESIGN: Retrospective, multicenter, consecutive case series. PARTICIPANTS: A total of 90 eyes of 87 patients with treatment-naïve PCV followed at 3 tertiary centers. METHODS: Clinical records were reviewed and imaging studies were analyzed of eyes with PCV that underwent 3 consecutive monthly aflibercept injections followed by injections every 2 months. Additional (rescue) injections were performed for worsening. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), optical coherence tomography (OCT), and angiographic findings at 1 year. RESULTS: The mean BCVA (logarithm of the minimum angle of resolution units) of the 90 eyes improved from 0.31 at baseline to 0.17 at 12 months (P < 0.001). The mean central retinal thickness decreased from 315 µm at baseline to 204 µm at 12 months (P < 0.001). At 12 months, 64 eyes (71.1%) achieved a dry macula, defined as absence of intraretinal or subretinal fluid on OCT. Of 83 eyes that underwent indocyanine green angiography at both baseline and 12 months, 46 (55.4%) showed complete and 27 (32.5%) showed partial resolution of polypoidal lesions. Eleven of 82 eyes (13.4%) showed decreased size of branching choroidal vascular networks. CONCLUSIONS: Intravitreal aflibercept administered over 1 year improved both visual acuity and macular morphology in a large number of treatment-naïve eyes with PCV.

MMP20 and ARMS2/HTRA1 Are Associated with Neovascular Lesion Size in Age-Related Macular Degeneration.

PURPOSE: Age-related macular degeneration (AMD) is the leading cause of severe visual impairment. Despite treatment, a central scotoma often remains. The size of the scotoma depends on the lesion size of the choroidal neovascular membrane and significantly affects the patient's quality of life, and the lesion size of neovascularization also affects response to treatments. The aim of this study was to identify genes associated with the neovascular lesion size in neovascular AMD. DESIGN: A genome-wide association study (GWAS). PARTICIPANTS: We included 1146 Japanese patients with neovascular AMD. METHODS: We performed a 2-stage GWAS for the lesion size of AMD as a quantitative trait among 1146 (first stage: 727, second stage: 419) Japanese patients with neovascular AMD. Lesion size was determined by the greatest linear dimension measured with fluorescein angiography examination before treatment. We examined the association between the genotypic distribution of each single nucleotide polymorphism (SNP) and the trait using an additive model adjusted for age and sex. To evaluate the associations between AMD development and SNPs associated with lesion size, we also performed a case-control study by using the genotype data from these 1146 Japanese patients as case subjects and the fixed dataset from the Nagahama Study as control subjects. MAIN OUTCOME MEASURES: Genes associated with the lesion size in neovascular AMD. RESULTS: In the discovery stage, rs10895322 in MMP20 showed a genome-wide significant P value of 6.95×10(-8), and rs2284665 in ARMS2/HTRA1 showed a P value of 1.55×10(-7). The associations of these 2 SNPs were successfully replicated in the replication stage, and a meta-analysis of both stages showed genome-wide significant P values (2.80×10(-9) and 4.41×10(-9), respectively). In a case-control study using 3248 Japanese subjects as controls, we could not find contribution of MMP20 rs10895322 for AMD development. Although MMP20 has been thought to be expressed only in dental tissues, we confirmed MMP20 expression in the human retina and retinal pigment epithelium/choroid with polymerase chain reaction. CONCLUSIONS: The growth of choroidal neovascularization in AMD would be affected by 2 genes: MMP20, a newly confirmed gene expressed in the retina, and ARMS2/HTRA1, a well-known susceptibility gene for AMD.

Subfoveal choroidal thickness changes after intravitreal ranibizumab and photodynamic therapy for retinal angiomatous proliferation.

PURPOSE: To evaluate the subfoveal choroidal thickness changes after intravitreal ranibizumab and photodynamic therapy in patients with retinal angiomatous proliferation. METHODS: Subfoveal choroidal thickness was retrospectively measured using enhanced depth imaging optical coherence tomography. RESULTS: Thirty-two eyes of 26 patients (average age, 82 years) with newly diagnosed retinal angiomatous proliferation were examined. All eyes were treated with intravitreal ranibizumab and photodynamic therapy. In 14 eyes without recurrence over 6-month follow-up (average, 8.4 months), mean subfoveal choroidal thickness decreased from 198 µm at baseline to 169 µm (85.4%) at 3 months and to 173 µm (87.3%) at 6 months after treatment (P < 0.01 compared with baseline, respectively). In 18 eyes with recurrence over 3-month follow-up, mean subfoveal choroidal thickness decreased from 199 µm at baseline to 171 µm (85.9%) at 3 months after treatment and 176 µm (88.4%) even at recurrence (P < 0.01 compared with baseline, respectively). CONCLUSION: Subfoveal choroidal thickness after intravitreal ranibizumab and photodynamic therapy for retinal angiomatous proliferation decreased to approximately 85% compared with baseline by 3 months after treatment, and the trend persisted in eyes with or without recurrence during follow-up. This may indicate that choroidal changes are not associated with recurrence in retinal angiomatous proliferation.

INITIAL VERSUS DELAYED PHOTODYNAMIC THERAPY IN COMBINATION WITH RANIBIZUMAB FOR TREATMENT OF POLYPOIDAL CHOROIDAL VASCULOPATHY: The Fujisan Study.

PURPOSE: To compare the 1-year results of initial or deferred photodynamic therapy (PDT) combined with intravitreal ranibizumab (IVR) for eyes with polypoidal choroidal vasculopathy. METHODS: Prospectively, 72 men with treatment-naive polypoidal choroidal vasculopathy were randomized to initial or later PDT combined with IVR. In both groups, 2 additional monthly IVR followed. From Month 3, PDT and IVR were administered according to the retreatment criteria. Mean changes in the best-corrected visual acuity between baseline and Month 12 and central retinal thickness, the rate of eyes showing regression of polypoidal lesions, and number of additional treatments were compared. RESULTS: The best-corrected visual acuity increased by a mean of 8.1 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters in the initial PDT group and 8.8 ETDRS letters in the later PDT group, and there was a no significant difference (P = 0.59). The mean central retinal thickness decreased significantly in both groups but more so with combination therapy within the first 4 months; the difference was not significant at Month 12 (P = 0.30). The rate of eyes showing resolution of polypoidal lesions at 12 months was 62.1% in the initial PDT group and 54.8% in the later PDT group and again, there was no significant difference (P = 0.53). The mean number of additional IVR was 1.5 in initial PDT and 3.8 in later PDT; that of additional PDTs was 0.14 and 0.45, respectively, and they were significantly different (P < 0.001 and P = 0.013, respectively). CONCLUSION: Both initial and deferred PDT combined with IVR to treat polypoidal choroidal vasculopathy show the similar visual and anatomical improvements at 12 months. Initial PDT combination leads to significantly fewer additional treatments.

[Chemotherapy-Induced Reactivation of Hepatitis B in Recurrent Breast Cancer - A Case Report].

It is known that reactivation of hepatitis B virus (HBV) is an important complication of chemotherapy, and it can cause fatally severe hepatitis in some cases. A 72-year-old woman, underwent radical mastectomy for left breast cancer at the age of 35 years. In January 2008, local recurrence and multiple bone metastases occurred, and chemotherapy was started. S-1(80 mg/day for 28 consecutive days followed by a 14-day rest period)was used as the fourth-line of treatment, but grade 3 anemia(Hb 6.6 g/dL)developed at the end of seventh course. Therefore, blood transfusion was performed. Five months after transfusion, blood tests showed elevated liver function markers and HBs antigen positivity, so post-transfusion hepatitis was suspected. However, it was diagnosed as de novo hepatitis caused by reactivation of HBV from occult infection, as the patient's stored sample before the transfusion tested positive for HBV-DNA. The hepatitis did not become severe, but it was a persistent infection with continued administration of a nucleoside analog. Identifying the reactivation risk and taking appropriate action based on guidelines are necessary for administering chemotherapy safely to patients with occult HBV infection.

DNA methylation alterations of AXIN2 in serrated adenomas and colon carcinomas with microsatellite instability.

BACKGROUND: Recent work led to recognize sessile serrated adenomas (SSA) as precursor to many of the sporadic colorectal cancers with microsatellite instability (MSI). However, comprehensive analyses of DNA methylation in SSA and MSI cancer have not been conducted. METHODS: With an array-based methylation sensitive amplified fragment length polymorphism (MS-AFLP) method we analyzed 8 tubular (TA) and 19 serrated (SSA) adenomas, and 14 carcinomas with (MSI) and 12 without (MSS) microsatellite instability. MS-AFLP array can survey relative differences in methylation between normal and tumor tissues of 9,654 DNA fragments containing all NotI sequences in the human genome. RESULTS: Unsupervised clustering analysis of the genome-wide hypermethylation alterations revealed no major differences between or within these groups of benign and malignant tumors regardless of their location in intergenic, intragenic, promoter, or 3' end regions. Hypomethylation was less frequent in SSAs compared with MSI or MSS carcinomas. Analysis of variance of DNA methylation between these four subgroups identified 56 probes differentially altered. The hierarchical tree of this subset of probes revealed two distinct clusters: Group 1, mostly composed by TAs and MSS cancers with KRAS mutations; and Group 2 with BRAF mutations, which consisted of cancers with MSI and MLH1 methylation (Group 2A), and SSAs without MLH1 methylation (Group 2B). AXIN2, which cooperates with APC and ß-catenin in Wnt signaling, had more methylation alterations in Group 2, and its expression levels negatively correlated with methylation determined by bisulfite sequencing. Within group 2B, low and high AXIN2 expression levels correlated significantly with differences in size (P = 0.01) location (P = 0.05) and crypt architecture (P = 0.01). CONCLUSIONS: Somatic methylation alterations of AXIN2, associated with changes in its expression, stratify SSAs according to some clinico-pathological differences. We conclude that hypermethylation of MLH1, when occurs in an adenoma cell with BRAF oncogenic mutational activation, drives the pathway for MSI cancer by providing the cells with a mutator phenotype. AXIN2 inactivation may contribute to this tumorigenic pathway either by mutator phenotype driven frameshift mutations or by epigenetic deregulation contemporary with the unfolding of the mutator phenotype.

Laparoscopic wedge resection of the stomach for gastrointestinal stromal tumor (GIST): non-touch lesion lifting method.

BACKGROUND: Laparoscopic surgery for GIST carries a risk of intraoperative tumor dissemination. To avoid tumor dissemination, we have utilized a "non-touch" method for surgical resection of GIST since 2000. METHODS: Forty-two patients with gastric GIST were treated at our institution between 2000 and 2012. Laparoscopic wedge resection of the stomach was used as the standard procedure for tumors that were 2-5 cm in size. Tumors larger than 5 cm were treated with open surgery. Our non-touch procedure included a lesion-lifting method using traction sutures at the normal stomach wall around the tumor. Intraoperative gastroscopy was utilized to confirm the location of the tumor with laparoscopy. After lifting of the tumor, tumors with a clear operative margin were resected using a linear stapler. Tumors located at the posterior wall of the stomach or located near the esophagogastric junction were resected using traction sutures. RESULTS: Median operative time was 140 min and median blood loss was 0 ml. Postoperative course was uneventful excepting one patient who experienced postoperative bleeding. The median postoperative stay was 7 days. One patient developed liver metastasis after surgery. None of the patients had local recurrence or peritoneal recurrence case. CONCLUSION: This non-touch lesion-lifting method was useful for the surgical management of gastric GIST.

Five-year results of photodynamic therapy with and without supplementary antivascular endothelial growth factor treatment for polypoidal choroidal vasculopathy.

BACKGROUND: To clarify the long-term efficacy of photodynamic therapy (PDT) in patients with symptomatic polypoidal choroidal vasculopathy (PCV). METHODS: We retrospectively reviewed 60 naive eyes of 59 patients (45 men, 14 women; mean age, 73.8 years) treated with full-fluence PDT (PDT group) and followed for at least 60 months. Retreatment was either antivascular endothelial growth factor (VEGF) therapy or intravitreal triamcinolone acetonide if PDT alone was ineffective (supplemental retreatment group). RESULTS: The mean logarithm of the minimum angle of resolution best-corrected visual acuity (BCVA) levels at baseline and 60 months were 0.66 and 0.71, respectively. The mean change at 60 months was a decrease of 0.50 line. In the PDT group (36 eyes), the mean BCVAs at baseline and month 60 were 0.73 and 0.68, respectively (p = 0.60). In the supplemental retreatment group (24 eyes), the mean BCVAs at baseline and month 60 were 0.55 and 0.74, respectively (p = 0.076). The percentage of eyes with decreased BCVA at the time of the additional anti-VEGF treatment was significantly (p = 0.031) higher than at month 60. The risk factors identified by multiple regression analysis with a significant decrease in BCVA at month 60 were a large greatest linear dimension (GLD), classic choroidal neovascularization at baseline, and a hemorrhage over the arcade vessels after PDT. CONCLUSIONS: The efficacy of PDT for PCV depends on the GLD. Twenty-four of the 60 eyes needed additional treatment other than only PDT during 60 months of follow-up. Additional anti-VEGF treatment may help maintain the BCVA of patients with exudative or anatomic recurrence.

Switching to intravitreal aflibercept injection for polypoidal choroidal vasculopathy refractory to ranibizumab.

PURPOSE: To clarify the efficacy of switching to intravitreal aflibercept injection to treat polypoidal choroidal vasculopathy refractory to ranibizumab. METHODS: In this retrospective study, 43 eyes of 42 patients (mean age, 76.5 years) with polypoidal choroidal vasculopathy treated with aflibercept (2 mg/0.05 mL) were reviewed. A treatment history of 3 consecutive monthly intravitreal injections of ranibizumab as an induction phase followed by a pro re nata maintenance phase over 12 months was seen for all patients. All patients who were refractory to ranibizumab (defined as having persist subretinal or intraretinal fluid by optical coherence tomography and unchanged or decreased visual acuity compared with the time of the first ranibizumab injection, despite receiving the last 3 consecutive monthly intravitreal ranibizumab injections after 12 months). RESULTS: The mean logarithm of the minimum angle of resolution best-corrected visual acuity levels (Snellen equivalent) improved significantly (P = 0.0074) from 0.38 (20/48) at baseline to 0.34 (20/43) 3 months after switching to aflibercept (Month 3) (mean best-corrected visual acuity improvement, 0.47 line). The central retinal thickness decreased significantly (P < 0.0001) from 245 µm at baseline to 131 µm at Month 3. Of 30 eyes with polypoidal lesions at baseline, the polypoidal lesions regressed completely in 15 eyes (50%) at Month 3. CONCLUSION: Administering intravitreal aflibercept injection for patients with polypoidal choroidal vasculopathy refractory to ranibizumab maintained or improved visual acuity and reduced or eliminated exudative lesions and occluding polypoidal lesions without adverse events with short-term follow-up.

Treatment of stage IV gastric cancer with induction chemotherapy using S-1 and cisplatin followed by curative resection in selected patients.

BACKGROUND: The standard treatment for stage IV gastric cancer is chemotherapy, but outcomes remain poor. The effectiveness of induction chemotherapy followed by surgery in selected patients who had a good response to chemotherapy is unclear. METHODS: A total of 59 patients with stage IV gastric cancer received induction chemotherapy with S-1 and cisplatin. In each cycle, oral S-1 (80 mg/m2) was administered for 3 weeks, followed by a 2-week drug holiday. Intravenous cisplatin (60 mg/m2) was administered on day 8 after adequate premedication and hydration. If unresectable features resolved after chemotherapy, patients underwent curative (R0) resection. The safety and outcomes of this treatment combination were evaluated, and predictive factors for survival were determined. RESULTS: Thirteen of 59 patients (22%) were eligible for R0 resection after induction chemotherapy. Kaplan-Meier analysis showed an overall median survival time of 13 months and a 3-year survival rate of 18.2%. Among patients who underwent R0 resection, the median survival time was 53 months and the 3-year survival rate was 53.8%. Multivariate analyses showed that negative para-aortic lymph nodes and undergoing R0 resection were independent predictors of survival. CONCLUSIONS: Treatment of stage IV gastric cancer with S-1 and cisplatin induction chemotherapy followed by R0 resection is safe and may improve survival compared with chemotherapy alone. Further study of this dual-modality therapy is warranted.

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.

Two-year results of combined intravitreal ranibizumab and photodynamic therapy for polypoidal choroidal vasculopathy.

BACKGROUND: To clarify the efficacy of combined therapy with intravitreal ranibizumab injections and photodynamic therapy (PDT) in patients with symptomatic polypoidal choroidal vasculopathy (PCV). METHODS: We retrospectively reviewed 57 treatment-naïve eyes of 57 patients. Thirty-two patients were treated with standard fluence PDT (PDT group), and 25 patients were treated with three consecutive monthly intravitreal injections of ranibizumab and standard fluence PDT (ranibizumab plus PDT group). All patients were followed for at least 24 months. RESULTS: In the ranibizumab plus PDT group, the mean best-corrected visual acuity (BCVA) levels of decimal (logMAR equivalent) significantly improved from 0.30 (0.52) at baseline to 0.55 (0.26) at 24 months (P < 0.001). In the PDT group, the BCVA levels stabilized from 0.26 (0.58) at baseline to 0.25 (0.60) at 24 months. The mean changes in the BCVA in the ranibizumab plus PDT group and the PDT group were improvement of 2.63 lines and decline of 0.16 lines respectively (P = 0.010). The mean number of PDTs at 24 months in the ranibizumab plus PDT group and the PDT group were 1.4 and 2.6 respectively. Increased subretinal hemorrhages were seen in eight (18.0 %) eyes, all of which were belonging to the PDT group. CONCLUSIONS: Combined intravitreal ranibizumab and PDT was significantly more effective in maintaining and improving VA for PCV patients compared with PDT monotherapy over 24 months.

Intravitreal cellular infiltrate imaged as punctate spots by spectral-domain optical coherence tomography in eyes with posterior segment inflammatory disease.

PURPOSE: To investigate the posterior segment in cases of clinically evident intraocular inflammation for punctate reflections consistent with that expected to arise from inflammatory cells. METHODS: Patients with ocular inflammatory diseases imaged with spectral-domain optical coherence tomography (SD-OCT) were retrospectively reviewed. RESULTS: There were 7 patients with mean age of 66.7 years, and the diagnosis was toxoplasmosis in 5 eyes, multiple evanescent white dot syndrome in 1 eye, and posttraumatic outer retinitis in 1 eye. At baseline, the SD-OCT showed vitreous cells as numerous punctate spots in the vitreous in all seven eyes. The SD-OCT also showed similar-sized hyperreflective dots in the retina in all seven eyes. During follow-up, reduced vitreous cellular infiltration was correlated with a decrease in the number of the punctate spots visible by SD-OCT. CONCLUSION: Eyes with intraocular inflammation had SD-OCT images of the vitreous containing punctate spots of a size consistent with that expected from inflammatory cells. Similarly sized punctate spots were seen within the retina in regions of retinitis. Additional characterization of the optical section should permit stereological estimations of actual cell counts per unit volume.

Combined intravitreal ranibizumab and photodynamic therapy for polypoidal choroidal vasculopathy.

PURPOSE: To clarify the efficacy of combined therapy with intravitreal ranibizumab injections and photodynamic therapy in patients with symptomatic polypoidal choroidal vasculopathy. METHODS: We retrospectively reviewed 28 naive eyes of 28 patients (17 men, 11 women; mean age, 73.4 years; range, 55-85 years) with 20/40 or less baseline visual acuity treated with 3 consecutive monthly intravitreal injections of ranibizumab (0.5 mg/0.05 mL) and photodynamic therapy and followed-up for at least 12 months. Photodynamic therapy was administered 1 day or 2 days after the initial injection of ranibizumab. RESULTS: : The mean best-corrected visual acuity levels significantly (P < 0.0001) improved from 0.33 at baseline to 0.61 at 12 months. The mean improvement in best-corrected visual acuity 12 months from baseline was 2.65 lines. The best-corrected visual acuity at 12 months improved in 15 eyes (53.6%) by ≥3 lines and was stable (defined as a loss of <3 lines of vision) in 13 eyes (46.4%). The central retinal thickness significantly (P < 0.0001) decreased from 366 µm to 151 µm at 12 months. The mean numbers of photodynamic therapy treatments and injections during 12 months including the treatments during the initial regimen were 1.1 and 3.7, respectively. No complications developed. CONCLUSION: Combined intravitreal ranibizumab and photodynamic therapy for polypoidal choroidal vasculopathy maintained or improved visual acuity and reduced the exudation without adverse events.