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A letter to the editor is presented in response to the article "Intraocular Soluble IL-2 Receptor Alpha in a Patient With Adult T Cell Leukemia With Intraocular Invasion," published in the previous issue.

A 70-year-old woman underwent a partial mastectomy with preoperative diagnosis of phyllodes tumor. Histopathological examination of the resected specimen revealed noninvasive ductal carcinoma of up to 20 mm in the phyllodes tumor. We note the possibility of a situation in which a phyllodes tumor is accompanied by cancer, and detailed pathological examination is necessary.

A 50s-year-old man was admitted to our hospital because of abdominal pain and vomitting. CT showed a thickened wall of the sigmoid colon, marked enlargement of the oral side, and a 30 mm tumor on the left lateral section of the liver. We diagnosed colonic obstruction due to sigmoid colon cancer with liver metastasis. We failed to place a colonic stent for decompression, so we performed a colostomy using the cecum. An exploratory laparoscopy was performed instead of curative surgery due to peritoneal disseminations, followed by chemotherapy and molecular targeted therapy. Although primary lesion, liver metastatic lesion and disseminated lesions were reduced by pharmacotherapy the patient developed a grade 2 skin disorder around the colostomy. Therefore, it was determined that molecular targeted therapy could not be continued. The resection of the primary lesion and closure of the colostomy were performed to continue pharmacotherapy. Pharmacotherapy was resumed after operation. The patient is currently getting complete remission, undergoing maintenance therapy with no skin disorders. In this case, surgery was performed as part of the multidisciplinary treatment. It suggested that palliative surgery might be an effective option in multidisciplinary treatment.

The case is a 17-year-old man. He had complained of right lower abdominal pain for a week. He had no symptoms such as fever, weight loss, or night sweats. He was diagnosed with intussusception by abdominal contrast-enhanced CT and was hospitalized. The day after hospitalization, lower gastrointestinal endoscopy was performed, and a tumor 25 mm in size was found in the invagination of the ileum. Intussusception was recovered by intestinal scope insufflation, and the tumor was found to be a type 1 tumor located approximately 5 cm proximal to the Bauhin's valve. On day 17 of hospitalization, he had intussusception again at the time of surgery, and performed laparoscopic reduction before performing laparoscopy-assisted partial resection of the small intestine and appendectomy. The postoperative course was good and he was discharged on POD12(on day 29 of hospitalization). Histopathological diagnosis was diffuse large B-cell lymphoma(DLBCL), and chemotherapy was to be administered at the referral hospital. In intussusception of the adolescents and young adults(AYA)generation, such as this case outside of childhood, it is necessary to treat the patient with consideration for the presence of neoplastic lesions such as malignant lymphoma. We report our case with some literature considerations.

The case was a woman in her 50s. Total pelvic resection was performed for advanced rectal cancer(cT4b[vagina]N3M0, cStage Ⅲc), after neoadjuvant chemoradiation therapy. Five months after the operation, she was unable to stand due to severe back pain. Spinal MRI revealed multiple bone metastases and lumbar fractures. In addition, dysphagia and dysarthria rapidly progressed almost simultaneously with back pain. Initially, brain metastasis was suspected, but head MRI revealed Collet-Sicard syndrome due to skull base metastasis. Irradiation to the skull base and high cervical spine, thoracolumbar spine was started. After irradiation, her back pain and cranial nerve symptoms improved. She was discharged and received palliative treatment. About a month after discharge, she was hospitalized for recurrent dysphagia and died on day 5 of hospitalization. Collet-Sicard syndrome is caused by damage to the cranial nerves Ⅸ to Ⅻ and is often caused by a tumor. Trauma, vasculitis, and internal carotid artery dissection have been reported as other causes. Symptoms such as hoarseness, dysarthria, tongue atrophy, dysphagia, and headache have been reported. Collet-Sicard syndrome due to bone metastasis of colorectal cancer were very rare, and we found only one other report. We report our case with some literature considerations.

We report a case of rapidly growing breast spindle cell carcinoma. The case was a 69-year-old female. Her chief complaint was right breast pain. She was being followed after surgery for left breast cancer but was seen because of right breast pain. In the right mammary gland CD area, a 27×27 mm large unclear mass lesion was observed, which had not been seen half a year prior. Right mastectomy and axillary dissection were performed following a preoperative diagnosis of pT2N1M0, pStage ⅡB ductal carcinoma. Currently, 2 years and 2 months have passed since the operation, and recurrence has not been observed. Case reports of rapidly growing breast spindle cell carcinoma are occasionally found, but no literature specifically defines acute growth. Here, we defined rapid growth using the tumor doubling time(DT)proposed by Gerstenberg et al. Of all the reported cases of breast spindle cell carcinoma, the DT was fewer than 90 days in most cases. Breast spindle cell carcinoma demonstrates rapid grown compared to normal breast cancer.

This paper reports a case of refractory ascites in a patient with gastric cancer. A peritoneo-venous shunt(PVS)was inserted in the patient, which contributed to extending the duration of home-based care as well as improving the patient's quality of life. The patient was a female in her 70s. She was diagnosed with gastric cancer and underwent total gastrectomy. Five years and 7 months after the surgery, she was diagnosed with peritoneal recurrence. Ascites temporarily decreased following chemotherapy, but gradually worsened thereafter. Since the patient required frequent puncture drainage for the ascites, cell-free concentrated ascites reinfusion therapy(CART)was performed. However, on the day prior to the scheduled second course of CART, marked abdominal distension was observed. Therefore, a PVS was inserted. No PVS-associated complications were observed. Following the insertion of the PVS, the patient's abdominal circumference and body weight markedly improved. Best supportive care(BSC)was provided to the patient as she became weak after undergoing several courses of chemotherapy on an outpatient basis. On the other hand, the PVS was working properly. The patient was able to continue her daily life activities at home. She died from the cancer after 164 days of the PVS insertion.

A 67-year-old female was diagnosed with Stage Ⅳ rectal cancer with paraaortic lymph node metastasis. The patient underwent Hartmann's operation with D3 lymph node and paraaortic lymph node dissection. Postoperative chemotherapy with FOLFIRI was then administered for 1 year. However, liver metastasis developed, for which partial hepatectomy was performed. Postoperative chemotherapy with S-1(20 courses)was then administered. Three years and 11 months following the first operation, lymph node metastases developed and resection of lymph nodes(No. 12p, No. 16b1int)was performed. Postoperative chemotherapy with capecitabine(Cape)(8 courses)was then administered. Five years and 7 months following the first operation, Virchow lymph node metastasis developed. Despite chemotherapy with Cape and bevacizumab (Bmab), Virchow lymph node swelling recurred, and resection was performed. Nine years and 4 months following the first operation, lymph node metastases developed, and resection of lymph nodes(Virchow, No. 16b1int)was performed. Postoperative chemotherapy with S-1(8 courses)was then administered. At present, 11 years and 4 months after the first operation, the patient, whose chemotherapy has been discontinued, is alive without recurrence.

An 87-year-oldwoman was admittedto our hospital with abdominal pain andfever. Computedtomography showeda 25 mm tumor mass in the pancreatic headandshowedd ilatation of the pancreatic duct andcommon bile duct. She was diagnosed with obstructive cholangitis due to pancreatic head cancer. An endoscopic naso-biliary drainage(EUS)tube was inserted, and an endoscopic ultrasound(ENBD)examination was performed. At this time, duodenal perforation occurred, and an emergency operation was performed. During the laparotomy, perforation was found in the anterior wall of the duodenum. The contamination in the abdominal cavity and the degree of tissue damage in the duodenum were mild. Gall bladder jejunal andd uodenal jejunal anastomoses were performedfor biliary bypass andto close the perforation andbypass the gastrointestinal tract, respectively. She hadno postoperative complications andwas discharged 13 days postoperatively. Oral intake was possible after discharge, andthe patient returnedhome without complications. She died 5 months postoperatively. In this case, we performedbile duct andgastrointestinal bypass surgery prophylactically. Although this surgery will not be effective for all patients, we thought that it wouldbe useful for predicting the patient's future condition and for increasing the procedural options, even in case of emergency surgery.

The patient was a 48-year-old woman. She consulted our hospital with a chief complaint of vomiting. Colonoscopy showed stenosis and edematous mucosa, and biopsy was performed. Histological examination demonstrated the lesion to be colonic metastasis of breast cancer, invasive lobular carcinoma. Although colorectal metastasis of breast cancer has a poor prognosis and chemotherapy is considered as the main treatment modality, hormone therapy is also a treatment option depending on the condition.

The patient was an 82-year-oldwoman. She consultedour hospital with a chief complaint of left breast mass. MRI showed enhancedtumor with skin andextensive pectoral muscle invasion, so it was unresectable. Immunohistopathological analysis revealeda HER2-positive lesion. We administerederibulin, trastuzumab andpertuzumab, after which the tumor became resectable. Histological examination revealedremarkable response. Combination therapy of eribulin, trastuzumab andpertuzumab was well toleratedandconsid eredto be effective.

The prognosis of patients with esophageal cancer recurrence is poor, and surgical treatment is rarely performed. Here, we report on a patient with long-term survival who underwent pulmonary metastasis resection twice after curative resection of esophageal cancer. A 62-year-old male underwent curative resection of esophageal cancer after preoperative chemoradiotherapy. The histopathological diagnosis was poorly differentiated squamous cell carcinoma(pT2N1M0, fStage Ⅱ). Five months after the operation, right lung metastasis(right-S2)was detected. Accordingly, pulmonary metastasis resection was performed. Fourteen months after the initial operation, left lung metastases(left-S3/S6)were detected. The patient underwent resection again for the pulmonary metastases. The patient died of pneumonia without recurrence 8 years 3 months after the initial operation. In selected cases, surgical resection seems effective for treating distant esophageal cancer metastasis, suggesting that surgery should be an option in cases of accumulation of numerous distant metastases in esophageal cancer.

Purpose: Emergency surgery for obstructive colorectal cancer is considered to be associated with a high degree of risk, and surgery may after decompression is considered to be safer. In cases of obstructive colorectal cancer, decompression can be achieved with surgery, an ileus tube, or a stent, depending on the disease condition. We herein compare the treatment methods for obstructive colorectal cancer., Methods: Forty-two patients with obstructive colorectal cancer underwent emergency treatment between January 2012 and December 2016., Results: Among the patients with obstructive colorectal cancer, 18 receiveda stent, 10 receiveda nasal ileus tube, 6 receiveda transanal ileus tube, 5 underwent stoma construction, and 3 underwent emergency surgery without decompression. The stent group showed the highest laparoscopic operation rate. There was no significant difference in the overall survival of the treatment groups. One patient in the stent group developed duplicated cancer., Conclusion: Stent placement can be considered to be a viable option in the emergency treatment for obstructive colorectal cancer because laparoscopic surgery anda preoperative examination can be performed.

Schwannomas are tumors and commonly occur in the head and neck region; however, they rarely present in the retroperitoneum. A 79-year-old man was admitted to our hospital for a follow-up of a tumor in the hepatic hilus. A 2.8 × 2.5 cm solid tumor located between the hepatic hilus and common hepatic artery was originally identified, and the size of the tumor had increased from 2.0 × 2.0 cm to 2.8 × 2.5 cm over the course of 3 years. The patient underwent percutaneous sonopsy, and the tumor was subsequently diagnosed as a benign schwannoma. Since the patient wished to undergo an operation, we performed laparoscopic surgery. During the operation, the tumor was detected in the retroperitoneal space, where it was strongly adhered between the left gastric artery and common hepatic artery. At this point, no major vessels had vascularized the tumor. We then completely removed the tumor from the retroperitoneal space without any complications. The clinical course was uneventful, and the patient was discharged on postoperative day 4 without any symptoms. Later, a definitive histopathologic examination revealed a benign schwannoma. Here, we report this rare case of a retroperitoneal schwannoma located in the hepatic hilus.

A 66-year-old female presented with the main complaint of defecation trouble and abdominal distention. With diagnosis of rectal cancer, cSS, cN0, cH0, cP0, cM0 cStage II, Hartmann's operation with D3 lymph node dissection was performed and a para-aortic lymph node and a disseminated node near the primary tumor were resected. Histological examination showed moderately differentiated adenocarcinoma, pSS, pN3, pH0, pP1, pM1 (para-aortic lymph node, dissemination) fStage IV. After the operation, the patient received chemotherapy with FOLFIRI regimen. After 12 cycles of FOLFIRI regimen, computed tomography (CT) detected an 11 mm of liver metastasis in the postero-inferior segment of right hepatic lobe. With diagnosis of liver metastatic recurrence, we performed partial hepatectomy. Histological examination revealed moderately differentiated adenocarcinoma as a metastatic rectal cancer with cut end microscopically positive. After the second operation, the patient received chemotherapy with TS1 alone for 2 years. Ten months after the break, CT detected a 20 mm of para-aortic lymph node metastasis and a 10 mm of lymph node metastasis at the hepato-duodenal ligament. With diagnosis of lymph node metastatic recurrences, we performed lymph node dissection. Histological examination revealed moderately differentiated adenocarcinoma as metastatic rectal cancer in para-aortic and hepato-duodenal ligament areas. After the third operation, we started chemotherapy with modified FOLFOX6 regimen. After 2 cycles of modified FOLFOX6 regimen, due to the onset of neutropenia and liver dysfunction, we switched to capecitabine alone and continued it for 6 mo and then stopped. Eleven months after the break, CT detected two swelling 12 mm of lymph nodes at the left supraclavicular region. With diagnosis of Virchow lymph node metastatic recurrence, we started chemotherapy with capecitabine plus bevacizumab regimen. Due to the onset of neutropenia and hand foot syndrome (Grade 3), we managed to continue capecitabine administration with extension of interval period and dose reduction. After 2 years and 2 mo from starting capecitabine plus bevacizumab regimen, Virchow lymph nodes had slowly grown up to 17 mm. Because no recurrence had been detected besides Virchow lymph nodes for this follow up period, considering the side effects and quality of life, surgical resection was selected. We performed left supraclavicular lymph node dissection. Histological examination revealed moderately differentiated adenocarcinoma as a metastatic rectal cancer. After the fourth operation, the patient selected follow up without chemotherapy. Now we follow up her without recurrence and keep her quality of life high.

Objective: Although laparoscopic surgery has become widespread, effective and efficient education in laparoscopic surgery is difficult. Instructive laparoscopy videos with appropriate annotations are ideal for initial training in laparoscopic surgery; however, the method we use at our institution for creating laparoscopy videos with audio is not generalized, and there have been no detailed explanations of any such method. Our objectives were to demonstrate the feasibility of low-cost simple methods for recording surgical videos with audio and to perform a preliminary safety evaluation when obtaining these recordings during operations., Design: We devised a method for the synchronous recording of surgical video with real-time audio in which we connected an amplifier and a wireless microphone to an existing endoscopy system and its equipped video-recording device. We tested this system in 209 cases of laparoscopic surgery in operating rooms between August 2010 and July 2011 and prospectively investigated the results of the audiovisual recording method and examined intraoperative problems., Setting: Numazu City Hospital in Numazu city, Japan., Participants: Surgeons, instrument nurses, and medical engineers., Results: In all cases, the synchronous input of audio and video was possible. The recording system did not cause any inconvenience to the surgeon, assistants, instrument nurse, sterilized equipment, or electrical medical equipment. Statistically significant differences were not observed between the audiovisual group and control group regarding the operating time, which had been divided into 2 slots-performed by the instructors or by trainees (p > 0.05)., Conclusions: This recording method is feasible and considerably safe while posing minimal difficulty in terms of technology, time, and expense. We recommend this method for both surgical trainees who wish to acquire surgical skills effectively and medical instructors who wish to teach surgical skills effectively., (Copyright © 2015 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

A 91-year-old man was referred to our hospital with intermittent dysphagia. He had undergone esophagectomy for esophageal cancer (T3N2M0 Stage III) 11 years earlier. Endoscopic examination revealed an anastomotic stricture; signs of inflammation, including redness, erosion, edema, bleeding, friability, and exudate with white plaques; and multiple depressions in the residual esophagus. Radiographical examination revealed numerous fine, gastrografin-filled projections and an anastomotic stricture. Biopsy specimens from the area of the anastomotic stricture revealed inflammatory changes without signs of malignancy. Candida glabrata was detected with a culture test of the biopsy specimens. The stricture was diagnosed as a benign stricture that was caused by esophageal intramural pseudodiverticulosis. Accordingly, endoscopic balloon dilatation was performed and anti-fungal therapy was started in the hospital. Seven weeks later, endoscopic examination revealed improvement in the mucosal inflammation; only the pseudodiverticulosis remained. Consequently, the patient was discharged. At the latest follow-up, the patient was symptom-free and the pseudodiverticulosis remained in the residual esophagus without any signs of stricture or inflammation.

We herein describe a case with an internal hernia that developed after laparoscopic abdominoperineal resection for rectal cancer. The small intestine passed through the space between the sigmoid colon loop of the stoma and the abdominal wall. Internal hernias associated with colostomy are rare; however, the condition is an important complication, because it causes ischemia in both the herniated intestine and the sigmoid colon pulled through the abdominal wall as a stoma., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To investigate the effectiveness and safety of a new surgical technique of fovea-sparing internal limiting membrane (ILM) peeling for the treatment of foveal retinal detachments (RDs) in eyes with myopic traction maculopathy., Design: Retrospective, consecutive, interventional case series., Methods: Forty-five eyes of 45 consecutive patients who underwent vitrectomy and ILM peeling for the treatment of a foveal RD attributable to myopic traction maculopathy were studied. The patients were divided into 2 groups by the area of ILM peeled: complete macular ILM peeled group (30 eyes) and fovea-sparing ILM peeled group (15 eyes). A gas tamponade was used in all of the eyes. The main outcome measures were the rate of development of a full-thickness macular hole (MH) and the best-corrected visual acuity (BCVA). All of the patients were followed for more than 6 months., Results: A full-thickness MH developed in 5 of 30 eyes (16.7%) in the complete ILM peeled group and in none of the 15 eyes in the fovea-sparing ILM peeled group. Postoperative OCT examination showed a contraction of the residual ILM on the fovea and reduction of the outer lamellar holes in the fovea-sparing ILM peeled group. The postoperative BCVA was significantly better than the preoperative BCVA in the fovea-sparing ILM peeled group (P = .04), but not in the complete ILM peeled group., Conclusions: Fovea-sparing ILM peeling results in better visual and anatomic outcomes for the treatment of foveal RD attributable to myopic traction maculopathy. These were accomplished by reducing the development of a full-thickness MH., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We examined the expression of ephrin-B1 and its cognate receptor EphB2, key regulators of angiogenesis and embryogenesis, in human abdominal aortic aneurysm (AAA) and analyzed their functional roles in cell migration. From 10 patients (9 males and 1 female; age, 68.5 ± 2.4) who underwent vascular surgery for AAA, we obtained AAA and adjacent control tissues. Using real-time RT-PCR, we analyzed expression of ephrin-B1 and EphB2. We also histologically localized these molecules in AAA tissues. Finally, effects of ephrin-B1 and EphB2 on inflammatory cell chemotaxis were examined by cell migration assay. Expression levels of ephrin-B1 (0.410 ± 0.046 versus 1.198 ± 0.252, P = 0.027) and EphB2 (0.764 ± 0.212 versus 1.272 ± 0.137, P = 0.594) were higher in AAA than normal control. Both ephrin-B1 and EphB2 were expressed in macrophages, T lymphocytes, and endothelial cells within AAA. In chemotaxis assay, ephrin-B1 and EphB2 inhibited mononuclear-cell chemotaxis induced by stromal derived factor-1 down to 54.7 ± 12.7% (P = 0.01) and 50.7 ± 13.1% (P = 0.01), respectively. These data suggest that ephrin-B1 and EphB2 might be functional in human adult inflammatory cells and involved in the pathogenesis of AAA, although specific roles of these molecules should further be sought.

Cardiomyopathy (CM) is degenerative disease of myocardium which leads to severe cardiac failure. Although many causative genes for CM have been identified, molecular pathogenesis of CM is not fully understood. In this study, we searched for a novel pathway recruited in the development of CM by using BIO14.6 hamster as an animal model for human CM. We screened upregulated genes in the left ventricle by differential display technique and searched for a gene which had never been linked to CM. We identified a novel gene overexpressed in BIO14.6 hamster ventricles, which was considered to be a new member of aldo-keto reductase (AKR) superfamily. The cloned cDNA encoded a 316 amino acid polypeptide with calculated molecular mass of 35,804, which showed high amino acid sequence similarities to aldose reductase and its relative: 69.6% to AKR1B1 (human aldose reductase), 68.4% to AKR1B3 (mouse aldose reductase), and 85.8% to AKR1B7 (mouse vas deferens protein). The upregulation of this aldose reductase-like gene in BIO14.6 hamster ventricles (6.3 ± 0.8-fold) seemed to be influenced by the overexpression of activator protein-1 present there. With the fact that AKR1B1, AKR1B3, and AKR1B7 have synthetic activities of prostaglandin F2α, the aldose reductase-like protein could cause cardiac hypertrophy through production of prostaglandin F2α whose precursor and receptor were abundant in BIO14.6 hamster ventricles. Aldose reductase and its related proteins would give a new clue to dissect the pathogenesis of CM including oxidative stress and cardiac hypertrophy, and to develop a new drug for the treatment of CM.

Aim: To measure the bacterial genome in ocular fluids and to analyse the clinical relevance of infectious endophthalmitis., Methods: Nineteen ocular fluid samples (eight aqueous humour and 11 vitreous fluid samples) were collected from 19 patients with suspected bacterial endophthalmitis. Fifty ocular samples from uveitis patients were also collected along with 40 samples from patients without ocular inflammation and used as controls. Bacterial ribosomal DNA (16S rDNA) was measured by a quantitative PCR assay., Results: Bacterial 16S rDNA was detected in patients with clinically suspected bacterial endophthalmitis (18/19, 95%). With the exception of one case, high copy numbers of bacterial DNA were detected (1.7×10(3)-1.7×10(9) copies/ml) in these patients. There were 10 samples (53%) with positive bacterial cultures while there were nine samples (47%) with positive Gram-staining. Real-time PCR detected bacterial 16S rDNA in three (6%) of the 50 samples from the control uveitis patients. In addition, none of the samples from the control patients without intraocular inflammation were positive., Conclusions: Quantitative broad-range PCR of bacterial 16S rDNA is a useful tool for diagnosing bacterial endophthalmitis.

Purpose: To evaluate the efficacy of prophylactic vitrectomy for acute retinal necrosis., Methods: The clinical charts of 17 patients (18 eyes) with acute retinal necrosis and no retinal break or rhegmatogenous retinal detachment (RRD) were retrospectively analyzed for the efficacy of prophylactic vitrectomy. The retinal necrotic lesions at the initial presentation were classified into three groups according to the lesion site as described by Holland: zone 1 (posterior pole; n = 3), zone 2 (midperiphery; n = 12), and zone 3 (periphery; n = 3). All patients were treated with intravenous antiviral therapy. Three zone 1 eyes and eight zone 2 eyes underwent prophylactic vitrectomy. Four zone 2 eyes and three zone 3 eyes did not receive prophylactic vitrectomy., Results: All zone 1 eyes developed RRD despite prophylactic vitrectomy. Among the 12 zone 2 eyes, eight of the eyes that underwent prophylactic vitrectomy did not develop RRD, whereas three of the four zone 2 eyes without prophylactic vitrectomy developed RRD. All zone 3 eyes were cured with only antiviral medication., Conclusions: Prophylactic vitrectomy is effective in preventing the development of RRD in eyes where necrotic lesions do not extend beyond the midperiphery (zone 2).

Purpose: To determine whether a diagnosis of intraocular lymphoma (IOL) can be made using a combination of polymerase chain reaction (PCR) analysis to detect gene rearrangement of immunoglobulin and cytokine concentrations in the vitreous fluid., Methods: Vitreous samples from 22 patients with clinically suspected IOL and ten control patients with acute retinal necrosis or cytomegalovirus retinitis were examined by PCR analysis and cytokine measurements. Genomic DNA was extracted from the cells in the vitreous, and the immunoglobulin heavy chain (IgH) gene was amplified by two PCR procedures: (1) microdissection and PCR to detect IgH gene rearrangement and (2) qualitative PCR to detect IgH VDJ gene rearrangement. The supernatants of the vitreous samples were used for enzyme-linked immunosorbent assay to determine interleukin (IL)-10 and IL-6 levels., Results: PCR examinations detected IgH rearrangement in the vitreous in 21 of the 22 IOL patients (95.5%) and in none of the ten control patients. Elevated IL-10 concentrations (>100 pg/ml) and the IL-10/IL-6 ratio (>1.0) were positive in 18 of the 22 IOL patients (81.8%), but negative in all of the control patients. Sensitivity, specificity, positive predictive value, and negative predictive value of PCR for the diagnosis of IOL were calculated to be 0.955, 1.000, 1.000, and 0.909, respectively, and those of the cytokine concentration assay to be 0.818, 1.000, 1.000, and 0.714, respectively. When both the intravitreal cytokine assay and PCR analysis of the vitreous samples are used, as well as diagnostic criteria of IOL defined as a positive outcome from one of the two assays together with clinical signs, the sensitivity and specificity of the criteria were 1.000., Conclusions: A combination of PCR assay to detect gene rearrangement of IgH and cytokine profiling (IL-10 and IL-6) is extremely useful for the diagnosis of intraocular lymphoma.

A 57-year-old man was admitted to our hospital because of persistent blurred vision for 5 months. He had opacity in the vitreous body and white lesions in the retina of the right eye. Although cytological examinations of the vitreous samples revealed Class II, the diagnosis of primary intraocular lymphoma (PIOL) was made by detecting both IgH rearrangement by PCR and an elevated ratio of IL-10/IL-6 concentration in the vitreous sample. Systemic examinations were performed simultaneously and no extra-ocular involvement was detected. Intravitreal methotrexate (MTX) injections were effective and the lesions disappeared following injections. Two months later (10 months after appearance of the right eye lesion), however, the same lesions appeared in the left eye. Cytological examinations of the left vitreous sample revealed Class V by detecting large abnormal lymphocytes. Although intravitreal MTX injections were also effective, central nervous system (CNS) involvement appeared only 2 months after the left eye lesions appeared. Open biopsy was performed and a diagnosis of diffuse large B-cell lymphoma was made. Despite starting with high-dose MTX, he died of CNS disease 1 year and 8 months after onset. Diagnosis of PIOL is difficult. Since local treatment was considered insufficient, an optimal treatment strategy for PIOL should be established.

Purpose: To measure the genomic DNA from Epstein-Barr virus (EBV) in ocular fluids and to analyze the clinical relevance of EBV in uveitis., Methods: Intraocular fluids (30 aqueous humor and 30 vitreous fluid samples) were taken from 55 patients with uveitis after informed consent was obtained. Samples were assayed for EBV DNA using qualitative multiplex polymerase chain reaction (PCR) and quantitative real-time PCR. Antibodies to EBV were examined using a complement fixation test., Results: EBV DNA was detected in 17 of 60 samples (28%) and 16 of 55 patients (29%) using multiplex PCR. However, only three of the 17 samples showed significantly high copy numbers of EBV DNA with real-time PCR. EBV DNA was not detected in the serum of all patients. EBV-specific antibodies were positive in the serum of all patients, but not in the vitreous fluid. Vitreous anti-EBV antibodies were positive only in patients displaying genomic DNA of EBV in the vitreous samples., Conclusions: EBV DNA was detected by qualitative PCR in ocular fluids of many uveitis patients, but only a small proportion of patients showed high viral loads on quantitative real-time PCR, indicating that replication of the virus takes place only in a few patients.

Although several cytokines and chemokines have been demonstrated to play pivotal roles in the pathophysiological conditions of atherosclerosis, few findings exist regarding the expression and function of cytokine-modulating molecules such as ephrin-Bs and their cognate receptors, EphBs, in human atherosclerosis. Therefore, in the present study, we screened novel genes modulating atherogenesis by cDNA array and quantitatively determined them by real-time RT (reverse transcription)-PCR in human carotid atherosclerotic plaques. Ephrin-B1 and EphB2, key regulators of embryogenesis, were significantly up-regulated in plaques compared with those in adjacent control tissues [ephrin-B1, 0.638+/-0.106 compared with 0.831+/-0.152, or 130% (P<0.05); EphB2, 1.296+/-0.281 compared with 2.233+/-0.506, or 172% (P<0.05)]. Immunohistological analysis demonstrated that both ephrin-B1 and EphB2 were expressed in macrophages and T-lymphocytes in plaques as well as in monocytes, T-lymphocytes and arterial endothelial cells isolated from healthy adults. Interestingly, the extracellular domains of ephrin-B1 and EphB2, the expression of which were both enhanced in stimulated THP-1 cells, significantly inhibited spontaneous (22.5 and 27.6% respectively; P<0.01) and MCP-1 (monocyte chemoattractant protein-1)-dependent (29.7 and 22.6% respectively; P<0.01) migration of monocytes. In conclusion, these results demonstrate that ephrin-B1 and EphB2 are overexpressed in atherosclerotic tissue and might locally regulate cell migration, possibly through modulating cytokine-related chemotaxic activity; however, the functional role of these molecules in atherogenesis should be investigated further.

Purpose: The human herpesvirus (HHV) family consists of types 1 to 8 (HHV1-8). The purpose of this study was to investigate the detection of HHV DNA, especially HSV1 (herpes simplex virus 1, HHV1), HSV2 (herpes simplex virus 2, HHV2), and VZV (varicella-zoster virus, HHV3) in ocular fluids of patients with acute retinal necrosis(ARN)., Methods: The intraocular genome for HHV1-8 was determined in 19 ocular fluid samples (12 vitreous fluid and 7 aqueous humor samples) taken from ARN patients (n=14). The samples were tested for the presence of virus DNA by two systems of polymerase chain reaction (PCR): the multiplex PCR screening test and real-time quantitative PCR., Results: Multiplex PCR demonstrated VZV (n=16, 84%), HSV1 (n = 1.5%) or HSV2 (n = 2.11%)genomic DNA in all the samples. In real-time PCR, a high copy number of virus DNA was detected. The virus DNA-positive samples contained Epstein-Barr virus (EBV, HHV4) DNA in 9 of 19 samples (47%). No HHV6-8 DNA was detected in the ocular samples, and no virus DNA was detected in the serum samples., Conclusions: The genome for HHV1-3 was detected in the patients with ARN. All cases contained a high copy number for the virus DNA that indicates viral replication. PCR systems are useful for determing whether virus infections are associated with uveitis.

Purpose: To evaluate the diagnostic values of ocular signs and systemic investigations in ocular sarcoidosis, in a retrospective case-control study., Methods: Subjects were 67 consecutive uveitis patients with biopsy-proven sarcoidosis and 111 control patients with other clinical uveitis entities. The predictive values analyzed were sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The five ocular signs for ocular sarcoidosis are (1) mutton fat keratic precipitates and iris nodules; (2) nodules at the trabecular meshwork and tent-shaped peripheral anterior synechia; (3) snowball vitreous opacities; (4) nodular periphlebitis, and (5) multiple chorioretinal lesions (active or atrophic) in the peripheral fundus. In addition, the results of the following five systemic investigations were considered: (1) negative tuberculin skin test; (2) elevated serum angiotensin-converting enzyme; (3) elevated serum lysozyme; (4) elevated serum gamma-globulin; and (5) bilateral hilar lymphadenopathy on chest X-ray., Results: The incidence of all ocular signs and positive results for the systemic investigations were significantly higher in sarcoidosis patients than in controls (P < 0.001). The presence of two or three of the five ocular signs were indicative of a positive finding in the diagnostic parameters. The presence of two positive results among the five systemic investigations showed values higher than 0.800 for all diagnostic parameters., Conclusions: Combinations of the specified ocular signs and the results of systemic investigations can be used for the diagnosis of ocular sarcoidosis.

Objective: To clarify prognostic factors of long-term visual outcome without treatment in patients with myopic choroidal neovascularization (CNV) and estimate a regression equation to predict visual acuity at 5 years after CNV onset., Methods: Fifty-four eyes of 54 consecutive patients with high myopia and subfoveal CNV who did not receive treatment were identified using clinical records from 1988 to 2004. Photodynamic therapy not approved for myopic CNV in Japan during this period. The association of best-corrected visual acuity (BCVA) at 5 years after CNV onset with patient age, refractive error, axial length, initial BCVA, myopic retinopathy grade, duration of persistent hemorrhage, CNV size at onset, and size of hemorrhage around the CNV was analyzed using Spearman's correlation and multiple linear regression analysis., Results: BCVA at 5 years after onset was significantly associated with patient age, CNV size, and initial BCVA (P<0.05, Spearman's correlation). The regression equation estimating BCVA at 5 years after CNV onset was based on age and initial BCVA (R2=0.43). When subjects were divided into groups according to age (<40 and >or=40 years), CNV size, axial length and duration of persistent hemorrhage influenced BCVA at 5 years in patients under 40 years; while only initial BCVA was an influence in those at least 40 years old., Conclusions: We developed a linear predictive model to estimate BCVA at 5 years after onset of myopic CNV without treatment based on the identified prognostic factors. This information might be important for managing patients with myopic CNV.

Purpose: To determine whether patients with Vogt-Koyanagi-Harada (VKH) disease have immune responses specific to the melanocyte antigens tyrosinase and gp100., Methods: T-cell clones (TCCs) were established from cells infiltrating the aqueous humor and from peripheral blood mononuclear cells (PBMCs) of patients with VKH. The target cells were LDR4-transfected cells (HLA-DRB1*0405). The TCCs were cocultured with LDR4 in the presence of tyrosinase (tyrosinase450-462: SYLQDSDPDSFQD), gp100 (gp100(44-59): WNRQLYPEWTEAQRLD), or a control peptide. The immune response was evaluated by cytokine production. The responding melanocyte peptide-specific VKH-TCCs were characterized by an immunofluorescence method with flow cytometry. A search was made for molecular mimicry among tyrosinase450-462, gp100(44-59), and exogenous antigens, such as viruses, by database screening., Results: Cells infiltrating the eye and PBMCs in HLA-DR4+ (HLA-DRB1*0405, 0410) patients with VKH contained a population of CD4+ T lymphocytes that recognized tyrosinase and gp100 peptides and produced RANTES and IFN-gamma in response to the two peptides. The T cells were active memory Th1-type lymphocytes, and they recognized the tyrosinase peptide and produced IFN-gamma in response to HLA-DRB1*0405+ melanoma cells. Cytomegalovirus envelope glycoprotein H (CMV-egH290-302) had high amino acid homology with the tyrosinase peptide. In addition, some of the VKH-TCCs recognized CMV-egH290-302 peptide, as well as the tyrosinase peptides., Conclusions: In VKH there are tyrosinase and gp100 peptide-specific T cells that can mediate an inflammatory response. Such melanocyte antigen-specific T cells could be associated with the cause and pathology of VKH disease.

Purpose: To investigate the expression and secretion of macrophage migration inhibitory factor (MIF) in human trabecular meshwork (HTM) and evaluate its role in ocular inflammation., Methods: Tissue samples of HTM cells were isolated from donor human eyes or corneoscleral buttons, and the HTM cells were cultured. The expression of MIF on HTM cells was evaluated by RT-PCR, Western blot analysis, and ELISA. T-cell clones (TCCs) were established from ocular infiltrating cells of patients with uveitis. ELISA was used to evaluate the pathologic role of MIF, in relation to regulatory effects on cytokine production by T cells., Results: MIF was detected in the HTM by RT-PCR and Western blot analysis. MIF was also shown by ELISA to be secreted by the HTM cells in culture. The HTM supernatant enhanced IFN-gamma production by TCCs, but not IL-10; and these effects were neutralized by anti-MIF antibodies. Similarly, recombinant MIF enhanced the IFN-gamma production by the TCCs., Conclusions: MIF is expressed and secreted in the HTM, and MIF has the capacity to enhance T helper 1 cytokines and may play a role as an inflammatory cytokine in the eye.

Effects of ATP on the intracellular free calcium ion concentration ([Ca2+]i) in the rabbit eye suprachoroid were investigated by means of fura-2 microfluorophotometry. ATP application (10 to 100 microM) elicited a dose-dependent biphasic [Ca2+]i-increase: a fast phase typically peaking within 30 s and a following slow plateau phase, which lasted during the presence of ATP. The slow plateau phase was markedly diminished by removal of extracellular Ca2+, whereas the fast phase remained. An inhibitor of Ca2+ release from the sarcoplasmic reticulum (TMB-8), an endoplasmic Ca2+-ATPase inhibitor (thapsigargin) and a phospholipase C (PLC) inhibitor (U-73122) diminished the fast phase. A P2 receptor antagonist (Suramin) inhibited the ATP-induced [Ca2+]i-response. The potency order of ATP and related substances in producing the [Ca2+]i-elevation was UTP approximately equals ATP>ATP-gamma-S>ITP>ADP. beta,gamma-MethyleneATP, 2-methylthioATP and UDP evoked no response. This order is consistent with the P2Y2 receptor characteristics. Cross-desensitization between ATP and UTP excludes the co-existence of the other types of receptors. In conclusion, the ATP-induced [Ca2+]i-elevation in the rabbit eye suprachoroid was elicited by the Ca2+ release from the PLC-dependent, thapsigargin-sensitive intracellular Ca2+ storage sites by activating P2Y2 nucleotide receptors.