Development of acute hydrops in eye with infectious keratitis: A case report.

Purpose: To determine the characteristics of an eye that developed acute hydrops while being treated for infectious keratitis. Observation: A 35-year-old man presented with pain and blurred vision in his left eye. He had undergone cataract surgery seven years earlier and was being treated for poorly controlled atopic dermatitis. The decimal best-corrected visual acuity (BCVA) of the left eye was 0.01. Slit-lamp microscopy showed conjunctival injection, corneal opacification, and a corneal ulcer. The patient was diagnosed with infectious keratitis and was treated with topical and systemic antibiotics. During the hospitalization, the patient was noted to rub his eyes frequently and vigorously. Five days after the first visit, the cornea protruded markedly, and the stroma surrounding the ulcerated area was edematous. These findings led to a diagnosis of acute hydrops.Penetrating keratoplasty was performed to prevent corneal perforation. Histopathological study of the excised cornea showed stromal edema, infiltration of leukocytes, and a tear in Descemet's membrane. Unfortunately, the patient developed endophthalmitis the day after the surgery. The anterior chamber was irrigated with antibiotics, and antibiotics were also injected into the vitreous. The endophthalmitis gradually subsided, and two years after the surgery, the patient's decimal BCVA had improved to 0.6. Conclusion and importance: Vigorous eye rubbing in cases of infectious keratitis can induce acute hydrops, and timely surgical intervention is recommended.

[A Case of COVID-19 Infection during Postoperative Chemotherapy for Breast Cancer Treated with Antibody Cocktail Therapy to Prevent Disease Aggravation].

The outbreak of COVID-19 has caused a global pandemic, and it has been reported that patients with cancer are at high risk of developing complications from the disease. However, we believe that prolonged interruption of chemotherapy due to extended COVID-19 treatment is not desirable, given the intensity of cancer treatment. We report a case of COVID-19 infection during postoperative chemotherapy for breast cancer, in which antibody cocktail therapy prevented disease aggravation and delayed breast cancer treatment. The patient is a 45-year-old woman who came to our hospital with a complaint of a right mammary mass. The mass was diagnosed as invasive ductal carcinoma with an ER and PR of 0%, a HER2 score of 1+, and a Ki-67 of 90%. After preoperative chemotherapy, she underwent a right mastectomy and axillary dissection. The pathology result showed non-pCR. The administration of capecitabine was started as adjuvant therapy. On day 8 of cycle 3, she developed a fever in the 39℃ range, and on the next day, a COVID-19 POC gene test confirmed that the patient was positive for infection. On the same day, neutralizing antibody drugs(casirivimab and imdevimab)were administered as antibody cocktail therapy. Two days after treatment(day 11), a blood test showed Grade 3 neutropenia, but there was no recurrence of fever or evidence of pneumonia. After 2 weeks, capecitabine was resumed, and the patient was able to complete 8 cycles of capecitabine therapy without any major complications.

[ESR1 Mutation-Positive Recurrent Breast Cancer Successfully Treated with Letrozole plus Abemaciclib].

Approximately 70% of breast cancers are estrogen receptor(ER)positive, an indication for endocrine therapy. The first choice of treatment for ER-positive metastatic recurrent breast cancer is endocrine therapy, which has relatively few side effects; however, many of these side effects become resistant during treatment. One of the resistance mechanisms is mutations in the ESR1 gene, which have also been found to occur after long-term aromatase inhibitor(AI)treatment. Here, we describe our experience of a case in which long-term PR was achieved with AI(letrozole)plus abemaciclib despite ESR1 mutation positivity in cancer genetic screening and review the literature.

[A Case Study of Successful Breast Cancer Treatment after Recovery from Drug-Induced Interstitial Lung Disease].

Drug-induced interstitial lung disease(DILD)is a possible complication of many anticancer drugs. When DILD occurs during breast cancer treatment, choosing the right drug for subsequent treatment is often difficult. In our first case, the patient developed DILD during dose-dense AC(ddAC)therapy; however, the disease resolved with steroid pulse therapy, and the patient underwent surgery without disease progression. In the second case, a patient on anti-HER2 therapy for recurrent disease developed DILD in response to docetaxel plus trastuzumab plus pertuzumab administered to treat T-DM1 after progressive disease. In this report, we describe a case of DILD that did not worsen and the patient had successful treatment outcome.

[Olaparib Could Be Re-Administered after Chemotherapy].

Olaparib, a PARP inhibitor, was approved in 2018 for BRCA1/2 gene mutation and HER2-negative inoperable or recurrent breast cancer with previous chemotherapy. Olaparib is an important drug with minor adverse events compared to chemotherapeutic drugs. In addition, it is expected to exert a high therapeutic effect on breast cancer with BRCA mutations due to its characteristics. We report a case of BRCA2-mutated breast cancer in a patient in whom olaparib was initiated. The patient complained of strong nausea; however, the treatment could be continued by reducing the dose of olaparib to 400 mg and using multiple drugs such as antiemetics and anxiolytics in advance.

[A Case of Severe Drug-Induced Lung Injury during Preoperative Chemotherapy for Breast Cancer in the Early Stages of the COVID-19 Epidemic].

Drug-induced interstitial lung disease(DILD)is defined as a drug-related respiratory disorder that occurs during drug administration. For diagnosis, it is important to differentiate similar diseases. We report a case of severe drug-induced lung injury during preoperative chemotherapy for breast cancer in the early stages of the COVID-19 epidemic, which was difficult to diagnose. The patient was a 48-year-old woman. The chief complaint was fever and dyspnea. She was diagnosed with left breast cancer(ER 30-40%, PR 0%, HER2 1+, Ki-67 84%), cT4bN1M0, cStage ⅢB and was treated with dose-dense AC therapy and docetaxel sequentially as preoperative chemotherapy. On the 21st day of the first course of docetaxel, the patient developed respiratory failure. A CT scan of the chest showed diffuse ground-glass shadows in the bilateral lung fields, suggesting severe viral pneumonia caused by COVID-19, and the patient was admitted to the isolation ward and managed with an intubated ventilator. PCR and LAMP were negative, and COVID-19 was ruled out. Based on the clinical course and CT findings, we started steroid pulse therapy with DILD in mind. The patient was extubated on the 5th day after the onset of the disease because the steroid pulse therapy was successful and her respiratory condition was stable. Preoperative chemotherapy was stopped, and a left mastectomy and axillary dissection were performed. In this case, COVID-19 should have been suspected first, but we were able to minimize the interruption of treatment by taking early action and keeping DILD in mind.

Laparoscopic Total Devascularization of the Upper Stomach and Splenectomy (Hassab's Procedure) Under Indocyanine Green Fluorescence Imaging: Initial Experience.

The use of surgical treatment for refractory isolated gastric varices has decreased owing to the development of endoscopic and radiologic procedures, although surgeries are sometimes required as the final method. A 75-year-old Japanese woman was diagnosed with solitary gastric varices. Initially, intraoperative splenic artery embolization was performed using the balloon transcatheter technique under general anesthesia. Laparoscopic splenectomy was performed safely owing to preoperative splenic artery embolization. Intraoperative indocyanine green (ICG) fluorescence angiography was performed following the injection of 5 mL of ICG; the remnant stomach was observed using laparoscopic equipment with an ICG imaging system, and blood flow from the remnant gastric artery was confirmed. The blood did not pool or wash out immediately, which confirmed successful devascularization of the stomach. The total operative time was 269 minutes, and the intraoperative blood loss was 500 mL. The patient's postoperative course was good, and at 21 days after the last operation, she was discharged from our hospital in remission. Real-time fluorescence angiography with ICG is a reliable and objective technique of assessing blood flow of the stomach. Accurate, extensive devascularization in the lower esophagus and upper stomach was performed using Hassab's procedure in combination with ICG imaging.

Surgical strategy for suspected early gallbladder carcinoma including incidental gallbladder carcinoma diagnosed during or after cholecystectomy.

PURPOSE: This paper presents an overview of the surgical strategy for patients with suspected gallbladder carcinoma (GBC), including incidental GBC cases, preoperatively or intraoperatively, as well as their outcomes. METHODS: Between April 2009 and December 2017, 529 patients underwent cholecystectomy for gallbladder disease at our hospital. Both intraoperative and postoperative histological examinations of the excised gallbladder facilitated the diagnosis of GBC. Surgery-related variables and surgical approaches were evaluated according to the extent of tumor invasion. RESULTS: Of 529 patients, eight were diagnosed with GBC during/after cholecystectomy, including four women and four men. Mean age was 75.4 (range, 59-89) years. Five patients had gallbladder stones and three had cholecystitis. Three patients with stages T1b and T2 underwent additional liver bed wedge resections with or without prophylactic common bile duct excision. Five of the eight patients are still alive and two of the remaining three died from other diseases; one patient with pT3 died of recurrent GBC (peritonitis carcinomatosa). CONCLUSION: Because of the ability to obtain full-thickness frozen biopsies during laparoscopic cholecystectomy, we could diagnose GBC intraoperatively, allowing for rapid diagnosis and tumor resection. We recommend developing a surgical treatment strategy for suspected early GBC in advance of cholecystectomy.

Laparoscopic Excisional Cholecystectomy with Full-Thickness Frozen Biopsy in Suspected Gallbladder Carcinoma.

Owing to the advantages of a laparoscopic approach, laparoscopic cholecystectomy (LC) is thought to be the treatment of choice in gallbladder disease, even in cases of suspected malignancy. However, it is difficult to differentiate between cholecystitis and gallbladder carcinoma (GBC). We performed radical hepatectomy in patients with pT2 GBC diagnosed by full-thickness frozen biopsy. A 75-year-old Japanese man presented to our hospital with discomfort in the right upper quadrant of the abdomen. This patient was diagnosed with suspected GBC and was scheduled to undergo LC and intraoperative histological examination. Following the procedure, we made a diagnosis of GBC with negative invasion of the cystic duct stump. We converted the laparoscopic procedure to an open surgery involving wedge liver resection with lymphadenectomy. The patient was discharged from our hospital in remission 14 days following the radical hepatectomy. Histological examination showed that the GBC had invaded the liver (T3a), but there was no lymph node metastasis (N0): stage IIIA. Between April 2009 and September 2018, 580 patients underwent cholecystectomy for gallbladder disease at our hospital. Among these, 8 (1.4%) were suspected to have GBC preoperatively and underwent laparoscopic excisional cholecystectomy. We performed elective surgery in the early stage in two patients and second-look surgery in two patients recently. We were able to perform what we termed a laparoscopic excisional cholecystectomy, involving LC with a full-thickness frozen biopsy, even in situations where intraoperative histological examination was not available. Altogether, laparoscopic excisional cholecystectomy is an effective surgical treatment for suspected early GBC.

Conjunctival Goblet Cell Density Following Cataract Surgery With Diclofenac Versus Diclofenac and Rebamipide: A Randomized Trial.

PURPOSE: To determine the effects of topical diclofenac or betamethasone with concomitant application of topical rebamipide on the conjunctival goblet cell density in eyes after cataract surgery. DESIGN: Randomized clinical trial. PARTICIPANTS: Eighty patients who were scheduled for cataract surgery. METHODS: Patients were randomized into 4 groups according to the postoperative topical drugs to be given; Group A, diclofenac alone; Group B, diclofenac and rebamipide; Group C, betamethasone alone; and Group D, betamethasone and rebamipide. Impression cytology was performed before and at 1 month after the surgery, and the mean density of goblet cells was determined. RESULTS: The mean (± SD) density of goblet cells before the surgery in Group A was 257.0 ± 188.7 cells/mm2, and it decreased significantly to 86.5 ± 76.7 cells/mm2 at 1 month after the surgery (P = .002). In Group B, the goblet cell density was not statistically different between before (238.5 ± 116.6 cells/mm2) and at 1 month after the surgery (211.3 ± 184.4 cells/mm2, P = .55). In Groups C and D, the mean density of goblet cells was decreased at 1 month after the surgery, but the decreases were not significant (P = .11 and P = .52, respectively). CONCLUSION: After cataract surgery with postoperative topical diclofenac, the conjunctival goblet cell density was significantly reduced, and this reduction was blocked by the concomitant use of topical rebamipide. These results suggest that the concomitant use of topical rebamipide with nonsteroidal anti-inflammatory drugs is beneficial, especially in cases with postoperative dry eyes.

Effect of topical rebamipide on conjunctival goblet cell recovery after vitrectomy.

In vitro and in vivo experiments have shown that topical rebamipide will increase the number of goblet cells in the bulbar conjunctiva. The purpose of this study was to determine whether topical rebamipide will enhance the recovery of conjunctival goblet cells that were damaged during vitrectomy. Forty patients who underwent vitrectomy surgery were studied. The 40 patients consisted of 20 with diabetes mellitus (DM) and 20 patients without DM. They were randomized in a 1:1 ratio into groups that were treated or not treated with topical 2% rebamipide after the surgery. Impression cytology was performed at the end of surgery and at 14 days after the surgery. The mean goblet cell density of each specimen was determined by averaging the total number of goblet cells obtained from three consecutive high magnification microscopic images. In patients without DM, the mean goblet cell density at 14 days after the vitrectomy was significantly higher in eyes with topical rebemipide than in eyes without rebemipide (P < 0.01). In patients with DM, a similar tendency was observed but the difference was not significant (P = 0.09). These results suggest that topical rebamipide can be helpful in patients with globlet cell damage that occur during and after vitrectomy.

Histopathological examination of Acanthamoeba sclerokeratitis.

PURPOSE: To report the histopathological findings in a case of severe Acanthamoeba sclerokeratitis (ASK). PATIENT AND METHODS: A 46-year-old patient was referred to the Department of Ophthalmology of Mie University Hospital because of a severe corneal ulcer of the right eye of 6 months' duration. Our initial examination showed a ring-shaped corneal opacity with extensive epithelial defects and nodular scleritis. Cysts of Acanthamoeba were identified in cultures from corneal scrapings, and he was diagnosed with ASK. He was started on antiamoebic treatment, including topical micafungin and chlorhexidine. The corneal ulcer was debrided several times. One month later, he developed necrotizing scleritis, and the cornea suddenly perforated. The eye was enucleated because of severe pain and prepared for histopathological examination. RESULTS: The histopathological examination showed an infiltration of polymorphonuclear leukocytes throughout the corneal stroma and also in the limbal area of the sclera, forming an abscess. Granulation tissue was observed in the anterior sclera close to the ciliary body, but the posterior regions of the eye were not affected by inflammation or tissue destruction. The cysts of Acanthamoeba were observed only in the cornea. CONCLUSION: Histopathological examination of an eye with severe ASK showed that the inflammation and tissue granulation were present only in the anterior part of eye, and the posterior segment was not affected. Because the inflammation and tissue destruction were confined to the anterior segment, enucleation might not have been necessary if the severe pain was able to be controlled.

Effect of orally administered KF66490, a phosphodiesterase 4 inhibitor, on dermatitis in mouse models.

Due to the broad anti-inflammatory and immunomodulatory actions of phosphodiesterase (PDE) 4 inhibitors, it has been proposed that PDE4 inhibitors might be efficacious for skin disorders such as atopic dermatitis. KF66490 is a newly developed PDE4 inhibitor that inhibits PDE4B (IC(50)=220 nM) and the production of tumor necrosis factor (TNF)-alpha by mouse peritoneal exudated cells stimulated with lipopolysaccharide (IC(50)=855 nM). To evaluate efficacy of KF66490 in atopic dermatitis (AD) models, on skin inflammation induced by repeated application of 2,4,6-trinitro-1-chlorobenzene (TNCB) on ear in BALB/c mice and on spontaneously AD-like skin diseases in NC/Nga mice. BALB/c mice were sensitized with 0.3% w/v TNCB applied to the ear on day-7, followed by application three times a week from days 0 to 21. NC/Nga mice spontaneously developed dermatitis symptoms under conventional conditions. Test compounds were administered orally once daily during experiments. In the TNCB-induced dermatitis model, KF66490 significantly inhibited the increase in ear thickness and interleukin (IL)-4 and IL-1beta levels in the ear. Histopathological and immunohistochemical analysis revealed that KF66490 significantly inhibited the proliferation of fibroblasts and CD3-positive T cells infiltration into the ear. In addition, KF66490 significantly suppressed the development of dermatitis in NC/Nga mice on all observation days, except for 5 and 6 weeks after the first dose. Furthermore, KF66490 produced less potent emetic effects than the first generation PDE4 inhibitor, rolipram. The present results suggest that KF66490 has excellent potential as an oral medicine for the treatment of atopic dermatitis.