Case report: Splenic inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDCS): a trial of immunotherapy and review of the literature.

Inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDCS) is a rare malignancy with fewer than 150 cases in the literature. IPT-like FDCS follows an indolent course with most cases definitively managed with surgical resection. We present a case of IPT-like FDCS with multiple recurrences with a trial of immunotherapy. The patient initially presented with splenic involvement requiring splenectomy, subsequently recurring in the liver requiring hepatic resections. Afterwards, there was recurrence with pelvic/small bowel involvement for which treatment was trialed with ipilimumab and nivolumab. The patient progressed despite dual immune checkpoint inhibitor therapy requiring a small bowel resection. To date, this is the first case of immunotherapy use in IPT-like FDCS. Therefore, more evidence is needed to support additional treatments in recurrent IPT-like FDCS after resection.

Using a novel computational drug-repositioning approach (DrugPredict) to rapidly identify potent drug candidates for cancer treatment.

Computation-based drug-repurposing/repositioning approaches can greatly speed up the traditional drug discovery process. To date, systematic and comprehensive computation-based approaches to identify and validate drug-repositioning candidates for epithelial ovarian cancer (EOC) have not been undertaken. Here, we present a novel drug discovery strategy that combines a computational drug-repositioning system (DrugPredict) with biological testing in cell lines in order to rapidly identify novel drug candidates for EOC. DrugPredict exploited unique repositioning opportunities rendered by a vast amount of disease genomics, phenomics, drug treatment, and genetic pathway and uniquely revealed that non-steroidal anti-inflammatories (NSAIDs) rank just as high as currently used ovarian cancer drugs. As epidemiological studies have reported decreased incidence of ovarian cancer associated with regular intake of NSAIDs, we assessed whether NSAIDs could have chemoadjuvant applications in EOC and found that (i) NSAID Indomethacin induces robust cell death in primary patient-derived platinum-sensitive and platinum- resistant ovarian cancer cells and ovarian cancer stem cells and (ii) downregulation of ß-catenin is partially driving effects of Indomethacin in cisplatin-resistant cells. In summary, we demonstrate that DrugPredict represents an innovative computational drug- discovery strategy to uncover drugs that are routinely used for other indications that could be effective in treating various cancers, thus introducing a potentially rapid and cost-effective translational opportunity. As NSAIDs are already in routine use in gynecological treatment regimens and have acceptable safety profile, our results will provide with a rationale for testing NSAIDs as potential chemoadjuvants in EOC patient trials.

A phase I trial of paclitaxel, cisplatin, and veliparib in the treatment of persistent or recurrent carcinoma of the cervix: an NRG Oncology Study (NCT#01281852).

Background: Preclinical studies demonstrate poly(ADP-ribose) polymerase (PARP) inhibition augments apoptotic response and sensitizes cervical cancer cells to the effects of cisplatin. Given the use of cisplatin and paclitaxel as first-line treatment for persistent or recurrent cervical cancer, we aimed to estimate the maximum tolerated dose (MTD) of the PARP inhibitor veliparib when added to chemotherapy. Patients and methods: Women with persistent or recurrent cervical carcinoma not amenable to curative therapy were enrolled. Patients had to have received concurrent chemotherapy and radiation as well as possible consolidation chemotherapy; have adequate organ function. The trial utilized a standard 3 + 3 phase I dose escalation with patients receiving paclitaxel 175 mg/m2 on day 1, cisplatin 50 mg/m2 on day 2, and escalating doses of veliparib ranging from 50 to 400 mg orally two times daily on days 1-7. Cycles occurred every 21 days until progression. Dose-limiting toxicities (DLTs) were assessed at first cycle. Fanconi anemia complementation group D2 (FANCD2) foci was evaluated in tissue specimens as a biomarker of response. Results: Thirty-four patients received treatment. DLTs (n = 1) were a grade 4 dyspnea, a grade 3 neutropenia lasting ≥3 weeks, and febrile neutropenia. At 400 mg dose level (DL), one of the six patients had a DLT, so the MTD was not reached. Across DLs, the objective response rate (RR) for 29 patients with measurable disease was 34% [95% confidence interval (CI), 20%-53%]; at 400 mg DL, the RR was 60% (n = 3/5; 95% CI, 23%-88%). Median progression-free survival was 6.2 months (95% CI, 2.9-10.1), and overall survival was 14.5 months (95% CI, 8.2-19.4). FANCD2 foci was negative or heterogeneous in 31% of patients and present in 69%. Objective RR were not associated with FANCD2 foci (P = 0.53). Conclusions: Combining veliparib with paclitaxel and cisplatin as first-line treatment for persistent or recurrent cervical cancer patients is safe and feasible. Clinical trial information: NCT01281852.

Non-Hodgkin's lymphoma mimicking gynecological malignancies of the vagina and cervix: a report of four cases.

Although in the past two decades there has been a sharp rise in the incidence of extranodal primary lymphomas in the United States, non-Hodgkin's lymphoma (NHL) of the female genital tract is still rare. We present four cases of extranodal NHL presenting with signs and symptoms consistent with cancer of the vagina or cervix and lacking the "B" symptoms often associated with systemic lymphoma such as fever, weight loss, night sweat, and fatigue. It is important for gynecologists to be aware of this neoplastic disease and to include cervical or vaginal lymphoma in the differential diagnosis of patients presenting with examinations suggestive of cervical or vaginal cancer. A correct diagnosis leads to the appropriate therapy, and radical gynecological surgery can be avoided for primary cervical and vaginal lymphoma.

Outcome of vitreoretinal surgery and penetrating keratoplasty using temporary keratoprosthesis.

PURPOSE: The use of a temporary keratoprosthesis has allowed earlier surgical intervention in eyes with coexisting vitreoretinal and corneal disease. We analyzed our experience with this type of surgery. METHODS: We retrospectively reviewed charts of patients in whom a temporary keratoprosthesis was used between 1987 and 1998. Analysis was focused on ocular history, indications for surgery, visual acuity (VA), intraocular pressure, anatomic results, and complications. RESULTS: A temporary keratoprosthesis was used in 31 eyes, 22 (71.0%) of which were for trauma-related indications. In 6 (19.4%) of the operated eyes, the fellow eye also had severely reduced VA. Retinal detachments were present in 30 (96.8%) eyes; most had evident proliferative vitreoretinopathy. Twelve (38.7%) eyes had vitreous hemorrhage, and 20 (64.5%) had corneal scars. Improvement in VA was seen initially in 45.1% of patients, and 51.6% maintained equal or better VA at their final visit as compared with before surgery. The common documented reasons for poor final VA were recurrent retinal detachments deemed inoperable (32.3%), phthisis (22.6%), and optic atrophy or macular scar (16.1%). Corneal grafts remained clear in 41.9%. Nine patients had further surgery. The most significant complication was one case of sympathetic ophthalmia. CONCLUSIONS: Combined vitreoretinal and corneal surgery using temporary keratoprostheses has been used in our institution to treat eyes with extreme abnormalities. Outcomes were less favorable than some reported in the literature, probably because of the severity of disease for which temporary keratoprostheses were reserved. Although results are probably better than the natural course of the disease, patients should be informed of realistic expectations for improvement and potential complications when offered this option.

Transscleral diode laser retinopexy in retinal detachment surgery: results of a multicenter trial.

PURPOSE: To evaluate the safety and efficacy of transscleral diode laser for retinopexy in rhegmatogenous retinal detachment surgery in a multicenter trial. METHODS: Seventy-two patients with primary rhegmatogenous retinal detachments were enrolled. No patient with chronic detachment, a retinal break greater than 90 degrees, history of uveitis or infectious retinopathy, or proliferative vitreoretinopathy was enrolled. RESULTS: Information from follow-up of 6 months or longer was available on 65 eyes. Retinas were attached at 6 months with a single operation in 58 (89%) of these eyes. Complications included apparent pinpoint breaks in Bruch's membrane in 15 eyes, scleral-thermal effect in 14 eyes, and limited hemorrhage, which was intraretinal in 10 eyes and extended into the vitreous in 3 eyes. In one case, hemorrhage was judged perhaps to have contributed to initial surgical failure. The other complications had no known adverse effects. Complications were significantly associated with the physician's experience in using transscleral laser retinopexy. CONCLUSIONS: In this multicenter study, transscleral diode laser retinopexy served as a safe and effective means of creating chorioretinal adhesion during retinal reattachment surgery. Minor complications were minimized by increasing experience with the technique.

Multicenter trial of transscleral diode laser retinopexy in retinal detachment surgery.

PURPOSE: To evaluate the safety and efficacy of transscleral diode laser for retinopexy in rhegmatogenous retinal detachment surgery in a multicenter trial. DESIGN: 67 patients with primary rhegmatogenous retinal detachment underwent scleral buckling surgery, using transscleral diode laser for retinopexy, at five study centers. STUDY PARTICIPANTS: 72 patients with primary rhegmatogenous retinal detachments were enrolled. No patient with chronic detachment, a retinal break greater than 90 degrees, history of uveitis or infectious retinopathy, or proliferative vitreoretinopathy was enrolled. Five eyes were excluded because they required additional nonprotocol treatment at the time of surgery (vitrectomy or supplementary cryotherapy due to probe malfunction). MAIN OUTCOME MEASURES: Retinal reattachment at six months after one operation. Secondary measures: visual acuity and complications, including choroidal, retinal, and vitreous hemorrhage, inflammation, and scleral damage. RESULTS: Six months or greater follow-up information was available on 65 eyes. Retinas were attached at 6 months with a single operation in 58 (89%) of these eyes. Complications included apparent pinpoint breaks in Bruch is membrane in 15 eyes, scleral thermal effect in 14 eyes, and limited hemorrhage, which was intraretinal in 10 eyes, and extended into the vitreous in 3 eyes. In one case, hemorrhage was judged to have contributed possibly to initial surgical failure. The other complications had no known adverse effects. Complications were significantly associated with the physicians experience with transscleral laser retinopexy. CONCLUSION: In this multicenter series, transscleral diode laser retinopexy served as a safe and effective means of creating chorioretinal adhesion during retinal reattachment surgery. Minor complications were minimized by increasing experience with the technique.

Extramedullary toxicity of a conditioning regimen containing busulphan, cyclophosphamide and etoposide in 84 patients undergoing autologous and allogenic bone marrow transplantation.

Relapse is still a common problem after bone marrow transplant (BMT) and teh value of adding etoposide to standard conditioning agents is being tested. The aim of the study was to assess the extramedullary toxicity which resulted from adding etoposide to busulphan 16 mg/kg and cyclophoshamide 120 mg/kg (BuCY2). Eighty four patients received etoposide 40 mg/kg in addition to BuCY2 as conditioning for autologous and allogeneic BMT for leukemia and lymphoma. The Bearman system of grading extramedullary toxicity was used along with a system of grading skin toxicity that we devised. There were seven acute toxic deaths (8%) and in total 15 patients experienced life-threatening or fatal toxicity. The major finding was a striking increase in pulmonary toxicity with six deaths (five alveolar hemorrhage and one pulmonary embolus). Five of seven of the patients with severe pulmonary toxicity had been given irradiation to the lung fields (P < 0.001). Thirty nine per cent of patients had veno-occlusive disease of the liver but the case fatality rate was low (1 of 33). Dermatologic toxicity was experienced by 82% of patients and was symptomatically troublesome but rapidly reversible. The addition of etoposide to BuCY2 increases non-hematological toxicity. This regimen is associated with severe pulmonary toxicity in patients with a history of prior chest irradiation. A high incidence of skin toxicity was seen; a system for describing this toxicity is proposed.

Incidence of cervical metastasis from uveal melanoma: implications for treatment.

BACKGROUND: Although the literature has focused on the propensity of uveal melanoma to metastasize to the liver, little attention has been directed to its spread in regional, cervical lymph nodes. METHODS: We reviewed records of 77 patients who underwent primary resection of uveal melanoma during a 15-year period at our institution. RESULTS: A total of only 6.5% of patients developed cervical metastasis. Factors such as age, race, sex, tumor location, and histology were not influential in identifying these patients. Tumor size and local orbital recurrence were, however, associated with a higher risk of cervical lymphadenopathy (p < 0.05). Cervical metastases were also associated with the presence of distant metastatic disease. CONCLUSION: Neck dissection should be reserved for patients with clinically demonstrable lymphadenopathy only after distant disease has been excluded.

Management of the dislocated crystalline lens with a perfluorocarbon liquid.

Vitreoretinal surgery allows the effective removal of soft to moderately dense crystalline lens fragments, using the vitrectomy probe and the ultrasonic fragmentation probe. Hard lenses cannot be removed with these instruments. Previously described techniques for removal of hard lenses include trapping the lens anteriorly with needles, cryoextraction of the lens in an air-filled eye, and manipulation with sodium hyaluronate. These methods are difficult and dangerous in some cases. We used perfluorocarbon liquid to facilitate the safe removal of a surgically luxated hard crystalline lens. Injection of the perfluorocarbon liquid floated the lens off the retinal surface and into the anterior vitreous cavity. In this location, the lens was delivered by using standard extracapsular cataract extraction techniques. This technique allowed removal of the hard crystalline lens with minimal manipulation, and was helpful in the setting of poor media clarity.

Penetrating ocular injury from contaminated eating utensils.

Although the rate of infectious endophthalmitis following penetrating ocular injury is generally less than 10%, certain settings may carry a greater risk of infection. One such setting is penetrating injury resulting from eating utensils contaminated with oral flora. We reviewed six of these injuries. Culture-positive bacterial endophthalmitis developed in four of the six eyes; only one of the eyes retained reading visual acuity (greater than 20/50) and two eyes lost light perception. The potential for infection and limited visual outcome in this series warrants aggressive prophylaxis and treatment. The unexpected isolation of Haemophilus influenzae in two of the four infections suggests that broad-spectrum antibiotic treatment should be considered in all such injuries since less common organisms may be encountered.

Cohen syndrome with bull's eye macular lesion.

The Cohen syndrome is an autosomal recessive disorder which is characterized by hypotonia, obesity, mental deficiency, and facial, oral and ocular anomalies. During a twelve-year period of observation, the authors' patient manifested pigmentary retinal degeneration and a bull's eye macular lesion. The Cohen syndrome must be included in the differential diagnosis of syndromes with retinitis pigmentosa.

Basal cell epithelioma: an unusual case.

A 59-year-old Caucasian male presented with a darkly pigmented inner canthal tumor with a six-month history of rapid growth. Histopathologic examination demonstrated to be a pigmented basal cell epithelioma. While basal cell epitheliomas of the eyelids are common ophthalmic disorders, pigmented lesions are unusual. Pigmented basal cell epitheliomas pose a difficulty in clinical diagnosis because of their resemblance to melanomas and pigmented nevi. The differential diagnosis and treatment of this lesion is reviewed.

Accessory tragi and associated syndromes involving the first branchial arch.

Although most deformities in front of the tragi are limited abnormalities, they may be signs of certain associated congenital syndromes that result from maldevelopment of the mandibular arch.