Long-term efficacy and safety of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis: subgroup analyses of an open-label, phase 3 study (UNCOVER-J).

BACKGROUND: Erythrodermic and generalized pustular psoriasis are rare, difficult to treat forms of psoriasis. In previous reports, we documented 24- and 52-week findings of an open-label, phase 3 trial (UNCOVER-J) of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis; most patients responded to treatment and maintained response through 52 weeks. OBJECTIVE: To assess the long-term (>3 years) efficacy and safety of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis. METHODS: These subgroup analyses were of a partial population of patients from UNCOVER-J (NCT01624233; Sponsored by Eli Lilly and Company), specifically those with erythrodermic psoriasis (N = 8) or generalized pustular psoriasis (N = 5). These patients received 160 mg ixekizumab at Week 0, ixekizumab 80 mg every 2 weeks through Week 12, and ixekizumab 80 mg every 4 weeks thereafter up to Week 244. This regimen is consistent with the regimen approved in Japan for plaque, erythrodermic, and generalized pustular psoriasis and psoriatic arthritis. Efficacy assessments included Global Improvement Score (GIS), Psoriasis Area and Severity Index (PASI), dermal symptoms (for patients with generalized pustular psoriasis), Dermatology Life Quality Index (DLQI) and Itch Numeric Rating Scale (NRS). Safety assessments included treatment-emergent adverse events and adverse events of special interest. RESULTS: Most patients had a GIS of resolved or improved from Week 12 onwards, and all patients had early and sustained improvement in PASI and dermal symptom (generalized pustular psoriasis only) scores. Mean improvements in DLQI and Itch NRS at Week 12 were sustained through Week 244. Ixekizumab was well tolerated over 3 years of treatment in patients with erythrodermic psoriasis or generalized pustular psoriasis, and no new safety concerns were identified. CONCLUSION: These findings suggest that ixekizumab can be an effective long-term treatment option for erythrodermic or generalized pustular psoriasis.

Long-term efficacy and safety results from an open-label phase III study (UNCOVER-J) in Japanese plaque psoriasis patients: impact of treatment withdrawal and retreatment of ixekizumab.

BACKGROUND: Long-term management of moderate-to-severe psoriasis is usually discussed in terms of continuous administration; however, there are many situations in clinical practice where treatment may be withdrawn with subsequent retreatment. OBJECTIVE: To assess the clinical course after ixekizumab treatment withdrawal and retreatment, as well as the effectiveness of ixekizumab retreatment, in Japanese patients with plaque psoriasis. METHODS: This single-arm, open-label study (UNCOVER-J; NCT01624233) comprised 78 patients with plaque psoriasis. After ixekizumab treatment (160-mg loading dose, 80 mg every 2 weeks for the first 12 weeks, and then 80 mg every 4 weeks (IXE Q4W) until Week 52), 70 patients achieved a Psoriasis Area Severity Index (PASI)75 response at Week 52. These 70 patients withdrew from ixekizumab treatment from Weeks 52 to 100. Patients who relapsed (PASI ≤50) during the Treatment Withdrawal Period were retreated with IXE Q4W for 192 weeks. RESULTS: At Weeks 52, 76 and 100, PASI75 response rates were 100%, 26% and 7%; PASI90 response rates were 87%, 11% and 3%; and PASI100 response rates were 53%, 0% and 0%. After treatment withdrawal, 87% of patients relapsed; median time to relapse was 143 days. After 12 weeks of retreatment with IXE Q4W, 83% of relapsed patients achieved PASI75, 68% achieved PASI90 and 25% achieved PASI100; improvements were maintained up to 120 weeks of retreatment. Treatment-emergent adverse events and serious adverse events were reported in 56% and 4% of patients during the Treatment Withdrawal Period, and in 88% and 14% of patients during the Retreatment Period. CONCLUSION: In patients withdrawn from ixekizumab after achieving PASI75, approximately half relapsed within 5 months of withdrawal; however, most patients recaptured response within 12 weeks, and response was maintained for up to 120 weeks of retreatment.

Efficacy and safety of open-label ixekizumab treatment in Japanese patients with moderate-to-severe plaque psoriasis, erythrodermic psoriasis and generalized pustular psoriasis.

BACKGROUND: Ixekizumab, an anti-IL-17A monoclonal antibody, demonstrated a high level of efficacy in moderate-to-severe plaque psoriasis (PP) patients. OBJECTIVE: To evaluate the efficacy and safety of open-label ixekizumab in Japanese patients with moderate-to-severe PP, erythrodermic psoriasis (EP) and generalized pustular psoriasis (GPP). METHODS: Patients received 160-mg subcutaneous ixekizumab injection at Week 0, 80-mg every 2 weeks through Week 12 and 80-mg every 4 weeks through Week 24. Efficacy and safety are reported through 24 weeks; additional safety data are available for some patients. RESULTS: A total of 78 patients with PP, 8 with EP and 5 with GPP enrolled. In PP patients, PASI75 and PASI90 response rates were 98.7% (77/78) and 83.3% (65/78) at Week 12 respectively. In EP patients, PASI75 and PASI90 were 100.0% (8/8) and 62.5% (5/8) and in GPP patients were 80.0% (4/5) and 60.0% (3/5). Overall, 84.0% (76/91) had a treatment-emergent AE through ≥24 weeks. There were no serious AEs, deaths, cases of tuberculosis or invasive fungal infections. LIMITATIONS: No control group and small sample sizes, especially for EP and GPP. CONCLUSION: By Week 12, nearly all patients with PP, EP and GPP achieved PASI75. The safety profile was consistent with reported results and no unexpected safety signals were observed.

A primary hepatic carcinoid tumor: evaluation by computed tomography and magnetic resonance imaging.

A case of primary hepatic carcinoid tumor is reported. A 40-year-old woman was admitted to our hospital because of an epigastric mass. Ultrasonography demonstrated a heterogeneous, hyperechoic mass with hypoechoic area in the left lobe of the liver. CT showed a hypodense lesion with more hypodense areas. Enhanced CT showed slight retention of contrast medium and a low density area that suggested necrosis in the tumor. The mass appeared as a heterogeneous area of low signal intensity with sharp margin on T1-weighted MRI. T2-weighted MRI revealed a high intensity mass with higher intensity foci. Left lateral segmental hepatic resection was performed. Immunohistochemical and electron microscopic studies revealed the carcinoid tumor. Postoperatively, careful, intensive search revealed no other primary source of the tumor. The higher intensity foci were microscopically identified as intratumoral hemorrhage, corresponding to hemorrhagic areas on the cut surface. Therefore, T2-weighted MRI might reflect the pathological characteristics of the tumor.

Malignant lymphoma in unusual areas of the head and neck: parapharyngeal space and temporal fossa.

Primary malignant lymphomas of the parapharyngeal space are rare and only 28 cases are known to have been reported. No case of malignant lymphoma arising in the temporal fossa has been previously documented. The present paper reports a case of primary non-Hodgkin's lymphoma of the parapharyngeal space in a child and two cases of lymphoma of the temporal fossa in adults. All three cases were diagnosed histopathologically from biopsy specimens as diffuse, B-cell lymphomas. For diagnosis, inspection and bimanual palpation were most important in the parapharyngeal case and the temporal cases required more than one biopsy for the final diagnosis.

[A case of schwannoma of intrathoracic right phrenic nerve].

A 22-year old man was admitted because of an abnormal shadow on his chest X-ray film. Radiographic findings revealed that the tumor was located in the right middle mediastinum. At operation a smooth round tumor was found arising from the right phrenic nerve. The tumor was removed with phrenic nerve. Pathohistological examination revealed this tumor was benign schwannoma. Intrathoracic schwannoma usually arise from intercostal and sympathetic nerve and that arising from phrenic nerve is very rare. We removed the tumor by means of cutting his right phrenic nerve because of complete resection. Postoperatively he did well without any respiratory distress. And his respiratory function studies recovered normal 9 months after the operation. We think that schwannoma arising from phrenic nerve should be removed completely and in such a case cutting of the one side phrenic nerve is at ease if the patient have normal respiratory function.

[Mitomycin-C-sensitive carcinoid tumor of the gallbladder: report of a case].

A case of carcinoid tumor of the gallbladder, which was sensitive to mitomycin-C is reported. A 49-year-old male was admitted to our hospital with a 2-month history of epigastralgia. He underwent right extended lobectomy of the liver, pancreaticoduodenectomy and lymph node dissection. Histology revealed a carcinoid tumor of the gallbladder with invasion of the liver and lymph node metastasis. About 2 months after the operation, right supraclavicular lymph node metastasis was detected and CT scan revealed abdominal paraaortic lymph node metastasis. The patient was given cis-platinum, but the right supraclavicular lymph node metastasis increased in size and number. After administration of mitomycin-C, the paraaortic lymph node metastasis disappeared. Carcinoid tumor obtained from the right supraclavicular lesion was inoculated into BALB/c nude mice, and sensitivity to anticancer drugs was assayed. This carcinoid tumor was sensitive to mitomycin-C but not to cisplatinum, adriamycin, or nimustine.

A new route to cyclopentenones via ruthenium-catalyzed carbonylative cyclization of allylic carbonates with alkenes

[RuCl2(CO)3]2/Et3N and (eta 3-C3H5)RuBr(CO)3/Et3N are highly effective catalyst systems for carbonylative cyclization of allylic carbonates with alkenes to give the corresponding cyclopentenones in high yields. For example, treatment of allyl methyl carbonate (1a) with 2-norbornene (2a) in the presence of a catalytic amount of [RuCl2(CO)3]2 (2.5 mol %) and Et3N (10 mol %) at 120 degrees C for 5 h under 3 atm of carbon monoxide gave the corresponding cyclopentenone, exo-4-methyltricyclo[5.2.1.0(2,6)]dec-4-en-3-one (3a), in 80% yield with high stereoselectivity (exo 100%).

[A solitary extramedullary plasmacytoma of the nasopharynx].

A 72-year-old male, complaining of epistaxis, was referred to our hospital where a physical exam revealed a tumorous mass in the nasopharynx. A subsequent immunohistopathological investigation found that the tumor mass was a plasmacytoma with IgG and a lambda chain. Electrophoresis of a serum sample revealed a normal value and there was no signs indicating a multiple myeloma on x-ray surveys of the skeleton, or from bone marrow aspiration or scintigraphy. Thus the diagnosis was an extramedullary plasmacytoma and the patient received a combined treatment of chemotherapy, radiotherapy, and surgery. Since surgery, the patient has had neither a recurrence or a metastasis of the tumor for four years and three months.

PCNA immunostaining combined with AgNOR staining in esophageal squamous cell carcinoma to identify patients with a poor prognosis.

Immunostaining of the proliferating cell nuclear antigen (PCNA) provides important information about cell kinetics and is easily performed on routinely obtained formalin-fixed, paraffin-embedded materials. We report herein the results of a retrospective study on PCNA staining in esophageal cancer undertaken to determine its significance. As this study indicated that immunoreactivity was preserved in specimens fixed within 24h, only 31 specimens from surgical patients were available for this investigation. The mean PCNA index of the patients without invasion to the adventitia (35.7 +/- 17.9) was significantly lower than that of those with invasion to the adventitia or neighboring structures (49.7 +/- 14.5), while the PCNA index did not correlate with other clinicopathologic parameters such as histologic type, lymph node metastases, or prognosis. However, when an analysis of PCNA staining was combined with an analysis of argyrophilic nucleolar organizer region (AgNOR) staining, a correlation with prognosis was found. In fact, seven patients with a high PCNA index (> or = 44) and AgNOR count (> or = 6) had a significantly poorer prognosis than the remaining 22 (P = 0.0014), and six of these seven patients died within 2 years. These results indicate that this combined evaluation may be useful for the identification of patients with a poor prognosis among those undergoing surgery for esophageal squamous cell carcinoma.

Successful combined resection of carcinoma of the esophagus and adrenal metastasis: report of a case.

We report herein the case of a 56-year-old man who underwent successful combined resection of carcinoma of the esophagus and an adrenal metastasis. The patient presented with carcinoma of the thoracic esophagus, and an adrenal tumor was incidentally detected by computed tomography(CT). Complete removal of the carcinoma was accomplished along with a combined resection of the thoracic esophagus and left adrenal gland. Surgery was followed by the administration of anticancer chemotherapeutic agents. He is currently doing well with a grade 1 performance status and no signs of recurrence 22 months after his operation. To our knowledge, no previous report of the successful simultaneous resection of esophageal carcinoma and an adrenal metastasis has been documented in the literature.

[A case of resected metastatic adrenal carcinoma from gastric cancer].

A case of a metastatic adrenal carcinoma is presented. A 67-year-old female underwent total gastrectomy for an adenocarcinoma of the stomach before 52 months. A mass was indicated at the left supra-renal region by computed tomography. The mass was successfully resected by an upper abdominal para-aortic lymph node dissection. Histologically, the mass was confirmed as a metastatic adrenal carcinoma with a lymph node metastasis from the gastric cancer. Metastatic adrenal carcinomas and local lymph node dissections for treating metastatic carcinomas are discussed.

[Complete resection of left apical invading lung cancer, following reconstruction of subclavian artery by artificial graft--a case report].

A cumurative operation for apical invading lung cancer was performed in a 49-year-old man. Left upper lobectomy was combined with resection of the chest wall, left subclavian artery and brachial nerve, following reconstruction of the left subclavian artery with an artificial vessel graft. Our approach involved sternotomy, antero-lateral thoracotomy and cutting of the clavicle. This approach is useful for apical lung cancer without wide invasion of the posterior chest wall, as in this patient. Although radiotherapy and chemotherapy were administered, the patient succumbed to hematogenous metastases 15 months after the operation. We suggest that adjuvant therapy may be needed for apical invading lung cancer, even if the tumor is believed to be completely resected.

[Complete resection of superior mediastinal seminoma, following reconstruction of superior vena cava--a case report].

The patient was a 37-year-old man with superior mediastinal seminoma, which invaded the bilateral brachiocephalic vein, superior vena cava, pericardium and left lung. These invaded organs were resected with the tumor and a vascular reconstruction was performed with EPTFE graft and pericardial patch. EPTFE graft was interposed between the left brachiocephalic vein and right atrium. Superior vena cava was reconstructed by means of pericardial patch. Histologically, the tumor was diagnosed as pure seminoma. He received the prophylactic irradiation (45 Gy). Although venography two years after operation demonstrated the obstruction of the EPTFE graft and marked stenosis of the pericardial patch, the patient remains free from the symptom and is doing well without recurrence 45 months after operation.

Simultaneous resection of gastric carcinoma and splenectomy in a patient with polycythemia vera: report of a case.

We report herein the case of a 57-year-old man who underwent resection of gastric carcinoma after being treated for polycythemia vera (PV) for 16 months. He was admitted with gastrointestinal bleeding; barium meal roentogenogram and endoscopic examination subsequently revealed a Borrmann type II carcinoma in the cardia of the stomach with extension into the lower esophagus. Thus, a lower esophagogastrectomy, distal pancreatectomy, splenectomy, and lymph node dissection were performed. Although an insufficiency of the esophagojejunal anastomosis occurred, the patient suffered no hematologic complications in the setting of careful myelosuppressive and antiplatelet coagulation therapy. He is currently doing well 5 years after his operation, with grade 1 performance status and no signs of recurrence or any hematologic complications.

Periosteal chondroma developing in a rib at the side of a chest wall wound from a previous thoracotomy: report of a case.

We describe herein the case of a 45-year-old man who developed a periosteal chondroma in a rib at the site of a thoracotomy that had been performed 24 years previously. To our knowledge, this is only the third case of a periosteal chondroma in a rib to be documented in the world literature. Some authors have suggested that trauma, including that of surgery, may induce chondroma formation and this association could have been an important contributing factor in the induction of the tumor in this patient.

Adenoid cystic carcinoma of the esophagus: report of a case and review of the Japanese literature.

We report herein the case of a 79-year-old man with adenoid cystic carcinoma (ACC) of the esophagus. The tumor had a polypoid appearance and was covered by thin esophageal mucosa. As the biopsy specimens suggested a diagnosis of poorly differentiated adenocarcinoma, the patient underwent subtotal esophagectomy with reconstruction of the gastric tube via the posterior mediastinum. Histologically, the carcinoma contained basaloid cells, cribriform foci, and a certain amount of eosinophilic hyaline substance. Some of the basaloid cells were stained immunohistochemically for keratin, muscle actin, and S-100 protein, a pattern which was identical to the pattern of immunoreactivity of the myoepithelium. We reviewed 36 other cases of ACC of the esophagus reported in Japan, with special reference to the criteria for histological diagnosis.