Effectiveness of prolonged exposure (PE) after implementation at a crime victim support centre.

Background: Recent practice guidelines strongly recommend evidence-based psychotherapies (EBPs) as the first-line treatment for post-traumatic stress disorder (PTSD). However, previous studies found barriers to the implementation of EBPs and a relatively high dropout rate in clinical settings. After proving the efficacy of prolonged exposure (PE) in Japan [Asukai, N., Saito, A., Tsuruta, N., Kishimoto, J., & Nishikawa, T. (2010). Efficacy of exposure therapy for Japanese patients with posttraumatic stress disorder due to mixed traumatic events: A randomized controlled study. Journal of Traumatic Stress, 23(6), 744-750. https://doi.org/10.1002/jts.20589], we began implementing PE in a real-world clinical setting at the Victim Support Center of Tokyo (VSCT).Objective: We aimed to investigate the effectiveness and benefit of PE for crime-induced PTSD among VSCT clients and what causes dropout from treatment.Method: Of 311 adult clients who received counselling from clinical psychologists at VSCT due to violent or physical crime victimization from April 2008 through December 2019, 100 individuals received PE and participated in this study. Their PTSD symptoms were evaluated before and after treatment using the Impact of Event Scale-Revised and the Clinician-Administered PTSD Scale for DSM-IV.Results: A total of 93 participants completed PE and seven dropped out after six sessions or less. The completers group improved in PTSD symptoms with significant score differences between pre- and post-treatment in IES-R and CAPS-IV. Participants' symptoms did not exacerbate after treatment. Forty of 49 completers who left their workplace or college/school after victimization returned to work or study shortly after treatment. Compared to the completers, all dropout participants were women and younger. The majority were rape survivors, with significantly shorter intervals between victimization and treatment. The reasons for dropout were difficulty scheduling treatment between work/study schedules and manifestation of bipolar disorder or physical illness.Conclusions: PE can be implemented with significant effectiveness and a low dropout rate in a real-world clinical setting if advantages in the system and policies, local organizational context, fidelity support and patient engagement are fortified.

We conducted prolonged exposure (PE) with a low dropout rate for crime-induced PTSD in a non-Western real-world practice setting.Patient outcomes and low dropout rate of PE for PTSD in this study may be due to advantages in the following areas: system and policies, local organizational context, fidelity support and patient engagement.When introducing PE for PTSD, it is important to confirm that patients can be reasonably engaged with PE, and to carefully assess the status of other psychiatric and physical illnesses.

Durable response to nivolumab in a lung adenocarcinoma patient with idiopathic pulmonary fibrosis.

The efficacy and safety of immune-checkpoint inhibitors in non-small cell lung cancer patients with idiopathic pulmonary fibrosis (IPF) remain unknown. Herein, we describe the case of a 62-year-old man with multiple pleural tumors and carcinomatous pleurisy. High-resolution computed tomography indicated usual interstitial pneumonia, and a respiratory function test revealed a restrictive disorder and decreased diffusion capacity. He was diagnosed with lung adenocarcinoma and IPF. After failure of initial chemotherapy, he was treated with nivolumab and achieved a complete response without any sign of exacerbation of IPF. The response to nivolumab has persisted for > 1 year. This is the first report of a non-small cell lung cancer patient with IPF who has been treated with immune-checkpoint inhibitors for such a long period and achieved a sustained response.

Preventive effect of kampo medicine (hangeshashin-to, TJ-14) plus minocycline against afatinib-induced diarrhea and skin rash in patients with non-small cell lung cancer.

PURPOSE: Diarrhea and oral mucositis induced by afatinib can cause devastating quality of life issues for patients undergoing afatinib treatment. Several studies have shown that hangeshashin-to (TJ-14) might be useful for chemotherapy-induced diarrhea and oral mucositis. In this study, we investigated the prophylactic effects of TJ-14 for afatinib-induced diarrhea and oral mucositis and minocycline for afatinib-induced skin rash. PATIENTS AND METHODS: First- and second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors have become the standard first-line treatment in patients with EGFR-mutated non-small cell lung cancer. The incidence of diarrhea was higher with afatinib than with gefitinib, and we conducted a single-arm Phase II study with afatinib. Patients who had previously undergone treatment with afatinib were ineligible. Both TJ-14 (7.5 g/day) and minocycline (100 mg/day) were administered simultaneously from the start of afatinib administration. The primary end point was the incidence of ≥ grade 3 (G3) diarrhea (increase of ≥7 stools/day over baseline) during the first 4 weeks of treatment. The secondary end points were the incidence of ≥ G3 oral mucositis (severe pain interfering with oral intake) and $ G3 skin toxicity (severe or medically significant but not immediately life-threatening). RESULTS: A total of 29 patients (nine men and 20 women; median age, 66 years; performance status, 0/1/2: 18/10/1) were enrolled from four centers. Four patients had undergone prior treatment with chemotherapy, including gefitinib or erlotinib. In all, 20 (68.9%) patients and one (3.4%) patient had diarrhea of any grade and ≥ G3, respectively. One (3.4%) patient had ≥ G3 oral mucositis; no patients had ≥ G3 skin rash. A total of 18 (62%) of the 29 patients achieved a partial response. CONCLUSION: The present study indicated a trend in which TJ-14 reduced the risk of afatinib-induced diarrhea and minocycline reduced the risk of afatinib-induced skin rash.

Acquisition of the T790M resistance mutation during afatinib treatment in EGFR tyrosine kinase inhibitor-naïve patients with non-small cell lung cancer harboring EGFR mutations.

The T790M secondary mutation of the epidermal growth factor receptor (EGFR) gene accounts for 50% to 60% of cases of resistance to the first-generation EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib. The prevalence of T790M in EGFR mutation-positive patients who acquire resistance to the irreversible, second-generation EGFR-TKI afatinib has remained unclear, however. We here determined the frequency of T790M acquisition at diagnosis of progressive disease in patients with EGFR-mutated non-small cell lung cancer (NSCLC) treated with afatinib as first-line EGFR-TKI. Among 56 enrolled patients, 37 individuals underwent molecular analysis at rebiopsy. Of these 37 patients, 16 individuals (43.2%) had acquired T790M, including 11/21 patients (52.4%) with an exon 19 deletion of EGFR and 5/13 patients (38.5%) with L858R. None of three patients with an uncommon EGFR mutation harbored T790M. T790M was detected in 14/29 patients (48.3%) with a partial response to afatinib, 1/4 patients (25%) with stable disease, and 1/4 patients (25%) with progressive disease as the best response. Median progression-free survival after initiation of afatinib treatment was significantly (P = 0.043) longer in patients who acquired T790M (11.9 months; 95% confidence interval, 8.7-15.1) than in those who did not (4.5 months; 95% confidence interval, 2.0-7.0). Together, our results show that EGFR-mutated NSCLC patients treated with afatinib as first-line EGFR-TKI acquire T790M at the time of progression at a frequency similar to that for patients treated with gefitinib or erlotinib. They further underline the importance of rebiopsy for detection of T790M in afatinib-treated patients.

Heterogeneous clinical features in patients with pulmonary fibrosis showing histology of pleuroparenchymal fibroelastosis.

BACKGROUND: The histological pattern of pleuroparenchymal fibroelastosis (PPFE) is well defined, but its clinical features remain unclear. METHODS: We retrospectively examined the predominantly involved lung-fields (based on abnormal opacities on computed tomography [CT] images), and the initial value and annual decline of respiratory function in patients with pulmonary fibrosis presenting with histologically confirmed PPFE. RESULTS: Thirteen female and nine male subjects were included. Eleven interpreters independently analyzed 231 CT image series. One-third of the CT series (78/231) was interpreted as demonstrating equal involvement of the upper and lower lung fields, i.e., six out of 21 patients had equal involvement of the upper and lower lung fields, based on a majority decision of the interpreters. The residual volume/total lung capacity (RV/TLC) was increased and correlated inversely with forced vital capacity (FVC) at the initial measurement. FVC followed two patterns of decline over time: a gradual decline over a follow-up period of more than 6 years (-55mL/year, R(2)=0.799), and a relatively rapid decline over a shorter period (-364mL/year, R(2)=0.855) as determined by mixed-effect linear regression. CONCLUSIONS: The predominantly involved sites seen on CT images of PPFE were not limited to the upper lobes. In some cases, upper lung fields were predominantly involved, but in other cases, both upper and lower lung fields were equally involved. Two patterns of FVC decline exists: a rapid decline over a short period and a slow decline over a longer period, suggesting that the disease follows a heterogeneous clinical course.

New Approach to Complete Video-assisted Thoracoscopic Lobectomy in T2 and T3 Non-Small Cell Lung Cancer.

Complete video-assisted thoracoscopic surgery (c-VATS) for lung cancer is minimally invasive because of the small incision required. c-VATS has recently become a standard procedure for treatment of stage IA/IB lung cancer. However, a long thoracic incision or extensive costal rib resection is required in patients with large lung tumors. We herein introduce an improved VATS lobectomy procedure for patients with T2 and T3 lung cancer. In this technique, resected tissue is removed through a small upper abdominal midline incision below the xiphoid through the retrosternal-extraperitoneal pathway. Five patients who underwent this new procedure were compared against 10 control patients who underwent hybrid VATS lobectomy. Significantly fewer patients who underwent c-VATS lobectomy complained of severe postoperative pain; however, there was no significant difference in the postoperative hospital stay between the two groups. The present study demonstrates that c-VATS lobectomy can be performed with minimal operative pain and without need for a long thoracic incision or extensive rib resection, even in patients with large lung tumors (T2 and T3). These results suggest that the indications for c-VATS lobectomy in patients with T2 and T3 non-small cell lung cancer can be expanded by implementation of our approach, which involves removal of the freed lobe through an abdominal incision.

Histological evolution of pleuroparenchymal fibroelastosis.

AIMS: To investigate the histological evolution in the development of pleuroparenchymal fibroelastosis (PPFE). METHODS AND RESULTS: We examined four patients who had undergone surgical lung biopsy twice, or who had undergone surgical lung biopsy and had been autopsied, and in whom the histological diagnosis of the first biopsy was not PPFE, but the diagnosis of the second biopsy or of the autopsy was PPFE. The histological patterns of the first biopsy were cellular and fibrotic interstitial pneumonia, cellular interstitial pneumonia (CIP) with organizing pneumonia, CIP with granulomas and acute lung injury in cases 1, 2, 3, and 4, respectively. Septal elastosis was already present in the non-specific interstitial pneumonia-like histology of case 1, but a few additional years were necessary to reach consolidated subpleural fibroelastosis. In case 3, subpleural fibroelastosis was already present in the first biopsy, but only to a small extent. Twelve years later, it was replaced by a long band of fibroelastosis. The septal inflammation and fibrosis and airspace organization observed in the first biopsies were replaced by less cellular subpleural fibroelastosis within 3-12 years. CONCLUSIONS: Interstitial inflammation or acute lung injury may be an initial step in the development of PPFE.

Prognostic significance of urine N1, N12-diacetylspermine in patients with non-small cell lung cancer.

BACKGROUND: Recently N(1),N(12)-diacetylspermine, a diacetylated polyamine derivative, was recognized as a tumor marker in patients with several kinds of cancers. However, the significance of its levels in urine as a prognostic factor has not been elucidated. In the present study, we examined whether the urine N(1),N(12)-diacetylspermine levels can be used as a prognostic factor in patients with NSCLC. PATIENTS AND METHODS: Urine samples from 251 patients with NSCLC were collected prior to surgery and the urinary N(1),N(12)-diacetylspermine concentration was measured. Thereafter, all 251 patients underwent curative surgery and the analysis of prognosis was performed for over 10 years. Out of the 251 patients, 91 had recurrent disease. The significance of the urinary N(1),N(12)-diacetylspermine level as a prognostic factor among all 251 patients and among the 91 patients with recurrence was evaluated. RESULTS: Univariate analysis of all 251 patients showed that the level of urinary N(1),N(12)-diacetylspermine was a significant prognostic factor for disease-free survival and overall survival; however, multivariate analysis showed it had no significance. Conversely, the univariate and multivariate analyses of post-recurrent survival of the 91 patients with recurrence showed that urinary N(1),N(12)-diacetylspermine was an independent prognostic factor for post-recurrent survival. CONCLUSION: Patients with recurrence with positive urinary N(1),N(12)-diacetylspermine should undergo more intensive care and determination of urinary N(1),N(12)-diacetylspermine may contribute to improvement of prognosis of NSCLC.

Preoperative chemoradiotherapy using cisplatin plus S-1 can induce downstaging in patients with locally advanced (stage III) non-small-cell lung cancer.

BACKGROUND: About 30% of patients with non-small cell lung cancer (NSCLC) have locally advanced cancer (stage IIIA or IIIB) at the time of presentation. Many institutions have reported treatment with preoperative chemoradiotherapy (PCRT) followed by curative resection in patients with stage III NSCLC, but the optimal therapeutic protocol for this group has not been established. PATIENTS AND METHODS: Nineteen patients with stage III NSCLC were treated with PCRT, followed by surgery at the Hamanomachi Hospital, Fukuoka, Japan from May 2000 to November 2011. We evaluated the effectiveness of PCRT for inducing downstaging using mainly three chemoradiotherapy regimens; cisplatin plus Tegafur-Gimeracil-Oteracil Potassium (S-1), cisplatin plus Tegafur-Uracil (UFT), or 1,1'cyclobutanedicarboxylate (Carboplatin, CBDCA) plus paclitaxel, with concurrent radiation therapy in 19 patients with stage III NSCLC. RESULTS: The overall 5-year survival rate was 57.1%, which is higher than the average survival rate for patients with stage III NSCLC in Japan. Among the regimens used, only cisplatin plus S-1 with concurrent radiation therapy significantly induced downstaging. There was a significant difference in survival time between the downstaged and non-downstaged groups. However, there was no significant difference in survival time between the S-1 plus cisplatin group and the other groups combined, because of the short observation period for the S-1 plus cisplatin group. CONCLUSION: PCRT using cisplatin plus S-1 with concurrent radiation therapy is useful for inducing downstaging in patients with locally advanced stage III NSCLC.

Pilot study on traumatic grief treatment program for Japanese women bereaved by violent death.

This pilot study aimed to refine a treatment approach for traumatic grief due to violent loss. Our Traumatic Grief Treatment Program, a modification of Shear's complicated grief treatment (Shear et al., 2005), comprises psychoeducation, in vivo exposure, imaginal exposure, discussion of memories about and imaginal conversation with the deceased. Thirteen of 15 Japanese women suffering from posttraumatic stress disorder (PTSD) due to traumatic grief completed 12 to 16 weekly individual sessions based on their therapists' recommendations. Assessment scales included the Inventory of Complicated Grief, the Impact of Event Scale-Revised, and the Center for Epidemiologic Studies Depression Scale. There was significant reduction in symptom severity at treatment end, and symptom levels remained low throughout the 12-month follow-up period. Based on Jacobson's Reliable Change Index, 46% showed change on all 3 measures. These findings suggest that our treatment model may be feasible for treating traumatic grief with PTSD in non-Western settings.

Efficacy of exposure therapy for Japanese patients with posttraumatic stress disorder due to mixed traumatic events: A randomized controlled study.

The authors examined the efficacy of Prolonged Exposure (PE) therapy in Japanese patients with posttraumatic stress disorder (PTSD). Twenty-four patients (21 women, 3 men) with PTSD due to mixed trauma were randomly assigned to the PE group (PE with or without treatment as usual [TAU]) or the control group (TAU) only. The control group received PE after a 10-week period. Intention-to-treat analysis showed the PE group achieved significantly greater reduction than the control group at posttreatment in either PTSD or depressive symptoms. The control group had significantly decreased symptom severity after PE treatment. Symptom levels of 19 PE completers in the both groups remained low in 12-month follow-up assessments. The study's findings will promote the future dissemination and implementation of evidence-based treatment for PTSD in non-Western settings.

[A case of disseminated actinomycosis which extended from the thoracic cavity].

A 74-year-old man was referred to our hospital with a high grade fever, a left abdominal tumor and bloody sputum since the beginning of April 2006. We made an incision of the abdominal tumor, and the Gram-stain smear demonstrated Gram-positive rods. Actinomycosis was diagnosed because tissue culture demonstrated Actinomyces israelii. Penicillin was administered, and his clinical features improved. It is difficult to distinguish actinomycosis from malignancy or tuberculosis, therefore actinomycosis should be considered in the differential diagnosis of a mass shadow, and it can be cured with penicillin.

[First case report of respiratory infection with Rothia aeria].

A 53-year-old woman was admitted to our hospital with dysbasia and forgetfulness. Her past history included uveitis at age 39. Medical examinations led to a diagnosis of neurosarcoidosis. Although she was treated with prednisolone, her symptoms remained, so she received steroid pulse therapy twice, and administration of azathioprine. In early January 2007, a chest X-ray film showed nodules in the right upper lung that rapidly increased in size and number. A CT scan revealed multiple nodules including cavitary lesions in both lung fields. Examination of bronchial lavage fluid and a transbronchial lung biopsy showed a mycelium-like gram-negative filament. After the treatment with benzylpenicillin for 1 month, her laboratory data and radiological abnormalities markedly ima proved. However, switching to oral administration of amoxicillin caused the regrowth of the nodules. She was retreated with intravenous benzylpenicillin for 8 weeks, followed by oral administration of amoxicillin for 5 months, and her condition completely resolved. The causative organism was identified as Rothia aeria (described in 2004) by 16S rRNA gene sequencing. This is the first report of a case of pulmonary infection with this species.

Pilot study on prolonged exposure of Japanese patients with posttraumatic stress disorder due to mixed traumatic events.

This pilot study investigated the feasibility of Prolonged Exposure (PE) treatment for Japanese patients with posttraumatic stress disorder (PTSD) due to mixed traumatic events. Among 12 participants in this study, 9 women and 1 man completed between 9 and 15 weekly individual PE sessions; 2 female participants dropped out in early sessions. Among completers, the authors identified a significant reduction of symptom severity scores from pretreatment to posttreatment in terms of PTSD and depression on therapist-rated and self-rated measurements. Symptom levels remained low in 3- and 6-month follow-up assessments. Our findings suggest that PE is feasible and can be accepted for PTSD patients not only in Western countries, but also for those in Japan.