BACKGROUND: In clinical practice, peritoneal dissemination after curative-intent surgery for pleural mesothelioma occasionally recurs. This study investigated the risk factors and prognosis associated with post-pleurectomy/decortication peritoneal dissemination in pleural mesothelioma, which are rarely reported.
METHODS: This retrospective review included 160 patients who experienced recurrence after pleurectomy/decortication for pleural mesothelioma between January 2011 and December 2021. Patients with recurrence were classified according to the initial recurrence pattern. The P group experienced recurrence with peritoneal dissemination, and the non-P group experienced recurrence without peritoneal dissemination. The analysis determined the risk factors for peritoneal dissemination using multivariable logistic regression analysis. Survival was analyzed using the Kaplan-Meier method and the log-rank test.
RESULTS: Of the 160 patients, 20 (12.5%) exhibited peritoneal dissemination and were assigned to the P group, whereas 140 (87.5%) had recurrence without peritoneal dissemination and were assigned to the non-P group. Multivariable logistic regression analysis showed that diaphragm reconstruction (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.0-8.0; p = 0.048) and female sex (OR, 3.7; 95% CI 1.26-10.8; p = 0.017) were associated with the P group. Post-recurrence survival was worse in the P group than in the non-P group (1-year post-recurrence survival: 22.2% vs. 65.3%; median: 6.7 months vs. 19.4 months; p = 0.0013).
CONCLUSIONS: Peritoneal dissemination occurred in approximately one of every eight patients with recurrence after pleurectomy/decortication for pleural mesothelioma, and the incidence was significantly higher among females and patients undergoing diaphragm reconstruction. Moreover, postoperative recurrence of peritoneal dissemination was associated with a poor prognosis.

BACKGROUND: Although the positive rate of preresection pleural lavage cytology (PLC) is low, it is an important indicator of poor prognosis for non-small-cell lung cancer patients with frequent pleural dissemination (PD) recurrence. Thin-section computed tomography (TSCT) can reveal relationships between a primary tumor and the pleura at 1 to 2 mm intervals, and this is associated with visceral pleural invasion (VPI). However, its association with PLC remains unclear. Therefore, we aimed to improve PLC efficiency and predict PD recurrence by understanding the relationship between PLC and preoperative TSCT findings.
METHODS: Between January 2014 and December 2018, we reviewed 978 patients with non-small-cell lung cancer who underwent PLC tests during complete resection surgery. Preoperative TSCT findings were evaluated, and factors with the highest specificity (proportion of patients with radiologically to pathologically diagnosed positive PLC) were investigated. We also evaluated their relationships with VPI and PD recurrence.
RESULTS: PLC positive was identified in 55 (5.6%) of the 978 patients. The two TSCT findings predicting PLC results, \"the absence of pleural findings,\" ie, tumor not attached to pleura or without pleural tag, and \"consolidation-to-tumor ratio ≤0.5\", had a specificity of 100% (95% confidence interval: 90.4%-100%); additionally, all cases with these findings were VPI negative and had no PD recurrence. And 24% of the cohort had either of these findings.
CONCLUSIONS: The absence of pleural findings and/or consolidation-to-tumor ratio ≤0.5 of primary tumor on preoperative TSCT can predict PLC negativity with very high probability; therefore, PLC can be omitted for such patients.

OBJECTIVE: This is a retrospective evaluation of whether percutaneous direct puncture biopsy of lung lesions contacting to the pleura is justified.
METHODS: Between August 2016 and July 2021, 163 consecutive patients (100 males, 63 females with a median age of 73 years) who had malignant lung tumors measuring 0.6-12.4 cm (median, 2.9 cm) that contacted to the pleura and underwent percutaneous lung biopsy under computed tomography fluoroscopic guidance using an 18-gauge end-cut needle were examined. The trajectory was direct puncture in 80 patients (49.1%, 80/163), and trans-lung in 83 patients (50.9%, 83/163). Diagnostic yield and major adverse event rates of direct and trans-lung puncture biopsies were compared.
RESULTS: No difference was found in diagnostic yield between direct puncture and trans-lung biopsies (93.8% vs. 98.8%, p=0.11). Major adverse events were major pneumothorax (n=13/163, 8.0%), pleural dissemination (n=18/163, 11.0%), and hemothorax requiring arterial embolization (n=1/163, 1.0%). Direct puncture caused major pneumothorax significantly less than trans-lung puncture did (0%, 0/80 vs. 15.7%, 13/83, p<0.001). No significant difference was found between the two biopsy methods regarding the incidence of pleural dissemination (11.0%, 11/80 vs. 8.4%, 7/83, p=0.32).
CONCLUSIONS: Direct puncture biopsy of malignant lung tumors contacting to the pleura is justified.

To investigate the effect of two modalities, radiotherapy (RT) and surgery plus entire hemithoracic radiotherapy (EHRT), on stage IVa thymoma. Patients enrolled in this study meet the following criteria: histologically proven thymoma; primary stage IVa or pleural dissemination after initial curative treatment. One treatment modality is intensity-modulated radiotherapy (IMRT) for pleural lesions with a dose ranging from 30-50 Gy, the other is macroscopically surgical resection plus EHRT with a dose of 13 Gy in 13 fractions. From July 2012 to April 2018, there were totally 56 patients enrolled in this study. The median age was 45 years old (range, 20-75 years old). There were 35 male and 21 female patients. The histology subtype distribution was 1 AB, 8 B1, 20 B2 and 27 B3, respectively. Thirty-one patients received IMRT for pleural dissemination and the response rate (CR + PR) was 97%. The mean local control time was 40 months (95% CI, 32.6-47.3 months). The in-field and out-field recurrence were 32% and 94%, respectively. The 2-year progression free survival (PFS) was 18%. While for patients who were treated by surgery plus EHRT, the in- and out-field recurrence were 8% and 16%, respectively. The 2-year PFS was 40%. The 2-year PFS for B1, B2 and B3 were 20%, 50% and 23%, respectively (P=0.255). Major toxicity occurred in IMRT group, 5 died of radiation-induced pneumonitis. Both IMRT and surgery plus EHRT showed good local control for stage IVa thymoma. Since stage IVa thymoma has a tendency to involve the whole hemithorax, surgery plus EHRT has a potential to produce longer PFS.

Pleural dissemination is a common pattern of failure after initial treatment of thymoma and thymic carcinoma, but there is no standardized treatment. As these tumors are relatively radiosensitive, we investigated the effectiveness of radiotherapy. Twenty patients underwent 33 series of local radiotherapy for 96 pleural dissemination lesions after initial treatment. Conventional radiotherapy (CRT), tomotherapy, and combination of the two were employed in 19, 13, and 1 series, respectively. The median follow-up period after the first irradiation for pleural dissemination was 46 months (range, 14-161). For all 20 patients, overall survival (OS) rates from initial radiotherapy for pleural dissemination were 100% at three years and 86% at five years. Progression-free survival (PFS) rates after 33 series of radiotherapy were 30% at three years and 16% at five years. Local control (LC) rates for 96 lesions were 98% at three years and 96% at five years. In-field recurrence was observed in only two among the 96 lesions. One patient (5%) developed grade 3 radiation pneumonitis and another (5%) developed grade 3 pericardial effusion. No other serious adverse events were observed. When disseminated nodules can be covered within localized fields, local radiotherapy may be a treatment option. Using tomotherapy, multiple lesions can be treated safely.

BACKGROUND: Whether patients with non-small cell lung cancer (NSCLC) with unexpected pleural dissemination (UPD) could get survival benefit from tumor resection remained controversial.
METHODS: Totally, 169 patients with NSCLC with UPD were included between 2012 and 2016. Patients were divided into the tumor resection and open-close group. Progression-free survival (PFS) and overall survival (OS) were compared with a log-rank test. The multivariable Cox analysis was applied to identify prognostic factors.
RESULTS: Sixty-five patients received open-close surgery and 104 patients underwent main tumor and visible pleural nodule resection. Tumor resection significantly prolonged OS (hazard ratio [HR]: 0.408, P < 0.001), local PFS (HR: 0.283, P < 0.001), regional PFS (HR: 0.506, P = 0.005), and distant metastasis (HR: 0.595, P = 0.032). Multivariable Cox analysis confirmed that surgical method was an independent prognostic factor for OS, local PFS and regional PFS, except distant metastasis. Subgroup analyses indicated that tumor resection could not improve OS in the patients who received targeted therapy (HR: 0.649, P = 0.382), however, tumor resection was beneficial for the patients who received adjuvant chemotherapy alone (HR: 0.322, P < 0.001). In the tumor resection group, lobectomy (HR: 0.960, P = 0.917) and systematic lymphadenectomy (HR: 1.512, P = 0.259) did not show survival benefit for OS.
CONCLUSIONS: Main tumor and visible pleural nodule resection could improve prognosis in patients with UPD who could not receive adjuvant targeted therapy. Sublobar resection without systematic lymphadenectomy may be the optimal procedure.

BACKGROUND: The prognosis of non-small-cell lung cancer (NSCLC) patients with pleural dissemination is poor, and pleural dissemination is generally considered a contraindication for radical surgery. However, if pleural dissemination is missed intraoperatively, patients with false-negative stage IV NSCLC cannot receive appropriate chemotherapy, and their prognosis might worsen.
METHODS: In the present study, we enrolled 144 patients who received surgery for NSCLC between January 2008 and December 2019 with available data on the maximum standardized uptake value (SUVmax) on positron emission tomography (PET) with lesions adjacent to the visceral pleura and without lesions invading the chest wall.
RESULTS: Seven patients who had pleural dissemination were compared with 137 patients who had not pleural dissemination. The relationships between pleural dissemination and the clinicopathological variables were analyzed, and significant differences in the histopathological type (P=0.03), and differentiation (P<0.01) were noted. It was suggested that squamous cell carcinoma tended not to show dissemination to the pleural cavity. The logistic regression analyses of the predictive factors related to pleural dissemination in non-squamous cell carcinoma patients were analyzed, and the age (P=0.01) and differentiation (P<0.01) were identified as significant predictive factors related to pleural dissemination.
CONCLUSIONS: Cases with non-squamous cell carcinoma, a young age, and poor differentiation of undifferentiated grade of histological differentiation are factors associated with early pleural cavity dissemination.

BACKGROUND: Local radiation therapy (RT) can provide pain relief and reduce bleeding resulting from pleural or peritoneal dissemination of primary tumors. However, the optimal RT exposure dose for such tumors is unclear and the response rate is unknown. In this study, we examined the effectiveness of palliative RT for pleural or peritoneal disseminated tumors to determine the optimal dose in these patients.
METHODS: The data of 22 patients with pleural- or peritoneal-disseminated tumors who were treated with local RT at our institution between 2011 and 2019 were retrospectively reviewed.
RESULTS: Among these patients, 9 (40.9%) had pleural tumors, 13 (59.1%) had peritoneal tumors and 2 had tumors in the peritoneum and umbilicus. The most common primary tumors were lung (22.8%) and pancreatic cancer (18.2%). RT was mainly administered for pain alleviation (72.7%). Three patients (13.6%) received RT for hemostasis. Thirteen patients (59.1%) received a regimen of 30 Gy/10 fractions (fr), with the total dosage for all patients ranging from 27 to 56 Gy. No grade 2 or higher RT-related adverse events occurred. Three and four patients obtained complete and partial responses, respectively. The timing of the measurement of response to pain relief ranged from 0 to 232 (median, 21) days upon completion of RT. Overall response to pain relief occurred in nine of 16 patients (56.3%) with pain before RT. Hemostasis was confirmed in 2 of the 3 patients (66.7%) with bleeding before RT. Twelve of 20 (60%) patients with symptoms before RT responded to RT. Disease-specific survival (DSS) time after RT ranged from 1 to 656 (median, 106) days.
CONCLUSIONS: Prompt palliative administration of RT to patients with advanced disease to alleviate pain from disseminated tumors may achieve therapeutic efficacy.

OBJECTIVE: We developed a diagnostic method for pleural disseminated lesions of lung cancer using a combination of 5-aminolevulinic acid (5ALA) and autofluorescence observation system. We utilized a phenomenon in which externally ingested 5ALA is metabolized to protoporphyrin IX, a precursor of heme, which remains inside malignant cells and emits red fluorescence of approximately 630 nm. The diagnosis was made employing an observation system based on autofluorescence emitted from normal tissues that we have investigated.
METHODS: Between January 2017 and April 2019, we examined 82 lung cancer patients with suspected pleural invasion. We orally administered 5ALA (20 mg/m2) to the patients 4 hours before surgery, and malignant pleural lesions were thoracoscopically visualized using the autofluorescence observation system.
RESULTS: (1) Pleural disseminated lesions were observed in six patients. Of these lesions, two were not detected by usual white light inspection, and the use of this method enabled the diagnosis of disseminated lesions. (2) Regarding the diagnosis of lung cancer pleural invasion to estimate the risk of pleural dissemination, if limited to adenocarcinoma, the sensitivity was 93.9%; specificity, 74.3%; positive predictive value, 60.8%; and negative predictive value, 96.2%.
CONCLUSIONS: This method may facilitate the detection of minute disseminated lesions that are difficult to detect by usual inspection. In addition, the degree of pleural invasion may be diagnosed to evaluate the need for limited resection such as segmentectomy.

IgG4-related disease is an evolving entity of immune-mediated origin. We report a case of IgG4-related disease mimicking lung cancer with pleural dissemination. A 76-year-old male non-smoker was admitted to our hospital because of chest X-ray abnormality. Chest computed tomography scan showed a lung nodule measuring 26 × 14 mm with tiny nodules on the adjacent pleural surface. Wedge resection by video-assisted thoracoscopic surgery (VATS) was performed to aid diagnosis. Pathological findings of the nodule consisted of lymphoid follicular hyperplasia with lymphoplasmacytic infiltrate, fibrosis, and obstructive vasculitis. Focal and scattered thickening of the pleura with lymphoplasmacytic infiltrate was also observed. The IgG4/IgG ratio in the most prominent area exceeded 80%. Thus, we made a diagnosis of IgG4-related lung and pleural disease. To our knowledge, there has been no report of IgG4-related lung disease mimicking lung cancer with pleural dissemination.