Reduced risk of recurrent pneumothorax for sirolimus therapy after surgical pleural covering of entire lung in lymphangioleiomyomatosis.

BACKGROUND: Patients with lymphangioleiomyomatosis (LAM) frequently experience pneumothorax. Although sirolimus is the standard therapy for LAM, its effect on pneumothorax is controversial. Recently, total pleural covering (TPC) and modified TPC (mTPC) were introduced as surgical treatment options for pneumothorax for patients with LAM. However, the effect of sirolimus on the recurrence of pneumothorax in patients who underwent the treatments is still uncertain. We hypothesized that some clinical factors including sirolimus treatment could predict postoperative recurrence of pneumothorax. In order to clarify this hypothesis, we retrospectively analyzed the clinical data from 18 consecutive patients with LAM who underwent 24 surgical pleural covering of entire lung (SPC) as 17 TPC and 7 mTPC against pneumothoraces from surgical database between January 2005 and January 2019, and we determined the predictors of postoperative recurrence. RESULTS: Of the 24 surgeries of SPC, 14 surgeries (58.3%) had a history of two or more ipsilateral pneumothoraces, and 11 surgeries (45.8%) had a history of ipsilateral pleural procedures before SPC. Sixteen surgeries (66.6%) in 12 patients received treatment of sirolimus after SPC (sirolimus group). With a median follow-up time of 69.0 months after SPC, four surgeries (16.6%) in three patients had a postoperative recurrence, and the 5-year recurrence-free survival (RFS) after SPC was 82.9%. In patients with postoperative recurrence, serum level of vascular endothelial growth factors D was significantly higher than that in those with non-recurrence (3260.5 vs. 892.7 pg/mL, p = 0.02), and the rate of sirolimus treatment in the recurrence group was significantly lower than that in the no-recurrence group (0 vs. 80%, p = 0.006). The log-rank test showed that the RFS of the sirolimus group (sirolimus use after SPC) was significantly better than that of the non-sirolimus group (p = 0.001), and no significant difference was observed for other factors. CONCLUSION: We first reported sirolimus might effectively suppress the recurrence of pneumothoraces in LAM patients who received SPC. Sirolimus induction after SPC (TPC or mTPC) might be a feasible option for frequent pneumothorax in LAM.

Programmed Death-ligand 1 Expression With Clone 22C3 in Non-small Cell Lung Cancer: A Single Institution Experience.

BACKGROUND: In recent years, the anti-programmed cell death 1 (PD-1) drug pembrolizumab (Keytruda) was approved for treatment of unresectable advanced non-small cell lung cancer (NSCLC) as first- or second-line therapy depending on the clone 22C3-programmed death-ligand 1 (PD-L1) immunohistochemical expression score by the companion diagnostic assay. We herein evaluated 22C3-PD-L1 expression of NSCLC in a single institution experience and compared it with clinicopathologic features. MATERIALS AND METHODS: We assessed 22C3-PD-L1 expressions of 411 patients with NSCLC from our institution, including in past specimens. Programmed death-ligand 1 immunohistochemistry (IHC) testing was performed using the PD-L1 clone 22C3 pharmDx kit (Agilent Technologies/Dako, Carpinteria, CA, USA). Patients were separated into 3 groups with <1% (no expression), 1% to 49% (low expression), or ⩾50% (high expression) positive tumor cells. RESULTS: In all, 137 patients (33%) did not express PD-L1, 155 (38%) showed low expression, and 119 (29%) demonstrated high expression. Archival samples showed lower PD-L1 expression than that of recent samples, and the ratios of no expression case significantly increased by using paraffin blocks embedded particularly in more than 4 years ago. Programmed death-ligand 1 positivity was significantly associated with male sex, smoking, higher tumor grade, squamous cell carcinoma in histologic type, wild-type EGFR, and ALK rearrangement positive. CONCLUSIONS: The rate of 22C3-PD-L1 expression of NSCLC detected in this study was similar to the frequencies of the previous reports, although the ratio of expression case decreased when using old paraffin blocks.

Assessment of ALK gene rearrangement in lung cancer using a new rapid automated SureFISH (Dako Omnis) assay.

The ALK fluorescence in situ hybridisation (FISH) method is the examination essential for pathological diagnosis and choice of molecular-targeted therapy in ALK-rearranged lung cancer. Here, for detection of ALK gene rearrangement in patients with lung cancer, we evaluated the rapid FISH technology (ALK SureFISH), a newly developed assay for the automated staining platform Dako Omnis, using 21 formalin-fixed paraffin-embedded (FFPE) samples. All cases could be evaluated with the SureFISH method. SureFISH provided excellent quality signals without any background staining. The SureFISH assay was able to offer a rapid turnaround time (approximately 3.5 hours) and was 100% concordant with prior Vysis FISH results in our laboratory.

A Case of Solitary Well-Differentiated Papillary Mesothelioma with Invasive Foci in the Pleura.

Well-differentiated papillary mesothelioma (WDPM) is a rare, distinct tumor consisting of mesothelial cells with a papillary architecture, bland cytological features, and a tendency toward superficial spread without invasion. Rare cases with superficial invasion are termed WDPM with invasive foci. We report a case of solitary WDPM with invasive foci in the pleura. A 61-year-old woman presented with a lung adenocarcinoma. A small papillary lesion measuring 29 × 10 × 8 mm was incidentally found in the parietal pleura during a lobectomy for the lung adenocarcinoma. The fibrovascular core of the small papillary lesion was surrounded by a single layer of cuboidal cells with mild to moderate atypia and large nucleoli. Atypical mesothelial cells focally invaded the submesothelial layer. The cells of the papillary lesion were positive for cytokeratins and mesothelial markers. The Ki67 index was <1 %. The lesion did not show p16 loss on fluorescence in situ hybridization. We could not detect atypical mesothelial cells in the specimen from an extrapleural pneumonectomy. WDPM with invasive foci is prone to multifocality; however, our case represents a solitary case in the pleura.

Life-threatening and Rapidly Growing Teratoma in the Anterior Mediastinum.

This report describes the case of a 23-year-old man with a mediastinal teratoma. Five months before admission, a chest radiograph during a routine health checkup was normal. Four months before admission, the patient developed sudden onset of mild right-sided chest pain. He gradually developed dyspnea and was admitted to our hospital. Computed tomography revealed a giant tumor that was markedly compressing the right atrium. Urgent surgery was performed, and a ruptured, benign mature teratoma was diagnosed. Mature mediastinal teratomas are benign tumors, but they can rupture and have the potential to grow rapidly, potentially leading to life-threatening complications.

Molecular analysis of human papillomavirus in never-smokers with non-small cell lung cancer.

The causes of lung cancer in never-smokers remain unclear. The potential contribution of human papillomavirus (HPV) to the carcinogenesis of non-small cell lung cancer (NSCLC) has been reported. In 2008, a prospective registry of never-smokers with NSCLC was established at the Kinki-Chuo Chest Medical Center, Sakai, Osaka, Japan. Never-smokers with NSCLC were consecutively enrolled onto the registry. Of these patients, 114 with large tumor specimens, the majority of which were surgical tissues, were selected. In total, 23 of the most clinically relevant HPV types were assayed using polymerase chain reaction amplification of the viral genome. Following exclusion of samples with suboptimal quality, DNA was extracted from 96 formalin-fixed paraffin-embedded samples. These 96 cases consisted of 82 females (85.4%) and 14 males (14.6%), with a median age of 67 years (range, 29-83). Almost all cases (93.8%) were of the adenocarcinoma histological subtype. Despite confirmation of the quality and amount of DNA, HPV type 6 was detected in only one case (1.1%). Furthermore, no other samples examined were positive for any other HPV types. The results therefore suggest that HPV does not play a major role as the driving oncogenic event in never-smokers with NSCLC.

Small calcifying fibrous pseudotumor of the heart confined to the epicardium.

A calcifying fibrous pseudotumor (CFPT) is a rare benign lesion that often presents in the upper and lower extremities of children and young adults. In the present report, we describe a case of a small CFPT arising from the epicardium (visceral pericardium) in a 32-year-old woman. The tumor presented as a 25-mm polypoid mass protruding into the pericardial cavity, without extending into the myocardium. A complete resection was performed, and the patient has not experienced any relapse for more than 2 years. On histological examination, the lesion contained densely hyalinized collagen with psammomatous and dystrophic calcifications, as well as patchy chronic inflammatory infiltrate. The localization in the epicardium with no involvement of the myocardium was confirmed by the elastic stain. Amyloid was negative by the Congo red stain. On immunohistochemical analysis, the lesional cells indicated diffuse positive staining for vimentin and factor XIIIa and focal positive staining for CD34, but did not indicate positive staining for other pertinent antigens such as cytokeratins, calretinin, desmin, α-smooth muscle actin, ALK, and estrogen and progesterone receptors as well as IgG4 in plasma cells. To our knowledge, only three cases of CFPT in the heart have been reported in the literature, all of which developed in young females as a large mass involving the epicardium; the lesion also extended to the parietal pericardium in two cases. Moreover, all cases presented with few symptoms, despite the large lesion. In the present case, the CFPT developed also in a young woman, but the lesion was much smaller than those previously published and was localized in the visceral serous membrane of the heart. The findings of this case suggest a potential preferable site of origin of CFPTs of the heart.

A pilot study of cisplatin and etoposide with and without radiotherapy for advanced malignant thymoma.

AIM: Thymoma is a rare neoplasm of the mediastinum, for which very few data on the efficacy and safety of chemotherapy and chemoradiotherapy are available. The objective of this pilot study was to assess the safety and efficacy of cisplatin, etoposide, and radiotherapy for thymoma. PATIENTS AND METHODS: Patients with advanced, previously-untreated thymoma (Masaoka classification), measurable disease, and a performance status of 0-2 were eligible, and were treated with cisplatin-plus-etoposide, together with radiotherapy when possible. RESULTS: One patient achieved complete response, and seven achieved partial responses. Progression-free survival was 37.7 months (95% confidence interval = 18.6-56.8 months). Ten patients had grade 4 neutropenia, and five patients had grade 3 febrile neutropenia. However, other toxicities were relatively mild. To date, only five patients (45.5%) have died, and the median survival time is 128.1 months (95% confidence interval = 51.6-204.6 months). Patients treated with chemoradiotherapy had a good response and long progression-free survival. CONCLUSION: The combination of cisplatin and etoposide with or without radiotherapy is effective for advanced thymoma, and has an acceptable toxicity.

Large cell neuroendocrine carcinoma of the mediastinum with alpha-fetoprotein production.

Large cell neuroendocrine carcinoma (LCNEC) is a relatively new category of pulmonary neuroendocrine tumor. Although it was first detected in the lung, LCNEC has since been found in a variety of extrapulmonary sites. We now describe a patient who was diagnosed with LCNEC originating from the mediastinum, an extremely rare disorder. An increased serum concentration of alpha-fetoprotein (AFP) in the patient was reduced by chemotherapy in association with tumor shrinkage. Furthermore, the tumor was confirmed immunohistochemically to produce AFP. To our knowledge, this is the first report of a LCNEC that produces AFP.

Pulmonary lymphoma of mucosa-associated lymphoid tissue type followed as a long-standing indeterminate lesion in immunoglobulin M-type paraproteinemia.

An 82-year-old woman with monoclonal immunoglobulin (Ig) M-type paraproteinemia had a large opacity in the right lung field. The abnormal shadow on roentgenogram had persisted for more than 6 years since the initial diagnosis of paraproteinemia, which had been diagnosed as Waldenström's macroglobulinemia (WM). Computed tomography revealed the lesion as a pulmonary tumor which was finally diagnosed as a marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) after surgical removal. MALT lymphoma constitutes the majority of primary pulmonary lymphomas and is often associated with monoclonal IgM-type paraproteinemia as well as WM, a distinctive lymphoproliferative disorder. Pulmonary MALT lymphoma should frequently be suspected in case of an indeterminate pulmonary tumor with IgM-type paraproteinemia.

Non-small-cell lung cancer associated with non-thymomatous myasthenia gravis.

A non-small-cell lung cancer without distant metastases was incidentally found in a 77-year-old man who had suffered from myasthenia gravis (MG) without thymoma. The patient's condition was stabilized by oral pyridostigmine bromide which he had taken during the past 6 years. He simultaneously underwent thymectomy and left lower lobectomy with regional lymph node dissection. Although postoperative myasthenic crisis occurred, mechanical ventilation and intravenous steroid pulse relieved the patient and the symptoms improved thereafter. Cases of operable lung cancer with non-thymomatous MG have rarely been reported and the appropriate therapeutic strategy for such cases remains to be debated. Their causal association remains to be identified, whereas some studies have implied that immune disorder due to the abnormal thymus might possibly enhance the oncogenesis of extrathymic malignancies. Myasthenic crisis should also be taken into account in postoperative management of MG patients who simultaneously undergo thymectomy and lobectomy for synchronous lung cancer.

Pulmonary nodules 10 mm or less in diameter with ground-glass opacity component detected by high-resolution computed tomography have a high possibility of malignancy.

OBJECTIVES: For the histological diagnosis of small lung cancers of 10 mm or less in diameter (< or =10), resection by video-assisted thoracic surgery (VATS) with computed tomography (CT)-guided marking is feasible. One problem is that a small number of these pulmonary nodules are malignant. We retrospectively analyzed CT images of pulmonary nodules to find better criteria to select candidates for resection among patients with small pulmonary nodules. METHODS: Ninety-four patients with indeterminate peripheral pulmonary nodules underwent wedge resection by VATS. High-resolution CT using a 1.25 mm slice included the area of lesions. Nodules were classified by size (< or =10, 11 to 20, >20 mm) and whether they had a ground-glass opacity (GGO) component. RESULTS: The histology of all 94 nodules showed 52 primary lung cancers, 6 metastatic tumors, 5 benign tumors, 8 intrapulmonary lymph nodes, and 23 inflammatory nodules. Ninety-three percent of nodules larger than 20 mm, 75% of nodules 10 to 20 mm, and 43% of nodules < or =10 mm were malignant. Introducing a classification according to GGO component to nodules, malignancy was detected in 88% of nodules with a GGO component and in 30% of nodules without a GGO component among nodules < or =10 mm. Nodules < or =10 mm with a GGO component showed a statistically significant (p < 0.01) correlation with malignancy. CONCLUSIONS: Pulmonary nodules < or =10 mm with GGO should be considered to have a high possibility of malignancy and to be candidates for resection by VATS.

[Extrapleural pneumonectomy of malignant pleural mesothelioma].

We analyzed 7 patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy. Six men and a woman had a mean age of 65 years old. The postoperative mortality rate was 14% (1 death) and morbidity, 43% (3 cases). According to staging of International Mesothelioma Interest Group, 2 patients had stage I disease, 1 did stage II, 3 did stage III and 1 did stage IV. Local recurrences were found in 3 patients and metastasis in 2. In patients with local recurrences, 2 had irradiation with chemotherapy and 1, irradiation. In patients with recurrences of metastasis, 1 had chemotherapy and 1, supportive care. Seven patients with extrapleural pneumonectomy and 10 without surgery had median survivals of 16 months and 10 months, 1-year survival rates of 71% and 40% and 2-year survival rates of 57% and 0% respectively (p=0.071). Extrapleural pneumonectomy with adjuvant therapy could be effective treatment for malignant pleural mesothelioma.

Laparoscopic resection of intra-abdominal esophageal duplication cyst.

Esophageal duplication cysts are frequently encountered in the mediastinum and rarely in the abdomen. A case of laparoscopic resection of an intra-abdominal esophageal duplication cyst is reported. An incidental 4.5 x 4.0 x 3.5-cm, well-circumscribed, homogenous mass anterior to the intra-abdominal esophagus was detected on staging CT examinations for breast cancer in a 51-year-old woman. Laparoscopic resection of the lesion was performed after completion of breast-conserving surgery and whole breast irradiation. The defect of the muscular layer of the esophagus caused by the complete removal of the lesion required repair with muscular sutures. It was helpful to inspect the integrity of the esophageal wall repair by examining the exterior wall of the esophagus laparoscopically while insufflating air into the esophageal lumen through a fiberoptic esophagoscope. A laparoscopic approach utilizing intraoperative esophagoscopy is easy and safe for removal of intra-abdominal esophageal duplication cysts.

Splenic artery embolization using contour emboli before laparoscopic or laparoscopically assisted splenectomy.

The present study assessed preoperative splenic artery embolization using spherical embolic material, super absorbent polymer microspheres (SAP-MS), before laparoscopic or laparoscopically assisted splenectomy. Distal splenic artery embolization using 250 to 400 microm SAP-MS was performed in nine cases with ITP and in seven cases with the other diseases with splenomegaly. Laparoscopic or laparoscopically assisted splenectomies, including a hand-assisted procedure and the procedure involving left upper minilaparotomy, were done 2 to 4 hours after embolization. Conversion to traditional laparotomy was not required in any of the 16 cases, while conversion to 12-cm laparotomy was required in one case with massive splenomegaly. Mean operating time was 161 minutes, and mean intraoperative blood loss was 290 mL. No major postoperative complications were identified, and only one patient reported postembolic pain before surgery. Preoperative splenic artery embolization using painless embolic material, SAP-MS, would be effective for easy and safe laparoscopic or laparoscopically assisted splenectomy.

Reduced thiamine (vitamin B1) levels following gastrectomy for gastric cancer.

BACKGROUND: Vitamin B1 deficiency is well known as a possible complication following gastric restrictive surgery for morbid obesity; however, reduced vitamin B1 levels in patients who have undergone gastrectomy for gastric cancer have not been discussed previously. METHODS: Serum vitamin B1 levels were determined after the return to normal daily activity in 54 patients with distal gastrectomy for gastric cancer, 32 patients with total gastrectomy for gastric cancer, and 30 patients with radical surgery for colorectal cancer. Changes from serum vitamin B1 levels before operation to those after return to normal daily activity, without nutritional support, were investigated in 25 patients with gastrectomy for gastric cancer and 26 patients with radical surgery for colorectal cancer. RESULTS: Decreased serum vitamin B1 levels, below the normal range, were recognized in 7 of the 54 distally gastrectomized patients and in 5 of the 32 totally gastrectomized patients, whereas no such decrease was recognized in any patient after colorectal surgery. Decreased serum vitamin B1 level was recognized within 6 months after the operation in 6 of the 7 distally gastrectomized patients showing a decreased vitamin B1 level and in 3 of the 5 totally gastrectomized patients showing a decreased vitamin B1 level. Postoperative serum vitamin B1 levels were significantly lower than those before operation in patients with gastrectomies, whereas there was no significant difference in serum vitamin B1 levels before and after the surgeries in patients with surgery for colorectal cancer. CONCLUSION: Vitamin B1 levels may be reduced in gastrectomized patients, especially within 6 months after operation, even after their return to normal daily activity without nutritional support.

Solitary necrotic nodule of the liver.

Solitary necrotic nodule of the liver is a rare benign lesion; only 22 cases have been reported to date. An unsolved problem in treating these lesions involves the difficulties in differential diagnosis; specific features of necrotic nodule of the liver in preoperative examinations have not been identified. Here, we report a patient with resected solitary necrotic nodule of the liver with preoperative features shown on ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) examinations. A 48-year-old woman was referred to our hospital on December 13, 1999 because a hypoechoic lesion in Couinaud's segment VIII of the liver had been incidentally detected on US. A CT scan confirmed the presence of a round hypodense lesion, measuring 2 cm in diameter. No significant enhancement was recognized on dynamic MRI study. T1-Weighted MRI examinations demonstrated a low intensity showing a triple-layered pattern with low-iso-low intensity in the lesion, while T2-weighted images demonstrated a slightly high intensity in the lesion. These features suggested fibrous tissue. Histological examinations following partial resection of the liver revealed a solitary necrotic nodule of the liver. Combination studies, including MRI examinations, would be useful for the preoperative diagnosis of a solitary necrotic nodule of the liver.