Thymic Mucoepidermoid Carcinoma: A Clinicopathologic and Molecular Study.

Thymic mucoepidermoid carcinoma (MEC) is a rare tumor, and its characteristics remain to be clarified. Here we investigated 20 cases of thymic MEC to systematically characterize its clinical, histopathologic, and molecular features. The median age of the patients was 56 years (range, 19 to 80 y), there was a slight male predilection (3:2), and 44% of the patients were asymptomatic at diagnosis. The median tumor size was 6.8 cm in diameter, 55% were pT1 tumors, and 50% were TNM stage I tumors. When 4 tumor grading systems for salivary MEC (Armed Forces Institutes of Pathology, Brandwein, modified Healey, and the Memorial Sloan-Kettering) were employed, low-grade, intermediate-grade, and high-grade tumors accounted for 35% to 70%, 5% to 25%, and 25% to 50%, respectively. Many histologic variants were noted, and 70% of the cases were classified as nonclassic variants. MAML2 rearrangement was detected in 56% of cases, and the fusion partner was CRTC1 in all cases. CRTC1-MAML2 fusion was associated with lower pT classification and lower TNM stage. The overall survival rate of all patients was 69% and 43% at 5 and 10 years, respectively. Worse overall survival was associated with higher pT stage, higher TNM stage, residual tumors, greater tumor size, high-grade tumor histology (Armed Forces Institutes of Pathology and Memorial Sloan-Kettering, but not the other 2), and with the absence of CRTC1-MAML2 fusion. Of note, none of the patients with CRTC1-MAML2 fusion-positive tumors died during the follow-up. In conclusion, the clinicopathologic and molecular findings of thymic MEC presented here are expected to contribute to the management of this rare tumor.

Radical Resection for Second EGFR-mutated Primary Lung Cancer Following Immune Checkpoint Inhibitor Monotherapy for Stage IV Lung Adenocarcinoma.

A 78-year-old woman with multiple lung nodules, epithelial growth factor receptor (EGFR) exon 20 insertion mutations, and diagnosed with advanced lung adenocarcinoma (cT4N3M1a, stage IVA), was referred to our hospital. She received immune checkpoint inhibitor (ICI) therapy. The therapy showed remarkable antitumor effects; only a single nodule remained in the right upper lobe. The nodule was diagnosed as adenocarcinoma through a biopsy. We subsequently performed right upper lobectomy for multiple primary lung cancer (MPLC). The surgical specimen contained EGFR exon 19 deletion mutations and not exon 20 insertion mutations.

[Bronchial Stump Coverage Technique by da Vinci Xi].

da Vinci's greatest attractions are the fine images acquired with a high-resolution 3-dimensional( 3D) endoscope and the precise operation by forceps equipped with an articulated arm. We believed that complicated procedures can benefit from robot-assisted surgery. We have been actively performing collection and sewing of viable tissue using da Vinci Xi for the purpose of preventing bronchial stump fistulas. Of the 44 cases of lobectomy performed by the end of November 2019 using da Vinci Xi, 13 cases underwent bronchial stump covering. The covering procedure was intended for patients with conditions such as diabetes and a history of internal use of steroids. As the dressing, pedicled intercostal muscle was used in 4 cases, and free pericardial fat tissue was used in 9 cases. A good visual field was obtained by appropriately turning the oblique mirror upside down. The smoke emission effect of AirSeal was useful for securing the visual field. The dressing was sutured and fixed using 3-0 or 4-0 Prolene( SH) cut to a length of 10 to 12 cm. The postoperative course was good and bronchial stump fistula did not occur in all cases.

Resected thymic large cell neuroendocrine carcinoma: report of a case.

BACKGROUND: Thymic large cell neuroendocrine carcinoma (LCNEC) is extremely rare. The detailed clinical features of thymic LNCECs remain unknown. CASE PRESENTATION: A 90-year-old man with a history of diabetes mellitus, chronic renal failure, and an abdominal aortic aneurysm underwent computed tomography for follow-up, which showed an anterior mediastinal tumor, measuring 31 mm × 28 mm in diameter. Magnetic resonance imaging showed an iso-intensity mass on T1-weighted images and high intensity on T2-weighted images. 18F-Fluorodeoxyglucose-positron emission tomography showed marked uptake in the mass, which was diagnosed as invasive thymoma or thymic carcinoma. Video-assisted thoracic surgery through the left thoracic cavity was converted to median sternotomy due to severe adhesions between the left lung and the chest wall. Partial thymectomy and combined partial resection of left upper lobectomy and the first and the second costal cartilages were performed. The pathologic diagnosis was thymic LCNEC, Masaoka stage III. The patient developed pleural dissemination and left lung metastases in 5 months and died 12 months after surgery. CONCLUSIONS: Thymic LCNEC has high malignant potential. More cases need to be studied.

SORORIN and PLK1 as potential therapeutic targets in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is an aggressive type of cancer of the thoracic cavity commonly associated with asbestos exposure and a high mortality rate. There is a need for new molecular targets for the development of more effective therapies for MPM. Using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and an RNA interference-based screening, we examined the SORORIN gene as potential therapeutic targets for MPM in addition to the PLK1 gene, which is known for kinase of SORORIN. Following in vitro investigation of the effects of target silencing on MPM cells, cell cycle analyses were performed. SORORIN expression was analyzed immunohistochemically using a total of 53 MPM samples on tissue microarray. SORORIN was found to be overexpressed in the majority of clinical MPM samples and human MPM cell lines as determined by qRT-PCR. Gene suppression of each SORORIN and PLK1 led to growth inhibition in MPM cell lines. Knockdown of SORORIN showed an increased number of G2M-phase population and a larger nuclear size, suggesting mitotic arrest. High expression of SORORIN (SORORIN-H) was found in 50.9% of all the MPM cases, and there is a tendency towards poorer prognosis for the SORORIN-H group but the difference is not significant. Suppression of SORORIN with PLK1 inhibitor BI 6727 showed a combinational growth suppressive effect on MPM cell growth. Given high-dose PLK1 inhibitor induced drug-related adverse effects in several clinical trials, our results suggest inhibition SORORIN-PLK1 axis may hold promise for the treatment of MPMs.

Kinesin family members KIF11 and KIF23 as potential therapeutic targets in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare and aggressive form of cancer commonly associated with asbestos exposure that stems from the thoracic mesothelium with high mortality rate. Currently, treatment options for MPM are limited, and new molecular targets for treatments are urgently needed. Using quantitative reverse transcription-polymerase chain reaction (RT-PCR) and an RNA interference-based screening, we screened two kinesin family members as potential therapeutic targets for MPM. Following in vitro investigation of the target silencing effects on MPM cells, a total of 53 MPMs were analyzed immunohistochemically with tissue microarray. KIF11 and KIF23 transcripts were found to be overexpressed in the majority of clinical MPM samples as well as human MPM cell lines as determined by quantitative RT-PCR. Gene knockdown in MPM cell lines identified growth inhibition following knockdown of KIF11 and KIF23. High expression of KIF11 (KIF11-H) and KIF23 (KIF23-H) were found in 43.4 and 50.9% of all the MPM cases, respectively. Patients who received curative resection with tumors displaying KIF23-H showed shorter overall survival (P=0.0194). These results provide that inhibition of KIF11 and KIF23 may hold promise for treatment of MPMs, raising the possibility that kinesin-based drug targets may be developed in the future.

[Investigation of lung cancer patients with cardiovascular disease].

BACKGROUND: According to the aging in Japan, surgery of lung cancer with cardiovascular disease is increasing. Among them, the merger of the heart and large blood vessel disease would be expected to be directly linked to the perioperative management. MATERIALS AND METHODS: We conducted a retrospective analysis of 1,005 patients who had undergone surgical resection of primary lung adenocarcinoma between January 1997 and June 2014 at Hokkaido University Hospital. Among them, 81 patients had more than one cardiovascular disease. RESULTS: The median age was 71 years old. Men are 62 cases(76%). 64 cases (79%)had smoking history. Ischemic heart disease( IHD) was 29 cases(33%), followed by atrial fibrillation(Af), arrhythmia other than Af, valve disease and macrovascular disease. Anticoagulant or antiplatelet therapy were preoperatively done in 41% of IHD cases, 39% of Af cases. Thirty four% of IHD, 50% of vascular disease received the treatment other than medication. Video-assisted thoracic surgery was performed in 67 cases(83%). Lobectomy, sublobectomy were performed for 59 cases(73%), 19 cases(23%), respectively. Postoperative complications were occurred in 32 cases(40%). Two patients(2.5%)died in hospital without discharge. Univariate analysis revealed tumor size, pStage, lymph node dissection, operation time or blood loss were correlated with postoperative complication. CONCLUSIONS: For the patients with cardiovascular disease, careful evaluation of surgical indication, perioperative management is required.

Giant primary angiosarcoma of the small intestine showing severe sepsis.

Primary malignant tumors of the small intestine are rare, comprising less than 2% of all gastrointestinal tumors. An 85-year-old woman was admitted with fever of 40 °C and marked abdominal distension. Her medical history was unremarkable, but blood examination showed elevated inflammatory markers. Abdominal computed tomography showed a giant tumor with central necrosis, extending from the epigastrium to the pelvic cavity. Giant gastrointestinal stromal tumor of the small intestine communicating with the gastrointestinal tract or with superimposed infection was suspected. Because no improvement occurred in response to antibiotics, surgery was performed. Laparotomy revealed giant hemorrhagic tumor adherent to the small intestine and occupying the peritoneal cavity. The giant tumor was a solid tumor weighing 3490 g, measuring 24 cm × 17.5 cm × 18 cm and showing marked necrosis. Histologically, the tumor comprised spindle-shaped cells with anaplastic large nuclei. Immunohistochemical studies showed tumor cells positive for vimentin, CD31, and factor VIII-related antigen, but negative for c-kit and CD34. Angiosarcoma was diagnosed. Although no postoperative complications occurred, the patient experienced enlargement of multiple metastatic tumors in the abdominal cavity and died 42 d postoperatively. The prognosis of small intestinal angiosarcoma is very poor, even after volume-reducing palliative surgery.

Histopathologic characterization of lung adenocarcinoma in relation to fluorine-18-fluorodeoxyglucose uptake on positron emission tomography.

BACKGROUND: Fluorine-18-fluorodeoxyglucose uptake on positron emission tomography is reported to have prognostic significance in patients after resection of lung adenocarcinoma. However, its relationship with histopathologic features remains unknown. METHODS: We conducted a retrospective analysis of 205 patients who had undergone surgical resection of primary lung adenocarcinoma (> 1.0 cm) after preoperative fluorine-18-fluorodeoxyglucose-positron emission tomography between January 1999 and December 2008 at Hokkaido University Hospital. Fluorine-18-fluorodeoxyglucose uptake was measured by the maximum standardized uptake value. A histopathologic review was performed according to the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification, and various histopathologic factors were evaluated semi-quantitatively. Correlations between these clinicopathologic factors and the maximum standardized uptake value (high ≥ 2.0 vs low < 2.0) were analyzed. RESULTS: Univariate analysis of clinicopathologic factors demonstrated that the following were significantly correlated with a high maximum standardized uptake value: an elevated carcinoembryonic antigen level, larger tumor size, upgraded pT, pN, pStage, non-lepidic histology, abundant fibroblastic/hyalinized stroma, necrosis, presence of pleural involvement, lymphatic and vascular invasion and more intra- and extracellular mucin. Multivariate analysis demonstrated that a tumor size of > 2.0 cm, non-lepidic histology and abundant fibroblastic/hyalinized stroma were significantly correlated with the high maximum standardized uptake value. CONCLUSION: More histopathologic factors are known to correlate with poor prognosis in lung adenocarcinomas showing high maximum standardized uptake values than in those showing low maximum standardized uptake values. Therefore, prognostication of patients with a resectable lung adenocarcinoma on the basis of preoperative fluorine-18-fluorodeoxyglucose uptake is histopathologically valid. Such observations may also help us to clarify the pathobiological mechanism responsible for the increased fluorine-18-fluorodeoxyglucose uptake in lung adenocarcinomas with a poor prognosis.

Differences in risk factors between patterns of recurrence in patients after curative resection for advanced gastric carcinoma.

BACKGROUND: Recurrence patterns in patients who have undergone curative gastrectomy for advanced gastric carcinoma can be classified as peritoneal, hematogenous, or lymphatic. The aim of this study was to clarify differences in risk factors between these different types of recurrence pattern. METHODS: Postoperative courses, including sites of recurrence and periods between surgery and recurrence, of patients who had undergone curative gastrectomy for advanced gastric carcinoma (more than pT2 invasion) were surveyed in detail. Clinicopathological factors were examined as potential independent risk factors for each recurrence pattern, based on recurrence-free survival, using multivariate analysis. RESULTS: Multivariate analysis identified depth of tumor invasion (pT4 vs. pT2/3; hazard ratio (HR), 7.05; P < 0.001), number of lymph node metastases (pN2/3 vs. pN0/1; HR, 4.02; P = 0.001), and histological differentiation (G3/4 vs. G1/2; HR, 2.22; P = 0.041) as independent risk factors for peritoneal metastasis. The number of lymph node metastases (HR, 26.21; P < 0.001) and venous vessel invasion (HR, 5.09; P = 0.001) were identified as independent risk factors for hematogenous metastasis. The number of lymph node metastases (HR, 6.00; P = 0.007) and depth of tumor invasion (HR, 4.70; P = 0.023) were identified as independent risk factors for lymphatic metastasis. CONCLUSIONS: This study clarified differences in risk factors between various patterns of recurrence. Careful examination of risk factors could help prevent oversight of recurrences and improve detection of recurrences during follow-up. The number of lymph node metastases represents an independent risk factor for all three patterns of recurrence; thus, patients with multiple lymph node metastases warrant particular attention.

Lymphoepithelial cyst of the pancreas.

Cystic lesions of the pancreas can be divided into true cysts, pseudocysts, and cystic neoplasms. Lymphoepithelial cysts (LECs) are a type of true cyst that can mimic pseudocysts and cystic neoplasms. LECs are rare lesions; fewer than 90 cases have been reported in the English language literature. The case of a 60-year-old man with an LEC of the pancreas is reported. He was admitted with upper abdominal discomfort. Computed tomography showed a 64 × 39 mm cystic mass in the retroperitoneum behind the duodenum and inferior caval vein. Magnetic resonance imaging revealed a right-sided mass on T1-weighted imaging, with a clear boundary between the mass and its surroundings, except for the pancreas. The mass had an inhomogeneous intensity on T2-weighted imaging. Within the mass, small floating nodules with low intensity were seen. Endoscopic ultrasound showed many high-echoic nodules and smaller grains scattered everywhere in the mass. Fine needle aspiration and cytologic examination were performed. Characteristic chylaceous fluid was obtained in which anucleate squamous cells were found. There were also a few atypical large cells with irregularly shaped marked nucleoli and degenerative cytoplasm. Cytologic diagnosis was suspicious for malignancy. The lesion was diagnosed as a retroperitoneal cyst, probably of pancreatic origin. Since a neoplastic lesion could not be ruled out, surgery was performed. The lesion was palpable on the dorsal side of the second portion of the duodenum. The mass was completely resected. Macroscopically, the lesion was a multilocular cyst with a thin septal wall. The cyst was filled with cottage cheese-like substance. Microscopically, the cyst wall was composed of stratified squamous epithelium and dense subepithelial lymphatic tissue with developed lymph follicles. The epithelial cells had no atypia. The histopathologic diagnosis was LEC of the pancreas. The patient's postoperative course was good.

New invagination procedure for pancreaticojejunostomy using only four sutures.

BACKGROUND: Pancreaticoenterostomy remains one of the most stressful parts of pancreatoduodenectomy. We introduce herein a new convenient and secure invagination procedure for pancreaticojejunostomy. METHODS: We performed our new procedure during pancreatoduodenectomy in 15 consecutive patients (7 men, 8 women). The features of the procedure are as follows. First, it is performed using only four sutures. Second, the pancreas stump is invaginated into the jejunum, mainly by two sutures that penetrate the parenchyma and are continuously purse-string sutured to the jejunum. Third, all needle holes on the surface of the pancreas are covered with the jejunal wall. RESULTS: Eight patients were classified as showing no pancreatic fistula, and seven displayed a grade A fistula, according to the International Study Group on Pancreatic Fistula criteria. The median operating time for these 15 patients using the present procedure was about 60 min shorter than that for the previous nine patients who underwent duct-to-mucosa pancreaticogastrostomy in our hospital. CONCLUSIONS: The present method allows pancreaticojejunostomy to be performed swiftly and conveniently.

Inadvertent Ingestion of a Press-Through Package Causing Perforation of the Small Intestine within an Incisional Hernia and Panperitonitis.

A 90-year-old woman was admitted to the emergency department of our hospital with abdominal pain and a fever of up to 39°C. She had a history of hysterectomy about 30 years previously, and redness and swelling were seen at the abdominal median scar. Serum biochemistry showed minor elevation of C-reactive protein and creatine phosphokinase. Abdominal computed tomography (CT) showed an edematous intestinal tract image over the median abdominal wall. Incarcerated incisional hernia and intestinal necrosis were suspected. Therefore, emergency surgery was performed. On laparotomy, abundant purulent ascitic fluid was found. The small intestine was incarcerated about 100 cm orally from the terminal ileum, and a 2-mm perforation was present in the incarcerated small intestine. In addition, some white areas measuring 1 mm were found in the small intestinal wall. A press-through package (PTP) of a tablet was confirmed in the intestinal tract near the perforated area. We removed the PTP through the perforation and performed direct suture. Postoperatively, we retrospectively reviewed the CT image and found a high-density shadow which seemed to represent the PTP.

Long-term survival of resected advanced gastric cancer with hepatic and pancreatic invasion.

A 64-year-old man was transferred to our division with a suspicion of gastric cancer. Computed tomography showed widespread irregular thickening of the stomach walls close to the liver and pancreas. Gastrointestinal fiberscopy showed a type 5 tumor in the upper to lower stomach, histologically diagnosed as tubular adenocarcinoma. Gastric cancer with hepatic and pancreatic invasion was diagnosed. Distant metastasis was not proven and complete resection was planned. At laparotomy, the tumor showed general expanding growth and invasion through the lateral segment of the liver and pancreas. Total gastrectomy and combined resection of the distal pancreas, spleen and left segment of the liver were performed. Hepatic and pancreatic invasion and lymph node metastasis were microscopically proven. Pancreatic fistula occurred postoperatively. On postoperative days 40, he was discharged. He received two cycles of adjuvant tegafur/gimeracil/oteracil chemotherapy. He has had no sign of recurrence for 7 years and 8 months.

Intrapulmonary cellular schwannoma.

A 75-year-old asymptomatic woman was admitted to our hospital after an abnormal shadow was found on a chest roentgenogram. Chest computed tomography showed a round mass in the right lower lobe. Magnetic resonance imaging showed the mass with high signal intensity on T2-weighted images and intermediate signal intensity on T1-weighted images. Fluorine-18-fluorodeoxyglucose-positron emission tomography showed high fluorine-18-fluorodeoxyglucose accumulation in the mass. A lobectomy was performed thoracoscopically. The pathologic diagnosis was cellular schwannoma. Immunohistochemical staining demonstrated the presence of S-100 protein, and the Ki67 labeling index was 12%. We present this case of intrapulmonary cellular schwannoma, which is extremely rare.

Endobronchial actinomycosis associated with a foreign body--successful short-term treatment with antibiotics--.

Primary endobronchial actinomycosis is a very rare condition. We report herein the case of a healthy 66-year-old woman who presented with right lower lobe endobronchial actinomycosis associated with aspiration of a foreign body, which was presumed to be a fish bone swallowed 28 months previously. The patient achieved complete clinical and radiological recovery after removal of the foreign body and 1-month antibiotic therapy of oral amoxycillin. Our experience in the management of this patient should help clinicians to realize the importance of bronchoscopic investigation and the management of this rare but treatable condition.