A case report of anaplastic carcinoma with osteoclast-like giant cells arising in the pancreatic body.

The patient is a 58-year-old woman. She was referred to our hospital following a computed tomography scan that revealed a 2-cm tumor-like lesion in the pancreatic body. Endoscopic ultrasound fine-needle aspiration examination revealed a suspected undifferentiated carcinoma with pleomorphic type. The patient was diagnosed with anaplastic carcinoma of the pancreas (ACP) and underwent distal pancreatectomy with lymph nodes dissection. The resected body and tail of the pancreas had a nodular tumor measuring 30 mm in diameter. Histologically, the main lesion of the tumor showed well-differentiated adenocarcinoma, and diffuse proliferation of atypical short spindle cells and round cells accompanied by multinucleated giant cells aggregation was observed around the tubular structure; hence, it was diagnosed with ACP. The postoperative course was uneventful, and the patient was discharged 14 days after the operation. It has already been about 5 years since the surgery, and although the tumor has recurred, the patient is still alive and undergoing chemotherapy.

Three-incision robotic major lung resection for cancer.

BACKGROUND: Regardless of the current trend in reduced port surgery, robotic surgery generally requires multiple (≥4) skin incisions for robotic arms and patient-side surgeons. In addition, the use of multiple arms results in interreference between the arms and the patient-side surgeon. In the current study, we reviewed our initial experience of a less invasive robotic approach for lung cancer. METHODS: We used 3 arms of the Da Vinci Xi system in an original manner: the camera was set at the most ventral arm for patients and the forceps for right and left hands were set at the more dorsal arms. We made a 4-cm incision in the eighth intercostal space along the middle-axillary line for the insertion of 2 ports for a camera and forceps. This window was eventually used for the extraction of the resected lobes. In addition, we made 1-cm incision along the posterior-axillary line for the remaining arm, and a 1.5-cm incision along the anterior-axillary line for a utility window for the patient-side surgeon. RESULTS: Our port setting contributed to preventing interference between the 2 adjacent arms (camera and forceps), as well as to improving the performance of the patient-side surgeon who does not experience interference from the robotic arms. During the initial experiences of 39 patients, the same procedure was successfully completed by 3 different console surgeons. There were no catastrophic events during the operations or in the 90-day postoperative period, although we experienced 2 open conversions (5%) for noncritical bleeding. CONCLUSIONS: We established a 3-incision robotic surgery for lung cancer, which in addition to being patient-friendly, may facilitates collaboration between the console-surgeon and patient-side surgeon without compromising the performance of the console surgeon.

An extremely rare case with right superior pulmonary vein translocation.

BACKGROUND: There have been a number of reports on pulmonary venous anomalies. However, most of the reports focused on the anatomical branching pattern of the peripheral pulmonary veins. CASE PRESENTATION: We report a 75-year-old female whose right superior pulmonary vein V1 existed dorsal to the right main pulmonary artery and V2+3 existed dorsal to V4+5. Thus, we could not find V1 and V2+3 in the hilum just after a thoracotomy to perform right upper lobectomy for lung cancer. Thus, the right main pulmonary artery and the superior trunk (A1+3) were exposed without cutting the superior pulmonary vein. CONCLUSION: There has been no report so far regarding this type of pulmonary vein translocation. Preoperative three-dimensional computed tomography images were helpful to identify this variant.

Targeted Therapy Followed by Cytotoxic Chemotherapy in Preoperative Patients With Locally Advanced Lung Adenocarcinoma.

BACKGROUND: Although oncogene-targeted therapy is a first-line treatment for advanced, unresectable lung adenocarcinoma harboring a target gene mutation, its effect on potentially resectable, locally advanced lung adenocarcinoma remains unclear. PATIENTS AND METHODS: Ten patients with clinically diagnosed stage III lung adenocarcinoma harboring a target gene mutation were enrolled in the current feasibility study of targeted therapy followed by cytotoxic chemotherapy (platinum and pemetrexed) before radical surgery. RESULTS: Complete resection was accomplished in all nine patients who went on to surgery (one patient refused surgery), and all of these patients recovered without major postoperative complications. Overall, almost all of the patients who underwent surgery remain disease-free after a median follow-up of 22 months since the initial treatment, with only one patient dying of recurrence. CONCLUSION: Radical surgery after the sequential use of cytostatic and cytotoxic drugs resulted in a favorable short-term outcome.

Computed tomography-guided thoracoscopic debridement for multiple loculated organizing empyema: a case report.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) for organizing empyema is challenging because fibrous septa and peel within the cavity are thickened and hardened. Some patients have multiple isolated empyema cavities that require debridement individually because firm intrathoracic adhesion was developed during this phase. If the debridement was incomplete as a result of worrying about an accidental injury of the surrounding organ, additional interventions may be required due to the persistent empyema cavity or insufficient expansion of the ipsilateral lung. We here describe a representative case with multiple loculated organizing empyema that could safely and reliably perform VATS debridement under C-arm cone-beam computed tomography (CBCT). CASE PRESENTATION: A 67-year-old woman was admitted to our department for the treatment of right empyema. Chest computed tomography showed fluid collection in three independent spaces within the right thoracic cavity. It was assumed that a firm adhesion between the lung and chest wall was developed because about 7 weeks passed since the onset. Therefore, we decided to use CBCT to completely debride three empyema cavities separately by VATS. One cavity was only in a narrow range with the chest wall, and it was located on the back of cost rib cartilage. By clicking any intended anatomical structures on CBCT images, the position was readily depicted by lase projection on the body surface, which helped to place the best skin incision. Moreover, in other cavities, CBCT after initial debridement showed insufficiently dissected cavity. Additional debridement resulted in a successful shrinkage of the empyema cavity. CONCLUSION: We believe that VATS debridement under CBCT guidance is one of the useful treatment options for multiple loculated organizing empyema.

Thoracoscopic en bloc resection of left upper lobe lung cancer.

In this video tutorial we demonstrate our procedure for en bloc resection of the left upper lobe and the regional lymph nodes via video-assisted thoracic surgery in patients with primary lung cancer and outline some key surgical points. First, the operation should start with dissection of the posterior portion of the hilar and lower paratracheal nodes, which will provide excellent visualization of the left recurrent laryngeal nerve and also facilitate dissection of the subaortic and para-aortic (aorto-pulmonary) nodes. Second, the lower paratracheal nodes and aorto-pulmonary nodes should be mobilized together with their dominant lymphatic drainage pathways from the left upper lobe. During this procedure, care must be taken not to divide the peribronchial lymphatic pathway toward the lower paratracheal nodes or the subpleural lymphatic pathway toward the aorto-pulmonary nodes.  By following these guidelines, the left upper lobe and the regional lymph nodes can be resected en bloc without any division of their lymphatic connection. We believe that this procedure will help prevent pleural dissemination as well as prevent the surgeon's missing any metastatic lymph nodes.

Expression of Bone Morphogenetic Protein-7 Significantly Correlates With Non-small Cell Lung Cancer Progression and Prognosis: A Retrospective Cohort Study.

BACKGROUND: Bone morphogenetic protein-7 (BMP-7) is a signaling molecule belonging to the transforming growth factor-ß superfamily. Recent studies have demonstrated that BMP-7 is expressed in various human cancers and plays an important role in the progression of their cancers. The purpose of this study was to investigate the clinicopathologic and prognostic impact of BMP-7 expression in clinical samples of non-small cell lung cancer. METHODS: This study enrolled 160 patients with non-small cell lung cancer who underwent complete resection. Expression of BMP-7 in cancer tissue was evaluated by immunohistochemistry. Correlations between expression of BMP-7 and clinicopathologic factors and prognosis were analyzed. RESULTS: In non-small cell lung cancer, BMP-7 expression was identified not only in cell membranes but also in the cytoplasm of cancer cells. Expression of BMP-7 correlated with p-T (P = .047), N factor (P = .013), and p-stage (P = .046). Overall survival rate was significantly lower in the BMP-7-positive group than in the BMP-7-negative group (P = .004). Multivariate analysis indicated that BMP-7 expression was one of the independent prognosis factors of overall survival (P = .021). Furthermore, among patients with postoperative recurrence (n = 58), the BMP-7-positive group (n = 29) had a significantly poorer prognosis than the BMP-7-negative group (n = 29) (P = .012). CONCLUSIONS: Expression of BMP-7 in non-small cell lung cancer was correlated with clinicopathologic factors and poorer prognosis. BMP-7 expression may be a useful predictor of aggressive activity of tumor behavior and postoperative outcome of patients with non-small cell lung cancer.

Thoracoscopic en bloc resection of left upper lobe lung cancer.

In this video tutorial we demonstrate our procedure for en bloc resection of the left upper lobe and the regional lymph nodes via video-assisted thoracic surgery in patients with primary lung cancer and outline some key surgical points. First, the operation should start with dissection of the posterior portion of the hilar and lower paratracheal nodes, which will provide excellent visualization of the left recurrent laryngeal nerve and also facilitate dissection of the subaortic and para-aortic (aorto-pulmonary) nodes. Second, the lower paratracheal nodes and aorto-pulmonary nodes should be mobilized together with their dominant lymphatic drainage pathways from the left upper lobe. During this procedure, care must be taken not to divide the peribronchial lymphatic pathway toward the lower paratracheal nodes or the subpleural lymphatic pathway toward the aorto-pulmonary nodes.  By following these guidelines, the left upper lobe and the regional lymph nodes can be resected en bloc without any division of their lymphatic connection. We believe that this procedure will help prevent pleural dissemination as well as prevent the surgeon's missing any metastatic lymph nodes.

Detection of alternative subpleural lymph flow pathways using indocyanine green fluorescence.

PURPOSE: Pulmonary lymphatic fluid predominately flows along the bronchi. However, there are reports suggesting that an alternative lymphatic pathway exist, which may result in skip metastases. The aim of this study was to evaluate the subpleural lymph flow in vivo using indocyanine green (ICG) fluorescence. METHODS: One hundred cases were enrolled. ICG was injected into the macroscopically healthy subpleural space. Intraoperative fluorescence images were then observed in real time. RESULTS: ICG fluorescence was observed moving through subpleural channels in 58/100 cases. ICG flowed into adjacent lobes over interlobar lines in 18 cases and flowed from the visceral pleura directly into the mediastinum in 5 cases. The frequency of mediastinal detection without hilar lymph node detection was significantly higher in the left lung compared to the right (p < 0.05). The subpleural lymph flow detection rates were significantly lower in patients with smoking pack-years ≥ 40 than those with < 40 (p < 0.05). CONCLUSIONS: The flow of lymphatic fluid directly into the mediastinum suggests one mechanism of skip metastasis. In addition, the reduction of the subpleural lymph flows in smokers with ≥ 40 pack-years suggests that smoking might modify lymph flow patterns. These findings may assist in selecting the optimal therapy for patients with possible skip metastasis.

[Metastatic Lung Tumor Diagnosed as Primary Lung Cancer due to its Accompanying Lesion Mimicking Atypical Adenomatous Hyperplasia by Intraoperative Needle Biopsy Findings;Report of a Case].

We reported a case of metastatic lung tumor, which was suspected as being a primary lung cancer because of its accompanying lesion mimicking atypical adenomatous hyperplasia(AAH) based on intraoperative needle biopsy findings. AAH is a preinvasive lesion or marginal lesion of primary lung cancer that is not accompanied by metastatic tumor. However, it needs to be distinguished pathologically from secondary changes of inflammation or fibrosis. In our case, the needle biopsy revealed AAH-like pathological findings, which indicates a primary lung cancer, and the standard lobectomy with lymph node dissection was performed, however, the final diagnosis turned out to be metastatic tumor. The rapidly enlarging tumor led to surrounding obstructive pneumonitis, which may have caused pathological changes mimicking AAH findings. In the case of obstructive pneumonitis, we must be careful to diagnose AAH, in addition to decisions about the surgical procedure especially when based on frozen section diagnosis.

Pulmonary Metastasectomy 31 Years After Surgery for Renal Cell Carcinoma.

An 82-year-old man underwent a left upper lobectomy for a solitary tumor on suspicion of lung cancer. Histopathologic findings of the resected specimen showed clear cell renal cell carcinoma, which was diagnosed as a metastasis from kidney cancer concealed for 31 years after nephrectomy. The Ki-67 labeling index of the metastatic tumor was high (36.1%). A few cases of recurrent renal cell carcinoma after a long interval from initial diagnosis have been seen. However, pulmonary metastasectomy more than 30 years after radical nephrectomy for renal cell carcinoma has not been reported. This remarkable case provides new and valuable clinical insights into metastatic renal cell carcinoma.

Successful closure of a tracheocutaneous fistula after tracheostomy using two skin flaps: a case report.

A tracheocutaneous fistula may develop when a tracheostomy orifice epithelializes during a prolonged course of healing or undernutrition. Various techniques for closing such fistulae have been reported. However, a standard procedure has not yet been established. We, herein, present a case involving a 35-year-old woman who developed a tracheocutaneous fistula after tracheostomy. We closed the fistula using two skin flaps to cover the tracheal lumen and skin defect, respectively. The advantage of this technique is that it allows the tracheal lumen to be covered by inversed skin epithelium and ensures that the suture line of the skin does not match up with that of the subcutaneous tissue.

Phrenic nerve reconstruction in complete video-assisted thoracic surgery.

OBJECTIVES: Primary or metastatic lung cancer or mediastinal tumours may at times involve the phrenic nerve and pericardium. To remove the pathology en bloc, the phrenic nerve must be resected. This results in phrenic nerve paralysis, which in turn reduces pulmonary function and quality of life. As a curative measure of this paralysis and thus a preventive measure against decreased pulmonary function and quality of life, we have performed immediate phrenic nerve reconstruction under complete video-assisted thoracic surgery, and with minimal additional stress to the patient. This study sought to ascertain the utility of this procedure from an evaluation of the cases experienced to date. METHODS: We performed 6 cases of complete video-assisted thoracic surgery phrenic nerve reconstruction from October 2009 to December 2013 in patients who had undergone phrenic nerve resection or separation to remove tumours en bloc. In all cases, it was difficult to separate the phrenic nerve from the tumour. Reconstruction involved direct anastomosis in 3 cases and intercostal nerve interposition anastomosis in the remaining 3 cases. RESULTS: In the 6 patients (3 men, 3 women; mean age 50.8 years), we performed two right-sided and four left-sided procedures. The mean anastomosis time was 5.3 min for direct anastomosis and 35.3 min for intercostal nerve interposition anastomosis. Postoperative phrenic nerve function was measured on chest X-ray during inspiration and expiration. Direct anastomosis was effective in 2 of the 3 patients, and intercostal nerve interposition anastomosis was effective in all 3 patients. Diaphragm function was confirmed on X-ray to be improved in these 5 patients. CONCLUSIONS: Complete video-assisted thoracic surgery phrenic nerve reconstruction was effective for direct anastomosis as well as for intercostal nerve interposition anastomosis in a small sample of selected patients. The procedure shows promise for phrenic nerve reconstruction and further data should be accumulated over time.

A case of resected plasma cell type castleman's disease with intramediastinal lymph nodes spread.

We report a case of resected plasma cell (PC) type Castleman's disease (CD) in a 21-year-old female who had an anterior mediastinal mass with additional surrounding nodules. She was aware of low-grade fever and fatigue for several years. From hematological and biochemical examinations, elevated inflammatory responses and levels of serum IgG (2908 mg/dL) and IL-6 (22.2 pg/mL) were observed. She was diagnosed with PC type CD by needle biopsy under computed tomography (CT) guidance. It was thought that the lesion was localized in the mediastinum. Then, mediastinal adipose tissue including the tumor, additional nodules and thymus were removed. The histological findings of PC type CD were found not only in the main tumor but also in surrounding swollen lymph nodes. Her symptoms improved and inflammatory responses decreased after the operation. No recurrence has been observed for 5 years after the operation.

EGFR mutations and human papillomavirus in lung cancer.

Our previous study reported a frequent detection of human papillomavirus (HPV) genome in primary lung adenocarcinomas of the recurrent patients who were responsive to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, suggesting that HPV presence in lung cancer may be related to a genetic background related to EGFR mutations. The present study examined the association between the HPV presence and mutations in exons 19 and 21 of EGFR gene in Japanese lung cancer patients. Thirteen (31%) out of 42 cases had EGFR mutations. Although these mutations were tended to be observed in females, non-smokers, or adenocarcinomas, there was no statistically significant associations. HPV DNA was found in 7/42 (17%) lung tumors. The frequency of HPV presence did not differ in histological types. The presence of HPV DNA was significantly related to EGFR mutations (P=0.021), especially in adenocarcinomas of the lung (P=0.014). HPV-positive lung tumors accounted for 38% and 7% of those with and without EGFR mutations, respectively. Our results suggest that EGFR mutations are associated with HPV presence in Japanese patients with lung cancer.

Nuclear expression of 14-3-3 sigma is related to prognosis in patients with esophageal squamous cell carcinoma.

BACKGROUND: The 14-3-3 sigma gene is transcriptionally activated by p53 after DNA damage and facilitates DNA repair during G2 arrest. The present study analyzed the clinical significance of 14-3-3 sigma expression in esophageal squamous cell carcinoma. PATIENTS AND METHODS: The relationship between 14-3-3 sigma and p53 expressions was investigated immunohistochemically in surgical specimens of primary tumors from 248 patients with esophageal squamous cell carcinoma. RESULTS: The positive expression rates of cytoplasmic and nuclear 14-3-3 sigma were 61.7% and 41.9%, respectively. There was no correlation between 14-3-3 sigma and p53 expression. Positive expression of nuclear 14-3-3 sigma was significantly correlated with depth of invasion, stage, lymphatic invasion, and poor prognosis. Multivariate analysis indicated that negative expression of nuclear 14-3-3 sigma was an independent prognostic factor. CONCLUSION: Evaluation of the expression of nuclear 14-3-3 sigma proteins may be useful in predicting the outcome in patients with esophageal squamous cell carcinoma.

Improvement in radiosensitivity using small interfering RNA targeting p53R2 in esophageal squamous cell carcinoma.

Chemoradiation therapy (CRT), a combination of X-ray irradiation and anticancer agents as a radiosensitizer, has been found to be an effective treatment for esophageal cancer and has been linked to p53 genetics. The p53 gene family regulates cell-cycle arrest, apoptosis and DNA damage repair. A recently identified ribonucleotide reductase, p53R2, is directly regulated by p53 in the supply of nucleotides for repairing damaged DNA. In the present study, we investigated the improvement in radiosensitivity of human esophageal squamous cell carcinoma (ESCC) cell lines using p53R2 small interfering RNA (siRNA). p53R2 expression in ESCC cells (TE-8) with or without transfection of p53R2 siRNA was examined by Western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR). The radiosensitivity of TE-8 cells was also measured by cell survival assay. In addition, we investigated the relationship between the expression of p53R2 mRNA in the biopsy specimens of untreated primary tumors and the efficacy of CRT, using RT-PCR. The expression of p53R2 was amplified after X-ray irradiation (14 Gy) and diminished after X-ray irradiation following the transfection of p53R2 siRNA in TE-8 cells. The radiosensitivity of the TE-8 cells significantly improved following the transfection of p53R2 siRNA. In the clinical study, a significantly lower p53R2 mRNA expression was detected in the effective response cases. We demonstrated that p53R2 is associated with the radiosensitivity of ESCC cell lines, and that p53R2 expression is reduced after X-ray irradiation following the transfection of p53R2 siRNA. This protocol could potentially improve the efficacy of radiation therapy.

alpha-catenin is a significant prognostic factor than E-cadherin in esophageal squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: The purpose of the present study was to analyze clinicopathologic variables in esophageal squamous cell carcinoma (ESCC) according to expression of E-cadherin and alpha-catenin which play an important role in cell adhesion. METHODS: We immunohistochemically examined E-cadherin and alpha-catenin in 205 patients with ESCC. The expression results were classified into two groups: preserved expression (+) and reduced expression (-). RESULTS: The incidence of E-cadherin (-) and alpha-catenin (-) was 52% and 54%, respectively and significantly related each other. For both E-cadherin and alpha-catenin, reduced expression was significantly related to tumor depth, nodal metastasis, stage, recurrence, and prognosis. In the E-cadherin (+) group, the alpha-catenin (+) and alpha-catenin (-) patients differed significantly in tumor depth, nodal metastasis, stage, hematogenous and lymphatic recurrences (P < 0.001, <0.001, <0.001, <0.001 and =0.007, respectively). According to coexpression of E-cadherin and alpha-catenin, the prognosis was best in patients with E-cadherin (+) and alpha-catenin (+), and worst in patients with E-cadherin (-) and alpha-catenin (-). Multivariate analysis revealed that alpha-catenin expression was an independent prognostic factor. CONCLUSIONS: The examination of expression of E-cadherin and especially alpha-catenin is useful for predicting lymph node metastasis and clinical outcome of ESCC.

Overexpression of vascular endothelial growth factor-C correlates with lymph node micrometastasis in submucosal esophageal cancer.

Lymph node metastasis, including lymph node micrometastasis (LMM), is one of the most important prognostic factors in esophageal squamous cell carcinoma (ESCC). Vascular endothelial growth factor C (VEGF-C) plays a key role in the process of lymphangiogenesis. We examined VEGF-C expression and tumor microvessel density of the primary tumors in ESCC and analyzed relationships between VEGF-C expression and clinicopathologic findings including LMM in submucosal ESCC. The subjects were 87 patients with submucosal ESCC. Immunohistochemical staining of VEGF-C and CD34 was performed with primary tumors, and staining of cytokeratin was performed with dissected lymph nodes. Microvessel density was calculated from CD34 expression, and LMM was detected by cytokeratin staining. VEGF-C overexpression significantly correlated with depth of tumor invasion, lymphatic invasion, and lymph node metastasis (P < 0.05, P < 0.0001, and P < 0.0001, respectively). High microvessel density also correlated with lymphatic invasion and lymph node metastasis (P < 0.005 and P < 0.05, respectively). LMM was detected in 8 cases and 14 lymph nodes by cytokeratin staining. VEGF-C overexpression and high microvessel density were found in tumors with lymph node metastasis and/or LMM, compared with tumors without nodal metastasis or LMM (P < 0.0001 and P < 0.01, respectively). The present findings indicate that in ESCC with submucosal invasion, VEGF-C overexpression of the primary tumor is a strong high risk factor for lymph node metastasis, including LMM.