Noriaki Sakakura

Assessment of Long-Term Postoperative Pain in Open Thoracotomy Patients: Pain Reduction by the Edge Closure Technique

BACKGROUND Long-term postoperative pain in open thoracotomy patients could be related to injured intercostal nerves, and several methods have been devised to protect these nerves. METHODS We retrospectively reviewed 184 consecutive patients who underwent posterolateral or anteroaxillary thoracotomy. Postoperative pain was routinely evaluated using an 11-point numerical pain rating scale (0 [no pain] to 10 [most severe pain]) at 1 to 2 weeks; 2 weeks to 1 month; and 1 to 2, 2 to 4, 4 to 6, 6 to 9, and 9 to 12 months after surgery. The following steps were considered to protect the intercostal nerves. During chest retraction, an intercostal muscle flap was harvested before using the retractor to prevent compression of the cranial intercostal nerve in posterolateral thoracotomy patients who needed buttressing of the bronchial stump. During closure, the thin space between the inferior edge of caudal rib and the intercostal neurovascular bundle was sutured to prevent strangulation of the intercostal nerve and vessels on the caudal side (edge closure technique). Subjects included 141 posterolateral and 43 anteroaxillary thoracotomies, 72 intercostal muscle flaps, and 87 conventional closures and 97 edge closures. RESULTS During a year postoperatively, posterolateral thoracotomy patients experienced more pain (range, 1.2 to 4.6) than anteroaxillary thoracotomy patients (range, 1.1 to 3.7; p=0.038 for all periods). Patients with the intercostal muscle flap tended to experience less pain than those without the flap during the first month postoperatively. The scores of patients having edge closure (range, 0.9 to 3.8) were significantly lower than those of patients undergoing conventional closure (range, 1.6 to 5.1; p<0.001 for all periods). CONCLUSIONS The edge closure technique, which preserved the caudal intercostal neurovascular bundle, successfully reduced pain.

Transformation to Sarcomatoid Carcinoma in ALK-Rearranged Adenocarcinoma, Which Developed Acquired Resistance to Crizotinib and Received Subsequent Chemotherapies

Journal of Thoracic Oncology ® • Volume 8, Number 8, August 2013 CASE REPORT A 32-year-old man presented with cough and bloody sputum. Computed tomography (CT) showed a mass in the S6 segment and diffuse consolidation throughout the lower lobe of the left lung. Transbronchial lung biopsy revealed adenocarcinoma (AC) with lymphangiosis. Immunohistochemistry (IHC) showed anaplastic lymphoma kinase (ALK) protein expression, and break-apart fluorescent in situ hybridization showed ALK gene rearrangement. First-line chemotherapy with cisplatin and docetaxel was started in June 2010. After tumor progression, the patient was enrolled in the randomized trial (PROFILE 1007) and was allocated to the pemetrexed arm. Subsequently, he was enrolled in PROFILE 1005 trial to receive crizotinib in July 2011 (Fig. 1A). After a partial response was observed, a nodule in the S9 segment developed in size to 2 cm, in February 2012 (Fig. 1B, C), and crizotinib was discontinued. CT scans performed after four cycles of carboplatin and gemcitabine showed a mixed response, with improvements in lymphadenopathy and lymphangiosis, but progression of the mass in S9. CT-guided core-needle biopsy revealed ALK-positive atypical cells, but it was impossible to distinguish histological types because of degeneration and necrosis. Thereafter, carboplatin, paclitaxel, and bevacizumab were administered, but the same mixed response was observed. The mass in S9 increased rapidly in size and reached 7 cm in August 2012 (Fig. 1D). Left lower lobectomy was performed in September 2012. The primary tumor in S6 was diagnosed as AC-positive for thyroid transcription factor (TTF)-1 immunostaining, whereas the tumor in S9 was TTF-1 negative sarcomatoid carcinoma (Figs. 2A-C, 3A-C). ALK was positive with IHC in both tumors, and fluorescent in situ hybridization revealed high-level gene amplification of the ALK gene only in the sarcomatoid carcinoma (Figs. 2D, E, 3D, E). Reverse-transcriptase polymerase chain reaction (RT-PCR) revealed the same variant of echinoderm microtubule-associated protein-like 4-ALK (E13; A20). Moreover, in the sarcomatoid carcinoma, DNA sequencing revealed no additional resistance point mutations from ALK exon 20 to exon 23.

The Significance of the Prognostic Nutritional Index in Patients with Completely Resected Non-Small Cell Lung Cancer

Objectives Immunological parameters and nutritional status influence the outcome of patients with malignant tumors. A prognostic nutritional index, calculated using serum albumin levels and peripheral lymphocyte count, has been used to assess prognosis for various cancers. This study aimed to investigate whether this prognostic nutritional index affects overall survival and the incidence of postoperative complications in patients with completely resected non-small cell lung cancer. Methods We retrospectively reviewed the medical records of 409 patients with non-small cell lung cancer who underwent complete resection between 2005 and 2007 at the Aichi Cancer Center. Results The 5-year survival rates of patients with high (≥50) and low (<50) prognostic nutritional indices were 84.4% and 70.7%, respectively (p = 0.0011). Univariate analysis showed that gender, histology, pathological stage, smoking history, serum carcinoembryonic antigen levels, and prognostic nutritional index were significant prognostic factors. Multivariate analysis identified pathological stage and the prognostic nutritional index as independent prognostic factors. The frequency of postoperative complications tended to be higher in patients with a low prognostic nutritional index. Conclusions The prognostic nutritional index is an independent prognostic factor for survival of patients with completely resected non-small cell lung cancer.

Fluid Drainage and Air Evacuation Characteristics of Blake and Conventional Drains Used After Pulmonary Resection

BACKGROUND The Blake drain (BD) has recently begun to be used as a chest tube after pulmonary resection; however, its fluid drainage and air evacuation characteristics remain unclear. We compared the performance of the 19F BD with that of the 32F conventional drain (CD). METHODS We studied 148 consecutive patients (74 with BD; 74 with CD) who underwent pulmonary resection. Postoperative drainage rates (daily drainage and total drainage) were analyzed to assess fluid drainage. Air evacuation was evaluated to determine whether subcutaneous emphysema or insufficient residual lung expansion developed when air leakage occurred. The BD group was initially managed with water seal or suction, whereas the CD group was managed with water seal. Furthermore, we experimentally measured the evacuation pressure required to expel a constant volume of air through various chest tubes to determine basic air evaluation performance of the tubes. RESULTS Drainage rates on the operative day were significantly lower in the BD group than in the CD group, but were similar in both groups on the following day with greater variation in the water-sealed BD group. Among cases with air leakage, air evacuation insufficiency was more frequent in the BD group (16 of 22, 73%) than in the CD group (4 of 17, 24%; p = 0.004). The experiment revealed that air evacuation performance of the 19F BD was equivalent to that of the 12F CD, indicating that the BD requires higher intrathoracic pressure for air evacuation. CONCLUSIONS Suction is required for the BD to obtain fluid drainage performance comparable to that of the water-sealed CD. When air leakage occurs, air evacuation by the BD tends to be insufficient, irrespective of suction conditions.

Subcategorization of Lung Cancer Based on Tumor Size and Degree of Visceral Pleural Invasion

BACKGROUND Lung cancer staging system proposed in 2007 adopts detailed tumor size cut-off values. Alternatively, visceral pleural invasion is deemed an important prognosticator, but has not been easily incorporated into the staging system. METHODS We studied 1,245 patients with resected nonsmall-cell lung cancer. Among patients with current pathologic stage IB (pT2N0M0) disease, those with worse prognosis were reclassified as stage IIA based on tumor size and degree of visceral pleural invasion defined by the Japan Lung Cancer Society: P0 = no pleural involvement beyond elastic layer; P1 = infiltration beyond elastic layer without exposure to pleural surface; and P2 = exposure to pleural surface. RESULTS The current pT2 category was divided into five groups based on size (<or= 3, > 3 to <or= 5, and > 5 cm) and degree of visceral pleural invasion (P0-1 or P2). Five-year survival rates in patients with P0-1 tumors greater than 3 cm to 5 cm or less were significantly better (59.5%) than those with tumors greater than 5 cm or P2 tumors (37.5% to 47.3%; p = 0.0014); we defined these two groups as T2a and T2b, respectively, and classified T2aN0M0 as stage IB and T2bN0M0 as stage IIA together with the current T1N1M0. Five-year survival rates for the modified IB and IIA diseases were 70.6% and 60.4%, respectively (p = 0.0414). CONCLUSIONS Modified subcategorization of the pT2 category resulted in T2a (> 3 to <or= 5 cm and P0-1) and T2b (> 5 cm or P2). Detailed assessment of the degree of visceral pleural invasion could provide more information on tumor characteristics and complement the pathologic staging of lung cancer.

Subcategorization of Resectable Non-Small Cell Lung Cancer Involving Neighboring Structures

BACKGROUND Although the prognoses of patients with resectable lung cancer involving neighboring structures vary, the current tumor-nodes-metastasis (TNM) classification system does not elucidate criteria for tumor subcategorization. METHODS We studied 196 consecutive patients who underwent resection of non-small cell lung cancer involving neighboring structures at the Aichi Cancer Center Hospital and were diagnosed as pathologic T3 diseases using the current staging system. Tumors were divided into six groups based on the involved neighboring structures: parietal or mediastinal pleura, subpleural soft tissue, ribs, main bronchus, pericardium, and diaphragm. RESULTS The overall 5-year survival rate was 39.8%. The survival rates for the six groups were: pleura (n = 62), 54.8%; subpleural soft tissue (n = 50), 30.0%; rib (n = 25), 24.0%; main bronchus (n = 33), 48.5%; pericardium (n = 14), 21.4%; and diaphragm (n = 12), 33.3%. The combined pleura and bronchus groups (n = 95) demonstrated significantly better survival outcome than the other groups (n = 101): 52.6% and 27.7%, respectively (p = 0.0002). Furthermore, among 108 patients with pT3N0 (stage IIB) disease, the prognostic difference between the pleura and bronchus groups (n = 50) and the other groups (n = 58) was significant: 64.0% and 25.9%, respectively (p < 0.0001). Similar results were confirmed in patients with complete resection (n = 159). CONCLUSIONS Subcategorization of resectable lung cancer involving neighboring structures resulted in tumor groups infiltrating pleura or main bronchus, and those involving subpleural structures, pericardium, or diaphragm.

Controversy about Small Peripheral Lung Adenocarcinomas: How Should We Manage Them?

In recent years, the clinical use of high-resolution computed tomography has greatly advanced the diagnosis of small lesions of the peripheral lung. Such small lesions are often associated with ground-glass opacity in computed tomography findings. The noninvasive bronchioloalveolar carcinoma component with a replacement growth pattern of alveolar lining cells manifests as ground-glass opacity. Bronchioloalveolar carcinoma is classified as a subset of lung adenocarcinoma, but has a distinct clinical presentation, tumor biology, and favorable prognosis. Most small peripheral lung lesions including bronchioloalveolar carcinoma putatively originate from the peripheral airway epithelium, in which the epidermal growth factor receptor gene is frequently mutated. As with other subsets of non-small cell lung cancer, surgical resection is a potentially curative treatment. For the ground-glass opacity type of tiny lesions, particularly those less than 1 cm in their greatest dimension, the question has been raised whether lobectomy is really needed. Although several authors in Japan suggest the suitability of limited resection including segmentectomy and wedge resection without any nodal dissections for these small lung adenocarcinomas, this procedure should be validated in future clinical trials.

Unique prevalence of oncogenic genetic alterations in young patients with lung adenocarcinoma.

Lung adenocarcinoma in the young is a rare entity, and the oncogenic genetic alterations (GAs) and clinical characteristics associated with this disease are poorly understood. Conversely, it has been demonstrated that young age at diagnosis defines unique biology in other cancers. For this report, the effects of young age on lung adenocarcinoma are reported.

Predictors of indocyanine green visualization during fluorescence imaging for segmental plane formation in thoracoscopic anatomical segmentectomy

BACKGROUND To determine factors predicting indocyanine green (ICG) visualization during fluorescence imaging for segmental plane formation in thoracoscopic anatomical segmentectomy. METHODS Intraoperatively, the intravenous ICG fluorescence imaging system during thoracoscopic anatomical segmentectomy obtained fluorescence emitted images of its surfaces during lung segmental plane formation after the administration of 5 mg/body weight of ICG. The subtraction of regularization scale for calculating the exciting peaks of ICG between the planned segments to resect and to remain was defined as ΔIntensity (ΔI). Variables such as the ratio of forced expiratory volume in 1 s to forced vital capacity (%FEV1.0), smoking index (SI), body mass index (BMI), and low attenuation area (LAA) on computed tomography (CT) took a leading part. RESULTS The formation of the segmental plane was successfully accomplished in 98.6% segments and/or subsegments. SI and LAA significantly affected ΔI levels. The area under the receiver operating characteristic curve for the %FEV1.0, SI, and LAA was 0.56, 0.70, and 0.74, respectively. SI >800 and LAA >1.0% were strong predictors of unfavorable ICG visibility (P=0.04 and 0.01, respectively). CONCLUSIONS Fluorescence imaging with ICG was a safe and effective method for segmental plane formation during thoracoscopic anatomical segmentectomy. In spite of its high success rate, unfavorable visibility may potentially occur in patients who are heavy smokers or those with a LAA (>1.0%) on CT.

Spinal Epidural Hematoma during Anticoagulant Therapy for Pulmonary Embolism: Postoperative Complications in a Patient with Lung Cancer

Spinal epidural hematoma (SEH) is rare but causes neurological disorders. Rapid diagnosis and treatment maximize neurological recovery. We present the case of SEH after lung cancer surgery under epidural and general anesthesia. A 64-year-old man underwent right upper lobectomy. Pulmonary embolism occurred on postoperative day 2. Anticoagulant therapy with fondaparinux and warfarin was started 2 hours after epidural catheter removal and he gradually recovered. On postoperative day 13, the level of prothrombin time-international normalized ratio reached 1.47 and fondaparinux administration was stopped. The next day, he developed back pain and paraplegia, and magnetic resonance imaging revealed a mass between Th4 and Th7 compressing the spinal cord. Emergency decompression laminectomy and hematoma evacuation were performed. After 2.5 months of rehabilitation, he regained almost all motor function and sensation. Late after epidural anesthesia, attention should be paid to possible SEH even though appropriate anticoagulant therapy had been initiated after epidural catheter removal.