Sarawut Kongkarnka

Retrospective Study of ALK Rearrangement and Clinicopathological Implications in Completely Resected Non- small Cell Lung Cancer Patients in Northern Thailand: Role of Screening with D5F3 Antibodies

BACKGROUND Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC) has been intensively studied. The gold standard for ALK detection is FISH, but this is not routinely conducted in clinical practice, so that the IHC method has a role. The aim of this study was to identify the incidence of ALK rearrangement and risk or prognostic factors for ALK positivity using both of IHC and FISH methods. MATERIALS AND METHODS From January 2008 to December 2012, 267 completely resected NSCLC patients in Chiang Mai University Hospital were enrolled in this study. Clinical and pathological variables and outcomes of treatment were retrospectively reviewed. IHC and FISH were used to evaluate ALK rearrangement. Sensitivity and specificity of IHC were analyzed. Multivariable analysis was used to identify clinico-pathological correlations with positive results of IHC and clinical outcomes. RESULTS Twenty-two (8.2%) of 267 specimens were IHC-positive for ALK with intense cytoplasmic staining, whereas only 10 (3.8%) were FISH-positive. Sensitivity, specificity and the positive likelihood ratio with IHC were 80.0%, 94.9%, and 15.8 respectively. Age less than 55 years (RR 4.4, 95%CI 1.78-10.73, p value=0.001) and presence of visceral pleural invasion (VPI) (RR 2.9, 95%CI 1.21-6.78, p value =0.017) were identified as risk factors for ALK rearrangement with FISH. There were no statistically significant differences in other clinical and pathological variables. ALK rearrangement was not a prognostic factor for tumor recurrence or overall survival. CONCLUSIONS The incidences of ALK positivity in completely resected NSCLCs in northern Thailand were 8.2% by IHC and 3.8% by FISH. IHC with mouse monoclonal, Ventana D5F3 antibody can be used as a screening tool before FISH method because of high specificity and high positive likelihood ratio. Age less than 55 years and VPI are risk factors for ALK positivity.

Impact of lymph node management on resectable non-small cell lung cancer patients

BACKGROUND A surgical lung resection with systematic mediastinal lymph node (LN) dissection is recommended by the National Comprehensive Cancer Network guideline. However, the effective number of dissected LNs, stations and positivity is still controversial. The aim of this study is to identify the impact of total numbers, LN stations and positivity of dissected LNs on tumor recurrence and overall death in resectable non-small cell lung cancer (NSCLC). METHODS This prognostic study used a retrospective data collection design. Adult patients with clinical resectable NSCLC who underwent pulmonary resection and mediastinal lymphadenectomy at Chiang Mai University between June 2000 and June 2012 were enrolled in this study. A multilevel mixed-effects parametric survival model was used to identify the effect of numbers, LN stations and positivity of dissected LNs to tumor recurrence and mortality. RESULTS The average number of dissected LNs was 22.7±12.8. Tumor recurrence was found in 51.3% and overall mortality was 43.3%. The number of dissected LNs was a prognostic factor for tumor recurrence [HR 0.98, 95% confidence interval (CI): 0.96-0.99]. There was a significant difference at the cut-pointed value of 11 dissected LNs for tumor recurrence (HR 2.22, 95% CI: 1.26-3.92). Dissection less than 11 nodes and less than 5 stations indicated a poor prognostic factor for tumor recurrence: for 3-4 stations (HR 3.01, 95% CI: 1.22-7.42) and for 1-2 stations (HR 1.96, 95% CI: 1.04-3.72). The positivity of dissected LNs was also a prognostic factor for tumor recurrence and overall mortality (HR 1.01, 95% CI: 1.01-1.02 and HR 1.01, 95% CI: 1.01-1.03, respectively). CONCLUSIONS Eleven or more LN dissection with at least 5 stations influenced recurrent-free survival. Systematic LN dissection (SLND) should be performed not only to identify the positivity of dissected LNs but also to determine an accurate tumor nodal stage. A larger cohort should be further conducted to support these findings.

P2.15-28 Effect of Insurance Types on Tumor Recurrence and Overall Survival in Resectable Non-Small Lung Cancer Patients in Northern Thailand

Background: High-precision three-dimensional (3D) image analysis system has been used for preoperative planning in various fields including thoracic surgery. Such software has made us quite easy to measure lung volume. Change of pulmonary function after surgery has been surveyed in some reports, but there are few reports about lung volume change after surgery. Method: We conducted a retrospective review of 49 patients who underwent lobectomy between January 2014 and June 2016 at General Hospital of Japan Railway Company. We used 3D image analysis system (SYNAPSE VINCENT, Fujifilm Corp, Tokyo, Japan) to calculate lung volume of each patient from computed tomography (CT) images which were taken twice, before surgery and 6 months after surgery. We estimated lung volume change from the difference between those two values. Result: There were 19 right upper lobectomies (RUL), 7 right middle lobectomies (RML), 8 right lower lobectomies (RLL), 5 left upper lobectomies (LUL), and 10 left lower lobectomies (LLL). We performed lobectomies in three different surgical approaches; Thoracotomy (n1⁄45), Hybrid Video-assisted thoracic surgery (VATS) (n1⁄424), Complete VATS (n1⁄420). 7 patients needed pleurodesis after surgery to treat air leakage. The average of total lung volume change was -10.4%. Right lobectomies showed 11.45% decrease of lung volume in average, while left lobectomies showed 5.34% decrease (p1⁄40.18). Decrease ratio seemed to depend on the way of approaches; Thoracotomy was -19.98% and VATS (hybrid and complete) was -8.58% (p1⁄40.12). Volume change of patients who underwent pleurodesis after surgery was -20.37%, while the ratio of the others was -7.84% (p1⁄40.03). Conclusion: VATS seemed to be better in the point of lung volume after lobectomy than thoracotomy. Pleurodesis turned out to reduce lung volume significantly. For furthur study, we will compare lung volume with pulmonary function on a lager aomount of data.

Lung Cancer: Diagnosis and Treatment Approach

Lung cancer is one of the most common causes of cancer death in the world. There are many risk factors for lung cancer including tobacco smoking, chronic lung disease, race and ethnicity, occupational carcinogen exposure, diet and genetic factors. Until now there have been no effective modalities for the early detection of lung cancer. The National Cancer Institute recently released results from its National Lung Screening Trial (NLST) which showed that low dose CT scans compared to chest x-rays can reduce lung cancer mortality by 20 %. For accurate lung cancer staging, multi-modality approaches are used such as positron emission tomography (PET) scan, computed tomography (CT) scan, endobronchial ultrasound (EBUS) biopsy or mediastinoscope biopsy of mediastinal lymph node, pleural tapping procedure, or video-assisted thoracoscopic surgery (VATS). Multi-modality methods have a vital role in lung cancer treatment including surgery, chemotherapy, radiotherapy, targeted therapy and immunotherapy. Anatomical resection and systematic lymphadenectomy is the treatment of choice for early stage lung cancer. Neo-adjuvant chemotherapy is utilized for resectable N2 disease or adjuvant chemotherapy for pathological N2 disease and unresectable advanced disease. Targeted therapies have already been proven as highly effective and less toxic therapies for positive molecular testing in advanced disease.

Intraductal papillary neoplasm of the bile duct: clinicopathological study of 10 cases

Background and aims: Intraductal papillary neoplasm of the bile duct (IPNB) is a new entity of biliary neoplasm that is characterized by predominant intraductal papillary growth with various degrees of malignant transformation. It has better prognosis compared with conventional cholangiocarcinoma. Although IPNB has been recently added to the WHO classification, preoperative diagnosis is still challenging and the classification system might need refinements. Methods: We retrospectively reviewed clinicopathological features of 10 surgically resected cases of IPNB, which were previously diagnosed as intraductal cholangiocarcinoma or papillary adenocarcinoma of the bile duct from 2008 to 2014. Histologic features are classified into intestinal, gastric, pancreaticobiliary, and oncocytic types as described in the literature, together with invasive growth pattern and immunohistochemistry. Results: Eight tumors (80%) were invasive IPNB and two (20%) were non-invasive. All of the non-invasive cases are IPNB with high-grade dysplasia. Three cases (30%) were cystic type which having a communication to the bile duct lumen. Discussion: Intraductal growth type cholangiocarcinoma (invasive IPNB) showed a worse prognosis than IPNB with high-grade dysplasia. Curative resection is the major treatment and an important favorable factor for long-term survival, especially in patients with early-stage. Due to its rarity, a mechanism of histopathogenesis remains to be studied.

Clear Cell Adenocarcinoma of the Renal Pelvis in a Male Patient

Carcinoma of the renal pelvis is an uncommon renal neoplasm. Clear cell adenocarcinoma in the urinary tract is rare and has a histomorphology resembling that of the female genital tract. We herein present a case of clear cell adenocarcinoma of the renal pelvis, which is the first example in a male patient to our knowledge. A 54-year-old man presented with right flank pain. The tumor was associated with renal stones and hydronephrosis and invaded into the peripelvic fat tissue with regional lymph node metastasis. The patient died of metastatic disease six months postoperatively. Histologically, the tumor showed complex papillary architecture lined with clear and hobnail cells. Clear cell adenocarcinoma of the renal pelvis may pose a diagnostic challenge on histological grounds, particularly in the distinction from renal cell carcinoma. The immunohistochemical stains could help confirm the diagnosis. Due to its rarity, an effective treatment regimen remains to be determined.