P-stage IB Research Articles

Is adjuvant chemotherapy for completely resected p-stage IA (>2cm) and stage IB non-small-cell lung cancer beneficial for elderly patients? A large, retrospective cohort study based on real-world data from Japan.

The efficacy of tegafur-uracil as adjuvant chemotherapy for patients with completely resected stage I non-small-cell lung cancer is proven; however, its efficacy for elderly patients remains unclear. Herein, we evaluated the effectiveness of adjuvant chemotherapy for elderly patients with completely resected stage I non-small-cell lung cancer based on real-world Japanese data using propensity score matching. This retrospective study extracted data from a nationwide registry study, performed in 2016, on patients ≥75years who underwent lobectomy with mediastinal nodal dissection for non-small-cell lung cancer in 2010 and were diagnosed with p-stage IA (>2cm) or stage IB non-small-cell lung cancer. We classified the 1294 patients into two groups-Group A, postoperative adjuvant chemotherapy (n=295, 22.8%) and Group N, no adjuvant chemotherapy (n=999, 77.2%)-and analyzed differences in postoperative overall survival between groups. Group A showed no advantage in overall survival over Group N as a whole (hazard ratio: 0.824 [95% confidence interval: 0.631-1.076]), in p-stage IA (hazard ratio: 0.617 [95% confidence interval: 0.330-1.156]) and in p-stage IB (hazard ratio: 0.806 [95% confidence interval: 0.597-1.088]) subsets. Even after propensity score matching, Group A showed no significant advantage in overall survival over Group N as a whole (hazard ratio: 0.975 [95% confidence interval: 0.688-1.381]), in p-stage IA (hazard ratio: 1.390 [95% confidence interval: 0.539-3.586]) and in p-stage IB (hazard ratio: 0.922 [95% confidence interval: 0.633-1.343]). adjuvant chemotherapy for completely resected p-stage IA (>2cm) and stage IB non-small-cell lung cancer showed no benefit for recommendation for elderly patients; considering the risk of adverse events, we do not recommend adjuvant chemotherapy for elderly patients.

Pancreatic ductal adenocarcinoma arising from the pancreatic parenchyma compressed by a huge pancreatic lipoma: a case report

BackgroundPancreatic lipomas (PLs) arising from the adipose tissue in the pancreatic parenchyma are rare among pancreatic tumors. Coexisting pancreatic ductal adenocarcinoma (PDAC) and PLs have not been previously reported. Herein, we report a case of PDAC arising from the pancreatic parenchyma with chronic pancreatitis compressed by a large PL.Case presentationThe patient was a 69-year-old male. He had been diagnosed with a PL using computed tomography (CT) 12 years previously. The tumor had been slowly growing and was followed up carefully because of the possibility of well-differentiated liposarcoma. During follow-up, laboratory data revealed liver damage and slightly elevated levels of inflammatory markers. Contrast-enhanced CT revealed the previously diagnosed 12 cm pancreatic head tumor and an irregular isodensity mass at the upper margin of the tumor that invaded and obstructed the distal common bile duct. Magnetic resonance cholangiopancreatography demonstrated no specific findings in the main pancreatic duct. Based on these imaging findings, the patient underwent endoscopic retrograde biliary drainage and bile duct brushing cytology, which revealed indeterminate findings. The differential diagnosis of the tumor at that time was as follows: (1) pancreatic liposarcoma (focal change from well-differentiated to dedifferentiated, not lipoma), (2) distal cholangiocarcinoma, and (3) pancreatic cancer. After the cholangitis improved, a pancreatoduodenectomy was performed. Histologically, hematoxylin–eosin staining revealed moderately differentiated PDAC compressed by proliferating adipose tissue. The adipose lesion showed homogeneous adipose tissue with no evidence of sarcoma, which led to a diagnosis of lipoma. Additionally, extensive fibrosis of the pancreatic parenchyma and atrophy of the acinar cells around the lipoma was suggestive of chronic pancreatitis. The pathological diagnosis was PDAC (pT2N0M0 pStage Ib) with chronic pancreatitis and PL. The postoperative course was uneventful, and the patient was discharged on the 15th day after surgery. The patient received adjuvant chemotherapy and has remained recurrence-free for more than 6 months.ConclusionsPL may be associated with the development of PDAC in the surrounding inflammatory microenvironment of chronic pancreatitis. In cases of growing lipomas, careful radiologic surveillance may be needed not only for the possibility of liposarcoma but also for the coincidental occurrence of PDAC.

Clinical, Pathologic, and Molecular Prognostic Factors in Patients with Early-Stage EGFR-Mutant NSCLC.

In early-stage, EGFR mutation-positive (EGFR-M+) non-small cell lung cancer (NSCLC), surgery remains the primary treatment, without personalized adjuvant treatments. We aimed to identify risk factors for recurrence-free survival (RFS) to suggest personalized adjuvant strategies in resected early-stage EGFR-M+ NSCLC. From January 2008 to August 2020, a total of 2,340 patients with pathologic stage (pStage) IB-IIIA, non-squamous NSCLC underwent curative surgery. To identify clinicopathologic risk factors, 1,181 patients with pStage IB-IIIA, common EGFR-M+ NSCLC who underwent surgical resection were analyzed. To identify molecular risk factors, comprehensive genomic analysis was conducted in 56 patients with matched case-controls (pStage II and IIIA and type of EGFR mutation). Median follow-up duration was 38.8 months (0.5-156.2). Among 1,181 patients, pStage IB, II, and IIIA comprised 577 (48.9%), 331 (28.0%), and 273 (23.1%) subjects, respectively. Median RFS was 73.5 months [95% confidence interval (CI), 62.1-84.9], 48.7 months (95% CI, 41.2-56.3), and 22.7 months (95% CI, 19.4-26.0) for pStage IB, II, and IIIA, respectively (P < 0.001). In multivariate analysis of clinicopathologic risk factors, pStage, micropapillary subtype, vascular invasion, and pleural invasion, and pathologic classification by cell of origin (type II pneumocyte-like tumor cell vs. bronchial surface epithelial cell-like tumor cell) were associated with RFS. As molecular risk factors, the non-terminal respiratory unit (non-TRU) of the RNA subtype (HR, 3.49; 95% CI, 1.72-7.09; P < 0.01) and TP53 mutation (HR, 2.50; 95% CI, 1.24-5.04; P = 0.01) were associated with poor RFS independent of pStage II or IIIA. Among the patients with recurrence, progression-free survival of EGFR-tyrosine kinase inhibitor (TKI) in those with the Apolipoprotein B mRNA Editing Catalytic Polypeptide-like (APOBEC) mutation signature was inferior compared with that of patients without this signature (8.6 vs. 28.8 months; HR, 4.16; 95% CI, 1.28-13.46; P = 0.02). The low-risk group with TRU subtype and TP53 wild-type without clinicopathologic risk factors might not need adjuvant EGFR-TKIs. In the high-risk group, with non-TRU subtype and/or TP 53 mutation, or clinicopathologic risk factors, a novel adjuvant strategy of EGFR-TKI with others, e.g., chemotherapy or antiangiogenic agents needs to be investigated. Given the poor outcome to EGFR-TKIs after recurrence in patients with the APOBEC mutation signature, an alternative adjuvant strategy might be needed.

A case of successful conversion surgery for locally advanced pancreatic cancer with synchronous triple cancer of the lung and esophagus: a case report

BackgroundThe number of reports of multiple primary cancer (MPC) is increasing because of the advancement in diagnostic imaging technology. However, the treatment strategy for MPCs involving pancreatic cancer is controversial because of the extremely poor prognosis. We herein report a patient with synchronous triple cancer involving the pancreas, esophagus, and lung who underwent conversion surgery after intensive chemotherapy for unresectable locally advanced pancreatic cancer.Case presentationA 59-year-old man was admitted to our hospital with epigastric pain, anorexia, and weight loss. Computed tomography and upper gastrointestinal endoscopy revealed that the patient had synchronous triple cancer of the pancreas, esophagus, and lung. While the esophageal and lung cancer were relatively non-progressive, the pancreatic tail cancer had invaded the aorta, celiac axis, and left kidney, and the patient was diagnosed with unresectable locally advanced disease. Because the described lesion could have been the prognostic determinant for this patient, we initiated intensive chemotherapy (gemcitabine plus nab-paclitaxel) for pancreatic cancer. After six courses of chemotherapy, the tumor size shrank remarkably and no invasion to the aorta or celiac axis was observed. No significant changes were observed in the esophageal and lung cancers; endoscopic submucosal dissection could be still a curative treatment for the esophageal cancer. Therefore, we performed curative resection for pancreatic cancer (distal pancreatomy, splenectomy, and left nephrectomy; ypT3N0cM0, ypStage IIA, UICC 8th). Pathologically, complete resection was achieved. The patient then underwent endoscopic submucosal dissection for early esophageal cancer (pT1a[M]-LPM) and video-assisted thoracoscopic right upper lobectomy in combination with right lower partial resection for early lung cancer (pT2aN0M0, pStage IB, UICC 8th). Eight months after pancreatic cancer surgery, the patient is alive and has no sign of recurrence; as a result of the successful treatment, the patient has a good quality of life.ConclusionsTreatment of MPC is challenging, especially for cases with unresectable tumors. Although synchronous triple cancer can involve unresectable pancreatic cancer, radical resection may be possible after careful assessment of the appropriate treatment strategy and downstaging of unresectable tumors.

New PET/CT criterion for predicting lymph node metastasis in resectable advanced (stage IB‐III) lung cancer: The standard uptake values ratio of ipsilateral/contralateral hilar nodes

BackgroundThe aim of the present study was to use surgical and histological results to develop a simple noninvasive technique to improve nodal staging using preoperative PET/CT in patients with resectable lung cancer.MethodsPreoperative PET/CT findings (pStage IB–III 182 patients) and pathological diagnoses after surgical resection were evaluated. Using PET/CT images to determine the standardized uptake value (SUV) ratio, the SUVmax of a contralateral hilar lymph node (on the side of the chest opposite to the primary tumor) was measured simultaneously. The I/C‐SUV ratio was calculated as ipsilateral hilar node SUV/contralateral hilar node SUV. Receiver operating characteristic (ROC) curves were then used to analyze those data.ResultsBased on ROC analyses, the cutoff I/C‐SUV ratio for diagnosis of lymph node metastasis was 1.34. With a tumor ipsilateral lymph node SUVmax ≥2.5, an IC‐SUV ratio ≥1.34 had the highest accuracy for predicting N1/N2 metastasis; the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of nodal staging were 60.66, 85.11, 84.09, 62.5 and 71.29%, respectively.ConclusionsWhen diagnosing nodal stage, a lymph node I/C‐SUV ratio ≥1.34 can be an effective criterion for determining surgical indications in advanced lung cancer.

Natural history of curatively resected stage IB-IIIA EGFR mutation (+) NSCLC: Clinicopathologic and molecular prognostic factors (ROOT-EGFR-ADJ).

8529 Background: Surgery is the primary therapy for patients with early-stage NSCLC. However, five-year recurrence rates were 45%, 62%, and 76% for pathologic stage (pStage) IB, II, and III respectively. In the ADARUA study, adjuvant osimertinib significantly improved DFS in patients with completely resected EGFR mutation (+) NSCLC. Though marked improvement of DFS is encouraging, OS is not mature yet and several questions remain unanswered; Does this DFS benefit translate to cure? Do all patients need to receive adjuvant Osiemrtinib? In order to address these questions we reviewed the clinical records of pStage IB-IIIA EGFR mutant NSCLC. Methods: From January 2008 and August 2020, total 2,340 patients with pStage IB-IIIA, non-SQ NSCLC underwent curative surgery at Samsung Medical Center. Using innovative in-house algorithm to retrieve medical big data-based cohort called ROOT (Realtime autOmetically updated data warehOuse in healTh care) detailed clinical data were analyzed to investigate any prognostic factors of recurrence. In order to identify any molecular prognostic factors, we did a comprehensive genomic analysis (WTS/WES)in a subset of patients with matched case-control. Results: Total 1,811 patients with pStage IB-IIIA, non-SQ EGFR mutation (+) NSCLC were included (367 patients : no EGFR mutation test). Median follow-up duration was 38.8 (range: 0.5 -156.2). Patient demographics; Deletion 19 was 52.7%, L858R was 47.3%. Female was 64.7% and never smoker was 72%. Stage IB, IIA, IIIA was 50.4%, 26.5%, and 23.2%. Among them, 6.7% of pStage IB, 72.8% of pStage II, and 88.7% of pStage IIIA received adjuvant chemotherapy. Median DFS were 74.0 months (95% CI 63.2-84.8), 48.6 months (95% CI: 40.2-57.0), and 22.4 months (95%: 19.5-25.3) for pStage IB, II, and IIIA, respectively. The median OS were 132.1 months (95% CI: 101.3-162.8), 124.3 months (95% CI: 61.8-186.9), and 82.1 months (95% CI: 71.2-93.1) for pStage IB, II, and IIIA, respectively. In univariate analysis, pStage, poorly differentiation, histologic subtype (micropapillary, solid), lymphatic invasion, vascular invasion, and pleural invasion were related with high recurrence rate statistically. In multivariate analysis, pStage, vascular invasion, and pleural invasion were related with recurrence statistically. To detect molecular factors, 76 patients performed the matched case -control (included pStage, type of EGFR mutation, and sex) analysis (WES/WTS). Conclusions: This study showed that the median DFS of pStage II-IIIA EGFR mutation (+) NSCLC was 31.9 months. With approximately 55% of patients with pStage II-IIIA EGFR mutation (+) NSCLC experienced recurrence at the 3rd year, we need to find the appropriate subset who need 3-year adjuvant osimertinib by comprehensive predictive marker for cure. Updated and detail exploratory biomarker outcome will be presented at the annual meeting.

Clinical usefulness of the 3-tier classification according to the proportion of morphological patterns for patients with pathological stage I invasive lung adenocarcinoma.

We classified pathological stage I invasive lung adenocarcinomas according to our 3-tier classification, which was based on the proportion of invasive morphological patterns as follows: (1) patients with each predominant subtype, (2) those with a minor histological subtype, even not the predominant subtype and (3) those without each invasive component. We aimed to evaluate the classification's clinical impact in survival, recurrence, malignant grade, and epidermal growth factor receptor (EGFR) mutational status. A total of 1,269 patients with p-stage I lung adenocarcinoma underwent curative surgical resection between January 2008 and December 2017. Of these, 620 patients (48.9%) met the inclusion criteria of this study. Postoperative recurrence was observed in 81 patients (13.1%). Multivariate analysis showed that vascular invasion (hazard ratio, 2.61; p < 0.001) and p-stage IB (hazard ratio, 2.19; p = 0.001) were significantly associated with an unfavorable RFS, while the presence of acinar component (hazard ratio, 1.64; p = 0.052) or solid component (hazard ratio, 1.60; p = 0.074) were marginally significant. The presence of lepidic or papillary component and the absence of acinar or solid component significantly correlated with an increased proportion of lung adenocarcinomas harboring EGFR mutations. In patients with p-stage I invasive lung adenocarcinoma, it is beneficial to use not only the predominant subtype but analyzing the extent of each histological component based on our classification to predict patient prognoses and form appropriate postoperative follow-up methods.

The impact of surgery induced immune-nutritional change on the outgrowth of micrometastasis after potentially curative resection for gastric cancer.

e16581 Background: Whereas radical resection for gastric cancer is only life-saving option, resulting host response have been suggested to trigger the outgrowth of previously disseminated foci at distant anatomical sites via alteration of anti-tumor immunity. The prognostic nutrition index (PNI) which was calculated as 10 × serum Alb concentration (g/dL) + 0.005 × peripheral total lymphocyte count (/µL) is a surrogate marker of inflammation related nutritional decline and the imbalance of T lymphocyte differentiation. The aim of study was to evaluate the impact of perioperative change of PNI. Methods: The medical record of 567 gastric cancer patients who matched with the following inclusion criteria, R0 resection between 2006 and 2018, no preoperative anticancer treatment, pStage IB-IIIC according to UICC TNM classification and no other organ cancer at surgery, was identified from the prospectively maintained database. The postoperative laboratory data was routinely evaluated at POD 1, 3, 7 and first visit after discharge (AD). The PNI was compared through the perioperative course. Then the predictive value of low PNI-AD which defined as PNI &lt; 40 on the relapse free survival (RFS) after surgery was estimated by COX proportional hazards analysis. Results: The median value of PNI at base line, 1, 3, 7 POD and AD was 51.0, 35.9, 34.0, 38.3 and 48.2, respectively. The PNI as significantly decreased at 1, 3 and 7 POD. Though the PNI at AD had a proclivity to recover, which was still significantly lower than that at base line. During observation period after surgery, the recurrence was encountered in 80 patients. The 5-year RFS rate in patients of pStage IB (n = 164), II (n = 228) and III (n = 175) was 97.4%, 88.9% and 64.7%, respectively. The multivariate analysis identified female gender (HR: 1.715, 95%CI; 1.018-2.890, p = 0.04), pT3-4 (HR:3.620, 95%CI; 2.011-6.518, p &lt; 0.01), pN1-3 (HR:2.741, 95%CI; 1.428-5.263, p = 0.02), vessel invasion (+) (HR:2.666, 95%CI; 1.681-4.229, p &lt; 0.01), PNI-AD &lt; 40 (HR:1.833, 95%CI; 1.002-3.352, p = 0.04) were independent predictors of recurrence. The low PNI-AD was significantly related to the recurrence in the population of pStage III, but not in pStage IB and II. Conclusions: The retardation of postoperative recovery of PNI might evoke the distant metastasis.

Clinicopathological variables influencing overall survival, recurrence and post-recurrence survival in resected stage I non-small-cell lung cancer

BackgroundTo investigate clinicopathological variables influencing overall survival, overall recurrence, and post-recurrence survival (PRS) in patients who experienced curative-intent surgical resection of stage I non-small-cell lung cancer (NSCLC).MethodsWe investigated a series of 1387 patients with stage I NSCLC who underwent surgical resection from 2008 to 2015. The effect clinicopathological factors on death, recurrence, and PRS were evaluated by Kaplan-Meier estimates and cox regression analysis.ResultsAmong the 1387 stage I patients, 301 (21.7%) experienced recurrence. The 5-year cumulative incidence of recurrence (CIR) for all patients was 20.2% and median PRS was 25.5 months. The older age (P = 0.036), p-stage IB (P = 0.001), sublobar resection(P<0.001), histology subtype (P<0.001), and lymphovascular invasion (LVI) (P = 0.042) were significantly associated with worse overall survival. Among 301 recurrent patients, univariable analysis indicated that p-stage IB (versus IA) (P<0.001), LVI (P<0.001) and visceral pleural invasion (VPI) (P<0.001) were remarkably correlated with the higher incidence of recurrence. Taking the effect of clinicopathological variables on PRS into consideration, smoking history (P = 0.043), non-adenocarcinoma (P = 0.013), high architectural grade of LUAD (P = 0.019), EGFR wild status (P = 0.002), bone metastasis (P =0.040) and brain metastasis (P = 0.042) were substantially related with poorer PRS. Multivariate analysis demonstrated that high architectural grade of LUAD (P = 0.008), brain metastasis (P = 0.010) and bone metastasis (P = 0.043) were independently associated with PRS.ConclusionIn patients with resected stage I NSCLC, the older age, p-stage IB (versus IA), sublobar resection, histology subtype, and LVI were significantly associated with worse overall survival. P-stage IB (versus IA), LVI, and VPI were significantly correlated with the higher incidence of recurrence. High architectural grade of LUAD, brain metastasis and bone metastasis were independent risk factors with PRS.

P2.18-08 The Necessity and Technique of the Upper Zone Lymph Node Dissection for Non-Small-Cell Carcinoma of the Left Upper Lobe

The removal of the whole regional lymphatic system together with primary tumor is one of the important rules in oncological surgery. According to the study of regional lymphatic drainage, we considered reasonable lymphadenectomy contributes the post-operative survival of the Left lung cancer patients with mediastinal lymph node metastasis. Due to anatomical limitations imposed by arch of aorta, it is difficult to perform complete dissection of upper zone mediastinal lymph nodes through the left thoracotomy in the left lung cancer. We had devised Systematic extended bilateral mediastinal dissection through a median sternotomy (ND3 operation) for patient with NSCLC of the left lung. This report aimed to introduce procedure of our operation and investigate the prognostic impact of Upper zone lymph node dissection for left upper lobe NSCLC. The our operative procedure is as follows. In the supine position, made a median sternotomy. We dissect the meidastinal nodes before pulmonary resection. The dissection is started on the highest area. Tape the right and left recurrent laryngeal nerve and dissect the highest paratracheal lymph nodes in the thoracic inlet. After making the pericardiotomy, the ascending aorta is retracted to the left. Remove the whole upper zone tissue lying in front of the trachea. And dissect the pre and paratracheal nodes, together with bilateral highest nodes. Then, dissect the subcarinal nodes. Tie off the blood vessels (arteries and veins) and airways leading to the affected lobe, and then remove the lobe. We retrospectively studied 213 patients [157 male and 61 female, mean ages 60.4 years (range, 29-75)], underwent ND3 operation due to NSCLC of the left upper lobe, from January 1990 till December 2017. The patients with NSCLC who are estimated to be able to conventional radical operation and aged 75 year-old or less becomes the adaptation of our operation. Overall 5-year survival rate in the 218 patients of left upper lung primary was 65.1%. Operative mortality in 218 patients was 2.8%. Lymph node metastasis to the mediastinum was confirmed in 70 (32.1%) patients (pN2 was 43, pN3α was 18, pN3γ was 9). According to pathological stages, five-year survival rate was 92.7% in stage IA ,80.1% in stage IB, 53.8% in stage IIA, 66.7% in stageIIB, 51.7% in stageIIIA, 38.4% in stageIIIB. And it was 52.1% in pN2 cases, and 55.0% in pN3α cases. Five-year disease free survival rate was was 85.6% in p-stage IA ,74.0% in p-stage IB,49.7% in p-stage IIA, 49.4% in p-stageIIB, 33.3% in p-stageIIIA, 19.4% in p-stageIIIB, 32.6% in pN2 cases, and 27.8% in pN3α cases. In this nonrandomized comrarision, the post-operative survival of patients with pN2 and pN3α NSCLC of the left upper lung primary would be remarkably improved by our Systematic Bilateral Mediastinal Dissection. And better local tumor control by our operation does not increase mortality. When faced with a patient with resectable mediastinal lymph node metastasis, we should consider Extended bilateral mediastinal lymph node dissection through a median sternotomy. To improve survival rate, it is important to perform curative operation with upper zone mediastinal dissection.

Impact of pathological stage and histological subtype on clinical outcome of adjuvant chemotherapy of paclitaxel plus carboplatin versus oral uracil-tegafur for non-small cell lung cancer: subanalysis of SLCG0401 trial.

Pathological stage (pStage) and histological subtype are strong determinants of the treatment strategy for non-small cell lung cancer (NSCLC). Setouchi Lung Cancer study Group (SLCG) recently reported the results of a multicenter trial (SLCG0401) indicating that paclitaxel plus carboplatin (CBDCA/PTX) as adjuvant chemotherapy does not yield better survival than uracil-tegafur (UFT) in NSCLC patients with pStage IB-IIIA disease, while stratified analyses considering the pStage and histological subtype have not been performed. We reanalyzed the overall survival (OS) and relapse-free survival (RFS) in 402 patients who had been randomly assigned to receive CBDCA/PTX or UFT by multivariate analysis with adjustments for the pStage and histological subtype. There were no significant differences in the OS or RFS between the two treatment settings either in the entire cohort (n = 402) and in some of subsets: pStage IB (n = 228), pStage II (n = 117), adenocarcinoma (AD, n = 265), and squamous cell carcinoma (SQ, n = 101). In pStage IIIA patients (n = 57), CBDCA/PTX yielded superior RFS to UFT [hazard ratio (HR) 0.44; P = 0.016]. Among the patients with non-AD and non-SQ histology (n = 36), UFT yielded both superior OS and RFS to CBDCA/PTX (HRs 0.16 and 0.23; P = 0.046 and 0.011, respectively). There are subsets of patients in which one or the other between UFT and CBDCA/PTX is significantly more effective. Selection of adjuvant therapy for NSCLC patients needs to be made taking into consideration the pStage and histological subtype.

Retrospective study of efficacy of adjuvant chemotherapy using tegafur-uracil in patients with non-small cell lung cancer with primary tumor size of 4.1-5.0 cm.

The staging of patients with a tumor of diameter 4.1-5.0 cm and no lymphatic/distant metastases have been up-graded to stage IIA in the latest 8th edition of the TNM staging system. However, the efficacy of adjuvant tegafur-uracil (UFT) therapy in these patients, which has been recommended in the guideline issued by The Japan Lung Cancer Society, remains unclear. We evaluated the efficacy of adjuvant UFT therapy among a cohort by retrospective analyses of multicentric database. In 2005-2007, 130 patients with p-stage IB non-small cell lung cancer (NSCLC) (diagnosed according to the 7th edition of the TNM staging system) and tumor size of ≥3.1 cm underwent anatomic complete resection at nine of our affiliated hospitals. We retrospectively reviewed the clinicopathological characteristics and the outcomes among these patients. Ninety-eight patients had tumor size of 3.1-4.0 cm (T2a group), whereas 32 patients had tumor size >4.0 cm (T2b group). Overall, patients who received adjuvant UFT showed a tendency of better outcomes than patients who did not [hazard ratio (HR) 0.564; 95% confidence interval (CI), 0.257-1.238, P=0.147]. In subgroup analyses, patients who received adjuvant UFT also tended to show better outcomes than those who did not in both T2a group and T2b group (HR 0.504; 95% CI, 0.202-1.255, P=0.132 in T2a group and HR 0.855; 95% CI, 0.181-4.033, P=0.843 in T2b group, respectively). Our results suggest that adjuvant UFT therapy have the potential to improve postoperative outcomes even in patients with p-stage IIA disease, as classified according to the 8th edition of the TNM staging system.

Adjuvant Chemotherapy Improves Survival in Surgically Resected Stage IB Squamous Lung Cancer

At present there is a significant lack of clinical data for patients with surgically resected stage I squamous lung cancer. The purpose of this study was to investigate the impact of postoperative chemotherapy in this specific population. We retrospectively identified patients who had undergone complete squamous lung cancer resection at the Shanghai Chest Hospital between January 2008 and January2014. A total of 596 patients (236 stage IA, 360 stage IB) were included in this study. Results demonstrated that adjuvant chemotherapy (ACT) could provide longer overall survival for patients with p-stage IB disease (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.34-0.90; p= 0.017). Among p-stage IB patients the ACT-treated cohort trended toward a benefit (HR, 0.69; 95% CI, 0.45-1.04) in recurrence-free survival but failed to reach statistical significance (p= 0.076). After propensity score matching the HRs of recurrence-free survival and overall survival were 0.58 (95% CI, 0.35-0.96; p= 0.033) and 0.49 (95% CI, 0.27-0.88; p= 0.017), respectively. With regards to patients with p-stage IA disease, neither overall survival (HR, 0.87; 95% CI, 0.34-2.27; p= 0.783) nor recurrence-free survival (HR, 0.79; 95% CI, 0.38-1.65; p= 0.534) was significantly different when compared between patients receiving ACT and those who did not. Similar results were also achieved after propensity score matching. The data presented herein demonstrated that ACT might provide survival benefits for squamous lung cancer patients with p-stage IB disease.

Oncological emergency surgery for metachronous large and small bowel metastases after pancreaticoduodenectomy for pancreatic cancer: a case report

BackgroundA surgical case of metachronous metastases of pancreatic head cancer (PC) to the large and small bowel is extremely rare. Therefore, there are only a few reports about surgery for intestinal metastases from PC. An oncologic emergency is defined as an acute, potentially life-threatening condition in a cancer patient that developed directly or indirectly because of the malignant disease or cancer treatment.Case presentationA 63-year-old man with PC underwent pancreaticoduodenectomy after receiving neoadjuvant chemotherapy with gemcitabine and S-1. Histopathologically, the tumor was diagnosed as poorly differentiated, tubular adenocarcinoma, with pT2, N0, pStage IB according to the UICC classification, seventh edition. R0 was achieved. Three months after pancreatoduodenectomy, blood tests showed coagulation derangements with high C-reactive protein (CRP 11.30 mg/dl). Computed tomography (CT) scan revealed a 55-mm mass alongside the transverse colon. During 2 weeks of follow-up, the coagulation derangement and elevated CRP persisted. Repeat CT showed that the tumor enlarged to 65 mm, and an additional mass, 25 mm in diameter, was detected in the jejunum. He was hospitalized due to abdominal pain and diarrhea with persistent high fever and was inspected; however, there was no evidence for infections. With the understanding that his life-threatening symptoms were secondary to the underlying malignancy, extirpation of the tumors combined with partial resection of the transverse colon and the jejunum was performed on the eighth day of hospitalization, on an emergency basis.The lesions were identified as large and small bowel metastases from PC because histopathological examination revealed morphological features similar to the primary disease.Immediately after the emergency surgery, the fever resolved and the CRP level normalized. He was discharged and received nab-paclitaxel with gemcitabine chemotherapy for 2 months postoperatively. He selected for best supportive care after this. The patient died due to a relapse with mesenteric lymph node metastasis 7 months after the emergency surgery.ConclusionSurgery as an oncological emergency for selected patients could sometimes contribute to improving patient’s quality of life.

挙上空腸再発を切除した内臓逆位症併存胃癌の1例

症例は70歳台，男性．約1年7カ月前に複数の内臓奇形を伴う部分内臓逆位症に併存した胃癌（pStage Ib）に対し胃全摘術を施行した．1年間のTS-1内服後に挙上空腸に再発をきたしたが，局所再発以外に非治癒因子は存在しなかった．本症例に対し挙上空腸切除術を施行し，quality of life（QOL）の改善を得ることができた．文献的考察を加えて報告する．

P1.08-005 Stratification of pStage I Lung Adenocarcinoma by the Scoring System Based on Prognostic Factors

In Stage I lung cancer, tumor size and PL factors are only reflected by the TNM staging system. However, other clinicopathological factors have the potential to influence recurrence and prognosis, especially in pStage I lung adenocarcinoma. This study aimed to evaluate prognostic factors, and to thereby stratify pStage I lung adenocarcinoma patients. A total of 203 patients who underwent curative resection for Stage I invasive adenocarcinoma, from 2006 to 2013, were retrospectively reviewed. 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) was performed in 194 patients and the maximum standardized uptake value (SUVmax) of the tumor was calculated. Invasive adenocarcinoma was classified into 3 predominant subtypes (lepidic, papillary and others) according to the IASLC/ATS/ERS classification. The associations between various clinicopathological factors and recurrence were evaluated, and disease-free survival (DFS) was analyzed. Twenty-eight patients had recurrent disease during the follow-up period (mean; 59.3±25 months). Uni-variable analysis showed male gender, smoking history >20 pack-years, BMI≦20, CEA>5ng/ml, T classification, tumor size>20mm, predominant histologic subtype (lepidic, papillary, others), pleural invasion, vascular invasion, and SUVmax>3.0 to be significantly associated with worse DFS. On multivariable analysis, tumor size>20mm (P=0.006), papillary predominant (P=0.023), other predominant (P=0.008), and SUVmax>3.0 (P=0.008) were extracted as independent prognostic factors associated with worse DFS. Predictive variables were scored as follows; tumor size>20mm (1 point), papillary predominant (1 point), other predominant (2 points) and SUVmax >3.0 (1 point). Patients were classified into 3 risk groups (low-risk; 0-2, intermediate-risk; 3, high-risk; 4) according to their aggregate scores. The 5-year DFS rate was 91% in the low-risk group, 55% in the intermediate group and 36% in the high-risk group. The 5-year DFS rates during the same period in our institute were 88% in pStage IA, 69.5% in pStage IB, 53% in pStage II, and 38% in pStage IIIA patients. Therefore, the DFS rate in the intermediate-risk group was comparable to that of pStage II, and the DFS rate in the high-risk group was comparable to that of pStage IIIA. In Stage I lung adenocarcinoma, tumor size, SUVmax and histologic subtypes were suggested to be prognostic factors. This scoring system may predict the groups, such as patients with pStage II and IIIA, requiring platinum based post-operative chemotherapy.

P2.02-026 Individualized Adjuvant Chemotherapy for Resected Lung Cancer According to Collagen Gel Droplet-Embedded Culture Drug Sensitivity Test

The efficacy of adjuvant chemotherapy for locally advanced lung cancer cannot be assessed during the treatment, since there is no measurable lesion after surgical resection. We conducted a prospective clinical trial according to the results of drug sensitivity test with an aim to individualize adjuvant chemotherapy. Patients with resectable c-Stage IB-IIIA non-small cell lung cancer were registered between 2005 and 2010. Collagen gel droplet-embedded culture drug sensitivity test (CD-DST) was performed on fresh surgical specimen. The clinical utility and prognostic outcome of adjuvant chemotherapy with carboplatin/paclitaxel in patients who showed chemo-sensitivity on CD-DST were evaluated. The primary endpoint was disease-free survival, and the secondary endpoints were overall survival and adverse effects during chemotherapy. Among 92 registered patients, 87 (p-Stage IB in 54, IIA in 4, IIB in 10, IIIA in 19) were eligible and were included in the analysis. All patients were followed up for more than 5 years. The median age was 66 years old. The success rate of CD-DST was 87% and chemo-sensitivity to carboplatin and/or paclitaxel was observed in 75% of patients. Adjuvant chemotherapy was completed in 70% and the 5-year disease-free and overall survival rates were 68% and 82%, respectively. The 5-year disease-free and overall survival rates in Stage II–IIIA patients were 58% and 75%, respectively. As for the adverse effects during adjuvant chemotherapy, grade 4 neutropenia was found in 13%. Chemo-sensitivity could be evaluated using CD-DST after lung cancer surgery. CD-DST might contribute to individualized adjuvant chemotherapy for locally advanced lung cancer.

Prognostic impact of vascular invasion and standardization of its evaluation in stage I non-small cell lung cancer.

BackgroundPatients with pathologic stage (p-Stage) IA non-small cell lung cancer (NSCLC) have a good survival rate because of possible curative resection. However, up to 10% of these patients relapse postoperatively. To identify unfavorable prognostic factors, we retrospectively analyzed the clinicopathological features of p-Stage IA disease, focusing on vascular invasion.MethodsOf 467 patients with p-Stage I NSCLC, 335 were diagnosed with p-Stage IA or IB disease based on a lesion size ≤3 cm and the presence of pleural invasion (PL). Univariate and multivariate analyses of recurrence-free survival (RFS) were performed with age, sex, PL, and vascular invasion (blood vessel invasion [v] and lymphatic vessel invasion [ly]) as variables. To examine vascular invasion, hematoxylin-eosin (HE), Elastica van Gieson staining, and immunostaining with anti-podoplanin antibody were performed. The presence or absence of v and ly was recorded; the number of involved vessels was counted. Survival rates were obtained using the Kaplan–Meier method and log-rank test. Multivariate analyses were performed using the Cox proportional hazards model.ResultsRFS differed significantly between patients with no or one involved blood vessel (0 v or 1 v) and those with ≥2 involved vessels (≥2 v). Similarly, RFS differed significantly between patients with no lymphatic vessel involvement (0 ly) and those with one involved lymphatic vessel (1 ly). Thus, BVI(+) and BVI(−) were defined as ≥2 v and 0 v + 1 v, and LVI(+) and LVI(−) as ≥1 ly and 0 ly, respectively. BVI and LVI together represented tumor vessel invasion (TVI). On multivariate analyses, PL and TVI were independently associated with recurrence. Additionally, patients with p-Stage IA TVI(+) disease had a comparable recurrence rate to those with p-Stage IB disease.ConclusionsSimilar to PL, TVI is an important factor increasing the likelihood of recurrence. As HE staining alone is insufficient for evaluating vascular invasion, specific staining is necessary. Moreover, patients with p-Stage IA TVI(+) disease had a recurrence rate comparable to those with p-Stage IB disease; therefore, further studies should aim to elucidate whether patients with p-Stage IA TVI(+) disease should be administered postoperative chemotherapy similar to that received by p-Stage IB patients.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5213064891369688

Evaluation of the 7th edition of the TNM classification for lung cancer at a single institution

To assess the utilities and drawbacks of the 7th edition of the TNM classification for lung cancer. Subjects included 1,469 patients who underwent pulmonary resection for primary non-small cell lung cancer. Survival characteristics were compared using the 6th and 7th editions of the staging system. According to the 6th and 7th editions, respectively, the 5-year survival rates based on stages were as follows: pStage IA (81.0, 81.0 %), pStage IB (70.6, 72.0 %), pStage IIA (61.3, 59.7 %), pStage IIB (56.6, 47.2 %), pStage IIIA (43.4, 37.6 %), pStage IIIB (8.9, 14.9 %), and pStage IV (14.0, 8.0 %). According to the 6th edition, there was no significant difference between pStages IB and IIA (P = 0.268), or between pStages IIA and IIB (P = 0.622), or between pStages IIIB and IV (P = 0.737). According to the 7th edition, there were significant differences between each adjacent stage group, except between pStages IIIB and IV (P = 0.424). According to the 7th edition staging system, 5-year survival rates by T classification were as follows: pT1a, 81.6 %; pT1b, 75.9 %; pT2a, 60.1 %; pT2b, 44.7 %; pT3, 24.4 %; and pT4, 13.2 %; with significant differences between each adjacent pT classification. The 5-year survival rates by M classification were as follows: M0, 57.2 %, M1a, 9.1 %, M1b, 0 %, with a significant difference between M0 and M1a, but there was no significant difference between M1a and M1b. The UICC 7th edition staging system is considered valid for non-small cell lung cancer patients and appears to be superior in defining different prognostic groups than the 6th edition.

Clinicopathological characteristics and surgical results of lung cancer patients aged up to 50 years: The Japanese Lung Cancer Registry Study 2004

ObjectiveThe clinicopathological characteristics and surgical results of young lung cancer patients were investigated. Materials and methodsSeven hundred and four (6.0%) patients with lung cancer, aged up to 50 years, were enrolled from among the 11,663 patients registered in the Japanese Lung Cancer Registry Study 2004, and their clinical data were compared with those of 10,959 patients older than 50 years. This epidemiological study is based on the single year registration of surgically treated patients in the major institutes in Japan. ResultsThe 5-year overall survival rate (5Y-OS) and the 5-year lung cancer-related survival rate was 79.2%/69.0% (p<0.001) and 81.3%/76.6% (p=0.005) in the young/old groups, respectively. In the young/old groups, lobectomy and pneumonectomy was performed in 76.9%/78.0% and 5.7%/3.2%, respectively; adjuvant therapies were given preoperatively in 10.4%/4.7% (p<0.001) and postoperatively in 31.4%/24.5% (p<0.001). The proportions of patients with p-stage IIIA (18.2%) and adenocarcinoma histology (78.7%) were higher in the young group. The 5Y-OS was 94.8%/86.2% for p-stage IA (p<0.001), 87.0%/73.2% for p-stage IB (p=0.001), 61.0%/61.6% for p-stage IIA (p=0.595), 71.0%/48.4% for p-stage IIB (p=0.003), 49.6%/39.4% for p-stage IIIA (p=0.020), and 80.0%/24.8% for p-stage IIIB (p=0.012); it was 83.5%/80.7% for females (p=0.106) and 75.1%/62.3% for males (p<0.001) in the young/old groups. The postoperative survival was significantly better with all operative procedures in the young group. The 5Y-OS after recurrence was 17.9%/13.4% in the young/old groups (p=0.016). In the young group, the 5Y-OS was better in females (83.5%) than in males (75.1%, p=0.002), and for patients with adenocarcinoma (80.3%) than for those with squamous cell carcinoma (68.5%, p=0.013). Age up to 50 years was identified as an independent better prognostic factor on multivariate analysis. ConclusionsThe postoperative survival in lung cancer patients aged up to 50 years was better than that in patients older than 50 years.