Yuta Ibuki

Role of lymphatic invasion in the prognosis of patients with clinical node-negative and pathologic node-positive lung adenocarcinoma

OBJECTIVE Some patients with clinical T1 N0 M0 lung adenocarcinoma have pathologic lymph node metastasis. However, neither the precise prognosis nor the factors predictive of the prognosis of such patients have yet been identified. METHODS Our study included 609 patients with clinical T1 N0 M0 lung adenocarcinoma; 568 (93.3%) pathologic node negative [pN(-)] and 41 (6.7%) pathologic node positive [pN(+)] patients, diagnosed after complete surgical resection. The association between prognosis and pathologic findings was analyzed retrospectively. RESULTS pN(+) patients had a significantly lower lepidic growth component ratio (10% vs 50%), a higher lymphatic invasion (LI) rate (68% vs 11%), vessel invasion rate (59% vs 14%), and visceral pleural invasion rate (29% vs 9%), compared with pN(-) patients (all Ps < .001). Surprisingly, 13 of 41 (32%) pN(+) patients showed no LI. In pN(-) patients, a multivariate analysis of recurrence-free survival revealed that lower lepidic growth component ratio, and lymphatic, vessel, and pleural invasion were significantly correlated with a poor prognosis (P = .008, .045, .031, and .024). However, in pN(+) patients, the multivariate analysis of recurrence-free survival showed that only LI was a significant independent prognostic factor (P = .037). The 5-year recurrence-free survival rates were as follows: 91.2% for pN(-)/LI(-) patients, 68.2% for pN(-)/LI(+) patients, 63.5% for pN(+)/LI(-) patients, and 41.9% for pN(+)/LI(+) patients. LI status stratified the prognosis not only in patients with no nodal metastasis but also in those with metastasis. CONCLUSIONS LI, which is not always present in node-positive adenocarcinoma, is an important prognostic variable in patients with node involvement.

Effects of neoadjuvant chemoradiotherapy on postoperative morbidity and mortality associated with esophageal cancer

We compared the surgical outcomes between 114 patients who did not receive neoadjuvant therapy (group 1) and 92 others who received neoadjuvant chemoradiotherapy (nCRT) (group 2), and assessed the preoperative and surgical factors that influence postoperative morbidity to determine the impact of nCRT on morbidity and mortality after esophagectomy via cervical, right transthoracic, and abdominal approaches. The overall postoperative morbidity rates were 44.7% and 55.4% in groups 1 and 2, respectively (P = 0.13). Rates of anastomotic leak (8.8% vs. 16.3%; P = 0.10), pneumonia (9.6% vs. 13.0%; P = 0.44), recurrent nerve palsy (15.8% vs. 10.9%; P = 0.31), and all other complications did not significantly differ between the groups. Multivariable analysis revealed cervical lymph node dissection (odds ratio [OR], 1.97; 95% confidence interval [CI], 1.01-3.84; P = 0.047) as the sole independent covariate for overall morbidity. Furthermore, a history of cardiovascular disease (OR, 2.90; 95% CI, 1.03-8.24; P = 0.045), the retrosternal reconstruction route (OR, 15.15; 95% CI, 3.56-62.50; P = 0.0002), and a longer surgical duration (OR, 1.01; 95% CI, 1.002-1.02; P = 0.01) were independent covariates for anastomotic leakage, and advanced age (OR, 1.08; 95% CI, 1.01-1.15; P = 0.02) and lower body mass index (OR, 1.16; 95% CI, 1.01-1.33; P = 0.04) were independent covariates for pneumonia. However, whether or not patients received nCRT was irrelevant. We found that nCRT is safe for three-incision esophagectomy and it does not increase the incidence of postoperative morbidity and mortality relative to esophagectomy alone.

Prediction for prognosis of resected pT1a-1bN0M0 adenocarcinoma based on tumor size and histological status: relationship of TNM and IASLC/ATS/ERS classifications.

OBJECTIVES This study aimed to estimate the relationship between 7th TNM classification and IASLC/ATS/ERS classification with regard to tumor size and pathological status and to determine the utility of these classifications for predicting prognosis in resected node-negative adenocarcinoma with tumor size ≤2.0 cm and >2.0-3.0 cm. MATERIALS AND METHODS We reviewed 321 pN0M0 lung adenocarcinoma cases resected at Hiroshima University Hospital from January 1991 to December 2010. Histological differences between T1a and T1b based on the IASLC/ATS/ERS classification were estimated and followed by evaluation of overall survival (OS) and recurrence-free interval (RFI) based on differences in tumor size and histological features. RESULTS We found 188 cases of pT1a-1bN0M0 (135 T1a, 53 T1b). Pathological T1a tumors included significantly more adenocarcinoma in situ (AIS) cases and minimally invasive adenocarcinoma (MIA) cases than T1b tumors (60.7% vs 18.8%, respectively; p<0.0001), while more invasive adenocarcinoma cases were included in pT1b. By considering the two classifications simultaneously, the 5-year OS rates of T1a AIS/MIA, T1b AIS/MIA, T1a invasive adenocarcinoma, and T1b invasive adenocarcinoma were 97.5%, 87.5%, 95.8%, and 86.8%, respectively. The 5-year RFIs of T1a AIS/MIA, T1b AIS/MIA, T1a invasive adenocarcinoma, and T1b invasive adenocarcinoma were 100%, 100%, 91.3%, and 72.5%, respectively. T1a AIS/MIA and T1b AIS/MIA could be separated as good prognostic cases with a 100% RFI. Multivariate analysis indicated that only T1b invasive adenocarcinoma was an independent factor for predicting recurrence (p=0.001). CONCLUSION Compared to a single classification, combining TNM and IASLC/ATS/ERS classifications could provide more detail information concerning disease recurrence. AIS and MIA should be handled equally, regardless of tumor size, because their non-/less invasive status is more useful for predicting prognosis than their tumor size classification. In contrast, the T descriptors based on TNM classification are important for predicting prognosis in invasive adenocarcinoma.

Preoperative prediction of a pathologic complete response of esophageal squamous cell carcinoma to neoadjuvant chemoradiotherapy

Background: The accurate prediction of a pathologic complete response (ypT0N0M [LYM] 0 ypStage 0) before operation is essential for selecting appropriate strategies for treating esophageal cancer after neoadjuvant chemoradiotherapy. Methods: We reviewed 130 consecutive patients with esophageal squamous cell carcinoma who were evaluated preoperatively using upper gastrointestinal endoscopy, computed tomography, and 18F‐fluorodeoxyglucose‐positron emission tomography after neoadjuvant chemoradiotherapy and subsequently underwent esophagectomy. Our aim was to determine the diagnostic abilities of computed tomography, 18F‐fluorodeoxyglucose‐positron emission tomography, and endoscopy to predict preoperatively a pathologic complete response of the primary site of the locally advanced esophageal squamous cell carcinoma and associated lymph nodes to trimodal neoadjuvant chemoradiotherapy. Associations between clinical complete response (ycT0N0M [LYM] 0 ycStage 0) and pathologic complete response were investigated preoperatively. Results: Twenty‐nine (22.3%) and 43 (33.1%) patients, respectively, achieved clinical complete response and pathologic complete response, which were associated (P = .001). The sensitivity and specificity, as well as the positive and negative predictive values of clinical complete response to define pathologic complete response were 39.5%, 86.2%, 58.6%, and 74.3%, respectively. Univariate and multivariate analyses selected clinical complete response as the sole independent preoperative predictor of pathologic complete response (clinical complete responses versus non–clinical complete responses: odds ratio: 0.26, 95% confidence interval, 0.10–0.65, P = .004). Recurrence‐free and overall survival (OS) rates were better in patients with than in those without clinical complete response (5‐year recurrence‐free and overall survival: 69.0% vs 41.4% and 75.9% vs 45.0%, respectively, both P = .02). Furthermore, clinical complete response was an independent preoperative predictor of recurrence‐free survival (clinical complete response versus nonclinical complete response: hazard ratio: 2.20, 95% confidence interval, 1.08–4.45, P = .03). Conclusion: Although pathologic complete response was predictable preoperatively to some extent, the accuracy was somewhat low. Considerable caution should be exercised when selecting the watch‐and‐wait approach with operation as needed and omitting planned operative intervention even for patients who achieve clinical complete response after neoadjuvant chemoradiotherapy.

Invasive micropapillary carcinoma component is an independent prognosticator of poorer survival in Stage III colorectal cancer patients

Background Invasive micropapillary carcinoma (IMPC) is an aggressive variant of adenocarcinoma found in several organs. Recent studies showed that IMPC in colorectal cancer leads to poorer prognosis than conventional colorectal cancer; however, the influence of IMPC on outcomes remains unclear. The present study aimed to identify the clinicopathological characteristics of colorectal cancers with IMPCs, and to evaluate the prognostic significance of IMPCs per se. Methods We retrospectively analyzed data from 837 patients with colorectal cancer who underwent surgical treatment. We compared the clinicopathological characteristics and survival outcomes of colorectal cancer patients with IMPCs to those without. Results Among 837 patients, 130 (16%) had an IMPC component, including 0 (0%) of 18, 9 (4.2%) of 215, 34 (13%) of 254, 59 (24%) of 249 and 28 (27%) of 101 patients with TNM Stages 0, I, II, III and IV, respectively. The 3-year disease-free survival (DFS) rates were significantly worse for Stage III patients with IMPC than for those without (55.3% vs. 78.7% respectively, P < 0.001), but not in patients with other stages. Multivariate analyses of patients with Stage III colorectal cancer found IMPC to be associated with significantly worse DFS (P = 0.026), as were high CEA levels, tumor budding and TNM staging. IMPC was only significantly associated with tumor invasion (P = 0.045) and venous invasion (P = 0.045) in Stage III tumors. Conclusions Identifying IMPC components in Stage III colorectal cancer is crucial, as their presence is significantly associated with poorer survival.

Preoperative predictors of distant recurrence in patients with clinical stage IA lung adenocarcinoma undergoing complete resection

Objective: We aimed to identify patients with clinical Stage IA lung adenocarcinoma who are at high risk for distant recurrence to preoperatively organize treatment strategies. Methods: We analyzed correlations between preoperative clinical factors and the incidence of distant recurrence in 609 patients with clinical Stage IA lung adenocarcinoma that had been completely resected at four institutions. We excluded 24 patients with only locoregional recurrence and analyzed data from 585 patients. Results: Distant recurrence after complete resection was identified in 34 patients during a median follow‐up period of 41.4 months. Multivariate Cox analysis identified solid tumor size on high‐resolution computed tomography and the maximum standardized uptake value on F‐18‐fluorodeoxyglucose positron emission tomography/computed tomography as independent predictors for distant recurrence‐free survival. Receiver operating characteristic analyses showed that solid tumor size ≥1.7 cm and the maximum standardized uptake value ≥3.3 were optimal criteria with which to detect patients at high risk for distant recurrence. In fact, 3‐year distant recurrence rates were higher in patients who met the criteria for high risk (n = 85) than those who did not (n = 500) (28.1% vs. 3.7%; P < 0.001). A similar trend was also found in patients with pathological node negative. Conclusions: Solid tumor size on high‐resolution computed tomography and the maximum standardized uptake value on F‐18‐fluorodeoxyglucose positron emission tomography/computed tomography were clinical predictors of distant recurrence among patients with clinical Stage IA lung adenocarcinoma. Our findings might be useful to determine personalized therapeutic strategies including systemic therapy.

The Difference in Maximum Standardized Uptake Value among Lung Adenocarcinomas Located at the Upper and Lower Zone on PET/CT

Background: Findings on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) are surrogate markers of malignancy in lung adenocarcinoma. Breathing during PET/CT can substantially reduce the maximum standardized uptake value (maxSUV) of lung tumors when they are located at the lower zone (LZ). Objectives: We assessed whether lung cancer location influences the malignancy predicted by maxSUV. Methods: 608 patients with clinical stage IA lung adenocarcinoma had been preoperatively examined by PET/CT and high-resolution computed tomography (HRCT). We evaluated the clinicopathological characteristics of these patients and the accuracy of precognition obtained by maxSUV between the upper zone (UZ, n = 395) and the LZ (n = 213). maxSUV was also analyzed for matched pairs between the two groups. Results: The mean maxSUV in the LZ group was significantly lower than that in the UZ group (1.98 ± 1.73 vs. 2.44 ± 2.43, respectively; p = 0.0145). The receiver operating characteristics curve of maxSUV for predicting high-grade malignancy (lymphatic, vascular, pleural invasion, or lymph node metastasis) was larger for the UZ group than for the LZ group [0.89, 95% confidence interval (CI) 0.86-0.93, vs. 0.82, 95% CI 0.76-0.88]. Analysis for maxSUV of 213 pairs matched for the solid component size on HRCT, pathological characteristics, and gender revealed that maxSUV in the LZ group was significantly lower than that in the UZ group (1.98 ± 1.73 vs. 2.47 ± 2.39, respectively; p < 0.001). Conclusions: maxSUV of a tumor in the LZ group is apparently lower than the value which reflects the potential malignancy of a tumor. We have to carefully consider these facts when selecting the appropriate surgical procedure for lung cancer with PET/CT and HRCT.

Coexistence of gastrointestinal stromal tumor and leiomyosarcoma of the stomach presenting as a collision tumor: A case report and review of literature: Collision tumor of GIST and LMS

Collision tumor of the stomach is rare. We report a rare case of a gastric collision tumor consisting of gastrointestinal stromal tumors (GISTs) and leiomyosarcoma (LMS). Computed tomography scan revealed a 15 cm sized mass in the posterior wall of the body of the stomach. Gross examination of the wedge resection specimen showed the tumor located in the muscularis propria with extramural protrusion into the peritoneal cavity and the gastric cavity with geographic necrosis, hemorrhage, and mucosal ulceration. Histologically, the majority of the tumor consisted of the GIST component and the minor area in the submucosal region consisted of the LMS component. The tumor showed an abrupt transition between GIST and LMS by histologically and immunohistochemically, suggesting a collision tumor. Furthermore, the GIST components exhibited a c‐kit exon 11 mutation. On the other hand, LMS component exhibited neither c‐kit nor platelet‐derived growth factor receptor‐alpha (PDGFRA) mutation. Here we describe a case of the collision tumor consisting of GIST and LMS and its literature review.

Impact of Interval Between Neoadjuvant Chemoradiation and Surgery Upon Morbidity and Survival of Patients with Squamous Cell Carcinoma of Thoracic Esophagus

Background/Aim: The present study aimed to determine the effects of intervals between neoadjuvant chemoradiotherapy (nCRT) and esophagectomy on therapeutic outcomes in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Patients and Methods: We analyzed data from 134 consecutive patients who were diagnosed with locally advanced ESCC of the thoracic esophagus and were treated by nCRT followed by esophagectomy between September 2003 and September 2015. We assigned the patients to groups A and B according to whether they underwent esophagectomy ≤8 or >8 weeks after nCRT. Results: The two groups were comparable in terms of age, gender, performance status, comorbidities, tumor location, clinical stage, R0 resection rates and pathological responses to nCRT. The incidences of pneumonia and respiratory failure were significantly higher in group B (p=0.03, p=0.009, respectively). Recurrence-free (RFS) and overall (OS) survival rates did not significantly differ between the two groups. However, RFS was significantly poorer among patients with R0 resection (p=0.04) and those of cStages III and IV (p=0.009) in group B. Conclusion: Esophagectomy should proceed within eight weeks after nCRT from the viewpoints of respiratory morbidity and impact of RFS on patients with R0 resection.