Microscopic Invasion Research Articles

Detailed pathological analysis of the advancing edge of the tumour can effectively stratify clinical T4b colorectal cancer patients.

Pathological staging of colorectal cancers (CRCs) that involve adhesion to adjacent organs (clinical stages T4b, cT4b) is sometimes difficult because the morphology of the invasive front varies. To resolve this issue, we reviewed 492 surgically resected CRC samples, comprising 96 cT4b tumours and, for comparison, 335 typical pathological stages (p) T3 and 61 pT4a tumours. Cases were subdivided into four groups according to the presence or absence of microscopic tumour invasion into the muscular wall of the adjacent organs and peritumoral abscess along invasive front. Those that directly invaded the wall of the adjacent organs without peritumoral abscess were associated with a significantly worse overall (OS) and recurrence-free survival (RFS) than the other three types of cT4b tumours. Those with peritumoral abscess showed similar prognosis to typical pT3 tumours, even when the advancing edge of the tumour invaded the wall of adjacent organs (staged as pT4b). Tumours showing fibrous adhesions without tumour cell invasion into the muscular wall of the adjacent organs showed a similar prognosis to typical pT3 tumours and showed a better prognosis than pT4a tumours. Only CRCs with tumour cell invasion into the muscular wall of the adjacent organs should be classified as pT4b, and it might be better to avoid 'the presence of tumour cells in fibrous adhesion' to define pathological T4b CRCs. In addition, the presence of a peritumoral abscess should be recorded as a predictor of better prognosis.

Evaluation of the histopathological extent of neoplastic infiltration in intestinal tumours in cats.

With the exception of intestinal lymphoma, surgery is the most commonly recommended treatment for solitary feline intestinal tumours. However, there is a lack of evidence to substantiate resection margin recommendations for these tumours. The aim of this study was to add knowledge concerning resection margins for discrete intestinal masses in cats. Thirty confirmed feline intestinal tumours removed at veterinary centres across the UK from March 2017 to March 2018 underwent histological assessment at the palpable edge of the intestinal tumour and then at every 1 cm increment to the surgeon‐cut tissue border in oral, aboral and mesenteric directions. Histological margin recommendations were developed for carcinoma and lymphoma tumour types and non‐lymphoma intestinal tumours collectively. Seventeen intestinal lymphomas, nine carcinomas, two sarcomas and two mast cell tumours were evaluated in this study. Seven of the nine intestinal carcinomas would have been completely removed with histological margins of 4 cm in oral and aboral directions. Both sarcomas and one mast cell tumour would have been removed in their entirety with 4 cm histological margins in oral and aboral directions. There was extensive and varied microscopic invasion of intestinal tissue away from discrete intestinal lymphomas in the majority of the cases in this study. There is increasing evidence in veterinary as well as human literature supporting the role of surgical resection in the treatment of discrete intestinal lymphoma. If surgery is to be considered this study supports the removal of the gross tumour only. A histological margin of 4 cm should be considered, where possible, for intestinal masses other than lymphomas.

Left kidney mobilization technique during radical antegrade modular pancreatosplenectomy (RAMPS).

Radical antegrade modular pancreatosplenectomy (RAMPS) has been accepted as a standard operation for distal pancreatic cancer. While enbloc retroperitoneal dissection in the "medial to lateral" direction is one of the most important steps in this oncologic procedure, it is technically challenging due to the depth of organs under the left costal margin, and poor exposure of the resecting organs in this area will increase the risk of incomplete oncologic dissection. To improve exposure of the left upper quadrant organs, left kidney was completely mobilized during RAMPS, and all the left upper quadrant organs were elevated and medialized by lap sponges packed in the retro-renal space. The operative and oncologic outcomes for patients who underwent our modified RAMPS with left kidney mobilization were evaluated. One hundred and forty-four patients with distal pancreatic cancer underwent this procedure from 2005 through 2016. The median operation time was 310min (range, 132-899), and blood loss was 440ml (25-2430). There was no complication associated to left kidney mobilization. The median number of harvested lymph nodes was 27 (3-87). While 77% of the tumors had microscopic retroperitoneal invasion, 96% of patients achieved negative retroperitoneal margin. Left kidney mobilization is useful for safe and oncologically sound lateral retroperitoneal dissection during RAMPS for distal pancreatic cancer.

Abstract PD8-05: POSNOC - Positive sentinel node: Adjuvant therapy alone versus adjuvant therapy plus clearance or axillary radiotherapy

Abstract Background: Role of additional axillary treatment (AxT) (axillary lymph node dissection (ALND) or axillary radiotherapy (ART)) in women with ≤2 macrometastases and undergoing systemic therapy remains unclear. Z11 included both micro and macrometastases (around 40% micrometastases) and showed that ALND may be omitted in women with ≤2 positive nodes undergoing breast conserving surgery (BCS) and receiving whole breast RT. Paradoxically, NCIC MA20, demonstrated improved DFS following the addition of regional RT. 51.8% (949/1832) had 1 or 2 positive nodes. 98.9% (1812/1832) had T1/T2 tumours. A post-Z11 survey shows that most US radiation oncologists treat the undissected axilla in women with macrometastases with ART rather than omitting AxT. Therefore, a confirmatory study is needed to clarify the role of additional AxT in women with ≤2 macrometastases undergoing BCS and other subgroups that were not included in Z11 e.g. mastectomy, microscopic extranodal invasion and sentinel node biopsy (SNB) before neoadjuvant chemotherapy. Methods: Primary objective is to assess whether for women with ≤2 macrometastases at SNB, systemic therapy alone is non-inferior to systemic therapy plus AxT in terms of axillary recurrence at 5 years. Secondary objectives are arm morbidity assessed by LBCQ and QuickDASH questionnaires; QoL assessed by FACT-B+4 questionnaire; anxiety assessed by STAI; loco-regional recurrence; distant metastasis; time to axillary recurrence; axillary recurrence-free survival; DFS; OS; contralateral breast cancer; non-breast malignancy; and economic evaluation. Eligibility criteria include: ≥18 y, uni or multifocal invasive cancer, T1/T2, 1 or 2 macrometastases, with or without extranodal invasion. Target sample size is 1900 with a projected drop-out and non-compliance with treatment allocation rate of 10%. Primary analysis will be per protocol. The following pre-specified subgroup analyses shall be performed: number of macrometastases (1, 2), age (<50, ≥50), breast surgery (mastectomy, BCS), ER (positive, negative), tumour grade (1 or 2, 3), SN assessment technique (OSNA, non-OSNA), extranodal invasion (present, absent). POSNOC opened to recruitment in July 2014. To date 1100 women have been recruited at 82 sites in the UK and 18 sites in Australia and New Zealand. Clinicaltrials.gov NCT02401685. Citation Format: Goyal A, Mann B, Thompson AM. POSNOC - Positive sentinel node: Adjuvant therapy alone versus adjuvant therapy plus clearance or axillary radiotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD8-05.

Suspected major vessel involvement in patients with colorectal liver metastases (CRLM): Single Center Experience of 13 Cases

Background: The role of major vessel involvement in the treatment of CRLM still remains unclear. Methods: From Jan. 2008 to Oct. 2016, 650 liver resections (LR)for CRLM were performed.13 cases included resection of major vessel with reconstruction because of suspect tumor infiltration. The portal vein (PV) was resected in 2 and the inferior vena cava (IVC) in 10 cases. Combined resection and reconstruction of the PV and IVC was performed in 1 case. Results: All PV-patients (n=2) received a segmental resection. PV resection was combined with 2 major LR.Regarding the IVC, tangential resection was performed in all cases (n=10). Minor and major LR were accomplished in 5 cases each. The patient with combined vessel resection received a segmental resection of the PV and a tangential resection of the IVC. Median hospital stay was 17d and major postoperative complications Grade III-IV, occurred in 3 patients. In-hospital-mortality was 0%.R0-resection was achieved in all cases. Histopathological examinations approved in each group 1 case of microscopic invasion. The patient with invasion of the IVC is still alive, receiving chemotherapy because of intrahepatic recurrence. The patient with invasion of the PV died after 33 months. Conclusion: Microvascular invasion is a rare event in CRLM (2 of 650 liver resections). Even in cases of macroscopic radiological adherence, microscopic invasion was rarely observed in 15%. Therefore, radiologic diagnosis of CRLM adjacent to major vessels is not a contraindication for surgery.

Prognostic impact of microscopic vessel invasion and visceral pleural invasion and their correlations with epithelial–mesenchymal transition, cancer stemness, and treatment failure in lung adenocarcinoma

ObjectivesMicroscopic vessel invasion (MVI) and visceral pleural invasion (VPI) have been recently reported as poor prognostic factors of non-small cell lung cancer. Epithelial–mesenchymal transition (EMT) and cancer stemness (CS) are known malignant phenotypes that induce resistance to cancer therapy. We aimed to assess the prognostic significance of MVI and the correlations among VPI/MVI, EMT, CS, and treatment failure for recurrent tumor. Materials and methodsFrom 2002 to 2013, 1034 consecutive patients with pathological T1-4N0-2M0 lung adenocarcinoma underwent complete resection. Moreover, we established 206 tissue microarray (TMA) samples from 2002 to 2007. We then evaluated the prognostic impact of MVI, including conventional clinicopathological factors, and analyzed the VPI/MVI, EMT, CS, and treatment failure by TMA immunohistochemical staining. ResultsAmong the 1034 cases, the proportion of patients with a 5-year overall survival (OS) period was 63.9% and 88.2% (MVI: +/−; p < .001). Multivariate analysis revealed that both MVI and VPI were independent predictors of OS (HR 1.57 and 1.47, respectively). Significant separation of the OS rate curves was observed among the 3 groups [VPI/MVI: both positive (2), either positive (1), and both negative (0)]. Among the 206 TMA cases, these 3 groups of VPI/MVI were significantly correlated with EMT and CS. The median time to progression after recurrence were 3.8, 8.9, and 15.9 months, respectively (VPI/MVI: 2/1/0; p = 0.016). ConclusionMVI and VPI are significant prognostic factors of lung cancer, and they are correlated with EMT, CS, and treatment failure for recurrent tumor.

Infantile myofibromatosis: review of imaging findings and emphasis on correlation between MRI and histopathological findings

BackgroundInfantile myofibromatosis (IM) is the most common fibrous tumor of infancy. MRI is considered the gold standard in IM evaluation. Very little has been published about IM with histopathology correlation in the pediatric age. PurposeDescribe imaging findings in IM and correlate MRI findings with histopathology. Material and methodsImaging findings of 17 patients with IM were retrospectively analyzed including CT, US and MRI. Signal characteristics on T1-, T2-weighted and STIR imaging, extent of T2-hyperintensity, degree & pattern of enhancement, diffusion restriction, location & margins, & involvement of adjacent structures were tabulated. Histopathology findings included cellularity, collagenization, myxoid changes, atypia, mitosis & microscopic invasion. Established grading scores were utilized. ResultsRelative to normal skeletal muscle, on T1-weighted imaging, 9 lesions had similar signal while the remaining had a mixture of iso & hypo intensity; whereas on T2-weighted and STIR imaging, all 12 lesions demonstrated a mixture of iso, hypo & hyperintensity. T2-hyperintensity was grade 2 in one, grade 3 in 8 & grade 4 in 3 lesions. Intensity of enhancement was grade 2 in one, grade 3 in 8 & grade 4 in 3 lesions. Enhancement was predominantly peripheral in all 12 lesions.Extent of T2-hyperintensity & degree of enhancement corresponded to variable grades on histopathology.CT and US showed nonspecific findings. ConclusionOn MRI, IM has a mixture of signal intensity with predominant hyperintense signal on T2W images. However various signal & enhancement features correlated poorly with specific histopathologic grades.

Adoption of AJCC 8th Edition for p16+ Oropharynx Cancers May Result in Decreased Utilization of Adjuvant Therapies Due to Shifts in Pathologic Nodal Staging

The 8th edition of the AJCC (American Joint Committee on Cancer) system no longer includes nodal laterality or size in the pN staging system for p16+ oropharynx cancers. This is because number of involved lymph nodes provides better discriminatory ability for recurrence than laterality, size, or presence of high risk nodal features (i.e. extracapsular extension [ECE]). At our institution, we have routinely offered adjuvant radiotherapy (+/- chemotherapy) for patients with traditional intermediate or high risk features independent of p16 status as per NCCN guidelines. Here, we examine a cohort of p16+ patients staged and treated according to AJCC 7th edition and reclassify them according to the 8th edition to determine rate of nodal downstaging based on the new system. Patients with pathologically node positive p16+ oropharyngeal cancer treated with primary surgery (most commonly TORS with selective neck dissection) followed by adjuvant intensity modulated radiation therapy (+/- chemotherapy) were included for analysis. Demographics, pathology, and treatment details were collected from the electronic medical record. Indications for adjuvant therapy were recorded and patients were re-staged according to the AJCC 8th edition. Rates of nodal downstaging were recorded. A total of 28 patients met inclusion criteria and were treated from 2012 to 2017. 93% were male. 24 (85%) primaries were tonsillar and 4 (15%) base of tongue. An ipsilateral selective neck dissection was performed in 17 (61%) cases. A total of 27 patients had pre-operative imaging (CT or PET) consistent with nodal involvement. The median number of involved lymph nodes was 2 (range 1-8). 13 (46%) had pathologic evidence of ECE, one (4%) microscopic perineural invasion (PNI), and five (18%) had lymphovascular space invasion (LVSI). Five patients (18%) had a microscopically positive margin. AJCC 7th edition N staging was as follows: N1: 10 (36%), N2a: 1 (4%), and N2b: 17 (60%). 15 of 18 (83%) AJCC 7th N2 patients were downstaged to AJCC 8th N1. Seven of these 15 (47%) patients did not have other adverse pathologic features (i.e. pT3, ECE, positive margin, PNI, LVSI). Radiation therapy was delivered using a simultaneous integrated boost technique in all cases. The median dose to the highest risk volume was 60 Gy (range 60-66 Gy). 13 patients (46%) received concurrent chemotherapy. At a median follow up of 25 months (range 3 months to 10 years), there have been no recurrences in this cohort. Nodal downstaging from pN2 to pN1 with the adoption of AJCC 8th edition is common for surgically-treated node positive p16+ oropharynx cancer. Although number of positive nodes has high discriminatory ability for recurrence, it is unknown whether the omission of adjuvant therapy in patients with < 5 positive nodes is safe. Until this is known, the decision to recommend adjuvant therapy should be highly dependent on a thorough understanding of pathologic findings rather than relying purely on the new pathologic N stage.

An Imager's Guide to Perineural Tumor Spread in Head and Neck Cancers: Radiologic Footprints on 18F-FDG PET, with CT and MRI Correlates.

Perineural spread (PNS) refers to tumor growth along large nerves, a macroscopic analog of microscopic perineural invasion. This phenomenon most commonly occurs in the head and neck, but its incidence varies with histologic tumor subtype. PNS results from a complex molecular interplay between tumor cells, nerves, and connective stroma. PNS is clinically underdiagnosed despite its impact on patients' prognosis and management. The role of 18F-FDG PET in assessment of PNS in head and neck cancer remains to be explored, in contrast to MRI as the established gold standard. In patients with PNS, 18F-FDG PET shows both abnormality along the course of the involved nerve and muscular changes secondary to denervation. Assessment of PNS on 18F-FDG PET requires knowledge of relevant neural pathways and can be improved by correlation with anatomic imaging, additional processing of images, and review of clinical context.

Primary Gallbladder Carcinosarcoma: A Rare Biliary Malignancy

Gallbladder cancer comprises approximately 85-90% of all biliary tract malignancies, with carcinosarcomas accounting for less than 1%. Karl Landsteiner first described sarcomatoid carcinoma in the gallbladder in 1907, with less than 100 cases reported since that time. A 49-year-old male presented with 1 month of sharp, epigastric pain. Initial labs revealed a lipase of 3785 U/l, AST 658, ALT 489, total bilirubin 2.4 mg/dl, and direct bilirubin 1.3 mg/dl. Computer tomography (CT) of abdomen and pelvis revealed intra and extra-hepatic biliary duct dilation, cholelithiasis with biliary sludge, and hyper-enhancement of the gallbladder wall. Magnetic resonance cholangiopancreatography (MRCP) revealed gallbladder wall thickening with a polyp or a large amount of gallbladder sludge. There was no definite evidence of choledocholithiasis. Patient underwent laparoscopic cholecystectomy. Pathology of the gallbladder showed a circumferential tumor at the gallbladder fundus measuring 3.2 cm with gross and microscopic invasion through the muscular wall (Figure 1). The tumor showed glandular differentiation with pleomorphic spindle cell components consistent with sarcomatoid carcinoma of the gallbladder (Figure 2). Tumor markers including AFP, Ca 19-9, and CEA were negative. He underwent further robotic-assisted liver resection with lymphadenectomy. Lymph nodes were negative for malignancy. He was evaluated by oncology and recommended adjuvant platinum based chemotherapy for six months.1243_A.tif Figure 1: Gross image of gallbladder showing a 3.2 cm, circumferential, intramural mass with associated mucosal ulceration1243_B.tif Figure 2: No Caption available.Carcinosarcoma is a rare gallbladder malignancy without clear diagnostic and treatment guidelines. Preoperative diagnosis is difficult as there are no specific radiographic findings. Histologically these tumors are characterized by malignant epithelial and mesenchymal cells, that stain positive for cytokeratin and vimentin respectively. Tumor markers are often nonspecific. Major prognostic factors may include tumor size, staging, and depth of invasion. Primary therapy is surgical resection. Some cases have reported chemotherapy regimens including a combination of 5-fluorouracil with a carboplatin. Overall prognosis is poor in locally advanced disease with a 5-year survival rate of approximately 16%. This case illustrates the importance of considering carcinosarcoma as a differential in a patient with prolonged epigastric pain with non-specific image findings. It stresses the importance of ongoing research to help define adjuvant chemotherapy or chemoradiation regimens to improve survival.

The New TNM Staging System for Thyroid Cancer and the Risk of Disease Downstaging.

In October 2016 the American Joint Committee on Cancer (AJCC) published the 8th edition of the AJCC/TNM cancer staging system and it has been introduced in clinical practice since 1st January 2018. The effect of most of the changes in the new edition was the downstaging of a significant number of patients into lower stages, reflecting their low risk of thyroid cancer-related death. One of the most relevant modification refers to the role of the microscopic extra-thyroidal tumor invasion, which is no longer considered as criterion for the classification of T3 tumors. With the present study we want to assess the impact of the changes of the new staging system and therefore we analyzed or casistic of 84 T1-T3 thyroid-cancer patients. The results of our analysis show that he downstaging of patients according to the 8th TNM edition does not necessarily reflect less aggressive disease: we actually reported 2 lymph-nodal recurrences (40%) in the five patients that were downstaged from pT3 to pT2 and the lypmh-nodal recurrence rate for stage I rises from 0% with the 7th TNM edition to 5.3% with the 8th edition.

Systemic Depletion of Nerve Growth Factor Inhibits Disease Progression in a Genetically Engineered Model of Pancreatic Ductal Adenocarcinoma.

In patients with pancreatic ductal adenocarcinoma (PDAC), increased expression of proinflammatory neurotrophic growth factors (eg, nerve growth factor [NGF]) correlates with a poorer prognosis, perineural invasion, and, with regard to NGF, pain severity. We hypothesized that NGF sequestration would reduce inflammation and disease in the KPC mouse model of PDAC. Following biweekly injections of NGF antibody or control immunoglobulin G, beginning at 4 or 8 weeks of age, inflammation and disease stage were assessed using histological, protein expression, and quantitative polymerase chain reaction analyses. In the 8-week anti-NGF group, indicators of neurogenic inflammation in the dorsal root ganglia (substance P and calcitonin gene-related peptide) and spinal cord (glial fibrillary acidic protein) were significantly reduced. In the 4-week anti-NGF group, TRPA1 mRNA in dorsal root ganglia and spinal phosphorylated ERK protein were elevated, but glial fibrillary acidic protein expression was unaffected. In the 8-week anti-NGF group, there was a 40% reduction in the proportion of mice with microscopic perineural invasion, and no macrometastases were observed. Anti-NGF treatment beginning at 4 weeks may increase inflammation and negatively impact disease. Treatment starting at 8 weeks (after disease onset), however, reduces neural inflammation, neural invasion, and metastasis. These data indicate that NGF impacts PDAC progression and metastasis in a temporally dependent manner.

Serum Elastase 1 Level as a Risk Factor for Postoperative Recurrence in Patients with Well-Differentiated Pancreatic Neuroendocrine Neoplasms.

This study was designed to assess the potential role of the preoperative serum level of elastase 1 as a risk factor for recurrence in patients with resectable well-differentiated pancreatic neuroendocrine neoplasms (PanNETs). Preoperative serum elastase 1 levels were measured in 53 patients with PanNETs who underwent complete tumor resection in two tertiary referral centers between January 2004 and June 2017. The preoperative elastase 1 levels were correlated with clinicopathological characteristics, including tumor recurrence and recurrence-free survival. The median elastase 1 level was 96ng/dL (range: 21-990ng/dL). Preoperative serum elastase 1 levels were significantly higher in those with tumors ≥ 20mm in diameter (vs. < 20mm, P = 0.018), WHO grade 2 (vs. grade 1, P = 0.035), and microscopic venous invasion (vs. without venous invasion, P = 0.039). The median preoperative serum level of elastase 1 was higher in patients with recurrence than in those without recurrence (251 vs. 80ng/dL, P = 0.004). Receiver operating characteristic analysis of elastase 1 levels showed that a cutoff level of 250ng/dL was associated with postoperative recurrence, with 63% sensitivity, 100% specificity, and 94% overall accuracy. Patients with higher elastase 1 levels showed significantly worse recurrence-free survival than that of those with lower levels (2-year recurrence-free survival rate: 25% and 92%, respectively, P < 0.001). Our data provide the first evidence that high preoperative elastase 1 levels may be a risk factor for postoperative recurrence in patients with resectable PanNETs.

TMEM165, a Golgi transmembrane protein, is a novel marker for hepatocellular carcinoma and its depletion impairs invasion activity.

Transmembrane protein 165 (TMEM165), a Golgi protein, functions in ion homeostasis and vesicular trafficking in the Golgi apparatus. While mutations in TMEM165 are known to cause human ‘congenital disorders of glycosylation’, a recessive autosomal metabolic disease, the potential association of this protein with human cancer development has not been explored to date. In the present study, we revealed that TMEM165 is overexpressed in HCC and its depletion weakens the invasive activity of cancer cells through suppression of matrix metalloproteinase-2 (MMP-2) expression. Levels of TMEM165 mRNA and protein were clearly increased in HCC patient tissues and cell cultures. Quantitative real-time RT-PCR analysis of fresh HCC tissues (n=88) revealed association of TMEM165 overexpression with more frequent macroscopic vascular invasion, microscopic serosal invasion and higher α-fetoprotein levels. Notably, depletion of TMEM165 led to a marked decrease in the invasive activity of two different HCC cell types, Huh7 and SNU475, accompanied by downregulation of MMP-2. Our collective findings clearly indicated that TMEM165 contributed to the progression of HCC by promoting invasive activity, supporting its utility as a novel biomarker and therapeutic target for cancer.

Prognostic importance of bile duct invasion in surgical resection with curative intent for hepatocellular carcinoma using PSM analysis.

There is not yet a consensus regarding a difference in prognosis for patients with hepatocellular carcinoma (HCC) with and without bile duct invasion (BDI). The present study aimed to clarify the prognostic importance of BDI on the short and long-term outcome of patients with HCC who underwent surgical resection. The present study evaluated HCC with BDI, including peripheral microscopic biliary invasion and revealed that the prognosis of patients with BDI was poorer compared with those without BDI. It should be noted that peripheral BDI also had a negative impact on the prognosis of patients with HCC. The clinical prognosis assessment revealed that BDI should be considered when assigning a disease stage. BDI, either macroscopic or microscopic, indicated a poor prognosis in patients with HCC who underwent curative resection, however it was not a surgical contraindication. Macroscopic BDI and hyperbilirubinemia were significantly associated with a dismal prognosis, which should alert surgeons.

Risk of pleural recurrence after percutaneous transthoracic needle biopsy in stage I non-small-cell lung cancer.

To determine whether percutaneous transthoracic needle biopsy (PTNB) increased the risk of pleural recurrence in stage I non-small-cell lung cancer (NSCLC). In this retrospective study, we reviewed 830 consecutive patients with stage I NSCLC who underwent curative resection between 2004 and 2010. Cox regression analyses with propensity score matching were performed to identify risk factors for pleural recurrence. Of 830 patients, 540 (65.1%) underwent PTNB before surgery, while 290 (34.9%) underwent preoperative bronchoscopic biopsy or intraoperative wedge resection for a pathological diagnosis. Concomitant pleural recurrence occurred in 42 patients (5.1% [95% CI, 3.8-6.8]; 34 [6.3%] PTNB patients and eight [2.8%] non-PTNB patients) and isolated pleural recurrence took place in 26 patients (3.1% [95% CI, 2.1-4.6]; 20 [3.7%] PTNB patients and 6 [2.1%] non-PTNB patients). On multivariate analysis after matching, only visceral pleural invasion was associated with concomitant pleural recurrence (hazard ratio [HR]=3.367; 95% CI, 1.262-8.986; p=0.015) and isolated pleural recurrence (HR=3.216; 95% CI, 1.037-9.978; p=0.043), while PTNB was associated with neither concomitant nor isolated pleural recurrence (p=0.605 and p=0.963, respectively). Among 540 patients undergoing PTNB, the transfissural approach did not have a significant association with pleural recurrence (p=0.539 and p=0.313, respectively); instead, visceral pleural invasion and microscopic lymphatic invasion were significantly associated with concomitant pleural recurrence, and microscopic lymphatic invasion was associated with isolated pleural recurrence (p<0.05). PTNB did not significantly increase the risk of pleural recurrence in stage I NSCLC, whereas visceral pleural invasion was responsible for pleural recurrence. • PTNB did not significantly increase the risk of pleural recurrence in stage I NSCLC, whereas visceral pleural invasion was responsible for pleural recurrence. • The transfissural approach in PTNB did not increase the risk of pleural recurrence. • PTNB can be performed for the confirmatory diagnosis of peripheral stage I lung cancer without concern for the risk of pleural recurrence.

The Predictors of Microscopic Vessel Invasion Differ Between Primary Hepatocellular Carcinoma and Hepatocellular Carcinoma with a Treatment History.

Previous studies have shown that microscopic vessel invasion (MVI) occurs in hepatocellular carcinoma (HCC) with a treatment history due to its poorer malignant behavior in comparison with primary HCC. The aim of the present study was to determine the predictors of MVI and overall survival in HCC patients with a treatment history. This retrospective study included 580 patients who underwent hepatectomy and whose preoperative imaging showed no evidence of macroscopic vessel invasion. The patients were classified into two groups: primary HCC (n = 425) and HCC with a treatment history (n = 155). MVI was defined as the presence of either microscopic portal vein invasion or venous invasion, which was invisible on preoperative imaging. MVI was identified in 34 (21.9%) patients with a treatment history. A multivariate analysis showed that a high des-gamma-carboxy prothrombin (odds ratio [OR] 5.16, P = 0.002) and a large tumor diameter (OR 2.57, P = 0.030) were the significant predictor of MVI in HCC with a treatment history. Moreover, the presence of MVI (hazard ratio [HR] 2.27, P = 0.001) and tumor diameter >27mm (HR 2.04, P = 0.006) remained significant predictors of the overall survival in HCC with a treatment history. The tumor diameter cutoff value for predicting MVI (27mm) in HCC with a treatment history was smaller than in primary HCC (37mm). The presence of MVI was a significant predictor in the HCC patients with a treatment history. The tumor diameter is an important factor that can be used to predict the presence of MVI, especially in HCC with a treatment history.

Multi-institutional Analysis of Vaginal Brachytherapy Alone for Women With Stage II Endometrial Carcinoma

To investigate the survival endpoints in women with International Federation of Gynecology and Obstetrics (FIGO) stage II endometrial cancer who received adjuvant vaginal brachytherapy (VBT) alone using multi-institutional pooled data. We performed a multi-institutional analysis of surgically staged patients with FIGO stage II endometrioid-type endometrial cancer treated with VBT alone. Patient, tumor, and treatment characteristics were collected and analyzed. Univariable and multivariable frailty survival models were performed to assess clinicopathologic risk factors for recurrence and death. One hundred six patients were included (92 VBT alone and 14 VBT with chemotherapy) with median follow-up of 39.0months. Pelvic node dissection was performed in 89.6% of patients. One hundred four patients (98.1%) and 2 patients (1.9%) had microscopic and macroscopic cervical stromal invasion, respectively. Grade 1 or 2 disease occurred in 88.6% of patients. For patients treated with VBT without chemotherapy, the 5-year estimates of vaginal failure, pelvic nodal failure, and distant metastases were 2.6%, 4.2%, and 7.2%, respectively. Five-year progression-free survival and overall survival were 74.0% and 76.2%, respectively. On univariable and multivariable models for progression-free survival, increasing age and lack of pelvic node resection were hazardous (P<.05). Vaginal and pelvic failure rates were low in this selected population of stage II patients receiving adjuvant VBT without external beam radiation therapy. It is reasonable to consider adjuvant VBT alone in selected patients with grade 1 or 2 disease and microscopic cervical stromal invasion who underwent pelvic lymphadenectomy.

The down-regulation of the CYP2C19 gene is associated with aggressive tumor potential and the poorer recurrence-free survival of hepatocellular carcinoma

Project HOPE (High-tech Omics-based Patient Evaluation) began in 2014 using integrated gene expression profiling (GEP) of cancer tissues as well as diathesis of each patient who underwent an operation at our institution. The aim of this study was to clarify the association between the expression of cytochrome P450s (CYP) genes and recurrence of hepatocellular carcinoma (HCC). The present study included 92 patients. Genes with aberrant expression were selected based on a ≥10-fold difference in the expression between tumor and non-tumor tissues. The GEP analysis showed that the down-regulated genes in tumor tissue were CYP3A4 in 56 patients (61%), CYP2C8 in 44 patients (48%), CYP2C19 in 30 patients (33%), CYP2D6 in 11 patients (12%), CYP3A5 in 7 patients (8%) and CYP1B1 in 2 patients (2%). There was no patients with down-regulation of the CYP17A1 gene. A multivariate analysis revealed that the presence of microscopic portal invasion (hazard ratio [HR] 2.57, 95% confidence interval [CI] 1.30–5.05 P = 0.006), the presence of intrahepatic-metastasis (HR 3.09 95% CI 1.52–6.29 P = 0.002) and down-regulation of the CYP2C19 gene (HR 3.69 95% CI 1.83–7.46 P < 0.001) were independent predictors for the recurrence-free survival (RFS). The down-regulation of the CYP2C19 gene were correlated with the RFS in HCC.

Defining and Predicting Early Recurrence in 957 Patients With Resected Pancreatic Ductal Adenocarcinoma.

To establish an evidence-based cut-off to differentiate between early and late recurrence and to compare clinicopathologic risk factors between the two groups. A clear definition of "early recurrence" after pancreatic ductal adenocarcinoma resection is currently lacking. Patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma between 2000 and 2013 were included. Exclusion criteria were neoadjuvant therapy and incomplete follow-up. A minimum P-value approach was used to evaluate the optimal cut-off value of recurrence-free survival to divide the patients into early and late recurrence cohorts based on subsequent prognosis. Potential risk factors for early recurrence were assessed with logistic regression models. Of 957 included patients, 204 (21.3%) were recurrence-free at last follow-up. The optimal length of recurrence-free survival to distinguish between early (n = 388, 51.5%) and late recurrence (n = 365, 48.5%) was 12 months (P < 0.001). Patients with early recurrence had 1-, and 2-year post-recurrence survival rates of 20 and 6% compared with 45 and 22% for the late recurrence group (both P < 0.001). Preoperative risk factors for early recurrence included a Charlson age-comorbidity index ≥4 (OR 1.65), tumor size > 3.0 cm on computed tomography (OR 1.53) and CA 19-9 > 210 U/mL (OR 2.30). Postoperative risk factors consisted of poor tumor differentiation grade (OR 1.66), microscopic lymphovascular invasion (OR 1.70), a lymph node ratio > 0.2 (OR 2.49), and CA 19-9 > 37 U/mL (OR 3.38). Adjuvant chemotherapy (OR 0.28) and chemoradiotherapy (OR 0.29) were associated with a reduced likelihood of early recurrence. A recurrence-free interval of 12 months is the optimal threshold for differentiating between early and late recurrence, based on subsequent prognosis.