Enhanced Clinical Utility of Molecular Budding Signature as a Recurrence Risk Determinant in Stage II and III Colon Cancer Patients.

BACKGROUND: A molecular budding signature (MBS), which consists of seven tumor budding-related genes, was recently presented as a prominent prognostic indicator in colon cancer (CC) using microarray data acquired from frozen specimens. This study aimed to confirm the predictive power of MBS for recurrence risk based on formalin-fixed, paraffin-embedded (FFPE) materials. METHODS: This research utilized the same microarray data from a prior multicenter study using FFPE whole tissue sections, which retrospectively reviewed 232 stage II CC patients without adjuvant chemotherapy and 302 stage III CC patients with adjuvant chemotherapy. All patients underwent upfront curative surgery without neoadjuvant therapy between 2009 and 2012. An MBS score was calculated using the mean of log2 [each signal] of seven genes (MSLN, SLC4A11, WNT11, SCEL, RUNX2, MGAT3, and FOXC1) as described before. RESULTS: The MBS-low group exhibited a better relapse-free survival (RFS) than the MBS-high group in stage II (P = 0.0077) and in stage III CC patients (P = 0.0003). Multivariate analyses revealed that the MBS score was an independent prognostic factor in both stage II (P = 0.0257) and stage III patients (P = 0.0022). Especially among T4, N2, or both (high-risk) stage III patients, the MBS-low group demonstrated markedly better RFS compared with the MBS-high group (P = 0.0013). CONCLUSIONS: This study confirmed the predictive power of the MBS for recurrence risk by employing FFPE materials in stage II/III CC patients.

Evaluation of a 55-gene classifier as a prognostic biomarker for adjuvant chemotherapy in stage III colon cancer patients.

BACKGROUND: Adjuvant chemotherapy reduces the risk of recurrence of stage III colon cancer (CC). However, more effective prognostic and predictive biomarkers are needed for better treatment stratification of affected patients. Here, we constructed a 55-gene classifier (55GC) and investigated its utility for classifying patients with stage III CC. METHODS: We retrospectively identified patients aged 20-79 years, with stage III CC, who received adjuvant chemotherapy with or without oxaliplatin, between the years 2009 and 2012. RESULTS: Among 938 eligible patients, 203 and 201 patients who received adjuvant chemotherapy with and without oxaliplatin, respectively, were selected by propensity score matching. Of these, 95 patients from each group were analyzed, and their 5-year relapse-free survival (RFS) rates with and without oxaliplatin were 73.7 and 77.1%, respectively. The hazard ratios for 5-year RFS following adjuvant chemotherapy (fluoropyrimidine), with and without oxaliplatin, were 1.241 (95% CI, 0.465-3.308; P = 0.67) and 0.791 (95% CI, 0.329-1.901; P = 0.60), respectively. Stratification using the 55GC revealed that 52 (27.3%), 78 (41.1%), and 60 (31.6%) patients had microsatellite instability (MSI)-like, chromosomal instability (CIN)-like, and stromal subtypes, respectively. The 5-year RFS rates were 84.3 and 72.0% in patients treated with and without oxaliplatin, respectively, for the MSI-like subtype (HR, 0.495; 95% CI, 0.145-1.692; P = 0.25). No differences in RFS rates were noted in the CIN-like or stromal subtypes. Stratification by cancer sidedness for each subtype showed improved RFS only in patients with left-sided primary cancer treated with oxaliplatin for the MSI-like subtype (P = 0.007). The 5-year RFS rates of the MSI-like subtype in left-sided cancer patients were 100 and 53.9% with and without oxaliplatin, respectively. CONCLUSIONS: Subclassification using 55GC and tumor sidedness revealed increased RFS in patients within the MSI-like subtype with stage III left-sided CC treated with fluoropyrimidine and oxaliplatin compared to those treated without oxaliplatin. However, the predictive power of 55GC subtyping alone did not reach statistical significance in this cohort, warranting larger prospective studies. TRIAL REGISTRATION: The study protocol was registered in the University Hospital Medical Education Network (UMIN) clinical trial registry (UMIN study ID: 000023879 ).

Preoperative fall risk assessment score as a prognostic factor in gastric cancer patients after gastrectomy.

OBJECTIVE: Falls are related to frailty, which is known as an unfavorable prognosticator of gastric cancer. In this study, we investigated the influence of the fall risk assessment score on short- and long-term prognoses in patients with gastric cancer after gastrectomy. METHODS: A total of 430 patients who underwent gastrectomy for gastric cancer were included in this retrospective study. The fall risk assessment score was scored by nursing staffs on admission. We investigated the relationships between the fall risk assessment score and clinicopathological findings, postoperative outcomes and prognoses. We assigned patients with a fall risk assessment score ≥7 to the high-risk group (92 cases, 21.4%) and those with a fall risk assessment score <6 to the low-risk group (338 cases, 78.6%). RESULTS: There were no significant differences between the two groups in pathological stage of gastric cancer and postoperative complications, but the high-risk group had significantly longer postoperative hospital stays than the low-risk group (P < 0.001). The overall and the relapse-free survival rates in the high-risk group were significantly lower than those in the low-risk group. The high-risk group was one of the independent poor prognostic factors for overall survival, with a hazard ratio of 2.91 (P ≤ 0.001) in univariate analysis and a hazard ratio of 2.74 (P = 0.008) in multivariate analysis. CONCLUSIONS: While the fall risk assessment score is an objective and easy-to-use method to assess fall risk and frailty, it may present a prognostic factor in gastric cancer.

Modified geriatric nutrition risk index as a prognostic predictor of esophageal cancer.

BACKGROUND: This study aimed to establish a simple and useful prognostic indicator for elderly esophageal cancer patients. We designed the modified geriatric nutrition risk index (mGNRI) using the inverse of C-reactive protein (CRP) instead of albumin and compared its prognostic value with those of the GNRI and other indices. METHODS: We included 128 patients aged > 65 years who underwent esophagectomy for esophageal cancer. We defined mGNRI as (1.489/CRP in mg/dL) + (41.7 × present/ideal body weight) and divided patients into two groups: the low-mGNRI (mGNRI < 70, n = 50) and high-mGNRI (mGNRI ≥ 70, n = 78) groups. We retrospectively examined the relationship between mGNRI and long-term prognosis. RESULTS: The low-mGNRI group had more advanced cancer by stage, higher rates of recurrence, and earlier recurrence than the high-mGNRI group. Univariate analysis identified the following factors as significantly associated with poor overall survival (OS): a lower American society of anesthesiologist performance status (ASA-PS), male gender, CRP-albumin ratio ≥ 0.1, CRP ≥ 1.0, low-mGNRI, tumor depth ≥ T3, Charlson comorbidity index ≥ 2, tumor size ≥ 40 mm, and age > 75 years. A low-mGNRI, ASA-PS 3, age > 75 years, and tumor depth ≥ T3 were independent unfavorable prognostic factors for OS. A low-mGNRI was an independent poor prognostic factor for relapse-free survival. We performed model selection analysis to identify the most clinically useful indices; mGNRI was the best predictive model. CONCLUSION: mGNRI in patients with esophageal cancer correlated with early recurrence and was a useful independent prognostic factor.

Prognostic Impact of Budding Grade in Patients With Residual Liver Recurrence of Colorectal Cancer After Initial Hepatectomy.

BACKGROUND: Many patients undergoing hepatectomy for colorectal liver metastases (CRLM) experience recurrence. However, no criteria for screening candidates to undergo repeat hepatectomy (RH) for CRLM have been established. Budding, one form by which colorectal carcinoma malignancies are expressed, is a new pathologic index. This study aimed to analyze prognostic factors, including budding, and to provide criteria for screening candidates to undergo RH for recurrent CRLM. METHODS: Data of 186 consecutive patients who underwent hepatectomy for CRLM between April 2008 and December 2015 were collected. Survival was calculated using the Kaplan-Meier method. Uni- and multivariate analyses were performed to determine factors significantly affecting mortality. RESULTS: Of 186 patients, 131 experienced recurrence after hepatectomy, with 83 of the 131 patients showing recurrence in the liver, and 52 of these 83 patients undergoing primary surgery at the authors' institution and having information on budding grade. In the univariate analysis, preoperative chemotherapy, budding grade, extrahepatic metastases, and number of liver metastases at the time of recurrence were associated with overall survival (OS) for the 52 patients. In the multivariate analysis, budding grade and number of liver metastases at the time of recurrence were associated with OS. CONCLUSION: The study examined simple prognostic factors that could help to screen patients better for RH. Repeat hepatectomy improved the prognosis for patients with recurrent CRLM. The independent prognostic factors for OS were number of liver metastases at recurrence as a conventional factor and budding grade as a new pathologic factor. With budding used as an index, patients who could benefit from hepatectomy can be screened more precisely.

Clinical Significance of a Gene Signature Generated from Tumor Budding Grade in Colon Cancer.

BACKGROUND: Tumor budding, a microscopic finding of dedifferentiation at the invasive margin, has been reported as a definite prognostic marker in colon cancer (CC). Herein, we aimed to generate a molecular budding signature (MBS) based on DNA microarray data and to examine its prognostic significance. METHODS: Frozen tissue samples from 85 patients with stage II/III CC were used for DNA microarray analyses. First, we selected candidate genes that were differentially expressed (twofold change) between the invasive frontal regions and corresponding tumor centers of three extremely high-grade budding tumors. Subsequently, using microarray data from whole-tissue sections of the 85 patients, we selected MBS-constituent genes from the candidates based on correlation to the pathological budding grade. The MBS score was calculated using the sum of the logarithm of the expression of each gene. RESULTS: We selected seven MBS-constituent genes: MSLN, SLC4A11, WNT11, SCEL, RUNX2, MGAT3, FOXC1. A comparison of relapse-free survival (RFS) rates revealed a significant impact of the MBS score [5-year RFS, 77.4% (score-high) vs. 95.1% (score-low); P = 0.044]. Analyses of public databases revealed that low MBS score patients exhibited better prognosis than those with high-score cancers (GSE14333: 5-year RFS, 83.1% vs. 66.6%, P = 0.028; GSE39582: 5-year disease-free survival, 72.2% vs. 58.1%, P = 0.0005). Multivariate analysis revealed that the MBS score is an independent prognostic indicator in GSE39582 (hazard ratio, 1.611; P = 0.013). CONCLUSIONS: We developed a new gene classification method, i.e., MBS, and demonstrated its clinical relevance as an indicator of high recurrence risk of CC.

A Validation Study for Recurrence Risk Stratification of Stage II Colon Cancer Using the 55-Gene Classifier.

INTRODUCTION: DNA microarrays, such as the consensus molecular subtype (CMS) classification using >600 genes, are used to predict cancer patient prognosis. We recently constructed a simple 55-gene classifier (55GC) system to risk stratify colon cancer (CC). OBJECTIVE: Here, we validate the 55GC specifically for stage II CC and compare it with CMS categories. METHODS: Tissue sections from 232 stage II CC patients who underwent curative surgery without adjuvant chemotherapy between 2009 and 2012 were subjected to DNA microarray analysis. RESULTS: Based on the 55GC, patients were classified into microsatellite instability-like (27%), chromosomal instability-like (41%), and stromal (32%) subtypes with 5-year relapse-free survival (RFS) rates of 88.5, 83.3, and 71.2%, respectively (stromal vs. others: p = 0.0049). Multivariate analysis by Cox's proportional hazard model revealed that the stromal subtype, pT4, and the number of lymph nodes examined (<12) were independent poor prognostic factors. The overall concordance rate between 55GC and CMS was 72%, and 5-year RFS rates of patients with CMS1, CMS2, CMS3, and CMS4 cancers were 100, 85.5, 92.3, and 73.0%, respectively (p = 0.0113). CONCLUSIONS: We conclude that the 55GC is a useful and reproducible grading system for stage II CC recurrence risk stratification.

Risk factors for nonalcoholic fatty liver disease after gastrectomy for gastric cancer.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) refers to hepatic steatosis caused by something other than alcoholic liver injury, and often occurs after gastrointestinal surgeries such as pancreatoduodenectomy and gastrectomy. This study aimed to identify the risk factors for NAFLD after gastrectomy for gastric cancer. METHODS: A total of 721 patients who underwent gastrectomy for gastric cancer and plane abdominal computed tomography (CT) preoperatively and 1 year after surgery were included in this study. NAFLD was defined as having a mean hepatic CT attenuation value of < 40 Hounsfield units. We retrospectively examined the relationship between the onset of NAFLD and clinicopathological findings to identify the risk factors associated with the development of NAFLD after gastrectomy. RESULTS: The incidence of postoperative NAFLD was 4.85% (35/721). The univariate analysis identified the following factors as being significantly associated with the incidence of NAFLD: age, preoperative BMI ≥ 25 kg/m2, tumor depth of pT3 ≤, lymph node metastasis grade of pN2 ≤, cholecystectomy, D2 lymphadenectomy, adjuvant chemotherapy, high preoperative cholinesterase serum level, and low grade of preoperative FIB-4 index. Adjuvant chemotherapy (p < 0.001) and high preoperative cholinesterase serum level (p = 0.021) were identified as independent risk factors for NAFLD 1 year after gastrectomy. CONCLUSION: Our study showed that adjuvant chemotherapy with S-1 and high level of serum cholinesterase were considered as the risk factors for NAFLD occurring after gastrectomy for gastric cancer.

Efficacy of artificial pneumothorax under two-lung ventilation in video-assisted thoracoscopic surgery for esophageal cancer.

BACKGROUND: One-lung ventilation (OLV) is the standard and widely applied ventilation approach used in video-assisted thoracoscopic surgery for esophageal cancer (VATS-e). To address the disadvantages of OLV with respect to difficulties in intubation and induction, as well as the risk of respiratory complications, two-lung ventilation (TLV) with artificial pneumothorax has been introduced for use in VATS-e. However, no studies have yet compared TLV and OLV with postoperative infection and inflammation in the prone position over time postoperatively. Here, we investigated the efficacy of TLV in patients undergoing VATS-e in the prone position. METHODS: Between April 2010 and December 2016, 119 patients underwent VATS-e under OLV or TLV with carbon dioxide insufflation. Clinical characteristics, surgical outcomes, and postoperative outcomes, including oxygenation and systemic inflammatory responses, were compared between patients who underwent OLV and those who underwent TLV. RESULTS: Clinical characteristics other than pT stage were comparable between groups. The TLV group had shorter thoracic operation time than the OLV group. No patients underwent conversion to open thoracotomy. The PaO2/FiO2 ratios of the TLV group on postoperative day (POD) 5 and on POD7 were significantly higher than those of the OLV group. C-reactive protein levels on POD7 were lower in the TLV group than in the OLV group. There were no significant differences with respect to postoperative complications between the OLV and TLV groups. In the TLV group, the white blood cell count on POD7 was significantly lower than that in the OLV group; body temperature showed a similar trend immediately after surgery and on POD1. CONCLUSIONS: In this study, we demonstrated that, compared with OLV, TLV in the prone position provides better oxygenation and reduced inflammation in the postoperative course. Accordingly, TLV might be more useful than OLV for ventilation during esophageal cancer surgery.

Association Between the Frequency of Glove Change and the Risk of Blood and Body Fluid Exposure in Gastrointestinal Surgery.

BACKGROUND: Surgical gloves are used to prevent the transmission of microorganisms from the surgeon's hands to the patient and vice versa. Little is known on the optimal frequency of glove changing. Therefore, we aimed to examine the optimal frequency of glove change during surgery by assessing the glove perforation rate in gastrointestinal surgery. METHODS: In this observational prospective cohort study, we investigated the incidence of perforation of 5,267 gloves during gastrointestinal surgeries. RESULTS: The overall glove perforation rate was 10.1%. There was no significant difference between single gloving (10.2%) and double gloving (10.0%; p = 0.8491). However, the perforation rate of the inner glove (5.7%) was found to be significantly lower than that of the outer glove (11.6%) (p < 0.0001). A significant difference in perforation rate was observed after wearing inner gloves for 240 min (< 240 min, 4.4%; ≤ 240 min, 7.2%; p = 0.0314), and outer gloves for 60 min (< 60 min, 7.1%; ≤ 60 min, 12.6%; p < 0.0001). We found cumulative perforation rate to rapidly increase until the wear time was 90 min. CONCLUSION: The inner gloves and outer gloves have a higher perforation rate as the wear time increased. To reduce the risk of intraoperative blood and fluid exposure and prevent healthcare-associated infection, gloves should be changed for approximately every 60-90 min for outer gloves and approximately every 240 min for inner gloves.

Factors affecting R0 resection of colorectal cancer with synchronous peritoneal metastases: a multicenter prospective observational study by the Japanese Society for Cancer of the Colon and Rectum.

BACKGROUND: In Japan, R0 resection has been recommended for colorectal cancer patients with peritoneal metastases confined to the adjacent peritoneum and those with a few metastases to the distant peritoneum. R0 resection for M1c disease has drawn attention in Western countries and is currently considered an acceptable therapeutic option in the US National Comprehensive Cancer Network guidelines. However, clinical factors that affect the choice of R0 resection are unknown. METHODS: This multicenter, prospective, observational study was conducted by the Japanese Society for Cancer of the Colon and Rectum. Colorectal cancer patients with synchronous peritoneal metastases were enrolled at 28 institutions in Japan from October 2012 to December 2016. To determine factors affecting R0 resection and R1 resection with intended R0 resection, stepwise logistic regression analyses were performed on clinical factors including age, sex, performance status (PS), body mass index, peritoneal cancer index (PCI) score, presence of ascites, presence of distant metastases, and primary tumor site. RESULTS: R0/R1 resection was performed in 36 (31/5; 25%) of 146 patients. No distant metastases [odds ratio (OR) 52.9; 95% confidence interval (CI) 13.3-210.1; p < 0.0001], low PCI score (1-6) (OR 20.0; 95% CI 4.8-83.4; p < 0.0001), and high PS (0) (OR 2.40; 95% CI 0.66-8.68; p = 0.18) were independent factors affecting R0/R1 resection. PCI score and PS were also independent factors affecting R0/R1 resection in M1c patients without non-peritoneal distant metastases (n = 59). CONCLUSION: Distant metastases, PCI score, and PS are three factors which affect R0 resection for M1c disease.

Successful surgical drainage with intraoperative ultrasonography for amebic liver abscess refractory to metronidazole and percutaneous drainage: a case report.

BACKGROUND: Metronidazole (MNZ) has been clearly established as a medication for amebic liver abscess. In uncomplicated cases, surgical drainage should be avoided. We report a case of amebic liver abscess refractory to MNZ that was successfully treated using preoperative computed tomography (CT) and percutaneous and surgical drainage with intraoperative ultrasonography (IOUS). CASE PRESENTATION: A 53-year-old man with high-grade fever was diagnosed with a cystic lesion on his right hepatic lobe using CT. Percutaneous drainage was performed, and antibacterial drugs were administered. However, the infection and condition of the patient worsened. Entamoeba histolytica was detected from pus within the mediastinal cavity. Hence, the patient was diagnosed with amebic liver abscess. After the diagnosis was established, we administered MNZ for 10 days. Despite this, the patient's physical condition did not improve. Blood tests suggested impending disseminated intravascular coagulation (DIC). We performed surgical intervention to drain the amebic liver abscess refractory to conservative treatment. During surgery, imaging information from preoperative CT and IOUS enabled us to recognize the anatomical structures and determine the incision lines of the hepatic capsule and hepatic tissue. The patient's DIC immediately regressed after surgery. Unfortunately, malnutrition and disuse syndrome contributed to the patient's long recovery period. He was discharged 137 days post-surgery. CONCLUSIONS: We reported a case of amebic liver abscess refractory to conservative treatment. Surgical drainage with preoperative CT and IOUS allowed us to safely and effectively perform complex abscess decompression.

Differential clinical impacts of tumour budding evaluated by the use of immunohistochemical and haematoxylin and eosin staining in stage II colorectal cancer.

AIMS: The aim of this study was to clarify the quantitative and qualitative differences in tumour budding identification between haematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for cytokeratin, and to estimate the respective clinical impacts in stage II colorectal cancer. METHODS AND RESULTS: We retrospectively examined 314 surgically resected cases of stage II colorectal cancer, and assessed tumour budding on serial section slides with H&E staining and IHC staining for cytokeratin. Tumour budding counts based on cytokeratin-stained slides were strongly correlated with those based on H&E-stained slides, and had higher detection and reproducibility. On the basis of receiver operating characteristic analyses, the optimal cut-off values of budding counts for relapse-free survival (RFS) were 7 and 16 in a ×200 microscopic field with H&E and IHC staining, respectively. With these cut-off values, tumour budding based on H&E staining had a significant correlation with RFS (80.3% and 93.2% of 5-year RFS in the high-budding group and the low-budding group, respectively), and similar results were observed for IHC staining (79.9% and 91.7%, respectively). The Akaike Information Criterion value for RFS with H&E staining was favourable as compared with that with IHC staining. CONCLUSIONS: Tumour budding counts based on cytokeratin-stained slides showed higher detection and better reproducibility, but did not have as satisfactory clinical impacts as those based on H&E staining.

Differential Survival Benefits of 5-Fluorouracil-Based Adjuvant Chemotherapy for Patients With Microsatellite-Stable Stage III Colorectal Cancer According to the Tumor Budding Status: A Retrospective Analysis.

BACKGROUND: Recent research has established tumor budding as a prognostic factor and a possible histomorphologic reflection of epithelial-mesenchymal transition in colorectal cancer, highlighting the ability of cancer cells exhibiting epithelial-mesenchymal transition to resist chemotherapy. OBJECTIVE: This study aimed to investigate the clinical benefits of adjuvant chemotherapy according to the tumor budding status in microsatellite-stable stage III colorectal cancer. DESIGN: This was a retrospective study of 2 cohorts. SETTINGS: The study was conducted at the National Defense Medical College in Japan. PATIENTS: We reviewed 2 data sets of patients with microsatellite-stable stage III colorectal cancer with curatively intended surgery (R0) from 1999 to 2005 (first cohort; n = 203) and 2006 to 2012 (second cohort; n = 346). In both cohorts, 128 and 203 patients received 5-fluorouracil-based adjuvant chemotherapy and 75 and 143 patients did not. MAIN OUTCOME MEASURES: We assessed the benefits of adjuvant chemotherapy according to the grades of tumor budding based on the cancer-specific survival. RESULTS: In low-budding tumors, the chemotherapy group exhibited better cancer-specific survival than the surgery-alone group (first cohort, 93.1% vs 65.5%, p = 0.001; second cohort, 94.0% vs 76.0%, p < 0.0001). Conversely, the prognostic difference between the chemotherapy and surgery-alone groups was statistically insignificant in high-budding tumors (first cohort, 59.7% vs 52.4%, p = 0.57; second cohort, 83.1% vs 75.6%, p = 0.19). The multivariate analysis corroborated the benefits of adjuvant chemotherapy in low-budding tumors (first cohort, p = 0.002, HR = 0.28; second cohort, p < 0.0001, HR = 0.23) but not in high-budding tumors. LIMITATIONS: Postoperative adjuvant chemotherapy and treatments for recurrence were not homogeneous, and the patient backgrounds differed between the chemotherapy and surgery alone groups. CONCLUSIONS: The high-budding group demonstrated resistance to 5-fluorouracil-based chemotherapy, whereas the low-budding group exhibited significant survival benefits from adjuvant chemotherapy in stage III colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B14. BENEFICIOS DE SUPERVIVENCIA DIFERENCIAL DE LA QUIMIOTERAPIA ADYUVANTE BASADA EN 5-FLUOROURACILO PARA PACIENTES CON CÁNCER COLORRECTAL EN ESTADIO III ESTABLE CON MICROSATÉLITE SEGÚN EL ESTADO DE BROTACIÓN DEL TUMOR: UN ANÁLISIS RETROSPECTIVO:: Investigaciones recientes han establecido la aparición de tumores como un factor pronóstico y una posible reflexión histomorfológica de la transición epitelial-mesenquimatosa en el cáncer colorrectal, destacando la capacidad de las células cancerosas que presentan una transición epitelio-mesenquimática para resistir la quimioterapia.El objetivo de este estudio es investigar los beneficios clínicos de la quimioterapia adyuvante según el estado de brotación del tumor en el cáncer colorrectal en estadio III estable con microsatélite.Este fue un estudio retrospectivo de dos cohortes.El estudio se realizó en la Escuela de Medicina de la Defensa Nacional de Japón.Revisamos dos conjuntos de datos de pacientes con cáncer colorrectal en estadio III estable con microsatélite con cirugía de intención curativa (R0) de 1999 a 2005 (primera cohorte; n = 203) y 2006 a 2012 (segunda cohorte; n = 346). En ambas cohortes, 128 y 203 pacientes recibieron quimioterapia adyuvante basada en 5-fluorouracilo y 75 y 143 pacientes no, respectivamente.Evaluamos los beneficios de la quimioterapia adyuvante de acuerdo con los grados de brotación del tumor en función de la supervivencia específica del cáncer.n los tumores con brotes bajos, el grupo de quimioterapia mostró una mejor supervivencia específica al cáncer que el grupo con cirugía sola (primera cohorte, 93.1% vs. 65.5%, p = 0.001; segunda cohorte, 94.0% vs. 76.0%, p < 0.0001). A la inversa, la diferencia pronóstica entre los grupos de quimioterapia y cirugía sola fue estadísticamente insignificante en los tumores de brotes elevados (primera cohorte, 59.7% vs. 52.4%, p = 0.57; segunda cohorte, 83.1% vs. 75.6%, p = 0.19). El análisis multivariado corroboró los beneficios de la quimioterapia adyuvante en los tumores de brotes bajos (primera cohorte, p = 0,002, índice de riesgo: 0,28; segundo cohorte, p <0,0001, índice de riesgo: 0,23) pero no en los tumores de alto brote.a quimioterapia adyuvante postoperatoria y los tratamientos para la recurrencia no fueron homogéneos, y los antecedentes de los pacientes difirieron entre los grupos de quimioterapia y cirugía sola.El grupo de alto brote demostró resistencia a la quimioterapia basada en 5-fluorouracilo, mientras que el grupo de bajo brote mostró beneficios significativos de supervivencia de la quimioterapia adyuvante en el cáncer colorrectal en estadio III. Vea el Resumen del Video en http://links.lww.com/DCR/B14.

A New N Staging System for Colorectal Cancer in the Era of Extended Lymphadenectomy.

BACKGROUND: Complete mesocolic excision is becoming popular in colon cancer surgery in Western countries, and in the tumor-node-metastasis (TNM) classification of rectal cancer, a part of the lateral pelvic lymph nodes is classified as regional. However, the appropriateness of TNM staging according to the assessment of nodal status exclusively by extended lymphadenectomy remains unclear. PATIENTS AND METHODS: Using a nationwide multicenter database in Japan, we retrospectively analyzed 6866 patients with stage III colorectal cancer (CRC) treated with extended (D3) dissection. First, the best cutoff values for the number of metastatic nodes were explored. Second, the utility of the metastatic status of the main lymph nodes (i.e., at the origin of the feeding artery) and the lateral pelvic lymph nodes ("jN3" category in the Japanese staging system) as N staging criteria was evaluated. The modified N staging system that had the best risk stratification power was determined according to the Akaike information criterion (AIC). RESULTS: Excellent performance was noted when the number of metastatic nodes was categorized by cutoff values of "3/4" and "6/7." Categorization of nodal metastasis was proven the most clinically efficacious when classified as modified-N1 (N1 and jN3-negative), modified-N2a (N2a and jN3-negative), and modified-N2b (N2b and/or jN3-positive; AIC, 22,810.8), rather than the classification based on the TNM (AIC, 22,849.2) or Japanese staging system (AIC, 22,811.1). CONCLUSIONS: We structured a modified N staging system according to the number and extent of lymph node metastases. The modified system may be used in stage III cases for precise risk stratification.

Prominent Information of jN3 Positive in Stage III Colorectal Cancer Removed by D3 Dissection: Retrospective Analysis of 6866 Patients From a Multi-institutional Database in Japan.

BACKGROUND: The presence of main or lateral lymph node metastasis in colorectal cancer is classified as jN3 by the Japanese Society for Cancer of the Colon and Rectum. Whether information on jN3 status adds value to the TNM classification remains unclear. OBJECTIVE: We aimed to assess the prognostic relevance of colorectal cancer nodal staging through the Japanese jN3 categorization compared with that through TNM. DESIGN: This was a retrospective study. SETTING: The study used the multi-institutional database of the Japanese Society for Cancer of the Colon and Rectum. PATIENTS: Clinical and pathological data of 6866 patients with histologically proven stage III colorectal cancer who underwent curative surgery (R0) with D3 dissection between 1995 and 2006 were derived from the database. MAIN OUTCOME MEASURES: We investigated the prognostic significance of jN3 status in each TNM N class (N1/N2a/N2b) and stage (IIIA/IIIB/IIIC) based on cancer-specific survival. RESULTS: Comparison of cancer-specific survival rates revealed significant differences between jN3+ and jN3- colorectal cancer patient groups according to the TNM N status (5-year cancer-specific survival; N1, 70.4% (jN3+) vs 85.5% (jN3-), p < 0.001; N2a, 59.2% vs 77.0%, p < 0.001; N2b, 39.2% vs 68.7%, p < 0.001) and the TNM stage (stage IIIA, 72.5% vs 94.9%, p < 0.001; stage IIIB, 67.9% vs 84.0%, p < 0.001; stage IIIC, 42.4% vs 70.6%, p < 0.001). LIMITATIONS: This study was limited by its retrospective nature. CONCLUSIONS: Assessment and inclusion of jN3 status are of clinical importance for patients with stage III colorectal cancer with D3 dissection, because it contributes to improved understanding of recurrence risk and subsequent decision-making for follow-up procedures and adjuvant therapy. See Video Abstract at http://links.lww.com/DCR/A506.

Impact of angiotensin-converting enzyme 2 levels on postoperative pneumonia after esophagectomy.

BACKGROUND: Pulmonary complications after esophagectomy are often fatal. The prediction of postoperative pulmonary complications remains a challenge. Accumulating evidence demonstrates a physiological and pathological role for angiotensin-converting enzyme 2 (ACE2) in the respiratory system. The purpose of this study was to evaluate the predictive value of ACE2 levels for the development of postoperative pneumonia. METHODS: To evaluate the association between serum ACE2 levels and pneumonia after esophagectomy, we retrospectively reviewed the medical records of 80 patients who underwent thoracoscopic esophagectomy for esophageal cancer from 2009 to 2014. RESULTS: Nineteen patients (23.8%) developed pneumonia after esophagectomy. Patients with pneumonia had significantly higher levels of ACE2 from the preoperative day to postoperative day (POD) 3, white blood cell count (POD7), and C-reactive protein (POD3, POD5, and POD7) than patients without pneumonia. Patients with postoperative pneumonia had higher serum ACE2 levels on POD3 than patients without pneumonia. CONCLUSIONS: The elevation of ACE2 levels on POD3 may predict the incidence of pneumonia.

Antimicrobial susceptibility of common pathogens isolated from postoperative intra-abdominal infections in Japan.

The principle of empirical therapy for patients with intra-abdominal infections (IAI) should include antibiotics with activity against Enterobacteriaceae and Bacteroides fragilis group species. Coverage of Pseudomonas aeruginosa, Enterobacter cloacae, and Enterococcus faecalis is also recommended for hospital-associated IAI. A nationwide survey was conducted to investigate the antimicrobial susceptibility of pathogens isolated from postoperative IAI. All 504 isolates were collected at 26 institutions and referred to a central laboratory for susceptibility testing. Lower susceptibility rates to ciprofloxacin and cefepime were demonstrated in Escherichia coli. Among E. coli, 24.1% of strains produced extended-spectrum ß-lactamase (ESBL). Carbapenems, piperacillin/tazobactam, cephamycins/oxacephem, aminoglycosides, and tigecycline had high activity against E. coli, including ESBL-producing isolates. Among E. cloacae, low susceptibility rates to ceftazidime were demonstrated, whereas cefepime retained its activity. P. aeruginosa revealed high susceptibility rates to all antimicrobials tested except for imipenem. Among B. fragilis group species, low levels of susceptibility were observed for cefoxitin, moxifloxacin, and clindamycin, and high susceptibility rates were observed for piperacillin/tazobactam, meropenem, and metronidazole. Ampicillin, piperacillin, and glycopeptides had good activity against E. faecalis. Imipenem had the highest activity against E. faecalis among carbapenems. In conclusion, we suggested the empirical use of antimicrobials with the specific intent of covering the main organisms isolated from postoperative IAI. Piperacillin/tazobactam, meropenem, or doripenem, are appropriate in critically ill patients. Combination therapy of cefepime (aztreonam in patients with ß-lactam allergy) plus metronidazole plus glycopeptides, imipenem/cilastatin or cephamycins/oxacephem plus ciprofloxacin plus metronidazole are potential therapeutic options.

MET4 expression predicts poor prognosis of gastric cancers with Helicobacter pylori infection.

The role of HGF/SF-MET signaling is important in cancer progression, but its relation with Helicobacter pylori-positive gastric cancers remains to be elucidated. In total, 201 patients with primary gastric carcinoma who underwent curative or debulking resection without preoperative chemotherapy were studied. MET4 and anti-HGF/SF mAbs were used for immunohistochemical analysis. Survival of gastric cancer patients was estimated by Kaplan-Meier method and compared with log-rank. Cox proportional hazards models were fit to determine the independent association of MET-staining status with outcome. The effect of live H. pylori bacteria on cell signaling and biological behaviors was evaluated using gastric cancer cell lines. MET4-positive gastric cancers showed poorer prognosis than MET4-negative cases (overall survival, P = 0.02; relapse-free survival, P = 0.06). Positive staining for MET4 was also a statistically significant factor to predict poor prognosis in H. pylori-positive cases (overall survival, P < 0.01; relapse-free survival, P = 0.01) but not in H. pylori-negative cases. Gastric cancers positively stained with both HGF/SF and MET4 showed a tendency of the worst prognosis. Stimulation of MET-positive gastric cancer cells with live H. pylori bacteria directly upregulated MET phosphorylation and activated MET downstream signals such as p44/42MAPK and Akt, conferring cell proliferation and anti-apoptotic activity. In conclusion, positive staining for MET4 was useful for predicting poor prognosis of gastric cancers with H. pylori infection. Helicobacter pylori stimulated MET-positive gastric cancers and activated downstream signaling, thereby promoting cancer proliferation and anti-apoptotic activity. These results support the importance of H. pylori elimination from gastric epithelial surface in clinical therapy.