Impact of surgical proximal and distal margins on the recurrence of resectable colon cancer: a single-center observational cohort study.

PURPOSE: Few studies have investigated the impact of the surgical proximal and distal margins on colon cancer recurrence. We conducted this study to investigate the effect of resection margins on the prognosis of resectable colon cancer. METHODS: We analyzed data on 1458 patients who underwent colorectal resection in our institute between January, 2004 and March, 2020, including 579 patients with resectable colon cancer. The association between the resection margin and recurrence for each oncological status was assessed and the value of the resection length that influenced recurrence was analyzed. RESULTS: Patients who had pT4 colon cancer with margins of more than 7 cm had a trend of fewer recurrences and longer relapse-free survival (RFS) than those with colon cancer of other stages (P = 0.033; hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.20-0.89). Multivariate analysis identified a margin of < 7 cm as an independent risk factor for RFS in patients with pT4 colon cancer (P = 0.023; HR, 2.65; 95% CI 1.013-6.17). No correlation was found between resection margins and recurrence, depending on the extent of lymph node metastasis and tumor location. CONCLUSION: A resection margin of at least 7 cm should be maintained for patients with pT4 colon cancer.

Evaluation of gastric tube blood flow by multispectral camera and fluorescence angiography.

Background: Evidence regarding the application of the multispectral camera for blood flow measurement is insufficient, and its performance has not been compared with the conventional indocyanine green (ICG) method. Therefore, we retrospectively compared the effectiveness of a new multispectral camera for non-invasive, real-time, quantitative imaging of tissue oxygen (O2) saturation and hemoglobin (Hb) levels and commercially available ICG fluorescence imaging in hemodynamic assessment of gastric tubes in esophagectomy. Methods: Thirty patients who underwent thoracoscopic esophagectomy and gastric tube reconstruction for esophageal cancer were included in this study. The multispectral camera was used to measure tissue O2 saturation and Hb levels. The ICG fluorescence imaging, with the analysis software tool Lumi view, was employed to record ICG luminance changes, with values measured at the anastomotic site. Furthermore, the usefulness of each assessment device was examined using the arterial and venous blood flow indices as cutoff lines for cases with anastomotic failure. Results: In the evaluation of arterial perfusion, anastomotic leak occurred in three of the five (60 %) patients with arterial insufficiency as assessed by the ICG imaging, while anastomotic leakage occurred in all three patients (100 %) who were assessed as having arterial insufficiency by the multispectral camera. In the evaluation of venous perfusion, anastomotic leakage occurred in three of the nine (33.3 %) patients diagnosed with venous stasis by the IC imaging and in three of the five (60 %) patients assessed by the multispectral camera. Conclusion: The multispectral camera assessed gastric tube blood flow more accurately than the ICG fluorescence method.

Neoadjuvant Chemotherapy in Patients With T4b or Obstructive Colon Cancer: A Single Center Retrospective Cohort Study.

BACKGROUND/AIM: The efficacy of neoadjuvant chemotherapy (NAC) for colon cancer remains unestablished. This study aimed to investigate the outcomes of NAC in patients with locally advanced T4b or obstructive T4a colon cancers (LACC). PATIENTS AND METHODS: Data of patients with LACC who underwent colon surgery between 2010 and 2022 after NAC at our institution were retrospectively reviewed. Patient characteristics, surgical outcomes, tumor features, and prognosis were analyzed. RESULTS: Among 800 patients with LACC who underwent radical resection, 11 received NAC because of cT4b or cT4a with mechanical obstruction. NAC, administered as a doublet regimen, had a median duration of three months, without grade ≥3 adverse events. R0 resection was achieved in all patients and downstaging was observed in eight patients. One patient developed a postoperative abdominal abscess, and adjuvant chemotherapy was administered to eight patients. Four patients experienced recurrence: liver metastasis in two, and local recurrence in two. Among these, three patients underwent resection of recurrent tumors. Median follow-up was 30 months. CONCLUSION: NAC is feasible for T4b or obstructive T4a colon cancer and may be a treatment option for LACC. Further large-scale studies are required to confirm the efficacy of NAC in these patients.

Evolution of Treatment Outcomes and Prognostic Factors in Esophageal Cancer Surgery: A Retrospective Analysis of 1500 Consecutive Esophagostomies.

Objective: To clarify the surgical outcomes of esophagectomy in Japan and comprehensively evaluate trends over time. It is important to analyze data from a large number of consecutive patients from a single institution. Methods: We evaluated the treatment outcomes, complications, and prognosis of 1500 consecutive patients who underwent esophagectomy during 5 periods: group A (n = 284), 1964-1984; group B (n = 345), 1985-1993; group C (n = 253), 1994-2002; group D (n = 297), 2003-2012; and group E (n = 321), 2013-March 2020. Results: The incidences of squamous cell carcinoma and adenocarcinoma were 93.8% and 3.3%, respectively. The proportion of adenocarcinoma cases has gradually increased over time. The in-hospital mortality rates for groups A, B, C, D, and E were 12%, 4.6%, 1.2%, 2.9%, and 1.5%, respectively. Group A had a significantly higher mortality rate than the other groups (P < 0.0001). Three-year survival rates were 22.2%, 47.8%, 53.4%, 69.9%, and 72.6% in groups A-E, respectively, 5-year survival rates were 17.2%, 41.3%, 49.2%, 63.9%, and 68.4%, respectively (P < 0.0001, group A vs groups D and E). The prognosis improved over time. Multivariate analysis revealed that depth of invasion, lymph node metastasis, the extent of lymph node resection, curative resection, pulmonary complications, and anastomotic leakage were significant independent prognostic factors. However, for recent surgeries (groups D and E), only the depth of invasion, lymph node metastasis, and curative resection were significant independent prognostic factors. Conclusions: Valuable changes in background and prognostic factors occurred over time. These findings will help optimize esophageal cancer management and improve patient outcomes.

Cachexia index as a prognostic predictor after resection of pancreatic ductal adenocarcinoma.

Aim: This study was performed to investigate the relationship between the preoperative cachexia index (CXI) and long-term outcomes in patients who have undergone radical resection of pancreatic ductal adenocarcinoma (PDAC). Methods: In total, 144 patients who underwent pancreatic resection for treatment of PDAC were retrospectively analyzed. The relationship between the CXI and the patients' long-term outcomes after PDAC resection was investigated. The CXI was calculated based on the preoperative skeletal muscle index, serum albumin level, and neutrophil-to-lymphocyte ratio. After propensity-score matching, we compared clinicopathological features and outcomes. Results: The multivariate analysis showed that lymph node metastasis (hazard ratio [HR], 1.93; 95% confidence interval [CI], 1.16-3.23; P = 0.0118), R1 resection (HR, 57.20; 95% CI, 9.39-348.30; P < 0.0001), and a low CXI (HR, 2.10; 95% CI, 1.27-3.46; P = 0.0038) were independent and significant predictors of disease-free survival (DFS) after PDAC resection. Moreover, a low CXI (HR, 3.14; 95% CI, 1.71-5.75; P = 0.0002) was an independent and significant predictor of overall survival (OS) after PDAC resection. After propensity-score matching, the low CXI group had a significantly worse prognosis than the high CXI group for both DFS and OS. Conclusion: The CXI can be a useful prognostic factor for DFS and OS after pancreatic resection for treatment of PDAC.

A new scoring system with simple preoperative parameters as predictors of early recurrence of pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) often recurs early after radical resection, and such early recurrence (ER) is associated with a poor prognosis. Predicting ER is useful for determining the optimal treatment. METHODS: One hundred fifty-three patients who underwent pancreatectomy for PDAC were divided into an ER group (n = 54) and non-ER group (n = 99). Clinicopathological factors were compared between the groups, and the predictors of ER and prognosis after PDAC resection were examined. RESULTS: The ER group had a higher platelet count, higher platelet-to-lymphocyte ratio (PLR), higher preoperative CA19-9 concentration, higher SPan-1 concentration, larger tumor diameter, and more lymph node metastasis. The receiver operating characteristic (ROC) curve analysis identified cut-off values for PLR, carbohydrate antigen 19-9 (CA19-9), SPan-1, and tumor diameter. In the multivariate analysis, a high PLR, high CA19-9, and tumor diameter of >3.1 cm were independent predictors of ER after resection (all p < 0.05). When the parameter exceeded the cut-off level, 1 point was given, and the total score of the three factors was defined as the ER prediction score. Next, our new ER prediction model using PLR, CA19-9 and tumor diameter (Logit(p) = 1.6 + 1.2 × high PLR + 0.7 × high CA19-9 + 0.5 × tumor diameter > 3.1cm) distinguished ER with an area under the curve of 0.763, a sensitivity of 85.2%, and a specificity of 55.6%. CONCLUSIONS: ER after resection of PDAC can be predicted by calculation of a score using the preoperative serum CA19-9 concentration, PLR, and tumor diameter.

Genomic characterization between HER2-positive and negative gastric cancer patients in a prospective trial.

BACKGROUND: We aimed to clarify the genomic characteristics of HER2-positive and negative gastric cancer cases that potentially affect tumor progression and treatment response in a prospective trial. METHODS: We collected 80 formalin-fixed paraffin-embedded (FFPE) samples (49 HER2+ and 31 HER2-) from gastric cancer patients who participated in the TROX-A1 trial (UMIN000036865). We queried a 435-gene panel (CANCERPLEX-JP) to generate comprehensive genomic profiling data, including the tumor mutation burden, somatic mutations, and copy number variations. In addition, the genomic differences between HER2+ and HER2- gastric cancer patients were analyzed. RESULTS: Mutational analyses showed that TP53 was the most frequently mutated gene regardless of HER2 status. ARID1A mutation was significantly enriched in HER2-negative patients. The number of total mutations in HER2-negative patients with ARID1A mutation was remarkably higher than that in HER2-positive patients. Next, copy number variation analyses showed that the number of amplified genes (such as CCNE1, PGAP3, and CDK12) in HER2-positive cases was significantly higher than that in HER2-negative cases. Moreover, PTEN deletion was more common in HER2-positive cases. Finally, we found that, compared with HER2-positive patients, HER2-negative patients tended to have a higher tumor mutation burden, particularly in patients with ARID1A mutation. Pathway analyses of the gene alterations showed an enrichment of several immune-related pathways in HER2-negative patients. CONCLUSIONS: According to the genomic profiling of HER2-positive and negative gastric cancer, several gene alterations in the HER2 pathway may be the potential mechanism underlying trastuzumab resistance. Relative to HER2-positive gastric cancer, HER2-negative gastric tumors with ARID1A mutation may be sensitive to immune checkpoint inhibitors.

Prognostic Significance of Preoperative Nutritional Assessment in Elderly Patients who Underwent Laparoscopic Gastrectomy for Stage I-III Gastric Cancer.

BACKGROUND/AIM: Surgery for elderly patients with gastric cancer is becoming more common. However, the risk factors of the laparoscopic surgery for these patients are unknown, and thus it is difficult to determine appropriate treatments for such patients. The aim of this retrospective study was to clarify the risk factors for the treatment outcomes after laparoscopic gastrectomy in elderly patients. PATIENTS AND METHODS: Two hundred twenty-two patients who underwent laparoscopic gastrectomy for primary gastric cancer between January 2014 and December 2017 were enrolled. Clinical characteristics and short- and long-term prognoses were analyzed in 47 patients aged 75 years or older (elderly group) and in 175 patients who were under 75 years old (non-elderly group). RESULTS: The presence of comorbidities was more common in the elderly group than in the non-elderly group (91.5% vs. 61.7%, p<0.0001). The rate of postoperative complications in the elderly group was significantly higher than that in the non-elderly group (42.6% vs. 22.9%, p=0.01). The 5-year overall survival rate was significantly lower in the elderly group than in the non-elderly group (66.9% vs. 92.2%; p<0.0001). In the elderly group, 5-year overall survival in patients with a low preoperative prognostic nutritional index (PNI) was significantly worse than that in patients with a high preoperative PNI (25.0% vs. 80.9%; p<0.05). Multivariate analysis showed that the PNI value was independently associated with overall survival in elderly patients who underwent laparoscopic gastrectomy (p<0.05). In particular, the rate of non-cancer deaths after surgery in elderly patients was significantly higher than that in non-elderly patients (p<0.05). CONCLUSION: PNI value is an independent prognostic factor for overall survival in elderly patients who have undergone laparoscopic gastrectomy for gastric cancer; therefore, in elderly patients with low preoperative PNI, attention should be paid not only to recurrence of cancer, but also to the deterioration of general condition caused by malnutrition.

Clinicopathological features and prognosis of gastric tube cancer after esophagectomy for esophageal cancer: a nationwide study in Japan.

BACKGROUND: Survivors of esophageal cancer post-esophagectomy may sometimes develop gastric tube cancer (GTC). However, its clinical characteristics have not been elucidated. We conducted a retrospective nationwide survey of GTCs to clarify them. METHODS: A questionnaire on GTCs was sent by e-mail and mail to 116 institutions certified by the Japan Esophageal Society. A total of 608 GTC cases diagnosed and treated between 2001 and 2015 were registered from 62 institutions. RESULTS: The median age at diagnosis was 71 years, with 88.9% being diagnosed with stage I. Sixty percent of GTC cases were in the anal third of the gastric tube and 79.7% were differentiated adenocarcinomas. The median interval between esophagectomy and GTC diagnosis was 6 years, with approximately 25% of patients being diagnosed more than 10 years later. The 5-year overall survivals (5-OSs) after endoscopic and surgical treatments for GTC were 75.9% and 52.7%, respectively. Patients whose GTC was diagnosed without symptoms or by regular follow-up examination showed better 5-OSs compared to others (69.7% vs. 41.2%, p < 0.0001; and 71.4% vs. 41.8%, p < 0.0001, respectively). The prognosis of GTC cases diagnosed within 2 years of the preceding upper gastrointestinal endoscopy (UGI) was better than that in cases diagnosed longer than 2 years (5-OS: 73.4% vs. 48.8%, p < 0.05). CONCLUSION: This nationwide survey revealed the clinicopathological features of GTCs for the first time. Early detection is important in improving the prognosis of GTC, and it is recommended that UGI endoscopy be continued every 2 years for 10 or more years after esophagectomy.

High Pretreatment Mean Corpuscular Volume Can Predict Worse Prognosis in Patients With Esophageal Squamous Cell Carcinoma who Have Undergone Curative Esophagectomy: A Retrospective Multicenter Cohort Study.

Objective: To establish the prognostic value of mean corpuscular volume (MCV) in patients with esophageal squamous cell carcinoma (ESCC) who have undergone esophagectomy. Background: The MCV increases in patients with high alcohol and tobacco consumption. Such a lifestyle can be a risk factor for malnutrition, comorbidities related to those habits, and multiple primary malignancies, which may be associated with frequent postoperative morbidity and poor prognosis. Methods: This study included 1673 patients with ESCC who underwent curative esophagectomy at eight institutes between April 2005 and November 2020. Patients were divided into normal and high MCV groups according to the standard value of their pretreatment MCV. Clinical background, short-term outcomes, and prognosis were retrospectively compared between the groups. Results: Overall, 26.9% of patients had a high MCV, which was significantly associated with male sex, habitual smoking and drinking, multiple primary malignancies, and malnutrition, as estimated by the body mass index, hemoglobin and serum albumin values, and the Geriatric Nutritional Risk Index. Postoperative respiratory morbidity (P = 0.0075) frequently occurred in the high MCV group. A high MCV was an independent prognostic factor for worse overall survival (hazard ratio, 1.27; 95% confidence interval, 1.049-1.533; P = 0.014) and relapse-free survival (hazard ratio, 1.23; 95% confidence interval, 1.047-1.455; P = 0.012). Conclusions: A high MCV correlates with habitual drinking and smoking, malnutrition, and multiple primary malignancies and could be a surrogate marker of worse short-term and long-term outcomes in patients with ESCC who undergo esophagectomy.

RAD51 Expression as a Biomarker to Predict Efficacy of Preoperative Therapy and Survival for Esophageal Squamous Cell Carcinoma: A Large-cohort Observational Study (KSCC1307).

OBJECTIVE: The aim of this study is to identify biomarkers that predict efficacy of preoperative therapy and survival for esophageal squamous cell carcinoma (ESCC). BACKGROUND: It is essential to improve the accuracy of preoperative molecular diagnostics to identify specific patients who will benefit from the treatment; thus, this issue should be resolved with a large-cohort, retrospective observational study. METHODS: A total of 656 patients with ESCC who received surgery after preoperative CDDP + 5-FU therapy, docetaxel + CDDP + 5-FU therapy or chemoradiotherapy (CRT) were enrolled. Immunohistochemical analysis of TP53, CDKN1A, RAD51, MutT-homolog 1, and programmed death-ligand 1 was performed with biopsy samples obtained before preoperative therapy, and expression was measured by immunohistochemistry. RESULTS: In all therapy groups, overall survival was statistically separated by pathological effect (grade 3 > grade 2 > grade 0, 1, P < 0.0001). There was no correlation between TP53, CDKN1A, MutT-homolog 1, programmed death-ligand 1 expression, and pathological effect, whereas the proportion of positive RAD51 expression (≥50%) in cases with grade 3 was lower than that with grade 0, 1, and 2 (P = 0.022). In the CRT group, the survival of patients with RAD51-positive tumor was significantly worse than RAD51-negative expressors (P = 0.0119). Subgroup analysis of overall survival with respect to positive RAD51 expression indicated preoperative chemotherapy (CDDP + 5-FU or docetaxel + CDDP + 5-FU) was superior to CRT. CONCLUSIONS: In ESCC, positive RAD51 expression was identified as a useful biomarker to predict resistance to preoperative therapy and poor prognosis in patients who received preoperative CRT. Administration of preoperative chemotherapy may be warranted for patients with positive RAD51 expression.

Health-related quality of life after esophagectomy in patients with esophageal cancer.

Esophageal cancer is one of the malignant tumors with the poorest prognosis. Esophagectomy, which is the mainstay of curative-intent treatments, imposes excessive surgical stress on the patients, and postoperative morbidity and mortality rates after esophagectomy remain high. On the other hand, the number of survivors after esophagectomy for esophageal cancer is increasing due to recent improvements in surgical techniques and multidisciplinary treatments for this cancer. However, esophagectomy still has a great influence on the fundamental aspect of patients' lives, that is, the health-related quality of life (HR-QOL), including their physical, emotional, and social functions in the short- and long-term postoperatively. HR-QOL is a multifactorial concept used to assess the symptoms and functional changes caused by the disease itself and treatments from the patients' perspectives. Therefore, assessing the HR-QOL of patients with esophageal cancer after esophagectomy is becoming increasingly important. However, the status of HR-QOL changes after esophagectomy has not been satisfactorily evaluated, and there is no worldwide consensus as to how the postoperative HR-QOL can be improved. This review aimed to raise awareness of healthcare providers, such as surgeons and nurses, on the importance of HR-QOL in patients with esophageal cancer after curative-intent esophagectomy by providing multifaceted information concerning the short- and long-term HR-QOLs, including the status of changes and the determinants of HR-QOL after esophagectomy, and furthermore, essential points for improvement of HR-QOL after esophagectomy.

Nationwide survey of the follow-up practices for patients with esophageal carcinoma after radical treatment: historical changes and future perspectives in Japan.

BACKGROUND: No post-treatment follow-up methods have been established yet for patients with esophageal carcinoma who undergo radical esophagectomy (Surg) or who show complete response to definitive chemoradiotherapy (dCRT-CR). The purpose of this study was to investigate the current status of follow-up of the Surg and dCRT-CR patients in Japan, and understand the current reality and problems to establish an optimal follow-up method. METHODS: A questionnaire on the follow-up method adopted was sent by e-mail to 124 institutions approved by the Japan Esophageal Society as training institutions for board-certified esophageal surgeons; responses were received from 89 institutions. The data were compared with those obtained by a similar survey conducted in 2014. RESULTS: Follow-up methods markedly varied among institutions. Almost all institutions scheduled computed tomography and upper gastrointestinal endoscopy at least once a year up to postoperative year 5 for both the Surg and dCRT-CR groups. At least 70% of the institutions continued follow-up up to postoperative year 10, and this proportion had increased as compared to that reported from the 2014 survey. Only 25-30% of the institutions scheduled follow-up screening for metachronous head and neck cancer for both groups, and the health-related quality of life (HR-QOL) after the treatment were seldom assessed. These trends remained unchanged as compared to those reported from the 2014 survey. CONCLUSIONS: The results suggest that the consensus of follow-up protocol could not be established. More attention is required for detection of metachronous cancers and assessment of the HR-QOL. Establishment of a consensus-based follow-up system and verification of its effectiveness are required.

Comparison of laparoscopic surgery with open standard surgery for advanced gastric carcinoma in a single institute: a propensity score matching analysis.

BACKGROUND: Compared with open standard gastrectomy (OG), laparoscopic gastrectomy (LG) did not result in inferior disease-free survival for early-stage and locally advanced gastric cancer (AGC). However, whether LG for AGC in elderly patients is more beneficial than OG is unclear. METHODS: This study examined 458 patients with AGC. The mortality, morbidity, and prognosis were compared by age, gender, T and N factors, and pathological stage in the LG and OG groups using propensity score matching analysis. For the final analysis, 151 pairs of patients were selected from at each group. RESULTS: The results showed that no significant difference in mortality and morbidity existed between the two groups. The 5-year relapse-free survival (RFS) rates were 70% and 62% in the LG and OG groups, respectively (p = 0.104). The 5-year RFS rates in patients with pathological stages I, II, and III who had undergone LG were 84%, 80%, and 55%, respectively, and 78%, 70%, and 45%, respectively, in those who had undergone OG (p < 0.005). The 5-year RFS rates in nonelderly patients who underwent LG or OG were 75% and 68%, respectively, and 58% and 40%, respectively, in elderly patients who underwent LG or OG (p < 0.005). CONCLUSION: The 5-year RFS rates in patients with AGC at each stage did not significantly differ between LG and OG. However, the benefits at 5-year RFS in patients who underwent LG compared with OG were larger in elderly patients than those in nonelderly patients.

Clinical outcomes of surgical resection for recurrent lesion after curative esophagectomy for esophageal squamous cell carcinoma: a nationwide, large-scale retrospective study.

BACKGROUND: Several studies have reported the efficacy of resection for recurrent lesions. However, they involved a limited number of subjects. This study aimed to identify a subset of patients who benefit from surgical resection of recurrent lesions after curative esophagectomy for esophageal squamous cell carcinoma. METHODS: Clinicopathological features of 186 patients with esophageal squamous cell carcinoma who underwent surgical treatment for postoperative recurrent lesions at 37 accredited institutions of the Japanese Esophageal Society were evaluated. RESULTS: The most common recurrence site was the lymph node (106 cases; 58.6%), followed by the lung (40 cases; 22.1%). Univariate analyses revealed that pN 0-1 at esophagectomy (P = 0.0348), recurrence-free interval of ≥ 550 days (P = 0.0306), R0 resection (P < 0.0001), and absence of severe complications after resection for recurrent lesions (Clavien-Dindo grade < IIIa) (P = 0.0472) were associated with better overall survival after surgical resection. According to multivariate analyses, pN 0-1 (P = 0.0146), lung metastasis (P = 0.0274), recurrence-free interval after curative esophagectomy of ≥ 550 days (P = 0.0266), R0 resection (P = 0.0009), and absence of severe complications after resection for recurrent lesions (Clavien-Dindo grade < IIIa) (P = 0.0420) were independent predictive factors for better overall survival. CONCLUSIONS: Surgical resection of recurrent esophageal squamous cell carcinoma lesions is a useful option, especially for cases involving lower pN stage, lung metastasis, long recurrence-free intervals after esophagectomy, and technically resectable lesions. Surgical risks should be minimized as much as possible.

Indications for conversion hepatectomy for initially unresectable colorectal cancer with liver metastasis.

PURPOSE: Selected patients with initially unresectable colorectal cancer (CRC) and liver metastases undergo conversion surgery after appropriate chemotherapy. The prognosis of these patients is good, with some even cured of the disease. This retrospective, single-institution study analyzes the clinical importance of patient characteristics on the outcomes of conversion hepatectomy. METHODS: We evaluated 229 consecutive patients with initially unresectable CRC and liver metastasis, who underwent systemic chemotherapy. The patients were assigned to groups depending on conversion hepatectomy. RESULTS: Conversion hepatectomy was performed in 30 patients (13.1%). The proportion of patients with extrahepatic metastasis was significantly lower in the conversion group than in the unresectable group (30.0 vs. 66.8%; P < 0.01). The rate of left-sided primary colorectal tumors was significantly higher in the conversion group than in the unresectable group (96.7 vs. 65.8%; P < 0.01). Multivariate analyses identified that left-sided tumors, no extrahepatic metastasis, H1 or H2 grade CLM, and treatment with molecular-targeted agents were associated with conversion hepatectomy (odds ratios: 16.314, 4.216, 7.631, and 4.070; P < 0.01). Overall survival was significantly longer in the conversion group than in the unresectable group (MST: 50.0 versus 14.7 months; P < 0.01). CONCLUSION: Left-sided primary tumors, absence of extrahepatic metastases, H1 or H2 grade, and use of molecular-targeted agents were associated with successful conversion hepatectomy; thus, patients with these characteristics may be candidates for conversion therapy.

Expression of CD44 variant 9 induces chemoresistance of gastric cancer by controlling intracellular reactive oxygen spices accumulation.

BACKGROUND: CD44 variant 9 (CD44v9) has been reported to suppress reactive oxygen spices (ROS) in association with antioxidant factors such as glutathione (GSH) and glutathione peroxidase 2 (GPx2), resulting in promoted tumor growth. METHODS: CD44v9 and GPx2 expression were investigated by immunohistochemistry in resected specimens from 193 gastric cancer (GC) patients without preoperative chemotherapy and in pretreatment biopsy specimens from 29 GC patients with preoperative chemotherapy. We analyzed the relationship between CD44v9 expression and clinicopathological factors, prognosis, and pathological response to chemotherapy. In GC cell lines, we examined the relationship between CD44v9 expression and chemotherapeutic sensitivity. RESULTS: In patients without preoperative chemotherapy, CD44v9 expression was significantly associated with depth of invasion, lymphatic permeation, vascular invasion, distant metastasis and GPx2 expression. In multivariate analysis, CD44v9 expression was an independent poor prognosis factor for overall survival and recurrence-free survival. In patients with preoperative chemotherapy, CD44v9 expression was significantly associated with worse pathological response and GPx2 expression. In GC cell lines, downregulation of CD44v9 expression enhanced chemotherapeutic sensitivity to 5-fluorouracil with changing GSH and ROS levels. CONCLUSIONS: CD44v9-positive expression was associated with chemotherapeutic resistance by controlling intracellular accumulated ROS, suggesting that CD44v9 may be a predictive biomarker for chemotherapy in GC.

Neutrophil-to-lymphocyte Ratio as a Predictor of Malignancy of Intraductal Papillary Mucinous Neoplasms.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) can lead, via the adenoma-carcinoma sequence, to invasive adenocarcinoma, which has a poor prognosis. Most IPMNs do not meet the indications for surgery and instead are monitored regularly, but no biomarkers of malignant transformation during surveillance have been established. PATIENTS AND METHODS: A total of 50 patients with IPMN who underwent pancreatectomy were evaluated retrospectively. Clinicopathological parameters during the surveillance period before surgery were assessed to explore biomarkers for predicting malignancy. RESULTS: The serum level of carbohydrate antigen 19-9 was significantly higher in IPMN-derived invasive adenocarcinoma. The neutrophil-to-lymphocyte ratio was significantly lower in low-grade IPMN than high-grade and Inv-IPMN cases by univariate and multivariate analysis. Disease-free survival was significantly shorter in patients with high-grade and invasive IPMN compared with those with low-grade IPMN. In patients whose preoperative surveillance was performed for more than 12 months, the neutrophil-to-lymphocyte ratio was significantly higher in those with high-grade and invasive IPMNs compared with patients with low-grade IPMN in the year before surgery. CONCLUSION: The NLR is a useful biomarker for distinguishing between low-grade and high-grade IPMN and thus should be monitored during surveillance.

Histological categorisation of the desmoplastic reaction is a predictor of patient prognosis in oesophageal squamous cell carcinoma.

AIMS: Histological categorisation of the desmoplastic reaction (DR) is an independent prognostic factor in colorectal cancer. However, it is unknown whether DR categorisation is predictive of oesophageal squamous cell carcinoma (OSCC) outcomes. This study aimed to evaluate the prognostic value of DR categorisation in OSCC patients. METHODS AND RESULTS: Data were collected from 118 patients with OSCC who underwent a curative oesophagectomy with T2 or deeper wall invasion. The DR in each tumour was classified as mature, intermediate or immature based on the presence or absence of keloid-like collagen and myxoid stroma. We identified 49 mature DR tumours, 41 intermediate DR tumours and 28 immature DR tumours. The 5-year overall survival (OS) rate was highest in the mature DR group (42.8%), followed by the intermediate DR group (25.0%) and the immature DR group (19.9%) (P = 0.022, log-rank test; P = 0.006, log-rank trend test). The 5-year disease-specific survival (DSS) rate was also highest in the mature DR group (48.5%), followed by the intermediate DR group (30.8%) and the immature DR group (26.8%) (P = 0.031, log-rank test; P = 0.010, log-rank trend test, respectively). Multivariate analysis revealed that an immature DR was an independent poor prognostic factor of OS and DSS (P = 0.002 and P = 0.004). CONCLUSIONS: DR categorisation of OSCC stroma following oesophagectomy is a useful diagnostic tool and an independent prognostic marker.