Days of the week and 90-day mortality after esophagectomy: analysis of 33,980 patients from the National Clinical Database.

PURPOSE: The effect of the days of the week on the short-term outcomes after elective surgeries has been suggested; however, such data on esophagectomies remain limited. This study aimed to investigate the association between the day of the week and mortality rates after elective esophagectomy using a large-scale clinical database in Japan. METHODS: The data of elective esophagectomies, registered in the National Clinical Database in Japan, for esophageal cancer treatment between 2012 and 2017 were analyzed. We hypothesized that the later days of the week could have higher odds ratios of death after elective esophagectomy. With 22 relevant clinical variables and days of surgery, 90-day mortality was evaluated using hierarchical logistic regression modeling. RESULTS: Ninety-day mortality rates among 33,980 patients undergoing elective esophagectomy were 1.8% (range, 1.5-2.1%). Surgeries were largely concentrated on earlier days of the week, whereas esophagectomies performed on Fridays accounted for only 11.1% of all cases. Before risk adjustment, lower odds ratios of 90-day mortality were found on Tuesday and a tendency towards lower odds ratios on Thursday. In the hierarchical logistic regression model, 21 independent factors of 90-day mortality were identified. However, the adjusted odds ratios of 90-day mortality for Tuesday, Wednesday, Thursday, and Friday were 0.87, 1.09, 0.85, and 0.88, respectively, revealing no significant difference. CONCLUSION: The results imply that the variation in 90-day mortality rates after esophagectomy on different days of the week may be attributed to differing preoperative risk factors of the patient group rather than the disparity in medical care provided.

Artificial intelligence-based classification of peripheral blood nucleated cells using label-free imaging flow cytometry.

Label-free image identification of circulating rare cells, such as circulating tumor cells within peripheral blood nucleated cells (PBNCs), the vast majority of which are white blood cells (WBCs), remains challenging. We previously described developing label-free image cytometry for classifying live cells using computer vision technology for pattern recognition, based on the subcellular structure of the quantitative phase microscopy images. We applied our image recognition methods to cells flowing in a flow cytometer microfluidic channel, and differentiated WBCs from cancer cell lines (area under receiver operating characteristic curve = 0.957). We then applied this method to healthy volunteers' and advanced cancer patients' blood samples and found that the non-WBC fraction rates (NWBC-FRs), defined as the percentage of cells classified as non-WBCs of the total PBNCs, were significantly higher in cancer patients than in healthy volunteers. Furthermore, we monitored NWBC-FRs over the therapeutic courses in cancer patients, which revealed the potential ability in monitoring the clinical status during therapy. Our image recognition system has the potential to provide a morphological diagnostic tool for circulating rare cells as non-WBC fractions.

Correlation between surgical mortality for perforated peritonitis and days of the week for operations: A retrospective study using the Japanese National Clinical Database.

BACKGROUND: The association between weekend interventions and poor outcomes is termed the "weekend effect." This retrospective study investigated whether the weekend effect exists in the surgical treatment of acute diffuse peritonitis due to gastrointestinal perforation. METHODS: Patients (n = 16,209) who underwent operation for acute diffuse peritonitis during 2016-2017 were included and grouped depending on the perforation site. Using 23 variables, we performed hierarchical logistic regression analysis and calculated odds ratios for surgical mortality. RESULTS: Surgical mortality rates were 8.8%, 15.0%, and 14.1% for patients with gastroduodenal, small bowel, and large bowel perforations, respectively. Unadjusted odds ratios for surgical mortality differed significantly on Wednesdays only for patients with large bowel perforation (odds ratio: 0.772, 95% confidence interval: 0.613-0.972, P = 0.03). However, there was no significant difference in adjusted odds ratios. CONCLUSION: The quality of emergency surgical treatment is uniform in Japan throughout the week in terms of mortality.

Association Between Preoperative HbA1c Levels and Complications after Esophagectomy: Analysis of 15,801 Esophagectomies From the National Clinical Database in Japan.

OBJECTIVE: To elucidate the association between preoperative hemoglobin A1c (HbAlc) levels and short-term outcomes after oncologic esophagectomy. SUMMARY BACKGROUND DATA: Although diabetes mellitus is associated with an increased risk of postoperative morbidity in several types of surgery, the association of diabetes mellitus with short-term outcomes after esophagectomy has shown conflicting results. METHODS: We analyzed 15,801 patients who underwent oncologic esophagectomy between 2015 and 2017 from the National Clinical Database. We evaluated the associations between preoperative HbA1c levels and short-term outcomes, using multivariable logistic regression and restricted cubic spline models. RESULTS: The cohort included 12,074, 1361, 1097, 909, and 360 patients with HbA1c levels of ≤5.9%, 6.0% to 6.4%, 6.5% to 6.9%, 7.0% to 7.9%, and ≥8.0%, respectively. There were value-dependent associations between HbA1c values and odds ratios for anastomotic leakage, surgical site infections, pneumonia, and composite outcomes. Compared with the HbA1c category of ≤5.9%, the categories of 7.0% to 7.9% and ≥8.0% were at higher risk for anastomotic leakage ( P < 0.001 and 0.031, respectively), the category of ≥8.0% was at higher risk for surgical site infections ( P = 0.001), the categories of 6.5% to 6.9% and 7.0% to 7.9% were at higher risk for pneumonia ( P = 0.016 and 0.002, respectively), and the categories of 7.0 to 7.9 and > 8.0% were at higher risk for composite outcomes (P < 0.001 and 0.001, respectively). CONCLUSIONS: Preoperative HbA1c levels are associated with the risk of postoperative complications after esophagectomy, and the threshold values differed among the outcomes. Preoperative HbA1c is useful in predicting the risk of postoperative complications.

Survival impact of perioperative changes in prognostic nutritional index levels after esophagectomy.

BACKGROUND: The correlation between perioperative changes in nutritional status during esophagectomy and prognosis remains unclear. This study aimed to evaluate the impact of changes in prognostic nutritional index levels during the perioperative period on esophageal cancer patient survivals. METHODS: From January 2009 to May 2019, 158 patients with esophageal squamous cell carcinoma were enrolled. From the time-dependent ROC analysis, the cutoff values of preoperative and postoperative prognostic nutritional index levels were 46.9 and 40.9. Patients were divided into preoperative-high group (Group H) and preoperative-low group (Group L). Then, patients in Group L were divided into preoperative-low and postoperative-high group (Group L-H) and preoperative-low and postoperative-low group (Group L-L). Long-term outcomes and prognostic factors were evaluated. RESULTS: Patients in Group L had significantly worse overall survival than those in Group H (p = 0.001). Patients in Group L-L had significantly worse overall survival than those in Group L-H (p = 0.023). However, there was no significant difference in overall survival between Groups H and L-H (p = 0.224). In multivariable analysis, advanced pathological stage (hazard ratio 10.947, 95% confidence interval 2.590-46.268, p = 0.001) and Group L-L (hazard ratio 2.171, 95% confidence interval 1.249-3.775, p = 0.006) were independent predictors of poor overall survival. CONCLUSIONS: Patients in Group L-H had a good prognosis, similar to those in Group H. This result indicated that increasing the postoperative prognostic nutritional index level sufficiently using various intensive perioperative support methods could improve prognosis after esophagectomy in patients with poor preoperative nutritional status.

Usefulness of wearable fitness tracking devices in patients undergoing esophagectomy.

BACKGROUND: Esophageal cancer surgery requires maintenance and enhancement of perioperative nutritional status and physical function to prevent postoperative complications. Therefore, awareness of the importance of preoperative patient support is increasing. This study examined the usefulness of using a diary in combination with a wearable fitness tracking device (WFT) in patients undergoing surgery for esophageal cancer. METHODS: Ninety-four patients who underwent esophagectomy between February 2019 and April 2021 were included. Physicians, nurses, dietitians, and physical therapists provided diary-based education for the patients. In addition, a WFT was used by some patients. The perioperative outcomes of patients who used both the diary and WFT (WFT group) and those who used the diary alone (non-WFT group) were compared. In addition, propensity score matching was performed to improve comparability between the two groups. RESULTS: After the propensity score matching, the rate of postoperative pneumonia was significantly lower in the WFT group (0% vs. 22.6%, P = 0.005). The postoperative hospital stay was shorter in the WFT group (P = 0.012). Nutritional status indices, such as the prognostic nutritional index, also improved significantly in the WFT group at 1 month after surgery (P = 0.034). The rate of diary entries was significantly higher in the WFT group (72.3% vs. 28.3%, P < 0.001). CONCLUSION: The use of a WFT reduced the incidence of postoperative pneumonia and improved postoperative nutritional status and rates of diary entries after esophagectomy, suggesting that its use may be useful for promoting recovery after esophagectomy.

Day of surgery and mortality after pancreatoduodenectomy: A retrospective analysis of 29 270 surgical cases of pancreatic head cancer from Japan.

BACKGROUND/PURPOSE: The day of the week can impact medical treatment outcomes; however, few large-scale, disease-specific studies have focused on the association between the day of the week and mortality in patients after pancreatoduodenectomy for pancreatic head cancer. METHODS: Data were obtained from the National Clinical Database. Twenty-two clinical variables were adopted for hierarchal logistic regression modeling to determine adjusted odds ratios (ORs) for surgical mortality after elective pancreatoduodenectomy. RESULTS: The 30-day mortality and surgical mortality rates were 1.0% and 1.7%, respectively (n = 29 720). Surgeries were performed the least on Fridays (13.4%) compared with other weekdays. Crude rates of severe postoperative complications (mean, 14.1%; range, 13.5%-14.8%) and pancreatic fistulas (mean, 10.0%; range, 9.6%-10.3%) remained stable throughout the week. Unadjusted/adjusted ORs did not significantly differ between Friday and Monday (0.868, 95% CI: 0.636-1.173, P = .365, and 0.928, 95% CI: 0.668-1.287, P = .653, respectively), and results were similar for the remaining weekdays. Nineteen independent factors were associated with surgical mortality. CONCLUSIONS: The rate of perioperative mortality for elective pancreatoduodenectomy is low in Japan, with no evidence of disparities in surgical mortality rates between weekdays.

Significance of the Glasgow prognostic score for short-term surgical outcomes: A nationwide survey using the Japanese National Clinical Database.

AIM: Preoperative inflammation-based Glasgow prognostic score (GPS) is a useful tool for predicting long-term prognosis in cancer patients. However, its association with postoperative short-term outcomes remains unknown. The aim of this study is to investigate the association between GPS and postoperative morbidity and mortality among patients undergoing surgery for various gastrointestinal malignancies. METHODS: Using the Japanese National Clinical Database, we analyzed the records of 312 357 patients with gastrointestinal malignancy who underwent six typical elective surgeries, including esophagectomy, distal gastrectomy, total gastrectomy, right hemicolectomy, low anterior resection, and pancreaticoduodenectomy, between January 2015 and December 2018. We assigned GPS of 0, 1, or 2 to patients with no, one, or both decreased albumin and elevated C-reactive protein levels, respectively. We investigated the relationship of GPS with operative morbidity and mortality for each procedure with adjustments for patients' demographics, preoperative status, comorbidities, and cancer stages. RESULTS: Crude operative morbidity was significantly higher for GPS 1 and 2 than GPS 0 patients in all procedures except pancreaticoduodenectomy. The postoperative length of hospital stay was significantly longer for GPS 1 and 2 patients in all procedures (P < .001). Operative mortality was also higher for GPS 1 and 2 patients in all procedures. The associations remained significant after adjustments for potential confounders of age, sex, physical status, tumor classification, use of preoperative therapy, and comorbidities. CONCLUSION: This nationwide study provides solid evidence on the strong association between GPS and postoperative outcomes.

Profiles of institutional departments affect operative outcomes of eight gastroenterological procedures.

AIM: We evaluated the association of profiles of institutional departments with operative outcomes of eight major gastroenterological procedures. METHODS: We administered a 15-item online survey to 2634 institutional departments in 2016 to investigate the association of questionnaire responses with operative mortality for the procedures. The proportions of conditions met were listed according to institutional volume and classified according to annual operative cases in 1464 departments. Group A included departments with annual performance of <40 cases of the eight procedures, B 40-79 cases, C 80-199 cases, D 200-499 cases, and E ≥ 500 cases. We evaluated the number of conditions met for 10 of 15 items that could be improved by efforts of institutional departments, to assess whether the profiles of institutional departments had impacts on operative mortality. We built a multivariable logistic regression model for operative mortality with facilities categorized based on the number of conditions met and procedure-specific predicted mortality as explanatory variables using generalized estimating equation to account for facility-level clustering. We also examined how operative outcomes differed between facilities meeting nine or more conditions and those that did not. RESULTS: We recognized meeting nine out of the 10 conditions as being a good indicator for having appropriate structural and process measures for gastroenterological surgery. The facilities meeting nine or more of the conditions had better operative mortality for all eight procedures. CONCLUSIONS: Our findings reveal that the profiles of institutional departments can reflect the outcomes of gastroenterological surgery in Japan.

Association of day of the week with mortality after elective right hemicolectomy for colon cancer: Case analysis from the National Clinical Database.

AIM: We aimed to investigate whether later weekdays are related to worse short-term outcomes after elective right hemicolectomy for colon cancer. METHODS: We retrospectively analyzed adult patients who underwent elective right hemicolectomy for colon cancer between 2012 and 2017. Records lacking details about surgical mortality were excluded, and multiple imputation was performed for other missing data (variables). The primary endpoint was surgical mortality, defined as the sum of 30-day mortality and in-hospital deaths within 90 days postoperatively. Using 22 clinical variables, hierarchal logistic regression modeling with clustering of patients from the same institutes was performed. RESULTS: Of the 112 658 patients undergoing elective right hemicolectomy for colon cancer, the 30-day mortality and surgical mortality were 0.6% and 1.1%, respectively. Surgery on Friday was less frequent, accounting for 17.1% of all cases. The occurrence of severe postoperative complications, anastomotic leakage, or unadjusted odds ratio for surgical mortality did not show significant differences between weekdays. A hierarchal logistic regression model identified 19 independent factors for surgical mortality. Adjusted odds ratios for surgical mortality were 1.01 (95% confidence interval: 0.83-1.22, P = .915), 0.86 (95% confidence interval: 0.71-1.05, P = .144), 0.86 (95% confidence interval: 0.71-1.05, P = .408), and 0.83 (95% confidence interval: 0.68-1.03, P = .176) for Tuesday, Wednesday, Thursday, and Friday, respectively, showing no significant differences. CONCLUSION: This study did not identify an evident difference in surgical mortality between weekdays; a safe elective right hemicolectomy for colon cancer is being offered throughout the week in Japan.

Evaluation of Definitive Chemoradiotherapy Versus Radical Esophagectomy in Clinical T1bN0M0 Esophageal Squamous Cell Carcinoma.

BACKGROUND: The standard treatment for patients with clinical T1bN0M0 esophageal squamous cell carcinoma is radical esophagectomy. Definitive chemoradiotherapy is regarded as a treatment option, and recently, good clinical outcomes of this treatment have been reported. This study compared prognosis after definitive chemoradiotherapy with radical esophagectomy. METHODS: From January 2011 to December 2019, 68 consecutive patients who were diagnosed clinical T1bN0M0 squamous cell carcinoma were enrolled and investigated retrospectively. Patients were classified into two groups whether treated by surgery or definitive chemoradiotherapy. Survival outcomes were compared, and subsequent therapies after recurrence were also investigated. RESULTS: Among 68 patients, 39 patients underwent surgery and 29 patients received definitive chemoradiotherapy. No significant difference was noted in overall survival between the two groups. However, the rate of 5-year recurrence-free survival was significantly lower in definitive chemoradiotherapy group than that of surgery group (91.1 vs. 62.7%, hazard ratio 3.976, 95% confidence interval 1.076-14.696, p = 0.039). Patients who had local recurrence after definitive chemoradiotherapy received endoscopic submucosal dissection or photodynamic therapy as salvage therapies, which resulted in no disease progression and a good prognosis. CONCLUSIONS: Definitive chemoradiotherapy may become a promising alternative therapy comparable with radical esophagectomy in patients with clinical T1bN0M0 esophageal squamous cell carcinoma. Early detection of recurrence by frequent follow-up after definitive chemoradiotherapy is important to control disease within local recurrence, and salvage therapy for local lesions could contribute to long-term survival.

Early detection of anastomotic leakage after esophagectomy using drain amylase levels.

BACKGROUND: Early diagnosis of anastomotic leakage (AL) after esophagectomy is essential to minimize postoperative complications. In this study, we hypothesized that drain amylase levels may be useful for early AL detection, and measuring drain amylase levels could reduce severe postoperative AL incidence. We, therefore, analyzed the usefulness of measuring drain fluid amylase levels after esophagectomy, in esophageal cancer patients. METHODS: From January 2016 to March 2020, 134 patients with esophageal cancer who underwent surgical resection with esophagogastric anastomosis in the cervical region were included. The patients were divided into a group whose cervical drain fluid amylase levels were not measured (No-AMY Group) and a group whose cervical drain fluid amylase levels were measured daily until postoperative day (POD) 7 (AMY Group). The incidence of severe AL was compared between groups. In the AMY Group, we also investigated the association between AL and drain amylase levels. RESULTS: Drain amylase levels were significantly higher in AL-positive cases than in AL-negative cases (P < 0.001). Receiver operating characteristic curve analysis revealed the drain amylase level cut-off value for AL diagnosis was 1800 U/L on POD 2 (Area under the curve = 0.835; P = 0.027). The incidence of ≥ grade III AL was significantly lower in the AMY Group than in the No-AMY Group (2 vs. 10%, P = 0.047). CONCLUSIONS: Cervical drain fluid amylase levels can be a useful screening method for early detection of AL after esophagectomy for esophageal cancer and may help reduce incidence of severe postoperative AL.

Postoperative chylothorax with a duplicated left-sided thoracic duct: a case report and review of the literature.

Postoperative chylothorax is a potentially lethal complication after esophagectomy. A 53-year-old woman underwent subtotal esophagectomy. The thoracic duct was resected due to swollen lymph nodes. Postoperative chylothorax was diagnosed but conservative treatment was ineffective. Lipiodol lymphangiography revealed leakage from a duplicated left-sided thoracic duct. Left-sided video-assisted thoracoscopic ligation of the left-sided thoracic duct was performed. Because anatomical variations in the thoracic duct contribute to refractory chylothorax, lymphangiography is useful in detecting the position of thoracic duct injury as well as any duct anomalies. Based on lymphangiography, left-sided video-assisted thoracoscopic surgery could be considered in case of left-sided thoracic duct injury.

Multidisciplinary team management for prevention of pneumonia and long-term weight loss after esophagectomy: a single-center retrospective study.

BACKGROUND: In April 2017, we launched the multidisciplinary Hamamatsu Perioperative Care Team (HOPE) for all surgical patients. We developed a reinforced intervention strategy, particularly for esophagectomy. We herein report the outcomes of the HOPE at 2 years after commencement. METHODS: A total 125 patients underwent esophagectomy and gastric conduit reconstruction for esophageal or esophagogastric junction cancer between January 2014 and December 2018 at the Department of Surgery in Hamamatsu University School of Medicine. The patients were divided into the pre-HOPE group including 62 patients who underwent esophagectomy before the introduction of the HOPE and the HOPE group including 63 patients who underwent esophagectomy after the introduction of the HOPE. The outcomes of surgery were compared between the two groups. RESULTS: There were no significant differences in the clinicopathological characteristics between the two groups. The incidence rates of atrial fibrillation and pneumonia were significantly lower in the HOPE group than in the pre-HOPE group (6% vs. 19%, p = 0.027 and 14% vs. 29%, p = 0.037, respectively). The estimated calorie doses at the time of discharge were approximately 750 and 1500 kcal/day in the pre-HOPE group and the HOPE group, respectively. The body weight loss was significantly less in the HOPE group than the pre-HOPE group at 1, 3, 6, and 12 months postoperatively than that before the surgery (p < 0.001). CONCLUSIONS: The introduction of the multidisciplinary HOPE was associated with a significant reduction in the incidence of postoperative pneumonia and significantly less weight loss.

Rapid recurrence of primary gastric choriocarcinoma after complete resection.

INTRODUCTION: Primary gastric choriocarcinoma (PGC) is a rare and rapidly invasive tumor. We report a case of PGC diagnosed by endoscopic biopsy and treated with gastrectomy and chemotherapy. PRESENTATION OF CASE: A 78-year-old man was referred to our hospital because esophagogastroduodenoscopy showed a tumor at the fornix of the stomach. Pathologic examination of biopsy specimens revealed choriocarcinoma. Abdominal computed tomography (CT) revealed no enlarged abdominal lymph nodes or distant metastases. Robot-assisted total gastrectomy with spleen-preserving D2 lymphadenectomy was performed on the basis of a diagnosis of cT2N0M0, stage cIB PGC. The pathologic diagnosis was pT2, ly0, v1, pN0, PM0, DM0, stage pIB PGC. The postoperative course was uneventful, and the patient was followed carefully without adjuvant chemotherapy. Three months after gastrectomy, blood tests indicated that serum ß-human chorionic gonadotropin (ß-hCG) levels had increased, and CT revealed multiple liver metastases. The patient underwent a standard nongestational choriocarcinoma chemotherapy regimen with etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine. Although ß-hCG levels temporarily decreased with chemotherapy, the patient experienced tumor recurrence with ascites and his serological test demonstrated an elevated level of ß-hCG (120 ng/mL). The patient died 10 months postoperatively. CONCLUSION: We report a case of stage pIB PGC with poor prognosis, recurring at only 3 months postoperatively despite curative surgery and chemotherapy.

Label-free classification of cells based on supervised machine learning of subcellular structures.

It is demonstrated that cells can be classified by pattern recognition of the subcellular structure of non-stained live cells, and the pattern recognition was performed by machine learning. Human white blood cells and five types of cancer cell lines were imaged by quantitative phase microscopy, which provides morphological information without staining quantitatively in terms of optical thickness of cells. Subcellular features were then extracted from the obtained images as training data sets for the machine learning. The built classifier successfully classified WBCs from cell lines (area under ROC curve = 0.996). This label-free, non-cytotoxic cell classification based on the subcellular structure of QPM images has the potential to serve as an automated diagnosis of single cells.

Recent advances in thoracoscopic esophagectomy for esophageal cancer.

Technical advances and developments in endoscopic equipment and thoracoscopic surgery have increased the popularity of minimally invasive esophagectomy (MIE). However, there is currently no established scientific evidence supporting the use of MIE as an alternative to open esophagectomy (OE). To date, a number of single-institution studies and several meta-analyses have demonstrated acceptable short-term outcomes of thoracoscopic esophagectomy for esophageal cancer, and we recently reported one of the largest propensity score-matched comparison studies between MIE and OE for esophageal cancer, based on a nationwide Japanese database. We found that, in general, MIE had a longer operative time and less blood loss than OE. Moreover, compared to OE, MIE was associated with a lower rate of pulmonary complications such as pneumonia, and both methods had similar mortality rates. Although MIE may reduce the occurrence of postoperative respiratory complications, MIE and OE seem to have comparable short-term outcomes. However, the oncological benefit to patients undergoing MIE remains to be scientifically proven, as no randomized controlled trials have been conducted to verify each method's impact on the long-term survival of cancer patients. An ongoing randomized phase III study (JCOG1409) is expected to determine the impact of each method with regard to short- and long-term outcomes.

Validity and significance of 30-day mortality rate as a quality indicator for gastrointestinal cancer surgeries.

BACKGROUND AND AIM: Benchmarking has proven beneficial in improving the quality of surgery. Mortality rate is an objective indicator, of which the 30-day mortality rate is the most widely used. However, as a result of recent advances in medical care, the 30-day mortality rate may not cover overall surgery-related mortalities. We examined the significance and validity of the 30-day mortality rate as a quality indicator. METHODS: The present study was conducted on cancer surgeries of esophagectomy, total gastrectomy, distal gastrectomy, right hemicolectomy, low anterior resection, hepatectomy, and pancreaticoduodenectomy that were registered in the first halves of 2012, 2013 and 2014 in a Japanese nationwide large-scale database. This study examined the mortality curve for each surgical procedure, "sensitivity of surgery-related death" (capture ratio) at each time point between days 30-180, and the association between mortality within 30 days, mortality after 31 days, and preoperative, perioperative, and postoperative factors. RESULTS: Surgery-related mortality rates of each surgical procedure were 0.6%-3.0%. Regarding 30-day mortality rates, only 38.7% (esophagectomy) to 53.3% (right hemicolectomy) of surgery-related mortalities were captured. The capture ratio of surgery-related deaths reached 90% or higher for 120-day to 150-day mortality rates. Factors associated with mortality rate within 30 days/after the 31st day were different, depending on the type of surgical procedure. CONCLUSION: Thirty-day mortality rate is useful as a quality indicator, but is not necessarily sufficient for all surgical procedures. Quality of surgery may require evaluation by combining 30-day mortality rates with other indicators, depending on the surgical procedure.

Surgery for metastatic gastrointestinal stromal tumor: to whom and how to?

Although imatinib is a standard treatment for metastatic or recurrent gastrointestinal stromal tumors (GISTs), acquired c-kit mutations reportedly cause secondary resistance to imatinib. Sunitinib is a tyrosine kinase inhibitor (TKI) that can be used as second-line therapy in imatinib-resistant or -intolerant GISTs. For sunitinib-resistant or -intolerant GISTs, regorafenib is a standard third-line treatment. Although TKI therapies have revolutionized the treatment of recurrent or metastatic GISTs, they cannot cure GISTs. Therefore, in the era of TKIs, role of cytoreductive surgery for recurrent or metastatic GISTs has been discussed. Retrospective studies of treatment strategies with front-line surgery prior to imatinib have shown that initial cytoreduction confers no benefit in cases of advanced or recurrent GIST, and administering imatinib is the principle treatment. Most retrospective studies report cytoreductive surgery to be feasible in patients with metastatic GIST whose disease is stable or responsive to imatinib. Cytoreductive surgery may be indicated in limited disease progression refractory to imatinib when complete resection is possible, but case selection is critical. Cytoreductive surgery for metastatic GIST treated with sunitinib seems less feasible because of high rates of incomplete resections and complications. The role of cytoreductive surgery for metastatic GISTs would be difficult to establish in a prospective study; individualized treatments need to be carefully designed based on c-kit and platelet-derived growth factor receptor alpha (PDGFRA) mutations and other factors.

Tenascin C in colorectal cancer stroma is a predictive marker for liver metastasis and is a potent target of miR-198 as identified by microRNA analysis.

BACKGROUND: Tumour stroma has important roles in the development of colorectal cancer (CRC) metastasis. We aimed to clarify the roles of microRNAs (miRNAs) and their target genes in CRC stroma in the development of liver metastasis. METHODS: Tumour stroma was isolated from formalin-fixed, paraffin-embedded tissues of primary CRCs with or without liver metastasis by laser capture microdissection, and miRNA expression was analysed using TaqMan miRNA arrays. RESULTS: Hierarchical clustering classified 16 CRCs into two groups according to the existence of synchronous liver metastasis. Combinatory target prediction identified tenascin C as a predicted target of miR-198, one of the top 10 miRNAs downregulated in tumour stroma of CRCs with synchronous liver metastasis. Immunohistochemical analysis of tenascin C in 139 primary CRCs revealed that a high staining intensity was correlated with synchronous liver metastasis (P<0.001). Univariate and multivariate analyses revealed that the tenascin C staining intensity was an independent prognostic factor to predict postoperative overall survival (P=0.005; n=139) and liver metastasis-free survival (P=0.001; n=128). CONCLUSIONS: Alterations of miRNAs in CRC stroma appear to form a metastasis-permissive environment that can elevate tenascin C to promote liver metastasis. Tenascin C in primary CRC stroma has the potential to be a novel biomarker to predict postoperative prognosis.