A Multicenter Analysis of Short-term and Long-term Outcomes Following Laparoscopic Multivisceral Resection for Advanced Colorectal Cancer.

Background/Aim: Recent research has demonstrated that laparoscopic multivisceral resection (MVR) for advanced colorectal cancer is safe, practicable, and yields satisfactory oncological results, which is in line with the growing usage of laparoscopic surgery. The effectiveness of laparoscopic MVR is still debatable, though. The goal of this study was to compare the short- and long-term results of patients with advanced colorectal cancer treated with open MVR with laparoscopic procedures. Patients and Methods: Data on 3,571 consecutive patients hospitalized at the Kyushu University National Kyushu Cancer Center for colorectal cancer surgery between 2004 and 2020 were gathered retrospectively. In the end, 84 individuals with advanced colorectal cancer who had a colectomy with MVR were examined. We evaluated invasiveness in terms of complications, blood loss, and operating time. Recurrence-free survival rates and overall 5-year survival were among the oncological outcomes. Results: Of the 84 patients examined, 29 underwent laparoscopic treatment, and 55 underwent open treatment. The laparoscopic surgery group experienced shorter hospital stays (15 vs. 18 days, p<0.05) and much less blood loss (median volume: 167 vs. 1,058 g, p<0.005) than the open surgery group. Following the exclusion of patients with stage IV colorectal cancer from the study (groups undergoing laparoscopic surgery, n=25; open surgery, n=38), the groups displayed comparable pathologic results and no discernible variations in either the 5-year overall survival (p=0.87) or recurrence-free survival (p=0.86). Conclusion: In certain individuals with advanced colorectal cancer, a laparoscopic method of manipulation with MVR may be less invasive than an open method without compromising the prognosis.

Clinicopathological Impact of High Preoperative CA19-9 in Early-stage Colorectal Cancer: A Single-center Retrospective Cohort Study.

BACKGROUND/AIM: This study examined the clinical significance of very high preoperative carbohydrate antigen 19-9 (CA19-9) levels in patients with early-stage colorectal cancer (CRC). PATIENTS AND METHODS: We retrospectively analyzed the clinicopathological data of patients who underwent curative resection for primary CRC (c-Stage I-III) between 2004 and 2022 in our facility. The patients were classified into three groups according to the preoperative CA19-9 level: normal (≤37.0 U/ml), high (>37.0 to ≤100.0 U/ml), and very high (>100.0 U/ml). RESULTS: Of 971 patients, 885 (91.1%), 67 (6.9%), and 19 (2.0%) had normal, high, and very high CA19-9 levels, respectively. Overall survival (very high vs. normal: p<0.0001, very high vs. high: p=0.01) and recurrence-free survival (very high vs. normal: p<0.0001, very high vs. high: p=0.18) were significantly worse in the very high group. On multivariate analysis including TNM stage, very high preoperative CA19-9 levels were independently associated with worse overall (odds ratio=4.54; 95% confidence interval=2.03-10.16; p=0.0002) and recurrence-free survival (odds ratio=3.49; 95% confidence interval=1.82-6.69; p=0.0002). CONCLUSION: High preoperative CA19-9 levels were associated with poor survival in early-stage CRC. Careful intraoperative observation and close follow-up might be necessary.

Book-Binding Technique in Totally Laparoscopic Distal Gastrectomy with Billroth I Reconstruction: Clinical Results and Outcomes in 188 Patients with Gastric Cancer.

BACKGROUND: Laparoscopic gastrectomy is widely used as a curative treatment for gastric cancer. Although delta-shaped anastomosis is commonly used for Billroth I anastomosis after totally laparoscopic distal gastrectomy (TLDG), it has some drawbacks. The book-binding technique (BBT) was developed as an alternative, and this study aimed to examine its short-term results in 188 consecutive cases. STUDY DESIGN: This retrospective study included patients who underwent BBT reconstruction after TLDG for gastric malignancy between 2011 and 2020. BBT is a technique for intracorporeal gastroduodenostomy, which is a triangular anastomosis with a linear stapler that does not require additional dissection or rotation of the duodenum. The short-term outcomes of BBT reconstruction and postoperative endoscopic findings were analyzed. RESULTS: This study evaluated 188 patients who underwent TLDG and BBT reconstruction. Anastomotic stenosis and leakage occurred in 1.1% and 0.5% of the patients, respectively. The median time to the first diet was 3.1 days, and the median postoperative hospital stay was 11.9 days. BBT anastomoses were performed by 19 surgeons and took an average of 32.8 minutes to complete, with completion times decreasing as the surgical team became more proficient. On endoscopy performed 1 year postoperatively, 5.2% had reflux esophagitis (grade A or higher), 67.8% had gastritis (grade 1 or higher), 37.4% had residual food (grade 1 or higher), and 37.4% had bile reflux (grade 1). CONCLUSIONS: BBT is a safe and feasible method for intracorporeal gastroduodenostomy in TLDG for patients with gastric malignancy and demonstrates good surgical outcomes.

Field experiment of a telesurgery system using a surgical robot with haptic feedback.

PURPOSE: To verify the usefulness of haptic feedback in telesurgery and improve the safety of telerobotic surgery. METHODS: The surgeon's console was installed at two sites (Fukuoka and Beppu; 140 km apart), and the patient cart was installed in Fukuoka. During the experiment, the surgeon was blinded to the haptic feedback levels and asked to grasp the intestinal tract in an animal model. The surgeon then performed the tasks at each location. RESULTS: No marked differences in task accuracy or average grasping force were observed between the surgeon locations. However, the average task completion time was significantly longer, and the system usability scale (SUS) was significantly lower rating for remote operations than for local ones. No marked differences in task accuracy or task completion time were observed between the haptic feedback levels. However, with haptic feedback, the organ was grasped with a significantly weaker force than that without it. Furthermore, with haptic feedback, experienced surgeons in robotic surgery tended to perform an equivalent task with weaker grasping forces than inexperienced surgeons. CONCLUSION: The haptic feedback function is a tool that allows the surgeon to perform surgery with an appropriate grasping force, both on site and remotely. Improved safety is necessary in telesurgery; haptic feedback will thus be an essential technology in robotic telesurgery going forward.

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.

Esophagectomy for esophageal stricture with systemic sclerosis: a case report.

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease characterized by frequent esophageal involvement. However, there are few reports on esophagectomy for esophageal strictures associated with SSc. Herein, we present a case of successful treatment of an esophageal stricture associated with SSc through subtotal esophagectomy. CASE PRESENTATION: A 53-year-old female patient was diagnosed with SSc, interstitial pneumonia, and gastroesophageal reflux disease (GERD). The patient developed an esophageal ulcer and benign stricture that required a subtotal esophagectomy 10 years after the diagnosis. Histopathological findings revealed thinning of the muscle layer, a characteristic feature of SSc. The patient was free of dysphagia or regurgitation. CONCLUSIONS: An esophagectomy is a valuable option for treating esophageal strictures in SSc. Therefore, surgical approaches should be established for patients with SSc.

A pathological complete response after immunotherapy with pembrolizumab for distal duodenal adenocarcinoma caused by Lynch syndrome: a case report.

Primary adenocarcinoma of the duodenum is a rare neoplasm that is often microsatellite instability-high (MSI-H). Pembrolizumab, a monoclonal antibody, has been recently approved in Japan for treatment of MSI-H solid tumors. Lynch syndrome is a frequent hereditary cancer predisposition syndrome. It is linked to an increased risk of various types of cancer, including colorectal and endometrial cancer, and is closely related to MSI-H. We present the case of a 55-year-old woman who was diagnosed with duodenal cancer. Biopsy findings revealed MSI-H, and pembrolizumab therapy was initiated because the tumor was in contact with the left renal vein and had metastasized to the mesenteric lymph nodes of the small intestine. Subsequently, after completing two courses of pembrolizumab therapy, the patient developed duodenal stenosis and underwent surgery. Pathological analysis of the resected specimen revealed no evidence of malignancy. Given the patient's previous cancer history and the occurrence of cancer in close relatives, genetic testing of peripheral blood was performed, which revealed the diagnosis of Lynch syndrome. Furthermore, the variant responsible for Lynch syndrome was found to be a mutation of NM_000251.3:c.211 + 1G > C in MSH2.

Left recurrent nerve lymph node dissection in robotic esophagectomy for esophageal cancer without esophageal traction.

BACKGROUND: Because the robotic arm is located on the dorsal side of the patient, when the esophagus is pulled dorsally for the left recurrent nerve lymph node (LRLN) dissection, the robotic arm interferes with the surgical field. This made it difficult to prepare for the left recurrent lymph node dissection. We developed LRLN dissection in robotic surgery with natural space creation by physiological organ movement and evaluated the short-term results. METHODS: In this retrospective study, we analyzed 102 cases of robot-assisted thoracoscopic subtotal esophagectomy (RATE) among radical subtotal esophagectomies performed between December 2018 and December 2022 using medical records. LRLN dissection is preceded by a dissection of the esophagus from the trachea. Leaving the esophagus on the vertebral side and away from the trachea resulted in a physiological elevation of the esophagus, providing space between the trachea and esophagus. RESULTS: The thoracic surgery time in RATE was 181 (115-394) min. The number of LRLNs dissected was 4 (1-14). Six patients (6%) had a postoperative recurrence in the mediastinal lymph nodes. Seven patients (7%) had grade ≥ 1 left recurrent nerve palsy. CONCLUSIONS: LRLN dissection with RATE using natural space creation was performed safely with a sufficient number of dissected lymph nodes and little left recurrent nerve palsy.

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.

Combined treatment with surgery and immune checkpoint inhibitor extended survival in a case of gastric intramural metastasis from esophageal cancer: a case report.

BACKGROUND: Intramural metastasis (IM) of esophageal cancer is classified as distant metastasis according to the Japanese Classification of Esophageal Cancer, and it is well-known to be associated with a poor prognosis. We herein report a case of perforated gastric IM of esophageal cancer that was successfully controlled with nonradical surgery and subsequent immune checkpoint inhibitor (ICI) treatment. CASE PRESENTATION: A 72-year-old woman was referred to our department for the treatment of esophageal cancer and perforated gastric ulcer. A histological examination of the main tumor and gastric ulcer lesion revealed squamous cell carcinoma. Since the gastric wall tumor had invaded the celiac artery, complete resection was considered impossible. Chemotherapy was administered but led to severe adverse events, so palliative resection was performed. Two months after surgery, computed tomography revealed enlargement of the residual tumor around the celiac artery. However, after nivolumab monotherapy was started, the tumor diminished remarkably, and the quality of life of the patient dramatically improved. Nine months after nonradical surgery, she is surviving without any disease concern. CONCLUSIONS: With the increased availability of ICIs, multidisciplinary treatment with surgery and ICIs can potentially lead to long-term survival, even in cases expected to have a poor prognosis.

Telesurgery and telesurgical support using a double-surgeon cockpit system allowing manipulation from two locations.

BACKGROUND: Although several studies on telesurgery have been reported globally, a clinically applicable technique has not yet been developed. As part of a telesurgical study series conducted by the Japan Surgical Society, this study describes the first application of a double-surgeon cockpit system to telesurgery. METHODS: Surgeon cockpits were installed at a local site and a remote site 140 km away. Three healthy pigs weighing between 26 and 29 kg were selected for surgery. Non-specialized surgeons performed emergency hemostasis, cholecystectomy, and renal vein ligation with remote assistance using the double-surgeon cockpits and specialized surgeons performed actual telesurgery. Additionally, the impact of adding internet protocol security (IPsec) encryption to the internet protocol-virtual private network (IP-VPN) line on communication was evaluated to address clinical security concerns. RESULTS: The average time required for remote emergency hemostasis with the double-surgeon cockpit system was 10.64 s. A non-specialized surgeon could safely perform cholecystectomy or renal vein ligation with remote assistance. Global Evaluative Assessment of Robotic Skills and System Usability Scale scores were higher for telesurgical support-assisted surgery by a non-specialized surgeon using the double-surgeon cockpits than for telesurgery performed by a specialized surgeon without the double-cockpit system. Adding IPsec encryption to the IP-VPN did not have a significant impact on communication. CONCLUSION: Telesurgical support through our double-surgeon cockpit system is feasible as first step toward clinical telesurgery.

Alterations in the gut microbiome in patients with esophageal carcinoma in response to esophagectomy and neoadjuvant treatment.

PURPOSE: Analyzing the gut microbiome is essential for planning treatment strategies to manage esophageal squamous cell carcinoma. This study aimed to characterize the gut microbiome of patients with esophageal squamous cell carcinoma and to identify alterations in its composition during treatment. METHODS: We observed alterations in the gut microbiome in 21 consecutive patients with esophageal squamous cell carcinoma at five different time points, from neoadjuvant treatment to postoperative surgery. Ten healthy individuals were used as a non-cancer control group. Fecal samples were collected and analyzed using 16S ribosomal ribonucleic acid sequencing. RESULTS: Before treatment, participants with esophageal squamous cell carcinoma had different alpha and beta diversity in comparison to healthy controls. The number of Streptococcus, a facultative anaerobic bacterium, was significantly higher, whereas that of Faecalibacterium, an obligate anaerobic bacterium, was significantly lower. Both alpha and beta diversity remained unchanged during neoadjuvant treatment, but the alterations were pronounced after surgery. The increase in the relative abundance of Streptococcus and the decrease in that of Faecalibacterium also tended to be more pronounced after surgery. CONCLUSIONS: The gut microbiome in patients with esophageal squamous cell carcinoma is altered with surgical intervention.

Effectiveness of taxanes following nivolumab in patients with advanced esophageal squamous cell carcinoma: a retrospective chart review of patients in ATTRACTION-3.

BACKGROUND: The phase III ATTRACTION-3 study showed that second-line nivolumab monotherapy for advanced esophageal squamous cell carcinoma prolonged overall survival (OS) but did not improve progression-free survival (PFS). Subsequent systemic therapy after discontinuing nivolumab may affect these outcomes. To test this possibility, we evaluated the outcomes of treatment with taxanes after nivolumab in ATTRACTION-3. METHODS: We reviewed the charts of Japanese patients who had discontinued second-line nivolumab in ATTRACTION-3 and started subsequent third-line taxanes between January 7, 2016, and November 12, 2018. The primary endpoint was objective response rate (ORR) to third-line taxanes. RESULTS: Of the 75 patients included in this study, 54 (72%), 18 (24%), and 3 (4%) patients received either paclitaxel, docetaxel, or combination therapy comprising docetaxel, cisplatin, and 5-fluorouracil, respectively. The ORR in the overall, paclitaxel, and docetaxel groups was 29.6%, 36.5%, and 12.5%, respectively; these numbers were comparable to those (20-44%) in patients receiving taxanes as first- and second-line therapy. The median OS in the overall, paclitaxel, and docetaxel groups was 9.9, 9.9, and 9.3 months, respectively, whereas the corresponding median PFS was 4.9, 4.7 and 6.5 months, respectively. Treatment-related adverse events were observed in 65 (87%) patients, of which grade 3-4 occurred in 37 (49%) patients. CONCLUSIONS: Favorable effectiveness and safety profile of taxanes following second-line nivolumab was observed in Japanese patients with advanced esophageal squamous cell carcinoma. When a patient with advanced esophageal squamous cell carcinoma receiving nivolumab becomes refractory or intolerant, subsequent taxane treatment may be a promising option.

Artificial Intelligence-Based Prediction of Recurrence after Curative Resection for Colorectal Cancer from Digital Pathological Images.

BACKGROUND: To develop an artificial intelligence-based model to predict recurrence after curative resection for stage I-III colorectal cancer from digitized pathological slides. PATIENTS AND METHODS: In this retrospective study, 471 consecutive patients who underwent curative resection for stage I-III colorectal cancer at our institution from 2004 to 2015 were enrolled, and 512 randomly selected tiles from digitally scanned images of hematoxylin and eosin-stained tumor tissue sections were used to train a convolutional neural network. Five-fold cross-validation was used to validate the model. The association between recurrence and the model's output scores were analyzed in the test cohorts. RESULTS: The area under the receiver operating characteristic curve of the cross-validation was 0.7245 [95% confidence interval (CI) 0.6707-0.7783; P < 0.0001]. The score successfully classified patients into those with better and worse recurrence free survival (P < 0.0001). Multivariate analysis revealed that a high score was significantly associated with worse recurrence free survival [odds ratio (OR) 1.857; 95% CI 1.248-2.805; P = 0.0021], which was independent from other predictive factors: male sex (P = 0.0238), rectal cancer (P = 0.0396), preoperative abnormal carcinoembryonic antigen (CEA) level (P = 0.0216), pathological T3/T4 stage (P = 0.0162), and pathological positive lymph node metastasis (P < 0.0001). CONCLUSIONS: The artificial intelligence-based prediction model discriminated patients with a high risk of recurrence. This approach could help decision-makers consider the benefits of adjuvant chemotherapy.

Influence of Robotic Rectal Resection Versus Laparoscopic Rectal Resection on Postoperative Ileus: A Single-center Experience.

AIM: This study was performed to clarify the relationship between robotic rectal resection and postoperative ileus (POI) by comparing robotic surgery with laparoscopic surgery. MATERIALS AND METHODS: We retrospectively reviewed 238 patients who underwent robotic (n=41) or laparoscopic (n=197) rectal resection for rectal cancer in our institution from January 2013 to June 2020. First, we compared the background factors and short-term surgical outcomes between robotic and laparoscopic surgery. Next, we investigated the postoperative complications of robotic and laparoscopic rectal resection. Finally, we identified the risk factors for POI following rectal cancer resection. RESULTS: The percentages of patients with an Rb tumor location, treatment by abdominoperitoneal resection/intersphincteric resection/low anterior resection, a temporary diverting ileostomy, and a long operation time were significantly higher in robotic than laparoscopic surgery ( P <0.0001, P =0.0002, P =0.0078, and P =0.0001, respectively). There was no significant difference in any individual postoperative complication between robotic and laparoscopic surgery. Risk factors for POI were male sex ( P =0.0078), neoadjuvant chemoradiotherapy ( P =0.0007), an Rb tumor location ( P =0.0005), treatment by abdominoperitoneal resection/intersphincteric resection/low anterior resection ( P =0.0044), a temporary diverting ileostomy ( P <0.0001), and operation time of ≥240 minutes ( P =0.0024). Notably, robotic surgery was not a risk factor for POI following rectal resection relative to laparoscopic surgery. CONCLUSION: Although patients who underwent robotic surgery had more risk factors for POI, the risk of POI was similar between robotic and laparoscopic rectal resection.

Clinical impact of the triple-layered circular stapler for reducing the anastomotic leakage in rectal cancer surgery: Porcine model and multicenter retrospective cohort analysis.

Aim: To investigate the impact of the triple-layered circular stapler compared with the double-layered circular stapler on anastomotic leakage after rectal cancer surgery. Methods: The bursting pressure was compared between porcine ileocolic anastomoses created using a double- or triple-layered stapler. We also retrospectively analyzed the incidence of severe anastomotic leakage in 194 patients who underwent colorectal anastomosis using a double- or triple-layered circular stapler during rectal cancer resection performed in two cancer centers between January 2015 and April 2021. Results: In the porcine model, the bursting pressure was higher in anastomoses created using the triple-layered stapler than the double-layered stapler (end-to-end anastomosis: 26.4 ± 6.2 mm Hg vs 14.5 ± 4.3 mm Hg, P = .0031; side-to-side anastomosis: 27.7 ± 5.0 mm Hg vs 18.0 ± 2.9 mm Hg, P = .0275). Intersectional leakage occurred in 41% and 83% of anastomoses created using the triple- or double-layered stapler, respectively (P = .0821). In the clinical cohort, the double- and triple-layered stapler was used in 153 and 41 patients, respectively. The incidence of anastomotic leakage was lower for anastomoses created using the triple-layered stapler vs the double-layered stapler (0.0% vs 5.8%, P = .0362). In multivariate analysis, the factors independently associated with a lower incidence of anastomotic leakage were female sex (odds ratio: 0.16, 95% confidence interval: 0.01-0.90, P = .0354) and triple-layered stapler usage (odds ratio: 0.00, 95% confidence interval: 0.00-0.96, P = .0465). Conclusion: Anastomoses created using a triple-layered circular stapler had high bursting pressure, which might contribute to a lower incidence of anastomotic leakage after rectal cancer surgery.

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.

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.