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Accumulating evidence demonstrates that bone marrow (BM)-derived mesenchymal stem cells (MSCs) play critical roles in regulating progression of various types of cancer. We have previously shown that Wnt5a-Ror2 signaling in MSCs induces expression of CXCL16, and that CXCL16 secreted from MSCs then binds to its cognate receptor CXCR6 on the surface of an undifferentiated gastric cancer cell line MKN45 cells, eventually leading to proliferation and migration of MKN45 cells. However, it remains unclear about a possible involvement of another (other) cytokine(s) in regulating progression of gastric cancer. Here, we show that CXCL16-CXCR6 signaling is also activated in MSCs through cell-autonomous machinery, leading to upregulated expression of CCL5. We further show that CCR1 and CCR3, receptors of CCL5, are expressed on the surface of MKN45 cells, and that CCL5 secreted from MSCs promotes migration of MKN45 cells presumably via its binding to CCR1/CCR3. These data indicate that cell-autonomous CXCL16-CXCR6 signaling activated in MSCs upregulates expression of CCL5, and that subsequent activation of CCL5-CCR1/3 signaling in MKN45 cells through intercellular machinery can promote migration of MKN45 cells. Collectively, these findings postulate the presence of orchestrated chemokine signaling emanated from MSCs to regulate progression of undifferentiated gastric cancer cells.

Background Retrosternal reconstruction is associated with a lower risk of mediastinitis, gastro-tracheal fistula, and hiatal hernia. Historically, traumatic manual creation of the retrosternal tunnel has been performed using one's fist. We report a novel and atraumatic laparoscopic procedure to create the retrosternal route. Methods We have laparoscopically created the retrosternal route in 25 thoracoscopic, mediastinoscopic, or robot-assisted minimally invasive esophagectomies since August 2019. Specifically, a peritoneal incision is started at the dorsal side of the xiphoid process. Through a 12-mm port inserted slightly to the right of and superior to the umbilical camera port, we dissect loose connective tissues from the caudal to the cranial side using behind the sternum and inside the internal thoracic vessels as landmarks. The time required to create the route was calculated. Then, the cumulative sum (CUSUM) method and the simple moving average of five cases were used to evaluate the learning curve of this novel procedure. Operative outcomes were analyzed according to the learning curve results and also compared with 25 cases of postmediastinal reconstruction counterparts. Results Twenty-five patients were divided into the early group (six patients) and late group (19 patients) based on the peak of the CUSUM chart. The time required for route creation was 28.5 min (median) in the early and 15 min in the late group, indicating a significant difference (P = 0.038). The overall incidence of pleural injury was 20% (5 of 25 patients), with no significant difference between the groups. There was no significant difference in the incidence of perioperative complications. Also, there were no significant differences in perioperative complications or gastric conduit functions 1 year after surgery between the retrosternal and the postmediastinal reconstruction. Conclusion Laparoscopic creation of a retrosternal route for gastric conduit reconstruction is safe and feasible and has a short learning curve.

Whether surgical device usage in laparoscopic gastrectomy differs with respect to operator’s skill levels is unknown. Further, device usage analysis using artificial intelligence has not been reported to date. Herein, we compared the patterns of surgical device usage during laparoscopic gastrectomy for gastric cancer among surgeons at different skill levels. The data of device usage was acquired from laparoscopic video recordings using an automated surgical-instrument detection system. In total, 100 video recordings of infrapyloric lymphadenectomy and 33 of D2 suprapancreatic lymphadenectomy during laparoscopic gastrectomy for gastric cancer were analyzed in this retrospective study. The system’s accuracy was evaluated by comparing the automatic and the manual usage time. Surgical device usage patterns were compared between qualified and nonqualified surgeons of The Japan Society for Endoscopic Surgery Endoscopic Surgical Skill Qualification System. For every device, the automatic detection time and manual detection time were consistent with each other. In infrapyloric lymphadenectomy, the usage time proportions of dissector forceps and clip applier were higher among nonqualified operators than among qualified operators (dissector, 5.1% vs. 2.3%, P

Background/aim Cancer stem cells (CSCs) contribute to resistance against neoadjuvant chemotherapy (NAC) in esophageal squamous cell carcinoma (ESCC). We conducted a retrospective observational study for the relationship between the expression levels of CSC markers in biopsy specimens prior to 5-fluorouracil plus cisplatin (FP)-NAC and the pathological responses. Patients and methods We included 171 patients with ESCC who underwent the FP-NAC followed by radical resection. Biopsy specimens prior to the FP-NAC were obtained and immunochemically stained for CD44, CD133, and CD24. Results The biopsy specimens of the non-responders had the CD44high/CD24low expression at high levels, which was found as an independent predictor of not only FP-NAC resistance but also poor overall survival by multivariate analyses. Conclusion CD44high/CD24low expression in the biopsy specimens prior to FP-NAC may be a predictor of FP-NAC resistance and poor prognosis of ESCC patients.

Despite the increasing utilization of transanal total mesorectal excision as a promising approach for low rectal cancer, the feasibility and safety of transperineal minimally invasive abdominoperineal resection (tp-APR) remain unclear. In total, 25 patients who underwent tp-APR between April 2017 and May 2020 (tp-APR group) and 27 patients who underwent conventional laparoscopic APR between May 2009 and September 2016 (lap-APR group) for low rectal cancer were enrolled in this retrospective study. Clinical outcomes were compared between the groups before and after propensity score matching. The primary outcome was the incidence of the overall postoperative complications with Clavien–Dindo grade II or above. Standardized technique of tp-APR was also demonstrated. On comparison, operative time, intraoperative blood loss, and overall postoperative complications with Clavien–Dindo grade II or above were significantly less in the tp-APR group both before and after propensity score matching. The rates of urinary disturbance and perineal wound infection were significantly less in the tp-APR group after matching. Further, postoperative hospital stay was significantly shorter in the tp-APR group both before and after matching. However, pathological outcomes did not differ between the groups before and after matching. There has been no local recurrence in the tp-APR group with a median follow-up period of 18 months. Standardized tp-APR for low rectal cancer is feasible and seems superior to conventional laparoscopic APR in terms of short-term outcomes. Further larger-scale studies with a longer follow-up period are required to evaluate oncological outcomes.

Aim The outcomes of gastrectomy for gastric cancer in patients at each severity of chronic kidney disease (CKD) remain unknown. Methods We retrospectively analyzed the outcomes of 560 patients who underwent distal or total gastrectomy for gastric cancer between 2009 and 2018. We classified the patients into four groups based on estimated glomerular filtration rate: stage 1/2 (normal to mild, n = 375), stage 3a (mild to moderate, n = 122), stage 3b (moderate to severe, n = 43), and stage 4/5 (severe to end‐stage, n = 20) CKD. The relationship between CKD stage and the incidence of postoperative morbidity was analyzed. Results CKD was a predictor of overall morbidity independent of age, gender, American Society of Anesthesiologists Performance Status, pulmonary comorbidity, extent of lymphadenectomy, and operation time in a multivariate analysis. The incidences of overall and severe morbidity were significantly increased with CKD progression (both P, Chronic kidney disease (CKD) progression increases the risk of morbidity following gastrectomy in gastric cancer patients. The risk elevates substantially at moderate CKD with an eGFR ≤ 45 ml/min/1.73 m2.

Given the worldwide popularization of conventional minimally invasive esophagectomy (C-MIE), robot-assisted MIE (RAMIE) can be expected to provide a finer procedure. However, controversy remains regarding whether RAMIE is superior to C-MIE in preventing recurrent laryngeal nerve (RLN) palsy. Considering the shallow learning curve for RAMIE, a novel procedure for lymphadenectomy along the RLN during RAMIE is needed. Based on a logical and simple understanding of the left upper mediastinum anatomy, the authors developed a novel “modified bascule method” for RAMIE that could simplify lymphadenectomy along the left RLN and prevent it from being touched and stretched. Between 2018 and 2020, 46 patients with esophageal carcinoma underwent RAMIE using this method at Kobe University. The modified bascule method was used to perform RAMIE for 29 men and 17 women with a median age of 67 years (range, 49–82 years). The median thoracoscopic procedure time was 438 min (range, 344–625 min), and the median console time was 351 min (range 273–518 min). The study harvested a median of 24 (range, 8–34) lymph nodes from the thoracic portion and 4 (range, 0–10) lymph nodes from along the left RLN. The mortality rate was 0%. Postoperative left RLN palsy classified as Clavien–Dindo (C–D) grade 1 or higher was observed for 9 patients (19%), whereas grade 2 or higher was not seen (0%). Pneumonia and anastomotic leakage rates higher than C–D grade 2 were respectively 13% and 19%. The novel modified bascule method for RAMIE can promote feasible lymphadenectomy along the left RLN even when performed during the learning period.

BACKGROUND/AIM The safety of neoadjuvant chemoradiotherapy (NACRT) combined with total mesorectal excision (TME) and selective lateral pelvic lymph node dissection (LLND) is unclear in elderly patients with locally advanced rectal cancer (LARC). PATIENTS AND METHODS Forty-two patients with LARC underwent TME and selective LLND following NACRT at Kobe University Hospital. The clinical outcomes were retrospectively compared between the elderly (aged ≥70 years, n=13) and non-elderly patients (aged

Esophageal squamous cell cancer (ESCC) is one of the deadliest cancers in the world. Esophagectomy remains the principal treatment, and minimally invasive esophagectomy (MIE) has been performed worldwide. This study aimed to clarify whether the lymph node ratio (LNR), defined as the ratio of metastatic lymph nodes (LNs) to examined, is a prognostic factor for ESCC after MIE. This study included 327 MIEs with the patient in the prone position at two institutions from 2010 to 2015. Cox proportional hazards regression analyses using clinicopathologic characteristics and the LNR were performed for the pN1 patients and the whole cohort. In the multivariate analysis for all stages, independent prognostic factors were depth of tumor invasion (P

Purpose Minimally invasive esophagectomy (MIE) has been increasingly used, but many reports have stated that recurrent laryngeal nerve (RLN) palsy after MIE is a major complication associated with postoperative pneumonia. Prevention of RLN palsy clearly has been a challenging task. The study aim was to determine if a three-dimensional (3-D) stereoscopic vision system can reduce the RLN palsy rate after MIE. Methods This was a retrospective study of MIE (McKeown esophagectomy) using a 3-D or 2-D stereoscopic vision system to treat 358 patients in the prone position between April 2010 and March 2019. The patients who underwent 3-D MIE (3-D group) or 2-D MIE (2-D group) were matched by using propensity score matching. After matching, the perioperative outcomes were compared between the groups. Results After propensity score matching, 154 patients were analyzed (77 patients, 3-D group; 77 patients, 2-D group). There were no significant differences in the patients’baseline characteristics in the matched cohort. There were no significant differences in the rates of pneumonia (Clavien–Dindo (C–D) grade ≥ II, 3-D vs. 2-D, 11 (14%) vs. 12 (16%)), anastomotic leakage (C–D grade ≥ II, 10 (13%) vs. 18 (23%)) and mortality. The rates of left RLN palsy (C–D grade ≥ IIIa, 1 (1.3%) vs. 7 (9.1%), P = 0.029), right RLN palsy (C–D grade ≥ I, 2 (3%) vs. 8 (10%), P = 0.049), comprehensive complication index (CCI®) (8.5 vs. 14.3, P = 0.011), and postoperative hospital stay period (median: 25 vs. 30 days, P = 0.034) were significantly lower in the 3-D group than in the 2-D group, respectively. Conclusions In MIE, the 3-D viewing system was one of the factors that reduced postoperative morbidities such as the rates of each RLN palsy and CCI®, leading to shorter postoperative hospital stay.

Esophageal cancer has a poor prognosis despite the fact that surgical techniques have been advanced and optimized, and systemic multimodality approaches have progressed recently. Adding chemotherapy, radiotherapy, and immunotherapy to the basic surgical approach have been shown to have therapeutic benefit for esophageal cancer. This review describes the latest development of chemoradiotherapy, chemotherapy, and immunotherapy, which have contributed to the reduction in esophageal cancer growth and improved the survival of patients. Chemoradiation is a treatment option for resectable esophageal cancer to preserve the esophagus for patients who cannot tolerate surgery. Moreover, a combination of chemoradiotherapy and salvage surgery could extend the survival of patients. The effects of a triplet chemotherapy regimen are currently being verified in some Phase III studies for unresectable advanced/recurrent esophageal cancer. In addition, with the great promise of immune checkpoint inhibitors, strategies that incorporate the use of immunotherapy may shift from the metastatic setting to the neoadjuvant/adjuvant setting as a result of clinical trials. More precise comprehension of the molecular biology of esophageal cancer is expected to further control disease progression using multimodality treatments in the future.

Objectives: Dissection of the No. 11p lymph nodes is technically challenging because of variations in anatomical landmarks. This study aimed to determine the accuracy and efficacy of predicting the dorsal landmark of No. 11p lymph node using three-dimensional computed tomography simulation. Methods: Laparoscopic gastrectomy with No. 11p lymph node dissection with preoperative simulation using three-dimensional computed tomography was performed in 24 patients at our institution from October 2016 to May 2018. Initially, preoperative three-dimensional computed tomography findings with operative videos in these 24 patients were compared. The dorsal landmark was defined as an anatomical structure behind the splenic artery on preoperative three-dimensional computed tomography and operative videos. The dorsal landmark of No. 11p lymph node was divided into four types: (1) splenic vein type, (2) splenic vein and pancreas type, (3) pancreas type, and (4) unclear type. Then, to investigate the efficacy of three-dimensional computed tomography, we compared the clinical and pathological features and surgical outcomes of nine patients who underwent preoperative three-dimensional computed tomography simulation (three-dimensional computed tomography group) and 23 patients who did not undergo three-dimensional computed tomography simulation from August 2014 to September 2016 (non-three-dimensional computed tomography group). All procedures were performed by one surgeon certified by the Endoscopic Surgical Skill Qualification System in Japan. Results: The concordance rate between three-dimensional computed tomography and operative videos of the dorsal landmark using three-dimensional computed tomography was 79% (19/24). The operative time of No. 11p lymph node dissection was significantly shorter in the three-dimensional computed tomography group than in the non-three-dimensional computed tomography group (7.7 versus 15.8 min, P = 0.044). Conclusion: The accuracy of predicting the dorsal landmark of No. 11p lymph node using three-dimensional computed tomography was extremely high. Preoperative simulation with three-dimensional computed tomography was useful in shortening the operative time of No. 11p lymph node dissection.

This study was conducted to determine whether establishing the proximal resection line using India ink tattooing can ensure safe resection margins during totally laparoscopic distal gastrectomy. This retrospective study included 81 patients who underwent totally laparoscopic distal gastrectomy for gastric cancer on the lower two-thirds of the stomach. The proximal resection margins were analyzed with respect to the macroscopic type and clinical T stage, and the intraoperative appearance of the stain on the serosa was classified by reviewing surgical videos. R0 resection was performed in all patients. The rates of the intended margins were 89.2% in patients without a frozen section diagnosis and 84.2% in patients with differentiated type lesions who underwent a frozen section diagnosis; however, most patients with undifferentiated advanced lesions failed to achieve the intended resection margins. Intraoperative appearance revealed that 85.2% of patients had localized type stains, whereas 11.1% had widespread-type stains. Our procedure to determine the proximal resection line in totally laparoscopic distal gastrectomy is oncologically safe. However, careful observation of the resected specimen and a frozen section analysis should be performed for undifferentiated advanced lesions.

Recent advances in treatment for esophageal cancer have improved prognosis after esophagectomy, but they have led to an increased incidence of gastric conduit cancer. In most gastric conduit cancer patients who underwent retrosternal reconstruction, median sternotomy is performed, which is associated with a risk of postoperative bleeding and osteomyelitis; pain often negatively affects respiration. To avoid these problems, we developed thoracoscopic retrosternal gastric conduit resection in the supine position (TRGR-S) as new procedure. Methods We performed the first case of TRGR-S for a 75-year-old male with retrosternal gastric conduit cancer. He was placed in the supine position. Four ports were placed in the left chest wall. The gastric conduit was separated from the epicardium, sternum, and left brachiocephalic vein. Due to adhesions between the gastric tube and the right pleura, combined resection of the right pleura was performed. Next, pediculated jejunal reconstruction via the presternal route was performed. Results Because there were few adhesions in the left thoracic cavity, this approach provided safety and a good surgical view, and it was easy to recognize the landmark including epicardium, sternum, and left brachiocephalic vein leading to appropriate resection of the tissue. Furthermore, there were few restrictions on the operative angle for the forceps and operability was quite ergonomic. Moreover, the lungs can be noninvasively contracted via an artificial pneumothorax. The pathological diagnosis was signet ring cell carcinoma (pT1b, pN0, M0, pStage I), indicating R0 resection. There were no post-operative complications. Conclusion This approach does not require sternotomy, so it has less risk of postoperative bleeding and osteomyelitis. Due to fewer adhesions, this approach is safe and provides a good surgical view. TRGR-S is a safe, ergonomic, and reliable procedure for resection of retrosternal gastric conduit cancer. Video This is the video of the operation ‘TRGR-S’, which is the new procedure for the gastric conduit cancer. https://www.dropbox.com/s/2whnekgp73hw1lz/video%20for%20ISDE2020.mov?dl=0.

Thoracoscopic esophagectomy in the prone position (TEP) for esophageal cancer is reported to have superiority in preserving postoperative respiratory function and reducing postoperative respiratory complications. In Japan, the majority of patients with esophageal cancer are smokers and have obstructive ventilation disorders. But, the feasibirity and safety of TEP for patients with low respiratory function is unclear. Objectives To clarify the feasibirity and safety of TEP for esophageal cancer patients with obstructive respiratory function. Methods The 95 patients with obstructive respiratory disorder who underwent TEP and gastric tube reconstruction via posterior mediastinal route for esophageal cancer from January 2016 to April 2019 were divided into the two groups, low respiratory function (LRF) group and the control group. Short-term outcomes were compared between two groups. Results The control group was 73 cases, and the LRF group was 22 cases. Propensity score matching using age, gender, cT, and cN as covariates was used to identify matched patients (22 per group) in both groups. There were no differences in operation time of overall and intrathoracic part, or blood loss in each group. In the postoperative complications, pneumonia (13.6% vs. 9.1%), recurrent laryngeal palsy (18.2% vs. 22.7%), anastomotic leakage (13.6% vs. 13.6%) and hospital stay (36.3 days vs 27.5 days) were no differences in both groups. Conclusion TEP can be feasible and safe for the patients with obstructive ventilation disorder and low respiratory function.

Granulocyte-colony stimulating factor (G-CSF) producing tumor is one type of growth factor producing tumor that induces leukocytosis. On the other hand, adenocarcinoma with enteroblastic differentiation disease is known as α-fetprotein (AFP), glypican3, and Sal-like protein 4 (SALL4) producing tumor. We report a first case of G-CSF producing esophageal cancer with enteroblastic differentiation which has never been reported in the world. Methods [Case presentation]: A fifty-six year-old man was admitted to our hospital to treat esophageal carcinoma. His body temperature was elevated. Blood biochemistry tests showed leukocytosis (WBC 14000/μl). Gastroscopy revealed a 10-cm diameter, superficial elevated lesion in the lower thoracic esophagus. Biopsy findings indicated a diagnosis of adenocarcinoma. No distant metastasis, but right subclavian and para esophageal lymph nodes swelling were identified via computed tomography. Thus, we planned neo adjuvant chemotherapy (NAC) (5-FU 800 mg/m2 plus Cisplatin 80 mg/m2) before surgical resection. The patient’s hyperthermia and leukocytosis improved by not antibiotics but NAC. Therefore, we suspected G-CSF producing tumor. Results The serum level of G-CSF was markedly elevated at 133 pg/ml (normal range, Additionally, PET/CT showed abnormally high uptake of (18) F-FDG not only by the tumor itself, but also diffusely throughout the bone marrow. The patient underwent minimally invasive esophagectomy in the prone position with two-field lymph node dissection. Immunohistochemical studies showed G-CSF producing adenocarcinoma with enteroblastic differentiation (AFP negative, glypican3 and SALL4 positive). Pathological stage was pT2N0M0, stageII. After resection, improvement of hyperthermia, leukocytosis, and serum level of G-CSF can be seen. Findings of (18) F-FDG throughout the bone marrow were also disappeared. Conclusion We experienced an extremely rare case of G-CSF producing, esophageal adenocarcinoma with enteroblastic differentiation.

The Japanese National Clinical Database (NCD) started its data registration since 2011, has grown up to a large nationwide database covering more than 95% of the surgeries performed by regular surgeons in Japan. The NCD grew rapidly harvesting over 11 million cases data between 2011 and 2018 from more than 5,000 facilities. Methods In this period, the surgeries of the esophagus were performed for 70,528 cases. In 2018, 93.8% of surgeries were performed at certified institutions, and 94.7% did with the participation of the board-certified surgeon. The board-certified surgeons operated 75.2% of the surgeries. Results Esophagectomy was performed for 47,055 patients in eight years. In 2018, 23.3% of the cases were 75 years old or more. Postoperative complications of Clavien Dindo classification grade III or higher occurred in 22.9% of all. As the patients have been getting older, the morbidities have been increasing. However, the mortalities have been kept at a low level. Postoperative 30-day and 90-day mortalities were 0.9% and 1.9%, respectively. The rates of endoscopic surgery have been increasing year by year, especially high in esophagectomy, which was 61.0% in 2018. Conclusion A risk-adjusted analysis based on nationwide data allows personnel to establish and provide feedback on the risks that patients face before undergoing a procedure. The risk calculator for eight main procedures are available on the websites of the hospitals that are a part of NCD. Nationwide this database is surely expecting to ensure the quality of board certification system and surgical outcomes in gastroenterological surgery.

Procedure of minimally invasive esophagectomy in prone position (Conventional prone-MIE) is standardized leading to feasible short outcomes. On the other hand, robot assisted MIE (Robotic MIE) was approved as Japanese health insurance treatment since 2018. Especially, reduction of recurrent laryngeal nerve (RLN) palsy leading to aspiration pneumonia is expected for Robotic MIE. The purpose of this study is to clarify the potential of Robotic MIE for improvement of short outcomes. Methods Twenty-four Robotic MIEs in introduction period since 2018 and 128 Conventional prone-MIEs in established period since 2015 from all of the 375 cases were compared using propensity score matching. Results Operative times in both entire and thoracic procedures were significantly longer in Robotic MIE. There were no significant differences between two groups in the number of harvested lymph nodes, amount of the blood loss, left RLN palsy rate (13% vs 14%, > Clavien-Dindo classification: C-D grade I), right RLN palsy rate (4% vs 8%, > C-D grade I), and pneumonia rate (7% vs 7%, > C-D grade II). Conclusion Short outcomes of Robotic MIE in introduction period were not inferior to those of Conventional prone-MIE in established period. More improvement is expected for Robotic MIE via learning curve. In conclusion, Robotic MIE has hidden potential to outstrip Conventional prone-MIE in outcomes. Video https://www.dropbox.com/s/7byc8nsqupgetsp/2020%20ISDE%20movie%20for%20submission.wmv?dl=0.

Reconstruction routes after esophagectomy include posterior mediastinal, retrosternal, and subcutaneous route. We have performed posterior mediastinal reconstruction, but this route has higher risks of gastro-tracheal fistula and hiatal hernia. To avoid these complications, now we take the retrosternal route as our first choice by creating the route laparoscopically before pulling-up gastric conduit. We report the successful and safe procedure. Methods We performed laparoscopic creation of retrosternal route in 13 thoracoscopic/robot-assisted minimally invasive esophagectomies since August 2019. In practice, a peritoneal incision at the dorsal side of the xiphoid process is started. Then, via 12 mm port on the surgeon's right hand inserted slightly to the right and cranial side of the umbilical camera port, we dissect loose connective tissues from the caudal side to the cranial side behind the sternum and inside the internal thoracic vessels as landmarks. The time required to create the route and pleural injury rate during the procedure was examined. Results Thirteen cases were divided into two groups as early period group (seven cases) and later period group (six cases) respectively. The time required for route creation was 31.3 minutes(average) in the early period group, and 16.7 minutes in the later period group. There is tendency towards faster in later period group than in earlier one. The overall pleural injury rate was 15% (2 of 13 cases). Although it was difficult to determine the amount of bleeding, it was visually observed that the bleeding during the route creation was lower in the later period group than in the early period group. Conclusion The entire laparoscopic procedure to create retrosternal route makes it easier to observe and preserve the pleura and internal thoracic vessels compared to blind blunt dissection. As a conclusion, laparoscopic creation of retrosternal route for gastric conduit reconstruction is safe and feasible with good learning curve. Video https://www.dropbox.com/sh/p0wc3x46n33jp23/AADwiWHYIEUNUX6qZsERVIOga?dl=0.

INTRODUCTION Laparoscopic surgery has become popular for colorectal cancer treatment in recent years. However, its success rate even among high-risk patients remains debatable. The present study aims to compare the short- and long-term outcomes between laparoscopic and open surgeries in the American Society of Anesthesiologists (ASA) classes 3 and 4 patients with colorectal cancer. METHODS This was a single-center, retrospective, cohort study performed at a university hospital, with 78 patients suffering from colorectal cancer who underwent surgery in ASA classes 3 and 4 as respondents. Patient and tumor characteristics, operative outcomes, and prognoses were factors compared between the open and laparoscopic groups. RESULTS Compared with the open group, laparoscopic group had longer operation time (median 287.5 vs 204.5 minutes, P = .001), less operative blood loss (median 40 vs 240 mL, P = .020), and fewer postoperative complications (24% vs 55%, P = .011). In addition, operative approach (open vs laparoscopic) served as an independent factor for the occurrence of postoperative complications [HR = 3.963 (1.344-12.269), P = .013]. In terms of overall survival and recurrence-free survival (P = .171 and .087, respectively), no significant difference was found between the two groups. CONCLUSION Laparoscopic surgery is thus associated with more favorable short-time outcomes and could be adopted as treatment even for colorectal cancer ASA class 3 and 4 patients.

Skeletal muscle loss after gastrectomy can worsen patients’ quality of life and prognosis. Laparoscopic gastrectomy is less invasive than open gastrectomy and has become commonly performed. However, the degree of skeletal muscle loss after laparoscopic procedures remains unclear. We herein report the degree and risk factors of psoas muscle loss after laparoscopic gastrectomy for gastric cancer. The total psoas area (TPA) on computed tomography of 50 consecutive patients who underwent laparoscopic total gastrectomy (LTG) and 167 consecutive patients who underwent laparoscopic distal gastrectomy (LDG) for gastric cancer was retrospectively evaluated at one postoperative year. The TPA loss was compared between LDG and LTG and univariate and multivariate analyses were performed to identify the risk factors for TPA loss > 10%. The median TPA decrease rate was 5.9% in the LDG group and 15.6% in the LTG group. LTG and postoperative respiratory complications were independent factors associated with a severe TPA loss of > 10%. In the LTG group, no independent factors were identified in a multivariate analysis. In the LDG group, postoperative complications were identified as an independent risk factor for TPA loss > 10%. Laparoscopic gastrectomy leads to postoperative TPA loss, especially in patients who underwent LTG and had postoperative respiratory complications. Postoperative complications after LDG were also a risk factor for TPA loss.

Oral health is associated with various diseases, including cancer. Tooth loss is a simple and objective index of oral health. The purpose of this study was to investigate the association between preoperative tooth loss and esophageal cancer prognosis after esophagectomy. This study included 191 patients who underwent esophagectomy for esophageal cancer after perioperative dental evaluation and oral care at Kobe University Hospital from April 2011 to March 2016. Patients were divided into two groups: Group A (tooth loss

Background/aim The aim of this study was to investigate PD-L1 expression and its association with prognosis in esophageal squamous cell carcinoma (ESCC) before and after neoadjuvant chemotherapy (5-fluorouracil and cisplatin, NAC-FP). Patients and methods Using a database of 69 ESCC patients, we analyzed PD-L1 expression on tumor cells (TCs) and immune cells (ICs), as well as the density of CD8+ tumor-infiltrating lymphocytes (TILs) in pretreatment biopsy specimens-versus-surgical specimens after resection. We determined the prognostic significance of these factors. Results The fraction of ESCC containing ICs expressing PD-L1 and having a high CD8+ TIL density was significantly increased after neoadjuvant treatment. However, PD-L1 expression on TCs or ICs, and CD8+ TIL density, was not significantly associated with patient survival in ESCC patients. Conclusion NAC-FP induced PD-L1 expression on ICs and CD8+ TILs in ESCC patients. This finding suggests that PD-1/PD-L1 blockade could be combined with NAC-FP to treat ESCC patients.

Esophagectomy with extended lymphadenectomy remains the mainstay of treatment for localized esophageal cancer. However, it is one of the most invasive procedures with high morbidity. To reduce invasiveness, minimally invasive esophagectomy (MIE), which includes thoracoscopic, laparoscopic, mediastinoscopic, and robotic surgery, is becoming popular worldwide. Thoracoscopic esophagectomy in the prone position is ergonomic for the surgeon and has better perioperative arterial oxygen pressure/fraction of inspired oxygen (P/F) ratio. Thoracoscopic esophagectomy in the left decubitus position is easy to introduce because it is similar to standard right posterolateral open esophagectomy (OE) in position. It has a relatively short operative time. Laparoscopic approach could potentially have a substantial effect on pneumonia prevention under the condition of thoracotomy. Mediastinoscopic surgery has the potential to reduce pulmonary complications because it can avoid a transthoracic procedure. In robotic surgery, in the future, less recurrent laryngeal nerve palsy will be expected as a result of polyarticular fine maneuvering without human tremors. In studies comparing MIE with OE, mediastinoscopic surgery and robotic surgery are usually not included; these studies show that MIE has a longer operative time and less blood loss than OE. MIE is particularly beneficial in reducing postoperative respiratory complications such as atelectasis, despite no dramatic decrease in pneumonia. Reoperation might occur more frequently with MIE. There is no significant difference in mortality rate between MIE and OE. It is important to recognize that the advantages of MIE, particularly “less invasiveness”, can be of benefit at facilities with experienced medical personnel.

We conducted a prospective clinical control study to identify the best imaging technology among three-dimensional (3-D) high-definition (HD) stereovision and two-dimensional (2-D) ultra-high-resolution (4 K) technology and confirm their effects on surgical outcomes of laparoscopic gastrectomy for gastric cancer. From April 2018 to August 2019, 50 patients were randomly classified into two groups based on the imaging technology (3-D/HD group = 25, 2-D/4 K = 25). After excluding eight patients based on laparoscopic findings, 42 patients were analyzed (3-D/HD group = 21, 2-D/4 K = 21). The primary endpoint was the operative time; the secondary endpoints were blood loss, postoperative infectious complications, and postoperative hospital stay. The patients’ backgrounds were similar (sex, age, body mass index [BMI], stage, procedure, and extent of lymph node dissection). There were no significant differences in operative time (252 vs. 238 min, P = 0.70), total blood loss, postoperative infectious complications, and postoperative hospital stay between the two groups. However, video analysis of surgeries revealed a significantly shortened median operative time (18 vs. 25 min, P = 0.04) in the suturing step with 3-D/HD; the median number of camera cleaning procedures during suprapancreatic lymph node dissection was significantly lower with 2-D/4 K than with 3-D/HD (n = 4.4 vs. 2.8, P = 0.02). 3-D/HD and 2-D/4 K laparoscopic radical gastrectomies provide similar surgical outcomes. However, the 3-D monitor reduces suturing time during reconstruction, while the 4 K monitor reduces the number of camera cleaning procedures during lymphadenectomy. Registered in the University Hospital Medical Information Network Clinical Trials Registry (identification number 000029227).

Supplemental material, Supplemental_Table_1 for Significance of prediction of the dorsal landmark using three-dimensional computed tomography during laparoscopic lymph node dissection along the proximal splenic artery in gastric cancer by Taro Ikeda, Shingo Kanaji, Gosuke Takiguchi, Naoki Urakawa, Hiroshi Hasegawa, Masashi Yamamoto, Yoshiko Matsuda, Kimihiro Yamashita, Takeru Matsuda, Taro Oshikiri, Tetsu Nakamura, Satoshi Suzuki and Yoshihiro Kakeji in SAGE Open Medicine

Additional file 1: S-Table 1. Comparison of clinical features between the more than 10% weight loss and less than 10% weight loss groups.

The aim of this study was to investigate PD-L1 expression and its association with prognosis in esophageal squamous cell carcinoma (ESCC) before and after neoadjuvant chemotherapy (5-fluorouracil and cisplatin, NAC-FP).Using a database of 69 ESCC patients, we analyzed PD-L1 expression on tumor cells (TCs) and immune cells (ICs), as well as the density of CD8The fraction of ESCC containing ICs expressing PD-L1 and having a high CD8NAC-FP induced PD-L1 expression on ICs and CD8

Introduction Three-dimensional (3D) laparoscopic vision can improve depth perception. However, it is a question whether 3D vision can improve motion in the depth direction. The aim of this study was to compare the impact of 3D vision on forceps motion in the depth and horizontal directions. Methods All data were obtained from our previous two studies, where, in total, 40 novices and 20 moderately experienced surgeons participated. A simple phantom task was performed in a training box. The participants were randomly assigned to two groups. Specifically, one group performed the task five times initially under a two-dimensional (2D) system, and the other group started under a 3D system. Both groups then performed the same task five times under the alternative system. Performances were recorded by an optical position tracker. We separately evaluated forceps motion in the x-, y-, and z-axis directions. Results Compared with the findings for 2D vision, the forceps path lengths were significantly decreased among novices and moderately experienced surgeons in almost all tasks under 3D vision. In a comparison of the path length ratio (3D/2D) in each direction, larger reduction was observed for the depth direction among novices, whereas no significant directional difference was noted among moderately experienced surgeons. Conclusions For novices, 3D laparoscopic vision improves depth perception and may give shorter forceps movement in the depth direction even for simple tasks.

Background During the past decade, minimally invasive esophagectomy (MIE) for esophageal cancer has been adopted worldwide with expectations of lower invasiveness. However, the rate of postoperative pneumonia, which is an independent risk factor for oncological prognosis in esophageal cancer, remains high. The aim of this retrospective follow-up study is to clarify whether there is a strong correlation between recurrent laryngeal nerve (RLN) palsy and postoperative pneumonia in MIE. Methods This retrospective follow-up study included 209 patients with esophageal cancer who underwent thoracoscopic esophagectomy in the prone position (TEP) at Kobe University between 2011 and 2018. Inclusion criteria included age 18-85 years; cT1-3, cN0-3 disease; upper mediastinal lymphadenectomy; and ability to undergo simultaneous esophagectomy and reconstruction of the gastric conduit or pedicled jejunum. Univariate and multivariate logistic regression were conducted to identify independent risk factors for pneumonia. Results Among 209 TEPs, pneumonia of Clavien-Dindo classification grade > II occurred in 44 patients (21%). In the pneumonia positive and negative groups, there were significant differences in age (67.9 ± 7.5 vs. 64.9 ± 8.6 years), 3-field lymph node dissection [27 (61%) vs. 67 (41%)], transfusion [20 (45%) vs. 41 (25%)], left RLN palsy [19 (43%) vs. 18 (11%)], and any RLN palsy [20 (45%) vs. 18 (11%)]. In multivariate analysis, any RLN palsy was associated with a higher incidence of pneumonia [odds ratio (OR), 6.210; 95% confidence interval (CI), 2.728-14.480; P < 0.0001]. In addition, age was associated with a higher incidence of pneumonia (OR, 1.049; 95% CI, 1.001-1.103; P = 0.046). Changes in the rate of any RLN palsy over time were quite similar to changes in the incidence of pneumonia. Conclusion There is a strong correlation between RLN palsy and pneumonia in MIE for esophageal cancer. Prevention of RLN palsy may reduce the incidence of pneumonia, leading to better oncological prognosis.

Several studies have suggested that thoracoscopic esophagectomy (TE) in the prone position (TEP) may be more feasible than TE in the lateral position (TEL); however, few studies have compared long-term survival between the two procedures. We evaluated whether TEP is oncologically equivalent to TEL. Surgical outcomes of TEs performed from January 2006 to December 2013 at our hospital were retrospectively analyzed. Propensity score matching was used to control for confounding factors. TE was performed in 200 patients diagnosed with esophageal squamous cell carcinoma; 78 patients were matched in two procedures. The mean thoracic operative time in TEL was shorter than in TEP (228.9 min vs. 299.1 min; p

Additional file 1. SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents.

Summary The inflammation-based modified Glasgow prognostic score (mGPS) has been shown to be a prognostic factor for esophageal cancer, but its changes in relation to neoadjuvant chemotherapy (NAC) have never been discussed. The purpose of this study was to evaluate the potential prognostic role of mGPS with regard to NAC. mGPS was evaluated on the basis of admission blood samples taken before chemotherapy and before surgery. Patients with elevated C-reactive protein (CRP) serum levels (>10 mg/L) and hypoalbuminemia (

Wnt5a-Ror2 signaling has been shown to play important roles in promoting aggressiveness of various cancer cells in a cell-autonomous manner. However, little is known about its function in cancer-associated stromal cells, including mesenchymal stem cells (MSCs). Thus, we examined the role of Wnt5a-Ror2 signaling in bone marrow-derived MSCs in regulating proliferation of undifferentiated gastric cancer cells. Coculture of a gastric cancer cell line, MKN45, with MSCs either directly or indirectly promotes proliferation of MKN45 cells, and suppressed expression of Ror2 in MSCs prior to coculture inhibits enhanced proliferation of MKN45 cells. In addition, conditioned media from MSCs, treated with control siRNA, but not siRNAs against Ror2, can enhance proliferation of MKN45 cells. Interestingly, it was found that expression of CXCL16 in MSCs is augmented by Wnt5a-Ror2 signaling, and that recombinant chemokine (C-X-C motif) ligand (CXCL)16 protein can enhance proliferation of MKN45 cells in the absence of MSCs. In fact, suppressed expression of CXCL16 in MSCs or an addition of a neutralizing antibody against CXCL16 fails to promote proliferation of MKN45 cells in either direct or indirect coculture with MSCs. Importantly, we show that MKN45 cells express chemokine (C-X-C motif) receptor (CXCR)6, a receptor for CXCL16, and that suppressed expression of CXCR6 in MKN45 cells results in a failure of its enhanced proliferation in either direct or indirect coculture with MSCs. These findings indicate that Wnt5a-Ror2 signaling enhances expression of CXCL16 in MSCs and, as a result, enhanced secretion of CXCL16 from MSCs might act on CXCR6 expressed on MKN45, leading to the promotion of its proliferation.

In esophageal squamous cell carcinoma (ESCC), lymph nodes (LNs) around the subcarina and main bronchi are thought to be highly involved. Therefore, complete dissection of these LNs with preservation of the pulmonary branches of the vagus nerves, which control important pulmonary functions, is recommended. The aim of this retrospective study was to investigate the feasibility of reliable method for lymphadenectomy around the subcarina and main bronchi, named the medial approach, during thoracoscopic esophagectomy in the prone position (TEP). This was a case-matched control study of patients who underwent TEP for ESCC. The fundamental concept in this method is to first exfoliate the LNs around the subcarina and main bronchi from the pericardium. Developing the operative field contributes to visualizing and preserving the pulmonary branches of the right vagus nerve. Twenty-three patients who underwent the medial approach and 23 patients who underwent the conventional approach were selected by the use of propensity score matching to compare the operative outcomes. The medial approach significantly reduced operative time for procedure (16 ± 3 vs 30 ± 6 min, p

The prognosis of esophageal cancer is dismal, and the 3-year overall survival of cStage III does not reach 50.0%. C-reactive protein (CRP) is a well-known protein that reflects the short- and long-term operative outcomes of esophageal cancer. However, since elevated CRP levels are often observed in cStage III esophageal cancer, whether or not CRP still reflects the prognosis is unclear. Eighty-four patients who were diagnosed with cStage III esophageal cancer and underwent R0/1 operation from January 2007 to December 2014 were retrospectively evaluated. The mean age was 66.8 years, and the majority of patients were male. The median preoperative and postoperative CRP levels were 0.15 and 1.47 mg/dl, respectively. A majority of the patients underwent thoracoscopic surgery, and the median blood loss and operation duration were 456 ml and 11.6 h, respectively. Forty-six patients (54.8%) died during the observation period, and the 3-year overall survival was 52.4%. A multivariate analysis showed that the preoperative CRP level, postoperative albumin level, blood loss, and complications were independent prognostic factors. A multiple linear regression analysis showed that an elevated postoperative CRP level was affected by the operation duration and preoperative CRP levels. These findings suggest that the preoperative CRP level is a prognostic factor for cStage III esophageal cancer and that postoperative elevation in the CRP level is affected by the operation duration.

Background While thoracoscopic esophagectomy is a widely performed surgical procedure, only few studies regarding the influence of body position on changes in circulation and breathing, after the surgery, have been reported. This study aimed at evaluating the effect of body position, during surgery, on the postoperative breathing functions of the chest. Methods A total of 266 patients who underwent right-sided transthoracic esophagectomy for esophageal cancer from 2004 to 2012 were included in this study. Fifty-four of them underwent open thoracotomies in the left lateral decubitus position (Group O), 108 underwent thoracoscopic esophagectomy in the left lateral decubitus position (Group L) and 104 patients were treated by thoracoscopic esophagectomy in the prone position (Group P). Two patients in Group P, who presented with intra-operative bleeding and underwent thoracotomy, were subsequently excluded from the pulmonary function analysis. Results Two patients in Group P had to be changed from the prone position to the lateral decubitus position and underwent thoracotomy in order to control intra-operative bleeding. Despite the significantly longer chest operation period in Group P, total blood loss was significantly lower in this group when compared to Groups O and L. Furthermore, patients in Group P presented with significantly lower water balance during the perioperative period and markedly higher SpO2/FiO2 ratio after the surgery. The incidence of respiratory complications was significantly higher in Group O when compared to the other two groups; however, no significant differences were observed between the Groups L and P. Conclusion From a surgical point of view, artificial pneumothorax and gravity improves the operative field view in the prone position without any compression of the right lung, thereby resulting in no mechanical damage to the lungs. Prone position esophagectomy is a useful surgical technique, which appears to preserve the postoperative pulmonary function. The patients are able to endure the surgical procedure and present with less respiratory complications. Disclosure All authors have declared no conflicts of interest.

Background Esophagectomy with extended lymphadenectomy remains the mainstay of treatment for localized esophageal cancer. Currently, transthoracic and abdominal esophagectomy with cervical anastomosis (McKeown esophagectomy) is a frequently used technique in Japan. However, cervical anastomosis is still an invasive procedure with a high incidence of anastomotic leakage. The use of a drainage tube to treat anastomotic leakage is effective, but the routine placement of a closed suction drain around the anastomosis at the end of the operation remains controversial. The objective of this study is to evaluate the postoperative anastomotic leakage rate, duration to oral intake, hospital stay, and analgesic use with nonplacement of a cervical drainage tube as an alternative to placement of a cervical drainage tube. Methods This is an investigator-initiated, investigator-driven, open-label, randomized controlled parallel-group, noninferiority trial. All adult patients (aged ≥20 and ≤85 years) with histologically proven, surgically resectable (cT1–3 N0–3 M0) squamous cell carcinoma, adenosquamous cell carcinoma, or basaloid squamous cell carcinoma of the intrathoracic esophagus, and European Clinical Oncology Group performance status 0, 1, or 2 are assessed for eligibility. Patients (n = 110) with resectable esophageal cancer who provide informed consent in the outpatient clinic are randomized to either nonplacement of a cervical drainage tube (n = 55) or placement of a cervical drainage tube (n = 55). The primary outcome is the percentage of Clavien–Dindo grade 2 or higher anastomotic leakage. Discussion This is the first randomized controlled trial comparing nonplacement versus placement of a cervical drainage tube during McKeown esophagectomy with regards to the usefulness of a drain for anastomotic leakage. If our hypothesis is correct, nonplacement of a cervical drainage tube will be recommended because it is associated with a similar anastomotic leakage rate but less pain than placement of a cervical drainage tube. Trial registration UMIN-CTR, 000031244. Registered on 1 May 2018.

Mirror image is one of the most difficult situations that the assistant surgeon encounters in laparoscopic colorectal surgery. The aim of the present study was to investigate whether task performance with mirror images improves by changing the position of the monitor and the rotation angle of the camera. Twenty-four surgeons performed the task under different conditions: Coaxial image (C), Mirror image (M), Mirror image + Monitor on the left side of participants (M + Mon), Mirror image + Camera rotated 90 degrees to the right (M + Cam), and Mirror image + Monitor on the left side + Camera rotated to the right (M + Mon + Cam) in a training box. The outcome measure was the mean time for completing the task. The mean time for completing the task, in decreasing order, was M (111.4 ± 58.9 seconds) > M + Mon (70.5 ± 29.4 seconds) > M + Cam (47.1 ± 17.1 seconds) > M + Mon + Cam (33.4 ± 10.3 seconds) > C (20.5 ± 3.5 seconds). (multivariable analysis of variance (MANOVA), p = 7.9 × 10−7) Task performance with mirror images improved by changing the monitor positioning and camera rotation angle. This novel method is a simple way to overcome mirror image in laparoscopic colorectal surgery.

Liposarcoma of the esophagus is very rare. We experienced a huge (27.5 × 11.6 cm) liposarcoma of the esophagus. A 73-year-old man presented with severe dyspnea requiring emergency tracheal intubation. Computed tomography and esophagogastroduodenoscopy showed a large submucosal tumor arising from the esophageal entrance and extending intraluminally to the lower esophagus. We successfully performed endoscopic submucosal dissection (ESD) and esophagotomy to remove the tumor, which preserved swallowing and phonation. The final diagnosis by histopathologic and immunohistologic examination was well-differentiated liposarcoma of the esophagus. Treatment by the combination of ESD and esophagotomy can be performed even for a very large tumor. This method preserves deglutition with a lower risk of recurrent laryngeal nerve paralysis than that with esophagectomy.

The present study reports the rare case of a patient with quintuple primary cancer that underwent systematic treatment, including surgical intervention. A 63-year-old male patient was initially diagnosed with primary esophageal cancer and hypopharyngeal cancer. The patient underwent total pharyngolaryngoesophagectomy using a thoracoscopic method and reconstruction using the free jejunal flap and gastric tube and was subsequently administered adjuvant chemotherapy (80 mg/m2 intravenously on day 1, cisplatin; 800 mg/m2 continuous intravenous administration on days 1-5, 5-fluorouracil). At 66 years old, the patient was diagnosed with left maxillary sinus cancer and underwent chemoradiotherapy (four 100 mg/m2 arterial cisplatin injections; 70 Gy/35 f radiotherapy, 2 Gy per day over 35 days). At 68 years old, the patient was diagnosed with gastric tube cancer and underwent gastric tube resection followed by pedicled jejunum flap reconstruction. At 69 years old, the patient was diagnosed with tongue cancer and underwent resection and reconstruction of the tongue by pectoralis major myocutaneous flap. Six years subsequent to the primary surgery, the patient remains alive, without metastasis of the lesions. To the best of our knowledge, the present study is the first report of a patient that underwent a curative procedure for the treatment of five primary multiple cancers in five organs, including esophageal cancer.