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

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

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.

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.

Auxiliary diagnosis of subepithelial lesions by impedance measurement during EUS-guided fine-needle biopsy.

BACKGROUND AND AIMS: EUS-guided FNA/biopsy (EUS-FNA/B) is the citerion standard for diagnosing subepithelial lesions (SELs); however, its diagnostic ability for SELs <20 mm is low. We developed a new diagnostic method to differentiate between GI stromal tumor (GIST) and non-GIST by measuring high-frequency impedance (H-impedance) using an EUS-FNB needle. METHODS: The H-impedance of gastric epithelial neoplasms from 16 cases were measured with a conventional impedance probe to confirm whether H-impedance is clinically useful for assessing cell density (study 1). The H-impedance values of exposed SELs from 25 cases with use of the conventional probe (study 2) and nonexposed SELs from 20 cases with use of the EUS-FNB needle probe (study 3) were measured to determine the diagnostic ability of H-impedance for differentiating GISTs from non-GISTs. RESULTS: H-impedance significantly positively correlated with cell density (P = .030) (study 1). The H-impedance of GIST (99.5) measured with a conventional probe was significantly higher than with those of the muscular layer (82.4) and leiomyoma (89.2) (P < .01) (study 2). The H-impedance of GIST measured with the EUS-FNB needle was also significantly higher than that of leiomyoma (GIST: 80.2 vs leiomyoma, 71.8; P = .015). The diagnostic yield of the impedance method for differentiating GISTs from non-GISTs had 94.4% accuracy, 88.9% sensitivity, 100% specificity, and 0.95 area under the curve. Diagnostic ability was not affected by lesion size (P = .86) (study 3). CONCLUSION: Auxiliary differential diagnosis between gastric GISTs and non-GISTs by the H-impedance measurement during EUS-FNB could be a good option, especially when the lesion is <20 mm.

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.

Real-time telementoring with 3D drawing annotation in robotic surgery.

BACKGROUND: In telementoring, differences in teaching methods affect local surgeons' comprehension. Because the object to be operated on is a three-dimensional (3D) structure, voice or 2D annotation may not be sufficient to convey the instructor's intention. In this study, we examined the usefulness of telementoring using 3D drawing annotations in robotic surgery. METHODS: Kyushu University and Beppu Hospital are located 140 km apart, and the study was conducted using a Saroa™ surgical robot by RIVERFIELD Inc. using a commercial guarantee network on optical fiber. Twenty medical students performed vertical mattress suturing using a swine intestinal tract under surgical guidance at the Center for Advanced Medical Innovation Kyushu University. Surgical guidance was provided by Beppu Hospital using voice, 2D, and 3D drawing annotations. All robot operations were performed using 3D images, and only the annotations were independently switched between voice and 2D and 3D images. The operation time, needle movement, and performance were also evaluated. RESULTS: The 3D annotation group tended to have a shorter working time than the control group (25.6 ± 63.2 vs. - 36.7 ± 65.4 min, P = 0.06). The 3D annotation group had fewer retries than the control group (1.3 ± 1.7 vs. - 1.1 ± 0.7, P = 0.006), and there was a tendency for fewer needle drops (0.4 ± 0.7 vs. - 0.5 ± 0.9, P = 0.06). The 3D annotation group scored significantly higher than the control group on the Global Evaluate Assessment of Robot Skills (16.8 ± 2.0 vs. 22.8 ± 2.4, P = 0.04). The 3D annotation group also scored higher than the voice (13.4 ± 1.2) and 2D annotation (16.2 ± 1.8) groups (3D vs. voice: P = 0.03, 3D vs. 2D: P = 0.03). CONCLUSION: Telementoring using 3D drawing annotation was shown to provide good comprehension and a smooth operation for local surgeons.

Phase II clinical trial to study the safety and efficacy of combined S-1 + oxaliplatin therapy as neoadjuvant chemotherapy for locally advanced gastric cancer in older patients.

BACKGROUND: Gastrectomy with D2 dissection and adjuvant chemotherapy is the standard treatment for locally advanced gastric cancer (LAGC) in Asia. However, administering chemotherapy with sufficient intensity after gastrectomy is challenging. Several trials demonstrated the efficacy of neoadjuvant chemotherapy (NAC). However, limited studies explored the feasibility of NAC-SOX for older patients with LAGC. This phase II study (KSCC1801) evaluated the safety and efficacy of NAC-SOX in patients with LAGC aged ≥ 70 years. METHODS: Patients received three cycles of SOX130 (oxaliplatin 130 mg/m2 on day 1, oral S-1 40-60 mg twice daily for two weeks every three weeks) as NAC, followed by gastrectomy with lymph node dissection. The primary endpoint was the dose intensity (DI). The secondary endpoints were safety, R0 resection rate, pathological response rate (pRR), overall survival, and relapse-free survival. RESULTS: The median age of 26 enrolled patients was 74.5 years. The median DI in NAC-SOX130 was 97.2% for S-1 and 98.3% for oxaliplatin. Three cycles of NAC were administered in 25 patients (96.2%), of whom 24 (92.3%) underwent gastrectomy with lymphadenectomy. The R0 resection rate was 92.3% and the pRR (≥ grade 1b) was 62.5%. The major adverse events (≥ grade 3) were neutropenia (20.0%), thrombocytopenia (11.5%), anorexia (11.5%), nausea (7.7%), and hyponatremia (7.7%). Postoperative complications of abdominal infection, elevated blood amylase, and bacteremia occurred in one patient each. Severe diarrhea and dehydration caused one treatment-related death. CONCLUSIONS: NAC-SOX130 is a feasible therapy for older patients, although systemic management and careful monitoring of adverse events are necessary.

Lineage of drug discovery research on fluorinated pyrimidines: chronicle of the achievements accomplished by Professor Setsuro Fujii.

Prof. Setsuro Fujii achieved significant results in the field of drug discovery research in Japan. He developed nine well-known drugs: FT, UFT, S-1 and FTD/TPI are anticancer drugs, while cetraxate hydrochloride, camostat mesilate, nafamostat mesilate, gabexate mesilate and pravastatin sodium are therapeutic drugs for various other diseases. He delivered hope to patients with various diseases across the world to improve their condition. Even now, drug discovery research based on Dr. Fujii's ideas is continuing.

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.

Child phonological responses to variegation in adult words: A cross-linguistic study.

Variegation - the presence of more than one supraglottal consonant per word - is a key challenge for children as they increase their expressive vocabulary toward the end of the single-word period. Here we consider the prosodic structures of target words and child forms in English, Finnish, French, Japanese and Mandarin to determine whether children learning these languages respond similarly to the challenge or instead differ in ways related to the phonological structure of the adult language. Based on proportional occurrence of each structure, we find that the word forms of children learning Mandarin and Japanese show more variegation than do those of children learning the European languages, although their target words do not; proportions of reduplication, consonant harmony and single-consonant words also differ by language. We conclude that experience with the structure of the language - and thus representation, as well as immature articulatory skills - shapes children's responses to variegation.

Significance of dissection in each regional lymph-node station of esophageal cancer based on efficacy index and recurrence patterns after curative esophagectomy.

BACKGROUND: The optimal extent of lymph-node (LN) dissection in esophageal cancer has not been established. Although the frequency and patterns of recurrence in each regional LN station after radical dissection are important in determining the regional LNs of thoracic esophageal cancer to be routinely dissected, this information has not been investigated sufficiently. We studied the significance of dissection at each LN station based on their recurrence patterns. METHODS: Six hundred and twelve patients with esophageal cancer who underwent curative esophagectomy were studied. The incidence and pattern of recurrence (systemic or non-systemic) at each regional LN station were analyzed. To compare the significance of dissection among regional LNs, the efficacy index (EI) was also calculated. RESULTS: Regional LN recurrence was diagnosed in 101 (16.5%) patients. Among the regional LNs, recurrent laryngeal nerve, paraesophageal, and perigastric LNs showed higher EIs (3.1-6.7). Pretracheal and posterior thoracic para-aortic LNs showed low EIs (0-0.2). Supraclavicular LNs had moderate EIs (1.7-2.0). The recurrence rate was highest in the pretracheal LN, followed by the supraclavicular LNs. The majority (81.8%) of the pretracheal LN had a systemic recurrence, while about half (right: 60.0%, left: 43.8%) of the supraclavicular LNs had a systemic recurrence. CONCLUSION: Due to the high incidence of systemic recurrence or low EI for pretracheal and posterior thoracic para-aortic LNs, we suggest that these LN stations be regarded as non-regional LNs and be excluded from routine dissection. Supraclavicular LNs may also be excluded from routinely dissected stations.

Tele-assessment of bandwidth limitation for remote robotics surgery.

PURPOSE: We investigated the communication bandwidth (CB) limitation for remote robotics surgery (RRS) using hinotori™ (Medicaroid, Kobe, Japan). METHODS: The operating rooms of the Hokkaido University Hospital and Kyushu University Hospital were connected using the Science Information NETwork (SINET). The minimum required CB for the RRS was verified by decreasing the CB from 500 to 100 Mbps. Ten surgeons were tested on a task (intracorporeal suturing) at different levels of video compression (VC) (VC1: 120 Mbps, VC2: 40 Mbps, VC3: 20 Mbps) with the minimum required CB, and assessed based on the task completion time, Global Evaluative Assessment of Robotic Skills (GEARS), and System and Piper Fatigue Scale-12 (PFS-12). RESULTS: Packet loss was observed at 3-7% and image degradation was observed at 145 Mbps CB. The task performance with VC1 was significantly worse than that with VC2 and VC3 according to the task completion time (VC1 vs VC2, P = 0.032; VC1 vs. VC3, P = 0.032), GEARS (VC1 vs VC2; P = 0.029, VC1 vs VC3; P = 0.031), and PFS-12 (VC1 vs. VC2; P = 0.032, VC1 vs. VC3; P = 0.032) with 145 Mbps. CONCLUSION: Our findings provide evidence that RRS using hinotori™ requires a CB ≥ 150 Mbps. We also found that when there is insufficient CB, RRS can be continued by compressing the image.

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

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

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

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

Prognostic Impact of the Neutrophil-to-Lymphocyte Ratio in Stage I-II Rectal Cancer Patients.

BACKGROUND: Systemic inflammation and immune response play crucial roles in tumor growth; neutrophil-to-lymphocyte ratio (NLR) is a known systemic inflammatory scoring system. Previous studies have reported that NLR is a prognostic biomarker in various human cancers. The aim of this study was to determine whether the NLR predicts tumor recurrence in patients with stage I-II rectal cancer after curative resection. METHODS: We retrospectively analyzed 130 consecutive patients with stage I-II rectal cancer who underwent curative resection between January 2006 and March 2015 at our institution without any preoperative treatment. We investigated whether clinicopathologic factors including NLR were associated with cancer recurrence after curative surgery. RESULTS: There were four cases (3.1%) of cancer-specific deaths and 16 cases (12.3%) of recurrence; the 5-year disease-free survival rate was 85.6%. NLR, pathologic T-category, and lymphatic invasion were significantly associated with disease-free survival. Multivariate analysis further showed that these three factors were independently associated with disease-free survival. CONCLUSIONS: Preoperative NLR could predict tumor relapse in stage I-II rectal cancer and might be a useful biomarker for predicting recurrence in patients undergoing curative resection.

Treatment strategies for neuroendocrine carcinoma of the upper digestive tract.

BACKGROUND: Neuroendocrine carcinoma (NEC) of the esophagus and the stomach is aggressive. The purpose of this study was to determine the optimal therapeutic strategy. METHODS: Both clinicopathological factors and treatment results were examined in 34 patients with immunohistochemically diagnosed NEC of the upper gastrointestinal tract (esophagus 22; stomach 12). RESULTS: Twenty-nine tumors showed protruding and localized type, like submucosal tumor. Esophagectomy and gastrectomy were performed in six and eight patients, respectively. Among the six patients with esophageal NEC, three with node metastasis developed recurrence within seven months, while the other three (pT1bN0) had no recurrence. Regarding gastric NEC, three patients with pT3N1 or 2 tumor received adjuvant chemotherapy and achieved a 5-year survival. However, the other five experienced recurrence after gastrectomy. Systemic chemotherapy was performed as the main treatment for 18 patients with advanced NEC. The median survival was 10 months after initial chemotherapy. No marked differences in the response were recognized between the 14 cases with esophageal NEC and the 4 with gastric NEC. The median survival was 14.3 and 5.3 months for the 11 effective and 7 non-effective patients, respectively. CONCLUSIONS: A macroscopically unique appearance, like submucosal tumor, suggests the possibility of NEC. Esophagectomy is an effective treatment option for limited-stage NEC without node metastasis, while gastrectomy followed by adjuvant chemotherapy may be effective for NEC even with node metastasis when R0 resection can be achieved. Systemic chemotherapy is relatively effective for advanced NEC, although early progression frequently develops.

Mitral annular disjunction in patients with primary severe mitral regurgitation and mitral valve prolapse.

BACKGROUND: Mitral annular disjunction is a structural abnormality of the mitral annulus fibrosus which is often associated with mitral leaflet prolapse. However, few reports have described mitral annular disjunction in mitral valve prolapse (MVP). This study aimed to investigate the characteristics of mitral annular disjunction in patients with severe mitral regurgitation (MR) caused by MVP. METHODS: We reviewed 185 consecutive patients with severe MR caused by fibroelastic deficiency (FED) and Barlow's syndrome from March 2009 to December 2010. The upper limit of the disjunction was defined at the level of the posterior scallop's insertion into the left atrial wall, whereas the lower limit was defined at the level of the left atrium's connection to the ventricular myocardium. The distance between the two levels was called mitral annular disjunction. Prolapse sites in FED patients were categorized into anterior leaflet, posterior leaflet, and commissure groups. Patients with a disjunction distance of ≥2 mm were diagnosed with mitral annular disjunction. RESULTS: Annular disjunction was found in 45 patients (24%). Among them, the most common site of prolapse was the posterior leaflet (n = 35, 77.8%). During a median follow-up of 20.3 years, arrhythmic events and sudden death occurred in seven patients (3.8%). CONCLUSIONS: Mitral annular disjunction was detected in 24% of patients with severe MR and in 90% of the patients with Barlow's syndrome. There were significant differences at its sites of prolapse in FED patients. The presence and site of prolapse with mitral annular disjunction should be actively determined in FED patients.

Reduplication facilitates early word segmentation.

This study explores the possibility that early word segmentation is aided by infants' tendency to segment words with repeated syllables ('reduplication'). Twenty-four nine-month-olds were familiarized with passages containing one novel reduplicated word and one novel non-reduplicated word. Their central fixation times in response to these as well as new reduplicated and non-reduplicated words introduced at test showed that familiarized reduplicated words were segmented better than familiarized non-reduplicated words. These results demonstrate that infants are predisposed to segment words with repeated phonological elements, and suggest that register-specific words in infant-directed speech may have evolved in response to this learning bias.