Impact of the COVID-19 pandemic on the number and short-term outcomes in hepatectomy for hepatocellular carcinoma: Results from the Japanese National Clinical Database, 2018-2021.

AIM: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the allocation of medical resources, including cancer screening, diagnosis, and treatment. We aimed to investigate the effects of the pandemic on morbidity and mortality following hepatectomy for hepatocellular carcinoma (HCC). METHODS: We identified patients who underwent hepatectomy for HCC between 2018 and 2021 from the Japanese National Clinical Database (NCD). The number of surgical cases, the use of intensive care units, and the incidence of morbidity were assessed. The standardized morbidity / mortality ratio (SMR) was used to evaluate the rates of morbidity (bile leakage and pneumonia) and mortality in each month, which compares the observed incidence to the expected incidence calculated by the NCD's risk calculator. RESULTS: The study included a total of 10 647 cases. The number of patients undergoing hepatectomy for HCC gradually decreased. The proportion of patients aged 80 years or older increased and that of cases with T1 stage decreased. The proportion of patients who were admitted to the intensive care unit did not change between the pre- and postpandemic period. The mean actual incidence rates of bile leakage, pneumonia, 30-day mortality, and surgical mortality were 9.2%, 2.3%, 1.4%, and 2.1%, respectively. The SMR for the mortalities and morbidities in each month did not increase mostly throughout the COVID-19 pandemic. CONCLUSIONS: The present study showed the decreasing number of resected cases for HCC, while the surgical safety for hepatectomy was enough to be maintained by managing medical resources in Japan.

Identifying intense inflammatory subtype of esophageal squamous cell carcinoma using clustering approach.

OBJECTIVE: To establish a risk-stratification system for predicting the postoperative recurrence of esophageal squamous cell carcinoma, this study aimed to evaluate the prognostic value of clusters based on blood inflammation and coagulation markers and investigate their correlation with serum cytokines and genetic alteration. METHOD: This single-center, retrospective cohort study enrolled 491 patients with esophageal cancer who underwent subtotal esophagectomy between 2004 and 2012. For cluster exploration, nonhierarchical cluster analysis and k-means were applied using serum C-reactive protein, albumin, fibrinogen, and platelet-lymphocyte ratio as variables. Then, multivariate survival analysis was conducted to investigate the association of clusters with recurrence-free survival. To characterize the clusters, serum interleukin-6, interleukin-8, and genetic alteration in primary tumors, the PleSSision-Rapid panel, which can evaluate 160 representative driver genes, was used. RESULTS: Patients were classified into clusters 1, 2, and 3, which included 24 (5%), 161 (33%), and 306 (62%) patients, respectively. Compared with cluster 3, cluster 1 or 2 had significantly worse recurrence-free survival. Based on the multivariable analysis using cluster, pStage, and age as covariates, cluster was an independent prognostic factor for recurrence-free survival (hazard ratio, 1.55; 95% confidence interval, 1.08-2.21; P = 0.02). The percentage of serum interleukin-6 and interleukin-8 levels was the highest in cluster 1, followed by clusters 2 and 3. In 23 patients with available genomic profiles, no significant difference in representative genomic alterations was observed. CONCLUSIONS: Non-biased clustering using inflammation and coagulation markers identified the intense inflammatory subtype, which had an independent prognostic effect on recurrence-free survival.

Impact of COVID-19 pandemic on short-term outcomes after low anterior resection in patients with rectal cancer: Analysis of data from the Japanese National Clinical Database.

Aim: The Coronavirus Disease 2019 (COVID-19) pandemic affected the allocation of various medical resources to several areas, including intensive care units (ICUs). However, currently, its impact on the short-term postoperative outcomes of gastrointestinal cancer surgeries remains unclear. We aimed to evaluate the impact of the pandemic on the incidence of complications occurring after low anterior resection in patients with rectal cancer in Japan. Methods: Data from the Japanese National Clinical Database between 2018 and 2021 were retrospectively examined. The primary outcome of the study was the postoperative morbidity and mortality rates before and after COVID-19 pandemic. Moreover, the postoperative ICU admission rate was assessed. Morbidity and mortality rates were also assessed using a standardized morbidity/mortality ratio (SMR, the ratio of the actual number of incidences to the expected number of incidences calculated by the risk calculator). Results: This study included 74 181 patients, including 43 663 (58.9%) from COVID-19 epidemic areas. The mean actual incidences of anastomotic leakage (AL) and pneumonia during the study period were 9.2% and 0.9%, respectively. The SMRs of these complications did not increase during the pandemic but those of AL declined gradually. The mean 30-day mortality and operative mortality rates were 0.3% and 0.5%, respectively. Moreover, SMRs did not change significantly in the pandemic or regional epidemic status. The ICU admission rate temporarily decreased, especially in the epidemic areas. Conclusion: Although the pandemic temporarily decreased the ICU admission rate, its impact on short-term outcomes following low anterior resection in patients with rectal cancer was insignificant in Japan.

Automated artificial intelligence-based phase recognition system for esophageal endoscopic submucosal dissection (with video).

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) for superficial esophageal cancer is a multistep treatment involving several endoscopic processes. Although analyzing each phase separately is worthwhile, it is not realistic in practice because of the need for considerable manpower. To solve this problem, we aimed to establish a state-of-the-art artificial intelligence (AI)-based system, specifically, an automated phase recognition system that can automatically identify each endoscopic phase based on video images. METHODS: Ninety-four videos of ESD procedures for superficial esophageal cancer were evaluated in this single-center study. A deep neural network-based phase recognition system was developed in an automated manner to recognize each of the endoscopic phases. The system was trained using videos, annotated, and verified by two gastrointestinal endoscopists. RESULTS: The overall accuracy of the AI model for automated phase recognition was 90%, while the average precision, recall, and f-value rates were 91%, 90%, and 90% respectively. Two representative ESD videos predicted by the model indicated the usability of AI in clinical practice. CONCLUSIONS: We demonstrated that an AI-based automated phase recognition system for esophageal ESD can be established with high accuracy. To the best of our knowledge, this is the first report on automated recognition of ESD treatment phases. Since this system enabled a detailed analysis of phases, collecting large volumes of data in the future may help identify quality indicators for treatment techniques and uncover unmet medical needs that necessitate the creation of new treatment methods and devices.

No difference in the incidence of postoperative pulmonary complications between abdominal laparoscopy and laparotomy for minimally invasive thoracoscopic esophagectomy: a retrospective cohort study using a nationwide Japanese database.

INTRODUCTION: There remains a lack of evidence regarding the optimal abdominal approach, including laparoscopy, hand-assisted, and open laparotomy for minimally invasive thoracoscopic esophagectomy. We aimed to compare the incidence of postoperative complications, particularly pulmonary complications, between laparoscopy and open laparotomy for minimally invasive thoracoscopic esophagectomy using nationwide Japanese databases. METHODS: Data from patients in the National Clinical Database (NCD) who underwent thoracoscopic esophagectomy for esophageal cancer were analyzed. The incidence of pulmonary complications was compared between abdominal laparoscopy and laparotomy after matching the propensity scores (PS) from preoperative factors to account for confounding bias. Laparoscopic-assisted surgery (LAS) was also compared to hand-assisted laparoscopic surgery (HALS). RESULTS: Of the 24,790 patients who underwent esophagectomy between 2018 and 2021, data from 12,633 underwent thoracoscopic procedure. The proportion of patients who experienced pulmonary complications did not significantly differ between the laparoscopy group and the laparotomy group after matching (664/3195 patients, 20.8% versus 702/3195 patients, 22.0%; P = 0.25). No difference in the incidence of pulmonary complications was observed among patients treated using the laparoscopic approach (508/2439 patients, 20.8% in the LAS group versus 498/2439 patients, 20.4% in the HALS group; P = 0.72). CONCLUSIONS: We observed no significant difference in the incidence of postoperative pulmonary complications between laparoscopy and laparotomy for thoracoscopic esophagectomy. Short-term outcomes were similar between the laparoscopic-assisted approach and the hand-assisted approach. This study provides valuable insights into the optimal abdominal approach for thoracoscopic esophagectomy using data from a nationwide database that reflect real-world clinical practice.

The impact of COVID-19 for postoperative outcomes using a nationwide Japanese database of patients undergoing distal gastrectomy for gastric cancer.

Background: The coronavirus disease 2019 (COVID-19) pandemic had resulted in either failure to provide required medical resources or delayed treatment for gastric cancer patients. This study aimed to investigate the impact of COVID-19 on the incidence of postoperative complications using a nationwide Japanese database of patients undergoing distal gastrectomy for gastric cancer. Methods: We collected the data of patients who underwent distal gastrectomy from January 2018 to December 2021 from the National Clinical Database (NCD), a web-based surgical registration system in Japan. The number of surgical cases, the use of intensive care units, and the incidence of morbidity per month were analyzed. We also calculated the standardized mortality ratio (SMR), defined as the ratio of the number of observed patients to the expected number of patients calculated using the risk calculator established in the NCD, for several morbidities, including pneumonia, sepsis, 30-day mortality, and surgical mortality. Results: A decrease of 568 gastrectomies was observed from April 2020 to May 2020. Although the absolute number of patients admitted to intensive care units had declined since 2020, the proportion of patients admitted to the ICU did not change before and after the pandemic. Mortality and critical morbidity (such as pneumonia and sepsis) rates were not worse during the pandemic compared to pre-pandemic periods per the SMR. Conclusions: Surgical management was conducted adequately through the organized efforts of the entire surgery department in our country even in a pandemic during which medical resources and staff may have been limited.

Endoscopic Evaluation of Pathological Complete Response Using Deep Neural Network in Esophageal Cancer Patients Who Received Neoadjuvant Chemotherapy-Multicenter Retrospective Study from Four Japanese Esophageal Centers.

BACKGROUND: Detecting pathological complete response (pCR) before surgery would facilitate nonsurgical approach after neoadjuvant chemotherapy (NAC). We developed an artificial intelligence (AI)-guided pCR evaluation using a deep neural network to identify pCR before surgery. METHODS: This study examined resectable esophageal squamous cell carcinoma (ESCC) patients who underwent esophagectomy after NAC. The same number of histological responders without pCR and non-responders were randomly selected based on the number of pCR patients. Endoscopic images were analyzed using a deep neural network. A test dataset consisting of 20 photos was used for validation. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of AI and four experienced endoscopists' pCR evaluations were calculated. For pathological response evaluation, Japanese Classification of Esophageal Cancer was used. RESULTS: The study enrolled 123 patients, including 41 patients with pCR, the same number of histological responders without pCR, and non-responders [grade 0, 5 (4%); grade 1a, 36 (30%); grade 1b, 21 (17%); grade 2, 20 (16%); grade 3, 41 (33%)]. In 20 models, the median values of sensitivity, specificity, PPV, NPV, and accuracy for endoscopic response (ER) detection were 60%, 81%, 77%, 67%, and 70%, respectively. Similarly, the endoscopists' median of these was 43%, 90%, 85%, 65%, and 66%, respectively. CONCLUSIONS: This proof-of-concept study demonstrated that the AI-guided endoscopic response evaluation after NAC could identify pCR with moderate accuracy. The current AI algorithm might guide an individualized treatment strategy including nonsurgical approach in ESCC patients through prospective studies with careful external validation to demonstrate the clinical value of this diagnostic approach including primary tumor and lymph node.

Effect of aqueous olanexidine versus alcohol-based chlorhexidine for surgical skin antisepsis on incidence of surgical site infections in gastrointestinal surgery: multicentre randomised controlled clinical trial (OEDO trial) protocol.

INTRODUCTION: Surgical site infections (SSIs) are among the most common nosocomial infections in surgery patients. Two types of preparations, povidone-iodine and chlorhexidine-alcohol, are commonly used in preoperative antiseptic procedures worldwide. However, there are inconsistencies among international guideline recommendations concerning skin antiseptics. This trial aimed to evaluate the superiority of olanexidine, which reduced SSI rates more than povidone-iodine in our previous randomised trial, over chlorhexidine-alcohol in clean-contaminated surgery. METHODS AND ANALYSIS: This multicentre randomised controlled clinical trial will compare two antiseptics (1.5% olanexidine and 1.0% chlorhexidine-alcohol) to prevent SSI in clean-contaminated gastrointestinal surgeries with surgical wounds. On providing consent, patients aged <18 years will be included. The primary outcome will be the postoperative 30-day overall SSI rate, while the secondary outcomes will be the postoperative 30-day superficial incisional SSI rate, deep incisional SSI rate, organ/space SSI rate, positive bacterial wound culture rate, cultured bacterial strains, rates of intervention-related toxicity and allergic events (eg, erythema, pruritus, dermatitis and other symptoms of allergy around the region disinfected by the antiseptic during surgery), rate of reoperations due to SSI, medical economic effect indicators (based on health insurance claims) and hospital duration. The Mantel-Haenszel method will be used to estimate the adjusted risk ratio and its 95% CI for the primary analysis, which will compare the treatment effects. ETHICS AND DISSEMINATION: The protocol was approved by the Institutional Review Board of Keio University School of Medicine and subsequently by the board of each participating site. Participant recruitment began in January 2023. The final results will be published in medical journals after international peer review. TRIAL REGISTRATION NUMBER: UMIN000049712.

The impact of thoracic duct resection on the long-term body composition of patients who underwent esophagectomy for esophageal cancer and survived without recurrence.

BACKGROUND: We have reported the possible benefits of radical esophagectomy with thoracic duct (TD) resection in elective esophageal cancer surgery. However, the effect of TD resection on the long-term nutrition status remains unclear. METHODS: Patients who underwent esophagectomy at Keio University between January 2006 and December 2018 were included, and those who had no recurrence for more than three years were evaluated. Changes in each body composition (muscle mass and body fat) were comparatively assessed between those who underwent TD resection or not, before and at, one, three and five years after surgery. Computed tomography images were analyzed on postoperative year 1, 3 and 5. RESULTS: This study included 217 patients categorized in the TD-resected (TD-R) (156 patients) and TD-preserved (TD-P) (61 patients) groups. The loss of muscle mass was comparable between the groups. On the other hand, the loss of adipose tissues was significantly greater in the TD-R group than in the TD-P group at one and three years after surgery, while there was no statistical difference five years after surgery. Additionally, among patients with cT1N0M0 disease in whom survival advantage of TD resection has been reported previously, the loss of muscle mass did not differ between each group. CONCLUSIONS: The change of muscle mass between the two groups was comparable. Although body fat mass was reduced by TD resection, it eventually recovered in the long term. In patients with esophageal cancer, TD resection may be acceptable without significant impact on body composition in the long term.

Analysis of the short-term outcomes after esophagectomy for esophageal cancer during the COVID-19 pandemic using data from a nationwide Japanese database.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic had adversely impacted cancer screening, diagnosis, and treatment. We investigated the change in medical resource, such as the intensive care unit use, and short-term outcomes after esophagectomy during the pandemic. METHODS: Data of patients who underwent esophagectomy for esophageal cancer registered in the National Clinical Database (NCD) in Japan from January 2018 to December 2021 were analyzed. The time series change in the number of surgical cases; usage of intensive care unit; incidence of morbidity and mortality; standardized mortality and morbidity ratio (SMR) for 30-days mortality; surgical mortality; and morbidities for pneumonia, sepsis, unplanned intubation, and anastomotic leakage were evaluated. RESULTS: The annual number of patients undergoing esophagectomy remained similar from 2018 to 2021. The negative impact of the pandemic on medical resources was strongly identified in the patients from an epidemic area where there is a higher cumulative number of infections per population as compared to all prefectures. The proportions of patients admitted to the intensive care unit were 91.4%, 93.0%, 91.6%, and 90.5% in 2018, 2019, 2020, and 2021, respectively. Moreover, 93.3%, 94.0%, 92.0%, and 90.9% patients who underwent surgery in an epidemic area were admitted to the intensive care unit in 2018, 2019, 2020, and 2021, respectively. However, the morbidity and mortality rates during the pandemic did not worsen according to the SMR values. CONCLUSIONS: Esophagectomy was performed during the pandemic despite limited medical resources by a systematic endeavor of the entire surgical department in Japan, without increasing the incidence rate of worse outcome.

Updates of perioperative multidisciplinary treatment for surgically resectable esophageal cancer.

Esophageal cancer has one of the poorest prognoses among all cancer types, due to the propensity for an early spread through the lymphatics and the difficulty to perform surgical treatment. To improve the prognosis, the management of esophageal cancer has been developed through the conduct of several clinical trials worldwide. In western societies, neoadjuvant chemoradiotherapy has been established as the standard treatment approach, as indicated by the results of the CROSS trial. Recently, the Japanese JCOG1109 trial demonstrated the significant improvement of survival by neoadjuvant triplet chemotherapy. As an adjuvant treatment, an immune checkpoint inhibitor has shown promising results in the CheckMate-577 trial. Including adjuvant S-1 mono therapy as another option, a randomised control phase III study will determine the ideal treatment for surgically resectable esophageal cancer. Furthermore, the efficacy and safety of neoadjuvant cisplatin +5-fluorouracil or DCF plus nivolumab are examined in the JCOG1804E (FRONTiER) study. In addition to definitive chemoradiation therapy, the SANO trial is examining the safety and efficacy of active surveillance after neoadjuvant chemoradiotherapy, which might give us the choice to adopt organ preservation approach. The development of treatment has progressed dramatically with the advent of immunotherapy. Considering the biomarkers to predict the treatment response and prognosis, individualised multidisciplinary treatment strategies should be established for esophageal cancer patients.

Oncological and physiological impact of thoracic duct resection in esophageal cancer.

Despite advances in multidisciplinary treatment, esophagectomy remains the main curative treatment for esophageal cancer. The advantages and disadvantages of thoracic duct (TD) resection have been controversial for decades. We have herein reviewed relevant published literature regarding 'thoracic duct,' 'esophageal cancer,' and 'esophagectomy' describing the anatomy and function of the TD, and incidence of thoracic duct lymph nodes (TDLN) and TDLN metastases, as well as the oncological and physiological effects of TD resection. The presence of lymph nodes around the TD, referred to as TDLN, has been reported previously. The delineation of TDLNs is clearly defined by a thin fascial structure covering the TD and the surrounding adipose tissue. Previous studies have examined the number of TDLNs and the percentage of patients with TDLN metastasis and revealed that each patient had approximately two TDLNs. The percentage of patients with TDLN metastasis was reported to be 6-15%. Several studies have been conducted to compare the survival after TD resection with that after TD preservation. However, no consensus has been reached because all studies were retrospective, precluding firm conclusions. Although the issue of whether the risk of postoperative complications is affected by TD resection is still unclear, resecting the TD has been shown to have a long-term impact on nutritional status after surgery. In summary, TDLNs are quite common and present in most patients, while metastasis in the TDLNs occurs in a minority. However, the oncological value of TD resection in esophageal cancer surgery remains controversial due to varying findings and methodological limitations of previous comparative studies. Considering the potential but unproven oncological benefits and possible physiological drawbacks of TD resection, including postoperative fluid retention and disadvantages in the long-term nutritional outcome, clinical stage, and nutritional status should be considered before deciding whether to perform TD resection or not.

Evaluation of Endoscopic Response Using Deep Neural Network in Esophageal Cancer Patients Who Received Neoadjuvant Chemotherapy.

BACKGROUND: We previously reported that endoscopic response evaluation can preoperatively predict the prognosis and distribution of residual tumors after neoadjuvant chemotherapy (NAC). In this study, we developed artificial intelligence (AI)-guided endoscopic response evaluation using a deep neural network to discriminate endoscopic responders (ERs) in patients with esophageal squamous cell carcinoma (ESCC) after NAC. METHOD: Surgically resectable ESCC patients who underwent esophagectomy following NAC were retrospectively analyzed in this study. Endoscopic images of the tumors were analyzed using a deep neural network. The model was validated with a test data set using 10 newly collected ERs and 10 newly collected non-ER images. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the endoscopic response evaluation by AI and endoscopists were calculated and compared. RESULTS: Of 193 patients, 40 (21%) were diagnosed as ERs. The median sensitivity, specificity, PPV, and NPV values for ER detection in 10 models were 60%, 100%, 100%, and 71%, respectively. Similarly, the median values by the endoscopist were 80%, 80%, 81%, and 81%, respectively. CONCLUSION: This proof-of-concept study using a deep learning algorithm demonstrated that the constructed AI-guided endoscopic response evaluation after NAC could identify ER with high specificity and PPV. It would appropriately guide an individualized treatment strategy that includes an organ preservation approach in ESCC patients.

Lymph node metastatic patterns and the development of multidisciplinary treatment for esophageal cancer.

Abundant lymphatic flow and the anatomical location of the esophagus can result in the widespread distribution of lymph node metastasis of esophageal cancer from the cervical to the abdominal field. Historically, the Japan Esophageal Society and American Joint Committee on Cancer offer two different classifications of lymph node group location surrounding the esophagus. The location of sentinel lymph nodes in midthoracic esophageal cancer reflects the variety of lymphatic drainage routes. In fact, in cT1N0 esophageal cancer, pathological lymph node metastasis has been observed from the cervical to the abdominal field, and the locations were shown to be closely linked to the primary tumor location in advanced stages. While the impact of histology on the distribution of LN metastasis has been extensively debated, a recent prospective study on esophagogastric junction cancer found that metastatic patterns did not differ by histology. Thoracic duct lymph nodes were defined as one of the regional lymph node stations in the mediastinum. Although lymph node metastasis around the thoracic duct has occasionally been observed, the oncologic impact of thoracic duct lymph node dissection has not been fully elucidated. To eradicate tumors locoregionally, three-field lymph node dissection, a strategy for extended lymph node clearance, has been established. In esophagectomy, three-field lymph node dissection is defined as a procedure for complete regional cervico-thoraco-abdominal lymph node dissection. However, its therapeutic efficacy must be evaluated based on the balance between oncological outcomes and possible added surgical risk. To further improve survival, multidisciplinary treatment consisting of surgery, chemotherapy, and radiotherapy has been established worldwide as a standard treatment for esophageal cancer. Now that neoadjuvant therapy followed by esophagectomy is the standard, adding adjuvant therapy including immunotherapy could be a promising treatment option. The ideal combination of various multidisciplinary treatment approaches and extensive LN dissection need to be established to improve the oncological outcomes for EC patients.