Effect of degalactosylated bovine glycoprotein formulations MAF and M сapsules on lymphopenia and clinical outcomes in hospitalized COVID-19 patients: a randomized clinical trial.

BACKGROUND: Targeting mucosal immunity of the gut, which is known to provide antigen processing, while avoiding excessive or unnecessary inflammation, was tested as a way to modulate COVID-19 severity. METHODS: Randomized open-label trial in 204 adults hospitalized with non-critical COVID-19 who received for 14 days in addition to standard of care (SOC) degalactosylated bovine glycoproteins formulations of either MAF capsules (MAF group) or M capsules (M group) or SOC only (control group). RESULTS: Median recovery time when patients did not require supplemental oxygen was 6 days in both study groups compared to 9 days in the control (MAF vs. control; P = 0.020 and M vs. control; P = 0.004). A greater reduction in mortality was seen in the MAF group compared to the control by day 14 (8.3% vs. 1.6%; P = 0.121) and by day 29 (15.3% vs. 3.2%; P = 0.020), and similarly in the M group by day 14 (8.3% vs. 2.9%; P = 0.276) and by day 29 (15.3% vs. 2.9%; P = 0.017). The proportion of those who had baseline absolute lymphocyte count (ALC) lower than 0.8 × 109/L was 13/63 (20.6%), 17/69 (24.6%), and 18/72 (25.0%) of patients in MAF, M, and control group respectively. Day 29 mortality among these lymphopenic patients was three times higher than for the intent-to-treat population (21% vs. 7%) and consisted in above subgroups: 2/13 (15%), 2/17 (12%), and 6/18 (33%) of patients. The decreased mortality in both study subgroups correlated with greater ALC restoration above 0.8 × 109/L level seen on day 14 in 91% (11/12) and 87.5% (14/16) of survivors in MAF and M subgroups respectively compared to 53.3% (8/15) of survivors in control subgroup. Incidences of any ALC decrease below the baseline level on day 14 occurred in 25.4% of patients in the MAF group and 29.0% of patients in the M group compared to 45.8% in control and ALC depletion by ≥ 50% from the baseline level consisted of 7.9%, 5.8%, and 15.3% of cases in these groups respectively. CONCLUSION: This study showed that both study agents prevented ALC depletion and accelerated its restoration, which is believed to be one of the mechanisms of improved crucial clinical outcomes in hospitalized COVID-19 patients. TRIAL REGISTRATION: The trial was registered after the trial start in ClinicalTrials.gov NCT04762628, registered 21/02/2021, https://www. CLINICALTRIALS: gov/ct2/show/NCT04762628 .

Neoadjuvant Chemotherapy Improves Feasibility of Larynx Preservation and Prognosis in Resectable Locally Advanced Cervical Esophageal Cancer.

BACKGROUND: The optimal strategy for cervical advanced esophageal cancer remains controversial in terms of oncologic outcome as well as vocal and swallowing function. Recently, in East Asian countries, neoadjuvant chemotherapy (NAC) has been a standard strategy for advanced esophageal cancer. METHODS: This study included 37 patients who underwent NAC, and 33 patients who underwent definitive chemoradiation therapy (dCRT) as larynx-preserving treatment for locally advanced cervical esophageal cancer from 2016 to 2021. This study retrospectively investigated outcomes, with comparison between NAC and dCRT for locally advanced cervical esophageal cancer. RESULTS: Larynx preservation was successful for all the patients with NAC and dCRT. After NAC, the rate of complete or partial response was 78.4%, and 30 patients underwent larynx-preserving surgery. On the other hand, after dCRT, the complete response rate was 71.9%, and 4 patients underwent larynx-preserving salvage surgery. Overall survival (OS) and progression free survival were similar between the two groups. However, for the patients with resectable cervical esophageal cancer (cT1/2/3), the 2-year OS rate was significantly higher with NAC (79.9%) than with dCRT (56.8%) (P = 0.022), and the multivariate analyses identified only NAC and cN0, one of the two as a significantly independent factor associated with a better OS (NAC: P = 0.041; cN0, 1: P = 0.036). CONCLUSION: The study showed that NAC as larynx-preserving surgery for resectable cervical esophageal cancer preserved function and had a better prognosis than dCRT. The authors suggest that NAC may be standard strategy for larynx preservation in patients with resectable cervical esophageal cancer.

Technical feasibility and oncological outcomes of robotic esophagectomy compared with conventional thoracoscopic esophagectomy for clinical T3 or T4 locally advanced esophageal cancer: a propensity-matched analysis.

BACKGROUND: Minimally invasive esophagectomy is the first-line approach for esophageal cancer; however, there has recently been a paradigm shift toward robotic esophagectomy (RE). We investigated the clinical outcomes of patients who underwent RE compared with those of patients who underwent conventional minimally invasive thoracoscopic esophagectomy (TE) for locally advanced cT3 or cT4 esophageal cancer using a propensity-matched analysis. METHODS: Overall, 342 patients with locally advanced cT3 or cT4 esophageal cancer underwent transthoracic esophagectomy with total mediastinal lymph node dissection between 2018 and 2022. The propensity-matched analysis was performed to assign the patients to either RE or TE by covariates of histological type, tumor location, and clinical N factor. RESULTS: Overall, 87 patients were recruited in each of the RE and TE groups according to the propensity-matched analysis. The total complication rate and the rates of the three major complications (recurrent laryngeal nerve paralysis, anastomotic leakage, and pneumonia) were not significantly different between the RE and TE groups. However, the peak C-reactive protein concentration on postoperative day 3, rate of surgical site infection, and intensive care unit length of stay after surgery were significantly shorter in the RE group than in the TE group. No significant differences were observed in the harvested total and mediastinal lymph nodes. The total operation time was significantly longer in the RE group, while the thoracic operation time was shorter in the RE group than in the TE group. There was no significant difference between the two groups in the recurrence rate of oncological outcomes after surgery. CONCLUSION: RE may facilitate early recovery after esophagectomy with total mediastinal lymph node dissection and has the same technical feasibility and oncological outcomes as TE.

Significance of Surgery for Resectable M1 Lymph Node Metastases Without Organ Metastasis in Esophageal Carcinoma in the Era of Neoadjuvant Treatment.

BACKGROUND: M1 esophageal carcinoma goes beyond localized disease and requires treatment with systemic therapy. M1 status is primarily divided into two categories: M1 lymph node metastasis and distant organ metastasis. Oligometastasis is defined as a state of limited metastatic disease, and surgery for oligometastasis of distant organs is reported to be beneficial in limited conditions. The aim of this study was to investigate resected cases of M1 lymph node metastases as the only metastatic site in stage IVB esophageal carcinoma. PATIENTS AND METHODS: This study was a single-center retrospective cohort study. Patients with esophageal carcinoma who underwent esophagectomy with curative intent between April 2017 and December 2021 were examined. Neoadjuvant chemotherapy was our standard therapy and administered in almost all cases. We hypothesized that four sites of metastatic M1LN (supraclavicular (no. 104), pretracheal (no. 106pre), posterior thoracic para-aortic (no. 112aoP), and abdominal para-aortic (no. 16a2lat) LNs) were potentially resectable M1LN (rM1LN) metastases with curative intent and compared the prognosis of patients with and without rM1LN metastasis. RESULTS: Six hundred eight-two patients were included in the study. Among these patients, 80 had rM1LN metastasis and received surgery for curative intent. Short-term safety outcomes were equivalent between patients with and without rM1LN metastases. After propensity score matching, there were no significant differences in overall survival between patients with and without rM1LN metastasis. Multivariate analyses revealed that the only independent prognostic factor was ypN status. CONCLUSION: The present study suggests the feasibility and favorable OS in the patients with resection of rM1LN metastasis.

Diet-related factors strongly shaped the gut microbiota of Japanese macaques.

Although knowledge of the functions of the gut microbiome has increased greatly over the past few decades, our understanding of the mechanisms governing its ecology and evolution remains obscure. While host genetic distance is a strong predictor of the gut microbiome in large-scale studies and captive settings, its influence has not always been evident at finer taxonomic scales, especially when considering among the recently diverged animals in natural settings. Comparing the gut microbiome of 19 populations of Japanese macaques Macaca fuscata across the Japanese archipelago, we assessed the relative roles of host genetic distance, geographic distance and dietary factors in influencing the macaque gut microbiome. Our results suggested that the macaques may maintain a core gut microbiome, while each population may have acquired some microbes from its specific habitat/diet. Diet-related factors such as season, forest, and reliance on anthropogenic foods played a stronger role in shaping the macaque gut microbiome. Among closely related mammalian hosts, host genetics may have limited effects on the gut microbiome since the hosts generally have smaller physiological differences. This study contributes to our understanding of the relative roles of host phylogeography and dietary factors in shaping the gut microbiome of closely related mammalian hosts.

Non-curative resection for surgical T4b esophageal cancer: esophagectomy or non-esophagectomy?

BACKGROUND: Recently, with the development of multidisciplinary treatment, the treatment outcomes of esophageal cancer (EC) have improved. However, despite advances in diagnostic imaging modalities, preoperative diagnosis of T4 EC is still difficult, and the prognosis of T4 EC remains very poor. In addition, the prognosis of surgical T4b EC (sT4b EC) after surgery remains unclear. In this study, we retrospectively reviewed sT4b EC. METHODS: We evaluated the clinical course of sT4b EC and compared palliative esophagectomy with R2 resection (PE group) with other procedures without esophagectomy (NE group) (e.g., only esophagostomy) for sT4b EC. RESULTS: Forty-seven patients with thoracic EC underwent R2 resection at our institution between January 2009 and December 2020. Thirty-four patients were in the PE group, and 13 patients were in the NE group. The 2-year overall survival rate was 0% in the PE group and 20.2% in the NE group (p = 0.882). There was one case of long-term survival in the NE group that underwent surgery followed by definitive chemoradiation. Postoperative complications (Clavien-Dindo grade ≥ 3) were observed in 25 patients (73.5%) in the PE group and in three patients (23.1%) in the NE group (p = 0.031). The median time to the initiation of postoperative treatment was 68.1 days in the PE group and 18.6 days in the NE group (p = 0191). CONCLUSIONS: If EC is diagnosed as sT4b, palliative esophagectomy should be avoided because of the high complication rate and the lack of long-term survival.

Oncologic significance of lymphovascular invasion in patients with superficial esophageal squamous cell carcinoma reaching the muscularis mucosae or with slight invasion of the submucosa.

BACKGROUND: The clinicopathological features and the distribution of lymph node metastasis in patients with T1a-MM and T1b-SM1 superficial esophageal squamous cell carcinoma remain unclear; therefore, the optimal treatment strategy is still controversial. METHODS: One hundred and ninety-one patients who had undergone a thoracic esophagectomy with 3-field lymphadenectomy and who were pathologically confirmed to have thoracic superficial esophageal squamous cell carcinoma that had reached the T1a-MM or T1b-SM1 stage were retrospectively reviewed. Risk factors of lymph node metastasis, the distribution of lymph node metastasis, and long-term outcomes were evaluated. RESULTS: A multivariate analysis revealed that lymphovascular invasion was the only independent risk factor of lymph node metastasis (odds ratio: 6.410, P < .001). Patients with primary tumors in the middle thoracic region had lymph node metastasis in all 3 fields, whereas patients with primary tumors in the upper or lower thoracic region did not have distant lymph node metastasis. The frequencies of neck (P = .045) and abdominal (P < .001) lymph node metastasis were significantly higher in lymphovascular invasion-positive patients than those in lymphovascular invasion-negative patients in all cohort. MM/lymphovascular invasion-positive patients with middle thoracic tumors had lymph node metastasis spread from the neck to the abdomen. SM1/lymphovascular invasion-negative patients with middle thoracic tumors did not have lymph node metastasis in the abdominal region. The SM1/pN+ group had a significantly poorer overall survival and relapse-free survival than the other groups. CONCLUSION: The present study revealed that lymphovascular invasion was associated with not only the frequency of lymph node metastasis, but also the distribution of lymph node metastasis. It also suggested that superficial esophageal squamous cell carcinoma patients with T1b-SM1 and lymph node metastasis had a significantly poorer outcome than those with T1a-MM and lymph node metastasis.

Significance of lymphovascular invasion in esophageal squamous cell carcinoma undergoing neoadjuvant chemotherapy followed by esophagectomy.

BACKGROUND: Lymphovascular invasion (LVI) was previously reported to be an independent factor associated with survival in locally advanced esophageal squamous cell carcinoma (LAESCC) patients receiving neoadjuvant chemotherapy (NAC); however, the detailed clinicopathological significance of LVI remains unclear. This study evaluated the prognostic impact of LVI in patients with LAESCC after NAC with cisplatin and 5-fluorouracil (CF) or docetaxel, cisplatin and 5-fluorouracil (DCF) followed by surgery and in LAESCC patients with recurrence after NAC and surgery. METHODS: 438 patients with thoracic LAESCC who had undergone NAC followed by an esophagectomy with three-field lymphadenectomy were assessed using a propensity score matched analysis, and their long-term outcomes were retrospectively reviewed. RESULTS: In matched cohort, a multivariate analysis of relapse-free survival (RFS) in the NAC-CF group suggested that ypN (≥ 1, HR = 3.715, p = 0.004) and LVI (positive, HR = 3.366, p = 0.012) were independent factors associated with RFS; in the NAC-DCF group, ypN (≥ 1, HR = 4.829, p < 0.001) was the only independent factor associated with RFS. Comparisons of overall survival (OS) between the ypN + /LVI + group and other groups among patients with recurrence in each NAC regimen showed significant differences in both of NAC groups (p < 0.001, respectively). The ypN + /LVI + group had a significantly poor OS in both an oligometastatic recurrence (OMR) group (p < 0.001) and a non-OMR group (p < 0.001). CONCLUSIONS: The present study suggested that the independent factor associated with prognosis of patients with LAESCC after NAC and surgery may differ according to the NAC regimen, and the presence of both ypN and LVI was a prognostic factor for patients with recurrence, including those with OMR. These results might be helpful when deciding on an additional treatment strategy for LAESCC patients.

Surveillance Strategy after Curative Resection for Oesophageal Squamous Cell Cancer Using the Hazard Function.

BACKGROUND: The optimal surveillance period and frequency after curative resection for oesophageal squamous cell carcinoma (OSCC) remain unclear, and current guidelines are mainly based on traditional Kaplan-Meier analyses of cumulative incidence rather than risk analysis. The aim of this study was to determine a suitable follow-up surveillance program following oesophagectomy for OSCC using the hazard function. METHODS: A total of 1187 patients who underwent curative resection for OSCC between 2000 and 2014 were retrospectively analyzed. The changes in the estimated hazard rates (HRs) of recurrence over time were analyzed according to tumour-node-metastasis stage. RESULTS: Four hundred seventy-eight (40.2%) patients experienced recurrence during the follow-up period (median, 116.5 months). The risk of recurrence peaked at 9.2 months after treatment (HR = 0.0219) and then decreased to half the peak value at 24 months post-surgery. The HRs for Stage I and II patients were low (< 0.007) post-treatment. The HR for Stage III patients peaked at 9.9 months (HR = 0.031) and the hazard curve declined to a plateau at 30 months. Furthermore, the HR peaked at 10.8 months (HR = 0.052) in Stage IV patients and then gradually declined from 50 months. CONCLUSIONS: According to tumour-node-metastasis stage, changes in the HRs of postoperative recurrence in OSCC varied significantly. Intensive surveillance should be undertaken for 3 years in Stage III patients and for 4 years in Stage IV patients, followed by annual screening. For Stage I OSCC patients, a reduction in the surveillance intensity could be taken into consideration.

Clinicopathological Features of Early-Stage Esophageal Carcinosarcoma.

Esophageal carcinosarcoma (EC) is a rare malignant tumor, accounting for 0.5-2.8% of esophageal cancers. Most are advanced cancers that are detected as polypoid lesions and are treated with multidisciplinary therapy with a focus on surgery. However, endoscopic findings, pathological findings, and long-term outcomes of early-stage EC are often unclear because there are very few reported cases. This paper reports three cases of EC confined to the mucosal layer. The macroscopic type of all tumors was polypoid lesion with a slightly depressed lesion. All cases were clinically diagnosed as invasive cancer before treatment. Pathological diagnosis of tumor depth showed that one case had invaded the lamina propria mucosae, and two cases had invaded the muscularis mucosae (MM). One case of diagnosed MM had lymphoid invasion and lymph node metastasis to the upper mediastinum. After 1 year, although adjuvant treatment had been administered, there was lymph node recurrence in the left upper clavicle, and thus chemoradiation therapy was performed. Two other cases survived without recurrence. Early-stage EC is characterized by polypoid lesions with a slightly depressed lesion, and it is challenging to predict the histology on biopsy. Furthermore, it is difficult to determine the depth of invasion in the MM and submucosal layer in squamous cell carcinoma by endoscopy alone, and hence depth diagnosis by multiple modalities should be considered.

Predictive Ability of the Five-time Chair Stand Test for Postoperative Pneumonia after Minimally Invasive Esophagectomy for Esophageal Cancer.

BACKGROUND: The revised sarcopenia guidelines proposed handgrip strength (HGS) and five-time chair stand test (5-CST) as the primary parameters of muscle function. HGS and 5-CST are associated with pulmonary function among community-dwelling people, although few reports have described an association between these parameters and surgical outcomes in carcinomas. We examined the predictive ability of 5-CST for postoperative pneumonia after minimally invasive esophagectomy (MIE) compared with that of HGS. METHODS: This retrospective, single-center, observational study evaluated 222 male patients who underwent MIE for esophageal cancer between February 2018 and October 2020. Sarcopenia parameters included 5-CST, HGS, and skeletal muscle index. Postoperative pneumonia predictors were determined by using multivariate logistic regression analysis. We assessed the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) to analyze the predictive ability of 5-CST and HGS. RESULTS: MIE was performed for squamous cell carcinoma (n = 179), adenocarcinoma (n = 38), and other cancers (n = 5). Forty-nine (22.1%) patients developed postoperative pneumonia. Multivariate logistic regression showed that age (odds ratio [OR] 1.05; 95% confidence interval [CI] 1.01-1.10; p = 0.027), 5-CST (OR, 1.19; 95% CI 1.00-1.40; p = 0.046), and recurrent laryngeal nerve palsy (RLNP) (OR, 3.37; 95% CI 1.60-7.10; p = 0.001) significantly predicted postoperative pneumonia. Category-free NRI and IDI showed that adding 5-CST in the prediction model with age and RLNP resulted in significantly greater reclassification and discrimination abilities than did HGS. CONCLUSIONS: The 5-CST significantly predicted postoperative pneumonia after MIE. NRI and IDI analyses suggested that 5-CST had significantly better predictive ability for postoperative pneumonia than did HGS.

Does Preoperative Corticosteroid Administration Improve the Short-Term Outcome of Minimally Invasive Esophagectomy for Esophageal Cancer? A Propensity Score-Matched Analysis.

BACKGROUND: In open esophagectomy for esophageal cancer, steroid administration is associated with attenuated postoperative inflammation and reduced complications. However, the efficacy of steroids in minimally invasive esophagectomy (MIE) is uncertain. This study aimed to investigate the impact of steroid administration on short-term postoperative outcomes in MIE. METHODS: The study compared 458 patients who underwent MIE between April 2017 and December 2021. The patients were divided into steroid (n = 206) and non-steroid (n = 252) groups, and 160 paired cases were compared by 1:1 propensity score-matching. RESULTS: In the steroid group versus the non-steroid group, the intensive care unit stay was significantly shorter (2.6 vs 3.3 days; P = 0.001), and the incidence of surgical-site infection (SSI) was significantly lower (1.2 % vs 13.1 %; P < 0.001). The incidence of pneumonia tended to be lower in the steroid group, but not significantly lower (19.3 % vs 29.3 %; P = 0.065). Multivariate analysis showed that steroid administration independently affected SSI (odds ratio, 11.6; 95 % confidence interval, 3.3-73.6; P < 0.001). Compared with the non-steroid group, the steroid group had more favorable arterial partial pressure of oxygen/fraction of inspired oxygen ratio (503 ± 178 vs 380 ± 104; P < 0.001) and body temperature (37.2 ± 0.54 °C vs 38.3 ± 0.66 °C; P < 0.001) on postoperative day (POD) 0, heart rate (beats per minute) (74.6 ± 8.9 vs 84 ± 11.4; P < 0.001) on POD 1, and C-reactive protein concentration (7.07 ± 3.4 vs 13.7 ± 6.4 mg/dL; P < 0.001) on POD 3. CONCLUSIONS: In MIE, steroid administration was associated with reduced SSI, suggesting an attenuated inflammatory response to surgical stress.

Handgrip strength predicts early postoperative dysphagia after thoracoscopic-laparoscopic esophagectomy in male patients with esophageal cancer.

BACKGROUND: Dysphagia after esophagectomy, especially in the early postoperative period, remains a severe complication. The association between sarcopenia and dysphagia has received attention in geriatric non-cancer populations. This study aimed to determine the associations between sarcopenia parameters and early postoperative dysphagia after esophagectomy. METHODS: This retrospective observational study included 201 consecutive male patients undergoing thoracoscopic-laparoscopic esophagectomy (TLE) for esophageal cancer between October 2018 and December 2020. We used three sarcopenia parameters: handgrip strength (HGS), skeletal muscle index, and gait speed. Postoperative swallowing function was assessed by videofluoroscopy using the penetration-aspiration scale (PAS; range 1-8). Logistic regression analyses were used to predict factors associated with postoperative aspiration (PAS 6-8). Furthermore, we compared values in patients with symptomatic aspiration (PAS 6-7) and with silent aspiration (PAS 8). RESULTS: Aspiration occurred in 38 of 201 patients (18.9%). On multivariate analysis, significant predictors of aspiration included age [odds ratio (OR) 1.11; 95% confidence interval (CI) 1.05-1.17; p < 0.001], low HGS (OR 3.05; 95% CI 1.06-8.78; p = 0.039), upper third esophageal cancer (OR 2.79; 95% CI 1.03-7.54; p = 0.044) and recurrent laryngeal nerve palsy (OR 2.98; 95% CI 1.26-7.06; p = 0.013). Furthermore, among patients with aspiration (PAS 6-8), low HGS was significantly associated with silent aspiration (OR 6.43; 95% CI 1.06-39.00; p = 0.043). CONCLUSIONS: Low HGS was significantly associated with early postoperative aspiration and impairment of airway protective reflexes after TLE.

Salvage minimally invasive esophagectomy after definitive chemoradiotherapy for esophageal cancer can improve postoperative complications compared with salvage open esophagectomy.

BACKGROUND: Although the advantage of minimally invasive esophagectomy (MIE) over open esophagectomy (OE) in planned esophagectomy is being established, the utility of salvage MIE (S-MIE) remains unclear. We aimed to investigate the feasibility and advantage of S-MIE compared with salvage OE (S-OE). METHODS: We retrospectively assessed 82 patients who underwent salvage esophagectomy after definitive chemoradiotherapy for thoracic esophageal cancer between January 2007 and April 2020. Perioperative factors and postoperative complications were compared between the S-OE group (n = 62) and the S-MIE group (n = 20). Logistic regression analysis was performed to analyze the factors associated with postoperative complications. RESULTS: Regarding the patients' preoperative characteristics, the S-OE group had a significant number of grade ≥ cT3 patients vs the S-MIE group (69% vs 35%, respectively; p = 0.006), whereas ycT rates were comparable. Compared with S-OE, S-MIE had comparable operative time, number of harvested thoracic lymph nodes, and R0 resection, but significantly less estimated blood loss (150 ml and 395 ml, respectively; p = 0.003). Regarding postoperative complications, total complications (79% vs 50%; p = 0.01) and pneumonia (48.3% vs 20%; p = 0.02) rates were significantly lower with S-OE vs S-MIE, respectively. On multivariate analysis, S-MIE was an independent factor associated with postoperative pneumonia (odds ratio: 0.29, 95% confidence interval: 0.06-0.99; p = 0.04) and total complications (odds ratio: 0.26, 95% confidence interval: 0.07-0.86; p = 0.02). CONCLUSION: S-MIE was feasible for salvage esophagectomy, with favorable short-term outcomes vs S-OE regarding postoperative pneumonia and total complications.

Novel pathological staging for patients with locally advanced esophageal squamous cell carcinoma undergoing neoadjuvant chemotherapy followed by surgery.

BACKGROUND: The aim of the present study was to clarify an appropriate staging system for patients with locally advanced esophageal squamous cell carcinoma (LAESCC) after neoadjuvant chemotherapy (NAC) prior to surgery. METHODS: A total of 388 patients with clinical stage II or III LAESCC who had undergone NAC followed by an esophagectomy with three-field lymphadenectomy were retrospectively reviewed. RESULTS: The relapse-free survival (RFS) curves plotted using ypN grading and ypTNM staging both monotonically decreased as the classification number increased, and the groups were more clearly separated than when the Japanese Classification (JC) was applied. A multivariate analysis of relapse free survival (RFS) suggested that ypN (HR = 2.911, P < 0.001), lymphovascular invasion (LVI) (HR = 2.608, P < 0.001) were independent factors associated with OS. The LVI+/ypN+ group had a significantly poorer outcome than the other groups (P < 0.001). The 5-year RFS rates for patients with ypStage IIIA or higher among the LVI-negative cases and ypStage II or higher among the LVI-positive cases were around 0.6 or under. The novel pathological staging which was based on the present results was proposed and RFS curves of each novel stage suggested the suitability of these staging for our cohort. CONCLUSIONS: The present results suggest that a novel pathological staging system using the ypTNM classification, in which the supraclavicular lymph node was regarded as a regional lymph node and the presence of LVI was included as a category, was appropriate for patients with LAESCC after NAC prior to surgery.

Feasibility of conversion thoracoscopic esophagectomy after induction therapy for locally advanced unresectable esophageal squamous cell carcinoma.

BACKGROUND: Recently, patients with cT4b esophageal cancer often require conversion surgery following induction therapy, for which the standard procedure is open esophagectomy. However, thoracoscopic esophagectomy, including thoracoscopic esophagectomy in the prone position, is increasingly used. We compared short-term outcomes of thoracoscopic esophagectomy and open esophagectomy in this setting. METHODS: We retrospectively analyzed 14 patients who underwent thoracoscopic esophagectomy, and 10 who underwent open esophagectomy, for locally advanced unresectable esophageal cancer after induction therapy between March 2007 and July 2020. RESULTS: The two groups did not significantly differ in patient background. Median total and thoracic surgical times were both significantly longer for open esophagectomy than for thoracoscopic esophagectomy. Median blood loss was also greater in the open esophagectomy group than in the thoracoscopic esophagectomy group. The thoracoscopic esophagectomy group also had significantly shorter median chest drain duration; and lower C-reactive protein levels on the second and third postoperative days. The two groups did not significantly differ in total complications or postoperative hospital stay. CONCLUSIONS: Thoracoscopic esophagectomy is as safe and feasible as open esophagectomy for conversion surgery after induction therapy for locally advanced unresectable esophageal squamous cell carcinoma.

[Synchronous Resection of Gallbladder Hyperplasia Polyps with Pancreaticobiliary Maljunction without Dilation of the Bile Duct and Sigmoid Colon Carcinoma].

We report synchronous resection of gallbladder hyperplasia polyps with pancreaticobiliary maljunction without dilation of the bile duct and sigmoid colon carcinoma. The patient was a 60-year-old woman diagnosed with sigmoid colon cancer. Gallbladder polyps were detected incidentally during a preoperative examination for sigmoid colon cancer that was discovered because of anemia. Detailed examination revealed a suspected gallbladder carcinoma along with pancreaticobiliary maljunction without dilation of the bile duct. The patient underwent synchronous open colectomy and cholecystectomy. Histopathological diagnosis excluded gallbladder carcinoma, so we did not perform bile duct resection or lymph node resection around the bile duct. The final diagnosis was gallbladder hyperplasia polyps, chronic cholecystitis, and sigmoid colon cancer (pT3N2M0, stage Ⅲb). Therefore, physicians should pay attention to the possibility of pancreaticobiliary maljunction if gallbladder polyps are detected incidentally during preoperative examination for other diseases. In the present case, we could treat the patient with minimally invasive techniques by adding the treatment to that performed for the other disease.

Macrophages Exhibit a Large Repertoire of Activation States via Multiple Mechanisms of Macrophage-activating Factors.

BACKGROUND/AIM: Macrophages are important components of human defense systems and consequently key to antitumor immunity. Human-serum macrophage activation factor (serum MAF) can activate macrophages, making it a promising reagent for anticancer therapy. MATERIALS AND METHODS: We established four different macrophage subtypes through introduction of different culture conditions to THP-1- and U937-derived macrophages. We assessed phagocytic activity to understand subtype responses to typical macrophage activation factors (MAFs) and the activation mechanisms of serum MAF. RESULTS: All four macrophage subtypes differed in their response to all MAFs. Moreover, serum MAF had two different activation mechanisms: N-acetylgalactosamine (GalNAc)-dependent and GalNAc-independent. CONCLUSION: Macrophage activation states and mechanisms are heterogeneous.