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Background: The clinical significance of the lymph node ratio (LNR), the number of metastatic lymph nodes per dissected lymph node, has not been sufficiently clarified in ampullary cancer., Methods: Among patients diagnosed histopathologically with ampullary cancer between 1980 and 2018, the study included 106 who underwent pathological radical resection by pancreaticoduodenectomy. The relationships between the LNR and metastatic lymph node sites and prognosis were examined., Results: Multivariate analysis revealed that sex and lymph node metastasis were independent prognostic factors. In the 46 patients (43%) with metastatic lymph nodes, the LNR in the recurrence group was significantly higher than that in the non-recurrence group (0.15 ± 0.11 vs. 0.089 ± 0.071, p = 0.025). The receiver operating characteristic curve demonstrated that the LNR cut-off value, 0.07 (area under the curve = 0.70, sensitivity 81%, specificity 56%), was a significant indicator for recurrence (22% vs. 61%, p = 0.016) and prognosis (5-year survival: 48% vs. 83%, p = 0.028). Among the metastatic lymph node sites in the 46 positive cases, lymph node metastases developed from the peripancreatic head region (80%, 37/46) to the superior mesenteric artery (33%, 15/46) and para-aortic (11%, 5/46) regions., Conclusion: Lymph node metastasis is an independent prognostic factor, and the LNR is a significant indicator for recurrence and prognosis in patients with ampullary cancer., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Identifying patients who can be spared nonbeneficial surgery is crucial, as pancreatic cancer surgery is highly invasive, with substantial negative effects on quality of life. The study objective was to investigate a useful indicator of patients who do not gain prognostic benefit from radical surgery after neoadjuvant therapy for resectable and borderline resectable pancreatic cancer., Method: We compared factors among 609 patients with resectable or borderline resectable pancreatic cancer receiving neoadjuvant therapy during 2005-2019. Patients were divided into a poor-prognosis group (no surgery or postresection recurrence within a year) and a good-prognosis group (no recurrence or recurrence >1 year after resection)., Results: Patients who experience a recurrence within a year of resection (poor-prognosis group) did no better than patients who received neoadjuvant therapy and progressed but never made it to surgery. The value of carbohydrate antigen 19-9 after neoadjuvant therapy was the most significant indicator to predict the poor prognosis group and the elevation of carbohydrate antigen 19-9 (>200 U/mL) identified only poor prognosis group with high specificity of 96.6%. The overall survival of patients with more than 200 of carbohydrate antigen 19-9 after neoadjuvant therapy was significantly very poor and their 2-year survival rate was only 41.4%., Conclusion: A striking elevation of carbohydrate antigen 19-9 after neoadjuvant therapy for resectable or borderline resectable pancreatic cancer is a good indicator of poor prognosis. Patients with carbohydrate antigen 19-9 >200 U/mL after neoadjuvant therapy should not undergo radical surgery., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Dysphagia caused by tumor strictures is a major symptom in patients with advanced esophageal cancer. However, the prognostic effect of dysphagia in resectable cases is insufficiently investigated. This study aimed to investigate the prognostic value of dysphagia scores in resectable advanced esophageal cancer who underwent radical esophagectomy after preoperative treatment., Methods: This retrospective study enrolled 302 consecutive patients with advanced resectable esophageal cancer who received preoperative treatment. The preoperative dysphagia score was used to assess the relationship between tumor stricture and clinical outcomes., Results: Almost half of the patients had dysphagia scores of 2 to 4 (n = 152 [50.3%]). Lower body mass index, circumferential tumors, and noncurative resection were significantly more common as dysphagia scores worsened. Patients with dysphagia had significantly more advanced ypT stage and worse histopathologic response than those without dysphagia. The 5-year disease-free survival and overall survival (OS) rates for dysphagia scores of 0 to 1, 2 to 3, and 4 were 52.9%, 35.3%, and 26.7% and 60.7%, 40.4%, and 26.7%, respectively. Multivariate analysis identified dysphagia score as an independent factor of OS, similar to surgical curability and ypN stage. The postoperative recurrence rate was significantly higher among patients with dysphagia scores of 2 to 3 (56%) and 4 (67%) than among those with dysphagia scores of 0 to 1 (36%) (P < .001 and P = .037, respectively). Furthermore, distant recurrence in dysphagia scores of 2 to 3 and 4 was higher than in dysphagia scores of 0 to 1 (26%, 46%, and 42%, respectively)., Conclusion: The dysphagia score before initial treatment is associated with postoperative survival in patients with resectable advanced esophageal cancer., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Background & Aims: This study aimed to investigate the temporal changes in body composition following esophagectomy in patients with esophageal cancer using bioelectrical impedance analysis and to assess the prognostic implications of these changes., Methods: Our study included 528 patients who underwent esophagectomy and preoperative body composition measurements between January 2013 and June 2020. Postoperative body composition was measured in 493 patients at discharge as follows: 184 at 1 month, 144 at 2 months, 143 at 3 months, 103 at 6 months, 58 at 9 months, and 78 at 12 months., Results: Body weight (BW) continuously decreased until the 6 postoperative months (POMs), reaching -11.5% compared with preoperative levels. Subsequently, almost no change was observed at 12 POMs. Skeletal muscle mass (SMM) decreased until 3 POMs but gradually recovered after 3 POMs. Conversely, body fat mass (BFM) consistently decreased over time post-esophagectomy. The patients were categorized into moderate (>-10%) and severe (≤-10%) groups based on % BW, % SMM, and % BFM losses at 3 POMs. Severe SMM loss at 3 POMs correlated with reduced overall survival (OS) (3-year OS: 85.9% in moderate vs. 75.1% in severe, p = 0.035). BFM loss was associated with reduced recurrence-free survival (3-year RFS: 83.3% in moderate vs. 62.0% in severe, p = 0.011). Multivariate analysis identified pStages Ⅲ and Ⅳ, % SMM loss ≤ -10%, and % BFM loss ≤ -10% as independent factors for worse OS., Conclusion: Post-esophagectomy, distinct temporal changes in BW, SMM, and BFM are observed. Significant reductions in SMM and BFM 3 POMs indicate a poor long-term prognosis., Competing Interests: Conflict of interest Authors declare no conflict of interests for this article., (Copyright © 2024. Published by Elsevier Ltd.)

Pembrolizumab plus chemotherapy has been indicated as the first-line treatment for metastatic or unresectable locally advanced esophageal cancer. However, pretreatment biomarkers for predicting clinical outcomes remain unclear. We investigated the predictive value of inflammation-based prognostic scores in patients treated with pembrolizumab and chemotherapy. The Prognostic Nutritional Index (PNI), C-reactive protein/albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were calculated before initial treatment in 65 eligible patients with metastatic or unresectable locally advanced esophageal cancer receiving pembrolizumab plus CF therapy, and the relationship between these biomarkers and clinical outcomes was analyzed. The objective response rate (ORR) and progression disease (PD) were observed in 51% and 21% of all patients. Patients with PNI<39 have significantly worse treatment responses than those with PNI≥39 (ORR; 28% vs. 60%, PD; 44% vs. 13%, P =0.020). Progression-free survival (PFS) is significantly associated with the PNI and CAR ( P <0.001 and P =0.004, respectively). Overall survival (OS) is associated with PNI, CAR, and PLR ( P <0.001, P =0.008, and P =0.018, respectively). The PNI cutoff value of 39 is identified as an independent factor for PFS (odds ratio=0.27, 95% CI: 0.18-0.81, P =0.012) and OS (odds ratio=0.22, 95% CI: 0.08-0.59, P =0.003). Patients with PNI<39 have significantly worse 6-month PFS and 1-year OS than those with PNI≥39 (27.8% vs. 66.7%, 27.2% vs. 81.1%, respectively). In conclusion, inflammation-based prognostic scores are associated with survival in patients treated with pembrolizumab plus CF therapy. Pretreatment PNI is a promising candidate for predicting treatment response and survival., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Nodal status is well known to be the most important prognostic factor for esophageal cancer patients, even if they are treated with neoadjuvant therapy. To establish an optimal postoperative adjuvant strategy for patients, we aimed to more accurately predict the prognosis of patients and systemic recurrence by using clinicopathological factors, including nodal status, in patients with esophageal cancer who received neoadjuvant chemotherapy. The clinicopathological factors associated with survival and systemic recurrence were investigated in 488 patients with esophageal squamous cell carcinoma who received neoadjuvant chemotherapy. Overall survival differed according to tumor depth, nodal status, tumor regression, and lymphovascular (LV) invasion. In the multivariate analysis, nodal status and LV invasion were identified as independent prognostic factors (P < 0.0001, P = 0.0008). Nodal status was also identified as an independent factor associated with systemic recurrence, although LV invasion was a borderline factor (P = 0.066). In each pN stage, patients with LV invasion showed significantly worse overall survival than those without LV invasion (pN0: P = 0.036, pN1: P = 0.0044, pN2: P = 0.0194, pN3: P = 0.0054). Patients with LV invasion were also more likely to have systemic, and any recurrence than those without LV invasion in each pN stage. Pathological nodal status and LV invasion were the most important predictors of survival and systemic recurrence in patients with esophageal cancer who underwent neoadjuvant chemotherapy followed by surgery. This finding could provide useful information about selecting candidates for adjuvant therapy among these patients. Our analysis showed that LV invasion was an independent prognostic factor in patients with esophageal cancer who underwent neoadjuvant chemotherapy and that combining LV invasion with pathological nodal status makes it possible to stratify the prognosis in those patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The standard treatment for advanced esophageal cancer with synchronous distant metastasis is systemic chemotherapy or immunotherapy. Conversion surgery is not established for esophageal cancer with synchronous distant metastasis. This study aimed to investigate the clinical impact of conversion surgery for esophageal cancer with synchronous distant metastasis after induction therapy., Methods: This multi-institutional retrospective study enrolled 66 patients with advanced esophageal cancer, including synchronous distant metastasis, who underwent induction chemotherapy or chemoradiotherapy followed by conversion surgery between 2005 and 2021. Short- and long-term outcomes were investigated., Results: Distant lymph node (LN) metastasis occurred in 51 patients (77%). Distant organ metastasis occurred in 15 (23%) patients. There were 41 patients with metastatic para-aortic LNs, and 10 patients with other metastatic LNs. Organs with distant metastasis included the lung in seven patients, liver in seven patients, and liver and lung in one patient. For 61 patients (92%), R0 resection was achieved. The postoperative complication rate was 47%. The in-hospital mortality rate was 1%, and the 3- and 5-year overall survival (OS) rates for all the patients were 32.4% and 24.4%, respectively. The OS rates were similar between the patients with distant LN metastasis and the patients with distant organ metastasis (3-year OS: 34.9% vs. 26.7%; P = 0.435). Multivariate analysis showed that pathologic nodal status is independently associated with a poor prognosis (hazard ratio, 2.43; P = 0.005)., Conclusions: Conversion surgery after chemotherapy or chemoradiotherapy for esophageal cancer with synchronous distant metastasis is feasible and promising. It might be effective for improving the long-term prognosis for patients with controlled nodal status., (© 2024. Society of Surgical Oncology.)

Nephrotic syndrome and hypothyroidism are respectively reported to influence renal hemodynamics and hypercholesterolemia. However, the relationship of proteinuria-associated thyroid function with renal hemodynamics and cholesterol metabolism has yet to be determined in a simultaneous analysis of thyroid, renal, and cholesterol variables. We investigated the hypothesis that the changes in thyroid hormones by proteinuria may contribute to changes in cholesterol metabolism and renal hemodynamics by proteinuria. Twenty-nine patients (17 men and 12 women) with proteinuric kidney disease (mean age 46 years) were enrolled in a pilot study. Data for serum free triiodothyronine (FT3), free thyroxine (FT4), total cholesterol, and filtration fraction (FF; assessed by para-aminohippuric acid clearance) were used in variable-adjusted correlation analyses. The patients had the following data (mean ± standard deviation): urinary protein 5.18 ± 3.28 g/day, FT3 2.18 ± 0.44 pg/mL, FT4 1.03 ± 0.26 ng/dL, FF 0.27 ± 0.07, and total cholesterol 327 ± 127 mg/dL. There was a significant positive correlation of FT3 with FF (β = 0.58, p = 0.01) and a significant inverse correlation of FT4 with total cholesterol (β = -0.40, p = 0.01). A positive correlation of FT3 with FF and an inverse correlation of FT4 with total cholesterol were demonstrated in patients with proteinuric kidney disease. The proteinuria-associated reduction in serum thyroid hormone levels was correlated with hypercholesterolemia and the reduced glomerular FF. Further studies of these relationships are required.

Background: The assessment of muscle mass loss, muscle strength, and physical function has been recommended in diagnosing sarcopenia. However, only muscle mass has been assessed in previous studies. Therefore, this study investigated the effect of comprehensively diagnosed preoperative sarcopenia on the prognosis of patients with esophageal cancer., Methods: The study analyzed 115 patients with esophageal cancer (age ≥ 65 years) who underwent curative esophagectomy. Preoperative sarcopenia was analyzed using the skeletal mass index (SMI), handgrip strength, and gait speed based on the Asian Working Group for Sarcopenia 2019 criteria. Clinicopathologic factors, incidence of postoperative complications, and overall survival (OS) were compared between the sarcopenia and non-sarcopenia groups. The significance of the three individual parameters also was evaluated., Results: The evaluation identified 47 (40.9%) patients with low SMI, 31 (27.0%) patients with low handgrip strength, and 6 (5.2%) patients with slow gait speed. Sarcopenia was diagnosed in 23 patients (20%) and associated with older age and advanced pT stage. The incidence of postoperative complications did not differ significantly between the two groups. Among the three parameters, only slow gait speed was associated with Clavien-Dindo grade 2 or greater complications. The sarcopenia group showed significantly worse OS than the non-sarcopenia group. Those with low handgrip strength tended to have worse OS, and those with slow gait speed had significantly worse OS than their counterparts., Conclusions: Preoperative sarcopenia diagnosed using skeletal muscle mass, muscle strength, and physical function may have an impact on the survival of patients with esophageal cancer., (© 2023. Society of Surgical Oncology.)

Background/aim: CheckMate 577 evaluated adjuvant nivolumab therapy after neoadjuvant chemoradiotherapy and surgery for esophageal cancers. However, the efficacy of this treatment in patients who received neoadjuvant chemotherapy remains unknown. This study investigated the short-term outcomes of adjuvant nivolumab therapy in patients with advanced esophageal squamous cell carcinoma post-neoadjuvant chemotherapy., Patients and Methods: Out of 956 patients with thoracic esophageal cancer who underwent radical esophagectomy, 227 who exhibited ypN1-3 after neoadjuvant chemotherapy and surgery were included in this study., Results: Among 227 patients, 30 received adjuvant nivolumab and 197 received non-nivolumab adjuvant therapy. The nivolumab group displayed a higher number of lymph node metastases compared to the control group. Patients with ypN1-2 tended to have longer recurrence-free survival (RFS) in the nivolumab group than in the non-nivolumab group (p=0.095). In the propensity score-matched cohort, no differences in patient characteristics were observed. Adjuvant nivolumab therapy significantly prolonged RFS in patients who received neoadjuvant chemotherapy (p=0.013). Patients with ypN1-2 in the nivolumab group had significantly longer RFS than their counterparts in the non-nivolumab group (p=0.001), but not in ypN3 (p=0.784). The 1-year postoperative recurrence rates were 59% for the non-nivolumab group and 24% for the nivolumab group (p=0.007). Nivolumab-related adverse events in patients receiving neoadjuvant chemotherapy were mostly consistent across all grades, while the frequency of increased aspartate aminotransferase (AST) levels was relatively higher compared to CheckMate577., Conclusion: Adjuvant nivolumab was more likely to prolong 1-year RFS in patients receiving neoadjuvant chemotherapy, especially in those with ypN1-2, and had acceptable adverse events., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Curative esophagectomy is not always possible in patients with locally advanced esophageal cancer. However, few studies have investigated patients who underwent non-curative surgery with intraoperative judgment. This study aimed to investigate patient characteristics and clinical outcomes for patients undergoing non-curative surgery and compare them between non-resectional and non-radical surgery., Methods: Among 989 consecutive patients with thoracic esophageal squamous cell carcinoma who were preoperatively expected for curative esophagectomy, 66 who were eligible for non-curative surgery were included in this study., Results: Intraoperative diagnosis of T4b accounted for 93% of the reasons for the failure of curative surgery. In those patients, esophageal cancer locally invaded into the aortobronchial constriction (70%), trachea (25%), or pulmonary vein (5%). Lymph node metastasis mainly invaded into the trachea (50%) or bronchus (28%). The overall survival of patients with non-curative surgery was 51.5%, 25.7%, and 10.4% at 6, 12, and 24 months after surgery, respectively. Although there were no differences in preoperative patient characteristics between non-resectional and non-radical surgery, distant metastasis, especially pleural dissemination, was significantly observed in T4b patients due to esophageal cancer with non-radical surgery than those with non-resectional surgery (35% vs. 15%, p = 0.002). Even in patients with non-curative surgery, R1 resection and postoperative chemoradiotherapy were identified as independent factors for survival 1 year after surgery (p = 0.047, and 0.019)., Conclusions: T4b tumor located in aortobronchial constriction or trachea/bronchus makes it difficult to diagnose whether it is resectable or unresectable. Moreover, surgical procedures and perioperative treatment were deeply associated with the clinical outcomes., (© 2023 S. Karger AG, Basel.)

Introduction: Metastatic or unresectable locally advanced oesophageal cancer remains a disease with high mortality. More recently, pembrolizumab plus chemotherapy has been indicated as the first-line treatment for those patients, but the predictive factors for treatment efficacy remain controversial. This study investigated the clinical utility of early tumour shrinkage (ETS) and depth of response (DpR) in metastatic or unresectable oesophageal cancer treated with pembrolizumab plus CF therapy., Methods: ETS and DpR, defined as the percent decreases at the second evaluation and the percentage of the maximal tumour shrinkage during treatment, were measured in 53 eligible patients. The ETS and DpR cut-off values were 20% and 30%, respectively, based on survival outcomes., Results: Twenty-seven patients (51%) were treatment naïve, while 26 (49%) had received any treatment before initiating pembrolizumab plus CF therapy. The median progression-free survival (PFS) and overall survival for ETS ≥20% and &lt;20% were 12.7 and 5.5 months and 14.4 and 8.2 months and 12.7 and 4.9 months and 14.4 and 8.0 months for DpR ≥30% and &lt;30%, respectively. ETS &lt;20% showed early tumour growth, whereas ETS ≥20% had a good response rate with sufficient longer response duration. In addition, an ETS cut-off of 20% predicted the best overall response and was not associated with prior treatment. In multivariable analysis, ETS ≥20% and DpR ≥30% were independent factors of longer PFS., Conclusion: Our findings suggest that an ETS is a promising on-treatment marker for early prediction of further sensitivity to pembrolizumab plus CF therapy., (© 2023 S. Karger AG, Basel.)

Introduction: The prognostic nutritional index (PNI) and D-dimer level are two useful measures for gastric cancer prognosis. As they each comprise different factors, it is possible to employ a more useful combined indicator. This study therefore aimed to establish a PNI-D score - which combines the PNI and D-dimer level - and validate its usefulness as a prognostic marker., Methods: We collected data from 1,218 patients with gastric cancer who had undergone radical gastrectomy (R0) between January 2004 and December 2015. Patients were divided into three PNI-D score groups based on the following criteria: score 2, low-PNI (≤46) and high D-dimer levels (&gt;1.0 µg/mL); score 1, either low-PNI or high D-dimer levels; and score 0, no abnormality. We defined the PNI-D score as low (score 0 or 1) and high (score 2), respectively., Results: The PNI-D score was significantly associated with overall, recurrence-free, and disease-specific survival (all log-rank p &lt; 0.0001). The 5-year overall survival rates of patients with PNI-D scores of low and high were 88.1% and 64.7%, respectively; their 5-year recurrence-free survival rates were 86.7% and 61.3%, respectively; and their 5-year disease-specific survival rates were 99.3% and 76.5%, respectively. Cox multivariate analysis revealed that a high-PNI-D score was an independent, statistically significant prognostic factor for poor overall (p = 0.01) survival in patients with gastric cancer., Conclusions: The PNI-D is an independent prognostic factor for patients with gastric cancer., (© 2024 S. Karger AG, Basel.)

Background/aim: The Japanese Gastric Cancer Treatment Guidelines recommend doublet chemotherapy (S-1 plus another chemotherapy) over S-1 alone for patients with pStage III gastric cancer who underwent radical gastrectomy. However, no consensus exists on adjuvant regimens for patients with pStage III gastric cancer. Therefore, we conducted a comparative study to evaluate the tolerability, safety, and survival outcomes of docetaxel plus S-1 (DS) and S-1 plus oxaliplatin (SOX) therapies as adjuvant chemotherapy for patients with pStage III gastric cancer., Patients and Methods: We retrospectively collected data from consecutive patients with gastric cancer who underwent gastrectomy and received DS or SOX therapies postoperatively at the Osaka International Cancer Institute between December 2016 and December 2021. We conducted a propensity score matching analysis to balance clinical backgrounds., Results: Eighty patients who met the eligibility criteria were analyzed. After matching, 40 patients were included in the study (20 each in the DS and SOX groups). No significant adverse events were observed. The mean ratios of the delivered dose to the planned dose were 74.1% and 86.6% for S-1 and docetaxel in the DS group, respectively, and 75.8% and 76.9% for S-1 and oxaliplatin in the SOX group, respectively. No significant differences were found in recurrence-free and overall survival between the DS and SOX groups (p=0.688 and p=0.772, respectively)., Conclusion: DS and SOX therapies as adjuvants were safe and manageable for patients with pStage III gastric cancer who underwent radical gastrectomy. No significant differences were found in prognosis between the two therapies., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The enhanced recovery after surgery (ERAS) program is expected to improve perioperative outcomes in patients with esophageal cancer. However, how ERAS impacts the postoperative body composition and factors related to compliance rate of ERAS have not been fully investigated., Patients and Methods: The study included 252 consecutive patients with thoracic esophageal cancer who underwent minimally invasive esophagectomy. We compared the postoperative outcomes including body composition between the old perioperative program and the new one that aimed to shorten postoperative length of stay (LOS). Compliance-related clinical factors were also examined., Results: From 252 patients, 129 underwent the old program and 123 the new program. Postoperative LOS, postoperative complications, and hospital costs were reduced with the new program. Body weight loss was significantly improved with the new program at discharge and 3-months after esophagectomy (94.9% vs. 96.6%, p=0.013, 89.5% vs. 91.1%, p=0.028, respectively). Patients in the new program had better body composition at discharge than those in the old program [body fat mass (91.6% vs. 94.1%), lean body mass (95.2% vs. 97.2), and skeletal muscle mass (95.3% vs. 97.0%)]. Major reasons for incompliance were dysphagia, pneumonia, and anastomotic leakage. Multivariate analysis revealed that age ≥70 years at surgery and sex (male) were independent risk factors for incompliance with the postoperative program., Conclusion: The new ERAS program aimed to shorten postoperative LOS had clinical benefits in body composition early after esophagectomy. Personalized ERAS programs based on age might lead to better postoperative outcomes because of low compliance rates for older patients., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Pretreatment metastatic lymph node (LN) size has been reported to be associated with prognosis in esophageal squamous cell carcinoma (ESCC). However, its relationship with response to preoperative chemotherapy or prognosis has not been clarified. We investigated the relationship between metastatic LN size and response to preoperative treatment, and prognosis in patients with metastatic esophageal cancer who underwent surgery., Patients and Methods: A total of 212 clinically node-positive patients who underwent preoperative chemotherapy followed by esophagectomy for ESCC were enrolled. Patients were stratified into three groups on the basis of the length of the short axis of the largest LN in pretreatment computed tomography images: < 10 mm (group A), 10-19 mm (group B), and ≥ 20 mm (group C)., Results: Group A had 90 patients (42%), group B had 103 patients (49%), and group C had 19 patients (9%). Group C had significantly lower percent reduction in total metastatic LN size than groups A and B (22.5% versus 35.7%, P = 0.037). Group C had significantly more metastatic LNs based on histological examination than groups A and B (10.1 versus 2.4, P < 0.001). Group C patients whose LNs responded had significantly fewer metastatic LNs than nonresponders (5.1 versus 11.9, P = 0.042). Group C had significantly poorer overall survival than groups A and B (3-year survival, 25.4% versus 67.3%, P < 0.001). However, group C patients whose LNs responded had better survival than nonresponders (3-year survival, 57.1% versus 0%, P = 0.008)., Conclusions: Patients with large metastatic LNs have poor response and poor prognosis. However, if a response is obtained, long-term survival can be expected., (© 2023. Society of Surgical Oncology.)

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., (© 2022. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Background/aim: Monoclonal antibodies (mAbs) that target tumor antigens have recently been developed. Their antitumor activity is mainly achieved through antibody-dependent cellular cytotoxicity (ADCC) via effector cells such as tumor-infiltrated macrophages and natural killer (NK) cells. CpG oligodeoxynucleotides (ODNs) have potent antitumor activity and are considered to increase the tumor infiltration of macrophages and NK cells; however, a completely solubilized novel CpG-schizophyllan (SPG) complex, K3-SPG, displays more potent antitumor activity. We recently reported the significant antitumor activity of anti-glypican-1 (GPC1) mAb against GPC1-positive esophageal squamous cell carcinoma (ESCC) via ADCC. The aim of this study was to evaluate the potential synergistic antitumor activity of anti-GPC1 mAb and K3-SPG and elucidate the underlying mechanisms using a xenograft model of GPC1-positive human ESCC cells., Materials and Methods: The established human esophageal cancer cell line TE14 was subcutaneously injected into SCID mice. Xenograft mice were treated with anti-GPC1 mAb, K3-SPG, or their combination. Antitumor activity was evaluated by measuring the tumor volume. For FACS analysis, agents were administrated, and tumors were resected 1 day after the final treatment., Results: Anti-GPC1 mAb or K3-SPG monotherapy showed dose-dependent antitumor activity, and combination therapy with anti-GPC1 mAb and K3-SPG showed antitumor activity (p=0.0859). Flow cytometry revealed significantly increased numbers of macrophages (p=0.0133) and of the ratio of activated NK cells/total NK cells (p=0.0058) following K3-SPG or combination therapy., Conclusion: Combination therapy with K3-SPG and anti-GPC1 mAb or another antitumor mAb may represent a new cancer treatment option acting via ADCC., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The use of minimally invasive esophagectomy (MIE) as a treatment for patients with esophageal cancer has recently become more common worldwide. However, differences in the pattern of recurrence between MIE and open esophagectomy (OE) using the transthoracic approach have not been fully investigated, particularly in patients treated with neoadjuvant chemotherapy., Methods: We searched the prospective databases of two institutes for patients with esophageal cancer who underwent neoadjuvant chemotherapy followed by esophagectomy between 2011 and 2018. Propensity score-matched analysis was performed to reduce bias from confounding patient-related variables. Operative outcomes, regionally harvested lymph nodes (LNs), recurrence pattern, and prognosis were investigated in two groups., Results: We identified 410 patients who underwent OE (n = 263) and MIE (n = 147). After propensity score matching, 131 pairs of patients were selected. There were no significant differences in baseline characteristics after matching. The total number of harvested LNs in both groups was similar (55.1 vs. 58.9, P = 0.132). The incidence of LN recurrence in the MIE group was significantly lower than that in the OE group (27% vs. 15%, P = 0.010). In particular, the incidence of mediastinal LN recurrence in the MIE group was significantly lower than that in the OE group (16% vs. 6%, P = 0.017). There were no significant differences between the two groups in hematogenous (19% vs.12%, P = 0.173), dissemination (5% vs. 4%, P = 0.769), local (4% vs. 1%. P = 0.213), and other recurrence (3% vs. 3%, P = 1.000). The 3-year disease-free and overall survival of MIE were significantly better than OE (71.4% vs. 50.5%, P = 0.004 and 80.3% vs. 61.2%, P = 0.002, respectively). Multivariate analysis showed that the thoracic approach (OE vs. MIE) (HR 1.93, P = 0.004) was an independent prognostic factor, along with the pathological N stage (HR 3.05, P < 0.001)., Conclusions: MIE has less intramediastinal LN recurrence than OE and may lead to a better long-term prognosis in patients with advanced esophageal cancer who underwent neoadjuvant chemotherapy., (© 2023. The Society for Surgery of the Alimentary Tract.)

The anastomotic technique after esophagectomy is of great interest in the prevention of anastomotic complications that adversely affect postoperative recovery. This study aimed to compare the clinical outcomes of modified Collard (MC) and circular stapled (CS) anastomoses after esophagectomy. A total of 504 consecutive patients with thoracic esophageal cancer who underwent esophagectomy and cervical esophagogastric CS or MC anastomosis from January 2013 to December 2019 were enrolled. Out of 504 patients, 134 and 370 underwent CS and MC anastomoses. The frequency of anastomotic leakage and stricture was significantly lesser in the MC group than in the CS group (3.0 vs. 10.5%, P = 0.0014 and 11.1 vs. 34.3%, P < 0.001, respectively). CS anastomosis was an independent risk factor for anastomotic stricture (odds ratio, 4.89; P < 0.001). Oral intake was significantly higher in the group without anastomotic stricture than in the group with anastomotic stricture at 2, 3, and 6 months postoperatively (P < 0.001, P = 0.013, and P < 0.001, respectively). The percentage body weight loss (%BWL) was -12.2% in the group with anastomotic stricture and -7.5% in the group without anastomotic stricture at 3 months postoperatively (P = 0.0012). Anastomotic stricture was an independent factor associated with %BWL (odds ratio, 4.86; P = 0.010). Propensity score-matched analysis, which included 88 pairs of patients, confirmed a significantly lower anastomotic stricture rate in the MC group than in the CS group (10.2 vs. 35.2%, P < 0.001). MC anastomosis is better than CS anastomosis for reducing the frequency of anastomotic stricture, which may be useful for maintaining early postoperative nutritional status., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Surgical site infections are common after pancreaticoduodenectomy. Our institution routinely performs intraoperative bile culture with pancreaticoduodenectomy. Herein we examined whether antibiotic selection based on bile culture analysis reduced the surgical site infection risk after pancreaticoduodenectomy., Methods: A total of 349 patients underwent pancreaticoduodenectomy with intraoperative bile cultures in our institution between 2008 and 2019. Patients were categorized into "group A" (196 patients who underwent pancreaticoduodenectomy between 2008 and 2013) or "group B" (153 patients who underwent pancreaticoduodenectomy between 2018 and 2019). Group A received cefazoline perioperatively and for 2 days postoperatively, whereas group B received piperacillin-tazobactam instead based on the bile culture findings in group A., Results: In group A, 91 (46.4%) intraoperative bile cultures were positive, and surgical site infections occurred in 61 patients (31.1%). A total of 32 patients had both positive bile culture and surgical site infection, of whom 23 (71.9%) exhibited the same microorganisms in the biliary and surgical site infection cultures. Due to the common finding of cefazoline-resistant Enterococcus spp. and Enterobacter spp. in group A, group B received piperacillin-tazobactam. Surgical site infection incidence in group B was 18.3% (n = 28), which was significantly lower than in group A (P = .006). Cefazoline-resistant Enterococcus spp. and Enterobacter spp., respectively, were cultured in 69.8% and 24.3% of patients with preoperative biliary drainage, compared with 32.2% and 9.7% of patients without preoperative biliary drainage., Conclusion: The perioperative selection of antibiotics based on bile culture findings at pancreaticoduodenectomy can reduce the incidence of surgical site infection., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Duke pancreatic mono-clonal antigen type 2 (DUPAN-II) is a famous tumour maker for pancreatic cancer (PC) as well as carbohydrate antigen 19-9 (CA19-9). We evaluated the clinical implications of DUPAN-II levels as a biological indicator for PC during preoperative chemoradiation therapy (CRT)., Methods: This retrospective analysis included data from 221 consecutive patients with resectable and borderline resectable PC at diagnosis who underwent preoperative CRT between 2008 and 2017. We focused on 73 patients with elevated pre-CRT DUPAN-II levels (> 230 U/mL; more than 1.5 times the cut-off value for the normal range). Pre- and post-CRT DUPAN-II levels and the changes in DUPAN-II ratio were measured., Results: Univariate analysis identified normalisation of DUPAN-II levels after CRT as a significant prognostic factor (hazard ratio [HR] = 2.06, confidence interval [CI] = 1.03-4.24, p = 0.042). Total normalisation ratio was 49% (n = 36). Overall survival (OS) in patients with normalised DUPAN-II levels was significantly longer than that in 73 patients with elevated levels (5-year survival, 55% vs. 21%, p = 0.032) and in 60 patients who underwent tumour resection (5-year survival, 59% vs. 26%, p = 0.039)., Conclusion: Normalisation of DUPAN-II levels during preoperative CRT was a significant prognostic factor and could be an indicator to monitor treatment efficacy and predict patient prognosis., (© 2023. The Author(s).)

Uveal melanoma (UM) is the most common intraocular tumor in adults, and up to 50% of patients develop metastatic disease, which remains uncurable. Because patients with metastatic UM have an average survival of less than 1 year after diagnosis, there is an urgent need to develop new treatment strategies. Although activating mutations in Gαq or Gα11 proteins are major drivers of pathogenesis, the therapeutic intervention of downstream Gαq/11 targets has been unsuccessful in treating UM, possibly due to alternative signaling pathways and/or resistance mechanisms. Activation of the insulin-like growth factor 1 (IGF1) signaling pathway promotes cell growth, metastasis, and drug resistance in many types of cancers, including UM, where expression of the IGF1 receptor (IGF1R) correlates with a poor prognosis. In this article, we show that direct inhibition of Gαq/11 by the cyclic depsipeptide YM-254890 in combination with inhibition of IGF1R by linsitinib cooperatively inhibits downstream signaling and proliferation of UM cells. We further demonstrate that a 2-week combination treatment of 0.3 to 0.4 mg/kg of YM-254890 administered by intraperitoneal injection and 25 to 40 mg/kg linsitinib administered by oral gavage effectively inhibits the growth of metastatic UM tumors in immunodeficient NOD scid gamma (NSG) mice and identifies the IGF1 pathway as a potential resistance mechanism in response to Gαq/11 inhibition in UM. These data suggest that the combination of Gαq/11 and IGF1R inhibition provides a promising therapeutic strategy to treat metastatic UM., (©2022 American Association for Cancer Research.)

Aim: The aim of this study was to investigate long-term changes in bone mineral density (BMD) after esophagectomy, identify the risk factors for postoperative osteoporosis in patients with esophageal cancer and survival outcomes related to osteoporosis., Methods: We retrospectively evaluated BMD changes for 197 consecutive patients with thoracic esophageal cancer who were disease-free for 5 years after radical esophagectomy. Osteoporosis was diagnosed using computed tomography with an L1 attenuation threshold of ≤110 HU. Survival analysis was performed on 381 consecutive patients with 5-year follow-up after radical esophagectomy., Results: BMD decreased annually after esophagectomy. The median attenuation (HU) was 134.2 before surgery and 135.2, 127.4, 123.3, 115.2, 105.6, and 102.4 at 6 months and 1, 2, 3, 4, and 5 years after surgery, respectively. Osteoporosis was diagnosed in 25.9% patients before surgery and 23.3%, 29.4%, 40.1%, 46.7%, 54.8%, and 60.4% patients with osteoporosis were observed at 6 months and 1, 2, 3, 4, and 5 years after surgery, respectively. Postoperative BMD did not decrease in patients aged ≤54 years, those who had never been smokers, and those with no weight loss after esophagectomy. Multivariate analysis identified that age (≥65 years) at surgery and smoking history were independent risk factors for osteoporosis at 5 years after esophagectomy. Patients with preoperative osteoporosis tended to have worse prognosis in disease-free survival and overall survival than those without osteoporosis, who were more likely to die due to non-esophageal cancer., Conclusion: Esophageal cancer survivors are more likely to develop osteoporosis after esophagectomy, and preoperative osteoporosis might be associated with prognosis., (© 2022 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)

Background: Laparoscopic Billroth-I gastroduodenostomy using a delta-shaped anastomosis is safe and feasible. However, it is often difficult to perform in patients who have a short posterior wall of the duodenum. Thus, we have developed a new method named duodenal overlap functional anastomosis with linear stapler (DOLFIN). We hereby report the technical details of the new method and our preliminary experience performing it., Methods: After the completion of lymphadenectomy, the duodenum was transected craniocaudally with an endoscopic linear stapler. The hepatoduodenal mesentery was dissected approximately 4 cm along the duodenal bulb, and the anastomosis between the posterior wall of the stomach and the lesser curvature of the duodenum was created. The common entry hole was then transected using an endoscopic linear stapler, and the anastomosis was finally completed., Results: There were 36 patients with gastric cancer who underwent laparoscopic distal gastrectomy (LDG) or robotic distal gastrectomy (RDG) with B-I reconstruction using DOLFIN. There were no postoperative complications classified as C-D grade 3 or more and complications related to anastomosis, such as anastomotic leak or stenosis., Conclusions: Our DOLFIN gastroduodenostomy can be performed safely. In addition, it results in good postoperative outcomes. A long-term comparative study is required to further evaluate the clinical usefulness of this method., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: We previously reported the stump closure method for the remnant pancreas in distal pancreatectomy, in which soft coagulation and polyglycolic acid felt attached with fibrin glue were utilized. Transpancreatic mattress suture with polyglactin 910 woven mesh was recently reported as a novel stump closure technique. We developed the modified transpancreatic mattress suture with polyglactin 910 woven mesh method, which combined our polyglycolic acid felt method with the transpancreatic mattress suture with polyglactin 910 woven mesh method., Methods: The polyglycolic acid felt group included patients undergoing distal pancreatectomy in whom the pancreatic stump was closed with the polyglycolic acid felt method from 2017 to 2018 (n = 54); whereas the modified transpancreatic mattress suture with polyglactin 910 woven mesh group included those whose stump was closed with the modified transpancreatic mattress suture with polyglactin 910 woven mesh method from 2019 to 2020 (n = 51). Perioperative parameters, including grade B/C postoperative pancreatic fistula (clinically relevant postoperative pancreatic fistula), were assessed according to the stump closure method., Results: The incidence of clinically relevant postoperative pancreatic fistula was significantly lower in the modified transpancreatic mattress suture with polyglactin 910 woven mesh group than in the polyglycolic acid felt group (7.8% vs 22.2%, P = .036). In multivariate analysis, the use of neoadjuvant chemoradiotherapy and the transpancreatic mattress suture with polyglactin 910 woven mesh method were independent factors for preventing clinically relevant postoperative pancreatic fistula (P = .011 and 0.0038, respectively). Moreover, in the modified transpancreatic mattress suture with polyglactin 910 woven mesh group, the incidence of clinically relevant postoperative pancreatic fistula in patients with a thick pancreas (≥13 mm, 6.7%) was comparably as low as that in patients with a thin pancreas (<13 mm, 9.5%)., Conclusion: The modified transpancreatic mattress suture with polyglactin 910 woven mesh method is an effective stump closure technique to prevent clinically relevant postoperative pancreatic fistula after distal pancreatectomy. Our results warrant further prospective investigation to evaluate the efficacy of the modified transpancreatic mattress suture with polyglactin 910 woven mesh method compared with other standard closure methods (eg, stapler closure or hand-sewn closure)., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Laparoscopic total gastrectomy for early proximal gastric cancer is widely performed. Recently, the number of laparoscopic proximal gastrectomies performed, a surgery limited to early proximal gastric cancer, has gradually increased. However, evidence for the long-term outcomes of laparoscopic total gastrectomy and laparoscopic proximal gastrectomy is insufficient. Therefore, this study aimed to clarify and compare the long-term outcomes of laparoscopic total gastrectomy and laparoscopic proximal gastrectomy with novel valvuloplastic esophagogastrostomy for treatment of clinical stage I proximal gastric cancer., Methods: This study included 111 patients who underwent laparoscopic total gastrectomy or laparoscopic proximal gastrectomy for the treatment of upper third clinical stage I gastric cancer between April 2004 and December 2017. After adjusting for propensity score matching analysis, we compared the postoperative complications, nutritional status, and long-term outcomes between the two groups., Results: After matching the inclusion criteria, 56 patients (28 in each group) were enrolled. No significant differences were noted in the postoperative complications between the two groups. While laparoscopic proximal gastrectomy was associated with lower albumin levels, lower body weight loss was seen by 1 year after surgery and higher hemoglobin levels by 1, 2, and 3 years after surgery. No significant differences were observed in the 3-year overall survival and 3-year recurrence-free survival between the laparoscopic total gastrectomy and laparoscopic proximal gastrectomy groups (P = 0.74 and 0.72, respectively)., Conclusion: Laparoscopic proximal gastrectomy and laparoscopic total gastrectomy for patients with upper third clinical stage I gastric cancer are feasible as regards its safety and outcomes., (© 2022. The Society for Surgery of the Alimentary Tract.)

Background: Outcomes of salvage surgery after failed definitive chemoradiation (CRT) for esophageal cancer have been well defined. However, only a few studies have focused on salvage esophagectomy for recurrent disease after CRT., Methods: In 227 patients with esophageal cancer who underwent salvage esophagectomy after definitive CRT, consisting of 116 patients who underwent esophagectomy for persistent disease (the persistent group) and 111 patients who underwent esophagectomy for recurrent disease (the recurrent group), the short- and long-term outcomes were investigated., Results: The rates of any postoperative complication were similar between the groups (49.1% in the persistent group vs. 49.5% in the recurrent group, p = 0.951), although there was a higher rate of anastomotic leakage in the recurrent group (p = 0.027). Thirty-day mortality was also similar between the groups (1.7% in the persistent group vs. 0.9% in the recurrent group, p = 0.587). The 3-year and 5-year overall survival rates were 33.7% and 28.0% in the persistent group and 48.7% and 41.7% in the recurrent group, respectively (p = 0.0175). In the recurrent group, clinically nodal status before CRT as well as pathologically nodal status and time to relapse were identified as independent prognostic factors. In the persistent group, pT and resection margin were identified as independent factors associated with survival., Conclusions: The present study showed that salvage surgery for recurrent disease can provide acceptable short- and long-term outcomes. Considering clinically and pathologically nodal status and time to relapse, adjuvant therapy might be offered for patients who underwent salvage esophagectomy for recurrent disease after definitive CRT., (© 2022. Society of Surgical Oncology.)

Purpose: Pancreatic fistula is a severe complication after laparoscopic distal gastrectomy (LDG). We previously evaluated the pancreas-left gastric artery angle (PLA) as a risk indicator for developing a pancreatic fistula after LDG. This study evaluated the incidence of pancreatic fistula with robotic distal gastrectomy (RDG) in comparison to LDG from the view of the PLA., Materials and Methods: An association between the PLA and the incidence of pancreatic fistula in 165 patients who underwent either RDG (n=45) or LDG (n=120) was investigated retrospectively., Results: RDG patients had significantly lower drain amylase values (postoperative day 2) than LDG patients. As opposed to LDG patients, drain amylase values were similar for patients with small (PLA <62 degrees) and large (PLA ≥62 degrees) PLA in RDG patients., Conclusion: Robotic surgery may reduce the risk of postoperative pancreatic fistula in patients with a small PLA., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Body composition changes during neoadjuvant therapy and their clinical significance have not been clarified. The present study aimed to investigate body composition changes during neoadjuvant chemoradiation therapy (NACRT) in patients with distal bile duct cancer and the clinical impact on postoperative complications and the prognosis. A total of 16 patients with distal bile duct cancer who underwent curative resection after NACRT were retrospectively evaluated. The area of skeletal muscle, visceral fat and subcutaneous fat on computed tomography and immunological and nutritional indices were assessed before and after NACRT. All 16 patients completed NACRT followed by pancreaticoduodenectomy without mortality. There was no significant change in the skeletal muscle mass index (SMI) during NACRT. Of the 16 patients, nine (56%) were defined as sarcopenic before NACRT, and eight (50%) met the criteria for sarcopenic after NACRT. The SMI and total fat area were significantly associated with postoperative pancreatic fistula (POPF) (P=0.019 and P=0.007, respectively). The patients with sarcopenia had a shorter disease-free survival time and overall survival time in comparison to patients without sarcopenia (P=0.025 and P=0.115, respectively). In conclusion, NACRT for distal bile duct cancer did not significantly affect the body composition, or the immunological or nutritional indices. Sarcopenia after NACRT was significantly associated with early recurrence in patients with distal bile duct cancer who received NACRT., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020, Spandidos Publications.)

Aim: Dysphagia is one of the most common complications after esophagectomy. However, no study has investigated the long-term postoperative outcomes in patients with postoperative dysphagia. Here, we aimed to identify risk factors for postoperative dysphagia and to investigate long-term postoperative outcomes in such patients., Methods: This study included 304 consecutive patients with thoracic esophageal cancer who underwent curative esophagectomy. They were diagnosed with postoperative dysphagia through a contrast videofluoroscopic swallowing study, and postoperative outcomes were compared based on swallowing function., Results: In total, 112 patients (37%) were diagnosed with postoperative dysphagia. Older age, low BMI, and recurrent laryngeal nerve palsy were identified as independent risk factors for postoperative dysphagia. In the dysphagia group, a significantly larger number of patients developed in-hospital pneumonia, and hospital stays were also significantly extended. After discharge, 37 (33%) patients with postoperative dysphagia developed pneumonia. Even more than 1 year after esophagectomy, a significantly larger number of patients (24 patients, 21%) with postoperative dysphagia developed pneumonia compared to those without postoperative dysphagia. Postoperative dysphagia was identified as an independent risk factor for out-of-hospital pneumonia. Regarding nutritional status, there was no difference in weight loss 1 year after esophagectomy, but significant weight loss was observed 2 years after esophagectomy in the dysphagia group., Conclusion: Postoperative dysphagia was associated with both preoperative patient factors and surgical factors. Moreover, patients with postoperative dysphagia had long-term and short-term pneumonia risk. The personalization of long-term follow-up through more aggressive rehabilitation and nutritional guidance is required for patients with postoperative dysphagia., (© 2022 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterology.)

Background: Gastric cancer with portal vein tumor thrombus (PVTT) is poor prognosis, and the treatment remains challenging. Regarding surgery, there are only reports of highly invasive laparotomy. We report some techniques of the completely robotic total gastrectomy with thrombectomy and portal vein reconstruction for the patient with gastric cancer and PVTT for the first time., Case Presentation: A 79-year-old man was diagnosed with a 5-cm gastric cancer on the side of the lesser curvature from the middle of the gastric body to the cardia. Computed tomography revealed a massive PVTT extending from the left gastric vein to the portal trunk (28 x 16 mm). There were no other distant metastases. After 3 cycles of the chemotherapy, the PVTT shrank to 19 x 12 mm. After obtaining informed consent from the patient, robotic total gastrectomy with regional lymphadenectomy and thrombectomy were performed. We used the da Vinci Xi Surgical System. A 3-cm incision was made at the umbilicus, and a wound retractor was placed. Five additional ports were placed. The right side suprapancreatic lymph nodes were performed at the time of the thrombectomy. It was important to identify the precise extent of the PVTT with intraoperative ultrasonography before the thrombectomy. After PVTT identification, the portal trunk was clamped above and below the tumor thrombus with vascular clips. The membrane on the anterior wall of the portal trunk around the PVTT was carefully incised with da Vinci Scissors. The tumor thrombus was completely enucleated without separation. The incised part of the portal trunk was reconstructed with continuous 5-0 synthetic monofilament nonabsorbable polypropylene sutures. After removing the vascular clamps, we made sure there was no leakage from the portal vein and no tumor thrombus remnants with intraoperative ultrasonography. Robotic total gastrectomy with lymphadenectomy and Roux-en-Y reconstruction were performed. The patient was discharged without complications. The patient has remained alive for 30 months after surgery., Conclusions: Robotic total gastrectomy with thrombectomy and portal vein reconstruction is a safe, minimally invasive, and precise surgery. It may contribute to improved prognosis of gastric cancer with PVTT when combined with chemotherapy., (© 2022. The Author(s).)

Background: Preoperative chemoradiation therapy (CRT) or chemotherapy (CT) followed by surgery is currently being administered for advanced esophageal cancer. However, few studies have directly compared CRT and CT for treating locally advanced esophageal carcinoma. This study aimed to assess postoperative recurrence patterns and post-recurrence outcomes in patients with radical esophagectomy after CRT or triplet CT regimen with docetaxel, cisplatin, and 5-fluorouracil (DCF)., Methods: This study included 325 consecutive patients with thoracic esophageal cancer who received preoperative CRT or DCF followed by curative esophagectomy between January 2010 and December 2019. We compared recurrence patterns after surgery and post-recurrence treatments between CRT and DCF. Locoregional recurrence was defined as recurrences at the primary tumor site or regional lymph nodes. Distant recurrence was defined as non-regional lymph node recurrences, systemic metastases, malignant pleural effusions, or peritoneal metastases., Results: Among 325 patients, 74 received preoperative CF + RT and 251 received preoperative DCF. A propensity score-matched cohort of 53 with CRT and 53 with DCF was included. CRT patients had tumors located in the upper esophagus and had more advanced cancer than DCF patients; however, no differences in patient characteristics were observed in the matched cohort. CRT patients had better histopathological responses and control of locoregional recurrence than DCF patients. On the other hand, distant recurrence, especially in the non-regional lymph node, lung, and pleural dissemination, significantly developed more frequently in CRT patients. Furthermore, CRT patients may have received insufficient post-recurrence treatment, owing to fewer treatment options. Therefore, although there was no difference in recurrence rate in the two groups, CRT patients had significantly poorer post-recurrence survival than DCF patients., Conclusions: Preoperative DCF could reduce distant recurrence after surgery compared to preoperative CRT. The differences in recurrence patterns can be related to the selection of post-recurrence treatment and their prognosis after recurrence., (© 2022 S. Karger AG, Basel.)

Introduction: The pancreas often interferes with the surgical field during laparoscopic gastrectomy (LG) and its disorders cause severe postoperative complications. This study aimed to evaluate the association between the anatomical location of the pancreas and surgical outcome and to investigate the optimal surgical position in LG., Methods: We newly defined the angle formed between the supra-pancreatic region and the root of the left gastric artery (LGA) as the pancreas-LGA angle (PLA). The association between PLA and surgical outcomes in 107 consecutive patients who underwent laparoscopic distal gastrectomy (LDG) was investigated. Then, the change in PLA before and after insertion of the back pillow in 30 patients with gastric cancer was examined., Results: The median PLA was 62° (range, 2°-157°). No differences were found in the patient background between patients with small PLA (PLA < 62°; n = 53) and those with large PLA (PLA ≧ 62°; n = 54). The postoperative inflammation response (white blood cells, neutrophils, and C-reactive protein) and amylase concentration in the drainage fluid (D-AMY) were significantly higher in the small PLA group than large PLA group. Multivariable analyses demonstrated that small PLA was an independent risk factor for high D-AMY. After insertion of a back pillow, PLA was noninvasively increased in all patients, and the median PLA was changed to 92° (range, 8°-151°) from 61° (range, 2°-140°). Of 17 patients with small PLA, nine developed large PLA., Conclusions: These results suggest that PLA can become one of the indicators of postoperative complications related to anatomical patient factors in LDG., (© 2021 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Purpose: The perforation of the upper gastrointestinal tract is still associated with a high risk of complications and mortality. We aimed to evaluate the optimal treatment and post-treatment complications for this condition., Methods: This was a retrospective, single-center study conducted between 2010 and 2019. We analyzed 50 patients with intraperitoneal free air caused by peptic ulcer (44 cases) or cancer (six cases)., Results: All patients initially received either conservative therapy (n = 7) or surgery (n = 43). The nonsurgically cured patients were significantly younger and had mild peritonitis and also had a shorter hospital stay. Two patients were converted to surgery due to worsening symptoms, and one of them was elderly and had a long perforation-to-treatment time. Regarding postoperative complications, patients with Grade II-V (n = 21) were significantly older and had a poorer physical status, longer perforation-to-surgery time, and higher preoperative CRP and lactate than those with Grade 0-I (n = 24). Multivariable analyses identified elevated preoperative lactate as an independent risk factor for postoperative complications. The patients with noncurative surgery for perforated advanced gastric cancer all died within 1 year after surgery., Conclusions: Consideration should be given to the nonsurgical indications in elderly and delayed treatment patients and the postoperative outcomes of patients with preoperatively elevated lactate levels., (© 2021. Springer Nature Singapore Pte Ltd.)

The propensity of uveal melanoma to metastasize to the liver hinders the accrual of micro-metastatic and end-stage disease tissue samples and restricts the investigation of metastatic uveal melanoma (MUM). Pre-clinical experimental animal models of MUM can help elucidate the pathophysiology of metastatic lesions and provide a tool for designing new therapeutic approaches for MUM. Here, we present an advanced model of hepatic metastases that enables quantitatively visualizing the development of individual hepatic tumor clones and estimating their growth kinetics and colonization efficiency. Similar to clinically observed liver metastases, these models enable the assessment of growth kinetics of the liver micro-metastases and the testing of therapeutic approaches for the treatment of MUM. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Experimental patient-derived xenograft mouse model of metastatic uveal melanoma Basic Protocol 2: Experimental liver micro-metastatic mouse model using splenic injection of metastatic uveal melanoma cells., (© 2021 Wiley Periodicals LLC.)

Background: Patients with metastatic uveal melanoma (MUM) in the liver usually die within 1 year. The development of new treatments for MUM has been limited by the lack of diverse MUM cell lines and appropriate animal models. We previously reported that orthotopic xenograft mouse models established by direct injection of MUM cells into the liver were useful for the analysis associated with tumor microenvironment in the liver. However, considering that patients with UM metastasize to the liver hematogenously, direct liver injection model might not be suitable for investigation on various mechanisms of liver metastasis. Here, we aim to establish new orthotopic xenograft models via hematogenous dissemination of tumor cells to the liver, and to compare their characteristics with the hepatic injection model. We also determine if hepatic tumors could be effectively monitored with non-invasive live imaging., Methods: tdtTomate-labeled, patient-derived MUM cells were injected into the liver, spleen or tail vein of immunodeficient NSG mice. Tumor growth was serially assessed with In Vivo Imaging System (IVIS) images once every week. Established hepatic tumors were evaluated with CT scan and then analyzed histologically., Results: We found that splenic injection could consistently establish hepatic tumors. Non-invasive imaging showed that the splenic injection model had more consistent and stronger fluorescent intensity compared to the hepatic injection model. There were no significant differences in tumor growth between splenic injection with splenectomy and without splenectomy. The splenic injection established hepatic tumors diffusely throughout the liver, while the hepatic injection of tumor cells established a single localized tumor. Long-term monitoring of tumor development showed that tumor growth, tumor distribution in the liver, and overall survival depended on the number of tumor cells injected to the spleen., Conclusion: We established a new orthotopic hepatic metastatic xenograft mouse model by splenic injection of MUM cells. The growth of orthotopic hepatic tumors could be monitored with non-invasive IVIS imaging. Moreover, we evaluated the therapeutic effect of a MEK inhibitor by using this model. Our findings suggest that our new orthotopic liver metastatic mouse model may be useful for preclinical drug screening experiments and for the analysis of liver metastasis mechanisms.

Background: Pancreatic cancer (PDAC) is the most lethal malignancy. New treatment options for it are urgently required. The aim was to develop an antibody-drug conjugate (ADC) targeting glypican-1 (GPC-1) as a new therapy for PDAC., Methods: We evaluated GPC-1 expression in resected PDAC specimens and PDAC cell lines. We then measured the antitumour effect of anti-GPC-1 monoclonal antibody conjugated with the cytotoxic agent monomethyl auristatin F (MMAF) in vitro and in vivo., Results: GPC-1 was overexpressed in most primary PDAC cells and tissues. The PDAC cell lines BxPC-3 and T3M-4 strongly expressed GPC-1 relative to SUIT-2 cells. Compared with control ADC, GPC-1-ADC showed a potent antitumour effect against BxPC-3 and T3M-4, but little activity against SUIT-2 cells. In the xenograft and patient-derived tumour models, GPC-1-ADC significantly and potently inhibited tumour growth in a dose-dependent manner. GPC-1-ADC-mediated G2/M-phase cell cycle arrest was detected in the tumour tissues of GPC-1-ADC-treated mice relative to those of control-ADC-treated mice., Conclusions: GPC-1-ADC showed significant tumour growth inhibition against GPC-1-positive pancreatic cell lines and patient-derived, GPC-1-positive pancreatic cancer tissues. Our preclinical data demonstrated that targeting GPC-1 with ADC is a promising therapy for patients with GPC-1-positive pancreatic cancer.