Prognostic impact of nodal status and lymphovascular invasion in patients undergoing neoadjuvant chemotherapy for esophageal squamous cell carcinoma.

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.

Significance of Comprehensive Analysis of Preoperative Sarcopenia Based on Muscle Mass, Muscle Strength, and Physical Function for the Prognosis of Patients with Esophageal Cancer.

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.

Short-term Outcomes of Adjuvant Nivolumab After Neoadjuvant Chemotherapy in Patients With Resected Esophageal Squamous Cell Carcinoma.

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.

Clinical Impact of Early Tumour Shrinkage in Metastatic or Unresectable Oesophageal Cancer Treated with Pembrolizumab plus Chemotherapy.

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 (OS) for ETS ≥20% and <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 <30%, respectively. ETS <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.

Prognostic value of a novel index combining the prognostic nutritional index and D-dimer levels for gastric cancer after gastrectomy.

INTRODUCTION: The prognostic nutritional index and D-dimer level are two useful measures for gastric cancer prognosis. Since they each comprise different factors, it is possible to employ a more useful combined indicator. This study therefore aimed to establish a prognostic nutritional index-D score-which combines the prognostic nutritional index 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 prognostic nutritional index-D score groups based on the following criteria: score 2, low prognostic nutritional index (≤46) and high D-dimer levels (>1.0 µg/ml); score 1, either a low prognostic nutritional index or high D-dimer levels; and score 0, no abnormality. We then defined the PNI-D score as low (score 0 or 1) and high (score 2). RESULTS: The prognostic nutritional index-D score was significantly associated with overall, recurrence-free, and disease-specific survival (all log-rank P<0.0001). The 5-year overall survival rates of the patients with prognostic nutritional index-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 prognostic nutritional index-D score was an independent, statistically significant prognostic factor for poor overall (P=0.01) survival in the patients with gastric cancer. CONCLUSIONS: The prognostic nutritional index-D is an independent prognostic factor for patients with gastric cancer.

Adjuvant Chemotherapy With S-1 Plus Docetaxel Versus S-1 Plus Oxaliplatin in Stage III Gastric Cancer.

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.

Metastases and treatment-resistant lineages in patient-derived cancer cells of colorectal cancer.

Circulating tumor cells (CTCs) play an important role in metastasis and recurrence. However, which cells comprise the complex tumor lineages in recurrence and are key in metastasis are unknown in colorectal cancer (CRC). CRC with high expression of POU5F1 has a poor prognosis with a high incidence of liver metastatic recurrence. We aim to reveal the key cells promoting metastasis and identify treatment-resistant lineages with established EGFP-expressing organoids in two-dimensional culture (2DOs) under the POU5F1 promotor. POU5F1-expressing cells are highly present in relapsed clinical patients' blood as CTCs. Sorted POU5F1-expressing cells from 2DOs have cancer stem cell abilities and abundantly form liver metastases in vivo. Single-cell RNA sequencing of 2DOs identifies heterogeneous populations derived from POU5F1-expressing cells and the Wnt signaling pathway is enriched in POU5F1-expressing cells. Characteristic high expression of CTLA4 is observed in POU5F1-expressing cells and immunocytochemistry confirms the co-expression of POU5F1 and CTLA4. Demethylation in some CpG islands at the transcriptional start sites of POU5F1 and CTLA4 is observed. The Wnt/ß-catenin pathway inhibitor, XAV939, prevents the adhesion and survival of POU5F1-expressing cells in vitro. Early administration of XAV939 also completely inhibits liver metastasis induced by POU5F1-positive cells.

Clinicopathological characteristics and survival outcomes in patients with advanced esophageal squamous cell carcinoma who were intraoperatively diagnosed non-curative.

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 (ESCC) 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%). LN 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 CRT 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.

A multicenter prospective observational study of lymph node metastasis patterns and short-term outcomes of extended lymphadenectomy in right-sided colon cancer.

Background: The lymph node metastasis rate in right-sided colon cancer is unknown, and the optimal central vascular ligation level remains controversial. We aimed to determine the lymph node metastasis rate and short-term results of radical surgery with extended lymph node dissection in right-sided colon cancer. Methods: This prospective multicenter observational study included patients with stage II/III right-sided colon cancer from five cancer hospitals. The metastasis rate of each node station was analyzed according to tumor location and main feeding artery. Results: Between April 2018 and August 2021, 208 patients underwent dissection around the superior mesenteric artery (SMA) and vein (SMV). In transverse colon cancer, 7.5% and 2.5% of metastases occurred around the SMV and SMA at the root of the middle colic artery (MCA), respectively; 6.7% and 6.7% at the root of the right colic artery. In caecal cancer, 1.9% of metastases occurred around the SMV and 1.9% around the SMA. In ascending colon cancer, the rate was 1.1% around the SMV. Of the tumors, 17% fed mainly by the ileocolic artery had node metastases along the middle or right colic artery, as did 66.7% fed mainly by the right colic artery and 41.2% fed by the MCA (p = 0.01). Postoperative complications occurred in 42 patients (20.2%). Conclusion: Routine prophylactic extended lymphadenectomy around the SMA might not be necessary in caecum and ascending colon cancer. Dissection around the SMA may be necessary in cases of transverse colon cancer or when the feeding artery is the MCA.

Clinical Impact of Enhanced Recovery After Esophagectomy in Patients With Esophageal Cancer.

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.

Efficacy of transanal drainage tube in preventing anastomotic leakage after surgery for rectal cancer: A meta-analysis.

BACKGROUND: Anastomotic leakage (AL) following rectal cancer surgery is an important cause of mortality and recurrence. Although transanal drainage tubes (TDTs) are expected to reduce the rate of AL, their preventive effects are controversial. AIM: To reveal the effect of TDT in patients with symptomatic AL after rectal cancer surgery. METHODS: A systematic literature search was performed using the PubMed, Embase, and Cochrane Library databases. We included randomized controlled trials (RCTs) and prospective cohort studies (PCSs) in which patients were assigned to two groups depending on the use or non-use of TDT and in which AL was evaluated. The results of the studies were synthesized using the Mantel-Haenszel random-effects model, and a two-tailed P value > 0.05 was considered statistically significant. RESULTS: Three RCTs and two PCSs were included in this study. Symptomatic AL was examined in all 1417 patients (712 with TDT), and TDTs did not reduce the symptomatic AL rate. In a subgroup analysis of 955 patients without a diverting stoma, TDT reduced the symptomatic AL rate (odds ratio = 0.50, 95% confidence interval: 0.29-0.86, P = 0.012). CONCLUSION: TDT may not reduce AL overall among patients undergoing rectal cancer surgery. However, patients without a diverting stoma may benefit from TDT placement.

Preoperative D-dimer Value and Lower Limb Venous Ultrasound for Deep Venous Thrombosis Prevents Postoperative Symptomatic Venous Thromboembolism in Patients Undergoing Colorectal Surgery: A Retrospective Study.

Objectives: Preoperative deep venous thrombosis (DVT) can cause potentially life-threatening postoperative venous thromboembolism (VTE). Lower limb venous ultrasound (LLVU) is a modality that can detect DVT. However, the threshold for performing preoperative LLVU in the population undergoing colorectal resection is controversial. In this context, we evaluated whether a preoperative D-dimer value can identify patients who benefit from LLVU from the perspective of preventing postoperative symptomatic VTE. Methods: Patients undergoing colorectal resection in our institute from 2013 to 2020 were retrospectively enrolled (n=2071). We divided the patients into two groups: the clinical indication group (CG: including patients from 2013 to 2016, n=875) and the D-dimer-orientated group (DG: including patients from 2017 to 2020, n=1196). In the CG, LLVU was performed when DVT was clinically suspected; in the DG, preoperative LLVU was performed in patients with a preoperative D-dimer>1.0 µg/ml. Results: In the surveyed period, 277 LLVUs were performed, among which DVT was detected in 34 cases (12.3%). In the CG, DVT was detected in 0.7% of patients, whereas in the DG, it was detected in 2.3% of patients. Postoperative symptomatic VTE was significantly reduced in the DG at both 3 and 6 months after surgery (p=0.041 and 0.020, respectively). Moreover, Multivariate analysis showed that a past medical history of PE and treatment following the CG protocol were independent risk factors for postoperative symptomatic VTE within 6 months of surgery (p<0.0001 and =0.036, respectively). Conclusions: LLVU in patients with a preoperative D-dimer>1.0 µg/ml is a useful method to prevent postoperative symptomatic VTE.

Long-term changes in bone mineral density in postoperative patients with esophageal cancer.

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.

Modified Collard technique is more effective than circular stapled for cervical esophagogastric anastomosis in prevention of anastomotic stricture: a propensity score-matched study.

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.

Blood Perfusion Assessment by Indocyanine Green Fluorescence Imaging for Minimally Invasive Rectal Cancer Surgery (EssentiAL trial): A Randomized Clinical Trial.

OBJECTIVE: The aim of the present randomized controlled trial was to evaluate the superiority of indocyanine green fluorescence imaging (ICG-FI) in reducing the rate of anastomotic leakage in minimally invasive rectal cancer surgery. BACKGROUND: The role of ICG-FI in anastomotic leakage in minimally invasive rectal cancer surgery is controversial according to the published literature. METHODS: This randomized, open-label, phase 3, trial was performed at 41 hospitals in Japan. Patients with clinically stage 0-III rectal carcinoma less than 12 cm from the anal verge, scheduled for minimally invasive sphincter-preserving surgery were preoperatively randomly assigned to receive a blood flow evaluation by ICG-FI (ICG+ group) or no blood flow evaluation by ICG-FI (ICG- group). The primary endpoint was the anastomotic leakage rate (grade A+B+C, expected reduction rate of 6%) analyzed in the modified intention-to-treat population. RESULTS: Between December 2018 and February 2021, a total of 850 patients were enrolled and randomized. After the exclusion of 11 patients, 839 were subject to the modified intention-to-treat population (422 in the ICG+ group and 417 in the ICG- group). The rate of anastomotic leakage (grade A+B+C) was significantly lower in the ICG+ group (7.6%) than in the ICG- group (11.8%) (relative risk, 0.645; 95% confidence interval 0.422-0.987; P =0.041). The rate of anastomotic leakage (grade B+C) was 4.7% in the ICG+ group and 8.2% in the ICG- group ( P =0.044), and the respective reoperation rates were 0.5% and 2.4% ( P =0.021). CONCLUSIONS: Although the actual reduction rate of anastomotic leakage in the ICG+ group was lower than the expected reduction rate and ICG-FI was not superior to white light, ICG-FI significantly reduced the anastomotic leakage rate by 4.2%.

Lymph node metastasis in T1 colorectal cancer: Risk factors and prediction model.

Endoscopic resection is typically performed for early T1 stage colorectal cancer (T1 CRC). Additional surgery is subsequently recommended based on pathological findings; however, the current criteria may result in overtreatment. The present study aimed to re-examine the reported risk factors for lymph node (LN) metastasis in T1 CRC and develop a prediction model using a large multi-institutional dataset. In this retrospective study, the medical records of 1,185 patients with T1 CRC who underwent surgery between January 2008 and December 2020 were investigated. Slides pathologically re-assessable for additional risk factors were re-examined. A total of 251 patients with inadequate data were excluded, and 934 patients were randomly assigned at a ratio of 3:1 to the training and validation datasets. In the univariate analysis, left-sided CRC (P=0.003), deep submucosal invasion depth (P=0.005), poor histological grade (P=0.020), lymphatic invasion (P<0.001), venous invasion (P<0.001) and tumor budding grade 2/3 (P<0.001) were significant risk factors for LN metastasis. A nomogram predicting LN metastasis was developed using these variables, with an area under the received operating characteristic curve (AUC) of 0.786. The nomogram was validated using a validation set with an AUC of 0.721, indicating moderate accuracy. No LN metastases were observed in patients with <90 points using the nomogram; therefore, patients with a low nomogram score may avoid undergoing surgical resection. Prediction of LN metastasis using this developed nomogram may help identify patients who are at high-risk who require surgery.

Tumor Deposit Is an Independent Factor Predicting Early Recurrence and Poor Prognosis in Gastric Cancer.

BACKGROUND: Accurate prognostic estimation is crucial; however, the prognostic value of tumor deposits in gastric cancer remains controversial. This study aimed to investigate their prognostic significance. METHODS: Clinicopathological and prognostic data of 1012 gastric cancer patients who underwent R0 or R1 surgery from 2010 to 2017 at the Osaka International Cancer Institute were retrospectively reviewed. RESULTS: Overall, 6.3% patients had tumor deposits, which were associated with Borrmann type, surgical procedure, type of gastrectomy, extent of lymphadenectomy, tumor size, histology, pT, pN, pM, pStage, lymphatic invasion, vascular invasion, preoperative chemotherapy, and postoperative chemotherapy. Tumor deposit-positive patients had worse 5-year disease-free survival (32.60% vs. 92.45%) and overall survival (41.22% vs. 89.37%) than tumor deposit-negative patients. Subgroup analysis regarding pStage II-III also showed significant differences between patients with and without tumor deposits for 5-year disease-free survival (34.15% vs. 80.98%) and overall survival (43.17% vs. 75.78%). Multivariable analysis showed that older age, undifferentiated histology, deeper tumor invasion, lymph node metastasis, distant metastasis, and presence of tumor deposits were significantly correlated with early tumor recurrence and shorter survival time; these factors were identified as independent prognostic factors. The 5-year disease-free survival of tumor deposit-positive patients was significantly worse than that of patients in the pStage III group and comparable to that of patients in the pT4, pN3, and pM1 groups. The 5-year overall survival of tumor deposit-positive patients was comparable to that of the pT4, pN3, pM1, and pStage III groups. CONCLUSIONS: Tumor deposits are strong and independent predictors of tumor recurrence and poor survival.

DUPAN-II normalisation as a biological indicator during preoperative chemoradiation therapy for resectable and borderline resectable pancreatic cancer.

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.