Long-term Outcome After Surgical Resection of Paraaortic Lymph Node Metastasis of Colorectal Cancer: A Multicenter Retrospective Study.

BACKGROUND: The significance of resection of paraaortic lymph node metastasis in colorectal cancer is controversial. OBJECTIVE: To clarify the prognosis of colorectal cancer after paraaortic lymph node metastasis resection. DESIGN: Multicenter retrospective study. SETTINGS: Thirty-six institutions in Japan participated in this study. PATIENTS: Patients with resected and pathologically proven paraaortic lymph node metastasis of CRC between 2010 and 2015. DATA SOURCES: Database and medical records at each institution. MAIN OUTCOME MEASURES: Overall survival after paraaortic lymph node metastasis resection, recurrence-free survival, and recurrence patterns after R0 resection of paraaortic lymph node metastasis. RESULTS: A total of 133 patients were included in the primary analysis population in this study. The 5-year overall survival rate (95% confidence interval [CI]) was 41.0% (32.0, 49.8), and the median survival (95% CI) was 4.1 (3.4, 4.7) years. Independent prognostic factors for overall survival were the pathological T stage (pT4 vs. pT1- 3, adjusted hazard ratio [aHR]: 1.91, p = 0.006), other organ metastasis (present vs. absent, aHR: 1.98, p = 0.005), time to metastases (synchronous vs. metachronous, aHR: 2.02, p = 0.02), and number of paraaortic lymph node metastasis (≥3 vs. <3, aHR: 2.13, p = 0.001). The 5-year recurrence-free survival rate (95% CI) was 21.1% (13.5, 29.7), with a median (95% CI) of 1.2 (0.9, 1.4) years. The primary tumor location (left- vs. right-sided colon, aHR: 4.77, p = 0.01; rectum vs. right-sided colon, aHR: 5.27, p = 0.006), other organ metastasis (present vs. absent, aHR: 1.90, p = 0.03), number of paraaortic lymph node metastasis (≥3 vs. <3, aHR: 2.20, p = 0.001), and hospital volume (<10 vs. ≥10, aHR: 2.18, p = 0.02) were identified as independent prognostic factors for recurrence-free survival. Paraaortic lymph node recurrence was the most common at 33.3%. LIMITATIONS: Selection bias cannot be ruled out because of the retrospective nature of the study. CONCLUSIONS: Less than three paraaortic lymph node metastasis was a favorable prognostic factor for both overall survival and recurrence-free survival. However, paraaortic lymph node metastases were considered to be a systemic disease and the significance of resection was limited. See Video Abstract.

Short- and long-term outcomes of surgical treatment for inguinal lymph node metastasis in rectal and anal canal adenocarcinoma.

AIM: The significance of lymphadenectomy and its indications in patients with inguinal lymph node metastasis (ILNM) of anorectal adenocarcinoma is unclear. This study aimed to clarify the surgical outcomes and prognostic factors of inguinal lymphadenectomy for ILNM. METHOD: This study included patients who underwent surgical resection for ILNM of rectal or anal canal adenocarcinoma with pathologically positive metastases between 1997 and 2011 at 20 participating centres in the Study Group for Inguinal Lymph Node Metastasis from Colorectal Cancer organized by the Japanese Society for Cancer of the Colon and Rectum. Clinicopathological characteristics and short- and long-term postoperative outcomes were retrospectively analysed. RESULTS: In total, 107 patients were included. The primary tumour was in the rectum in 57 patients (53.3%) and in the anal canal in 50 (46.7%). The median number of ILNMs was 2.34. Postoperative complications of Clavien-Dindo Grade III or higher were observed in five patients. The 5-year overall survival rate was 38.8%. Multivariate analysis identified undifferentiated histological type (P < 0.001), pathological venous invasion (P = 0.01) and pathological primary tumour depth T0-2 (P = 0.01) as independent prognostic factors for poor overall survival. CONCLUSION: The 5-year overall survival after inguinal lymph node dissection was acceptable, and it warrants consideration in more patients. Further larger-scale studies are needed in order to clarify the surgical indications.

The preliminary analysis of lymphatic flow around the connective tissues surrounding SMA and SpA elucidates patients' oncological condition in borderline-resectable pancreatic cancer.

BACKGROUND: In pancreatic ductal adenocarcinoma (PDAC), invasion of connective tissues surrounding major arteries is a crucial prognostic factor after radical resection. However, why the connective tissues invasion is associated with poor prognosis is not well understood. MATERIALS AND METHODS: From 2018 to 2020, 25 patients receiving radical surgery for PDAC in our institute were enrolled. HyperEye Medical System (HEMS) was used to examine lymphatic flow from the connective tissues surrounding SMA and SpA and which lymph nodes ICG accumulated in was examined. RESULTS: HEMS imaging revealed ICG was transported down to the paraaortic area of the abdominal aorta along SMA. In pancreatic head cancer, 9 paraaortic lymph nodes among 14 (64.3%) were ICG positive, higher positivity than LN#15 (25.0%) or LN#18 (50.0%), indicating lymphatic flow around the SMA was leading directly to the paraaortic lymph nodes. Similarly, in pancreatic body and tail cancer, the percentage of ICG-positive LN #16a2 was very high, as was that of #8a, although that of #7 was only 42.9%. CONCLUSIONS: Our preliminary result indicated that the lymphatic flow along the connective tissues surrounding major arteries could be helpful in understanding metastasis and improving prognosis in BR-A pancreatic cancer.

Impact of resection for ovarian metastases from colorectal cancer and clinicopathologic analysis: A multicenter retrospective study in Japan.

Aim: The aim of this study was to clarify the significance of resection of ovarian metastases from colorectal cancer and to identify the clinicopathologic characteristics. Methods: In this multicenter retrospective study, we evaluated data on ovarian metastases from colorectal cancer obtained from patients at 20 centers in Japan between 2000 and 2014. We examined the impact of resection on the prognosis of patients with ovarian metastases and examined prognostic factors. Results: The study included 296 patients with ovarian metastasis. The 3-y overall survival rate was 68.6% for solitary ovarian metastases. In all cases of this cohort, the 3-y overall survival rates after curative resection, noncurative resection, and nonresection were 65.9%, 31.8%, and 6.1%, respectively (curative resection vs noncurative resection [P < 0.01] and noncurative resection vs nonresection [P < 0.01]). In the multivariate analysis of prognostic factors, tumor size of ovarian metastasis (P < 0.01), bilateral ovarian metastasis (P = 0.01), peritoneal metastasis (P < 0.01), pulmonary metastasis (P = 0.04), liver metastasis (P < 0.01), and remnant of ovarian metastasis (P < 0.01) were statistically significantly different. Conclusion: The prognosis after curative resection for solitary ovarian metastases was shown to be relatively favorable as Stage IV colorectal cancer. Resection of ovarian metastases, not only curative resection but also noncurative resection, confers a survival benefit. Prognostic factors were large ovarian metastases, bilateral ovarian metastases, the presence of extraovarian metastases, and remnant ovarian metastases.

Assessing Intra-abdominal status for clinically relevant postoperative pancreatic fistula based on postoperative fluid collection and drain amylase levels after distal pancreatectomy.

Aim: The aim of this study was to evaluate the intra-abdominal status related to postoperative pancreatic fistula by combining postoperative fluid collection and drain amylase levels. Methods: We retrospectively reviewed the data of 203 patients who underwent distal pancreatectomy and classified their postoperative abdominal status into four groups based on postoperative fluid collection size and drain amylase levels. We also evaluated the incidence of clinically relevant postoperative pancreatic fistula in each group according to C-reactive protein values. Results: The incidence of clinically relevant postoperative pancreatic fistula in the entire cohort (n = 203) was 28.1%. Multivariate analysis revealed that postoperative fluid collection, drain amylase levels, and C-reactive protein levels are considerable risk factors for clinically relevant postoperative pancreatic fistula. In the subgroup with large postoperative fluid collection and high drain amylase levels, 65.9% of patients developed clinically relevant postoperative pancreatic fistula. However, no significant difference was observed in C-reactive protein levels between patients with clinically relevant postoperative pancreatic fistula and those without it. In contrast, in the subgroup with a large postoperative fluid collection size or a high amylase level alone, a significant difference was observed in C-reactive protein values between the patients with clinically relevant postoperative pancreatic fistula and those without it. Conclusion: Postoperative fluid collection status and the C-reactive protein value provide a more precise assessment of intra=abdominal status related to postoperative pancreatic fistula after distal pancreatectomy. This detailed analysis may be a clinically reasonable approach to individual drain management.

Metastatic pathways to the lower zone by segment in patients with clinical T1 lower lobe non-small cell lung cancer.

OBJECTIVE: Segmentectomy and mediastinal lymph node dissection (LND) may increasingly be used for non-small cell lung cancer (NSCLC). Lymph node metastasis (LNM) distribution varies by lower lobe segments; however, its segment-specific spread to the lower zone (#8, 9) (LZ) in lower lobe NSCLC is seldom reported. METHODS: In total, 352 patients with clinical T1 lower lobe NSCLC who underwent lobectomy with systematic or lobe-specific LND were included for analysis between January 2006 and December 2018. RESULTS: Fifty-eight (16.2%) patients had LNM (pN1: 24, pN2: 34), and nine (2.6%) had LZ metastasis. LZ metastasis was significantly more frequent in tumors with diameter > 2 cm, tumors without ground-glass opacity on radiological findings, left lung cancer, and basal segment lung cancer (respectively, p = 0.039, 0.006, 0.0177, 0.0024). None of the S6 NSCLC patients had LZ metastasis. Two patients with right basal segment NSCLC had LZ metastases (tumor on S10) as well as N1 lymph node and subcarinal zone metastasis. Seven (8.4%) patients with left basal segment NSCLC had LZ metastasis (tumor on S8: 3, tumor on S10: 4). Of them, three patients with left basal NSCLC had isolated LZ metastasis. CONCLUSIONS: The LND of the LZ can be omitted for clinical T1 patients with S6 NSCLC. In addition, the LND of the LZ may be omitted in right basal NSCLC if intraoperative confirmation of negative N1 and subcarinal zone lymph nodes is obtained; however, it is necessary for left basal segment NSCLC.

Prediction for oxaliplatin-induced liver injury using patient-derived liver organoids.

BACKGROUND: Liver injury associated with oxaliplatin (L-OHP)-based chemotherapy can significantly impact the treatment outcomes of patients with colorectal cancer liver metastases, especially when combined with surgery. To date, no definitive biomarker that can predict the risk of liver injury has been identified. This study aimed to investigate whether organoids can be used as tools to predict the risk of liver injury. METHODS: We examined the relationship between the clinical signs of L-OHP-induced liver injury and the responses of patient-derived liver organoids in vitro. Organoids were established from noncancerous liver tissues obtained from 10 patients who underwent L-OHP-based chemotherapy and hepatectomy for colorectal cancer. RESULTS: Organoids cultured in a galactose differentiation medium, which can activate the mitochondria of organoids, showed sensitivity to L-OHP cytotoxicity, which was significantly related to clinical liver toxicity induced by L-OHP treatment. Organoids from patients who presented with a high-grade liver injury to the L-OHP regimen showed an obvious increase in mitochondrial superoxide levels and a significant decrease in mitochondrial membrane potential with L-OHP exposure. L-OHP-induced mitochondrial oxidative stress was not observed in the organoids from patients with low-grade liver injury. CONCLUSIONS: These results suggested that L-OHP-induced liver injury may be caused by mitochondrial oxidative damage. Furthermore, patient-derived liver organoids may be used to assess susceptibility to L-OHP-induced liver injury in individual patients.

Prognostic Relevance of Primary Tumor Sidedness in Early-stage Colorectal Cancer: An Integrated Analysis of 4 Randomized Controlled Trials (JCOG2003A).

OBJECTIVE: The aim of this study was to determine the genuine prognostic relevance of primary tumor sidedness (PTS) in patients with early-stage colorectal cancer (CRC). BACKGROUND: The prognostic relevance of PTS in early-stage CRC remains a topic of debate. Several large epidemiological studies investigated survival only and did not consider the risk of recurrence so far. METHODS: Patients with stage II/III adenocarcinoma of the colon and upper rectum from 4 randomized controlled trials were analyzed. Survival outcomes were compared according to the tumor location: right-sided (cecum to transverse colon) or left-sided (descending colon to upper rectum). RESULTS: A total of 4113 patients were divided into a right-sided group (N=1349) and a left-sided group (N=2764). Relapse-free survival after primary surgery was not associated with PTS in all patients and each stage [hazard ratio (HR) adjusted =1.024 (95% CI: 0.886-1.183) in all patients; 1.327 (0.852-2.067) in stage II; and 0.990 (0.850-1.154) in stage III]. Also, overall survival after primary surgery was not associated with PTS in all patients and each stage [HR adjusted =0.879 (95% CI: 0.726-1.064) in all patients; 1.517 (0.738-3.115) in stage II; and 0.840 (0.689-1.024) in stage III]. In total, 795 patients (right-sided, N=257; left-sided, N=538) developed recurrence after primary surgery. PTS was significantly associated with overall survival after recurrence (HR adjusted =0.773, 95% CI: 0.627-0.954). CONCLUSIONS: PTS had no impact on the risk of recurrence for stage II/III CRC. Treatment stratification based on PTS is unnecessary for early-stage CRC.

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.

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.

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.

A proposed new Japanese classification of synchronous peritoneal metastases from colorectal cancer: A multi-institutional, prospective, observational study conducted by the Japanese Society for Cancer of the Colon and Rectum.

Aim: To establish a new Japanese classification of synchronous peritoneal metastases from colorectal cancer. Methods: This multi-institutional, prospective, observational study enrolled patients who underwent surgery for colorectal cancer with synchronous peritoneal metastases. Overall survival rates were compared according to the various models using objective indicators. Each model was evaluated by Akaike's information criterion (AIC). The region of peritoneal metastases was evaluated by the peritoneal cancer index (PCI). Results: Between October 2012 and December 2016, 150 patients were enrolled. The AIC of the present Japanese classification was 1020.7. P1 metastasis was defined as confined to two regions. The minimum AIC was obtained with the cutoff number of 10 or less for P2 metastasis and 11 or more for P3 metastasis. As for size, the best discrimination ability between P2 and P3 metastasis was obtained with a cutoff value of 3 cm. The AIC of the proposed classification was 1014.7. The classification was as follows: P0, no peritoneal metastases; P1, metastases localized to adjacent peritoneum (within two regions of PCI); P2, metastases to distant peritoneum, number ≤10 and size ≤3 cm; P3, metastases to distant peritoneum, number ≥11 or size >3 cm; P3a, metastases to distant peritoneum, number ≥11 and size ≤3 cm, or number ≤10 and size >3 cm; P3b, metastases to distant peritoneum, number ≥11 and size >3 cm. Conclusion: This objective classification could improve the ability to discriminate prognosis in patients with synchronous peritoneal metastases from colorectal cancer.

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.

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.

Definitive S-1/mitomycin-C chemoradiotherapy for stage II/III anal canal squamous cell carcinoma: a phase I/II dose-finding and single-arm confirmatory study (JCOG0903).

BACKGROUND: Definitive chemoradiotherapy (CRT) with 5-fluorouracil plus mitomycin-C is a standard treatment for stage II/III squamous cell carcinoma of the anal canal (SCCA). We performed this dose-finding and single-arm confirmatory trial of CRT with S-1 plus mitomycin-C to determine the recommended dose (RD) of S-1 and evaluate its efficacy and safety for locally advanced SCCA. METHODS: Patients with clinical stage II/III SCCA (UICC 6th) received CRT comprising mitomycin-C (10 mg/m2 on days 1 and 29) and S-1 (60 mg/m2/day at level 0 and 80 mg/m2/day at level 1 on days 1-14 and 29-42) with concurrent radiotherapy (59.4 Gy). Dose-finding used a 3 + 3 cohort design. The primary endpoint of the confirmatory trial was 3-year event-free survival. The sample size was 65, with one-sided alpha of 5%, power of 80%, and expected and threshold values of 75% and 60%, respectively. RESULTS: Sixty-nine patients (dose-finding, n = 10; confirmatory, n = 59) were enrolled. The RD of S-1 was determined as 80 mg/m2/day. Three-year event-free survival in 63 eligible patients who received the RD was 65.0% (90% confidence interval 54.1-73.9). Three-year overall, progression-free, and colostomy-free survival rates were 87.3%, 85.7%, and 76.2%, respectively; the complete response rate was 81% on central review. Common grade 3/4 acute toxicities were leukopenia (63.1%), neutropenia (40.0%), diarrhea (20.0%), radiation dermatitis (15.4%), and febrile neutropenia (3.1%). No treatment-related deaths occurred. CONCLUSIONS: Although the primary endpoint was not met, S-1/mitomycin-C chemoradiotherapy had an acceptable toxicity profile and favorable 3-year survival and could be a treatment option for locally advanced SCCA. CLINICAL TRIAL INFORMATION: jRCTs031180002.

Clinical outcomes of neoadjuvant chemotherapy for resectable colorectal liver metastasis with intermediate risk of postoperative recurrence: A multi-institutional retrospective study.

Aims: Risk-scoring systems for colorectal liver metastasis (CRLM) after hepatectomy allow prognoses to be predicted preoperatively. We investigated the clinical outcomes of neoadjuvant chemotherapy for resectable CRLM according to patient risk status, aiming to determine the subgroup of patients who could benefit from neoadjuvant chemotherapy. Methods: In this multi-institutional retrospective analysis, the preoperative risk score was calculated from six previously reported factors: synchronous metastases, primary lymph node positivity, tumor number, largest tumor diameter, extrahepatic metastasis, and the preoperative carbohydrate antigen 19-9 level. Patients were divided into three groups according to their risk scores: low risk (score = 0), intermediate risk (score 1-10), and high risk (score ≥11). Overall and recurrence-free survival curves were calculated using the Kaplan-Meier method. After propensity-score matching in the intermediate-risk group, we compared clinicopathological features and outcomes. Results: There were 318 cases, from 20 institutions. The preoperative risk score could be calculated in 277 cases. There were 34, 192, and 51 patients in the low-, intermediate-, and high-risk groups, respectively. Intermediate-risk group patients who received neoadjuvant chemotherapy had significantly better recurrence-free survival than that of patients without neoadjuvant chemotherapy (P = .0453). After propensity-score matching in the intermediate-risk group, the recurrence-free survival rate was better in patients who received neoadjuvant chemotherapy (P = .0261). But the overall survival rate was not improved after the matching. Conclusion: Neoadjuvant chemotherapy for resectable CRLM might prolong the recurrence-free survival period for intermediate-risk patients with preoperative risk scores in the range of 1-10, but the overall survival was not improved by neoadjuvant chemotherapy.

Optimal bowel resection margin in colon cancer surgery: prospective multicentre cohort study with lymph node and feeding artery mapping.

Background: There are no standardised criteria for the 'regional' pericolic node in colon cancer, which represents a major cause of the international uncertainty regarding the optimal bowel resection margin. This study aimed to determine 'regional' pericolic nodes based on prospective lymph node (LN) mapping. Methods: According to preplanned in vivo measurements of the bowel, the anatomical distributions of the feeding artery and LNs were determined in 2996 stages I-III colon cancer patients who underwent colectomy with resection margin >10 cm at 25 institutions in Japan. Findings: The mean number of retrieved pericolic nodes was 20.9 (standard deviation, 10.8) per patient. In all patients except seven (0.2%), the primary feeding artery was distributed within 10 cm of the primary tumour. The metastatic pericolic node most distant from the primary tumour was within 3 cm in 837 patients, 3-5 cm in 130 patients, 5-7 cm in 39 patients and 7-10 cm in 34 patients. Only four patients (0.1%) had pericolic lymphatic spread beyond 10 cm; all of whom had T3/4 tumours accompanying extensive mesenteric lymphatic spread. The location of metastatic pericolic node did not differ by the feeding artery's distribution. Postoperatively, none of the 2996 patients developed recurrence in the remaining pericolic nodes. Interpretation: The pericolic nodes designated as 'regional' were those located within 10 cm of the primary tumours, which should be fully considered when determining the bowel resection margin, even in the era of complete mesocolic excision. Funding: Japanese Society for Cancer of the Colon and Rectum.

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.

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.