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.

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.

Clinical Impact of Metastatic Lymph Node Size on Therapeutic Effect and Prognosis in Patients with Esophageal Squamous Cell Carcinoma Who Underwent Preoperative Chemotherapy Followed by Esophagectomy.

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.

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.

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.

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.

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.

The Conventional Technique Versus the No-touch Isolation Technique for Primary Tumor Resection in Patients With Colon Cancer (JCOG1006): A Multicenter, Open-label, Randomized, Phase III Trial.

OBJECTIVE: This phase III trial evaluated whether the no touch was superior to the conventional in patients with cT3/T4 colon cancer. BACKGROUND: No touch involves ligating blood vessels that feed the primary tumor to limit cancer cell spreading. However, previous studies did not confirm the efficacy of the no touch. METHODS: This open-label, randomized, phase III trial was conducted at 30 Japanese centers. The eligibility criteria were histologically proven colon cancer; clinical classification of T3-4, N0-2, andM0; and patients aged 20 to 80years. Patients were randomized (1:1) to undergo open surgery with conventional or the no touch. Patients with pathological stage III disease received adjuvant capecitabine chemotherapy. The primary endpoint was disease-free survival (DFS) according to the intention-to-treat principle. RESULTS: Between January 2011 and November 2015, 853 patients were randomized to the conventional group (427 patients) or the no touch group (426 patients). The 3-year DFS were 77.3% [95% confidence interval (CI) 73.1%-81.0%] and 76.2% (95% CI 71.9%-80.0%) in the conventional and no touch groups, respectively. The superiority of no touch was not confirmed: hazard ratio for DFS = 1.029 (95% CI 0.800- 1.324; 1-sided P = 0.59). Operative morbidity was observed in 31 of 427 conventional patients (7%) and 26 of 426 no touch patients (6%). All grade adverse events were similar between the conventional and no touch groups. No in-hospital mortality occurred in either group. CONCLUSION: The present study failed to confirm the superiority of the no touch.

Aberrant activation of Rho/ROCK signaling in impaired polarity switching of colorectal micropapillary carcinoma.

Micropapillary carcinoma (MPC) is a morphologically distinctive form of carcinoma, composed of small nests of cancer cells surrounded by lacunar spaces. Invasive MPC is associated with poor prognosis. The nests of tumor cells in MPC reportedly exhibit reverse polarity, although the molecular mechanisms underlying MPC patterns are poorly understood. Using the cancer tissue-originated spheroid (CTOS) method, we previously reported polarity switching in colorectal cancer (CRC). When cultured in suspension, the apical membrane promptly switches from the outside surface of the CTOSs to the surface of the lumen inside the CTOSs under extracellular matrix (ECM)-embedded conditions, and vice versa. Here, we investigated two CTOS lines from CRC patient tumors with MPC lesions. Xenograft tumors from the CTOSs exhibited the MPC phenotype. The MPC-CTOSs did not switch polarity in vitro. Time-course analysis of polarity switching using real-time imaging of the apical membrane revealed that local switching was continually propagated in non-MPC-CTOSs, while MPC-CTOSs were unable to complete the process. Integrin ß4 translocated to the outer membrane when embedded in ECM in both MPC and non-MPC-CTOSs. Protein levels, as well as the active form of RhoA, were higher in MPC-CTOSs. The suppression of RhoA activity by GAP overexpression enabled MPC-CTOSs to complete polarity switching both in vitro and in vivo, while overexpression of active RhoA did not affect polarity switching in non-MPC-CTOSs. Pretreatment with a ROCK inhibitor enabled MPC-CTOSs to complete polarity switching both in vitro and in vivo, although delayed treatment after becoming embedded in ECM failed to do so. Thus, the inability to switch polarity might be a cause of MPC, in which the aberrant activation of RhoA plays a critical role. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

A randomized controlled trial comparing perioperative vs. postoperative mFOLFOX6 for lower rectal cancer with suspected lateral pelvic lymph node metastasis (JCOG1310): a phase II/III randomized controlled trial.

OBJECTIVE: The optimal perioperative chemotherapy for lower rectal cancer with lateral pelvic lymph node metastasis remains unclear. We evaluated the efficacy and safety of perioperative mFOLFOX6 in comparison with postoperative mFOLFOX6 for rectal cancer patients undergoing total mesorectal excision with lateral lymph node dissection. METHODS: We conducted an open label randomized phase II/III trial in 18 Japanese institutions. We enrolled patients with histologically proven lower rectal adenocarcinoma with clinical pelvic lateral lymph node metastasis who were randomly assigned (1:1) to receive postoperative mFOLFOX6 (12 courses of intravenous oxaliplatin [85 mg/m2] with L-leucovorin [200 mg/m2] followed by 5-fluorouracil [400 mg/m2, bolus and 2400 mg/m2, continuous infusion, repeated every 2 weeks]) or perioperative mFOLFOX6 (six courses each preoperatively and postoperatively). The primary endpoint was overall survival (OS). The trial is registered with Japan Registry of Clinical Trials, number jRCTs031180230. RESULTS: Between May 2015, and May 2019, 48 patients were randomized to the postoperative arm (n = 26) and the perioperative arm (n = 22). The trial was terminated prematurely due to poor accrual. The 3-year OS in the postoperative and perioperative groups were 66.1 and 84.4%, respectively (HR 0.58, 95% CI [0.14-2.45], one-sided P = 0.23). The pathological complete response rate in the perioperative group was 9.1%. Grade 3 postoperative surgical complications were more frequently observed in the perioperative arm (50.0 vs. 12.0%). One treatment-related death due to sepsis from pelvic infection occurred in the postoperative group. CONCLUSIONS: Perioperative mFOLFOX6 may be an insufficient treatment to improve survival of lower rectal cancer with lateral pelvic lymph node metastasis.

Challenges needed to be overcome in multi-institutional surgical trials: accumulated experience in the JCOG Colorectal Cancer Study Group (CCSG).

JCOG-CCSG has been conducting several surgical trials and experienced several challenges. The first point is the appropriate timing of conducting the trial. Once a certain number of surgeons acquire the new technique and its utility is accepted, it suddenly becomes difficult to maintain 'equipoise' between the standard and new treatment, which may lead to poor patient accrual. Smooth preparation and commencement of the trial at an appropriate timing is necessary for its success. Second is the appropriate quality assurance of surgery. High-level quality assurance will strengthen the comparability of randomized control trials and minimize the heterogeneity among hospitals. On the other hand, it may impair the generalizability of the trial. Large observational studies help to bridge the gap of heterogeneity among hospitals. Third is the selection of an appropriate endpoint. Overall survival (OS) is the gold-standard primary endpoint; however, the number of events is much less due to more effective treatment. JCOG0212 and JCOG0404 were unable to demonstrate the non-inferiority of omission of lateral lymph node dissection and laparoscopic surgery partly due to a lack of power. Disease-free survival (DFS) is also a promising candidate for primary endpoint, but as in JCOG0603, special attention must be paid when DFS does not correlate with OS. Although careful discussion is required because the precision of the hazard ratio depends on the number of events, an alternative population-level summary of variables, including restricted mean survival time, can be considered as the primary endpoint. Future surgical trials should be planned considering these points.

Preoperative and postoperative prognostic factors of patients with stage II/III lower rectal cancer without neoadjuvant therapy in the clinical trial (JCOG0212).

BACKGROUND: The JCOG0212 trial was a randomized controlled trial comparing mesorectal excision alone to mesorectal excision with lateral lymph node dissection for stage II/III lower rectal cancer patients without clinical lateral lymph node enlargement. This study aimed to identify clinicopathological prognostic factors for relapse-free survival and overall survival of lower rectal cancer in the trial. METHODS: Prospective data were selected from 663 patients with complete data. Uni and multivariable Cox regression model was applied to evaluate the preoperative and the combined preoperative and postoperative factors, respectively. Preoperative factors included age, sex, performance status, clinical T, clinical N and operative procedures. Postoperative factors included histological grade, pathological T, number of metastatic lymph nodes and number of dissected lymph nodes. No patient received neoadjuvant treatment. RESULTS: Regarding preoperative factors, multivariable analysis revealed that performance status 1 (vs. 0: HR 2.079, P = 0.0041) and cT4a (vs. cT2-3: HR 2.721, P = 0.0002) were independent risk factors for relapse-free survival, and those for overall survival were male (vs. female: HR 1.660, P = 0.0228) and cT4a (vs. cT2-3: HR 2.486, P = 0.0473). The only independent preoperative risk factor common for relapse-free survival and overall survival was cT4a. Taking preoperative and postoperative factors together, the number of metastatic lymph nodes was the only independent risk factor common for relapse-free survival and overall survival. CONCLUSIONS: Clinical stage II/III lower rectal cancer patients with cT4a should be a target of therapeutic development of neoadjuvant therapy. Postoperatively, intensive chemotherapy should be investigated for patients with more metastatic lymph nodes.

Management of inguinal lymph node metastases from rectal and anal canal adenocarcinoma.

AIM: The surgical treatment of inguinal lymph node (ILN) metastases secondary to anorectal adenocarcinoma remains controversial. This study aimed to clarify the surgical treatment and management of ILN metastasis according to its classification. METHODS: This retrospective, multi-centre, observational study included patients with synchronous or metachronous ILN metastases who were diagnosed with rectal or anal canal adenocarcinoma between January 1997 and December 2011. Treatment outcomes were analysed according to recurrence and prognosis. RESULTS: Among 1181 consecutively enrolled patients who received treatment for rectal or anal canal adenocarcinoma at 20 referral hospitals, 76 (6.4%) and 65 (5.5%) had synchronous and metachronous ILN metastases, respectively. Among 141 patients with ILN metastasis, differentiated carcinoma, solitary ILN metastasis and ILN dissection were identified as independent predictive factors associated with a favourable prognosis. No significant difference was found in the frequency of recurrence after ILN dissection between patients with synchronous (80.6%) or metachronous (81.0%) ILN metastases. Patients who underwent R0 resection of the primary tumour and ILN dissection had a 5-year survival rate of 41.3% after ILN dissection (34.1% and 53.1% for patients with synchronous and metachronous ILN metastases, respectively, P = 0.55). CONCLUSION: The ILN can be appropriately classified as a regional lymph node in rectal and anal canal adenocarcinoma. Moreover, aggressive ILN dissection might be effective in improving the prognosis of low rectal and anal canal adenocarcinoma with ILN metastases; thus, prophylactic ILN dissection is unnecessary.

Comparison of robotic gastrectomy and laparoscopic gastrectomy for gastric cancer: a propensity score-matched analysis.

BACKGROUND: The benefits of robotic gastrectomy (RG) over laparoscopic gastrectomy (LG) remain controversial. This single-center, propensity score-matched study aimed to compare the outcomes of RG with those of LG for treating gastric cancer. METHODS: We searched the prospective gastric cancer database of our institute for patients with gastric cancer who underwent RG or LG between January 2014 and December 2019, excluding patients with remnant stomach cancer and those who underwent concurrent surgery for comorbid malignancies. One-to-one propensity score matching was performed to reduce bias from confounding patient-related variables, and short- and long-term outcomes were compared between the groups. RESULTS: We identified 1189 patients who underwent LG (n = 979) or RG (n = 210). After propensity score matching, we selected 210 pairs of patients who underwent LG (distal gastrectomy, 138; total or proximal gastrectomy, 72) or RG (distal gastrectomy, 143; total or proximal gastrectomy, 67). RG was associated with a significantly shorter operative time (RG = 201 min vs. LG = 231 min, p = 0.0051), less blood loss (RG = 13 mL vs. LG = 42 mL, p < 0.0001), lower postoperative morbidity (RG = 1.0% vs. LG = 4.8%, p = 0.0066), and a shorter postoperative hospital stay (p = 0.0002) than LG. Drain amylase levels on postoperative Days 1 and 3 in the RG group were significantly lower than those in the LG group (p < 0.0001). CONCLUSIONS: RG is a safe and feasible treatment for gastric cancer, with a shorter operative time, less blood loss, and lower postoperative morbidity than LG. The application of robotics in minimally invasive gastric cancer surgery may offer an alternative to conventional surgery. Multicenter, prospective, randomized controlled trials comparing RG with conventional LG are needed to establish the feasibility and efficacy of minimally invasive gastric cancer surgery.

Clinical importance of carcinoembryonic antigen messenger RNA level in peritoneal lavage fluids measured by transcription-reverse transcription concerted reaction for advanced gastric cancer in laparoscopic surgery.

BACKGROUND: Transcription-reverse transcription concerted reaction (TRC) is recognized as a useful method for detecting free cancer cells in the peritoneal cavity and predicting peritoneal recurrence in patients with gastric cancer. Nonetheless, the clinical significance of TRC in laparoscopic surgery remains unclear. This study aimed to evaluate the clinical importance of carcinoembryonic antigen (CEA) messenger RNA (mRNA) level in peritoneal lavage fluids measured by TRC in laparoscopic surgery for locally advanced gastric cancer. METHODS: We enrolled patients with locally advanced gastric cancer who underwent laparoscopic gastrectomy. Peritoneal lavage fluids were collected prior to gastrectomy, and the TRC method was employed to quantify CEA mRNA in peritoneal washes. Overall survival (OS), recurrence-free survival (RFS), and peritoneal recurrence-free survival (PRFS) were analyzed using the Kaplan-Meier method and compared using the log-rank test. Adjusted Cox proportional hazards regression models were used to calculate the hazard ratios (HRs) for CEA mRNA positivity. RESULTS: A total of 100 patients were analyzed in this study. Overall, 22 patients (22%) exhibited CEA mRNA positivity in peritoneal lavage fluids, as measured by TRC. No significant association between CEA mRNA levels and clinicopathological characteristics was observed. Patients who were CEA mRNA-positive in peritoneal lavage fluids had significantly worse OS, RFS, and PRFS than those who were CEA mRNA-negative (p = 0.0059, p < 0.0001, and p = 0.0022, respectively). In the univariate Cox model, the HR for all-cause mortality in CEA mRNA-positive versus CEA mRNA-negative patients was 3.60 (95% CI, 1.33-9.55; p = 0.0129). Multivariate analysis revealed that CEA mRNA positivity was a significant independent factor for recurrence. CONCLUSIONS: TRC enables the detection of free cancer cells in the peritoneal cavity and CEA mRNA levels can help predict the prognosis, even in laparoscopic gastrectomy.

Safety and efficacy of preoperative indocyanine green fluorescence marking in laparoscopic gastrectomy for proximal gastric and esophagogastric junction adenocarcinoma (ICG MAP study).

PURPOSE: The incidence of adenocarcinoma of the esophagogastric junction (AEG) and proximal gastric cancer (PGC) is rising worldwide. Recently, the use of indocyanine green (ICG) tracer-guided surgery has been reported; however, its efficacy for total/proximal gastrectomy has not been clarified. We evaluated the feasibility and safety of ICG fluorescent marking for tumor localization in AEG/PGC treatment by laparoscopic surgery. METHODS: We enrolled patients with AEG/PGC from October 2016 to March 2019 from a prospectively registered database. On the day before surgery, ICG markings were made at four locations just at the edge of the tumor by gastrointestinal fiberscope examination. Surgery was performed while viewing the fluorescence image of ICG, and the proximal portions of the esophagus and the distal portion of the stomach were resected at the edge of the area where ICG had spread. RESULTS: We enrolled 130 patients with AEG/PGC. Overall, 107 patients were eventually included in the study: AEG n = 64 (60%) and PGC n = 43 (40%). ICG markings were detected intraoperatively in all cases, and cancer invasion into the resection lines of the esophagus and stomach, performed based on ICG fluorescence images, was negative in all cases. The median visible range of ICG fluorescence was 22.5 mm. ICG diffusion expanded 20 mm proximal for AEG. There were no adverse events associated with endoscopic ICG injection. CONCLUSION: ICG fluorescence imaging is feasible and safe and can potentially be used as a tumor-marking agent for determining the surgical resection line for total/proximal gastrectomy in AEG and PGC treatment.

Postoperative aggressive diuresis prevents postoperative tissue edema and complications in patients undergoing distal pancreatectomy.

PURPOSE: Intraoperative fluid restriction is reported to be associated with reduced postoperative tissue edema and decreased incidence of postoperative pancreatic fistula (POPF) in pancreatic surgery. However, there is limited information regarding the postoperative approach to prevent postoperative tissue edema and reduce POPF. METHODS: Patients undergoing distal pancreatectomy from 2013 to 2018 in our institute were retrospectively enrolled (n = 128). The patients were classified into the two groups: an early diuresis group (ED group: patients administered diuretic agents on postoperative day 2 or earlier between 2016 and 2018, n = 69) and a conventional diuresis group (CD group: patients administered diuretic agents on postoperative day 3 or later between 2013 and 2015, n = 59). Postoperative tissue edema assessed by CT imaging and the incidence of clinically relevant POPF (CR-PF; grade B or C) were compared. RESULTS: Postoperative tissue edema was significantly reduced in the ED group (p < 0.0001). The incidence of CR-PF was lower in the ED group (19% vs. 32%, p = 0.082), especially in patients with postoperative diuresis on POD 1 (12%, p = 0.044). CONCLUSION: Early and aggressive postoperative diuresis potentially reduced postoperative visceral tissue edema. This postoperative approach to prevent tissue edema may reduce the incidence of CR-PF in pancreatic surgery.

The DOLFIN method: a novel laparoscopic Billroth-I gastroduodenostomy for gastric cancer with duodenal invasion.

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.

Combination of extramural venous invasion and lateral lymph node size detected with magnetic resonance imaging is a reliable biomarker for lateral lymph node metastasis in patients with rectal cancer.

PURPOSE: Pathological extramural venous invasion (EMVI) is defined as the active invasion of malignant cells into veins beyond the muscularis propria in colorectal cancer. It is associated with poor prognosis and increases the risk of disease recurrence. Specific findings on MRI (termed MRI-EMVI) are reportedly associated with pathological EMVI. In this study, we aimed to identify risk factors for lateral lymph node (LLN) metastasis related to rectal cancer and to evaluate whether MRI-EMVI could be a new and useful imaging biomarker to help LLN metastasis diagnosis besides LLN size. METHODS: We investigated 67 patients who underwent rectal resection and LLN dissection for rectal cancer. We evaluated MRI-EMVI grading score and examined the relationship between MRI-EMVI and LLN metastasis. RESULTS: Pathological LLN metastasis was detected in 18 cases (26.9%), and MRI-EMVI was observed in 32 cases (47.8%). Patients were divided into two cohorts, according to LLN metastasis. Multivariate analyses demonstrated that higher risk of LLN metastasis was significantly associated with MRI-EMVI (P = 0.0112) and a short lateral lymph node axis (≥ 5 mm) (P = 0.0002). The positive likelihood ratios of MRI-EMVI alone, LLN size alone, and the combination of both factors were 2.12, 4.84, and 16.33, respectively. Patients negative for both showed better 2-year relapse-free survival compared to other patients (84.4% vs. 62.1%, P = 0.0374). CONCLUSIONS: MRI-EMVI was a useful imaging biomarker for identifying LLN metastasis in patients with rectal cancer. The combination of MRI-EMVI and LLN size can improve diagnostic accuracy.