How Does Omitting Additional Surgery After Local Excision Affect the Prognostic Outcome of Patients With High-risk T1 Colorectal Cancer?

OBJECTIVE: To investigate how omitting additional surgery after local excision (LE) affects patient outcomes in high-risk T1 colorectal cancer (CRC). BACKGROUND: It is debatable whether additional surgery should be performed for all patients with high-risk T1 CRC regardless of the tolerability of invasive procedures. METHODS: Patients who had received LE for T1 CRC at the Japanese Society for Cancer of the Colon and Rectum institutions between 2009 and 2016 were analyzed. Those who had received additional surgical resection and those who did not were matched one-on-one by the propensity score-matching method. A total of 401 propensity score-matched pairs were extracted from 1975 patients at 27 Japanese Society for Cancer of the Colon and Rectum institutions and were compared. RESULTS: Regional lymph node metastasis was observed in 31 (7.7%) patients in the LE + surgery group. Comparatively, the incidence of oncologic adverse events was low in the LE-alone group, such as the 5-year cumulative risk of local recurrence (4.1%) or overall recurrence (5.5%). In addition, the difference in the 5-year cancer-specific survival between the LE + surgery and LE-alone groups was only 1.8% (99.7% and 97.9%, respectively), whereas the 5-year overall survival was significantly lower in the LE-alone group than in the LE + surgery group [88.5% vs 94.5%, respectively ( P = 0.002)]. CONCLUSIONS: Those who had decided to omit additional surgery at the dedicated center for CRC treatment presented a small number of oncologic events and a satisfactory cancer-specific survival, which may suggest an important role of risk assessment regarding nononcologic adverse events to achieve a best practice for each individual with high-risk T1 tumors.

Long-Term Outcomes of Additional Surgery After Endoscopic Resection Versus Primary Surgery for T1 Colorectal Cancer.

INTRODUCTION: There is considerable concern about whether endoscopic resection (ER) before additional surgery (AS) for T1 colorectal cancer (CRC) has oncologically potential adverse effects. Therefore, the aim of this study was to compare the long-term outcomes, including overall survival (OS), of patients treated with AS after ER vs primary surgery (PS) for T1 CRC using a propensity score-matched analysis from a large observational study. METHODS: This study investigated 6,105 patients with T1 CRC treated with either ER or surgical resection between 2009 and 2016 at 27 high-volume Japanese institutions, with those undergoing surgery alone included in the PS group and those undergoing AS after ER included in the AS group. Propensity score matching was used for long-term outcomes of mortality and recurrence analysis. RESULTS: After propensity score matching, 1,219 of 2,438 patients were identified in each group. The 5-year OS rates in the AS and PS groups were 97.1% and 96.0%, respectively (hazard ratio: 0.72, 95% confidence interval: 0.49-1.08), indicating the noninferiority of the AS group. Moreover, 32 patients (2.6%) in the AS group and 24 (2.0%) in the PS group had recurrences, with no significant difference between the 2 groups (odds ratio: 1.34, 95% confidence interval: 0.76-2.40, P = 0.344). DISCUSSION: ER before AS for T1 CRC had no adverse effect on patients' long-term outcomes, including the 5-year OS rate. ER is a viable first-line treatment option for endoscopically resectable T1 CRC.

Treatment Decision for Locally Resected T1 Colorectal Carcinoma-Verification of the Japanese Guideline Criteria for Additional Surgery Based on Long-Term Clinical Outcomes.

INTRODUCTION: To verify the value of the pathological criteria for additional treatment in locally resected pT1 colorectal carcinoma (CRC) which have been used in the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines since 2009. METHODS: We enrolled 4,667 patients with pT1 CRC treated at 27 institutions between July 2009 and December 2016 (1,257 patients with local resection alone [group A], 1,512 patients with additional surgery after local resection [group B], and 1,898 patients with surgery alone [group C]). All 5 factors of the JSCCR guidelines (submucosal resection margin, tumor histologic grade, submucosal invasion depth, lymphovascular invasion, and tumor budding) for lymph node metastasis (LNM) had been diagnosed prospectively. RESULTS: Any of the risk factors were present in 3,751 patients. The LNM incidence was 10.4% (95% confidence interval 9.4-11.5) in group B/C patients with risk factors, whereas it was 1.8% (95% confidence interval 0.4-5.3) in those without risk factors ( P < 0.01). In group A, the incidence of recurrence was 3.6% in patients with risk factors, but it was only 0.4% in patients without risk factors ( P < 0.01). The disease-free survival rate of group A patients classified as risk positive was significantly worse than those of groups B and C patients. However, the 5-year disease-free survival rate in group A patients with no risk was 99.6%. DISCUSSION: Our large-scale real-world multicenter study demonstrated the validity of the JSCCR criteria for pT1 CRC after local resection, especially regarding favorable outcomes in patients with low risk of LNM.

Novel Artificial Intelligence Combining Convolutional Neural Network and Support Vector Machine to Predict Colorectal Cancer Prognosis and Mutational Signatures From Hematoxylin and Eosin Images.

Reducing recurrence following radical resection of colon cancer without overtreatment or undertreatment remains a challenge. Postoperative adjuvant chemotherapy (Adj) is currently administered based solely on pathologic TNM stage. However, prognosis can vary significantly among patients with the same disease stage. Therefore, novel classification systems in addition to the TNM are necessary to inform decision-making regarding postoperative treatment strategies, especially stage II and III disease, and minimize overtreatment and undertreatment with Adj. We developed a prognostic prediction system for colorectal cancer using a combined convolutional neural network and support vector machine approach to extract features from hematoxylin and eosin staining images. We combined the TNM and our artificial intelligence (AI)-based classification system into a modified TNM-AI classification system with high discriminative power for recurrence-free survival. Furthermore, the cancer cell population recognized by this system as low risk of recurrence exhibited the mutational signature SBS87 as a genetic phenotype. The novel AI-based classification system developed here is expected to play an important role in prognostic prediction and personalized treatment selection in oncology.

[Significance of Colorectal Cancer Resection for the Elderly].

INTRODUCTION: Elderly patients requiring surgical treatment is increasing in Japan, and while surgical treatment is expected to be effective even in the very elderly, there is a lack of evidence for the safety and efficacy of surgical resection due to problems with perioperative management and operative tolerance. We therefore retrospectively examined the short-term and long-term outcomes of colorectal cancer surgery for the very elderly at our hospital. SUBJECTS: The study included 14 cases of colorectal cancer in the very elderly who underwent radical resection at our hospital between January 2010 and March 2020. RESULTS: The mean age was 92 years, PS; 1/2=8/6, ASA-PS; 2/3/4=8/4/2, primary site was C/A/T/S/R= 2/5/2/2/3, pStage; 1/2/3=1/9/4, and only 1 case of decompression with ileus tube due to obstructive symptoms was treated before surgery. All patients underwent radical surgery. Median blood loss was 61 mL, median operation time was 190.5 min, and median postoperative hospital stay was 16 days. 5 patients had CD≥2 complications. All patients did not receive adjuvant chemotherapy, and recurrence in was observed 3 patients. CONCLUSION: Surgical treatment of very elderly patients seems to be acceptable under appropriate patient selection.

Effect of Biologics on the Risk of Advanced-Stage Inflammatory Bowel Disease-Associated Intestinal Cancer: A Nationwide Study.

INTRODUCTION: The aim of this study was to evaluate the effect of biologics on the risk of advanced-stage inflammatory bowel disease (IBD)-associated intestinal cancer from a nationwide multicenter data set. METHODS: The medical records of patients with Crohn's disease (CD) and ulcerative colitis (UC) diagnosed with IBD-associated intestinal neoplasia (dysplasia or cancer) from 1983 to 2020 were included in this study. Therapeutic agents were classified into 3 types: biologics, 5-aminosalicylic acid, and immunomodulators. The pathological cancer stage was compared based on the drug used in both patients with CD and UC. RESULTS: In total, 1,042 patients (214 CD and 828 UC patients) were included. None of the drugs were significantly associated with cancer stage in the patients with CD. In the patients with UC, an advanced cancer stage was significantly associated with less use of biologics (early stage: 7.7% vs advanced stage: 2.0%, P < 0.001), 5-aminosalicylic acid, and immunomodulators. Biologic use was associated with a lower incidence of advanced-stage cancer in patients diagnosed by regular surveillance (biologics [-] 24.5% vs [+] 9.1%, P = 0.043), but this was not the case for the other drugs. Multivariate analysis showed that biologic use was significantly associated with a lower risk of advanced-stage disease (odds ratio = 0.111 [95% confidence interval, 0.034-0.356], P < 0.001). DISCUSSION: Biologic use was associated with a lower risk of advanced IBD-associated cancer in patients with UC but not with CD. The mechanism of cancer progression between UC and CD may be different and needs to be further investigated.

Nomogram as a novel predictive tool for lymph node metastasis in T1 colorectal cancer treated with endoscopic resection: a nationwide, multicenter study.

BACKGROUND AND AIMS: Since 2009, the Japanese Society for Cancer of the Colon and Rectum guidelines have recommended that tumor budding and submucosal invasion depth, in addition to lymphovascular invasion and tumor grade, be included as risk factors for lymph node metastasis (LNM) in patients with T1 colorectal cancer (CRC). In this study, a novel nomogram was developed and validated by usirge-scale, real-world data, including the Japanese Society for Cancer of the Colon and Rectum risk factors, to accurately evaluate the risk of LNM in T1 CRC. METHODS: Data from 4673 patients with T1 CRC treated at 27 high-volume institutions between 2009 and 2016 were analyzed for LNM risk. To prepare a nonrandom split sample, the total cohort was divided into development and validation cohorts. Pathologic findings were extracted from the medical records of each participating institution. The discrimination ability was measured by using the concordance index, and the variability in each prediction was evaluated by using calibration curves. RESULTS: Six independent risk factors for LNM, including submucosal invasion depth and tumor budding, were identified in the development cohort and entered into a nomogram. The concordance index was .784 for the clinical calculator in the development cohort and .790 in the validation cohort. The calibration curve approached the 45-degree diagonal in the validation cohort. CONCLUSIONS: This is the first nomogram to include submucosal invasion depth and tumor budding for use in routine pathologic diagnosis based on data from a nationwide multi-institutional study. This nomogram, developed with real-world data, should improve decision-making for an appropriate treatment strategy for T1 CRC.

Analysis of Circulating DNA to Assess Prognoses for Metastatic Colorectal Cancer Patients Treated with Regorafenib Dose-Escalation Therapy: A Retrospective, Exploratory Analysis of the RECC Trial.

INTRODUCTION: Regorafenib is a multi-kinase inhibitor approved for patients with metastatic colorectal cancer (mCRC) who were previously treated with standard therapies. A few reports showed the impact of KRAS mutation on therapeutic efficacy of regorafenib. Only one study reported poor prognoses for patients treated with regorafenib who had large amounts of circulating cell-free DNA (cfDNA). In the present study, we evaluated the impact of KRAS mutations in tissue or plasma and amounts of cfDNA on prognoses of mCRC patients treated with regorafenib. METHOD: This is a biomarker investigation of the RECC study, which evaluated efficacy of regorafenib dose-escalation therapy. Plasma samples were obtained just before initiation of treatment with regorafenib. KRAS mutations were evaluated using tissue and plasma samples. cfDNA was extracted from plasma samples and quantified. RESULTS: Forty-five patients were enrolled in this biomarker study. Median progression-free survival (PFS) and overall survival (OS) of patients without KRAS mutations in tissues were 1.9 months (95% confidence interval [CI] 1.7-2.0) and 8.9 months (95% CI: 6.5-11.2), and those of patients with KRAS mutations were 1.4 months (95% CI: 1.3-1.5) and 6.8 months (95% CI: 5.0-8.5). Median PFS and OS of patients with plasma KRAS mutations were 1.9 months (95% CI: 1.8-1.9) and 7.0 months (95% CI: 5.3-8.7), respectively. Median PFS and OS of patients without plasma KRAS mutations were 1.7 months (95% CI: 1.1-2.3) and 8.9 months (95% CI: 6.7-11.2), respectively. Prior to administration of regorafenib, KRAS mutations were detected in 6 of 16 (37.5%) patients who had no tissue KRAS mutations. Median OS of patients with high cfDNA concentration (>median) was significantly poorer than that of patients with low cfDNA. CONCLUSION: KRAS mutations in the tissue or plasma have no impact on efficacy of regorafenib. KRAS emerging mutations were observed in quite a few patients. Large amounts of cfDNA may indicate poorer prognoses for patients receiving late-line regorafenib chemotherapy.

[Migration of Internal Pancreaticojejunostomy Stents into the Bile Ducts in Patients Undergoing Pancreaticoduodenectomy].

The patient was a 68-year-old male. Pancreaticoduodenectomy(PD)for papillary carcinoma was performed. Computed tomography(CT)3 months after surgery revealed the migration of a lost Pit-stent into the bile duct. However, there were no symptoms. On CT 2 years after surgery, the lost stent had spontaneously fallen off. However, hepaticolithiasis was observed, and lithotripsy was performed using endoscopic retrograde cholangiopancreatography(ERCP). A pancreatic fistula after PD is an important complication. To prevent pancreatic fistulae, pancreatic stenting at the site of PD is performed in many cases. The postoperative in vivo kinetics of a lost stent remains to be clarified. Several case reports on complications have been published. In this study, we report a patient in whom the migration of a lost Pit-stent into the intrahepatic bile duct after PD led to hepaticolithiasis, and review the literature.

[A Patient with Small Intestinal Leiomyosarcoma and Intussusception Who Underwent Single Port Surgery].

The patient was a 33-year-old female. She was referred to our hospital from a previous clinic with abdominal pain and vomiting. Contrast-enhanced abdominal CT revealed intussusception, leading to a diagnosis of intussusception with a small intestinal tumor as an advanced part. Intestinal obstruction symptoms were observed, and emergency surgery was performed on the same day. As a technique, single port surgery was selected, and laparoscopic reduction was attempted. However, it was ineffective. The site of intussusception was induced outside the body through a small laparotomy wound, and reduction was performed using Hutchinson's procedure. As an adjacent lymph node was markedly swollen, the mesentery involving this lymph node was dissected in a fan shape, and the tumor was extirpated. The tumor measured 40 mm in long diameter, being a hemicircular, protruding lesion. Histologically, disarray of short spindle tumor cells was observed. Immunostaining showed Kit- and DOG1-negtive reactions and partially α-SMA and desmin-positive reactions, suggesting leiomyosarcoma. With the establishment of an immunostaining-test-based classification, leiomyosarcoma is currently rare. In this study, we report a patient in whom single port surgery for intussusception related to small intestinal leiomyosarcoma was successful.

[Short-Term and Long-Term Results of Robot-Assisted Rectal Resections Performed in Our Department].

BACKGROUND: We introduced the da Vinci robotic surgical system in 2006 for the first time in Japan, and have been performing robot-assisted rectal cancer surgeries since 2010, after receiving approval from the hospital's Ethics Review Committee in 2009. Here we report the long-term and short-term outcomes of robot-assisted rectal cancer surgeries performed in our department. METHODS: Target patients were those who underwent robot-assisted radical rectal resection for rectal cancer; 165 patients in the short term(2010-2021), and 49 patients in the long term(2010-2016). Data were retrospectively analyzed, and Kaplan-Meier curves were used for the survival analysis. RESULTS: The short-term results are summarized in Table 1. The long-term results were as follows: 5-year overall survival rate, 90.8%; 5-year recurrence-free survival rate, 90.6%; 5-year cumulative local recurrence rate, 7.3%; 5-year cumulative distant metastasis rate, 9.4%. CONCLUSION: In our department, 11 years have passed since we began performing robotic rectal surgeries, and the short- and long-term results have generally been acceptable.

[Preoperative Prognostic Factors in CRS plus HIPEC for Patients with Peritoneal Dissemination of Colorectal Cancer].

Peritoneal dissemination of colorectal cancer has the poorest prognosis among metastatic sites, with an average overall survival of less than 6 months. Various treatment methods have been reported for these patients, and recently there have been several reports showing the usefulness of cytoreductive surgery(CRS)combined with hyperthermic intraperitoneal chemotherapy (HIPEC). However, the studies on this treatment are limited. In this study, we retrospectively reviewed cases of CRS plus HIPEC. Twenty-one patients who underwent CRS plus HIPEC at Tokyo Medical University Hospital and Toda Central General Hospital between August 2014 and December 2017 were included in this study. The long-term and short-term survival groups were analyzed separately, and predictors of preoperative treatment efficacy were examined. The surgical approach was open in 16 cases and laparoscopic in 5 cases. Complete resection was achieved in 10 of these patients. Postoperative complications occurred in 6 patients. There were no deaths within 90 days of surgery. The median overall survival was 17.0 months, and the 1-year survival rate was 65%. Median progression-free survival was 11.0 months. In a multivariate analysis predicting long-term versus short-term survival groups, sex, primary tumor location, and P factor were independent predictors of treatment response. CRS plus HIPEC therapy is considered an effective treatment option. The predictors of preoperative treatment response include sex, primary tumor location, and P factor.

[A Case of Rectal Cancer with Solitary Lymph Node Metastasis in the Stomach after Hepatectomy for Liver Metastasis].

A 44-year-old woman had undergone a laparoscopic low anterior resection and lymph node dissection for rectal cancer (pT4aN2aH0P0M0, pStage Ⅲc)in 20XX. Six months postoperatively, a CT scan revealed recurrent liver metastasis. She underwent surgery and adjuvant chemotherapy. Three years after the initial surgery, her liver metastasis recurred again, and the patient underwent another cycle of surgical treatment and adjuvant chemotherapy. Five years after the initial surgery, a lesion was found in a gastric lesser curvature lymph node. Gastric kyphosis lymph node dissection was performed under the suspicion of a solitary lymph node metastasis. The resected lymph node was diagnosed as a medium-differentiated adenocarcinoma, with findings consistent with a lymph node metastasis from the initial rectal cancer. Postoperative adjuvant chemotherapy was administered. No recurrence was noted 6 years and 6 months after the initial surgery. Rectal cancer rarely metastasizes to the gastric lymph nodes in a solitary fashion. We describe a case of a solitary gastric regional lymph node metastasis observed after the resolution of previous liver metastases.

Salivary metabolomics with machine learning for colorectal cancer detection.

As the worldwide prevalence of colorectal cancer (CRC) increases, it is vital to reduce its morbidity and mortality through early detection. Saliva-based tests are an ideal noninvasive tool for CRC detection. Here, we explored and validated salivary biomarkers to distinguish patients with CRC from those with adenoma (AD) and healthy controls (HC). Saliva samples were collected from patients with CRC, AD, and HC. Untargeted salivary hydrophilic metabolite profiling was conducted using capillary electrophoresis-mass spectrometry and liquid chromatography-mass spectrometry. An alternative decision tree (ADTree)-based machine learning (ML) method was used to assess the discrimination abilities of the quantified metabolites. A total of 2602 unstimulated saliva samples were collected from subjects with CRC (n = 235), AD (n = 50), and HC (n = 2317). Data were randomly divided into training (n = 1301) and validation datasets (n = 1301). The clustering analysis showed a clear consistency of aberrant metabolites between the two groups. The ADTree model was optimized through cross-validation (CV) using the training dataset, and the developed model was validated using the validation dataset. The model discriminating CRC + AD from HC showed area under the receiver-operating characteristic curves (AUC) of 0.860 (95% confidence interval [CI]: 0.828-0.891) for CV and 0.870 (95% CI: 0.837-0.903) for the validation dataset. The other model discriminating CRC from AD + HC showed an AUC of 0.879 (95% CI: 0.851-0.907) and 0.870 (95% CI: 0.838-0.902), respectively. Salivary metabolomics combined with ML demonstrated high accuracy and versatility in detecting CRC.

Prognostic value of preoperative high-sensitivity modified Glasgow prognostic score in advanced colon cancer: a retrospective observational study.

BACKGROUND: Several studies have demonstrated that the preoperative Glasgow prognostic score (GPS) and modified GPS (mGPS) reflected the prognosis in patients undergoing curative surgery for colorectal cancer. However, there are no reports on long-term prognosis prediction using high-sensitivity mGPS (HS-GPS) in colorectal cancer. Therefore, this study aimed to calculate the prognostic value of preoperative HS-GPS in patients with colon cancer. METHODS: A cohort of 595 patients with advanced resectable colon cancer managed at our institution was analysed retrospectively. HS-GPS, GPS, and mGPS were evaluated for their ability to predict prognosis based on overall survival (OS) and recurrence-free survival (RFS). RESULTS: In the univariate analysis, HS-GPS was able to predict the prognosis with significant differences in OS but was not superior in assessing RFS. In the multivariate analysis of the HS-GPS model, age, pT, pN, and HS-GPS of 2 compared to HS-GPS of 0 (2 vs 0; hazard ratio [HR], 2.638; 95% confidence interval [CI], 1.046-6.650; P = 0.04) were identified as independent prognostic predictors of OS. In the multivariate analysis of the GPS model, GPS 2 vs 0 (HR, 1.444; 95% CI, 1.018-2.048; P = 0.04) and GPS 2 vs 1 (HR, 2.933; 95% CI, 1.209-7.144; P = 0.017), and in that of the mGPS model, mGPS 2 vs 0 (HR, 1.51; 95% CI, 1.066-2.140; P = 0.02) were independent prognostic predictors of OS. In each classification, GPS outperformed HS-GPS in predicting OS with a significant difference in the area under the receiver operating characteristic curve. In the multivariate analysis of the GPS model, GPS 2 vs 0 (HR, 1.537; 95% CI, 1.190-1.987; P = 0.002), and in that of the mGPS model, pN, CEA were independent prognostic predictors of RFS. CONCLUSION: HS-GPS is useful for predicting the prognosis of resectable advanced colon cancer. However, GPS may be more useful than HS-GPS as a prognostic model for advanced colon cancer.

Novel and Simple Nomograms Using Inflammation and Nutritional Biomarkers for Stage II-III Colon Cancer, Taking "Time after Curative Surgery" into Consideration.

PURPOSE: Recurrence of colon cancer is associated with time after curative surgery. This study aimed to construct novel nomograms to predict relapse-free survival (RFS) in stage II-III colon cancer, considering "time after surgery" and using various inflammatory and nutritional biomarkers. METHODS: All 542 patients who underwent radical surgery for stage II-III colon cancer between January 2000 and August 2015 at our institute were retrospectively analyzed. Time-dependent receiver operating characteristic curves and cutoff values were obtained for neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio, platelet-lymphocyte ratio, Japanese modified Glasgow prognostic score (mGPS), C-reactive protein-albumin ratio (CAR), prognostic nutritional index, and controlling nutritional status (CONUT) for each postoperative period (1 - 5 years). We used Cox proportional hazard analyses to evaluate independent risk factors and to construct nomograms in each period. RESULTS: We obtained a good accuracy in NLR, CAR, mGPS, and CONUT (area under the curve > 0.5). NLR was the only preoperative independent risk factor, except age, in multivariate analysis. We constructed the nomograms and obtained a good discrimination value of the concordance index in each period (>0.75). CONCLUSION: Using inflammatory and nutritional biomarkers, we established and calibrated novel nomograms for predicting time-dependent RFS for stage II-III colon cancer patients.

Postoperative complications, bowel function, and prognosis in restorative proctocolectomy for ulcerative colitis-a single-center observational study of 320 patients.

PURPOSE: To determine the selection criteria, postoperative complications, bowel function, and prognosis of stapled ileal pouch-anal anastomosis (IPAA) and hand-sewn IPAA for ulcerative colitis (UC). METHODS: We defined our surgical indications and strategy, and compared the postoperative complications, bowel function, and prognoses between patients who underwent stapled and hand-sewn IPAA for UC at the Yokohama City University Medical Center between 2004 and 2017. RESULTS: Among 320 patients enrolled, 298 patients underwent stapled IPAA while 22 underwent hand-sewn IPAA. There was no significant difference in the postoperative complications between the two groups. Regarding postoperative bowel function, stapled IPAA caused significantly less soiling (stapled vs hand-sewn: 9.1% vs 41.0%, odds ratio (OR) = 0.14, p < 0.0002), spotting (stapled vs hand-sewn: 23.2% vs 63.6%, OR = 0.17, p < 0.0001), and difficulty in distinguishing feces from flatus (stapled vs hand-sewn: 39.9% vs 63.6%, OR = 0.36, p < 0.026). No postoperative neoplasia was observed at the final follow-up in all patients. CONCLUSION: In this study, there was no clear difference in the postoperative complications between stapled and hand-sewn IPAA, but stapled IPAA resulted in better postoperative bowel function. Postoperative oncogenesis from the residual mucosa is rare. However, future cancer risk remains; thus, careful follow-up is required.

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.

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.

A new technique for robotic lateral pelvic lymph node dissection for advanced low rectal cancer with emphasis on en bloc resection and inferior vesical vessel preservation.

BACKGROUND: Lateral pelvic lymph node (LPLN) dissection is becoming increasingly important in the treatment of advanced low rectal cancer patients. However, the surgery has several disadvantages, including its technical complexity and high risk of urinary dysfunction. Herein, we report a new technique for robotic lateral pelvic lymph node dissection for advanced low rectal cancer with emphasis on en bloc resection and inferior vesical vessel preservation. METHODS: Robotic LPLN dissection was performed in 12 consecutive patients between April 2020 and December 2021. Six surgical ports were placed in the abdomen under general anesthesia. Fascia-oriented LPLN dissection of the internal iliac region and obturator region was performed using the ureterohypogastric nerve fascia, vesicohypogastric fascia, and internal obturator muscles as anatomical landmarks. Lymph nodes were resected en bloc via the caudal side of the inferior vesical vessels. The inferior vesical vessels were spared to prevent urinary dysfunction. RESULTS: The median patient age was 62 years (range, 43-82 years), and eight patients were male. The median operative time was 498 min (range, 424-661 min), the median bleeding volume was 56 ml (range, 13-467 ml), and the median number of harvested LPLN was 16 (range, 1-70). The conversion rate to open surgery was 0%. Clavien-Dindo Grade ≥ II urinary dysfunction rated was not observed. CONCLUSION: A new technique for robotic LPLN dissection for advanced low rectal cancer with emphasis on en bloc resection and inferior vesical vessel preservation can be safely performed, making it a promising surgical procedure.