Enhancing surgical outcomes in elderly gastric cancer patients: the role of comprehensive preoperative assessment and support.

BACKGROUND: As the prevalence of gastric cancer rises in aging populations, managing surgical risks and comorbidities in elderly patients presents a unique challenge. The Comprehensive Preoperative Assessment and Support (CPAS) program, through comprehensive preoperative assessments, aims to mitigate surgical stress and improve outcomes by enhancing patient awareness and preparation. This study investigates the efficacy of a CPAS program, incorporating frailty and sarcopenia evaluations, to improve short-term outcomes in elderly gastric cancer patients. METHODS: A retrospective analysis was conducted on 127 patients aged 75 or older who underwent surgery with CPAS between 2018 and August 2023, compared to 170 historical controls from 2012 to 2017. Propensity score matching balanced both groups based on age-adjusted Charlson Comorbidity Index and surgical details. The primary focus was on the impact of CPAS elements such as rehabilitation, nutrition, psychological support, oral frailty, and social support on short-term surgical outcomes. RESULTS: Among 83 matched pairs, the CPAS group, despite 40.4% of patients in the CPAS group and 21.2% in the control group had an ASA-PS score of 3 or higher (P < 0.001), demonstrated significantly reduced blood loss (100 ml vs. 190 ml, P = 0.026) and lower incidence of serious complications (19.3% vs. 33.7%, P = 0.034), especially in infections and respiratory issues. Sarcopenia was identified in 38.6% of CPAS patients who received tailored support. Additionally, the median postoperative hospital stay was notably shorter in the CPAS group (10 days vs. 15 days, P < 0.001), with no in-hospital deaths. These results suggest that personalized preoperative care effectively mitigates operative stress and postoperative complications. CONCLUSION: Implementing CPAS significantly enhances surgical safety and reduces complication rates in elderly gastric cancer patients, emphasizing the critical role of personalized preoperative care in surgical oncology for this demographic.

Early detection of occupational cholangiocarcinoma in a high-risk patient under intensive surveillance: a case study.

BACKGROUND: Occupational cholangiocarcinoma is associated with exposure to organic solvents, such as dichloromethane (DCM) and 1,2-dichloropropane (DCP). This report describes a case of occupational cholangiocarcinoma detected through regularly imaging following the discovery of elevated serum γ-glutamyl trans peptidase (γ-GTP) levels revealed during regular checkup. CASE PRESENTATION: A 43-year-old man who had been working in a printing company with 15 years of exposure to organic solvents presented to our hospital owing to abnormalities found during a routine checkup. Ultrasound (US) imaging revealed thickening of the gallbladder wall accompanied by gallstones, although in the blood tests, γ-GTP levels were within normal range. Given the high risk of cholangiocarcinoma development, the patient underwent regular monitoring with abdominal US and blood tests at a local doctor's office. At the age of 48, his serum γ-GTP level mildly elevated for the first time, prompting the initiation of semi-annual magnetic resonance cholangiopancreatography (MRCP). By the age of 50 years, dilation in B8 was detected, and one and a half years later, a tumor on the central side of the B8 dilation appeared. The patient was diagnosed with intrahepatic cholangiocarcinoma, which was treated with anterior sectionectomy. Pathological examination revealed an adenocarcinoma with a papillary glandular ductal structure at the root of the B8. In addition, biliary intraepithelial neoplasia (BilIN) and dysplasia have been identified around the tumor and periphery bile ducts and in noncancerous bile ducts. Postoperatively, the patient received 6 months of adjuvant chemotherapy with S-1monotherapy. Eight months after surgery, the patient remained under observation with no signs of recurrence. CONCLUSIONS: We report a case of occupational cholangiocarcinoma detected during a prolonged period of regular follow-up after exposure to DCM and DCP. Given the delayed carcinogenesis process, occupational cholangiocarcinomas manifest long after exposure to organic solvents, therefore, ongoing screening is extremely important. Vigilance is essential to avoid underdiagnosis, particularly for individuals who are at an increased risk of developing this form of cancer. Continuous monitoring is key to the early detection and effective management of occupational cholangiocarcinoma.

A comprehensive study on non-cancer-related mortality risk factors in elderly gastric cancer patients post-curative surgery.

BACKGROUND: The increasing incidence of gastric cancer in the elderly underscores the need for an in-depth understanding of the challenges and risks associated with surgical interventions in this demographic. This study aims to investigate the risk factors and prognostic indicators for non-cancer-related mortality following curative surgery in elderly gastric cancer patients. METHODS: This retrospective analysis examined 684 patients with pathological Stage I-III gastric cancer who underwent curative resection between January 2012 and December 2021. The study focused on patients aged 70 years and above, evaluating various clinical and pathological variables. Univariate analysis was utilized to identify potential risk factors with to non-cancer-related mortality and to access prognostic outcomes. RESULTS: Out of the initial 684 patients, 244 elderly patients were included in the analysis, with 33 succumbing to non-cancer-related causes. Univariate analysis identified advanced age (≥ 80 years), low body mass index (BMI) (< 18.5), high Charlson Comorbidity Index (CCI), and the presence of overall surgical complications as significant potential risk factors for non-cancer related mortality. These factors also correlated with poorer overall survival and prognosis. The most common cause of non-cancer-related deaths were respiratory issues and heart failure. CONCLUSION: In elderly gastric cancer patients, managing advanced age, low BMI, high CCI, and minimizing postoperative complications are essential for reducing non-cancer-related mortality following curative surgery.

[A Case of 30s Female with Advanced Anal Canal Adenocarcinoma Managed with Adolescent-And-Young-Adult Team].

A 30s female complaining of anal pain and melena was referred to our hospital. The support by adolescent-and-young- adult(AYA)team was initiated after the first encounter. Colonoscopic examination revealed an ulcerated tumor on the anterior wall of anal canal with its anal margin on anal verge and the tumor was diagnosed as an adenocarcinoma. Contrast- enhanced CT and MRI revealed adjacency of tumor and vagina, enlarged lymph nodes and multiple pulmonary nodules. 18F-fluorodeoxyglucose(FDG)-positron emission tomography(PET)additionally revealed tracer accumulation in left sciatica, which led us to the diagnosis of advanced anal cancer. We planned and safely performed concomitant partial vaginal resection in robot-assisted laparoscopic abdominoperineal resection for the palliative purpose after discussion on physical and psychosocial issues including stoma and fertility with the patient, her family and AYA members. The pathological diagnosis was pT4b(vagina)N1aM1b, pStage ⅣB, and the local margin was pathologically negative. The postoperative course was smooth and she was discharged on postoperative day 16. Fifty one days after operation, she started systemic chemotherapy after decision on not to take ovarian samples and continues systemic chemotherapy as of writing. Support by AYA team was effective to facilitate the patient's decision-making and the communication between the patient and the medical team.

A distal ileum malignant peripheral nerve sheath tumour after abdominal radiation therapy: case report of a rare tumour.

Malignant peripheral nerve sheath tumours (MPNSTs) are malignant tumours arising from a peripheral nerve or displaying nerve sheath differentiation. Most MPNSTs are found on the head, body trunk and extremities, whereas cases in the gastrointestinal are extremely rare. About half arise in neurofibromatosis type 1 patients and 10% arise post-irradiation. This is probably the first small bowel MPNST post-radiation therapy case reported. A 72-year-old female who received radiotherapy 30 years ago for cervical cancer was admitted with progressive abdominal pain and weight loss. Computed tomography revealed a mass with inhomogeneous enhancement in the lumen of the small intestine. Tumour excision was performed with ileocecal and sigmoid colon resection due to suspicion for peripheral tissue invasion. Histopathological examination revealed spindle-shaped cells with focal cartilage differentiation. Together with immunochemistry stain showing complete loss of H3K27me3, a final diagnosis of MPNST was made. The patient is presently under regular follow-ups, and has remained disease-free for 24 months.

A rare intrahepatic splenosis mimicking hepatocellular carcinoma: A case report.

Intrahepatic splenosis (IHS) is a rare disease that is considered to result from heterotopic autotransplantation or implantation of splenic tissue after splenic trauma or surgery. A 46-year-old man with a treatment history of a left lateral liver segmentectomy and splenectomy for a road traffic injury 30 years earlier presented to Sakai City Medical Center (Sakai, Japan) with acute abdominal pain in November 2019. Physical examination showed no significant signs, and serum data were normal. Computed tomography revealed a hypodense mass measuring 2.5x1.7 cm in segment 7 of the liver. Gadoxetic acid-enhanced magnetic resonance imaging showed early enhancement in the arterial phase and washout in the delayed phase. Therefore, laparoscopic surgery was performed with a preoperative diagnosis of hepatocellular carcinoma. Pathological examination of the tumor showed IHS. The postoperative course was uneventful, and the patient developed no new abnormal region in the liver during 2 years of follow-up. The present study presented a case of IHS assumed to be hepatocellular carcinoma. IHS should be considered as a differential diagnosis of a liver mass detected years after splenic trauma or surgery, even in cases with imaging patterns suggesting malignancy.

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.

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

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

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

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

Minimizing invasiveness and simplifying the surgical procedure for upper and middle early gastric cancer with near-infrared light and organ traction.

BACKGROUND: Surgeons are often faced with optimal resection extent and reconstructive method problems in laparoscopic gastrectomy for gastric cancer in the upper and middle body of the stomach. Indocyanine green (ICG) marking and Billroth I (B-I) reconstruction were used to solve these problems with the organ retraction technique. CASE PRESENTATION: A 51-year-old man with upper gastrointestinal endoscopy revealed a 0-IIc lesion in the posterior wall of the upper and middle gastric body 4 cm from the esophagogastric junction. Clinical T1bN0M0 (clinical stage IA) was the preoperative diagnosis. Laparoscopic distal gastrectomy (LDG) and D1 + lymphadenectomy was decided to be performed considering postoperative gastric function preservation. The ICG fluorescence method was used to determine the accurate tumor location since the determination was expected to be difficult to the extent of optimal resection with intraoperative findings. By mobilizing and rotating the stomach, the tumor in the posterior wall was fixed in the lesser curvature, and as large a residual stomach as possible was secured in gastrectomy. Finally, delta anastomosis was performed after increasing gastric and duodenal mobility sufficiently. Operation time was 234 min and intraoperative blood loss was 5 ml. The patient was allowed to be discharged on postoperative day 6 without complications. CONCLUSION: The indication for LDG and B-I reconstruction can be expanded to cases where laparoscopic total gastrectomy or LDG and Roux-en-Y reconstruction has been selected for early-stage gastric cancer in the upper gastric body by combining preoperative ICG markings and gastric rotation method dissection.

Phase II dose titration study of regorafenib in progressive unresectable metastatic colorectal cancer.

Regorafenib has shown significant survival benefit as a salvage therapy for colorectal cancer; however, its starting dose has been controversial in recent studies. Therefore, we conducted a prospective study on the efficacy and safety of the dose reduction of regorafenib to 120 mg. Patients received 120 mg regorafenib once per day for 3 weeks, followed by a 1-week off-treatment period. The primary endpoint was the investigator-assessed disease control rate (DCR). Sixty patients were registered, and the DCR was 38.3% with a median progression-free survival of 2.5 months (95% confidence interval [CI] 1.9-3.7) and median overall survival of 10.0 months (95% CI 6.9-15.2). Common grade 3-4 adverse events were hand-foot skin reaction and hypertension (20.0% each). The results of administration of 120 mg regorafenib as the starting dose are consistent with reports from prior phase III trials, which used starting doses of 160 mg. This lower initiating dose of regorafenib may be beneficial to certain patient populations. This clinical trial was registered in the UMIN Clinical Trials Registry (UMIN-CTR number UMIN000018968, registration date: 10/09/2015).

Robot-assisted laparoscopic surgery with a fluorescent near-infrared ray ureteral catheter for a rectal cancer patient with pelvic kidney: A case report.

An 85-year-old woman presented with a stomachache after a meal and was admitted to the previous clinic. Multi-detector computed tomography (CT) of the abdomen showed wall thickening in the rectum and right ectopic pelvic kidney. Colonoscopy revealed a mass at the rectum, and a biopsy showed adenocarcinoma. CT showed no lymphadenopathy or distant metastasis. Hartmann's procedure with fluorescent near-infrared ray ureteral catheters was used to avoid causing urinary injury. Robotic surgery was performed while checking the route of the ureter in near-infrared mode. The patient was discharged on postoperative day 14 without specific complications. This case appears to be the first of robot-assisted laparoscopic surgery for a rectal cancer patient with pelvic kidney.

Clinicopathological features of appendiceal goblet cell adenocarcinoma in Japan: a multicenter retrospective study.

PURPOSE: In the 5th edition of the World Health Organization classification, appendiceal goblet cell adenocarcinoma (GCA) is categorized separately from neuroendocrine tumors and other appendiceal adenocarcinomas. We clarified the clinicopathological characteristics of Japanese appendiceal GCA. METHODS: We designed a retrospective multicenter cohort study and retrieved the data of patients with appendiceal neoplasms and histologically diagnosed appendiceal goblet cell carcinoid (GCC) treated from January 2000 to December 2017 in Japan. The available GCC slides were reviewed and diagnosed with a new grading system of GCA. RESULTS: A total of 922 patients from 43 institutions were enrolled; of these, 32 cases were patients with GCC (3.5%), and 20 cases were ultimately analyzed. The 5-year survival rate was 61.4% (95% confidence interval: 27.4-83.2), and the median survival time was 93.1 months. For peritoneal metastasis, regional lymph node metastasis was a significant factor (p = 0.04), and Grade 3 was a potential factor (p = 0.07). No peritoneal metastasis was observed in either T1/2 patients (n = 2) or Grade 1 patients (n = 4). We were unable to detect any significant factors associated with regional lymph node metastasis. CONCLUSION: For peritoneal metastasis, regional lymph node metastasis was a significant factor, and Grade 3 was a potential factor.

The Phase II Study of Panitumumab in Chemotherapy-Naïve Frail or Elderly Patients with RAS Wild-type Colorectal Cancer: OGSG 1602 Final Results.

BACKGROUND: We previously reported the response rate of a phase II OGSG1602 study on panitumumab in chemotherapy-naive frail or elderly patients with RAS wild-type unresectable colorectal cancer (CRC) [Terazawa T, Kato T, Goto M, et al. Oncologist. 2021;26(1):17]. Herein, we report a survival analysis. METHODS: Patients aged ≥65 years and considered unsuitable for intensive chemotherapy or aged ≥76 years were enrolled. Primary tumors located from the cecum to the transverse colon were considered right-sided tumors (RSTs); those located from the splenic flexure to the rectum were considered left-sided tumors (LSTs). RESULTS: Among the 36 enrolled patients, 34 were included in the efficacy analysis, with 26 and 8 having LSTs and RSTs, respectively. The median progression-free survival (PFS) and overall survival (OS) were 6.0 [95% CI, 5.4-10.0] and 17.5 months (95% CI, 13.8-24.3), respectively. Although no significant differences existed in PFS between patients with LST and RST {6.6 (95% CI, 5.4-11.5) vs. 4.9 months [95% CI, 1.9-not available (NA), P = .120]}, there were significant differences in OS [19.3 (95% CI, 14.2-NA) vs.12.3 months (95% CI, 9.9-NA), P = .043]. CONCLUSION: Panitumumab showed favorable OS in frail or elderly patients with RAS wild-type CRC and no prior exposure to chemotherapy. Panitumumab may be optimal for patients with LSTs (UMIN Clinical Trials Registry Number UMIN000024528).

[A Case of Locally Advanced Giant Sigmoid Colon Cancer Successfully Treated with Neoadjuvant Chemotherapy].

A 51-year-old woman presented to our hospital complaining of a lower abdominal mass and dysuria. She was diagnosed with advanced sigmoid colon cancer. The tumor was large, involving the bladder, and occupying the pelvic cavity. She received neoadjuvant chemotherapy with 4 courses of mFOLFOX6, in addition to panitumumab. The treatment resulted in a marked reduction of the tumor. A laparoscopic sigmoid colon resection, total cystectomy, neobladder reconstruction, complete uterine and bilateral adnexa resection and partial ileal resection were performed. The histopathological diagnosis was ypT4b(bladder), ypN0, ypStage Ⅱc, all with negative surgical margins. Adjuvant chemotherapy was not administered owing to the patient's refusal. She remained recurrence-free for 3 years of postoperative follow up.

Impact of the COVID-19 pandemic on colorectal cancer surgery in Japan: Clinical Study Group of Osaka University-A multicenter retrospective study.

Aim: Due to the overwhelming spread of SARS-CoV-2 and its disruption of the healthcare system, delays and reduced numbers were reported for colorectal cancer screening, colonoscopies, and surgery during the COVID-19 pandemic. This multicenter retrospective study investigated the still poorly understood impact of the COVID-19 pandemic on colorectal cancer treatment in Japan. Methods: This study was organized by the Clinical Study Group of Osaka University, which comprised 32 major institutions in Osaka. We retrospectively analyzed the number of surgeries and colonoscopies performed and the characteristics of patients who underwent surgery for colorectal cancer between March 2019 and February 2021. We compared data collected before and during the COVID-19 pandemic. We also assessed the methods used for detecting colorectal cancer, including fecal occult blood test, abdominal symptoms, and anemia. Results: The COVID-19 pandemic caused reductions in the annual numbers of surgeries (3569 vs 3198) and colonoscopies (67 622 vs 58 183) performed in the 2020 fiscal year, compared to the 2019 fiscal year. During the COVID-19 pandemic, a significantly lower proportion of patients were treated for clinical stages ≤I (24.2% vs 26.9%; P = .011), compared to the proportion treated before the pandemic. Fecal occult blood tests for detecting colorectal cancer were used significantly less frequently during the COVID-19 pandemic (26.2% vs 29.6%; P = .002). These trends were more significant in larger institutions. Conclusion: The COVID-19 pandemic reduced the number of colonoscopies and surgeries performed for colorectal cancer and hindered the detection of asymptomatic early-stage cancers, and its impact varied by hospital size.

Higher Body Mass Index Is a Simple Favorable Non-cancer Prognostic Marker for Japanese Elderly Colorectal Cancer Patients after Curative Resection.

Objectives: In elderly colorectal cancer (CRC) patients, preoperative surgical indications can be controversial in some cases depending on the patient's physical condition. In comparison with younger patients, both cancer-specific survival (CSS) and non-CCS (NCSS) have an impact on the prognosis and both CSS and NCSS should be considered in the preoperative assessment. We aimed to investigate the impact of body mass index (BMI) on CSS and NCSS in Japanese elderly CRC patients. Methods: We retrospectively collected data from 471 Japanese elderly patients (≥80 years) with stage I-III CRC who underwent curative surgery from 1998 to 2017. A Kaplan-Meier survival analysis with propensity score matching (PSM) and a multivariate Cox regression analysis were performed. Results: After PSM, 123 higher BMI (≥23) and 123 lower BMI (<23) cases were matched. The higher BMI group had significantly better survival than the lower BMI group regarding NCSS and overall survival (OS; P < .001 and P < .001, respectively). The multivariate survival analysis further confirmed that the higher BMI group had significantly better survival than the lower BMI group regarding CSS, NCSS, and OS (P = .027, P < .001, and P < .001, respectively). Conclusions: In Japanese elderly patients with stage I-III CRC who underwent curative surgery, preoperative higher BMI was a significant and simple favorable prognostic predictor, especially for NCSS and OS.

Lymph Node Diameter as a Predictor of Lymph Node Metastasis in Patients with Colorectal Neuroendocrine Neoplasms.

Objectives: The ideal cut-off value for the diameter of metastasis-positive lymph nodes (LNs) in patients with colorectal neuroendocrine neoplasms (NENs) is unclear. Thus, in this study, we investigated the correlation between the LN diameter and LN metastasis. Methods: A total of 148 LNs of 42 patients with colorectal NEN who underwent surgical dissection or local resection from April 2010 to March 2016 were included in the present study. The LN diameters were measured on computed tomography, and LN metastases were either pathologically proven or evaluated during the follow-up period. Results: Overall, 18 (12.2%) LNs were positive for LN metastasis, and 130 (87.8%) were negative. The short diameter in metastatic-positive LNs was longer than that in negative LNs (4.9 [3.0-6.3] vs. 2.0 [1.0-2.0] mm; P = 0.01). An LN of >3 mm predicted LN metastasis with 88.8% sensitivity and 78.5% specificity with an area under the curve of 0.852. Conclusions: Surgical resection with lymphadenectomy should be considered for patients with LNs of >3 mm in diameter.

Phase 3 trial of sequential versus combination treatment in colorectal cancer: The C-cubed study.

BACKGROUND: An optimal treatment strategy using oxaliplatin and bevacizumab for metastatic colorectal cancer has not been defined. We investigated whether the sequential treatment using fluoropyrimidines with bevacizumab followed by the addition of oxaliplatin at first progression was better than a combination treatment using fluoropyrimidines and oxaliplatin with bevacizumab. METHODS: In the sequential treatment, the escalation from fluoropyrimidines plus bevacizumab to fluoropyrimidines plus oxaliplatin with bevacizumab was recommended in case of progressive disease. Time to failure of strategy was the primary end-point, whereas the secondary end-points were overall survival, progression-free survival, overall response rate and safety. RESULTS: Three hundred patients with previously untreated metastatic colorectal cancer were randomised to receive either the sequential treatment (n = 151) or the combination treatment (n = 149). The sequential treatment was superior to the combination treatment about time to failure of strategy (15.2 months; 95% CI, 12.5-17.2 months vs. 7.8 months: 95% CI, 6.3-9.5 months; P < 0.001). However, the median overall survival was 27.5 (95% CI, 24.4 to 32.7) months in the sequential treatment and 27.0 (95% CI, 22.8 to 36.0) months in the combination treatment (hazard ratio, 0.92; 95% CI, 0.66 to 1.28; P = 0.61). The overall response rate was 33.1% in the sequential treatment arm and 51.7% in the combination treatment. CONCLUSIONS: The findings support the extension of the sequential treatment starting from fluoropyrimidine plus bevacizumab to selected patients who do not need an objective response to the threatening disease.