Adjuvant chemotherapy after hepatectomy is controversial in liver-only metastatic colorectal cancer (CRC). We conducted a randomized controlled trial to examine if adjuvant modified infusional ...fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) is superior to hepatectomy alone for liver-only metastasis from CRC.
In this phase II or III trial (JCOG0603), patients age 20-75 years with confirmed CRC and an unlimited number of liver metastatic lesions were randomly assigned to hepatectomy alone or 12 courses of adjuvant mFOLFOX6 after hepatectomy. The primary end point of phase III was disease-free survival (DFS) in intention-to-treat analysis.
Between March 2007 and January 2019, 300 patients were randomly assigned to hepatectomy alone (149 patients) or hepatectomy followed by chemotherapy (151 patients). At the third interim analysis of phase III with median follow-up of 53.6 months, the trial was terminated early according to the protocol because DFS was significantly longer in patients treated with hepatectomy followed by chemotherapy. With median follow-up of 59.2 months, the updated 5-year DFS was 38.7% (95% CI, 30.4 to 46.8) for hepatectomy alone compared with 49.8% (95% CI, 41.0 to 58.0) for chemotherapy (hazard ratio, 0.67; 95% CI, 0.50 to 0.92; one-sided
= .006). However, the updated 5-year overall survival (OS) was 83.1% (95% CI, 74.9 to 88.9) with hepatectomy alone and 71.2% (95% CI, 61.7 to 78.8) with hepatectomy followed by chemotherapy. In the chemotherapy arm, the most common grade 3 or higher severe adverse event was neutropenia (50% of patients), followed by sensory neuropathy (10%) and allergic reaction (4%). One patient died of unknown cause after three courses of mFOLFOX6 administration.
DFS did not correlate with OS for liver-only metastatic CRC. Adjuvant chemotherapy with mFOLFOX6 improves DFS among patients treated with hepatectomy for CRC liver metastasis. It remains unclear whether chemotherapy improves OS.
Background Routine creation of a diverting stoma (DS) in every patient who undergoes low anterior resection (LAR) remains controversial. We aimed to investigate the effect of DS on symptomatic ...anastomotic leakage (AL) after LAR. Study Design Patients with rectal cancer within 10 cm from the anal verge were eligible for this prospective, multicenter, cohort study (UMIN-CTR, number 000004017). Propensity score matching (PSM) was used to compare groups of patients with and without DS. Results One thousand fourteen consecutive patients were registered, of whom 936 patients who underwent LAR were analyzed. Before PSM, the overall rate of symptomatic AL was 13.2% (52 of 394) in patients with DS vs 12.7% (69 of 542) in cases without DS (p = 0.84). Symptomatic AL requiring re-laparotomy occurred in 4.7% (44 of 936) of all patients, occurring in 1.0% (4 of 394) of patients with DS vs 7.4% (40 of 542) of patients without DS (p < 0.001). After PSM, the 2 groups were nearly balanced, and the incidence rates of symptomatic AL in patients with and without DS were 10.9% and 15.8% (p = 0.26). The incidences of AL requiring re-laparotomy in patients with and without DS were 0.6% and 9.1% (p < 0.001). Multivariate analysis identified male sex (p < 0.001; odds ratio OR 3.2; 95% confidence interval CI 1.8 to 5.7) and tumor size (p < 0.001; OR 1.2; 95% CI 1.1 to 1.4) as independent risk factors of symptomatic AL. Conclusions Diverting stoma did not have a significant relationship with symptomatic AL before and after PSM. However, DS does seem to mitigate the consequences of leakage, reducing the need for urgent abdominal reoperation.
Background
In this study we examined whether histopathological findings, specifically lymphatic vessel invasion identified by an anti-human podoplanin antibody, and several other factors are ...associated with lymph node metastasis in T1 colorectal cancer.
Methods
We searched PubMed and Cochrane Library, and also handsearched relevant journals, for reports written in English and published between 1998 and 2012, utilizing combination headings, such as ‘colorectal cancer,’ ‘lymph node metastasis,’ and ‘risk factors.’ For the report to be included in our study, the following criteria had to be met: (1) data on the frequency of lymph node metastasis in T1 colorectal cancer in relation to histopathological factors were reported; (2) patients had undergone bowel resection and had histologically diagnosed T1 colorectal cancer; (3) lymphatic vessel invasion was identified by immunohistochemistry with an anti-human podoplanin antibody rather than by hematoxylin and eosin staining; (4) univariate and multivariate analyses were conducted. Studies investigating molecular markers were excluded. The independent predictive factors were confirmed in at least one study included in the meta-analysis in the present systematic review. Microsoft Excel 2013 for Windows was used for the statistical analysis.
Results
Initially, 369 publications were identified in the database searches and handsearches, of which five ultimately met all of the inclusion criteria and selected for this systematic review. The meta-analysis revealed that only two factors were significantly associated with T1 colorectal cancer lymph node metastasis: (1) lymphatic vessel invasion identified by an anti-human podoplanin antibody Mantel–Haenszel odds ratio (OR) 5.19; (95 % confidence interval (CI) 3.31–8.15;
P
= 0.01; (2) tumor budding (OR 7.45; 95 % CI 4.27–13.02;
P
= 0.0077).
Conclusion
Our meta-analysis revealed that lymphatic vessel invasion identified by an anti-human podoplanin antibody and tumor budding were significantly associated with T1 colorectal cancer lymph node metastasis.
Several studies suggest the involvement of dietary habits and gut microbiome in allergic diseases. However, little is known about the nutritional and gut microbial factors associated with the risk of ...allergic rhinitis (AR). We recruited 186 participants with symptoms of AR and 106 control subjects without symptoms of AR at the Hitachi Health Care Center, Japan. The habitual consumption of 42 selected nutrients were examined using the brief-type self-administered diet history questionnaire. Faecal samples were collected and subjected to amplicon sequencing of the 16S ribosomal RNA gene hypervariable regions. Association analysis revealed that four nutrients (retinol, vitamin A, cryptoxanthin, and copper) were negatively associated with AR. Among 40 genera examined, relative abundance of Prevotella and Escherichia were associated with AR. Furthermore, significant statistical interactions were observed between retinol and Prevotella. The age- and sex-adjusted odds of AR were 25-fold lower in subjects with high retinol intake and high Prevotella abundance compared to subjects with low retinol intake and low Prevotella abundance. Our data provide insights into complex interplay between dietary nutrients, gut microbiome, and the development of AR.
Summary Background Mesorectal excision is the international standard surgical procedure for lower rectal cancer. However, lateral pelvic lymph node metastasis occasionally occurs in patients with ...clinical stage II or stage III rectal cancer, and therefore mesorectal excision with lateral lymph node dissection is the standard procedure in Japan. We did a randomised controlled trial to confirm that the results of mesorectal excision alone are not inferior to those of mesorectal excision with lateral lymph node dissection. Methods This study was undertaken at 33 major hospitals in Japan. Eligibility criteria included histologically proven rectal cancer of clinical stage II or stage III, with the main lesion located in the rectum with the lower margin below the peritoneal reflection, and no lateral pelvic lymph node enlargement. After surgeons had confirmed macroscopic R0 resection by mesorectal excision, patients were intraoperatively randomised to mesorectal excision alone or with lateral lymph node dissection. The groups were balanced by a minimisation method according to clinical N staging (N0 or N1, 2), sex, and institution. Allocated procedure was not masked to investigators or patients. This study is now in the follow-up stage. The primary endpoint is relapse-free survival and will be reported after the primary analysis planned for 2015. Here, we compare operation time, blood loss, postoperative morbidity (grade 3 or 4), and hospital mortality between the two groups. Analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov , number NCT00190541. Findings 351 patients were randomly assigned to mesoretcal excision with lateral lymph node dissection and 350 to mesorectal excision alone, between June 11, 2003, and Aug 6, 2010. One patient in the mesorectal excision alone group underwent lateral lymph node dissection, but was analysed in their assigned group. Operation time was significantly longer in the mesorectal excision with lateral lymph node dissection group (median 360 min, IQR 296–429) than in the mesorectal excision alone group (254 min, 210–307, p<0·0001). Blood loss was significantly higher in the mesorectal excision with lateral lymph node dissection group (576 mL, IQR 352–900) than in the mesorectal excision alone group (337 mL, 170–566; p<0·0001). 26 (7%) patients in the mesorectal excision with lateral lymph node dissection group had lateral pelvic lymph node metastasis. Grade 3–4 postoperative complications occurred in 76 (22%) patients in the mesorectal excision with lateral lymph node dissection group and 56 (16%) patients in the mesorectal excision alone group. The most common grade 3 or 4 postoperative complication was anastomotic leakage (18 6% patients in the mesorectal excision with lateral lymph node dissection group vs 13 5% in the mesorectal excision alone group; p=0·46). One patient in the mesorectal excision with lateral lymph node dissection group died of anastomotic leakage followed by sepsis. Interpretation Mesorectal excision with lateral lymph node dissection required a significantly longer operation time and resulted in significantly greater blood loss than mesorectal excision alone. The primary analysis will help to show whether or not mesorectal excision alone is non-inferior to mesorectal excision with lateral lymph node dissection. Funding National Cancer Center, Ministry of Health, Labour and Welfare of Japan.
BACKGROUND:Mesorectal excision with lateral lymph node dissection is the standard treatment for locally advanced low rectal cancer in Japan. However, the safety and feasibility of laparoscopic ...lateral lymph node dissection remain to be determined.
OBJECTIVE:The purpose of this study was to evaluate the safety and feasibility of laparoscopic versus open lateral lymph node dissection for locally advanced low rectal cancer.
DESIGN:This was a retrospective cohort study using an exact matching method.
SETTING:We conducted a multicenter study of 69 specialized centers in Japan.
PATIENTS:Patients with consecutive midrectal or low rectal adenocarcinoma cancer stage II to III who underwent mesorectal excision with curative intent between 2010 and 2011 were recruited.
MAIN OUTCOME MEASURES:Short-term and oncological outcomes were compared between the laparoscopic and open-surgery groups.
RESULTS:Of the 1500 eligible patients, 676 patients who underwent lateral lymph node dissection were analyzed, including 137 patients who were treated laparoscopically and 539 patients who were treated with open surgery. After matching, the patients were stratified into laparoscopic (n = 118) and open-surgery (n = 118) groups. Operative times in the overall cohort were significantly longer (461 vs 372 min) in the laparoscopic versus the open-surgery group. In the laparoscopic group, the blood loss volume was significantly smaller (193 vs 722 mL), with fewer instances of blood transfusion (7.3% vs 25.5%) compared with the open-surgery group. The postoperative complication rates were 35.8% and 43.6% for the laparoscopic and open-surgery groups (p = 0.10). The 3-year relapse-free survival rates were 80.3% and 72.6% for the laparoscopic and open-surgery groups (p = 0.07).
LIMITATIONS:The study was limited by its retrospective design and potential selection bias.
CONCLUSIONS:Laparoscopic lateral lymph node dissection is safe and feasible for cancer stage II to III low rectal cancer and is associated with similar oncological outcomes as open lateral lymph node dissection. See Video Abstract at http://links.lww.com/DCR/A334.
This is a prospective observational cohort study aiming to include 4000 patients with stages I to III colon cancer treated at 35 specialist institutions in Japan, South Korea, Germany, Russia, ...Lithuania and Taiwan. The anatomical distribution of lymph nodes and feeding arteries are investigated using surgical specimens according to pre-specified categorizing methods using intraoperative anatomical markings. Primary analyses are performed to identify the general principles of metastatic lymph node distribution in terms of its relation to the location of the primary tumor and feeding arteries. Secondary analyses will be used to estimate prognostic outcomes according to bowel resection length and central radicality and will be used to evaluate the quality of resected surgical specimens. Through in-depth lymph node mapping, standardized criteria for the definite area of 'regional' lymph node resection in routine surgical procedures can be identified, which is expected to contribute to international standardization in colon cancer surgery (ClinicalTrials.gov NCT02938481).
Background
Laparoscopic gastrectomy is becoming more commonly performed, but acquisition of its technique remains challenging. We investigated whether laparoscopy-assisted distal gastrectomy (LDG) ...performed by trainees (TR) supervised by a technically qualified experienced surgeon (QS) is feasible and safe.
Methods
The short-term outcomes of LDG were assessed in patients with gastric cancer between 2008 and 2018. We compared patients who underwent LDG performed by qualified experienced surgeons (QS group) with patients who underwent LDG performed by the trainees (TR group).
Results
The operation time was longer in the TR group than in the QS group (median time: 270 min vs. 239 min, p < 0.001). The median duration of the postoperative hospital stay was 9 days in the QS group and 8 days in the TR group (
p
= 0.003). The incidence of postoperative complications did not differ significantly between the two groups. Grade 2 or higher postoperative complications occurred in 18 patients (12.9%) in the QS group and 47 patients (11.7%) in the TR group (
p
= 0.763). Grade 3 or higher postoperative complications occurred in 9 patients (6.4%) in the QS group and 17 patients (4.2%) in the TR group (
p
= 0.357). Multivariate analysis showed that the American Society of Anesthesiologist Physical Status was an independent predictor of grade 2 or higher postoperative complications and that gender was an independent predictor of grade 3 or higher postoperative complications. The main operator (TR/QS) was not an independent predictor of complications.
Conclusions
Laparoscopy-assisted distal gastrectomy performed by trainees supervised by an experienced surgeon is a feasible and safe procedure similar to that performed by experienced surgeons.
Background
Lymph node ratio (LNR), defined as the ratio of metastatic nodes to the total number of examined lymph nodes, has been proposed as a sensitive prognostic factor in patients with gastric ...cancer (GC). We investigate its association with survival in pathological stage (pStage) II/III GC and explore whether this is a prognostic factor in each Union for International Cancer Control pStage (7th edition).
Patients and Methods
We retrospectively examined 838 patients with pStage II/III GC who underwent curative gastrectomy between June 2000 and December 2018. Patients were classified into low-LNR (L-LNR), middle-LNR (M-LNR), and high-LNR (H-LNR) groups according to adjusted X-tile cutoff values of 0.1 and 0.25 for LNR, and their clinicopathological characteristics and survival rates were compared.
Results
The 5-year recurrence-free survival (RFS) and overall survival (OS) rates postsurgery showed significant differences among the groups (
P
< 0.001). Multivariate analysis demonstrated that LNR was a significant predictor of poor RFS M-LNR: hazard ratio (HR) 3.128, 95% confidence interval (CI) 2.254–4.342,
P
< 0.001; H-LNR: HR 5.148, 95% CI 3.546–7.474,
P
< 0.001 and OS (M-LNR: HR 2.749, 95% CI 2.038–3.708,
P
< 0.001; H-LNR: HR 4.654, 95% CI 3.288–6.588,
P
< 0.001). On subset analysis stratified by pStage, significant differences were observed between the groups in terms of the RFS curves of pStage II and III GC (
P
< 0.001 and < 0.001, respectively) and OS curves of pStage II and III GC (
P
= 0.001 and < 0.001, respectively).
Conclusions
High LNR is a predictor of worse prognosis in pStage II/III GC, including each substage.
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