Short-term outcomes of a multicentre randomized clinical trial comparing D2 versus D3 lymph node dissection for colonic cancer (COLD trial).

Current guidelines indicate that D2 resection is the standard of care for patients with locally advanced gastric cancer. To assess the impact of quality assurance of lymph node removal, non-compliance and contamination in the D1 and D2 study arms of the Dutch Gastric Cancer Trial were investigated with respect to recurrence and survival. The location and numbers of lymph nodes detected at pathological investigation in the Dutch Gastric Cancer Trial were compared according to the guidelines of the Japanese Research Society for the study of Gastric Cancer. Non-compliance was defined as inadequate removal of lymph node stations. Contamination was defined as lymph nodes removed outside the intended level of resection. The dissection groups D1 and D2 were divided into non-compliance, compliance and contamination categories. Long-term overall survival was calculated for minor (2 or fewer lymph nodes) and major (more than 2 lymph nodes) non-compliance and contamination in the D1 and D2 group, using Kaplan-Meier plots. Some 1078 patients were included, of whom 711 with potentially curative surgical resections were evaluated. Overall non-compliance was 80·5 per cent in the D1 and 81·6 per cent in the D2 group. Major non-compliance occurred in 15·3 per cent of the D1 and 26·0 per cent of the D2 group. Major contamination hardly occurred. Overall 15-year survival rates in the randomized groups were 21·2 per cent (D1) and 29·0 per cent (D2) (P = 0·351). After exclusion of patients with major non-compliance and/or major contamination, survival rates were 23·2 per cent (319 patients) and 32·6 per cent (245) respectively (P = 0·261). Where there was major non-compliance, survival rates in the D1 (58 patients) and D2 (86) groups were 10 and 17 per cent respectively (P = 0·302). Survival in the D2 compliant + contaminated group (139 patients) was significantly better than that in the D1 group without contamination (282): 35·7 versus 19·9 per cent (P = 0·041). In the D2 group, there was a significant difference in survival between contaminated (95 patients) and non-contaminated (236) groups: 39 versus 25·1 per cent (P = 0·041). Non-compliance in the D2 dissection group may have obscured a significant difference in survival between the randomized groups. A D2 dissection with contamination was associated with the best survival, suggesting that extended D2 lymph node dissections improve survival.

The survival of patients with advanced gastric cancer after D2 dissection is still poor. Asian surgeons have proposed a more radical lymph node dissection, designated as D4 dissection, where paraaortic lymph nodes are removed in combination with D2 dissection. To evaluate the survival benefit of D4 dissection, a multi-institutional randomized trial of D2 vs D4 gastrectomy was conducted. Patients enrolled in the study had potentially curable gastric adenocarcinoma at an advanced stage. Patients were randomized to undergo either D2 or D4 gastrectomy. Two hundred and ninety-three patients were registered and 269 patients were eligible; 135 patients were allocated to the D2 group and 134 to the D4 group. Five-year survival was 52.6% after D2 surgery and 55.0% after D4 gastrectomy. There was no significant difference in survival between the D2 and D4 groups (chi(2) = 0.064; P = 0.801). Hospital deaths occurred in 1 patients (0.7%) in the D2 group and 5 in the D4 group D4 gastrectomy is a more risky surgery than D2 dissection. Seven patients (5.2%) in the D2 and 15 (11.2%) in the D4 group died of causes other than gastric cancer recurrence. Sixty-three patients (46.7%) in the D2 group and 52 (38.8%) in the D4 group had disease recurrence. Prophylactic D4 dissection is not recommended for patients with potentially curable advanced gastric cancer.

BackgroundIn non-inferiority trials, there is a concern that intention-to-treat (ITT) analysis, by including participants who did not receive the planned interventions, may bias towards making the treatment and control arms look similar and lead to mistaken claims of non-inferiority. In contrast, per protocol (PP) analysis is viewed as less likely to make this mistake and therefore preferable in non-inferiority trials. In a systematic review of antibiotic non-inferiority trials, we compared ITT and PP analyses to determine which analysis was more conservative.MethodsIn a secondary analysis of a systematic review, we included non-inferiority trials that compared different antibiotic regimens, used absolute risk reduction (ARR) as the main outcome and reported both ITT and PP analyses. All estimates and confidence intervals (CIs) were oriented so that a negative ARR favored the control arm, and a positive ARR favored the treatment arm. We compared ITT to PP analyses results. The more conservative analysis between ITT and PP analyses was defined as the one having a more negative lower CI limit.ResultsThe analysis included 164 comparisons from 154 studies. In terms of the ARR, ITT analysis yielded the more conservative point estimate and lower CI limit in 83 (50.6%) and 92 (56.1%) comparisons respectively. The lower CI limits in ITT analysis favored the control arm more than in PP analysis (median of − 7.5% vs. -6.9%, p = 0.0402). CIs were slightly wider in ITT analyses than in PP analyses (median of 13.3% vs. 12.4%, p < 0.0001). The median success rate was 89% (interquartile range IQR 82 to 93%) in the PP population and 44% (IQR 23 to 60%) in the patients who were included in the ITT population but excluded from the PP population (p < 0.0001).ConclusionsContrary to common belief, ITT analysis was more conservative than PP analysis in the majority of antibiotic non-inferiority trials. The lower treatment success rate in the ITT analysis led to a larger variance and wider CI, resulting in a more conservative lower CI limit. ITT analysis should be mandatory and considered as either the primary or co-primary analysis for non-inferiority trials.Trial registrationPROSPERO registration number CRD42020165040.

Curative resection is the treatment of choice for gastric cancer. Although it has been concluded that D2 lymphadenectomy plus para-aortic nodal dissection does not improve survival rate in curable gastric cancer, it is unclear whether D2 plus para-aortic nodal dissection has a benefit in some groups of patients. We conducted a retrospective study in our hospital, in which we compared D2 with D2 plus para-aortic nodal dissection lymphadenectomy for gastric cancer in subgroups of each clinical characteristic in terms of long-term survival after surgery. We selected 1792 patients who had undergone the treatment with curative intent between 1990 and 2007, 1344 in the D2 group and 448 in the D2 plus para-aortic nodal dissection group. Each procedure was verified by pathological analyses. The primary end points were 5-year overall survival. Median follow-up periods were 50 months for patients assigned to D2 group and 54 months for patients assigned to D2 plus para-aortic nodal dissection group. Overall 5-year survival was not significantly higher in patients assigned to D2 plus para-aortic nodal dissection surgery compared to those assigned to D2 surgery (31.2% (95% confidence interval: 19.8%-42.6%) vs 26.6% (95% confidence interval: 20.3%-32.9%); log-rank p = 0.433). D2 plus para-aortic nodal dissection surgery should only be used for curable gastric cancer of T3-4 and N2 stage and should not be used for T1 disease and total gastrectomy.

Aging societies comprise an increasing number of elderly gastric cancer (GC) patients. We herein attempted to determine whether D2 lymphadenectomy is beneficial for older GC patients. We retrospectively analyzed a multi-institutional dataset including 3484 patients who received surgical resection for GC. For the analysis, we selected patients aged ≥ 80years who were clinically diagnosed with T1N + or T2-4 GC. To balance the essential variables including the type of gastrectomy and the stage of progression, propensity score matching was conducted, and we compared the background clinical factors and postoperative outcomes of the patients allocated to the D2 (n = 87) and non-D2 (n = 87) dissection groups. The D2 group had significantly longer operative times, more blood loss, and more retrieved lymph nodes (median 32 vs 24, P < 0.001) than the non-D2 group. The D2 group had a greater incidence of intra-abdominal abscesses (grade ≥ II in the Clavien-Dindo classification) than the non-D2 group (3.5% vs 0%, P = 0.040). The overall disease-specific and relapse-free survival rates of the D2 group tended to be poorer than those of the non-D2 group (hazard ratios 1.49, 1.70 and 1.14, respectively). D2 lymphadenectomy for older patients with GC conferred little benefit regarding overall survival despite an occurrence of increased complication rates.

To evaluate the clinical effect of a 10-day sequential therapy which was made up of omeprazole, clarithromycin, amoxicillin-clavulanate and metronidazole for the eradication of Helicobacter pylori (Hp) infection in children. A total of 214 children with abdominal pain, who were confirmed to have Hp infection through endoscopy, biopsy, and Hp culture. The 214 cases were randomly divided into four groups. A 10-day sequential therapy group accepted omeprazole 0.8 - 1.0 mg/(kg·d) plus amoxicillin-clavulanate 50 mg/(kg·d) for five days and omeprazole 0.8 - 1.0 mg/(kg·d), clarithromycin 20 mg/(kg·d) and metronidazole 20 mg/(kg·d) for the remaining five days. The 7-day triple therapy group, 10-day triple therapy group and 14-day triple therapy group received omeprazole 0.8 - 1.0 mg/(kg·d), amoxicillin-clavulanate 50 mg/(kg·d) and clarithromycin 20 mg/(kg·d) for 7 days,10 days,14 days, respectively. All drugs were given twice daily. All these patients received (13)C urea breath test ((13)C-UBT) four weeks after the treatment. Finally, 199 patients were followed up, and the total rate of loss to follow-up was 7.0% (15/214). Hp eradication rate was 85.2% and 90.2% in the 10-day sequential therapy group on intention to treat (ITT) and per protocol (PP) analyses, 66.0% and 71.4% in the 7-day triple therapy group on ITT and PP analyses; 60.0% and 67.3% in 10-day triple therapy group on ITT and PP analyses, and 78.8% and 82.0% in patients who received the 10-day sequential regimen on ITT and PP analyses, respectively. By ITT analysis, there was significantly difference between the 10-day sequential therapy group and 7-day or 10-day triple therapy group (P < 0.05), while no significant difference was found between the 10-day sequential therapy group and 14-day triple therapy group (P > 0.05). The results of the ITT analysis and the PP analysis were the same. The four groups had neither significant difference in abdominal pain relief (P > 0.05) nor in incidence of adverse reactions (P > 0.05). The 10-day sequential regimen was significantly more effective than both 7-day triple regimen and 10-day triple regimen, while had the same eradication rate compared with the 14-day sequential therapy. But 10-day triple regimen to eradicate Hp infection in children had the advantages such as short course of treatment and better compliance.

Few studies have reported the incidence and clinical outcomes of gallstone disease after extended (D2) lymph node dissection for gastric cancer. The present study was designed to retrospectively compare limited (D1) and D2 dissections in terms of gallstone formation, presentation of gallstones, and surgery for gallstone disease. A total of 805 Japanese gastric cancer patients (595 male, 210 female) who underwent curative resection with D1 (n = 490) or D2 (n = 315) dissection were retrospectively reviewed. Of those subjects followed for 70.5 +/- 44.3 months (range: 2-196 months), 102 (12.7%) developed gallstones. The incidence of gallstone formation was higher in the D2 group than in the D1 group (17.8% vs. 9.4%, p = 0.001). The interval between gastrectomy and detection of gallstones was shorter in the D2 group than in the Dl group (18.8 +/- 11.4 months vs. 29.4 +/- 18.3 months, p = 0.002). Of those with gallstones followed for 48.0 +/- 28.6 months (range: 1-158 months), 74 (72.5%) remained asymptomatic, and 15 (14.7%) experienced mild biliary pain. Thirteen patients (12.7%) developed recurrent biliary pain (n = 3) or biliary complications (n = 10; 6 acute cholecystitis, 3 obstructive jaundice, and 1 cholangitis), and required surgical treatment. Surgery was more frequently sought in the D2 group than in the D1 group (19.5% vs. 4.3%, p = 0.033). In conclusion, patients with D2 dissection developed gallstones more frequently and earlier than patients with D1 dissection. Of those with gallstones, patients with D2 dissection required surgery more often than patients with D1 dissection. A closer follow-up should be mandatory for gallstone disease after D2 dissection, but further studies are needed before generalizations can be made.

The standard procedure of lymph node (LN) dissection for rectal or sigmoid colon cancer remains controversial. Many laparoscopic surgeons cut the inferior mesenteric artery (IMA) at the root; however, this may cause bowel ischemia around the site of anastomosis. We performed D3 or D2 LN dissection with the preservation of the IMA. The aim of this study was to evaluate the oncologic outcomes of IMA-preserving LN dissection. We retrospectively analyzed 142 consecutive patients with upper-rectal or sigmoid colon cancer who underwent laparoscopic LN dissection with the preservation of the IMA. The number of LNs dissected and the overall and disease-free survival rates were retrospectively evaluated. Laparoscopic D3 (n = 92) or D2 (n = 50) LN dissection were performed with the preservation of the IMA. The left colic artery was preserved in all cases, the superior rectal artery was also preserved in 30 cases. The mean number of LNs dissected was 19.6 in the D3 group and 12.9 in the D2 group. The median operative time was 230 minutes, and the median volume of blood loss was 17 mL. There was no treatment-related mortality. The estimated 5-year disease-free survival rates of the stage I, II, and III patients were 93%, 83%, and 74%, respectively. No patients developed LN recurrence. Laparoscopic surgery with IMA-preserving LN dissection is an oncologically acceptable treatment strategy in patients with upper-rectal or sigmoid colon cancer.

Short-Term Outcomes of Complete Mesocolic Excision Versus D2 Dissection in Patients Undergoing Laparoscopic Colectomy for Right Colon Cancer (RELARC Trial): A Multicentre Randomised Controlled Phase III Trial

Gastric cancer is a common malignancy worldwide. Effective treatment by interdisciplinary cooperation is important, and surgery still plays an important role. In a ten-year period, 355 patients were diagnosed to have gastric cancer. One hundred and sixty-two patients with a median (range) age of 58 (23-83) years were eligible for the study. There were 107 patients in D2 and 55 patients in D2 lymphadenectomy plus para-aortic lymph node (PALN) dissection group. The two groups were compared in terms of complications, morbidity, mortality and long-term survival. Length of stay was 12 (8-34) days for D2 and 14 (8-42) days for D2 plus PALND. Total number of operative mortality was 8/162 (5%), and it was not different between the groups. Twenty patients (18%) had complications in D2 group and 9 (17%) patients in D2 plus PALND group. Overall survival was also similar between the groups, but patients with T3-T4 tumors, patients with stage IIIA and IIIB disease had better survival with D2 plus PALN dissection. We found that the depth of invasion, PLN, ratio (PLN/TLN), stage and LND were all prognostic variables. This study showed that D2 plus PALN dissection for advanced gastric cancer can be performed as safely as a standard D2 dissection by experienced surgeons without increasing postoperative morbidity and mortality. D2 plus PALN dissection should be preferred in the advanced stage of the disease (IIIA-IIIB) as it increases the rate of survival.

According to Japanese guidelines, D2 or D3 lymph node dissection (LND) is indicated for cT2N0M0 colorectal cancer (CRC). In this study, we retrospectively compared the long-term outcomes between D2 and D3 LND among patients with cT2N0M0 CRC. Our sample included 515 patients from the Japanese Study Group for Postoperative Follow-Up of Colorectal Cancer database, who underwent surgical resection for cT2N0M0 CRC between January 2009 and December 2012, 195 (37.9%) of whom underwent D2 LND and 320 (62.1%) D3 LND. The D2 and D3 groups were retrospectively compared in terms of long-term outcomes including overall survival (OS) and relapse-free survival (RFS). The prognostic factors for these outcomes were also evaluated. The D2 group had significantly older patients and higher proportion of men than the D3 group. The rates of OS (5-year OS; 94.8% in the D3 group vs. 93.4% in the D2 group, p = 0.38) and RFS (5-year RFS; 89.3% in the D3 group vs. 89.1% in the D2 group, p = 0.91) were comparable for both groups. On multivariate analysis, age ≥ 80years was significantly associated with poor OS. The extent of LND was not associated with either OS or RFS. Long-term outcomes were similar between the two groups, independent of tumor location. The long-term outcomes did not differ between the D2 and D3 groups and the extent of LND was not associated with prognosis for cT2N0M0 CRC. Therefore, D2 LND may be sufficient for cT2N0N0 CRC treatment.

Objective: To investigate the effect of entropy index targeted monitoring combined with dexmedetomidine infusion on cognitive function after thoracic and abdominal surgery in elderly patients. Methods: 60 elderly patients undergoing abdominal surgery in our hospital on October ~2017 and October 2019 were selected, ASAⅡ~ grade III, and the random digital table method was divided into 3 groups ,20 cases in each group. entropy index monitoring combined with dexmedetomidine group (D1 group), entropy index monitoring combined with dexmedetomidine group (D2 group) and dexmedetomidine monitoring combined with saline group (D0 group). All patients were subjected to sequential rapid induction of endotracheal intubation general anesthesia. D1, D2, the group was injected with 0.5μg/kg dexmedetomidine hydrochloride intravenously in the first 15 min of induction, followed by a 0.3μg•kg-1•h-1, 0.6μg•kg-1•h-1 maintenance pump until 30 minutes before the end of operation, respectively. The D0 group was injected with the same amount of saline intravenously before induction, and then maintained with the same amount of saline. D1 and D2 groups were calibrated at 40~60. preoperative (T1), tracheal intubation immediate (T2),30 min after operation (T3) and extubation immediate (T4) M after operation were compared in 3 groups AP (mmhg), hr (sub/ min), blood oxygen saturation (SpO2) and intraoperative anesthetic dosage, vasoactive drug use, and postoperative recovery status; simple intelligent mental state examination scale (MMSE) test was completed 1 day before ,1 day after ,3 days after and 7 days after operation to record the incidence of perioperative neurocognitive disorders (PND). To detect the necrosis factor-α(TNF-α) and C-reactive protein (CRP) of the above-mentioned concurrent serum tumors; Results Compared with D0 group, the MAP of D1 group and D2 group decreased significantly and the HR slowed down significantly (P&lt;0.05), The MAP, HR of T3, T4 in D2 group was significantly decreased compared with that in the D1 group (P&lt;0.05), but the difference was not significant at all time points (0.05);The respiratory recovery time (min), dialling time (min) and restoring directional force time (min) were significantly shortened compared with the D0 group and the D2 group, and the consumption of propofol and sufentanil during the operation was significantly decreased. Compared with the D2 group, the use of vasoactive drugs in the D1 group was significantly decreased (P&lt;0.05). The TNF-α, CRP of patients in the first day and the third day were higher than those in the first day of operation, but the TNF-α, CRP of D1 group and D2 group were lower than those in the D0 group (0.05). The MMSE scores of l days and 3 days after operation in D1 and D2 groups were higher than those in D0 groups. Significantly decreased (P&lt;0.05), and there was no significant difference between the groups 7 days after operation (P&gt;0.05): Conclusion entropy index targeted monitoring combined with dexmedetomidine infusion (0.3μg/kg/h) in the elderly patients during surgery can improve the intraoperative and postoperative hemodynamic stability, can improve the perioperative neurocognitive disorders of patients, worthy of clinical promotion.

Extended lymph node dissection for gastric cancer from a European perspective

To explore the impact of clinicopathological features and extent of lymph node dissection on the prognosis in early gastric cancer (EGC) patients. A total of 142 EGC cases screened from database of gastric cancer of Sun Yat-sen University, from Aug. 1994 to Jan. 2010, were included in this study. According to the lymph node metastasis status, they were divided into lymph node negative (n = 116) and lymph node positive (n = 26) groups. The clinicopathological features of the two groups and the impact of extent of lymph node dissection on the prognosis were analyzed. There were no significant differences in age, gender, tumor size and location, Borrmann typing, WHO TNM staging, histological typing, and CEA value between the two groups (P > 0.05). The TNM stages in the lymph node positive group were higher than that in the lymph node negative group (P < 0.001). Between the cases who underwent D1 (n = 21) and D2 (n = 121) dissection, there were no significant differences in postoperative hospital days, blood transfusion volume, and operation time (P > 0.05). The median numbers of LN dissected in D1 and D2 cases were 4 (0 to 16) and 20 (12 to 30), with a significant difference (P = 0.000), but the number of positive LN without significant difference (P = 0.502). The postoperative complication rates were 9.5% in the D1 and 3.3% in the D2 dissection groups, without a significant difference (P = 0.128). The median survival time of the lymph node negative and positive groups was 156 vs. 96 months (P = 0.010). In cases who received D2 and D1 lymph node dissection, the median survival time (MST) was 156 vs. 96 months (P = 0.0022). In the lymph node positive group, D2 dissection prolonged survival time significantly than D1 dissection (96 vs. 27months) (P = 0.001). Cox regression analysis showed that the extent of lymph node dissection and LN metastasis were independent prognostic factors for EGC patients. It is not able to accurately assess the LN metastasis status preoperatively according to the routine clinicopathological features. For the patients with unknown LN metastasis status, D2 dissection should be the first choice. Comparing with D1 dissection, the morbidity of D2 dissection are not increased, but survival time is prolonged.

Complete mesocolic excision (CME) is being increasingly used for the treatment of right-sided colon cancer, although there is still no strong evidence that CME provides better long-term oncological outcomes than D2 dissection. The controversy is mainly regarding the survival benefit from extended lymph node dissection emphasized by CME. This multicenter, open-label, randomized controlled trial (ClinicalTrials.gov identifier: NCT02619942) was performed across 17 hospitals in China. Patients diagnosed with stage T2-T4aNanyM0 or TanyN + M0 right-sided colon cancer were randomly assigned (1:1) to undergo either CME or D2 dissection during laparoscopic right colectomy. The primary outcome was the 3-year disease-free survival (DFS), and the main secondary outcome was the 3-year overall survival (OS). Between January 11, 2016, and December 26, 2019, 1,072 patients were randomly assigned (536 patients to CME and 536 patients to D2 dissection). In total, 995 patients (median age 61 years, 59% male) were included in the primary analysis (CME [n = 495] v D2 dissection [n = 500]). No significant differences were found between the groups in 3-year DFS (hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.02]; P = .06; 86.1% in the CME group v 81.9% in the D2 group) or in 3-year OS (HR, 0.70 [95% CI, 0.43 to 1.16]; P = .17; 94.7% in the CME group v 92.6% in the D2 group). This trial failed to find evidence of superior DFS outcome for CME compared with standard D2 lymph node dissection in primary surgical excision of right-sided colon cancer. Standard D2 dissection should be the routine procedure for these patients. CME should only be considered in patients with obvious mesocolic lymph node involvement.