The pivotal role of neoadjuvant chemotherapy and radiotherapy in enhancing the management of gastrointestinal cancers is incontrovertible. However, their implications for surgical outcomes, particularly the risk of postoperative anastomotic fistulas, necessitate comprehensive analysis. This review examines the intricate relationship between neoadjuvant treatments and anastomotic fistula formation across a spectrum of gastrointestinal cancers, integrating findings from diverse clinical studies to elucidate risk factors and potential mitigation strategies. The timing and duration of neoadjuvant therapy emerge as critical considerations, with evidence suggesting that optimized intervals between therapy completion and surgical intervention may significantly influence fistula risk. Furthermore, patient-specific factors, including underlying health conditions and tumor characteristics, are highlighted as influential in determining fistula susceptibility. Through synthesizing current research, this review aims to guide clinical decision-making by providing insights into the balancing act of maximizing oncological efficacy while minimizing surgical complications. Future directions call for tailored treatment approaches, incorporating individual risk profiles and emerging therapeutic modalities to enhance patient outcomes in the neoadjuvant setting. 

Neoadjuvant Chemoradiotherapy and Postoperative Digestive Fistula

Objective: To investigate the safety and efficacy of the TRIANGLE operation after neoadjuvant chemotherapy in locally advanced pancreatic cancer(LAPC). Methods: This study is a retrospective case series analysis. Between January 2020 and December 2022, a total of 103 patients were diagnosed as LAPC who underwent neoadjuvant chemotherapy at the Pancreas Center, the First Affiliated Hospital of Nanjing Medical University. Among them, 26 patients (25.2%) underwent the TRIANGLE operation. There were 15 males and 11 females,with a age of (59±7) years (range: 49 to 74 years). The pre-treatment serum CA19-9(M(IQR)) was 248.8(391.6)U/ml (range: 0 to 1 428 U/ml),and the serum carcinoembryonic antigen was 4.1(3.8)μg/L(range: 1.4 to 13.4 μg/L). The neoadjuvant chemotherapy regimens included: mFOLFIRINOX regimen in 6 cases(23.1%), GnP regimen in 14 cases(53.8%), and mFOLFIRINOX+GnP regimen in 6 cases(23.1%). The follow-up duration extended until June 2023 or until the occurrence of the patient's death or loss to follow-up. The Kaplan-Meier method was employed to estimate the 1-year and 3-year overall survival rates. Results: After neoadjuvant chemotherapy,CA19-9 levels decreased by 92.3(40.1)%(range:2.1% to 97.7%). Evaluation of the response to treatment revealed 13 cases(50.0%) of stable disease,11 cases(42.3%) of partial response,and 2 cases(7.7%) of complete response. The surgical operation consisted of 12 cases(46.2%) of pancreaticoduodenectomy,12 cases(46.2%) of distal pancreatectomy,and 2 cases(7.7%) of total pancreatectomy. Margin determination was based on the "standardised pathology protocol" and the "1 mm" principle. No R2 and R1(direct) resections were observed,while the R0 resection rate was 61.5%(16/26), and the R1(1 mm) resection rate was 38.5%(10/26).The R1(1 mm) resection rates for the anterior margin,posterior margin,transected margin,portal vein groove margin,and uncinate margin were 23.1%(6/26),19.2%(5/26),12.5%(3/24),2/14, and 1/12, respectively. The overall postoperative complication rate was 57.8%(15/26),with major complications including grade B/C pancreatic fistula 25.0%(6/24,excluding 2 cases of total pancreatectomy),delayed gastric emptying in 23.1%(6/26),wound complications 11.5%(3/26),postoperative hemorrhage 7.7%(2/26), chylous fistula 7.7%(2/26) and bile fistula 3.8%(1/26). No reoperation was performed during the perioperative period(<90 days). One patient died on the 32nd day postoperatively due to a ruptured pseudoaneurysm. A total of 25 patients were followed up,with a follow-up time of 21(24)months(range: 8 to 42 months). During the follow-up period,8 cases(32.0%) died due to tumor recurrence and metastasis,while 17 patients(68.0%) remained alive,including 11 cases of disease-free survival,5 cases of distant metastasis,and 1 case of local recurrence. The overall survival rates at 1- and 3-year after the initiation of neoadjuvant chemotherapy were 95.8% and 58.9%, respectively. The overall survival rates at 1- and 3-year after surgery were 77.7% and 57.8%, respectively. Conclusion: Performing pancreatoduodenectomy according to the Heidelberg triangle protocol in LAPC patients after neoadjuvant chemotherapy might increase the R0 resection rate without increasing perioperative mortality or the incidence of major postoperative complications.目的： 探讨局部进展期胰腺癌（LAPC）转化治疗后行海德堡三角清扫的安全性和有效性。 方法： 本研究为回顾性病例系列研究。回顾性收集2020年1月至2022年12月于南京医科大学第一附属医院胰腺中心接受转化治疗的103例LAPC患者资料，将其中26例（25.2%）行海德堡三角清扫胰腺癌切除术的患者纳入研究。男性15例，女性11例，年龄（59±7）岁（范围：49~74岁）。治疗前CA19-9［M（IQR）］为248.8（391.6）U/ml（范围：0~1 428 U/ml），癌胚抗原为4.1（3.8）μg/L（范围：1.4~13.4 μg/L）。转化治疗方案包括mFOLFIRINOX方案（6例，23.1%）、GnP方案（14例，53.8%）、mFOLFIRINOX+GnP 方案（6例，23.1%）。随访时间截至2023年6月或患者死亡、失访。采用Kaplan-Meier法估算患者1年和3年总体生存率。 结果： 转化治疗后疗效评估，血清CA19-9下降92.3（40.1）%（范围：2.1%~97.7%）。疾病稳定13例（50.0%），部分缓解11例（42.3%），完全缓解2例（7.7%）。手术方式包括胰十二指肠切除术（12例，46.2%）、胰体尾切除术（12例，46.2%）、全胰切除术（2例，7.7%）。遵循标准化病理流程和“1 mm原则”，R0切除率为61.5%（16/26），R1（1 mm）切除率为38.5%（10/26）。各切缘R1（1 mm）切除率如下：前切缘23.1%（6/26），后切缘19.2%（5/26），断端切缘12.5%（3/24），门静脉沟切缘2/14，钩突切缘1/12。术后总体并发症发生率为57.7%（15/26），其中B、C级胰瘘发生率为25.0%（6/24），胃排空延迟发生率为 23.1%（6/26），切口并发症发生率为11.5%（3/26），术后出血发生率为7.7%（2/26），乳糜瘘发生率为7.7%（2/26），胆瘘发生率为3.8%（1/26）。围手术期（术后90 d内）无二次手术，1例患者术后第32天因胃十二指肠动脉残端假性动脉瘤破裂死亡。余25例患者获得随访，随访时间为21（24）个月（范围：8~42个月）。随访期间，8例（32.0%）患者因肿瘤复发转移死亡，17例（68.0%）存活，包括无瘤生存11例、远处转移5例、局部复发1例。开始转化治疗后1、3年总体生存率分别为95.8%、58.9%，术后1、3年总体生存率分别为77.7%、57.8%。 结论： LAPC转化治疗后行联合海德堡三角清扫胰腺癌切除术的R0切除率较高，围手术期病死率及术后主要并发症发生率未见明显升高，可能改善患者的远期生存。. 

[Short-term outcomes of the TRIANGLE operation after neoadjuvant chemotherapy in locally advanced pancreatic cancer].

Objective: To compare the outcomes of modified Appleby procedure and sub-adventitial divestment technique for locally advanced or borderline resectable pancreatic body cancer. Methods: A total of consecutive 58 patients(33 males and 25 females) who were diagnosed as locally advanced or borderline resectable pancreatic body cancer and underwent distal pancreatectomy at Pancreas Center, First Affiliated Hospital of Nanjing Medical University between September 2013 and May 2019 were retrospectively reviewed. The age(M(IQR)) was 62(9)years(range: 43 to 79 years). Thirty-one patients underwent distal pancreatectomy with celiac axis resection (DP-CAR) and 27 patients underwent distal pancreatectomy with sub-adventitial divestment technique(SDT). Perioperative parameters and follow-up data of these patients were analyzed. Quantitative data were compared with Wilcoxon test while categorical variables were compared with χ2 test or Fisher's exact test. Survival results were estimated by the Kaplan-Meier survival method with a Log-rank test. Results: There were no differences in age,gender,body mass index,abdominal symptoms,comorbidity or preoperative serum CA19-9 between two groups(all P>0.05). Obvious preoperative weight loss was more common in the group of SDT(48.1%(13/27) vs. 19.4%(6/31),χ²=5.431,P=0.020). Longer operative time(310(123) minutes vs. 254(137)minutes, Z=2.277,P=0.023),higher rate of combined organ resection(41.9%(13/31) vs. 14.8%(4/27),χ²=5.123,P=0.041) and longer postoperative hospital stay(15(10) days vs. 11(5)days,Z=2.292,P=0.022) were observed in the group of DP-CAR. Moreover,rate of overall morbidities was also higher (71.0%(22/31) vs. 29.6%(8/27),χ2=9.876,P=0.003),implicated by clinically relevant postoperative pancreatic fistula(61.3%(19/31) vs. 29.6%(8/27),χ2=5.814,P=0.020) in the DP-CAR group. Tumor size of the DP-CAR group was bigger(4.9(1.5)cm vs. 4.0(1.2)cm,Z=2.343,P=0.019) but no difference was seen between the DP-CAR group and SDT group in R0+R1(<1 mm) resection rate (84.0%(21/25) vs. 90.0%(18/20),P=0.678) and LNR(12.0(23.0)% vs. 9.0(18.0)%,Z=1.238,P=0.216),as well as median disease free survival(11.7 months vs. 11.4 months,Z=0.019,P=0.892) and median overall survival(16.3 months vs. 13.7 months,Z=0.172,P=0.679). Conclusions: Both DP-CAR and distal pancreatectomy with SDT are relatively safe and feasible for locally advanced or borderline resectable pancreatic body cancer. Compared with arterial resection,SDT may contribute to lower rates of postoperative complications and shorter duration of hospitalization,but no significant benefit is seen in long-term survival.

[Comparison of distal pancreatectomy with celiac axis resection and sub-adventitial divestment technique for locally advanced or borderline resectable pancreatic body cancer].

Objectives: To evaluate the positive rate of left posterior lymph nodes of the superior mesenteric artery (14cd-LN) in patients undergoing pancreaticoduodenectomy for pancreatic head carcinoma,to analyze the impact of 14cd-LN dissection on lymph node staging and tumor TNM staging. Methods: The clinical and pathological data of 103 consecutive patients with pancreatic cancer who underwent pancreaticoduodenectomy at Pancreatic Center,the First Affiliated Hospital of Nanjing Medical University from January to December 2022 were analyzed,retrospectively. There were 69 males and 34 females,with an age(M (IQR))of 63.0 (14.0) years (range:48.0 to 86.0 years). The χ2 test and Fisher's exact probability method was used for comparison of the count data between the groups,respectively. The rank sum test was used for comparison of the measurement data between groups. Univariate and multivariate Logistic regression analyzes were used for the analysis of risk factors. Results: All 103 patients underwent pancreaticoduodenectomy successfully using the left-sided uncinate process and the artery first approach. Pathological examination showed pancreatic ductal adenocarcinoma in all cases. The location of the tumors was the pancreatic head in 40 cases,pancreatic head-uncinate in 45 cases,and pancreatic head-neck in 18 cases. Of the 103 patients,38 cases had moderately differentiated tumor and 65 cases had poorly differentiated tumor. The diameter of the lesions was 3.2 (0.8) cm (range:1.7 to 6.5 cm),the number of lymph nodes harvested was 25 (10) (range:11 to 53),and the number of positive lymph nodes was 1 (3) (range:0 to 40). The lymph node stage was stage N0 in 35 cases (34.0%),stage N1 in 43 cases (41.7%),and stage N2 in 25 cases (24.3%). TNM staging was stage ⅠA in 5 cases (4.9%),stage ⅠB in 19 cases (18.4%),stage ⅡA in 2 cases (1.9%),stage ⅡB in 38 cases (36.9%),stage Ⅲ in 38 cases (36.9%),and stage Ⅳ in 1 case (1.0%). In 103 patients with pancreatic head cancer,the overall positivity rate for 14cd-LN was 31.1% (32/103),and the positive rates for 14c-LN and 14d-LN were 21.4% (22/103) and 18.4% (19/103),respectively. 14cd-LN dissection increased the number of lymph nodes (P<0.01) and positive lymph nodes (P<0.01). As a result of the 14cd-LN dissection,the lymph node stage was changed in 6 patients,including 5 patients changed from N0 to N1 and 1 patient changed from N1 to N2. Similarly,the TNM stage was changed in 5 patients,including 2 patients changed from stage ⅠB to ⅡB,2 patients changed from stage ⅡA to ⅡB,and 1 patient changed from stage ⅡB to Ⅲ. Tumors located in the pancreatic head-uncinate (OR=3.43,95%CI:1.08 to 10.93,P=0.037) and the positivity of 7,8,9,12 LN (OR=5.45,95%CI:1.45 to 20.44,P=0.012) were independent risk factors for 14c-LN metastasis; while tumors with diameter >3 cm (OR=3.93,95%CI:1.08 to 14.33,P=0.038) and the positivity of 7,8,9,12 LN (OR=11.09,95%CI:2.69 to 45.80,P=0.001) were independent risk factors for 14d-LN metastasis. Conclusion: Due to its high positive rate in pancreatic head cancer,dissection of 14cd-LN during pancreaticoduodenectomy should be recommended,which can increase the number of lymph nodes harvested,provide a more accurate lymph node staging and TNM staging.

[Clinical value of lymph node dissection of No. 14cd during pancreaticoduodenectomy in patients with pancreatic head carcinoma].

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[Short-term outcomes of the TRIANGLE operation after neoadjuvant chemotherapy in locally advanced pancreatic cancer].

[Comparison of distal pancreatectomy with celiac axis resection and sub-adventitial divestment technique for locally advanced or borderline resectable pancreatic body cancer].

[Clinical value of lymph node dissection of No. 14cd during pancreaticoduodenectomy in patients with pancreatic head carcinoma].