Development and validation of a preoperative "difficulty score" for laparoscopic transabdominal adrenalectomy: a multicenter retrospective study.

BACKGROUND: A difficulty score for laparoscopic adrenalectomy (LA) is lacking in the literature. A retrospective cohort study was designed to develop a preoperative "difficulty score" for LA. METHODS: A multicenter study was conducted involving four Italian tertiary centers for adrenal disease. The population was randomly divided into two subsets: training group and validation one. A multicenter study was undertaken, including 964 patients. Patient, adrenal lesion, surgeon's characteristics, and the type of procedure were studied as potential predictors of target events. The operative time (pOT), conversion rate (cLA), or both were used as indicators of the difficulty in three multivariate models. All models were developed in a training cohort (70% of the sample) and validated using 30% of patients. For all models, the ability to predict complicated postoperative course was reported describing the area under the curve (AUCs). Logistic regression, reporting odds ratio (OR) with p-value, was used. RESULTS: In model A, gender (OR 2.04, p = 0.001), BMI (OR 1.07, p = 0.002), previous surgery (OR 1.29, p = 0.048), site (OR 21.8, p < 0.001) and size of the lesion (OR 1.16, p = 0.002), cumulative sum of procedures (OR 0.99, p < 0.001), extended (OR 26.72, p < 0.001) or associated procedures (OR 4.32, p = 0.015) increased the pOT. In model B, ASA (OR 2.86, p = 0.001), lesion size (OR 1.20, p = 0.005), and extended resection (OR 8.85, p = 0.007) increased the cLA risk. Model C had similar results to model A. All scores obtained predicted the target events in validation cohort (OR 1.99, p < 0.001; OR 1.37, p = 0.007; OR 1.70, p < 0.001, score A, B, and C, respectively). The AUCs in predicting complications were 0.740, 0.686, and 0.763 for model A, B, and C, respectively. CONCLUSION: A difficulty score based on both pOT and cLA (Model C) was developed using 70% of the sample. The score was validated using a second cohort. Finally, the score was tested, and its results are able to predict a complicated postoperative course.

Converted laparoscopic distal pancreatectomy: is there an impact on patient outcome and total cost?

PURPOSE: Recent studies have reported worse outcomes of converted laparoscopic distal pancreatectomy (CLDP) with respect to total laparoscopic (TLDP) and open (ODP). The aim of the study was to evaluate the impact of conversion on patient outcome and on total cost. METHODS: Patients requiring a conversion (CLDP) were compared with both TLDP and ODP patients. The relevant patient- and tumour-related variables were collected for each patient. Both intra and postoperative data were extracted. Propensity score matching (PSM) analysis was carried out to equate the groups compared. RESULTS: Two hundred and five patients underwent DP, 105 (51.2%) ODPs, 81 (39.5%) TLDPs, and 19 (9.3%) CLDPs. After PSM, 19 CLDPs, 38 TLDPs, and 38 ODPs were compared. Patients who underwent CLDP showed a significantly longer operative time (P < 0.001), and an increase in blood loss (P = 0.032) and total cost (P = 0.034) with respect to TLDP, and a significantly longer operative time (P < 0.001), less frequent postoperative morbidity (P = 0.050), and a higher readmission rate (P = 0.035) with respect to ODP. CONCLUSION: Total laparoscopic pancreatectomy was superior regarding operative findings and total costs with respect to CLDP; ODP showed a higher postoperative morbidity rate and a lower readmission rate with respect to CLDP. However, the reasons for the readmission of patients who underwent CLDP were mainly related to postoperative pancreatic fistula (POPF) grade B which is usually due to pancreas texture. Thus, the majority of distal pancreatectomies can be started using a minimally invasive approach, performing an early conversion if necessary.

Minimally invasive adrenalectomy: a comprehensive systematic review and network meta-analysis of phase II/III randomized clinical controlled trials.

PURPOSE: The best approach for minimally invasive adrenalectomy is still under debate. METHODS: A systematic search of randomized clinical trials was carried out. A frequentist random-effects network meta-analysis was made reporting the surface under the cumulative ranking (SUCRA). The primary endpoint regarded both in-hospital mortality and morbidity. The secondary endpoints were operative time (OP), blood loss (BL), length of stay (LOS), conversion, incisional hernia, and disease recurrence rate. RESULTS: Eight studies were included, involving 359 patients clustered as follows: 175 (48.7%) in the TPLA arm; 55 (15.3%) in the RPLA arm; 10 (2.8%) in the Ro-TPLA arm; 25 (7%) in the TPAA arm; 20 (5.6%) in the SILS-LA arm; and 74 (20.6%) in the RPA arm. The RPLA had the highest probability of being the safest approach (SUCRA 69.6%), followed by RPA (SUCRA 63.0%). TPAA, Ro-TPLA, SILS-LA, and TPLA have similar probability of being safe (SUCRA values 45.2%, 43.4%, 43.0%, and 38.5%, respectively). Analysis of the secondary endpoints confirmed the superiority of RPA regarding OP, BL, LOS, and incisional hernia rate. CONCLUSIONS: The best choice for patients with adrenal masses candidate for minimally invasive surgery seems to be RPA. An alternative could be RPLA. The remaining approaches could have some specific advantages but do not represent the first minimally invasive choice.

Treatment for Infected Pancreatic Necrosis Should be Delayed, Possibly Avoiding an Open Surgical Approach: A Systematic Review and Network Meta-analysis.

OBJECTIVE: To evaluate all invasive treatments for suspected IPN. SUMMARY OF BACKGROUND DATA: The optimal invasive treatment for suspected IPN remains unclear. METHODS: A systematic search of randomized clinical trials comparing at least 2 invasive strategies for the treatment of suspected IPN was carried out. A frequentist random-effects network meta-analysis was made reporting the surface under the cumulative ranking (SUCRA). The primary endpoint regarded both the in-hospital mortality and major morbidity rates. The secondary endpoints were mortality, length of stay, intensive care unit stay, the pancreatic fistula rate, and exocrine and endocrine insufficiency. RESULTS: Seven studies were included, involving 400 patients clustered as following: 64 (16%) in early surgical debridement (ED); 27 (6.7%) in peritoneal lavage (PL); 45 (11.3%) in delayed surgical debridement (DD), 169 (42.3%) in the step-up approach with minimally invasive debridement (SUA-DD) and 95 (23.7%) with endoscopic debridement (SUA-EnD). The step-up approach with endoscopic debridement had the highest probability of being the safest approach (SUCRA 87.1%), followed by SUA-DD (SUCRA 59.5%); DD, ED, and PL had the lowest probability of being safe (SUCRA values 27.6%, 31.4%, and 44.4%, respectively). Analysis of the secondary endpoints confirmed the superiority of SUA-EnD regarding length of stay, intensive care unit stay, pancreatic fistula rate, and new-onset diabetes. The SUA approaches are similar regarding exocrine function. Mortality was reduced by any delayed approaches (DD, SUA-DD, or SUA-EnD). CONCLUSIONS: The first choice for suspected IPN seemed to be SUA-EnD. An alternative could be SUA-DD. PL, ED, and DD should be avoided.

Neoadjuvant Therapy for Resectable Pancreatic Cancer: A New Standard of Care. Pooled Data From 3 Randomized Controlled Trials.

OBJECTIVE: The aim of this study was to pool data from randomized controlled trials (RCT) limited to resectable pancreatic ductal adenocarcinoma (PDAC) to determine whether a neoadjuvant therapy impacts on disease-free survival (DFS) and surgical outcome. SUMMARY BACKGROUND DATA: Few underpowered studies have suggested benefits from neoadjuvant chemo (± radiation) for strictly resectable PDAC without offering conclusive recommendations. METHODS: Three RCTs were identified comparing neoadjuvant chemo (± radio) therapy vs. upfront surgery followed by adjuvant therapy in all cases. Data were pooled targeting DFS as primary endpoint, whereas overall survival (OS), postoperative morbidity, and mortality were investigated as secondary endpoints. Survival endpoints DFS and OS were compared using Cox proportional hazards regression with study-specific baseline hazards. RESULTS: A total of 130 patients were randomized (56 in the neoadjuvant and 74 in the control group). DFS was significantly longer in the neoadjuvant treatment group compared to surgery only [hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.4-0.9] (P = 0.01). Furthermore, DFS for the subgroup of R0 resections was similarly longer in the neoadjuvant treated group (HR 0.6, 95% CI 0.35-0.9, P = 0.045). Although postoperative complications (Comprehensive Complication Index, CCI®) occurred less frequently (P = 0.008), patients after neoadjuvant therapy experienced a higher toxicity, but without negative impact on oncological or surgical outcome parameters. CONCLUSION: Neoadjuvant therapy can be offered as an acceptable standard of care for patients with purely resectable PDAC. Future research with the advances of precision oncology should now focus on the definition of the optimal regimen.

The learning curve for the second generation of laparoscopic surgeons: lesson learned from a large series of laparoscopic adrenalectomies.

BACKGROUND: Laparoscopic adrenalectomy has a well-demonstrated learning curve in the first generation of laparoscopic surgeons. Data about the second generation of laparoscopic surgeons are lacking. METHODS: In this retrospective observational study, data from patients undergoing laparoscopic adrenalectomy from 2000 to 2019 in a high-volume center were collected and analyzed. The cumulative sum of procedures of each surgeon and the operating time were evaluated. A multivariate analysis with backward stepwise logistic regression was carried out to define which factors influenced the operative time. Three surgeons performed the analyzed procedures: a senior surgeon who began his laparoscopic activity without receiving specific training or supervision and two young surgeons, who performed their procedures under the guidance of the "senior" experienced surgeon. The first 38 procedures of the three surgeons were then compared. RESULTS: A total of 244 laparoscopic adrenalectomies were performed. Age, clinical diagnosis, side of the lesion, body mass index, comorbidities, Charlson index, American Society of Anaesthesiologists (ASA) score, and lower abdominal surgery were found to have no significant relationship with the operative time (p > 0.05). Gender, symptoms, previous upper abdominal surgery, size of the lesion, and cumulative sum of procedures were independent predictors of operative time. In the comparison between different surgeons, operative time resulted significantly longer for the senior (165 min; 140-180) than for the two junior surgeons (137.5 min; 115-160; p = 0.003 and 130 min; 120-170; p = 0.001). CONCLUSIONS: The presence of a mentor in operative theater and specific training programs could be useful during the learning period. The cumulative sum of procedures related to the operative time represents a good parameter to measure the acquired expertise of a surgeon.

Blumgart Anastomosis After Pancreaticoduodenectomy. A Comprehensive Systematic Review, Meta-Analysis, and Meta-Regression.

BACKGROUND: The superiority of Blumgart anastomosis (BA) over non-BA duct to mucosa (non-BA DtoM) still remains under debate. METHODS: We performed a systematic search of studies comparing BA to non-BA DtoM. The primary endpoint was CR-POPF. Postoperative morbidity and mortality, post-pancreatectomy hemorrhage (PPH), delayed gastric emptying (DGE), reoperation rate, and length of stay (LOS) were evaluated as secondary endpoints. The meta-analysis was carried out using random effect. The results were reported as odds ratio (OR), risk difference (RD), weighted mean difference (WMD), and number needed to treat (NNT). RESULTS: Twelve papers involving 2368 patients: 1075 BA and 1193 non-BA DtoM were included. Regarding the primary endpoint, BA was superior to non-BA DtoM (RD = 0.10; 95% CI: -0.16 to -0.04; NNT = 9). The multivariate ORs' meta-analysis confirmed BA's protective role (OR 0.26; 95% CI: 0.09 to 0.79). BA was superior to DtoM regarding overall morbidity (RD = -0.10; 95% CI: -0.18 to -0.02; NNT = 25), PPH (RD = -0.03; 95% CI -0.06 to -0.01; NNT = 33), and LOS (- 4.2 days; -7.1 to -1.2 95% CI). CONCLUSION: BA seems to be superior to non-BA DtoM in avoiding CR-POPF.

The Usefulness of a Preoperative Nomogram for Predicting the Probability of Conversion from Laparoscopic to Open Distal Pancreatectomy: A Single-Center Experience.

BACKGROUND: Laparoscopic distal pancreatectomy (LDP) represents a challenging procedure with a high conversion rate. A nomogram is a simple statistical predictive tool which is superior to risk groups. The aim of this study was to develop and validate a preoperative nomogram for predicting the probability of conversion from laparoscopic to open distal pancreatectomy. METHODS: This is a retrospective study of 100 consecutive patients who underwent LDP. For each patient demographic, pre-intra- and postoperative data were collected. Univariate and multivariate analyses were carried out to identify the factors significantly influencing the conversion rate. The effect of each factor was weighted using the beta coefficient (ß), and a nomogram was built. Finally, a logistic regression between the score and the conversion rate was carried out to calibrate the nomogram. RESULTS: The conversion rate was 19.0%. At multivariate analysis, female (ß = - 1.8 ± 0.9; P = 0.047) and tail location of the tumor (ß = - 2.1 ± 1.1; P = 0.050) were significantly related to a low probability of conversion. Body mass index (BMI) (ß = 0.2 ± 0.1; P = 0.011) and subtotal pancreatectomy (ß = 2.4 ± 0.9; P = 0.006) were factors independently related to a high probability of conversion. The nomogram constructed had a minimum value of 4 and a maximum value of 18 points. The probability of conversion increased significantly starting from a minimum score of 6 points (P = 0.029; conversion probability 14.4%; 95%CI, 1.5-27.3%) up to 16 (P = 0.048; 27.8%; 95%CI, 0.2-48.7%). CONCLUSION: The nomogram proposed could serve as an effective preoperative tool capable of assessing the probability of conversion, allowing to take reliable decisions regarding indications and adequate stepwise training program of LDP.

The use of comprehensive complication Index® in pancreatic surgery: a comparison with the Clavien-Dindo system in a high volume center.

BACKGROUND: The Clavien-Dindo classification (CDC) system and Comprehensive Complication Index (CCI®) are both widely used methods for reporting the burden of postoperative complications. This study aimed to compare the accuracy of the CDC and CCI® in predicting outcomes associated with pancreatic surgery. METHODS: The CCI® and CDC were applied to 668 patients who underwent pancreatic resection. Length of postoperative stay (LOS) was chosen as the primary outcome variable. The comparison between CCI® and CDC was made with the Spearman test, reporting þs with standard error (SE) and logistic regression, reporting the Odds Ratio (OR) and Area Under the Curve with SE. RESULTS: The median value with the interquartile range (IQR) of CCI® was 20.9 (0-29.6). Both CCI® (þs = 0.609) and CDC (0.590) were significantly (P < 0.001) correlated to LOS. CCI (OR 1.056 and OR 1.052) and CDC (OR 1.978, and OR 1.994) predicted (P < 0.001) LOS over the median and 75th percentile. The accuracy of CCI® was superior to CDC for LOS over 50th (0.785 vs. 0.740; P = 0.004) and over 75th (0.835 vs. 0.761; P < 0.001) percentile. CONCLUSION: The accuracy of CCI® in measuring the complicated postoperative course was superior to CDC, correctly classifying eight patients every ten tested.

Adjuvant chemoradiation in pancreatic cancer: impact of radiotherapy dose on survival.

BACKGROUND: To evaluate the impact of radiation dose on overall survival (OS) in patients treated with adjuvant chemoradiation (CRT) for pancreatic ductal adenocarcinoma (PDAC). METHODS: A multicenter retrospective analysis on 514 patients with PDAC (T1-4; N0-1; M0) treated with surgical resection with macroscopically negative margins (R0-1) followed by adjuvant CRT was performed. Patients were stratified into 4 groups based on radiotherapy doses (group 1: < 45 Gy, group 2: ≥ 45 and < 50 Gy, group 3: ≥ 50 and < 55 Gy, group 4: ≥ 55 Gy). Adjuvant chemotherapy was prescribed to 141 patients. Survival functions were plotted using the Kaplan-Meier method and compared through the log-rank test. RESULTS: Median follow-up was 35 months (range: 3-120 months). At univariate analysis, a worse OS was recorded in patients with higher preoperative Ca 19.9 levels (≥ 90 U/ml; p < 0.001), higher tumor grade (G3-4, p = 0.004), R1 resection (p = 0.004), higher pT stage (pT3-4, p = 0.002) and positive nodes (p < 0.001). Furthermore, patients receiving increasing doses of CRT showed a significantly improved OS. In groups 1, 2, 3, and 4, median OS was 13.0 months, 21.0 months, 22.0 months, and 28.0 months, respectively (p = 0.004). The significant impact of higher dose was confirmed by multivariate analysis. CONCLUSIONS: Increasing doses of CRT seems to favorably impact on OS in adjuvant setting. The conflicting results of randomized trials on adjuvant CRT in PDAC could be due to < 45 Gy dose generally used.

Is radical surgery always curative in pancreatic neuroendocrine tumors? A cure model survival analysis.

BACKGROUND: Adjuvant therapy after curative surgery for sporadic pancreatic neuroendocrine tumor (pNETs) is not currently recommended, assuming that all patients could be cured by a radical resection. The aim of our study is to establish how many and which kind of patients remained uncured after radical resection of pNET. METHODS: Retrospective study involving 143 resected sporadic pNETs. The survival analysis was carried out using the cure model, describing the cure fraction and the excess of risk recurrence. Multivariate analyses were made in order to evaluate the non negligible effect of demographics, clinical and pathological factors on survival parameters. The results were reported as percentages, fractions, ORs and HRs with 95% confidence interval (95 CI %). RESULTS: The cure fraction and the excess of hazard rate of the whole population were 57.1% (37.4-74.6, 95% CI) and 0.06 (0.03-0.07, 95% CI), respectively. Two independent factors were related to the cure fraction: TNM stage (OR 0.27 ±â€¯0.17; P = 0.002) and grading (OR 0.11 ±â€¯0.18; P = 0.004). Considering the excess of hazard rate, only two independent factors were related to an increased risk of recurrence: TNM stage (HR 3.49 ±â€¯1.12; P = 0.004) and grading (HR 4.93 ±â€¯1.82; P < 0.001). CONCLUSION: The radical surgery has a high probability of cure in stages I-II or in grading 1 while, in stages III-IV or in grading 3 tumors, surgery alone failed to achieve a "cure". A multimodal treatment should be employed in order to avoid a recurrence of the disease.

Laparoscopic distal pancreatectomy: which factors are related to open conversion? Lessons learned from 68 consecutive procedures in a high-volume pancreatic center.

BACKGROUND: Laparoscopic distal pancreatectomy represents a difficult surgical procedure with an high conversion rate to open procedure. The factors related to its difficulty and conversion to open distal pancreatectomy were rarely reported. The aim of the present study was to identify which factors are related to conversion from laparoscopic to open distal pancreatectomy. METHODS: A retrospective study of a prospective database of 68 patients who underwent laparoscopic distal pancreatectomy was conducted at a high-volume center by pancreatic surgeons experienced with laparoscopic surgery. Pre-intra and postoperative data were collected. Patients who completed a laparoscopic distal pancreatectomy were compared with those who needed a conversion to the open approach as regard demographic, clinical, radiological, and surgical data. Univariate and multivariate analyses were carried out. RESULTS: Univariate analysis suggested that the site of the lesion, the extension of pancreatic resection, and the requirement for an extended procedure to adjacent organs were significantly associated with the risk of conversion to the open approach. Multivariate analysis showed that only the extension of the pancreatic resection (subtotal pancreatectomy) was significantly related to the odds of conversion [odds ratio (OR) 19.5; 95% confidence interval (CI) 1.1-32.3; P = 0.038]. Preoperative suspicion of malignancy differed between the two groups; however, this difference did not reach statistical significance (P = 0.078). CONCLUSIONS: Despite the limitations of the study, only the extension of pancreatic resection seemed to be the main factor related to conversion during laparoscopic distal pancreatectomy.

Minimally Invasive Pancreaticoduodenectomy: What is the Best "Choice"? A Systematic Review and Network Meta-analysis of Non-randomized Comparative Studies.

BACKGROUND: Many mini-invasive pancreaticoduodenectomy (MIPD) techniques have been reported, but their advantages with respect to an open technique (OPD) and with respect to each other are unclear. METHOD: A systematic literature search of studies comparing different types of MIPD was carried out: laparoscopic-assisted (LAPD), totally robotic (TRPD), totally laparoscopic (TLPD) or totally laparoscopic-robotic assisted (TLPD-RA) to OPD. The primary endpoint was postoperative mortality. The secondary endpoints were intraoperative, postoperative and oncological outcomes. A network meta-analysis was designed to generate direct, indirect and mixed estimate effects, between different approaches, for each variable. The effects were reported as pairwise comparisons and hierarchical ranking as to each approach could be the best or the worst for each outcome, expressed by the surface under the cumulative ranking curve. RESULTS: Twenty studies were identified, involving 2759 patients: 1813 OPDs, 81 LAPDs, 505 TRPDs, 224 TLPDs and 136 TLPD-RAs. No differences regarding postoperative mortality were found in pairwise comparison. The LAPD technique had a high probability of being the worst approach, while TRPD had a high probability of being one of the best. Regarding the secondary endpoints, OPD was the best regarding operative time and postoperative bleeding, but the worst regarding blood loss and wound infection. The TRPD or TLPD-RA techniques seemed to be the best for delayed gastric emptying, length of hospital stay, harvested lymph nodes and postoperative morbidity. The TLPD technique was often the worst approach, especially for overall and major complications, postoperative bleeding and biliary leak. CONCLUSION: The safest MIPDs are those involving a robotic system which seems to have a promising role in ameliorating the outcomes of OPD, especially when compared to a laparoscopic approach.

Sporadic Small (≤20 mm) Nonfunctioning Pancreatic Neuroendocrine Neoplasm: is the Risk of Malignancy Negligible When Adopting a More Conservative Strategy? A Systematic Review and Meta-analysis.

BACKGROUND: The management of small (≤20 mm), nonfunctioning pancreatic neuroendocrine neoplasms (pNENs) remains under debate. The European Neuroendocrine Tumor Society guidelines advocate the possibility of a conservative approach. METHODS: A systematic literature search was conducted to identify all studies comparing the risk of malignancy in small pNENs with respect to large ones (>20 mm). Malignancy was defined based on the presence of nodal metastases. Distant metastases, tumor grading (G2-3), vascular microscopic invasion, stage III-IV, and overall and disease-free survival also were evaluated. The data were reported in two ways: using the risk difference (RD) and the likelihood of being helped or harmed (LHH). RESULTS: The search identified only 6 eligible studies with an overall population of 1697 resected pNENs: 382 (22.5%) small and 1315 (77.5%) large. The RD of lymph nodal metastases was -0.26 (95% confidence interval (CI): -0.31 to -0.22; P < 0.001). The LHH was 0.34, suggesting that the risk of leaving a malignancy during follow-up due to the adoption of a conservative strategy was three times higher than the benefits. The risk difference of distant metastases, G3 lesions, G2-G3 lesions, stage III/IV, microscopic vascular invasion, death, and recurrence of the disease were lower in small NF-PNETs than large ones. The related LHH values suggested that a watch-and-wait policy never provided a benefit. CONCLUSIONS: Even if the malignancy rate in sporadic, small pancreatic neuroendocrine neoplasms was lower than in large ones, this difference did not justify a watch-and-wait policy.

Is pancreaticogastrostomy safer than pancreaticojejunostomy after pancreaticoduodenectomy? A meta-regression analysis of randomized clinical trials.

OBJECTIVE: To evaluate the clinically relevant POPF rate between Pancreatogastrostomy (PG) and pancreaticojejunostomy (PJ) after pancreaticoduodenectomy (PD). To evaluate the confounding factors affecting meta-analytic results. METHODS: A systematic literature search of randomized clinical trials (RCTs) comparing PG to PJ with an International Study Group of Pancreatic Fistula (ISGPF) definition of postoperative pancreatic fistula (POPF). Risk difference (RD) and number needed to treat or harm (NNT and NNH) were used. Fixed and random-effect models were applied. Impact of confounding covariates on the meta-analytic results was evaluated using meta-regression analysis, reporting ß coefficient ± standard error (SE). RESULTS: Seven RCTs were identified involving 1184 patients: 603 PG and 581 PJ. RD in the fixed model of clinically relevant POPFs suggested that PG was superior to PJ (RD-0.07; 95% CI: -0.11 to -0.03) with an NNT of 14 (95% CI: 9 to 33). In random model, PG was not superior to PJ (RD-0.06; 95% CI: -0.13 to 0.01) with an NNT of 17 and a possibility of harm in some cases (NNH = 100). Meta-regression suggested that the increase in the proportion of "soft pancreas" in the PG arm corresponded to a more positive value of RD (ß = 0.47 ± 0.19; P value: 0.045 ± 0.003). CONCLUSION: A PG could be slightly superior to PJ in the prevention of clinically relevant POPF. The presence of high risk pancreatic remnant remains the main limitation of PG.

Is surgery the best treatment for sporadic small (≤2 cm) non-functioning pancreatic neuroendocrine tumours? A single centre experience.

BACKGOUND: There is currently there is substantial controversy regarding the best management of non-functioning pancreatic neuroendocrine tumours ≤2 cm. METHODS: Retrospective study involving 102 surgically treated patients affected by non-functioning pancreatic neuroendocrine tumours. Patients having small tumours (≤2 cm) (Group A) and those having large tumours (>2 cm) (Group B) were compared regarding demographics, clinical and pathological factors with the aim of evaluating the risk of malignancy and survival times. RESULTS: The small tumours were T3-4 in 11% and G2-3 in 36.6% of cases; lymph node and distant metastases were present in 31% and 8% of the cases, respectively. When small and large tumours were compared, significant differences were found in relation to the presence of symptoms (P = 0.012), tumour status (P > 0.001), grading (P > 0.001) and years lost due to disability (P = 0.002). Multivariate analysis of the factors predicting malignancy and survival times showed that tumour size was related only to grading (P < 0.001). The years of life lost and disability adjusted life years were influenced by age at of diagnosis, the presence of symptoms and years lost due to disability only by grading. CONCLUSIONS: Tumour size alone did not seem to be reliable in predicting malignancy because, first, small tumours (≤2 cm) could present lymph node or distant metastases, and could be G2-3 in a non-negligible percentage of cases and second, their risk of malignancy and survival time are similar to large tumours. Additional parameters have to be considered in order to establish the proper management of small tumours, such as age at diagnosis, presence of symptoms and grading.

A critical and comprehensive systematic review and meta-analysis of studies comparing intracorporeal and extracorporeal anastomosis in laparoscopic right hemicolectomy.

PURPOSE: Two main techniques are commonly used during laparoscopic right hemicolectomy in order to perform the ileocolic anastomosis: intracorporeal (IA) and extracorporeal (EA). The aim of this study was to evaluate the safety of the two techniques. METHODS: A systematic review was carried out to identify studies comparing IA and EA. The primary endpoint was anastomotic leakage. The secondary endpoints were intra- and postoperative results. A meta-analysis was carried out using the random-effects model. RESULTS: Fourteen studies matched the selection criteria, enrolling 1717 patients (50.3 % IA, 49.7 % EA). The anastomotic leakage was similar in the IA and the EA groups (3.4 vs. 4.6 %, respectively) with a risk difference (RD) of -0.01 (95 % CI = -0.03 to 0.01; P = 0.120). IA group had lower overall complication rate (27.6 vs. 38.4 %; RD = -0.15; 95 % CI = 0.27 to -0.04; P = 0.009) and wound infection rate (4.9 vs. 8.9 %; RD = 0.52; -0.03; 95 % CI = -0.06 to -0.01; P = 0.030). Time to first oral intake (weighted mean difference (WMD) = -1; 95 % CI = -1.59 to -0.41; P < 0.001), length of hospital stay (WMD = -1.13; 95 % CI = -1.90 to -0.35; P = 0.004) and minilaparotomy size (WMD = -26; 95 % CI = -38 to -13; P < 0.001) were shorter in IA patients. The incisional hernia rate was lower in the IA group (2.3 vs. 13.7 %) with an RD of -0.09 (95 % CI = -0.17 to -0.02; P = 0.020). There were no differences in operative time, blood loss, conversion, internal hernia, reoperation, mortality, time to first flatus and defecation, analgesic required, number of lymph nodes harvested and length of distal margin. CONCLUSIONS: Laparoscopic right hemicolectomy with IA is a safe alternative to EA. Additional well-structured, prospective randomised trials are needed to confirm all the advantages regarding postoperative results which were pointed out in our study.

Prognostic role of nodal ratio, LODDS, pN in patients with pancreatic cancer with venous involvement.

BACKGROUND: The UICC/AJCC TNM staging system classifies lymph nodes as N0 and N1 in pancreatic cancer. Aim of the study is to determine whether the number of examine nodes, the nodal ratio (NR) and the logarithm odds of positive lymph nodes (LODDS) may better stratify the prognosis of patients undergoing pancreatectomy combined with venous resection for pancreatic cancer with venous involvement. METHODS: A multicenter database of 303 patients undergoing pancreatectomy in 9 Italian referral centers was analyzed. The prognostic impact of number of retrieved and examined nodes, NR, LODDS was analyzed and compared with ROC curves analysis, Pearson test, univariate and multivariate analysis. RESULTS: The number of metastatic nodes, pN, the NR and LODDS was significantly correlated with survival at multivariate analyses. The corresponding AUC for the number of metastatic nodes, pN, the NR and LODDS were 0.66, 0.69, 0.63 and 0.65, respectively. The Pearson test showed a significant correlation between the number of retrieved lymph nodes and number of metastatic nodes, pN and the NR. LODDS had the lower coefficient correlation. Concerning N1 patients, the NR, the LODDS and the number of metastatic nodes were able to significantly further stratify survival (p = 0.040; p = 0.046; p = 0.038, respectively). CONCLUSIONS: The number of examined lymph nodes, the NR and LODDS are useful for further prognostic stratification of N1 patients in the setting of pancreatectomy combined with PV/SMV resection. No superiority of one over the others methods was detected.

Pancreatectomy with Mesenteric and Portal Vein Resection for Borderline Resectable Pancreatic Cancer: Multicenter Study of 406 Patients.

PURPOSE: The role of pancreatectomy with en bloc venous resection and the prognostic impact of pathological venous invasion are still debated. The authors analyzed perioperative, survival results, and prognostic factors of pancreatectomy with en bloc portal (PV) or superior mesenteric vein (SMV) resection for borderline resectable pancreatic carcinoma, focusing on predictive factors of histological venous invasion and its prognostic role. METHODS: A multicenter database of 406 patients submitted to pancreatectomy with en bloc SMV and/or PV resection for pancreatic adenocarcinoma was analyzed retrospectively. Univariate and multivariate analysis of factors related to histological venous invasion were performed using logistic regression model. Prognostic factors were analyzed with log-rank test and multivariate proportional hazard regression analysis. RESULTS: Complications occurred in 51.9 % of patients and postoperative death in 7.1 %. Histological invasion of the resected vein was confirmed in 56.7 % of specimens. Five-year survival was 24.4 % with median survival of 24 months. Vein invasion at preoperative computed tomography (CT), N status, number of metastatic lymph nodes, preoperative serum albumin were related to pathological venous invasion at univariate analysis, and vein invasion at CT was independently related to venous invasion at multivariate analysis. Use of preoperative biliary drain was significantly associated with postoperative complications. Multivariate proportional hazard regression analysis demonstrated a significant correlation between overall survival and histological venous invasion and administration of adjuvant therapy. CONCLUSIONS: This study identifies predictive factors of pathological venous invasion and prognostic factors for overall survival, including pathological venous invasion, which may help with patients' selection for different treatment protocols.

Validation of the 2010 WHO classification and a new prognostic proposal: A single centre retrospective study of well-differentiated pancreatic neuroendocrine tumours.

BACKGOUND: In 2010, the World Health Organization (WHO) modified the classification for pancreatic neuroendocrine tumours (NETs). Recently, some modifications were proposed to improve its prognostic value. The aim of this study was to test the prognostic value of both the original and the modified 2010 WHO grading systems. METHODS: One hundred and twenty consecutive patients surgically resected for well-differentiated NETs were evaluated in multivariate Cox regression models. Age, sex, hormonal status, size, lymph node ratio, stage, margin status and grading were evaluated in order to predict disease-free survival (DFS). Four models were evaluated: model 1: grading according to the 2010 WHO; model 2: modified grading with cut-off at 5% of the Ki-67 index; model 3: modified grading in which the G2 category was divided into two subgroups (2-5% and 5-20%) and model 4: the Ki-67 index as a continuous variable. Decision curve analysis (DCA) was carried out to evaluate the clinical utility of the various cut-offs. RESULTS: All the grading systems remained independent factors in predicting DFS. Model 2 (c index = 0.814 and P = 0.012) and model 3 (c index = 0.865 and P = 0.015) showed higher predictive powers with respect to model 1 (c index = 0.799). Model 4 had a high predictive value (c index 0.848, P = 0.013). Decision curve analysis confirmed that biological behaviour represented the best prognostic parameter. CONCLUSION: This study presented some limitations: single centre, retrospective design and a long period of enrolment. The result showed that, by increasing the cut-off of the G2 category to 5% or by creating two subgroups in the G2 category, it was possible to obtain a better stratification of patients.