Thoracic Epidural Analgesia Is Not Associated With Improved Survival After Pancreatic Surgery: Long-Term Follow-Up of the Randomized Controlled PAKMAN Trial.

BACKGROUND: Perioperative thoracic epidural analgesia (EDA) and patient-controlled intravenous analgesia (PCIA) are common forms of analgesia after pancreatic surgery. Current guidelines recommend EDA over PCIA, and evidence suggests that EDA may improve long-term survival after surgery, especially in cancer patients. The aim of this study was to determine whether perioperative EDA is associated with an improved patient prognosis compared to PCIA in pancreatic surgery. METHODS: The PAKMAN trial was an adaptive, pragmatic, international, multicenter, randomized controlled superiority trial conducted from June 2015 to October 2017. Three to five years after index surgery a long-term follow-up was performed from October 2020 to April 2021. RESULTS: For long-term follow-up of survival, 109 patients with EDA were compared to 111 patients with PCIA after partial pancreatoduodenectomy (PD). Long-term follow-up of quality of life (QoL) and pain assessment was available for 40 patients with EDA and 45 patients with PCIA (questionnaire response rate: 94%). Survival analysis revealed that EDA, when compared to PCIA, was not associated with improved overall survival (OS, HR, 1.176, 95% HR-CI, 0.809-1.710, P = .397, n = 220). Likewise, recurrence-free survival did not differ between groups (HR, 1.116, 95% HR-CI, 0.817-1.664, P = .397, n = 220). OS subgroup analysis including only patients with malignancies showed no significant difference between EDA and PCIA (HR, 1.369, 95% HR-CI, 0.932-2.011, P = .109, n = 179). Similar long-term effects on QoL and pain severity were observed in both groups (EDA: n = 40, PCIA: n = 45). CONCLUSIONS: Results from this long-term follow-up of the PAKMAN randomized controlled trial do not support favoring EDA over PCIA in pancreatic surgery. Until further evidence is available, EDA and PCIA should be considered similar regarding long-term survival.

A Simple Classification of Pancreatic Duct Size and Texture Predicts Postoperative Pancreatic Fistula: A classification of the International Study Group of Pancreatic Surgery.

OBJECTIVE: The aim of this study was to develop a classification system for pancreas-associated risk factors in pancreatoduodenectomy (PD). SUMMARY BACKGROUND DATA: Postoperative pancreatic fistula (POPF) is the most relevant PD-associated complication. A simple standardized surgical reporting system based on pancreas-associated risk factors is lacking. METHODS: A systematic literature search was conducted to identify studies investigating clinically relevant (CR) POPF (CR-POPF) and pancreas-associated risk factors after PD. A meta-analysis of CR-POPF rate for texture of the pancreas (soft vs not-soft) and main pancreatic duct (MPD) diameter was performed using the Mantel-Haenszel method. Based on the results, the International Study Group of Pancreatic Surgery (ISGPS) proposes the following classification: A, not-soft (hard) texture and MPD >3 mm; B, not-soft (hard) texture and MPD ≤3 mm; C, soft texture and MPD >3 mm; D, soft texture and MPD ≤3 mm. The classification was evaluated in a multi-institutional, international cohort. RESULTS: Of the 2917 articles identified, 108 studies were included in the analyses. Soft pancreatic texture was significantly associated with the development of CR-POPF [odds ratio (OR) 4.24, 95% confidence interval (CI) 3.67-4.89, P < 0.01) following PD. Similarly, MPD diameter ≤3 mm significantly increased CR-POPF risk compared with >3 mm diameter MPDs (OR 3.66, 95% CI 2.62-5.12, P < 0.01). The proposed 4-stage system was confirmed in an independent cohort of 5533 patients with CR-POPF rates of 3.5%, 6.2%, 16.6%, and 23.2% for type A-D, respectively ( P < 0.001). CONCLUSION: For future pancreatic surgical outcomes studies, the ISGPS recommends reporting these risk factors according to the proposed classification system for better comparability of results.

Oncological recurrence following pathological complete response after neoadjuvant treatment in patients with esophageal cancer - a retrospective cohort study.

BACKGROUND: To evaluate recurrence in patients with post-neoadjuvant pathological complete response (pCR) and in patients with complete response of primary tumor but persisting lymphatic spread of disease (non-pCR, ypT0ypN +) of esophageal cancer. METHODS: Seventy-five patients (63 pCR, 12 non-pCR) were analyzed retrospectively. Pattern and incidence of local and distant recurrence as well as the impact on overall (OS) and disease-free survival (DFS) were evaluated. The efficacy of neoadjuvant chemotherapy according to FLOT protocol was compared to neoadjuvant chemoradiation according to CROSS protocol. RESULTS: In the pCR group, isolated local recurrence was diagnosed in 3%, while no isolated local recurrence was observed in the non-pCR group due to the high incidence of distant recurrence. Distant recurrence was most common in both cohorts (isolated distant recurrence: pCR group 10% to non-pCR group 55%; simultaneous distant and local recurrence: pCR group 3% to non-pCR group 18%). Median time to distant recurrence was 5.5 months, and median time to local recurrence was 8.0 months. Cumulative incidence of distant recurrence (with and without simultaneous local recurrence) was 16% (± 6%) in pCR patients and 79% (± 13%) in non-pCR patients (hazard ratio (HR) 0.123) estimated by Kaplan-Meier method. OS (HR 0.231) and DFS (HR 0.226) were significantly improved in patients with pCR compared to patients with non-pCR. Advantages for FLOT protocol compared to CROSS protocol, especially with regard to distant control of disease (HR 0.278), were observed (OS (HR 0.361), DFS (HR 0.226)). CONCLUSION: Distant recurrence is the predominant site of treatment failure in patients with pCR and non-pCR grade 1a regression, whereby recurrence rates are much higher in patients with non-pCR.

Pathological complete response in multimodal treatment of esophageal cancer: a retrospective cohort study.

To evaluate pathological complete response (pCR, ypT0ypN0) after neoadjuvant treatment compared with non-complete response (non-CR) in patients with esophageal cancer (EC), and 393 patients were retrospectively analyzed. Survival probability was analyzed in patients with: (i) pCR vs non-CR; (ii) complete response of the primary tumor but persisting lymphatic metastases (non-CR-T0N+) and (iii) pCR and tumor-free lymphnodes exhibiting signs of postneoadjuvant regression vs. no signs of regression. (i) Median overall survival (mOS) was favorable in patients with pCR (pCR: mOS not reached vs. non-CR: 41 months, P < 0.001). Multivariate analysis revealed that grade of regression was not an independent predictor for prolonged survival. Instead, the achieved postneoadjuvant TNM-stage (T-stage: Hazard ratio [HR] ypT3-T4 vs. ypT0-T2: 1.837; N-stage: HR ypN1-N3 vs. ypN0: 2.046; Postneoadjuvant M-stage: HR ypM1 vs. ycM0: 2.709), the residual tumor (R)-classification (HR R1 vs. R0: 4.195) and the histologic subtype of EC (HR ESCC vs. EAC: 1.688) were prognostic factors. Patients with non-CR-T0N+ have a devastating prognosis, similar to those with local non-CR and lymphatic metastases (non-CR-T + N+) (non-CR-T0N+: 22.0 months, non-CR-T + N-: mOS not reached, non-CR-T + N+: 23.0 months; P-values: non-CR-T0N+ vs. non-CR-T + N-: 0.016; non-CR-T0N+ vs. non-CR-T + N+: 0.956; non-CR-T + N- vs. non-CR-T + N+: <0.001). Regressive changes in lymphnodes after neoadjuvant treatment did not influence survival-probability in patients with pCR (mOS not reached in each group; EAC-patients: P = 0.0919; ESCC-patients: P = 0.828). Particularly, the achieved postneoadjuvant ypTNM-stage influences the survival probability of patients with EC. Patients with non-CR-T0N+ have a dismal prognosis, and only true pathological complete response with ypT0ypN0 offers superior survival probabilities.

Arterial Resection in Pancreatic Cancer Surgery: Effective After a Learning Curve.

OBJECTIVE: To investigate the perioperative and oncologic long-term outcomes of patients with LAPC after surgical resection at a high-volume center for pancreatic surgery. BACKGROUND: The role of surgery in LAPC with arterial involvement is controversial. METHODS: We analyzed 385 consecutive patients undergoing PAR (n = 195) or PAD (n = 190) of the encased artery for LAPC between January 1, 2003 and April 30, 2019. RESULTS: There were 183 total pancreatectomies, 113 partial pancreatoduodenectomies, 79 distal pancreatectomies, and 10 resections for tumor recurrences, including 121 multivisceral resections and 171 venous resections. Forty-three patients (11.4%) had resectable oligometastatic disease. All of the 190 patients undergoing PAD (100%) and 95 of the 195 patients undergoing PAR (48.7%) received neoadjuvant chemotherapy. The R0 (circumferential resection margin negative) resection rate was 28%. The median hospital stay was 15 days (range: 3-236). The median survival after surgery for LAPC was 20.1 months and the overall 5-year survival rate 12.5%. In-hospital mortality was 8.8% for the entire patient cohort (n = 385). With increasing case load and growing expertise, there was a significant reduction of in-hospital mortality to 4.8% (n = 186) after 2013 (P = 0.005). The learning curve of experienced pancreatic surgeons for PAR was 15 such procedures. CONCLUSION: Our data demonstrate that an arterial surgical approach is effective in LAPC with promising long-term survival. PAD after neoadjuvant treatment is safe. PAR is a technically demanding procedure and requires a high level of expertise.

Actual Five-year Survival After Upfront Resection for Pancreatic Ductal Adenocarcinoma: Who Beats the Odds?

OBJECTIVE: To determine actual five-year survival (5YS) rates associated with a strategy of upfront surgery and adjuvant therapy in pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: The rate of actual 5YS in PDAC remains controversial. Available data is restricted to cohorts acquired over several decades and series of resection after patient selection by neoadjuvant therapy. METHODS: All patients undergoing upfront resection for resectable and borderline-resectable PDAC from 10/2001 to 12/2011 were identified from a prospective database. Actual overall survival was assessed after a follow-up of at least 5 years. Uni- and multivariable logistic regression analyses were performed. RESULTS: Median survival of 937 patients was 22.1 months. The actual 5YS rate was 17.0% (n = 159) including 89 (9.5%) patients without evidence of disease >5 years after resection. 5YS rates in patients with or without adjuvanttherapy were 18.8% vs. 12.2%, respectively. Tumorgrading, number of positive lymph nodes, a context of intraductal papillary mucinous neoplasia, and vascular resections were independently associated with 5YS. Patient-related parameters and CA 19-9 levels were associated with observed survival up to 3 years, but lost relevance thereafter. The extent of lymph node involvement was the strongest predictor of 5YS. Patients with pN0R0 had a 5YS rate of 38.2%. in patients with exclusively favorable factors the observed 5YS rate was above 50%. CONCLUSIONS: This is the largest series of long-term survivors with histologically confirmed PDAC. With upfront resection and adjuvant therapy an actual overall 5YS rate of 18.8% can be expected. in favorable subgroups actual 5YS is above 50%.

Gastric Venous Congestion After Total Pancreatectomy is Frequent and Dangerous.

OBJECTIVE: The aim of this study was to determine the role of GVC in mortality after TP. BACKGROUND: Data from a nationwide administrative database revealed that TP is associated with a 23% mortality rate in Germany. Methods: A total of 585 consecutive patients who had undergone TP (n = 514) or elective completion pancreatectomy (n = 71) between January 2015 and December 2019 were analyzed. Univariable and multivariable analyses were performed to identify risk factors for GVC and 90-day mortality. Results: GVC was observed in 163 patients (27.9%) requiring partial or total gastrectomy. Splenectomy (odds ratio 2.14, 95% confidence interval 1.253.80, P = 0.007) and coronary vein resection (odds ratio 5.49,95% confidence interval 3.19-9.64, P < 0.001) were independently associated with GVC. The overall 90-day mortality after TP was 4.1% (24 of 585 patients), 7.4% in patients with GVC and 2.8% in those without GVC ( P = 0.014). Of the 24 patients who died after TP, 12 (50%) had GVC. CONCLUSION: GVC is a frequent albeit not well-known finding after TP, especially when splenectomy and resection of the coronary vein are performed. Adequate decision making for partial gastrectomy during TP is crucial. Insufficient gastric venous drainage after TP is life-threatening.

Pancreatic surgery with or without drainage: propensity score-matched study.

BACKGROUND: A recent RCT has shown that routine intraoperative drain placement after pancreatoduodenectomy (PD) is not necessary. The aim was to confirm this in real-world conditions. METHODS: A propensity score-matched (PSM) analysis of patients with and without drainage after PD or distal pancreatectomy (DP) at a high-volume centre was undertaken. Main outcomes were complications and duration of hospital stay. Multivariable regression analysis was used to assessed which factors led to intraoperative drainage after the standard was changed from drain to no drain. RESULTS: Of 377 patients who underwent PD, 266 were included in PSM analysis. No drain was associated with fewer major complications (42 (31.6 per cent) versus 62 (46.6 per cent); P = 0.017), shorter duration of hospital stay (mean(s.d.) 14.7(8.5) versus 19.6(14.9) days; P = 0.001), and required fewer interventional drain placements (8.4 versus 19.8 per cent; P = 0.013). In PSM analysis after DP (112 patients), no drainage was associated with fewer clinically relevant postoperative pancreatic fistulas (9 versus 18 per cent; P = 0.016), fewer overall complications (mean(s.d.) comprehensive complication index score 15.9(15.4) versus 24.8(20.4); P = 0.012), and a shorter hospital stay (9.3(7.0) versus 13.5(9.9) days; P = 0.011). Multivisceral resection (OR 2.80, 95 per cent c.i. 1.10 to 7.59; P = 0.034) and longer operating times (OR 1.56, 1.04 to 2.36; P = 0.034) influenced the choice to place a drain after PD. Greater blood loss was associated with drainage after DP (OR 1.14, 1.02 to 1.30; P = 0.031). CONCLUSION: Standard pancreatic resections can be performed safely without drainage. Surgeons were more reluctant to omit drainage after complex pancreatic resections.

Pancreatic surgery has traditionally relied on the use of drains placed during surgery that should facilitate outflow of fluids from the operating site. This principle has recently been challenged by specially designed studies showing that patients who do not receive a drain may have fewer complications. The present study has demonstrated that these results also apply to routine clinical settings outside the constraints of surgical trials.

Antecolic versus retrocolic reconstruction after partial pancreaticoduodenectomy.

BACKGROUND: Pancreatic cancer remains one of the five leading causes of cancer deaths in industrialised nations. For adenocarcinomas in the head of the gland and premalignant lesions, partial pancreaticoduodenectomy represents the standard treatment for resectable tumours. The gastro- or duodenojejunostomy after partial pancreaticoduodenectomy can be reestablished via either an antecolic or retrocolic route. The debate about the more favourable technique for bowel reconstruction is ongoing. OBJECTIVES: To compare the effectiveness and safety of antecolic and retrocolic gastro- or duodenojejunostomy after partial pancreaticoduodenectomy. SEARCH METHODS: In this updated version, we conducted a systematic literature search up to 6 July 2021 to identify all randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Library 2021, Issue 6, MEDLINE (1946 to 6 July 2021), and Embase (1974 to 6 July 2021). We applied no language restrictions. We handsearched reference lists of identified trials to identify further relevant trials, and searched the trial registries clinicaltrials.govand World Health Organization International Clinical Trials Registry Platform for ongoing trials. SELECTION CRITERIA: We considered all RCTs comparing antecolic with retrocolic reconstruction of bowel continuity after partial pancreaticoduodenectomy for any given indication to be eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the identified references and extracted data from the included trials. The same two review authors independently assessed risk of bias of included trials, according to standard Cochrane methodology. We used a random-effects model to pool the results of the individual trials in a meta-analysis. We used odds ratios (OR) to compare binary outcomes and mean differences (MD) for continuous outcomes. MAIN RESULTS: Of a total of 287 citations identified by the systematic literature search, we included eight randomised controlled trials (reported in 11 publications), with a total of 818 participants. There was high risk of bias in all of the trials in regard to blinding of participants and/or outcome assessors and unclear risk for selective reporting in six of the trials. There was little or no difference in the frequency of delayed gastric emptying (OR 0.67; 95% confidence interval (CI) 0.41 to 1.09; eight trials, 818 participants, low-certainty evidence) with relevant heterogeneity between trials (I2=40%). There was little or no difference in postoperative mortality (risk difference (RD) -0.00; 95% CI -0.02 to 0.01; eight trials, 818 participants, high-certainty evidence); postoperative pancreatic fistula (OR 1.01; 95% CI 0.73 to 1.40; eight trials, 818 participants, low-certainty evidence); postoperative haemorrhage (OR 0.87; 95% CI 0.47 to 1.59; six trials, 742 participants, low-certainty evidence); intra-abdominal abscess (OR 1.11; 95% CI 0.71 to 1.74; seven trials, 788 participants, low-certainty evidence); bile leakage (OR 0.82; 95% CI 0.35 to 1.91; seven trials, 606 participants, low-certainty evidence); reoperation rate (OR 0.68; 95% CI 0.34 to 1.36; five trials, 682 participants, low-certainty evidence); and length of hospital stay (MD -0.21; 95% CI -1.41 to 0.99; eight trials, 818 participants, low-certainty evidence). Only one trial reported quality of life, on a subgroup of 73 participants, also without a relevant difference between the two groups at any time point. The overall certainty of the evidence was low to moderate, due to some degree of heterogeneity, inconsistency and risk of bias in the included trials. AUTHORS' CONCLUSIONS: There was low- to moderate-certainty evidence suggesting that antecolic reconstruction after partial pancreaticoduodenectomy results in little to no difference in morbidity, mortality, length of hospital stay, or quality of life. Due to heterogeneity in definitions of the endpoints between trials, and differences in postoperative management, future research should be based on clearly defined endpoints and standardised perioperative management, to potentially elucidate differences between these two procedures. Novel strategies should be evaluated for prophylaxis and treatment of common complications, such as delayed gastric emptying.

The TRIANGLE operation for pancreatic head and body cancers: early postoperative outcomes.

BACKGROUND: Surgical resection is the mainstay of potential cure for patients with pancreatic cancer, however, local recurrence is frequent. Previously, we have described an extended resection technique for pancreatoduodenectomy aiming at a radical resection of the nerve and lymphatic tissue between celiac artery, superior mesenteric artery and mesenteric-portal axis (TRIANGLE operation). Until now, data on postoperative outcome have not been reported, yet. METHODS: Patients who underwent either partial (PD) or total pancreatoduodenectomy (TP) applying the TRIANGLE procedure were identified. These cohorts were compared to matched historic cohorts with standard resections. RESULTS: Overall, 330 patients were analysed (PDTRIANGLE and PDSTANDARD, each n = 108; TPTRIANGLE and TPSTANDARD, each n = 57). More lymph nodes were harvested in TRIANGLE compared to standard resection (PD: 27.5 (21-35) versus 31.5 (24-40); P = 0.0187, TP: 33 (28-49) versus 44 (29-53); P = 0.3174) and the rate of tumour positive resections margins, R1(direct), dropped. Duration of operation was significantly longer and blood loss higher. Postoperative mortality and complications did not differ significantly. CONCLUSION: Pancreatoduodenectomy according to the TRIANGLE protocol can be performed without increased morbidity and mortality at a high-volume centre. Long-term survival and quality of life need to be investigated in prospective clinical trials with adequate sample size.

Characteristics and Prognostic Factors of Metachronous Second Primary Upper Gastrointestinal Cancer.

BACKGROUND: Patients with metachronous malignancies before carcinomas of the upper gastrointestinal tract were analyzed regarding clinical parameters, oncological outcome, and prognosis. METHODS: We analyzed the data of 1583 patients with gastroesophageal cancer who underwent oncological resections between 2002 and 2018. Of 1583 patients, 172 had a malignant tumor before the upper gastrointestinal cancer (second primary carcinomas) and 1411 without preceding malignancies served as the control group. The analyses were performed between both groups and within the subgroup of second primary carcinomas. RESULTS: Patients with second primary carcinomas were older (P < 0.0001), had more comorbidities (P < 0.0001), and underwent longer surgical resections (P = 0.0024). They had lower (y)pT-categories (P = 0.0427) and had longer stays in intensive care unit (P = 0.0002) and hospital (P = 0.0018). R0-resection was more frequent (P = 0.0275) while having more surgical complications (P = 0.0378). The median survival was 39.5 mo (primary carcinoma) versus 32.9 mo for (second primary carcinoma) and was not significantly different (P = 0.5359).In the subgroup analysis of second primaries, there were no significant survival differences depending on primary tumor entity (P = 0.4989). pT status (P = 0.0062), pN status (P < 0.0001), pM status (P < 0.0001), and R-status (P < 0.0001) were significant prognostic factors. A time period >9 y after the primary cancer could be identified as a novel and beneficial survival factor (P = 0.0496). Most patients with primary colorectal, prostate, hematogenous, or breast cancer had adenocarcinoma, whereas patients with initial otolaryngologic cancers mainly had squamous cell carcinoma. CONCLUSIONS: Second primary carcinomas of the upper gastrointestinal tract show distinct clinical and oncological characteristics. Common prognostic factors are applicable, and oncologic resection is recommended.

Self-Expanding Metal Stents for Anastomotic Leaks After Upper Gastrointestinal Cancer Surgery.

BACKGROUND: Anastomotic leakage (AL) is a common and severe complication after upper gastrointestinal (UGI) surgery. Although evidence is scarce, endoscopic deployed self-expanding metal stents (SEMS) are well-established for the management of AL in UGI surgery. The present study aimed to evaluate the feasibility, effectiveness, and safety of SEMS in terms of success, mortality, and morbidity in patients with AL after UGI cancer surgery. MATERIALS AND METHODS: Patients with AL after primary UGI cancer surgery were retrospectively analyzed with regard to demographics, disease, surgical and endoscopic procedures, and complications. Stent treatment success was divided into technical, primary (within 72 hours of stent deployment), sustained (after 72 hours of stent deployment), and sealing success. RESULTS: In a total of 63 patients, 74 stents were used and 11 were deployed in endoscopic reinterventions. Stent deployment was successful in all patients. Primary and sustained success rates were 68.3% (n = 43) and 65.1% (n = 41), respectively. Of the primarily successfully treated patients, 87.8% remained successfully treated. If primary treatment was unsuccessful, it remained unsuccessful in 66.6% of the patients (P = 0.002). Final sealing of the leakage was observed in 65.1% of patients (n = 41). Longer stent shafts and wider stent end widths were correlated with successful stent treatment (P < 0.05). CONCLUSION: SEMS are a safe and sufficient tool in the treatment of AL after UGI cancer surgery. Treatment success is improved with longer stent shafts and wider stent end widths. Switching to alternative treatments is strongly suggested if signs of persistent leakage are present beyond 72 hours after stent placement, as this is highly indicative of sustained stent failure.

Feasibility, effectiveness, and safety of endoscopic vacuum therapy for intrathoracic anastomotic leakage following transthoracic esophageal resection.

BACKGROUND: Anastomotic leakage (AL) in the upper gastrointestinal (GI) tract is associated with high morbidity and mortality rates. Especially intrathoracic anastomotic leakage leads to life-threatening complications. Endoscopic vacuum therapy (EVT) for anastomotic leakage after transthoracic esophageal resection represents a novel concept. However, sound clinical data are still scarce. This retrospective, single-center study aimed to evaluate the feasibility, effectiveness, and safety of EVT for intrathoracic anastomotic leakage following abdomino-thoracic esophageal resection. METHODS: From March 2014 to September 2019 259 consecutive patients underwent elective transthoracic esophageal resection. 72 patients (27.8%) suffered from AL. The overall collective in-hospital mortality rate was 3.9% (n = 10). Data from those who underwent treatment with EVT were included. RESULTS: Fifty-five patients were treated with EVT. Successful closure was achieved in 89.1% (n = 49) by EVT only. The EVT-associated complication rate was 5.4% (n = 3): bleeding occurred in one patient, while minor sedation-related complications were observed in two patients. The median number of EVT procedures per patient was 3. The procedures were performed at intervals of 3-5 days, with a 14-day median duration of therapy. The mortality rate of patients with AL was 7.2% (n = 4). Despite successfully terminated EVT, three patients died because of multiple organ failure, acute respiratory distress syndrome, and urosepsis (5.4%). One patient (1.8%) died during EVT due to cardiac arrest. CONCLUSIONS: EVT is a safe and effective approach for intrathoracic anastomotic leakages following abdomino-thoracic esophageal resections. It offers a high leakage-closure rate and the potential to lower leakage-related mortalities. TRIAL REGISTRATION: This trial was registered and approved by the Institutional Ethics Committee of the University of Heidelberg on 16.04.2014 (Registration Number: S-635/2013).

Health-related quality of life in primary hepatic cancer: a systematic review assessing the methodological properties of instruments and a meta-analysis comparing treatment strategies.

PURPOSE: Patient-reported outcomes including health-related quality of life (HRQoL) are important oncological outcome measures. The validation of HRQoL instruments for patients with hepatocellular and cholangiocellular carcinoma is lacking. Furthermore, studies comparing different treatment options in respect to HRQoL are sparse. The objective of the systematic review and meta-analysis was, therefore, to identify all available HRQoL tools regarding primary liver cancer, to assess the methodological quality of these HRQoL instruments and to compare surgical, interventional and medical treatments with regard to HRQoL. METHODS: A systematic literature search was conducted in MEDLINE, the Cochrane library, PsycINFO, CINAHL and EMBASE. The methodological quality of all identified HRQoL instruments was performed according to the COnsensus-based Standards for the selection of health status Measurements INstruments (COSMIN) standard. Consequently, the quality of reporting of HRQoL data was assessed. Finally, wherever possible HRQoL data were extracted and quantitative analyses were performed. RESULTS: A total of 124 studies using 29 different HRQoL instruments were identified. After the methodological assessment, only 10 instruments fulfilled the psychometric criteria and could be included in subsequent analyses. However, quality of reporting of HRQoL data was insufficient, precluding meta-analyses for 9 instruments. CONCLUSION: Using a standardized methodological assessment, specific HRQoL instruments are recommended for use in patients with hepatocellular and cholangiocellular carcinoma. HRQoL data of patients undergoing treatment of primary liver cancers are sparse and reporting falls short of published standards. Meaningful comparison of established treatment options with regard to HRQoL was impossible indicating the need for future research.

Ligamentum teres augmentation (LTA) for hiatal hernia repair after minimally invasive esophageal resection: a new use for an old structure.

PURPOSE: Hiatal hernias with intrathoracic migration of the intestines are serious complications after minimally invasive esophageal resection with gastric sleeve conduit. High recurrence rates have been reported for standard suture hiatoplasties. Additional mesh reinforcement is not generally recommended due to the serious risk of endangering the gastric sleeve. We propose a safe, simple, and effective method to close the hiatal defect with the ligamentum teres. METHODS: After laparoscopic repositioning the migrated intestines, the ligamentum teres is dissected from the ligamentum falciforme and the anterior abdominal wall. It is then positioned behind the left lobe of the liver and swung toward the hiatal orifice. Across the anterior aspect of the hiatal defect it is semi-circularly fixated with non-absorbable sutures. Care should be taken not to endanger the blood supply of the gastric sleeve. RESULTS: We have used this technique for a total of 6 patients with hiatal hernias after hybrid minimally invasive esophageal resection in the elective (n = 4) and emergency setting (n = 2). No intraoperative or postoperative complications have been observed. No recurrence has been reported for 3 patients after 3 months. CONCLUSION: Primary suture hiatoplasties for hiatal hernias after minimally invasive esophageal resection can be technically challenging, and high postoperative recurrence rates are reported. An alternative, safe method is needed to close the hiatal defect. Our promising preliminary experience should stimulate further studies regarding the durability and efficacy of using the ligamentum teres hepatis to cover the hiatal defect.

Systematic reviews in surgery-recommendations from the Study Center of the German Society of Surgery.

BACKGROUND: Systematic reviews are an important tool of evidence-based surgery. Surgical systematic reviews and trials, however, require a special methodological approach. PURPOSE: This article provides recommendations for conducting state-of-the-art systematic reviews in surgery with or without meta-analysis. CONCLUSIONS: For systematic reviews in surgery, MEDLINE (via PubMed), Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) should be searched. Critical appraisal is at the core of every surgical systematic review, with information on blinding, industry involvement, surgical experience, and standardisation of surgical technique holding special importance. Due to clinical heterogeneity among surgical trials, the random-effects model should be used as a default. In the experience of the Study Center of the German Society of Surgery, adherence to these recommendations yields high-quality surgical systematic reviews.

Meta-analysis of primary open versus closed cannulation strategy for totally implantable venous access port implantation.

BACKGROUND: There is still no reference standard for the implantation of totally implantable venous access ports (TIVAPs). A recently published multicentre randomised controlled trial (RCT) revealed a significantly greater risk of pneumothorax after closed cannulation than after an open strategy. The aim of this meta-analysis was to provide an update of the available evidence for the safety and effectiveness of primary open versus closed cannulation strategy. METHODS: RCTs comparing outcomes of open cut-down of the cephalic vein and closed cannulation of the subclavian vein were sought systematically in MEDLINE, Web of Science and CENTRAL. The primary outcome was the occurrence of pneumothorax. A beta-binominal model was applied to combine the respective outcomes, and results are presented as odds ratios (OR) with 95% confidence interval (CI). RESULTS: Six RCTs with a total of 1831 patients were included in final analysis. Meta-analysis showed statistically significant superiority of the open cut-down technique regarding pneumothorax (OR 0.308, 95% CI 0.122 to 0.776), but a statistically significant higher failure of the primary technique for the open cut-down technique than for closed cannulation (OR 2.364, 95% CI 1.051 to 5.315). There were no significant differences between the two procedures regarding other morbidity endpoints. CONCLUSION: This meta-analysis shows a general superiority of open cut-down of the cephalic vein over closed cannulation of the subclavian vein regarding the occurrence of pneumothorax. Open cut-down should be the first-line approach for TIVAP implantation. Closed cannulation should be performed with ultrasound as second-line procedure if the open technique fails. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42013005180.

Sub-adventitial divestment technique for resecting artery-involved pancreatic cancer: a retrospective cohort study.

PURPOSE: To introduce sub-adventitial divestment technique (SDT), a procedure to remove the tumor while preserving the artery during curative pancreatectomy. Peri-operative safety profile was also evaluated. METHODS: In a single center consecutive series of pancreatectomy for pancreatic cancer, the outcome of patients who had pancreatectomy with SDT was compared to standard pancreatic surgery. RESULTS: From June 2014 to June 2016, 72 patients had pancreatectomy with SDT and 235 had standard surgery. Tumor stage was T4 in all 72 (100%) tumors removed using SDT compared to four (2%) with standard pancreatectomy (p < 0.001). All 72 (100%) tumors in the SDT group were stage III compared to 24 (10%) in the standard surgery group (p < 0.001). Both groups had a high proportion of poorly differentiated tumors (52 (72%) and 163 (69%) respectively) and perineural tumor invasion (62 (86%) and 186 (79%) respectively). R1 (< 1 mm) was found in 24 (86%) of 28 tumors in the SDT group, and in 72 (60%) out of 120 standard pancreatectomy tumors (p = 0.01). Complications occurred in 29 (40%) of the SDT group and in 88 (37%) of the standard group. The in-hospital mortality was four (6%) in the SDT group and one (0.4%) in the standard group (p = 0.01), with a 90-day mortality of 5 (8%)/60 and 6 (3%)/209 (p = 0.07) respectively. CONCLUSIONS: The sub-adventitial divestment technique appeared to be an effective surgical technique to remove the tumor while preserving the artery. This approach warrants further validation in prospective studies.

A systematic review and meta-analysis of randomized controlled trials comparing laparoscopic and open liver resection.

BACKGROUND/PURPOSE: The dissemination of laparoscopic liver resection (LLR) has been based on non-randomized studies and reviews of these. Aim of this study was to evaluate if the randomized evidence comparing LLR to open liver resection (OLR) supports these findings. METHODS: A prospectively registered (reviewregistry866) systematic review and meta-analysis following Cochrane and PRISMA guidelines comparing LLR to OLR for benign and malignant diseases was performed via Medline, Web of Science, CENTRAL up to 31.12.2020. The main outcome was postoperative complications. Risk of bias was assessed with the Cochrane Risk of Bias tool 2.0, certainty of evidence was assessed using the GRADE approach. RESULTS: The search yielded 2080 results. 13 RCTs assessing mostly minor liver resections with 1457 patients were included. There were reduced odds of experiencing any complication (Odds ratio (OR) [95% confidence interval (CI)]: 0·42 [0·30, 0·58]) and severe complications (OR[CI]: 0·51 [0·31, 0·84]) for patients undergoing LLR. LOS was shorter (Mean difference (MD) [CI]: -2·90 [-3·88, -1·92] days), blood loss was lower (MD: [CI]: -115·41 [-146·08, -84·75] ml), and functional recovery was better for LLR. All other outcomes showed no significant differences. CONCLUSIONS: LLR shows significant postoperative benefits. RCTs assessing long-term outcomes and major resections are needed.

Postoperative acute pancreatitis is a serious but rare complication after distal pancreatectomy.

BACKGROUND: The clinical relevance of hyperamylasemia after distal pancreatectomy (DP) remains unclear and no internationally accepted definition of postoperative acute pancreatitis (POAP) exists. The aim of this study was to characterize POAP after DP and to assess the role of serum amylase (SA) in POAP. METHODS: Outcomes of 641 patients who had undergone DP between 2015 and 2019 were analyzed. Postoperative SA was determined in all patients. POAP was defined based on contrast-enhanced computed tomography (CT) or intraoperative findings during relaparotomy. RESULTS: An elevation of SA on postoperative day 1 (hyperamylasemiaPOD1) was found in 398 patients (62.1%). Twelve patients (1.87%) were identified with POAP. Ten patients demonstrated radiologic criteria for POAP and in two patients POAP was diagnosed during relaparotomy. Outcome of POAP patients was worse than that of patients with hyperamylasemiaPOD1 alone and that with normal SAPOD1 without POAP evidence (postoperative pancreatic fistula 50% vs 30.6% vs 18.5%; length of hospital stay 26 days vs 12 vs 11, respectively). The overall 90-day mortality of all 641 patients was 0.6%. CONCLUSION: POAP is a serious but rare complication after DP. HyperamylasemiaPOD1 is of prognostic relevance after DP, but it seems not sufficient as a single parameter to diagnose POAP.