Robotic versus laparoscopic distal pancreatectomy: multicentre analysis.

BACKGROUND: The role of minimally invasive distal pancreatectomy is still unclear, and whether robotic distal pancreatectomy (RDP) offers benefits over laparoscopic distal pancreatectomy (LDP) is unknown because large multicentre studies are lacking. This study compared perioperative outcomes between RDP and LDP. METHODS: A multicentre international propensity score-matched study included patients who underwent RDP or LDP for any indication in 21 European centres from six countries that performed at least 15 distal pancreatectomies annually (January 2011 to June 2019). Propensity score matching was based on preoperative characteristics in a 1 : 1 ratio. The primary outcome was the major morbidity rate (Clavien-Dindo grade IIIa or above). RESULTS: A total of 1551 patients (407 RDP and 1144 LDP) were included in the study. Some 402 patients who had RDP were matched with 402 who underwent LDP. After matching, there was no difference between RDP and LDP groups in rates of major morbidity (14.2 versus 16.5 per cent respectively; P = 0.378), postoperative pancreatic fistula grade B/C (24.6 versus 26.5 per cent; P = 0.543) or 90-day mortality (0.5 versus 1.3 per cent; P = 0.268). RDP was associated with a longer duration of surgery than LDP (median 285 (i.q.r. 225-350) versus 240 (195-300) min respectively; P < 0.001), lower conversion rate (6.7 versus 15.2 per cent; P < 0.001), higher spleen preservation rate (81.4 versus 62.9 per cent; P = 0.001), longer hospital stay (median 8.5 (i.q.r. 7-12) versus 7 (6-10) days; P < 0.001) and lower readmission rate (11.0 versus 18.2 per cent; P = 0.004). CONCLUSION: The major morbidity rate was comparable between RDP and LDP. RDP was associated with improved rates of conversion, spleen preservation and readmission, to the detriment of longer duration of surgery and hospital stay.

Laparoscopic versus open extended radical left pancreatectomy for pancreatic ductal adenocarcinoma: an international propensity-score matched study.

BACKGROUND: A radical left pancreatectomy in patients with pancreatic ductal adenocarcinoma (PDAC) may require extended, multivisceral resections. The role of a laparoscopic approach in extended radical left pancreatectomy (ERLP) is unclear since comparative studies are lacking. The aim of this study was to compare outcomes after laparoscopic vs open ERLP in patients with PDAC. METHODS: An international multicenter propensity-score matched study including patients who underwent either laparoscopic or open ERLP (L-ERLP; O-ERLP) for PDAC was performed (2007-2015). The ISGPS definition for extended resection was used. Primary outcomes were overall survival, margin negative rate (R0), and lymph node retrieval. RESULTS: Between 2007 and 2015, 320 patients underwent ERLP in 34 centers from 12 countries (65 L-ERLP vs. 255 O-ERLP). After propensity-score matching, 44 L-ERLP could be matched to 44 O-ERLP. In the matched cohort, the conversion rate in L-ERLP group was 35%. The L-ERLP R0 resection rate (matched cohort) was comparable to O-ERLP (67% vs 48%; P = 0.063) but the lymph node yield was lower for L-ERLP than O-ERLP (median 11 vs 19, P = 0.023). L-ERLP was associated with less delayed gastric emptying (0% vs 16%, P = 0.006) and shorter hospital stay (median 9 vs 13 days, P = 0.005), as compared to O-ERLP. Outcomes were comparable for additional organ resections, vascular resections (besides splenic vessels), Clavien-Dindo grade ≥ III complications, or 90-day mortality (2% vs 2%, P = 0.973). The median overall survival was comparable between both groups (19 vs 20 months, P = 0.571). Conversion did not worsen outcomes in L-ERLP. CONCLUSION: The laparoscopic approach may be used safely in selected patients requiring ERLP for PDAC, since morbidity, mortality, and overall survival seem comparable, as compared to O-ERLP. L-ERLP is associated with a high conversion rate and reduced lymph node yield but also with less delayed gastric emptying and a shorter hospital stay, as compared to O-ERLP.

C-Reactive Protein and Procalcitonin as Predictors of Postoperative Inflammatory Complications After Pancreatic Surgery.

BACKGROUND: The association between postoperative inflammatory markers and risk of complications after pancreaticoduodenectomy (PD) is controversial. We sought to assess the diagnostic value of perioperative C-reactive protein (CRP) and procalcitonin (PCT) levels in the early identification of patients at risk for complications after PD. METHODS: In 2014, 84 patients undergoing elective PD were enrolled in a prospective database. Clinicopathological characteristics, CRP and PCT, as well as short-term outcomes, such as complications and pancreatic fistula, were analyzed. Complications and pancreatic fistula were defined based on the Clavien-Dindo classification and the International Study Group on Pancreatic Fistula (ISGPF) classification, respectively. High CRP and PCT were classified using cut-off values based on ROC curve analysis. RESULTS: The majority (73.8 %) of patients had pancreatic adenocarcinoma. CRP and PCT levels over the first 5 postoperative days (POD) were higher among patients who experienced a complication versus those who did not (p < 0.001). Postoperative CRP and PCT levels were also higher among patients who developed a grade B or C pancreatic fistula (p < 0.05). A CRP concentration >84 mg/l on POD 1 (AUC 0.77) and >127 mg/l on POD 3 (AUC 0.79) was associated with the highest risk of overall complications (OR 6.86 and 9.0, respectively; both p < 0.001). Similarly patients with PCT >0.7 mg/dl on POD 1 (AUC 0.67) were at higher risk of developing a postoperative complication (OR 3.33; p = 0.024). On POD 1, a CRP >92 mg/l (AUC 0.72) and a PCT >0.4 mg/dl (AUC 0.70) were associated with the highest risk of pancreatic fistula (OR 5.63 and 5.62, respectively; both p < 0.05). CONCLUSIONS: CRP and PCT concentration were associated with an increased risk of developing complications and clinical relevant pancreatic fistula after PD. Use of these biomarkers may help identify those patients at highest risk for perioperative morbidity and help guide postoperative management of patients undergoing PD.

The prognostic impact of para-aortic lymph node metastasis in pancreatic cancer: A systematic review and meta-analysis.

PURPOSE: To evaluate by a meta-analytic approach the long-term prognostic impact of para-aortic lymph node (PALN) involvement in resected ductal adenocarcinoma of the pancreas. METHODS: MEDLINE, Embase, PubMed and the Cochrane Library were searched from January 1990 to June 2015. Trials reporting Kaplan-Meier curves and comparing overall long-term survival of negative and metastatic PALN in patients who underwent resection for pancreatic cancer were included. Lymph nodes were classified according to the Japan Pancreatic Society rules and identified using hematoxylin and eosin staining. Hazard ratios (HRs) and 95%CI were estimated for each trial and pooled in a meta-analysis. RESULTS: Thirteen eligible studies including 2141 patients (364 positive PALN; 1777 negative PALN) were identified. Most of the studies were retrospective. Heterogeneity among trials was high (I(2) = 98.7%; p < .001). PALN metastasis was associated with increased mortality when compared with patients with negative PALN regardless regional nodal status [HR 1.85, 95%CI 1.48-2.31; p < .001]. Median survival was significantly decreased in patients with positive PALN (WMD = -4.92 months 95%CI -6.40; -3.43; p < .001). Moreover, metastatic PALN affected mortality also when regional lymph nodes were positive [HR 1.67, 95%CI 1.34-2.08; p < .001]. No publication bias was detected. CONCLUSIONS: PALN metastasis appears to correlate with poor prognosis in patients with pancreatic adenocarcinoma. The assessment of PALN status may be considered for a more accurate staging of the disease and appropriated subgroup survival reporting. However, the definitive avoidance of the resection in case of intraoperative metastatic PALN needs further investigation.

Serum apolipoprotein C-II is prognostic for survival after pancreatic resection for adenocarcinoma.

BACKGROUND: Pancreaticoduodenectomy remains a major undertaking. A preoperative blood test, which could confidently predict the benefits of surgery would improve the selection of pancreatic cancer patients for surgery. This study aimed to identify protein biomarkers prognostic for long-term survival and to validate them with clinico-pathological information. METHODS: Serum from 40 preoperative patients was used to train for predictive biomarkers using surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI), and the results were verified on 21 independent samples. Two predictive proteins were identified by tryptic peptide mass fingerprinting and sequencing, and validated on serum from another 57 patients by enzyme-linked immunosorbent assay (ELISA). The influence of these proteins on growth and invasion of two cancer cell lines was tested in-vitro. RESULTS: The SELDI panel of m/z 3700, 8222 and 11 522 peaks predicted <12 months' survival (ROC AUC: 0.79, 0.64-0.90; P<0.039). When CA19-9 was added, the ROC AUC increased to 0.95 (0.84-0.99; P<0.0001). The six subjects in the verification group who died within 12 months were correctly classified. The m/z 8222 and 11 522 proteins were identified as Serum ApoC-II and SAA-1, respectively. In the validation samples, ELISA results confirmed that ApoC-II was predictive of survival (Kaplan-Meier P<0.009), but not SAA-I. ApoC-II, CA19-9 and major-vessel involvement independently predicted survival. ApoC-II and SAA-1 increased cell growth and invasion of both cancer cell lines. CONCLUSION: Serum ApoC-II, CA19-9 and major-vessel invasion independently predict survival and improves selection of patients for pancreaticoduodenectomy.

Discovery of serum biomarkers for pancreatic adenocarcinoma using proteomic analysis.

BACKGROUND AND AIMS: The serum/plasma proteome was explored for biomarkers to improve the diagnostic ability of CA19-9 in pancreatic adenocarcinoma (PC). METHODS: A Training Set of serum samples from 20 resectable and 18 stage IV PC patients, 54 disease controls (DCs) and 68 healthy volunteers (HVs) were analysed by surface-enhanced laser desorption and ionisation time-of-flight mass spectrometry (SELDI-TOF MS). The resulting protein panel was validated on 40 resectable PC, 21 DC and 19 HV plasma samples (Validation-1 Set) and further by ELISA on 33 resectable PC, 28 DC and 18 HV serum samples (Validation-2 Set). Diagnostic panels were derived using binary logistic regression incorporating internal cross-validation followed by receiver operating characteristic (ROC) analysis. RESULTS: A seven-protein panel from the training set PC vs DC and from PC vs HV samples gave the ROC area under the curve (AUC) of 0.90 and 0.90 compared with 0.87 and 0.91 for CA19-9. The AUC was greater (0.97 and 0.99, P<0.05) when CA19-9 was added to the panels and confirmed on the validation-1 samples. A simplified panel of apolipoprotein C-I (ApoC-I), apolipoprotein A-II (ApoA-II) and CA19-9 was tested on the validation-2 set by ELISA, in which the ROC AUC was greater than that of CA19-9 alone for PC vs DC (0.90 vs 0.84) and for PC vs HV (0.96 vs 0.90). CONCLUSIONS: A simplified diagnostic panel of CA19-9, ApoC-I and ApoA-II improves the diagnostic ability of CA19-9 alone and may have clinical utility.

Pancreatic cystic tumours: when to resect, when to observe.

BACKGROUND AND OBJECTIVES: In recent years there has been an increase in the diagnosis of cystic tumors of the pancreas. In this setting, difficult diagnostic problems and different therapeutic management can be proposed. MATERIAL AND METHODS: A review of the literature and authors experience were undertaken. RESULTS: Cystic tumors of the pancreas include different neoplasms with a different biological behaviour. While most serous cystadenomas (SCAs) can be managed nonoperatively, patients with mucinous cystic neoplasms (MCNs), solid pseudopapillary tumors (SPTs), main-duct intraductal papillary mucinous neoplasms (IPMNs) should undergo surgical resection. Branch-duct IPMNs can be observed with radiological and clinical follow-up when asymptomatic, < 3 cm in size and without radiologic features of malignancy (i.e. nodules). CONCLUSIONS: Cystic tumors of the pancreas are common. Differential diagnosis among the different tumor-types is of paramount importance for appropriate management. Nonoperative management seems appropriate for most SCAs and for well-selected branch-duct IPMNs.

"Paraduodenal" pancreatitis: results of surgery on 58 consecutives patients from a single institution.

BACKGROUND: Cystic dystrophy of heterotopic pancreas, groove pancreatitis, pancreatic hamartoma of the duodenum, paraduodenal wall cyst, and myoadenomatosis are all terms grouped together, from a pathological viewpoint, as definitions of paraduodenal pancreatitis (PP). The objective of the present study was to investigate the clinical characteristics, therapeutic strategies, and results in 58 patients undergoing pancreatic resection for PP. METHODS: From January 1990 to December 2006 data were prospectively collected on 58 patients who were diagnosed with PP who then underwent pancreaticoduodenectomy. RESULTS: In this patient cohort the median age was 44.7 years; only 4 patients were women, and only 3 had non-drinker and/or non smoker habits. The overall morbidity was 18.9%, and the median hospitalization was 11 days. There were no postoperative deaths. In a median follow-up of 96.3 months, all patients noted a decrease in the pain associated with PP; 35 patients (76%) had complete disappearance of pain, whereas occasional relapsing pain occurred in the remaining 11 (24%). CONCLUSIONS: Patients with PP have clinical characteristics similar to those of chronic pancreatitis. The diagnostic imaging modalities of choice are ultrasonographic endoscopy and magnetic resonance cholangiopancreaticography. Based on our surgical experience, pancreaticoduodenectomy seems to be a reasonable choice of treatment in patients with PP.

Enucleation of pancreatic neoplasms.

BACKGROUND: Standard resections for benign and borderline neoplasms of the pancreas are associated with a significant risk of long-term functional impairment, whereas enucleation preserves healthy parenchyma and pancreatic function. The aim of this study was to evaluate postoperative and long-term oncological and functional results after pancreatic enucleation. METHODS: Data collected prospectively from 61 consecutive patients who underwent pancreatic enucleation were analysed. RESULTS: There were no deaths. A clinically significant pancreatic fistula was reported in 14 patients (23 per cent), and five patients (8 per cent) had a further operation for fistula-related complications. The most common indication for surgery was endocrine neoplasm (38 patients; 62 per cent) and two patients (3 per cent) had a final histopathological diagnosis of malignant neoplasm. At a median follow-up of 61 months no patient had developed tumour recurrence or exocrine insufficiency. Two elderly patients developed non-insulin-dependent diabetes. CONCLUSION: Enucleation is an effective procedure for the radical treatment of benign and borderline neoplasms of the pancreas, with good long-term outcomes.

Predictive factors of efficacy of the somatostatin analogue octreotide as first line therapy for advanced pancreatic endocrine carcinoma.

About 40% of nonfunctioning pancreatic endocrine carcinomas (NF-PEC) cannot be cured by surgery due to advanced stage disease. Somatostatin analogues have been proposed as first line therapy in these cases. We performed a prospective phase IV study to assess the efficacy of octreotide in advanced NF-PEC and identify factors predictive of response to therapy. Twenty-one consecutive patients with octreoscan-positive advanced-stage well-differentiated NF-PEC were treated with long-acting release octreotide 20 mg i.m. at diagnosis. The immunohistochemical expression of somatostatin receptor 2 (SSTR2) and the quantitative mRNA analysis of SSTR2 and SSTR5 were assessed in 12 tumours. The tumour proliferative fraction was assessed by immunohistochemistry for Ki-67. Eight patients (38%) had stable disease (SD) after a median follow-up of 49.5 months. Thirteen patients (62%) developed progression after a median of 18 months. Tumour progression correlated with a proliferative index>or=5% (P=0.016), weight loss (P=0.006) and absence of abdominal pain (P=0.003) at diagnosis. Other clinical (age, gender and primary tumour resection) or pathological parameters (site, size and liver metastasis) lacked significant correlation with tumour progression. No difference in the amount of SSTR2 mRNA and protein or SSTR5 mRNA was found between tumours that were stable (n=5) and seven tumours that progressed (n=7). Treatment with long-acting release octreotide was associated with stabilization of disease and a good quality of life in 38% of patients. A Ki-67 index>or=5% and/or the presence of weight loss may justify more aggressive therapy without waiting for radiologically proven progression of disease.

Value of regional lymphadenectomy in pancreatic cancer.

Radical surgical resection and adjuvant chemotherapy are the goal standard to attempt significant long term survival in patients suffering from ductal pancreatic cancer. The role of extended lymph-node dissection is still a debated issue. In this paper a deep review of the experiences reported in the literature is carried out. Several studies are limited, not randomized and retrospective: generally speaking they seem to suggest a positive role in node dissection. Unfortunately, this trend is not confirmed in the only two trials conducted in a prospective and randomized setting. Moreover the results of these studies are also difficult to compare. At the moment we can say that extended lymphadenectomy does not play a determinant role for long term survival but a positive trend has been shown for node positive patients.

Pancreatic cystic tumors.

Cystic tumors of the pancreas are less frequent than other tumors in neoplastic pancreatic pathology, but in recent years the literature has reported an increasing number. After the first report by Becourt in 1830, cystic tumors were classified into 2 different types by Compagno and Oertel in 1978: benign tumors with glycogen-rich cells and mucinous cystic neoplasms with overt and latent malignancy. The WHO classification of exocrine tumors of the pancreas, published in 1996, is based on the histopathological features of the epithelial wall, which are the main factor in differential diagnosis with cystic lesions of the pancreas. Thanks to the knowledge acquired up to now, a surgical procedure is not always required because the therapeutic choice is conditioned by the correct classification of this heterogeneous group of tumors. Clinical signs are not really useful in the clinical work up, most patients have no symptoms and when clinical signs are present, they may help us to pinpoint the organ of origin but never to identify the type of pathology. In the last few years, the great improvement in imaging has enabled us not only to discriminate cystic from solid lesions, but also to identify the features of the lesions and label them preoperatively. More invasive diagnostic procedures such as fine needle aspiration and intracystic fluid tumor marker level are not really useful because they are not sensitive and the cystic wall can show different degrees of dysplasia and de-epithelialization. These are the reasons for sending the entire specimen to pathology. Good cooperation between surgeons, pathologists, radiologists and gastroenterologists is mandatory to increase the chances of making a proper diagnosis. Therefore, we must analyze all the information we have, such as age, sex, clinical history, location of the tumor and radiological features, in order to avoid the mistake of treating a cystic neoplasm as a benign lesion or as a pseudocyst, as described in the literature. Except for inoperable cases due to the critical condition of the patient or non-resectable lesions, surgical treatment differs with the diagnosis. Cystic tumors of the pancreas, therefore, are a heterogeneous group of tumors, with a real problem regarding differential diagnosis between neoplastic and inflammatory lesions. Even with a proper work up, some perplexity may remain about the nature of the lesion and in these cases the surgical procedure has a therapeutic value as well as playing a diagnostic role. The role of surgery is central in the treatment of these tumors because it could be curative when complete resection is possible. In this way, the lack of good therapeutic results with chemotherapy and radiotherapy force the surgeon to go ahead with the procedure. Intraductal papillary mucinous neoplasms represent a new and, from the epidemiological point of view, important chapter in the world of cystic tumors. The margin of resection is important and the surgeon has to be aware that in order to have a curative resection, total pancreatectomy is sometimes required. In the last few years the therapeutic approach has changed thanks to new knowledge of the biological behavior of these tumors. In fact, from a surgical approach in all cases, we are now discussing the possibility of a follow-up not only for asymptomatic serous cystadenomas but also for the little branch side intraductal papillary mucinous neoplasms (IPMNs) in critical patients. A follow-up could be planned even for solid pseudopapillary tumors but it seems risky to leave untreated big tumors in young patients without a certain diagnosis and with so few studies reported in the literature.

Role of unlabelled somatostatin analogues in the prevention of complications after elective pancreatic and peripancreatic surgery: a critical review.

Although studies on the use of the somatostatin analogues in the elective pancreatic surgery are mostly prospective, double blind and randomised, the results are contradictory and not univocally interpretable. Through the examination of all randomised perspective works published on this subject, a critical interpretation is attempted which may give relevant suggestions for further studies. A new clinical, randomised, double blind and multicentric prospective trial should take into proper consideration even the changes which have occurred in the care of the patients. Over the years a significant decrease of postoperative hospital stay and a deeper awareness of the medical expenses have been observed. Moreover, since the drug has a potential advantage on specific pancreatic complications, only these must be considered among the end points of the study and the population studied will be limited exclusively to patients who underwent resection of the pancreatic head or of the periampullar region because of neoplastic disease. Finally, the selection of the centres that enrol the patients must be considered, since the expertise of each operator or of the team, affects, as an independent variable, both morbidity and mortality.

Outcome of open necrosectomy in acute pancreatitis.

Twenty percent of all acute pancreatitis patients present with necrotizing pancreatitis. Infected necrosis is responsible for 80% of deaths in the course of the disease though, thanks to antibiotic prophylaxis, the infection rate is decreasing. When infection occurs, the prognosis is poor, and the need for debridement and drainage of the necrosis is mandatory. The aim of this study was to review the most recent literature in order to present an update of open surgical management of infected necrosis.

High recurrence rate after atypical resection for pancreatic metastases from renal cell carcinoma.

BACKGROUND: Pancreatic metastases from renal cell carcinoma are rare but highly resectable. The aim of this study was to review a series of patients with this condition. METHODS: The study involved 22 consecutive patients with histologically proven pancreatic metastases from renal cell cancer. RESULTS: Seventeen of the 22 patients had surgery. No patient died but eight of the 17 patients had a postoperative complication. Median follow-up was 33 (range 1-96) months. The 24- and 60-month survival probabilities were 0.84 and 0.53 respectively. Five patients who did not undergo surgery had 24- and 60-month survival probabilities of 0.53 and 0.26 respectively. The difference between the two groups was significant (P = 0.040). CONCLUSION: Despite the slow development of these secondaries and their well encapsulated morphology, the high rate of recurrence after limited resection suggests that radical resection should be recommended.

Incidental carcinoma of the gallbladder.

Incidental gallbladder carcinoma (GBC) is a difficult management issue as there are no established guidelines. Laparoscopic cholecystectomy is associated with increased dissemination of the tumour cells (both in the peritoneal cavity and port sites). Depth of tumour invasion (T stage) and positive surgical margins are the most important prognostic factors, although tumour differentiation, lymphatic, perineural and vascular invasion may also affect the outcome. Simple cholecystectomy is adequate for mucosal (T1a) lesions only. For T1b tumours port site/wound excision with second radical operation (probably extended cholecystectomy -- wedge liver excision with regional lymphadenectomy) should be advised. T2 tumours should be treated with second radical operation (extended cholecystectomy or excision of medial liver segments 4b and 5 or 4, 5 and 8 with regional lymphadenectomy with or without excision of the extra-hepatic bile duct). Few T3 tumours can be cured and in some survival time may be prolonged by a second radical operation. More extensive liver resection (segments 4b and 5 or segments 4, 5 and 8) with regional lymphadenectomy with excision of the extra-hepatic bile duct should be advised. A second radical operation may palliate some T4 tumours. In the absence of extensive nodal disease, this operation may prolong the survival time. Excision of the extra-hepatic bile duct should be undertaken whenever the tumour involves the cystic duct margin or the extra-hepatic biliary tree. Epidemiology, risk factors, aetiopathogenesis and the modes of spread of GBC are discussed in relation to appropriateness of the second radical operation. Indications, types and role of the second radical operation are discussed.

Infection prevention in necrotizing pancreatitis: an old challenge with new perspectives.

Necrotizing pancreatitis still remains a life-threatening disease despite several improvements in diagnosis, prevention and treatment. In recent years, some important questions have been answered such as the need for early intensive medical treatment rather than early surgery, but others are still strongly debated. The aim of this paper is to present an up-to-date assessment of current challenges in the management of necrotizing pancreatitis in order to prevent infection.

A single-institution experience with fistulojejunostomy for external pancreatic fistulas.

External pancreatic fistulas resistant to medical treatment are an indication for surgery. Over the period from May 1986 to March 1999, we operated on 17 patients suffering from a stabilized external pancreatic fistula as a result of surgical treatment for severe acute pancreatitis in 12 cases, chronic pancreatitis in 3, duodenopancreatectomy in 1, and islet cell tumor enucleation in 1. The surgical repair consisted of precise identification of the fistula tract around the drainage tube and its anastomosis with a Roux-en-Y jejunal loop (fistulojejunostomy). The surgical mortality was nil, and the postoperative outcome was uneventful in 12 patients. Four patients experienced surgical complications, all of which were treated conservatively. After a median follow-up of 93 months, 14 patients are still alive and healthy, 1 had died of neoplastic cachexia, and 2 were lost to follow-up. In our experience, fistulojejunostomy appears to be safe, easy to perform, and curative.