Background The prognosis of patients with liver metastasis is generally considered dismal, and combined resections of the primary tumor and metastasectomies are not recommended. In highly selected ...patients, however, resections are performed. The evidence for this indication is limited. The aim of the current study was to assess the operative and oncologic outcomes of patients with combined pancreatic and liver resections of synchronous liver metastases. Methods In a retrospective analysis of 6 European pancreas centers, we identified 69 patients with pancreatic ductal adenocarcinoma and synchronous liver metastasis who underwent simultaneous pancreas and liver metastasis resections. Patients receiving exploration without tumor resection served as the control group. Results Overall survival (OS) appeared to be prolonged in the group of resected patients (median 14 vs 8 months, P < .001). Subgroup analysis revealed that the survival benefit of the resected patients was driven by pancreatic ductal adenocarcinomas localized in the pancreatic head (median OS 13.6 vs 7 months, P < .001). Body/tail pancreatic ductal adenocarcinomas showed no benefit of resection (median OS 14 vs 15 months, P = .312). In the multivariate analysis, tumor resection was the only independent prognosticator for OS (hazard ratio 2.044, 95% confidence interval 1.342–3.114). Conclusion The data of this retrospective and selective patient cohort suggested a clear survival benefit for patients undergoing synchronous pancreas and liver resections for pancreatic ductal adenocarcinoma, but due to the limitations of this retrospective study and very strong potential for selection bias, a strong conclusion for resection cannot be drawn. Prospective trials must validate these data and investigate the use of combined operative and systemic treatments in case of resectable metastatic pancreatic cancer. Is it time for a multicenter, prospective trial?
Background This position statement was developed to expedite a consensus on definition and treatment for borderline resectable pancreatic ductal adenocarcinoma (BRPC) that would have worldwide ...acceptability. Methods An international panel of pancreatic surgeons from well-established, high-volume centers collaborated on a literature review and development of consensus on issues related to borderline resectable pancreatic cancer. Results The International Study Group of Pancreatic Surgery (ISGPS) supports the National Comprehensive Cancer Network criteria for the definition of BRPC. Current evidence supports operative exploration and resection in the case of involvement of the mesentericoportal venous axis; in addition, a new classification of extrahepatic mesentericoportal venous resections is proposed by the ISGPS. Suspicion of arterial involvement should lead to exploration to confirm the imaging-based findings. Formal arterial resections are not recommended; however, in exceptional circumstances, individual therapeutic approaches may be evaluated under experimental protocols. The ISGPS endorses the recommendations for specimen examination and the definition of an R1 resection (tumor within 1 mm from the margin) used by the British Royal College of Pathologists. Standard preoperative diagnostics for BRPC may include: (1) serum levels of CA19-9, because CA19-9 levels predict survival in large retrospective series; and also (2) the modified Glasgow Prognostic Score and the neutrophil/lymphocyte ratio because of the prognostic relevance of the systemic inflammatory response. Various regimens of neoadjuvant therapy are recommended only in the setting of prospective trials at high-volume centers. Conclusion Current evidence justifies portomesenteric venous resection in patients with BRPC. Basic definitions were identified, that are currently lacking but that are needed to obtain further evidence and improvement for this important patient subgroup. A consensus for each topic is given.
Background The lymph node (Ln) status of patients with resectable pancreatic ductal adenocarcinoma is an important predictor of survival. The survival benefit of extended lymphadenectomy during ...pancreatectomy is, however, disputed, and there is no true definition of the optimal extent of the lymphadenectomy. The aim of this study was to formulate a definition for standard lymphadenectomy during pancreatectomy. Methods During a consensus meeting of the International Study Group on Pancreatic Surgery, pancreatic surgeons formulated a consensus statement based on available literature and their experience. Results The nomenclature of the Japanese Pancreas Society was accepted by all participants. Extended lymphadenectomy during pancreatoduodenectomy with resection of Ln's along the left side of the superior mesenteric artery (SMA) and around the celiac trunk, splenic artery, or left gastric artery showed no survival benefit compared with a standard lymphadenectomy. No level I evidence was available on prognostic impact of positive para-aortic Ln's. Consensus was reached on selectively removing suspected Ln's outside the resection area for frozen section. No consensus was reached on continuing or terminating resection in cases where these nodes were positive. Conclusion Extended lymphadenectomy cannot be recommended. Standard lymphadenectomy for pancreatoduodenectomy should strive to resect Ln stations no. 5, 6, 8a, 12b1, 12b2, 12c, 13a, 13b, 14a, 14b, 17a, and 17b. For cancers of the body and tail of the pancreas, removal of stations 10, 11, and 18 is standard. Furthermore, lymphadenectomy is important for adequate nodal staging. Both pancreatic resection in relatively fit patients or nonresectional palliative treatment were accepted as acceptable treatment in cases of positive Ln's outside the resection plane. This consensus statement could serve as a guide for surgeons and researchers in future directives and new clinical studies.
The optimal nutritional therapy in the field of pancreatic surgery is still debated.
An international panel of recognized pancreatic surgeons and pancreatologists decided that the topic of ...nutritional support was of importance in pancreatic surgery. Thus, they reviewed the best contemporary literature and worked to develop a position paper to provide evidence supporting the integration of appropriate nutritional support into the overall management of patients undergoing pancreatic resection. Strength of recommendation and quality of evidence were based on the approach of the grading of recommendations assessment, development and evaluation Working Group.
The measurement of nutritional status should be part of routine preoperative assessment because malnutrition is a recognized risk factor for surgery-related complications. In addition to patient's weight loss and body mass index, measurement of sarcopenia and sarcopenic obesity should be considered in the preoperative evaluation because they are strong predictors of poor short-term and long-term outcomes.
The available data do not show any definitive nutritional advantages for one specific type of gastrointestinal reconstruction technique after pancreatoduodenectomy over the others. Postoperative early resumption of oral intake is safe and should be encouraged within enhanced recovery protocols, but in the case of severe postoperative complications or poor tolerance of oral food after the operation, supplementary artificial nutrition should be started at once. At present, there is not enough evidence to show the benefit of avoiding oral intake in clinically stable patients who are complicated by a clinically irrelevant postoperative pancreatic fistula (a so-called biochemical leak), while special caution should be given to feeding patients with clinically relevant postoperative pancreatic fistula orally. When an artificial nutritional support is needed, enteral nutrition is preferred whenever possible over parenteral nutrition.
After the operation, regardless of the type of pancreatic resection or technique of reconstruction, patients should be monitored carefully to assess for the presence of endocrine and exocrine pancreatic insufficiency. Although fecal elastase-1 is the most readily available clinical test for detection of pancreatic exocrine insufficiency, its sensitivity and specificity are low. Pancreatic enzyme replacement therapy should be initiated routinely after pancreatoduodenectomy and in patients with locally advanced disease and continued for at least 6 months after surgery, because untreated pancreatic exocrine insufficiency may result in severe nutritional derangement.
The importance of this position paper is the consensus reached on the topic. Concentrating on nutritional support and therapy is of utmost value in pancreatic surgery for both short- and long-term outcomes.
Summary Although millions of cells are shed from a tumour every day, haematogenous metastasis is believed to be very inefficient. This inefficiency is widely assumed to be a result of the destruction ...of cells in the bloodstream by shear stress and the immune system and a slow rate of extravasation and proliferation in the stroma at a secondary site. Here, we propose that, whereas active intravasation of cells into the circulation is important in some tumours, others might shed cells passively into the blood or lymphatic vessels without the involvement of active cell migration. We discuss the evidence for and against this passive-shedding hypothesis and the implications for future treatments.
Aim of this study was to assess the biological function in tumor progression and metastatic process carcinoembryonic antigen-related cell adhesion molecules (CEACAM) 1, 5 and 6 in pancreatic ...adenocarcinoma (PDAC).
CEACAM knock down cells were established and assessed in vitro and in a subcutaneous and intraperitoneal mouse xenograft model. Tissue and serum expression of patients with PDAC were assessed by immunohistochemistry (IHC) and by enzyme linked immunosorbent assays.
Presence of lymph node metastasis was correlated with CEACAM 5 and 6 expression (determined by IHC) and tumor recurrence exclusively with CEACAM 6. Patients with CEACAM 5 and 6 expression showed a significantly shortened OS in Kaplan-Meier survival analyses. Elevated CEACAM6 serum values showed a correlation with distant metastasis and. Survival analysis revealed a prolonged OS for patients with low serum CEACAM 1 values. In vitro proliferation and migration capacity was increased in CEACAM knock down PDAC cells, however, mice inoculated with CEACAM knock down cells showed a prolonged overall-survival (OS). The number of spontaneous pulmonary metastasis was increased in the CEACAM knock down group.
The effects mediated by CEACAM expression in PDAC are complex, though overexpression is correlated with loco-regional aggressive tumor growth. However, loss of CEACAM can be considered as a part of epithelial-mesenchymal transition and is therefore of rather importance in the process of distant metastasis.
Anastomotic leakage after esophageal surgery remains a feared complication. During the last decade, management of this complication changed from surgical revision to a more conservative and ...endoscopic approach. However, the treatment remains controversial as the indications for conservative, endoscopic, and surgical approaches remain non-standardized.
Between 2010 and 2020, all patients who underwent Ivor Lewis esophagectomy for underlying malignancy were included in this study. The data of 28 patients diagnosed with anastomotic leak were further analyzed.
Among 141 patients who underwent resection, 28 (19.9%) developed an anastomotic leak, eight (28.6%) of whom died. Thirteen patients were treated with endoluminal vacuum therapy (EVT), seven patients with self-expanding metal stents (SEMS) four patients with primary surgery, one patient with a hemoclip, and three patients were treated conservatively. EVT achieved closure in 92.3% of the patients with a large defect and no EVT-related complications. SEMS therapy was successful in clinically stable patients with small defect sizes.
EVT can be successfully applied in the treatment of anastomotic leakage in critically ill patients, while SEMS should be limited to clinically stable patients with a small defect size. Surgery is only warranted in patients with sepsis with graft necrosis.
Anastomotic leakage after esophagectomy with gastric-pullup is the most feared postoperative complication associated with high morbidity and mortality rates. Management of anastomotic leakage ...underwent an evolution in the last decade from surgical and conservative to an endoscopic management. However, to date there is no clear consensus on management and if endoluminal vacuum therapy (EVT) is the most superior therapy.
Between 2012 and 2022 all patients that underwent Ivor-Lewis esophagectomy for an underlying malignancy were included in this study. Patients that developed an anastomotic leakage and received endoscopic vacuum therapy were further analysed.
A total of 17 patients were treated with EVT following AL after esophagectomy. The median duration of EVT was 23 days with a median number of 5,5 vacuum sponge changes per patient. EVT-systems were placed 12 times intraluminal and 5 times extraluminal. Successful closure of the defect was achieved in 14 patients.
Endoscopic vacuum therapy can be successfully applied in the treatment of anastomotic leakage after esophagectomy even in septic patients with an extraluminal cavity. Event-related complications are present but rare.
Concomitant liver cirrhosis is a crucial risk factor for major surgeries. However, only few data are available concerning cirrhotic patients requiring esophagectomy for malignant disease.
From a ...prospectively maintained database of esophageal cancer patients, who underwent curative esophagectomy between 01/2012 and 01/2016, patients with concomitant liver cirrhosis (liver-cirrhotic patients, LCP) were compared to non-liver-cirrhotic patients (NLCP).
Of 170 patients, 14 cirrhotic patients with predominately low MELD scores (≤ 9, 64.3%) were identified. Perioperative outcome was significantly worse for LCP, as proofed by 30-day (57.1% vs. 7.7, p<0.001) and 90-day mortality (64.3% vs. 9.6%, p<0.001), anastomotic leakage rate (64.3 vs. 22.3%, p = 0.002) and sepsis (57.1 vs. 21.5%, p = 0.006). Even after adjustment for age, gender, comorbidities, and surgical approach, LCP revealed higher odds for 30-day and 90-day mortality compared to NLCP. Moreover, 5-year survival analysis showed a significantly poorer long-term outcome of LCP (p = 0.023). For risk stratification, none of the common cirrhosis scores proved prognostic impact, whereas components as Bilirubin (auROC 94.4%), INR (auROC = 90.0%), and preoperative ascites (p = 0.038) correlated significantly with the perioperative outcome.
Curative esophagectomy for cirrhotic patients is associated with a dismal prognosis and should be evaluated critically. While MELD and Child score failed to predict perioperative mortality, Bilirubin and INR proofed excellent prognostic capacity in this cohort.
Background Pancreatoduodenectomy (PD) provides the best chance for cure in the treatment of patients with localized pancreatic head cancer. In patients with a suspected, clinically resectable ...pancreatic head malignancy, the need for histologic confirmation before proceeding with PD has not historically been required, but remains controversial. Methods An international panel of pancreatic surgeons working in well-known, high-volume centers reviewed the literature and worked together to establish a consensus on when to perform a PD in the absence of positive histology. Results The incidence of benign disease after PD for a presumed malignancy is 5–13%. Diagnosis by endoscopic cholangiopancreatography brushings and percutaneous fine-needle aspiration are highly specific, but poorly sensitive. Aspiration biopsy guided by endoscopic ultrasonography (EUS) has greater sensitivity, but it is highly operator dependent and increases expense. The incidence of autoimmune pancreatitis (AIP) in the benign resected specimens is 30–43%. EUS-guided Trucut biopsy, serum levels of immunoglobulin G4, and HISORt (Histology, Imaging, Serology, Other organ involvement, and Response to therapy) are used for diagnosis. If AIP is suspected but not confirmed, the response to a short course of steroids is helpful for diagnosis. Conclusion In the presence of a solid mass suspicious for malignancy, consensus was reached that biopsy proof is not required before proceeding with resection. Confirmation of malignancy, however, is mandatory for patients with borderline resectable disease to be treated with neoadjuvant therapy before exploration for resection. When a diagnosis of AIP is highly suspected, a biopsy is recommended, and a short course of steroid treatment should be considered if the biopsy does not reveal features suspicious for malignancy.
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