The first purpose of diagnostic and therapeutic interventions in patients with pancreatic and periampullary tumors is permanent cure, second to offer the best possible palliation. The roles of surgery and chemotherapy are crucial. As shown in , the net outcome of the pre- and peroperative practice was 135 patients undergoing surgery, whereas 125 patients with malignancies were considered unresectable, 73 because of metastases, 56 due to locally advanced tumors. An opportunity of improvement for patients with locally advanced tumors might be, either neoadjuvant chemoradiation for downstaging, followed by surgery, or upfront surgery including more advanced dissection techniques for distal resections [21
] or more comprehensive reconstructive vascular surgery on mesenteric vessels. Increased response rate and overall survival have also been documented in patients with metastatic disease and good performance status treated with the FOLFIRINOX regimen [22
The present observational study is searching for opportunities of improvement in diagnostic and therapeutic practice for the collective cohort of patients with solid and cystic pancreatic and/or periampullary tumors. Altogether 243 patients (73.6%) had malignant lesions, illustrating that diagnostic accuracy is critically important: ability to clarify whether or not a lesion is malignant and if it is resectable. Identification and implementation of improved diagnostic and therapeutic algorithms are prerequisites for future interventional studies. Quality indicators enabling faster and more accurate diagnosis/staging, then radical surgery, are crucial.
The authors' first critical analysis focused on the intraoperative technique described above, resulting in the outcome shown in and . The heterogeneity of periampullary tumors influence outcome, measured as rate of R0 resections. All carcinomas of the papilla of Vater, duodenal carcinomas and cholangiocarcinomas were resected with free margin with one exception, whereas 32 patients, 58% of those with pancreatic adenocarcinoma, were R1. illustrates that survival is profoundly influenced by treatment modality, as all patients with metastatic pancreatic adenocarcinoma died during the first year after diagnosis. R0N0 resection was found only in 12 (21%) of 55 patients, resected for pancreatic adenocarcinoma. The aggressive tumor biology of pancreatic adenocarcinoma is well known [23
]. In the group of 12 patients with R0/N0 status (), 3 patients died within the first year after radical surgery and adjuvant chemotherapy, 1 additional after 13 months. These observations make the question of neoadjuvant chemotherapy highly relevant. The residual nine patients are recurrence free after median 23.5 (15–36) months follow-up. A recent report from a more comprehensive database reported 54.5% 5-year survival without neoadjuvance in a similar subgroup of patients, resected for pancreatic adenocarcinoma, who also had low lymph node ratio and G1-differentiation [24
]. With focus on the quality of care analysis, illustrates how the surgical technique has failed: small tumors, that is, with diameter less than 30 mm, have been resected without a free margin in 10 patients. An improvement opportunity would be to resect the SMV/PV whenever a close anatomical relationship between tumor and vessel makes radicality questionable. A prerequisite for this strategy is that the vascular reconstructions are performed with minimal rate of added complications. The present frequency (6.3%) of reconstructive vascular surgery during right-sided pancreatic resection has probably been too low during this investigation, also compared with other pancreatic centers [25,26
], even though different patient selection makes direct comparison of frequencies difficult. PV infiltration may be predicted radiographically [27
] and survival benefits of radical surgery, also in this situation, have again been documented. Improvements of local clearance have been reported by other centers after vascular resection without neoadjuvant chemotherapy [12
], and resected patients experience prolonged survival together with improved patient reported quality of life during the first 2 years after diagnosis [28
]. A recent report support the hypothesis that vascular invasion above all is an indicator of unfavorable topography, rather than a robust parameter for adverse tumor biology [29
Postoperative morbidity and mortality are important quality indicators, found valid by the ACSPCQD Expert Panel (quality indicator 28 and 29). The present figures are listed in , illustrating that the second highest postoperative complication rate, 40%, was recorded after double bypass in unresectable carcinoma. Combined with , illustrating that survival for metastatic pancreatic adenocarcinoma was 5.2 (3.1–8.2) months, this information puts focus on an obvious staging problem: In 9 (60%) patients, of those found unresectable during laparotomy, preoperative radiology did not recognize distant metastasis. Adequate palliation should have been offered these patients by endoscopic stenting [30
]. Postoperative recovery is protracted in this group [31
]: preoperative level of quality of life was regained 12 weeks after surgery. Failed preoperative staging have thus forced unresectable patients to spend more than half of their residual lifetime on unnecessary postoperative recovery. The most dramatic quality failure in this series is the intraoperative injury of mesenteric vessels, resulting in death 4 days later. This case is included in , listing avoidable negative outcome. During the failure analysis, the authors concluded that closer cooperation with the liver transplantation team should focus on early dissection of the superior mesenteric artery/celiac trunk, if this is mandatory during a debulking procedure. This can almost always be performed without long-lasting ischemia of abdominal organs, which was the main reason for intractable postoperative problems in the present case.
The best outcome for patients with any of the malignant tumors in the present cohort is early, radical surgical removal, that is, before spread of tumor cells, as illustrated by the survival curve for R0N0 resected adenocarcinoma (). Several quality indicators are focused on the diagnostic process, one of them, applicable to the whole preoperative work-up, is time, as published by the ACSPCQD Expert Panel (quality indicator 26) [7
]: if a patient is to receive treatment, then the time from diagnosis to surgery or first treatment should be less than 2 months. The local limit for this time interval is 3 weeks. The present data support a defined time limit as a valid quality indicator, and surgical delay should be as close to zero as possible. But accuracy requirements must also be taken care of during a fast preoperative investigation.
Histological documentation of cancer was lacking in 12.6% of those discharged with the diagnosis of unresectable pancreatic cancer. These patients may receive incorrect prognostic information, and even wrong treatment. In one of these patients, referred to the authors' clinic for a second opinion, the primary diagnosis of an unresectable locally advanced pancreatic tumor was revised to a pseudoaneurysm, secondary to pancreatitis (). The present data also underline the risk of misdiagnosis when applying radiological follow-up for cystic lesions. In the two cases of misconceived serous cystic neoplasms/pseudocysts/branch duct IPMN (intraductal papillary mucinous neoplasm), diagnostic delay resulted in unresectable pancreatic carcinoma. But also the opposite problem is illustrated by the patient with AIP, undergoing total pancreatectomy. The accuracy of the preoperative workup has to be improved. Preoperative analysis of IgG4 level and EUS-guided biopsy should always be performed [32,33
] in advance of surgical resection of a pancreatic focus, possible caused by AIP. But sensitivity and specificity are limited, and resection of some benign lesions is still accepted in most pancreatic centers [18,34,35
Removal of the malignant tumor is the greatest available benefit of treatment, recently documented also in a comprehensive report 5736 cases who underwent an oncologic resection compared with 31,399 who did not [36
]. The main question, generated from this observational study, is how outcome can be improved for the 143 patients with unresectable malignant tumors. There is evidence that patients with locally advanced disease might benefit from neoadjuvant chemotherapy or upfront surgery, when the risk of R1 resection seems higher. But in the neoadjuvant protocols more than 50% of included patients lost the possible benefit of an R0/R1 resection, that is, never became resectable. This underlines the need of prospective investigation of both alternatives, as the postoperative complications rates after pancreatic surgery [37
] are improving. The benefit of FOLFIRINOX should also be further investigated, particularly the downstaging capacity in metastatic disease.