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- Insulander, J., et al.
(författare)
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Prognosis following surgical bypass compared with laparotomy alone in unresectable pancreatic adenocarcinoma
- 2016
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Ingår i: British Journal of Surgery. - : John Wiley & Sons. - 0007-1323 .- 1365-2168. ; 103:9, s. 1200-1208
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Tidskriftsartikel (refereegranskat)abstract
- Background: Resection with curative intent has been shown to prolong survival of patients with locoregional pancreatic ductal adenocarcinoma (PDAC). However, up to 33 per cent of patients are deemed unresectable at exploratory laparotomy owing to unanticipated locally advanced or metastatic disease. In these patients, prophylactic double bypass (PDB) procedures have been considered the standard of care. The aim of this study was to compare PDB with exploratory laparotomy alone in terms of impact on postoperative course, chemotherapy and overall survival.Methods: This retrospective observational cohort study (2004-2013) was conducted using a prospective institutional database. Patients with histologically confirmed, unresectable PDAC were included. Relationships between PDB procedures, exploratory laparotomy alone, postoperative chemotherapy and best supportive care were investigated by means of Cox regression. Overall survival was compared using Kaplan-Meier estimations and log rank test.Results: Of 503 patients with PDAC scheduled for resection with curative intent, 104 were deemed unresectable at laparotomy (resection rate 79·3 per cent). Seventy-four patients underwent PDB procedures and 30 had exploratory laparotomy alone. PDB and exploratory laparotomy were similar in terms of perioperative mortality, initiation of chemotherapy and overall survival. Compared with best supportive care, postoperative chemotherapy prolonged survival (8·0 versus 14·4 months in locally advanced PDAC, P = 0·007; 2·3 versus 8·0 months in metastatic PDAC, P < 0·001). Patients undergoing chemotherapy following exploratory laparotomy alone had longer median overall survival than patients undergoing chemotherapy following PDB procedures (16·3 versus 10·3 months; P = 0·040).Conclusion: Patients with pancreatic cancer deemed unresectable at laparotomy may derive survival benefit from subsequent chemotherapy as opposed to supportive care alone. At laparotomy, proceeding with a bypass procedure for prophylactic symptom control may be prognostically unfavourable.
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| 2. |
- Sanjeevi, Srinivas
(författare)
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Advances in the Perioperative Management of Pancreatic Cancer
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Surgery is currently the only form of curative treatment for pancreatic cancer, yet five-year survival rates following resection are just 15-20%. Improved hospital care has decreased postoperative mortality to 2% yet morbidity remains high at 50%. Poor survival and high morbidity are driven by several perioperative factors. The aims of this thesis were to (I) understand the impact of waiting times between imaging and surgery, (II) evaluate the best strategy for patients deemed unresectable at surgery, (III) explore novel pancreaticojejunal anastomotic techniques and (IV) to evaluate systemic treatment options for patients with borderline resectable pancreatic cancer. In paper I, the time between diagnosis and surgical treatment was evaluated with regards to cancer progression at the time of surgery. The rate of unresectable disease at surgery was significantly lower with a waiting of time of 32 days or less compared with longer waiting times (13.9 vs 32.5%). Tumor size and vascular involvement also increased the risk of unresectable disease at surgery. In paper II, the palliative double bypass (PDB) and just an exploratory laparotomy were compared in cases of unresectable disease at surgery. Perioperative mortality and initiation of chemotherapy were similar between the groups. Patients undergoing chemotherapy following exploratory laparotomy alone had longer median overall survival compared to patients undergoing chemotherapy following a PDB (16.3 versus 10.3 months).In paper III, an end-to-end invaginated pancreaticojejunostomy was compared to the traditional duct to mucosa anastomosis in the setting of a randomized controlled trial. Patients at high risk for developing a post-operative pancreatic fistula (POPF) were selected The results showed no difference in clinically significant pancreatic leaks. There were however significantly fewer cases of grade C POPF associated with the invaginated pancreaticojejunostomy. In paper IV the role of neoadjuvant chemotherapy (NACT) and upfront resection was retrospectively evaluated for patients with borderline resectable pancreatic tumors. Patients who underwent upfront resection versus NACT had comparable median overall survival rates when drop-outs were included in an intention-to-treat principle (9 vs 10.9 months respectively). Per-protocol analysis of patients that completed their intended therapy revealed no difference in the upfront surgery group (9.5 months) and a significantly longer survival in the NACT group (21.8 months).
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| 3. |
- Sanjeevi, Srinivas, et al.
(författare)
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Comparison of end-to-end invagination and duct-to-mucosa pancreaticojejunostomies following Whipple's resection : A randomized controlled trial in patients at high risk of postoperative pancreatic fistula
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Postoperative pancreatic fistula (POPF) is a major cause of morbidity and mortality after pancreatic resection. Various pancreatoenteric reconstruction techniques exist, yet there is no consensus on the optimal strategy to decrease POPF. The aim of this trial was to compare a novel end-to-end invaginated pancreaticojejunostomy (INV) with the duct-to-mucosa anastomosis (DM) in patients at high risk for POPF. Methods: Consecutive patients between September 2011 and 2015 that were evaluated at a multidisciplinary tumor board and planned for a pancreaticoduodenectomy were randomized prospectively to INV or DM, in an unblinded dual-institution superiority trial. All patients had an assessment of their pancreatic gland both pre- and intra-operatively to select for patients at high risk for POPF. The primary end point was clinically relevant POPF as classified by established definitions. Secondary outcomes were postoperative mortality and morbidity.Results: Hundred and twenty-three patients were included in the final analysis (61 DM, 62 INV). All patients had a soft pancreas with a main pancreatic duct <3mm. There was no difference in clinically significant pancreatic leaks (POPF B-C) between the groups (p=0.72). Significantly fewer cases of POPF C were observed in the INV group compared to the DM group (DM n=13, INV n=2, p=0.002). Six life-threatening complications (Clavien-Dindo IV) occurred in the DM group, compared to one in the INV group (p=0.06). Grade C post-pancreatectomy hemorrhage was significantly higher in the DM group (DM n=7, INV n=0, p=0.006). There were no differences between the groups in median operating times, in-hospital mortality, or blood loss. Conclusion: The end-to-end invagination pancreaticojejunostomy is not significantly superior with regards to clinically significant POPF. It does however appear to be a safe reconstruction technique, possibly associated with a lower incidence of severe POPF and post-pancreatectomy hemorrhage.
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| 4. |
- Sanjeevi, Srinivas, et al.
(författare)
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Impact of delay between imaging and treatment in patients with potentially curable pancreatic cancer
- 2015
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Ingår i: British Journal of Surgery. - : John Wiley & Sons. - 0007-1323 .- 1365-2168. ; 103:3, s. 267-275
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Tidskriftsartikel (refereegranskat)abstract
- Background: Locoregional pancreatic ductal adenocarcinoma (PDAC) may progress rapidly and/or disseminate despite having an early stage at diagnostic imaging. A prolonged interval from imaging to resection might represent a risk factor for encountering tumour progression at laparotomy. The aim of this study was to determine the therapeutic window for timely surgical intervention.Methods: This observational cohort study included patients with histologically confirmed PDAC scheduled for resection with curative intent from 2008 to 2014. The impact of imaging-to-resection/reassessment (IR) interval, vascular involvement and tumour size on local tumour progression or presence of metastases at reimaging or laparotomy was evaluated using univariable and multivariable regression. Risk estimates were approximated using hazard ratios (HRs).Results: Median IR interval was 42 days. Of 349 patients scheduled for resection, 82 had unresectable disease (resectability rate 76.5 per cent). The unresectability rate was zero when the IR interval was 22 days or shorter, and was lower for an IR interval of 32 days or less compared with longer waiting times (13 versus 26.2 per cent; HR 0.42, P = 0.021). It was also lower for tumours smaller than 30 mm than for larger tumours (13.9 versus 32.5 per cent; HR 0.34, P < 0.001). Tumours with no or minor vascular involvement showed decreased rates of unresectable disease (20.6 per cent versus 38 per cent when there was major or combined vascular involvement; HR 0.43, P = 0.007). However, this failed to reach statistical significance on multivariable analysis (P = 0.411), in contrast to IR interval (P = 0.028) and tumour size (P < 0.001).Conclusion: Operation within 32 days of diagnostic imaging reduced the risk of tumour progression to unresectable disease by half compared with a longer waiting time. The results of this study highlight the importance of efficient clinical PDAC management.
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| 5. |
- Sanjeevi, Srinivas, et al.
(författare)
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Upfront Surgery versus Neoadjuvant Therapy for Borderline Resectable Pancreatic Cancer
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- IntroductionBorderline resectable pancreatic cancer (BRPC) is characterized by varying definitions and treatment regimens. In our institution BRPC is defined according to mesenteric and hepatic vessel involvement. Treatment consists of either upfront resection with adjuvant chemotherapy (ACT) or neoadjuvant chemotherapy (NACT) with potential resection. The aim of the current study was to evaluate the potential benefits of these treatment concepts with regards to overall survival. MethodsBRPC patients from Karolinska University Hospital were prospectively studied between 2008-2013. Patients were divided into two categories; Upfront resectable with ACT and potentially resectable with NACT. Toxicity, therapy response, postoperative morbidity and mortality were recorded according to established classifications and overall survival (OS) analyzed. Results101 patients with BRPC, radiologically defined as either upfront resectable or potentially resectable after NACT were included. Of 30 patients deemed upfront resectable, 20 proceeded to undergo a curative-intent resection. 71 patients were recommended to receive NACT of which 66 initiated therapy and 17 underwent a curative-intent resection. The surgical resection rate in the upfront resectable group (67%) was significantly higher than in the NACT group (24%, p>0.001). 45% of patients who underwent upfront resection proceeded to adjuvant chemotherapy compared to 24% in the NACT group. Patients who underwent upfront surgery versus NACT had comparable median overall survival rates when drop-outs were included in an intention-to-treat principle (9 vs 10.9 months respectively). Per-protocol analysis of patients that completed their intended therapy revealed no difference in the upfront surgery group (9.5 months) and a significantly longer survival in the NACT group (21.8 months)ConclusionUpfront resection followed by ACT has not proven to be a sustainable treatment concept for patients with BRPC. In comparison, NACT with potential surgical resection showed significantly improved survival rates in patients with more advanced disease. The indication for this treatment concept should be extended to include all patients with BRPC with future studies focusing on minimizing drop-out from chemotherapy regimens.
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