Perioperative factors associated with survival following surgery for pancreatic cancer - a nationwide analysis of 473 cases from Denmark.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers worldwide, with an overall 5-year survival rate of only 5%. The effect of perioperative treatment factors including duration of surgery, blood transfusions as well as choice of anesthesia and analgesia techniques on overall survival (OS) following pancreatic resections for PDAC, is currently not well known. We hypothesized that these perioperative factors might be associated with OS after pancreatic resections for PDAC. METHODS: This is a retrospective study from a nationwide cohort of patients who underwent surgery for PDAC in Denmark from 2011 to 2020. Kaplan-Meier 1, 2 and 5-year survival estimates were 73%, 49% and 22%, respectively. Data were obtained by joining the national Danish Pancreatic Cancer Database (DPCD) and the Danish Anaesthesia Database (DAD). Associations between the primary endpoint (OS) and perioperative factors including duration of surgery, type of anesthesia (intravenous, inhalation or mixed), use of epidural analgesia and perioperative blood transfusions were assessed using Hazard Ratios (HRs). These were calculated by Cox regression, controlling for relevant confounders identified through an assessment of the current literature. These included demographics, comorbidities, perioperative information, pre and postoperative chemotherapy, tumor staging and free resection margins. RESULTS: Overall, data from 473 resected PDAC patients were available. Multivariate Cox regression indicated that perioperative blood transfusions were associated with shorter OS (HR 2.53, p = 0.005), with survival estimates of 8.8% in transfused vs. 28.0% in non-transfused patients at 72 months after surgery. No statistically significant associations were identified for the duration of surgery or anesthesia/analgesia techniques. CONCLUSION: In this study, the use of perioperative blood transfusions was associated with shorter OS.

The results of surgery for renal cell carcinoma metastases of the pancreas.

BACKGROUND: Pancreatic metastases from renal cell carcinoma (RCC) are rare. This study evaluated the surgical pathology and outcomes after resection of RCC metastases to the pancreas. MATERIAL AND METHODS: A retrospective review of from 1 January 2011 to 31 December 2021, of patients who underwent pancreatic surgery for metastases from RCC. Data were retrieved from a prospectively managed database and patient demographics, comorbidities, pathology, perioperative outcomes, and overall survival were analyzed. Median overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan-Meier method. RESULTS: There were 25 patients (17 males, 8 females, median age 66 range 51 - 79 year), all with metachronous metastases. Median time from resection of the primary to operation for pancreatic RCC was 95.6 (12.0 - 309.7) months. Twenty-four patients were operated with intended cure (four pancreaticoduodenectomies, three total pancreatectomies, 17 distal pancreatectomies) and one patient had abortive surgery due to dissemination. Postoperative surgical complications occurred in nine patients (36%), and one patient died during hospital stay. Eight patients (33.3%) developed exocrine and/or endocrine insufficiency after pancreatic resection. Fifteen patients (60%) had recurrence 21.7 (4.9 - 61.6) months after pancreatic operation. Five patients (25%) died from RCC during follow-up 46.3 (25.6 - 134.8) months after pancreatic resection. Five-year OS and DFS were83.6% and 32.3%, respectively. Median OS after pancreatic surgery was 134.8 months, independent of resection of previous extrapancreatic metastases. CONCLUSIONS: Pancreatic resection for metastases from RCC offers favorable prognosis with a curative potential and should be considered a valuable treatment option even in the era of novel targeted treatment.

Impact of para aortic lymph node removal on survival following resection for pancreatic adenocarcinoma.

INTRODUCTION: For PDAC patients undergoing resection, it remains unclear whether metastases to the paraaortic lymph nodes (PALN+) have any prognostic significance and whether metastases should lead to the operation not being carried out. Our hypothesis is that PALN + status would be associated with short overall survival (OS) compared with PALN-, but longer OS compared with patients undergoing surgical exploration only (EXP). METHODS: Patients with registered PALN removal from the nationwide Danish Pancreatic Cancer Database (DPCD) from May 1st 2011 to December 31st 2020 were assessed. A cohort of PDAC patients who only had explorative laparotomy due to non-resectable tumors were also included (EXP group). Survival analysis between groups were performed with cox-regression in a multivariate approach including relevant confounders. RESULTS: A total of 1758 patients were assessed, including 424 (24.1%) patients who only underwent explorative surgery leaving 1334 (75.8%) patients for further assessment. Of these 158 patients (11.8%) had selective PALN removal, of whom 19 patients (12.0%) had PALN+. Survival analyses indicated that explorative surgery was associated with significantly shorter OS compared with resection and PALN + status (Hazard Ratio 2.36, p < 0.001). No difference between PALN + and PALN- status could be demonstrated in resected patients after controlling for confounders. CONCLUSION: PALN + status in patients undergoing resection offer improved survival compared with EXP. PALN + should not be seen as a contraindication for curative intended resection.

Major vascular and pancreatic penetrating trauma in patient with pre-existing MALS.

We report a case regarding a 24-year-old male with severe intraabdominal complex vascular lesions involving the superior mesenteric vein (SMV), portal vein (PV), inferior vena cava (IVC), the Common Hepatic and Gastroduodenal arteries (CHA and GDA) in combination with a total transection of the pancreatic neck following a single penetrating trauma to the upper abdomen. The management of the splanchnic vascular lesions were further complicated by the patient having pre-existing vascular condition known as Median Arcuate Ligament Syndrome (MALS). The MALS aspect makes this case unique and interesting to all trauma surgeons. Furthermore, this case report also reflects on the management of severe pancreatic trauma in the setting of the aforementioned vascular lesions.

Relieving the bile ducts prior to pancreatoduodenectomy - A retrospective cohort study.

Introduction: Obstructive jaundice is a common problem in pancreatic and periampullary tumors, but preoperative biliary drainage in patients with hyperbilirubinemia is still controversial. This study aimed to assess the risk of complications after preoperative drainage of biliary obstruction in patients who underwent pancreaticoduodenectomy. Method: A retrospective cohort study of all patients who underwent pancreaticoduodenectomy from January 1st, 2015 to September 30th, 2021. Patients who had preoperative bile duct drainage were compared to patients without intervention. Type of interventions, complications, and outcomes after surgery were compared using univariate and multivariate analysis. Results: Of 722 patients who underwent pancreatoduodenectomy, 389 patients had preoperative drainage of the bile ducts by ERC or PTC. There was an incidence of 27% drainage-related complications, all categorized as minor (Clavien-Dindo <3) and mainly related to PTC-aided drainage. After pancreaticoduodenectomy, 23% of patients who had a preoperative biliary drain, had minor complications. Patients without biliary drainage had a higher risk of a complicated postoperative course (p = 0.001) and had a higher 30-day (p = 0.002) and 90-day mortality (p = 0.025). Conclusion: Our study found preoperative bile duct drainage to be a safe procedure without severe complications. Patients undergoing preoperative bile duct drainage had fewer post-pancreatoduodenectomy complications and lower mortality.

Pancreatic surgery during the COVID-19 pandemic 2020-2021: an observational cohort study from a third level referral center.

BACKGROUND: During the COVID pandemic there has been limited access to elective surgery including oncologic surgery in several countries world-wide. The aim of this study was to investigate if there was any lockdown effect on pancreatic surgery with special focus on malignant pancreatic and periampullary tumours. METHODS: Patients who underwent pancreatic surgery during the two Danish lockdown periods from 11. March 2020 and the following 12 months were compared with patients who were operated the preceding 3 years. Data on patients' characteristics, waiting time, operations, and clinical outcomes were evaluated. RESULTS: During lockdown and the previous three years the annual number of resections were 242, 232, 253, and 254, respectively (p = 0.851). Although the numbers were not significantly different, there were fluctuations in operations and waiting time during the lockdown. During the second outbreak of COVID October 2020 to March 2021 the overall median waiting time increased to 33 days (quartiles 26;39) compared to 23 (17;33) days during the first outbreak from March to May 2020 (p = 0.019). The same difference was seen for patients with malignant tumours, 30 (23;36) vs. 22 (18;30) months (p = 0.001). However, the fluctuations and waiting time during lockdown was like the preceding three years. Neither 30- nor 90-days mortality, length of stay, number of extended operations, and complications and tumour stage were significantly different from previous years. CONCLUSIONS: There were significant fluctuations in waiting time for operations during the lockdown, but these variations were not different from the preceding three years, wherefore other explanations than an impact from COVID are conceivable.

Long-Term Outcomes of Venous Resections in Pancreatic Ductal Adenocarcinoma Patients: A Nationwide Cohort Study.

To investigate whether pancreatic resections (PR) for pancreatic ductal adenocarcinoma (PDAC) is associated with worse survival when resection of the superior mesenteric vein/portal vein (SMV/PV) is required. Background: PR for PDAC with resection of the superior mesenteric vein/portal vein (SMV/PV, PR+V resection) may be associated with inferior overall survival (OS) compared with PR without the need for SMV/PV resection (PR-V). We hypothesized that PR+V results in lower OS compared with PR-V. Method: Retrospective study using data from the nationwide Danish Pancreatic Cancer Database from 2011 to 2020. Data on patients who underwent PR for PDAC were extracted. A group of PR patients found nonresectable on exploratory laparotomy (EXP) was also included. OS was assessed using Kaplan-Meier and Cox proportional hazards models adjusting for confounders (age, sex, R-resection level, chemotherapy, comorbidities, histology T and N classification, procedure subtype as well as tumor distance to the SMV/PV). Results: Overall, 2403 patients were identified. Six hundred two underwent exploration only (EXP group), whereas 412 underwent pancreatic resection with (PR+V group) and 1389 (PR-V) without SMV/PV resection. Five-year OS for the PR+V group was lower (20% vs 30%) compared with PR-V, although multivariate Cox proportional hazards modeling could not associate PR+V status with OS (Hazard ratio 1.11, P = 0.408). Conclusion: When correcting for confounders, PR+V was not associated with lower OS compared with PR-V.

The diagnostic value of C-reactive protein for predicting pancreatic fistula following pancreatoduodenectomy.

INTRODUCTION: Pancreaticoduodenectomy is the preferred treatment of neoplasms in the pancreas and duodenum. Postoperative pancreatic fistula is a critical complication. A potential predictive marker is C-reactive protein. This retrospective study examined the predictive value of C-reactive protein as a marker for development of postoperative pancreatic fistulas. METHODS: All patients who had a pancreaticoduodenectomy from 1 January 2015 to 31 December 2019, were included. Levels of the biomarker and linear trajectory were determined for postoperative days one to four. Univariate analysis was used to identify predictive variables for a postoperative pancreatic fistula. Receiver operating characteristics curves, specificity, and sensitivity were calculated. RESULTS: Five hundred and fifty-two patients underwent pancreaticoduodenectomy. C-reactive protein level greater than 121.5mg/L on the third postoperative day and an increase in C-reactive protein level between the first and fourth postoperative days, greater than 21.7mg/L, seemed to be reliable predictors. For Grade C postoperative pancreatic fistulas, increases in C-reactive protein, greater than 40.6ml/L the first four postoperative days, had a sensitivity of 100%. White blood cell count did not have similar reliability in predicting postoperative pancreatic fistulas. CONCLUSION: Our findings indicate that small rises in C-reactive protein during the first postoperative days after pancreaticoduodenectomy are associated with an increased risk of developing postoperative pancreatic fistula.

Biliary Leakage Following Pancreatoduodenectomy: Experience from a High-Volume Center.

Purpose: Hepaticojejunostomy leak and bile fistula after pancreaticoduodenectomy (PD) are less frequent than pancreatic leaks. Patients with biliary fistula (BF) have an increased risk of serious complications and an extended hospital stay. This study has investigated the occurrence and outcome of BF. Methods: All patients who underwent a PD from January 1st, 2015 to December 31st, 2019 were included. The significance of multiple risk factors was examined. Univariate analysis was used to identify predictive variables for postoperative BF. Results: Of the 552 patients who underwent PD, 38 patients (6.7%) developed a BF. Patients with nonmalignant diagnoses and malignancies without bile duct obstruction had a greater risk of developing BF. BF did not increase the mortality, though most patients had complications, including surgical site infections, intraabdominal abscesses, and an extended hospital stay. Conclusion: BF after PD leads to an increased risk of subsequent complications and an extended hospital stay but does not increase mortality. Patients with nonmalignant diagnoses and malignancies without bile duct obstruction have an increased risk of BF.

The results of pancreatic operations after the implementation of multidisciplinary team conference (MDT): A quality improvement study.

BACKGROUND: Centralization has improved the outcome of complex operations including cancer surgery. Moreover, the implementation of multidisciplinary team conferences (MDT) has ameliorated the decision making, but the impact on patient outcome is controversial. The aim of the study was to investigate the outcome of pancreatic surgery in the setting of centralization and upfront multidisciplinary decision making. METHOD: The decisions of MDT from 2010 to 2016 and the outcome of operations were compared with operations from 2003 to 2009 before centralization of pancreatic surgery and implementation of MDT. Data were drawn from the department's database and from hospital's electronic patient files. RESULTS: From 2010 to 2016, 7.015 patients were evaluated at the MDT. In 72.6% of patients a treatment plan followed the first evaluation, the referral diagnosis was changed in 12.4% of cases. Of 3.362 solid neoplasms, 1.680 (50.0%) were evaluated as resectable and 1.080 (32.1%) patients were operated. The annual resection rate of operated patients was78.3%-88.5% (median 80.0%) compared to 21.4% to 80.% (median 68.6%, p = 0.0001) from 2003 to 2009 with 279 operated patients. The post-operative 30 - and 90-days mortality from 2003 to 2009 and 2010 to 2016 was 3.4% vs. 1.8% (NS) and 5.0% vs 3.6% (NS). In the same periods explorative laparotomies and palliative resections decreased from 18.3% to 3.6% (p = 0.0001) and 18.6%-10.2% (p = 0.0002). The median survival of radically resected pancreatic adenocarcinoma (PAC) from 2003 to 2009 and from 2010 to 2016 was 20.2 and 21.9 months, respectively (p = 0.687). CONCLUSION: The MDT increased patient flow, improved quality of decision-making and offered more patients surgical treatment without increasing morbidity or mortality. But an impact on the long-term survival of patients with PAC was not found.

Solid pseudopapillary neoplasm of the pancreas: Clinical-pathological features and management, a single-center experience.

Solid pseudopapillary neoplasm of the pancreas is a rare tumor of low malignancy that occurs most often in females. The study describes the clinicopathologic characteristics of the tumor and common differential diagnoses. Data were collected from a prospectively maintained database. Of 1661 patients operated for pancreatic tumors between January 2001 and September 2018, 15 patients were recorded. Patients included 12 females and 3 males, median age 40 (range 10 -87) years. Computed tomography or magnetic resonance imaging was diagnostic in eight patients and a preoperative biopsy in eight out of 10 patients. Median tumor size was 5 cm (range 2 -16 cm), 12 tumors were in the head, six in the body, and three in the tail of the gland. All patients except one had radical resection including one with hepatic and lymph node metastases, no patient underwent oncologic treatment. All patients are alive from 17.5 to 209.4 months postoperatively and without recurrence. Radical operation is usually curative and should also be offered to patients with metastases or recurrence as oncologic treatment has limited effect.

Mesenterico-portal vein resection in patients with pancreatico-duodenal cancer is safe and may increase survival.

INTRODUCTION: Pancreatic cancer is one of the most serious gastrointestinal cancers, and in the US and Europe it is a leading cause of cancer-related mortality. Radical surgery is the only option available for long-term survival. The aim of this study was to describe the surgical technique and the results of portal vein/superior mesenteric vein resection in patients with pancreatic cancer. MATERIAL AND METHODS: Between 1 April 2009 and 1 April 2013, 354 patients underwent resection for pancreatic malignancy. A total of 47 portal vein/superior mesenteric vein resections were performed in 22 men and 25 women. RESULTS: A total of 44 patients (93.7%) had ductal adenocarcinomas. In all, 39 patients (83%) had T3 tumours, and 38 patients (80.9%) had involvement of lymph nodes. Furthermore, 29 patients (62%) had a pancreaticoduodenectomy, 15 patients (32%) a total pancreatectomy and three patients (6%) had a distal pancreatectomy. Six patients (17%) were reconstructed with interposition grafts, and vessels (83%) were reconstructed with an end-to-end anastomosis in the remaining 39 patients. Surgical morbidity was 29.8%, and 19.1% had non-surgical complications. The perioperative mortality (30 days) was 0%. The median survival was 25.2 months (confidence interval: 19-31.4). CONCLUSION: Resection of the portal vein/superior mesenteric vein is a safe procedure. It is not associated with an increased perioperative morbidity and mortality. This latter finding is in accordance with the findings in other high-volume centres. The median survival was far better than expected, especially since our material included a considerable number of patients with lymph node metastases. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

Spontaneous and bolus-induced motility in the chronically obstructed guinea-pig small intestine in vitro.

Partial obstruction of the small intestine results in dysmotility and morphometric changes proximal to the site of obstruction. However, our understanding of the relation between the morphometric remodeling and change in the motility pattern during chronic obstruction is sparse. The aim of this study was to investigate the effect of partial chronic intestinal obstruction on motility, morphology, and collagen content proximal and distal to the site of obstruction. Twenty guinea-pigs with partial intestinal obstruction and eight sham-operated controls lived for four weeks. Spontaneous and bolus-induced motility was recorded in isolated intestinal segments proximal and distal to the site of obstruction using a perfused low-compliance pressure-measuring system in vitro. After the motility experiments, the specimens were fixed at 2 kPa luminal distension pressure and sampled for histomorphometric determination of luminal radius, layer thickness, and wall thickness. Total wall collagen was also determined. The area under the curve (AUC) of spontaneous contractions and the amplitude, frequency, and AUC for the bolus-induced motility were higher in the proximal segments of the banded animals compared to distal segments and to the intestinal segments in the control animals (P < 0.05). The radius-to-thickness ratio was lowest in the proximal segments of the obstructed animals (P < 0.01). The collagen content was three times higher proximal to the site of obstruction when compared to distal locations and to the controls (P < 0.01). The AUC at 2 ml bolus injections plotted against the radius-to-thickness ratio showed a strong association (r = 0.97 for control, and r = 0.99 for obstruction, P < 0.01). No correlation was found between the collagen content and AUC. In conclusion, partial intestinal obstruction in guinea pigs caused pronounced changes in morphology and motility. An association was found between the radius-to-thickness ratio and bolus-induced motility.

Biomechanical remodeling of the chronically obstructed Guinea pig small intestine.

Small intestinal obstruction is a frequently encountered clinical problem. To understand the mechanisms behind obstruction and the clinical consequences, data are needed on the relation between the morphologic and biomechanical remodeling that takes place in the intestinal wall during chronic obstruction. We sought to determine the effect of partial obstruction on mechanical and morphologic properties of the guinea pig small intestine. Partial obstruction was created surgically in 2 groups of animals living for 2 and 4 weeks. Controls were sham operated and lived for 4 weeks. A combined impedance planimetry-high-frequency ultrasound system was designed to measure the luminal cross-sectional area and wall thickness. These measures were used to compute the circumferential stress and strain of the excised intestinal segments. The incremental elastic modulus was obtained by using nonlinear fitting of the stress-strain curve. Histologic analysis and the measurements of total wall collagen were also performed. The luminal cross-sectional area, wall thickness, and elastic modulus in circumferential direction increased in a time-dependent manner proximal to the obstruction site (P < 0.01), whereas no differences in these parameters were found distal to the obstruction site (P > 0.25). The circumferential stress-strain curves of the proximal segments in 2- and 4-week groups shifted to the left, indicating the intestinal wall became stiffer. Histologic examination revealed a massive increase in the thickness of the muscle layer especially the circular smooth muscle layer (P < 0.05). The collagen content proximal to the obstruction site was significantly larger in the partially obstructed animals compared to controls (P < 0.05). No difference was found distal to the obstruction site. Strong correlation was found between the collagen content and the elastic modulus at stress levels of 70 kPa stress (P < 0.01) and 10 kPa (P < 0.05) proximal to the obstruction site suggesting that the alteration of collagen has great impact on the mechanical remodeling. The morphologic and biomechanical remodeling likely influence the function of the intestine affected by partial obstructed intestine.