Surveillance after surgery for pancreatic cancer: a global scoping review of guidelines and a nordic Survey of contemporary practice.

OBJECTIVES: Most patients with pancreatic cancer who have undergone surgical resection eventually develop disease recurrence. |This study aimed to investigate whether there is evidence to support routine surveillance after pancreatic cancer surgery, with a secondary aim of analyzing the implementation of surveillance strategies in the Nordic countries. MATERIALS AND METHODS: A scoping review was conducted to identify clinical practice guidelines globally and research studies relating to surveillance after pancreatic cancer resection. This was followed by a survey among 20 pancreatic units from four Nordic countries to assess their current practice of follow-up for operated patients. RESULTS: Altogether 16 clinical practice guidelines and 17 research studies were included. The guidelines provided inconsistent recommendations regarding postoperative surveillance of pancreatic cancer. The clinical research data were mainly based on retrospective cohort studies with low level of evidence and lead-time bias was not addressed. Active surveillance was recommended in Sweden and Denmark, but not in Norway beyond the post-operative/adjuvant period. Finland had no national recommendations for surveillance. The Nordic survey revealed a wide variation in reported practice among the different units. About 75% (15 of 20 units) performed routine postoperative surveillance. Routine CA 19-9 testing was used by 80% and routine CT by 67% as part of surveillance. About 73% of centers continued follow-up until 5 years postoperatively. CONCLUSION: Evidence for routine long-term (i.e. 5 years) surveillance after pancreatic cancer surgery remains limited. Most pancreatic units in the Nordic countries conduct regular follow-up, but protocols vary.

Quality-of-life after bile duct injury repaired by hepaticojejunostomy: a national cohort study.

OBJECTIVES: Reports on quality-of-life (QoL) after bile duct injury (BDI) show conflicting results. The aim of this cohort study was to evaluate QoL stratified according to type of treatment. METHODS: QoL assessment using the SF-36 (36-item short form health survey) questionnaire. Patients with post-cholecystectomy BDI needing hepaticojejunostomy (HJ) were compared to all other treatments (BDI repair) and to patients without BDI at cholecystectomy (controls). RESULTS: Patients needing a HJ after BDI reported reduced long-term QoL irrespective of time for diagnosis and repair in both the physical (PCS; p < .001) and mental (MCS; p < .001) domain compared to both controls and patients with less severe BDI. QoL was comparable for BDI repair (n = 86) and controls (n = 192) in both PCS (p = .171) and MCS (p = .654). As a group, patients with BDI (n = 155) reported worse QoL than controls, in both the PCS (p < .001) and MCS (p = .012). Patients with a BDI detected intraoperatively (n = 124) reported better QoL than patients with a postoperative diagnosis. Patients with an immediate intraoperative repair (n = 99), including HJ, reported a better long-term QoL compared to patients subjected to a later procedure (n = 54). CONCLUSIONS: Patients with postoperative diagnosis and patients with BDIs needing biliary reconstruction with HJ both reported reduced long-term QoL.

Ultrasound-guided Percutaneous Irreversible Electroporation for Treatment of Locally Recurrent Pancreatic Cancer After Surgical Resection.

BACKGROUND/AIM: Irreversible electroporation (IRE) has recently been used as an experimental treatment for cancers including locally advanced pancreatic cancer. There is very limited data on IRE in pancreatic cancer that is locally recurrent after surgical resection. The aim of this study was to evaluate the safety and efficacy of IRE in this setting. PATIENTS AND METHODS: Ten patients with locally recurrent pancreatic cancer without distant metastases after surgical resection were included and treated with ultrasound-guided percutaneous IRE. RESULTS: Two patients had severe complications, of whom one died. Median disease-free survival was 3.3 months and overall median survival after IRE and resection was 16.5 and 42.7 months, respectively. Two patients are alive 42.1 and 23.9 months after the IRE without signs of local recurrence. CONCLUSION: Percutaneous IRE in locally recurrent pancreatic cancer following curative resection is feasible, but should be regarded as a high-risk procedure that, at present, cannot be recommended outside of clinical trials. Further research is needed to select patients who might benefit from this treatment.

The Value of CA19-9 After Irreversible Electroporation for Pancreatic Cancer.

BACKGROUND/AIM: Carbohydrate antigen 19-9 (CA19-9) is a tumor marker for pancreatic cancer. Irreversible electroporation (IRE) is an experimental treatment modality for pancreatic cancer. The aim of this study was to evaluate whether percutaneous IRE lowers the CA19-9 level in pancreatic cancer and whether this correlates with improved overall survival. PATIENTS AND METHODS: Seventy-one patients with locally advanced pancreatic cancer or local recurrence after resection were treated. Patients with missing data, metastatic disease and normal serum CA19-9 before IRE were excluded. This left 35 cases for analysis. RESULTS: The median CA19-9 did not decrease in the cohort after IRE treatment (282 U/ml before versus 315 U/ml after; p=0.80). The 25th percentile of patients with the best CA19-9 response had improved overall survival compared to the 25th percentile with the worst response (mean 13.1 versus 8.1 months, respectively; p=0.01). CONCLUSION: IRE did not lower the level of CA19-9 in pancreatic cancer cases. However, a response in CA19-9 was correlated with improved survival.

Percutaneous Irreversible Electroporation as First-line Treatment of Locally Advanced Pancreatic Cancer.

BACKGROUND/AIM: Irreversible electroporation (IRE) has recently been used as an experimental ablation treatment following systemic chemotherapy in locally advanced pancreatic cancer (LAPC). The primary aim of this study was to evaluate survival of LAPC patients after IRE prior to chemotherapy. The secondary aim was to examine the complication rates. PATIENTS AND METHODS: Twenty-four patients with LAPC were included and treated with percutaneous ultrasound-guided IRE under general anesthesia. Survival data from the National Quality Registry for Pancreatic and Periampullary Cancer for LAPC during the same period were used for comparison. RESULTS: The median survival after diagnosis was 13.3 months in the IRE group compared to 9.9 months in the registry group (p=0.511). Six patients had a severe complication after IRE treatment. CONCLUSION: No obvious gain in survival was observed with IRE as the first line treatment of LAPC and IRE was associated with severe complications. This study does not support percutaneous IRE in this setting.

Severe complications with irreversible electroporation of the pancreas in the presence of a metallic stent: a warning of a procedure that never should be performed.

Irreversible electroporation (IRE) is an ablation technique that is being investigated as a potential treatment of pancreatic cancer. However, many of these patients have a metallic stent in the bile duct, which is recognized as a contraindication for IRE ablation. We report a case in which an IRE ablation in the region of the pancreatic head was performed on a patient with a metallic stent which led to severe complications. After the treatment, the patient suffered from several complications including perforation of the duodenum and transverse colon, and bleeding from a branch of the superior mesenteric artery which eventually lead to her death. Therefore, we believe it is important to be aware of this if an IRE ablation close to a metallic stent is considered.

Safety and preliminary efficacy of ultrasound-guided percutaneous irreversible electroporation for treatment of localized pancreatic cancer.

BACKGROUND: Irreversible electroporation (IRE) is a local tumor treatment. Thin needles are placed percutaneously around the tumor under ultrasound guidance. Short pulses of direct current sent through the tissue irreversibly increase cell membrane permeability leading to cell death. We report a phase 1 study assessing the safety of ultrasound guided percutaneous IRE in patients with localized pancreatic cancer (LPC). PATIENTS AND METHODS: Five patients (three males) with LPC, judged unsuitable for surgery, chemotherapy, or non-resectable after standard oncological treatment, were treated with IRE. The treatment was given under general anesthesia with muscle relaxation. RESULTS: No serious treatment-related adverse events were observed. There was no 30-day mortality. One patient went on to laparotomy and had a R0 pancreaticoduodenectomy with portal vein resection. Six months after the treatment, two patients had no signs of recurrence on computed tomography or contrast-enhanced ultrasound. CONCLUSION: IRE for LPC can be safely performed percutaneously under ultrasound guidance, with promising initial results regarding efficacy.

An unusual presentation of a solid pseudopapillary pancreatic tumor.

Solid pseudopapillary pancreatic tumor (SPPT) is a rare tumor that constitutes 1-2% of all pancreatic tumors and most of the patients are young females. SPPT has low malignancy potential and radical resection is associated with good results and a high survival rate, even in cases with large tumors: the 5-year survival rate is estimated as 95%. This paper describes an unusual presentation of an SPPT discovered after blunt trauma to the abdomen during a basketball game. Computed tomography revealed a large tumor in the pancreatic head and the patient was operated by pylorus-preseving pancreaticoduodenectomy. The histopathologic examination indicated an SPPT with R0-resection and after 4 years there were no signs of recurrence.

Factors involved in the inflammatory events of cervical ripening in humans.

BACKGROUND: Cervical ripening is an inflammatory reaction. The glucocorticoid receptor (GR) mediates glucocorticoid anti-inflammatory reactions, whereas nuclear factor (NF)kappaB is a key pro-inflammatory transcription factor. Prostaglandins as well as platelet activating factor (PAF) are inflammatory mediators. Inducible nitric oxide synthase (iNOS) regulates the level of nitric oxide (NO) in response to various inflammatory stimuli. We hypothesize that a changed biological response to glucocorticoids could be a mechanism regulating the inflammatory events resulting in cervical ripening. METHODS: We monitored GR and NFkappaB, prostaglandin synthases cyclooxygenase (COX)-1 and -2, iNOS, as well as the PAF-receptor (PAF-R) in the uterine cervix from term pregnant women (with unripe cervices) before the onset of labor (TP), immediately after parturition (PP), as compared to non-pregnant (NP), using immunohistochemistry and RT-PCR. RESULTS: The GR protein was detected by immunohistochemistry in the nuclei of stroma and squamous epithelium (SQ). Stromal GR staining was increased in TP as compared to the NP group and decreased again after parturition. GR staining in SQ was decreased after parturition as compared to term. NFkappaB was present in SQ and glandular epithelium (GE), stroma and vascular endothelium. Increased nuclear NFkappaB staining was observed postpartum as compared to term pregnancy in stroma and GE. Stromal immunostaining for COX-1 as well as COX-2 was increased in the TP and PP groups as compared to the NP, and GE displayed an intensely increased COX-2 immunostaining at term and postpartum. Stromal PAF-R immunostaining was highest at term, while it was greatly increased in GE postpartum. No difference in the immunostaining for iNOS was found between the groups. RT-PCR showed a predominance of GRalpha to GRbeta mRNA in cervical tissue. The COX-2 mRNA level was increased in the PP group as compared to the TP group. CONCLUSIONS: There is a decrease in GR levels in human cervix at parturition. Concomitantly there is an increase of factors such as NFkappaB, PAF-R, COX-1 and COX-2, suggesting that they may participate in the sequence of events leading to the final cervical ripening.