Systematic Review and Meta-analysis of the Role of Total Pancreatectomy as an Alternative to Pancreatoduodenectomy in Patients at High Risk for Postoperative Pancreatic Fistula: Is it a Justifiable Indication?

OBJECTIVE: Examine the potential benefit of total pancreatectomy (TP) as an alternative to pancreatoduodenectomy (PD) in patients at high risk for postoperative pancreatic fistula (POPF). SUMMARY BACKGROUND DATA: TP is mentioned as an alternative to PD in patients at high risk for POPF, but a systematic review is lacking. METHODS: Systematic review and meta-analyses using Pubmed, Embase (Ovid), and Cochrane Library to identify studies published up to October 2022, comparing elective single-stage TP for any indication versus PD in patients at high risk for POPF. The primary endpoint was short-term mortality. Secondary endpoints were major morbidity (i.e., Clavien-Dindo grade ≥IIIa) on the short-term and quality of life. RESULTS: After screening 1212 unique records, five studies with 707 patients (334 TP and 373 high-risk PD) met the eligibility criteria, comprising one randomized controlled trial and four observational studies. The 90-day mortality after TP and PD did not differ (6.3% vs. 6.2%; RR=1.04 [95%CI 0.56-1.93]). Major morbidity rate was lower after TP compared to PD (26.7% vs. 38.3%; RR=0.65 [95%CI 0.48-0.89]), but no significance was seen in matched/randomized studies (29.0% vs. 36.9%; RR = 0.73 [95%CI 0.48-1.10]). Two studies investigated quality of life (EORTC QLQ-C30) at a median of 30-52 months, demonstrating comparable global health status after TP and PD (77% [±15] vs. 76% [±20]; P =0.857). CONCLUSIONS: This systematic review and meta-analysis found no reduction in short-term mortality and major morbidity after TP as compared to PD in patients at high risk for POPF. However, if TP is used as a bail-out procedure, the comparable long-term quality of life is reassuring.

Total pancreatectomy as an alternative to high-risk pancreatojejunostomy after pancreatoduodenectomy: a propensity score analysis on surgical outcome and quality of life.

BACKGROUND: Total pancreatectomy (TP) is mentioned as alternative to pancreatoduodenectomy (PD) with high-risk pancreatojejunostomy (PJ) to avoid severe pancreatic fistula-related complications, but its benefit is controversial and comparative studies are scarce. METHODS: Cross-sectional single-center study among patients after PD with high-risk PJ versus patients after single-stage elective TP for any indication (2015-2017), using propensity scores to evaluate surgical outcomes and long-term quality of life (QoL) in three risk strata. EORTC QLQ-C30 and EQ-5D-5L were used for QoL assessment. RESULTS: Overall, 77 patients after TP (68.8%) and 102 patients after high-risk PD (34.5%) were included. Major morbidity (29.9% vs. 41.2%; p = 0.119) and 90-day mortality (5.2% vs. 8.8%; p = 0.354) did not differ significantly between TP and high-risk PD. Interventions for intra-abdominal fluid collections (9.1% vs. 23.5%, p = 0.011) and postpancreatectomy haemorrhage (6.5% vs. 18.6%; p = 0.018) were more often required after high-risk PD, but these differences did not remain after stratification. QoL was comparable after TP and high-risk PD (75% vs. 83%; p = 0.720), even after stratification. CONCLUSIONS: TP seems not to be inferior to high-risk PD regarding surgical outcomes and QoL. TP could be considered as an alternative to a very high-risk PD, but reluctance persists since TP does not appear to reduce mortality.

[Intraductal papillary mucinous cystic neoplasm and other common cystic pancreatic lesions]. / ABC om Intraduktal papillär mucinös neoplasi och andra vanliga cystor i pankreas.

Pancreatic cysts are common. Some harbor malignant potential but are not always distinguishable from benign lesions. Premalignant cysts offer an opportunity for preventive surgery. Pancreatic surgery is associated with morbidity and mortality; hence appropriate patient selection is mandated. The most common pancreatic cystic neoplasms are intraductal papillary mucinous neoplasm and mucinous cystic neoplasm, both of which have a malignant potential, while serous cystic neoplasm is benign. Clinical, biochemical and radiological signs of increased risk for malignancy may constitute an absolute or relative indication for surgery. All patients fit for surgery with newly discovered cysts should be evaluated at a tertiary center. Follow up MRI (or EUS) and S-CA19-9 is recommended 6 months from diagnosis for premalignant cysts, and - if there is no progress - annually, for as long as the patient is fit for surgery.

Inhibition by methylated organo-arsenicals of the respiratory 2-oxo-acid dehydrogenases.

Inorganic arsenic that is ingested through drinking water or inhalation is metabolized by biological methylation pathways into organoarsenical metabolites. It is now becoming understood that this metabolism that was formerly considered to be detoxification may contribute as much or more to increasing the toxicity of arsenic. One proposed mode of the toxic action of arsenic and its organoarsenic metabolites is through its binding to proteins and inactivating their enzymatic activity. The classic case has been considered the affinity of the proximal 1,3 sulfhydryl groups of the lipoic acid cofactor of the pyruvate dehydrogenase complex for arsenic. A 2:1 stoichiometry of sulfhydryl to arsenic groups has been measured in proteins and arsenical complexes can be synthesized using free D,L-lipoic acid. The relative importance of this site for arsenic binding has come in to question through the use of methylating bifunctional arsenic complexes that suggested the methylation of an active site histidine may also be important, and the suggestion that arsenic inhibits the pyruvate dehydrogenase complex indirectly by elevating mitochondrial hydrogen peroxide generation. In order to separate the effects of direct trivalent arsenite toxicity from that of hydrogen peroxide and activated oxygen, we studied the inhibition of the PDH complex under conditions that did not generate hydrogen peroxide but did expose the lipoic acid group in its reduced state to arsenicals. We also studied the effects of arsenicals in the inhibition of the α-ketoglutarate dehydrogenase complex. We found that only trivalent arsenical compounds inhibited the activity of both dehydrogenase complexes and only when the lipoic acid was in its reduced form. Arsenite inhibited both enzyme complexes approximately equivalently while monomethylarsenite inhibited the PDH complex to a greater extent than the KGDH complex - although both complexes were very sensitive to inhibition by this complex. Dimethylarsenite inhibition of both complexes was only observed with longer pre-incubation periods. Cumulative inhibition by the reduced arsenical was observed for all complexes indicating a binding mode of inhibition that is dependent upon lipoic acid being in its reduced state.

Timing and appropriate use of electrodiagnostic studies.

Electrodiagnostic studies are powerful tools used to objectively examine the physiologic status of a nerve. These consist of nerve conduction studies, which directly examine motor and sensory function of the nerve, and electromyography, which examines spontaneous and voluntary motor unit action potentials in the muscle. Together these studies enable characterization, localization, and duration of nerve pathology. Appropriate timing and use of electrodiagnostic studies assist medical providers in treating nerve pathology.