Novel ACTA1 mutation causes late-presenting nemaline myopathy with unusual dark cores

ACTA1 gene encodes the skeletal muscle alpha-actin, the core of thin filaments of the sarcomere. ACTA1 mutations are responsible of several muscle disorders including nemaline, cores, actin aggregate myopathies and fiber-type disproportion. We report clinical, muscle imaging, histopatological and genetic data of an Italian family carrying a novel ACTA1 mutation. All affected members showed a late-presenting, diffuse muscle weakness with sternocleidomastoideus and temporalis atrophy. Mild dysmorphic features were also detected. The most affected muscles by muscle MRI were rectus abdominis, gluteus minimus, vastus intermedius and both gastrocnemii. Muscle biopsy showed the presence of nemaline bodies with several unusual dark areas at Gomori Trichrome, corresponding to unstructured cores with abundant electrodense material by electron microscopy. The molecular analysis revealed missense variant c.148G>A; p.(Gly50Ser) in the exon 3 of ACTA1, segregating with affected members in the family. We performed a functional essay of fibre contractility showing a higher pCa50 (a measure of the calcium sensitivity of force) of type 1 fibers compared to control subjects’ type 1 muscle fibers. Our findings expand the clinico-pathological spectrum of ACTA1-related congenital myopathies and the genetic spectrum of core-rod myopathies

The Brescia Internationally Validated European Guidelines on Minimally Invasive Pancreatic Surgery (EGUMIPS)

Objective: To develop and update evidence-based and consensus-based guidelines on laparoscopic and robotic pancreatic surgery. Summary Background Data: Minimally invasive pancreatic surgery (MIPS), including laparoscopic and robotic surgery, is complex and technically demanding. Minimizing the risk for patients requires stringent, evidence-based guidelines. Since the International Miami Guidelines on MIPS in 2019, new developments and key publications have been reported, necessitating an update. Methods: Evidence-based guidelines on 22 topics in 8 domains were proposed: terminology, indications, patients, procedures, surgical techniques and instrumentation, assessment tools, implementation and training, and artificial intelligence. The Brescia Internationally Validated European Guidelines on Minimally Invasive Pancreatic Surgery (EGUMIPS, September 2022) used the Scottish Intercollegiate Guidelines Network (SIGN) methodology to assess the evidence and develop guideline recommendations, the Delphi method to establish consensus on the recommendations among the Expert Committee, and the AGREE II-GRS tool for guideline quality assessment and external validation by a Validation Committee. Results: Overall, 27 European experts, 6 international experts, 22 international Validation Committee members, 11 Jury Committee members, 18 Research Committee members, and 121 registered attendees of the 2-day meeting were involved in the development and validation of the guidelines. In total, 98 recommendations were developed, including 33 on laparoscopic, 34 on robotic, and 31 on general MIPS, covering 22 topics in 8 domains. Out of 98 recommendations, 97 reached at least 80% consensus among the experts and congress attendees, and all recommendations were externally validated by the Validation Committee. Conclusions: The EGUMIPS evidence-based guidelines on laparoscopic and robotic MIPS can be applied in current clinical practice to provide guidance to patients, surgeons, policy-makers, and medical societies

The Brescia Internationally Validated European Guidelines on Minimally Invasive Pancreatic Surgery (EGUMIPS)

Objective: To develop and update evidence-based and consensus-based guidelines on laparoscopic and robotic pancreatic surgery. Summary Background Data: Minimally invasive pancreatic surgery (MIPS), including laparoscopic and robotic surgery, is complex and technically demanding. Minimizing the risk for patients requires stringent, evidence-based guidelines. Since the International Miami Guidelines on MIPS in 2019, new developments and key publications have been reported, necessitating an update. Methods: Evidence-based guidelines on 22 topics in 8 domains were proposed: terminology, indications, patients, procedures, surgical techniques and instrumentation, assessment tools, implementation and training, and artificial intelligence. The Brescia Internationally Validated European Guidelines on Minimally Invasive Pancreatic Surgery (EGUMIPS, September 2022) used the Scottish Intercollegiate Guidelines Network (SIGN) methodology to assess the evidence and develop guideline recommendations, the Delphi method to establish consensus on the recommendations among the Expert Committee, and the AGREE II-GRS tool for guideline quality assessment and external validation by a Validation Committee. Results: Overall, 27 European experts, 6 international experts, 22 international Validation Committee members, 11 Jury Committee members, 18 Research Committee members, and 121 registered attendees of the 2-day meeting were involved in the development and validation of the guidelines. In total, 98 recommendations were developed, including 33 on laparoscopic, 34 on robotic, and 31 on general MIPS, covering 22 topics in 8 domains. Out of 98 recommendations, 97 reached at least 80% consensus among the experts and congress attendees, and all recommendations were externally validated by the Validation Committee. Conclusions: The EGUMIPS evidence-based guidelines on laparoscopic and robotic MIPS can be applied in current clinical practice to provide guidance to patients, surgeons, policy-makers, and medical societies.</p

Differences in Lymph Node Metastases Patterns Among Non-pancreatic Periampullary Cancers and Histologic Subtypes: An International Multicenter Retrospective Cohort Study and Systematic Review

Abstract Background Standard lymphadenectomy for pancreatoduodenectomy is defined for pancreatic ductal adenocarcinoma and adopted for patients with non-pancreatic periampullary cancer (NPPC), ampullary adenocarcinoma (AAC), distal cholangiocarcinoma (dCCA), or duodenal adenocarcinoma (DAC). This study aimed to compare the patterns of lymph node metastases among the different NPPCs in a large series and in a systematic review to guide the discussion on surgical lymphadenectomy and pathology assessment. Methods This retrospective cohort study included patients after pancreatoduodenectomy for NPPC with at least one lymph node metastasis (2010–2021) from 24 centers in nine countries. The primary outcome was identification of lymph node stations affected in case of a lymph node metastasis per NPPC. A separate systematic review included studies on lymph node metastases patterns of AAC, dCCA, and DAC. Results The study included 2367 patients, of whom 1535 had AAC, 616 had dCCA, and 216 had DAC. More patients with pancreatobiliary type AAC had one or more lymph node metastasis (67.2% vs 44.8%; P &lt; 0.001) compared with intestinal-type, but no differences in metastasis pattern were observed. Stations 13 and 17 were most frequently involved (95%, 94%, and 90%). Whereas dCCA metastasized more frequently to station 12 (13.0% vs 6.4% and 7.0%, P = 0.005), DAC metastasized more frequently to stations 6 (5.0% vs 0% and 2.7%; P &lt; 0.001) and 14 (17.0% vs 8.4% and 11.7%, P = 0.015). Conclusion This study is the first to comprehensively demonstrate the differences and similarities in lymph node metastases spread among NPPCs, to identify the existing research gaps, and to underscore the importance of standardized lymphadenectomy and pathologic assessment for AAC, dCCA, and DAC. </jats:sec