Survival Analysis of Conversion Surgery in Borderline Resectable and Locally Advanced Unresectable Pancreatic Ductal Adenocarcinoma Addressing Selection and Immortal Time Bias: A Retrospective Single-Center Study.

BACKGROUND: The purpose of this study was to provide a detailed evaluation of the oncological advantages of surgery following neoadjuvant chemotherapy (NAC) for patients with borderline resectable (BR) or unresectable (UR) pancreatic ductal adenocarcinoma (PDAC), with a focus on minimizing biases. Recently, NAC has become the standard care for BR or UR locally advanced (UR-LA) PDAC, however, many studies have assessed survival benefits and favorable variables without consideration for biases, particularly immortal time bias. PATIENTS AND METHODS: This study included patients diagnosed with BR or UR-LA PDAC at Juntendo University Hospital from 2019 to 2022. To mitigate bias, we applied methods such as propensity score matching (PSM), time-dependent covariate Cox proportional hazard regression analysis (TDC), landmark analysis, and multivariable Cox proportional hazards regression model. RESULTS: The study analyzed 124 patients, dividing them into a surgery group (n = 57) and a chemotherapy-only group (n = 67). After PSM, there were 21 matched pairs. Survival analysis using TDC analysis showed that the surgery group had significantly better overall survival compared with the chemotherapy-only group in both the entire cohort and the matched pairs. Cox regression analysis of the entire cohort also revealed a similar superiority of surgery, while the landmark analysis showed varying results depending on the landmark setting. CONCLUSIONS: After careful adjustment for selection and immortal time biases, surgery following NAC appears to significantly extend survival in patients with BR or UR PDAC.

Pancreatoduodenectomy with superior mesenteric vein resection and non-reconstruction for pancreatic head cancer paying particular attention to hemodynamics.

PURPOSE: Locally advanced pancreatic ductal adenocarcinoma (PDAC) with an unreconstructible superior mesenteric vein (SMV) invasion is one of the criteria of unresectability in the National Comprehensive Cancer Network guidelines. Advances in chemotherapy have improved downstaging and conversion surgery outcomes, thereby broadening surgical options for locally advanced PDAC. However, operations for PDAC with an unreconstructible SMV is less well-documented. If the collateral route is well-developed and can be preserved or reconstructed, SMV resection can be performed without reconstruction. In this paper, we detail our surgical technique and the outcomes for patients undergoing pancreatoduodenectomy with SMV resection and non-reconstruction (PD-SMVR-NR). METHODS: All consecutive patients with pancreatic head cancer who underwent PD at Juntendo University Hospital, Japan, between January 2019 and December 2022 were evaluated from a prospectively maintained preoperative database. Demographic data, clinical history, operative record, morbidity, mortality, and pathologic data were reviewed. RESULTS: Over four years at our Institute, 161 patients with pancreatic head cancer underwent PD, and 86 of these patients underwent PD with portal vein (PV) or SMV resection. There were three patients who underwent PD-SMVR-NR. Each patient had well-developed collateral vessels bypassing the obstructed segment of the SMV. All three patients had no hospital mortality with acceptable complications (Clavien-Dindo grade 2). Two patients achieved R0 resection. CONCLUSION: By understanding the hemodynamics of venous flow and preserving collateral vessels, especially the superior right colic vein arcade and porto-mesenterico-splenic confluence, pancreatoduodenectomy with superior mesenteric vein resection and non-reconstruction can be performed safely.

Characterization of deamidation at Asn138 in L-chain of recombinant humanized Fab expressed from Pichia pastoris.

A method was previously established for evaluating Asn deamidation by matrix-assisted laser desorption/ionization time of flight-mass spectrometry using endoproteinase Asp-N. In this study, we demonstrated that this method could be applied to the identification of the deamidation site of the humanized fragment antigen-binding (Fab). First, a system for expressing humanized Fab from methylotrophic yeast Pichia pastoris was constructed, resulting in the preparation of ∼30 mg of the purified humanized Fab from 1 l culture. Analysis of the L-chain derived from recombinant humanized Fab that was heated at pH 7 and 100°C for 1 h showed the deamidation at Asn138 in the constant region. Then, we prepared L-N138D Fab and L-N138A Fab and examined their properties. The circular dichroism (CD) spectrum of the L-N138D Fab was partially different from that of the wild-type Fab. The measurement of the thermostability showed that L-N138D caused a significant decrease in the thermostability of Fab. On the other hand, the CD spectrum and thermostability of L-N138A Fab showed the same behaviour as the wild-type Fab. Thus, it was suggested that the introduction of a negative charge at position 138 in the L-chain by the deamidation significantly affected the stability of humanized Fab.