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Simple Summary Extensive portal vein (PV) resection, including porto-mesenterico-splenic confluence (PMSC) during pancreaticoduodenectomy (PD) may sometimes be necessary for pancreatic head cancer, if the tumor is close to the portal venous system. However, as a late-onset postoperative complication, this extensive PV resection may result in sinistral portal hypertension (SPH) and cause variceal bleeding due to congested venous flow from the spleen. Since the prognosis of patients with pancreatic cancer has improved, owing to the development of chemotherapy and surgical techniques, SPH is no longer a negligible matter in the field of pancreatic cancer surgery. This review clarifies the pathogenesis and frequency of SPH after PD with PMSC resection and discusses its prediction and prevention. Abstract To achieve curative resection for pancreatic cancer during pancreaticoduodenectomy (PD), extensive portal vein (PV) resection, including porto-mesenterico-splenic confluence (PMSC), may sometimes be necessary if the tumor is close to the portal venous system. Recently, this extended resection has been widely accepted in high-volume centers for pancreatic resection due to its favorable outcomes compared with non-operative treatment. However, in patients with long-term survival, sinistral portal hypertension (SPH) occurs as a late-onset postoperative complication. These patients present gastrointestinal varices due to congested venous flow from the spleen, which may cause critical variceal bleeding. Since the prognosis of patients with pancreatic cancer has improved, owing to the development of chemotherapy and surgical techniques, SPH is no longer a negligible matter in the field of pancreatic cancer surgery. This review clarifies the pathogenesis and frequency of SPH after PD through PMSC resection and discusses its prediction and prevention.

Simple Summary Aggressive arterial resection or total pancreatectomy in surgical treatment for locally advanced pancreatic cancer (LAPC) has gradually been encouraged thanks to new chemotherapy regimens such as FOLFIRINOX or Gemcitabine and nab-paclitaxel, which have provided more adequate patient selection and local tumor suppression, justifying aggressive local resection. The development of surgical techniques provides the safety of arterial resection (AR) for even major visceral arteries, such as the celiac axis or superior mesenteric artery. Total pancreatectomy has been re-evaluated as an effective option to balance both the local control and postoperative safety. In this review, we investigate the recent reports focusing on arterial resection and total pancreatectomy for locally advanced pancreatic cancer (LAPC) and discuss the rationale of such an aggressive approach in the treatment of PC. Abstract Aggressive arterial resection (AR) or total pancreatectomy (TP) in surgical treatment for locally advanced pancreatic cancer (LAPC) had long been discouraged because of their high mortality rate and unsatisfactory long-term outcomes. Recently, new chemotherapy regimens such as FOLFIRINOX or Gemcitabine and nab-paclitaxel have provided more adequate patient selection and local tumor suppression, justifying aggressive local resection. In this review, we investigate the recent reports focusing on arterial resection and total pancreatectomy for LAPC and discuss the rationale of such an aggressive approach in the treatment of PC. AR for LAPCs is divided into three, according to the target vessel. The hepatic artery resection is the simplest one, and the reconstruction methods comprise end-to-end, graft or transposition, and no reconstruction. Celiac axis resection is mainly done with distal pancreatectomy, which allows collateral arterial supply to the liver via the pancreas head. Resection of the superior mesenteric artery is increasingly reported, though its rationale is still controversial. Total pancreatectomy has been re-evaluated as an effective option to balance both the local control and postoperative safety. In conclusion, more and more aggressive pancreatectomy has become justified by the principle of total neoadjuvant therapy. Further technical standardization and optimal neoadjuvant strategy are mandatory for the global dissemination of aggressive pancreatectomies.

Cancer tissues are composed of cancer cells and the surrounding stromal cells (e.g., fibroblasts, vascular endothelial cells, and immune cells), in addition to the extracellular matrix. Most studies investigating carcinogenesis and the progression, invasion, metastasis, and angiogenesis of cancer have focused on alterations in cancer cells, including genetic and epigenetic changes. Recently, interactions between cancer cells and the stroma have attracted considerable attention, and increasing evidence has accumulated on this. Several researchers have gradually clarified the origins, features, and roles of cancer-associated fibroblasts (CAFs), a major component of the cancer stroma. CAFs function in a similar manner to myofibroblasts during wound healing. We previously reported the relationship between CAFs and angiogenesis. Interleukin-6 (IL-6), a multifunctional cytokine, plays a central role in regulating inflammatory and immune responses, and important roles in the progression, including proliferation, migration, and angiogenesis, of several cancers. We showed that CAFs are an important IL-6 source and that anti-IL-6 receptor antibody suppressed angiogenesis and inhibited tumor-stroma interactions. Furthermore, CAFs contribute to drug-resistance acquisition in cancer cells. The interaction between cancer cells and the stroma could be a potential target for anti-cancer therapy.