Macrophages (Mfs) are instrumental in maintaining immune homeostasis in the intestine, yet studies on the origin and heterogeneity of human intestinal Mfs are scarce. Here, we identified four ...distinct Mf subpopulations in human small intestine (SI). Assessment of their turnover in duodenal transplants revealed that all Mf subsets were completely replaced over time; Mf1 and Mf2, phenotypically similar to peripheral blood monocytes (PBMos), were largely replaced within 3 wk, whereas two subsets with features of mature Mfs, Mf3 and Mf4, exhibited significantly slower replacement. Mf3 and Mf4 localized differently in SI; Mf3 formed a dense network in mucosal lamina propria, whereas Mf4 was enriched in submucosa. Transcriptional analysis showed that all Mf subsets were markedly distinct from PBMos and dendritic cells. Compared with PBMos, Mf subpopulations showed reduced responsiveness to proinflammatory stimuli but were proficient at endocytosis of particulate and soluble material. These data provide a comprehensive analysis of human SI Mf population and suggest a precursor-progeny relationship with PBMos.
Macrophages are a heterogeneous population of cells involved in tissue homeostasis, inflammation, and cancer. Although macrophages are densely distributed throughout the human intestine, our ...understanding of how gut macrophages maintain tissue homeostasis is limited. Here we show that colonic lamina propria macrophages (LpMs) and muscularis macrophages (MMs) consist of monocyte-like cells that differentiate into multiple transcriptionally distinct subsets. LpMs comprise subsets with proinflammatory properties and subsets with high antigen-presenting and phagocytic capacity. The latter are strategically positioned close to the surface epithelium. Most MMs differentiate along two trajectories: one that upregulates genes associated with immune activation and angiogenesis, and one that upregulates genes associated with neuronal homeostasis. Importantly, MMs are located adjacent to neurons and vessels. Cell-cell interaction and gene network analysis indicated that survival, migration, transcriptional reprogramming, and niche-specific localization of LpMs and MMs are controlled by an extensive interaction with tissue-resident cells and a few key transcription factors.
In patients presenting with colorectal cancer and synchronous liver metastases, the disease burden related to the liver metastasis is the driving cause of limited longevity and, eventually, risk of ...death. Surgical resection is the potentially curative treatment for colorectal cancer liver metastases. In the synchronous setting where both the liver metastases and the primary tumor are resectable with a relative low risk, the oncological surgeon and the patient may consider three potential treatment strategies. Firstly, a "staged" or a "simultaneous" surgical approach. Secondly, for a staged strategy, a 'conventional approach' will suggest removal of the primary tumor first (either colon or rectal cancer) and plan for liver surgery after recovery from the first operation. A "Liver first" strategy is prioritizing the liver resection before resection of the primary tumor. Planning a surgical trial investigating a two-organ oncological resection with highly variable extent and complexity of resection as well as the potential impact of perioperative chemo(radio)therapy makes it difficult to find the optimal primary endpoint. Here, we suggest running investigational trials with carefully chosen composite endpoints as well as embedded risk-stratification strategies to identify subgroups of patients who may benefit from simultaneous surgery.
Background and Methods
Gastro- or duodenojejunostomy leaks after pancreatoduodenectomy is rare. This study aims to analyze the incidence, management, and outcome of gastro- or duodenojejunostomy ...leaks after pancreatoduodenectomy based on a single center experience from 2004 to 2020 with a narrative literature review.
Results
Of a total of 1494 pancreatoduodenectomies, eight patients with gastrojejunostomy (n=1) or duodenojejunostomy (n=7) leak were identified from the institutional pancreatic database. All leaks were treated operatively. In two patients dismantling of the duodenojejunostomy, distal gastrectomy, and closure of the pyloric and jejunal side, a percutaneous endoscopic gastrostomy and a feeding jejunostomy ultimately had to be performed after an unsuccessful attempt of gastrojejunostomy and suture of the duodenojejunostomy, respectively. The literature search revealed three more studies specifically addressing this complication after pancreatoduodenectomy (36 patients of a total of 4739 pancreatoduodenectomies). Based on an analysis of the current study and the literature review, the overall incidence of gastro- or duodenojejunostomy leaks after pancreatoduodenectomy was 0.71 % (44/6233 pancreatoduodenectomies). The occurrence of a gastro- or duodenojejunostomy leak was associated with a concomitant postoperative pancreatic fistula in 50 % of the cases, an increased length of hospital stay, and a mortality rate of 15.9 %. Surgical treatment was performed in 84 % of the cases.
Conclusion
Gastro- or duodenojejunostomy leak is a rare complication after pancreatoduodenectomy. Prompt diagnosis and early repair is important. In most cases, a surgical intervention is necessary for a good outcome. Under salvage conditions, a bailout strategy may be to temporarily dismantle the gastro- or duodenojejunal anastomosis.
Plasma cells (PCs) produce antibodies that mediate immunity after infection or vaccination. In contrast to PCs in the bone marrow, PCs in the gut have been considered short lived. In this study, we ...studied PC dynamics in the human small intestine by cell-turnover analysis in organ transplants and by retrospective cell birth dating measuring carbon-14 in genomic DNA. We identified three distinct PC subsets: a CD19
PC subset was dynamically exchanged, whereas of two CD19
PC subsets, CD45
PCs exhibited little and CD45
PCs no replacement and had a median age of 11 and 22 yr, respectively. Accumulation of CD45
PCs during ageing and the presence of rotavirus-specific clones entirely within the CD19
PC subsets support selection and maintenance of protective PCs for life in human intestine.
Background and Purpose
Previous abdominal surgery can be a risk factor for perioperative complications in patients undergoing laparoscopic procedures. Today, distal pancreatectomy is increasingly ...performed laparoscopically. This study investigates the consequences of prior upper abdominal surgery (PUAS) for laparoscopic distal pancreatectomy (LDP).
Methods
Patients who had undergone LDP from April 1997 to January 2020 were included. Based on the history and type of PUAS, these were categorized into three groups: minimally invasive (I), open (II), and no PUAS (III). To reduce possible confounding factors, the groups were matched in 1:2:4 fashion based on age, sex, body mass index (BMI) and American Society of Anesthesiology grade.
Results
After matching, 30, 60, and 120 patients were included in the minimally invasive, open and no PUAS groups, respectively. No statistically significant differences were found in terms of intraoperative outcomes. Postoperative morbidity, mortality and length of hospital stay were similar. Open PUAS was associated with higher Comprehensive Complication Index (33.7 vs 20.9 vs 26.2,
p
= 0.03) and greater proportion of patients with ≥ 2 complications (16.7 vs 0 vs 6.7%,
p
= 0.02) compared with minimally invasive and no PUAS. Male sex, overweight (BMI 25–29.9 kg/m
2
), diagnosis of neuroendocrine neoplasia, and open PUAS were risk factors for severe morbidity in the univariable analysis. Only open PUAS was statistically significant in the multivariable model.
Conclusions
PUAS does not impair the feasibility and safety of LDP as its perioperative outcomes are largely comparable to those in patients without PUAS. However, open PUAS increases the burden and severity of postoperative complications.
Managing postoperative pancreatic fistula (POPF) presents a formidable challenge after pancreatoduodenectomy. Some centers consider pancreatic duct occlusion (PDO) in reoperations following ...pancreatoduodenectomy as a pancreas-preserving procedure, aiming to control a severe POPF. The aim of the current study was to evaluate the short- and long-term outcomes of employing PDO for the management of the pancreatic stump during relaparotomy for POPF subsequent to pancreatoduodenectomy.
Retrospective review of consecutive patients at Oslo University Hospital undergoing pancreatoduodenectomy and PDO during relaparotomy. Pancreatic stump management during relaparotomy consisted of occlusion of the main pancreatic duct with polychloroprene Faxan-Latex, after resecting the dehiscent jejunal loop previously constituting the pancreaticojejunostomy.
Between July 2005 and September 2015, 826 pancreatoduodenectomies were performed. Overall reoperation rate was 13.2% (
= 109). POPF grade B/C developed in 113 (13.7%) patients. PDO during relaparotomy was performed in 17 (2.1%) patients, whereas completion pancreatectomy was performed in 22 (2.7%) patients. Thirteen (76%) of the 17 patients had a persistent POPF after PDO, and the time from PDO until removal of the last abdominal drain was median 35 days. Of the PDO patients, 13 (76%) patients required further drainage procedures (
= 12) or an additional reoperation (
= 1). In-hospital mortality occurred in one patient (5.9%). Five (29%) patients developed new-onset diabetes mellitus, and 16 (94%) patients acquired exocrine pancreatic insufficiency.
PDO is a safe and feasible approach for managing severe POPF during reoperation following pancreatoduodenectomy. A significant proportion of patients experience persistent POPF post-procedure, necessitating supplementary drainage interventions. The findings suggest that it is advisable to explore alternative pancreas-preserving methods before opting for PDO in the management of POPF subsequent to pancreatoduodenectomy.
PDF
