Colorectal cancers comprise a complex mixture of malignant cells, nontransformed cells, and microorganisms. Fusobacterium nucleatum is among the most prevalent bacterial species in colorectal cancer ...tissues. Here we show that colonization of human colorectal cancers with Fusobacterium and its associated microbiome—including Bacteroides, Selenomonas, and Prevotella species—is maintained in distal metastases, demonstrating microbiome stability between paired primary and metastatic tumors. In situ hybridization analysis revealed that Fusobacterium is predominantly associated with cancer cells in the metastatic lesions. Mouse xenografts of human primary colorectal adenocarcinomas were found to retain viable Fusobacterium and its associated microbiome through successive passages. Treatment of mice bearing a colon cancer xenograft with the antibiotic metronidazole reduced Fusobacterium load, cancer cell proliferation, and overall tumor growth. These observations argue for further investigation of antimicrobial interventions as a potential treatment for patients with Fusobacterium-associated colorectal cancer.
Increasing evidence links the gut microbiota with colorectal cancer. Metagenomic analyses indicate that symbiotic Fusobacterium spp. are associated with human colorectal carcinoma, but whether this ...is an indirect or causal link remains unclear. We find that Fusobacterium spp. are enriched in human colonic adenomas relative to surrounding tissues and in stool samples from colorectal adenoma and carcinoma patients compared to healthy subjects. Additionally, in the ApcMin/+ mouse model of intestinal tumorigenesis, Fusobacterium nucleatum increases tumor multiplicity and selectively recruits tumor-infiltrating myeloid cells, which can promote tumor progression. Tumors from ApcMin/+ mice exposed to F. nucleatum exhibit a proinflammatory expression signature that is shared with human fusobacteria-positive colorectal carcinomas. However, unlike other bacteria linked to colorectal carcinoma, F. nucleatum does not exacerbate colitis, enteritis, or inflammation-associated intestinal carcinogenesis. Collectively, these data suggest that, through recruitment of tumor-infiltrating immune cells, fusobacteria generate a proinflammatory microenvironment that is conducive for colorectal neoplasia progression.
•Fusobacterium is enriched in human adenomas, suggesting an early role in tumorigenesis•Fusobacterium nucleatum accelerates tumorigenesis in ApcMin/+ mice•F. nucleatum drives myeloid cell infiltration in intestinal tumors•Fusobacterium is associated with a proinflammatory signature in mouse and human tumors
Background
Robotic surgery is gaining acceptance for distal pancreatectomy (DP). Nevertheless, no multi-institutional data exist to demonstrate the ideal clinical circumstances for use and the ...efficacy of the robot compared to the open or laparoscopic techniques, in terms of perioperative outcomes.
Methods
The 2014 ACS-NSQIP procedure-targeted pancreatectomy data for patients undergoing DP were analyzed. Demographics and clinicopathological and perioperative variables were compared between the three approaches. Univariate and multivariable analyses were used to evaluate outcomes.
Results
One thousand eight hundred fifteen DPs comprised 921 open distal pancreatectomies (ODPs), 694 laparoscopic distal pancreatectomies (LDPs), and 200 robotic distal pancreatectomies (RDPs). The three groups were comparable with respect to demographics, ASA score, relevant comorbidities, and malignant histology subtype. Compared to the ODP group, patients undergoing RDP had lower T-stages of disease (
P
= 0.0192), longer operations (
P
= 0.0030), shorter hospital stays (
P
< 0.0001), and lower postoperative 30-day morbidity (
P
= 0.0476). Compared to the LDP group, RDPs were longer operations (
P
< 0.0001) but required fewer concomitant vascular resections (
P
= 0.0487) and conversions to open surgery (
P
= 0.0068). On multivariable analysis, neoadjuvant therapy (
P
= 0.0236), malignant histology (
P
= 0.0124), pancreatic reconstruction (
P
= 0.0006), and vascular resection (
P
= 0.0008) were the strongest predictors of performing an ODP.
Conclusions
The open, laparoscopic, and robotic approaches to distal pancreatectomy offer particular advantages for well-selected patients and specific clinicopathological contexts; therefore, clearly demonstrating the most suitable use and superiority of one technique over another remains challenging.
There is substantial interest in liquid biopsy approaches for cancer early detection among subjects at risk, using multi-marker panels. CA19-9 is an established circulating biomarker for pancreatic ...cancer; however, its relevance for pancreatic cancer early detection or for monitoring subjects at risk has not been established.
CA19-9 levels were assessed in blinded sera from 175 subjects collected up to 5 years before diagnosis of pancreatic cancer and from 875 matched controls from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. For comparison of performance, CA19-9 was assayed in blinded independent sets of samples collected at diagnosis from 129 subjects with resectable pancreatic cancer and 275 controls (100 healthy subjects; 50 with chronic pancreatitis; and 125 with noncancerous pancreatic cysts). The complementary value of 2 additional protein markers, TIMP1 and LRG1, was determined.
In the PLCO cohort, levels of CA19-9 increased exponentially starting at 2 years before diagnosis with sensitivities reaching 60% at 99% specificity within 0 to 6 months before diagnosis for all cases and 50% at 99% specificity for cases diagnosed with early-stage disease. Performance was comparable for distinguishing newly diagnosed cases with resectable pancreatic cancer from healthy controls (64% sensitivity at 99% specificity). Comparison of resectable pancreatic cancer cases to subjects with chronic pancreatitis yielded 46% sensitivity at 99% specificity and for subjects with noncancerous cysts, 30% sensitivity at 99% specificity. For prediagnostic cases below cutoff value for CA19-9, the combination with LRG1 and TIMP1 yielded an increment of 13.2% in sensitivity at 99% specificity (P = .031) in identifying cases diagnosed within 1 year of blood collection.
CA19-9 can serve as an anchor marker for pancreatic cancer early detection applications.
Background
Previous studies have found racial disparity in pancreatectomies for resectable pancreatic adenocarcinoma. The aim of this study was to investigate if racial disparities were worse in the ...performance of pancreaticoduodenectomy for borderline resectable pancreatic adenocarcinoma.
Methods
This study used the National Cancer Database (2004–2016) and included patients with non-metastatic and head of the pancreas borderline resectable pancreatic adenocarcinoma. Multivariable, Poisson regression models with robust standard errors evaluated the relative risk (RR) of undergoing a pancreaticoduodenectomy among non-White patients (Black, Asian, and non-White Hispanic) compared with White patients. A Poisson regression model with hospital fixed effects was performed to evaluate if findings were due to within-hospital or between-hospital variation. Interaction between race and neoadjuvant therapy was also evaluated.
Results
There were 15,482 patients (median age 68 years, interquartile range 60–76 years; 48.6% male) with borderline resectable pancreatic adenocarcinoma who were predominantly White (84.3%,
n
= 13,058; non-White, 15.7%,
n
= 2424). Overall, 18.4% (
n
= 2853) had a pancreatic resection. Non-White patients had a significantly lower likelihood of undergoing a pancreatic resection for borderline resectable pancreatic adenocarcinoma when compared with White patients (RR 0.75, 95% confidence interval 0.68–0.83;
p
< 0.001). These findings persisted in the hospital fixed-effects model. In the interaction analysis, there were no significant differences in the likelihood of pancreatic resection if patients received neoadjuvant therapy.
Conclusions
Non-White patients were 25% less likely to undergo a pancreatic resection for borderline resectable pancreatic adenocarcinoma compared with White patients. This racial disparity was due to variation in care within-hospitals and disappeared if non-White patients were treated with neoadjuvant therapy.
Surgery for Pancreatic Cancer Clancy, Thomas E
Hematology/oncology clinics of North America,
08/2015, Letnik:
29, Številka:
4
Journal Article
Recenzirano
Surgical resection remains the only potentially curative therapy for pancreatic cancer, despite a high rate of systemic recurrence. Because of local invasion or distant spread, a minority of patients ...presenting with pancreatic cancer are candidates for surgery. Although perioperative mortality is low in high-volume settings, pancreatic surgery remains associated with considerable morbidity. Minimally invasive and robotic surgical techniques are increasingly used for pancreatic resection, although not always applicable to all patients. Strategies to extend the benefits of margin-negative surgical resection to more patients include surgery with vascular resection and reconstruction for locally invasive tumors, and resection after neoadjuvant therapy.
Background
Although a β-catenin mutated hepatocellular adenoma (HCA) is a benign liver tumor, it can cause bleeding, obstruction, pain, and hepatocellular carcinoma.
1
–
3
Because surgery needs to ...balance these risks with its morbidity, a minimally invasive approach may be well suited.
4
–
6
In this report, a strategic approach to minimally invasive resection of HCA encompassing segment 4a (S4a) is reviewed.
Patient
A 22-year-old woman with abdominal pain was found to have two liver lesions involving segment 4a (5 cm) and segment 8 (S8) (4.5 cm). Liver biopsy confirmed a β-catenin mutated HCA in the S4a lesion. After embolization, an anatomic S4a segmentectomy and a partial S8 resection were planned.
Technique
Three-dimensional modeling was used to perform a preoperative virtual hepatectomy; to visualize the spatial relationship between the HCA, the portal bifurcation, and the hepatic veins; and to preplan the port sites.
7
With the patient in the French position, after port placement, intraoperative ultrasound was performed to identify the transection plane.
8
The main left portal pedicle and Rex’s recessus were exposed, and the branches of S4a were dissected out, clipped, and divided. Using ultrasound, the middle hepatic vein was exposed to define the lateral border of the dissection plane.
Conclusion
Although a β-catenin mutated HCA in S4a does not necessitate a formal segmentectomy, understanding the anatomic structures outlining its borders can facilitate the resection, especially for a large HCA. Virtual hepatectomy helps to achieve a detailed comprehension of the complex borders of segment 4a. Preoperative embolization can firm up the tumor and minimize the risk of intraoperative rupture from manipulation.
Background
Liver-directed therapies have been used to treat neuroendocrine liver metastases (NELM) for both symptomatic improvement and tumor growth control. We reviewed our experience with NELM to ...investigate the outcomes of available treatment modalities and to identify prognostic factors for survival.
Methods
We identified all patients with NELM, who were managed at our institution, from a prospectively collected institutional database. Overall survival (OS) was determined for each treatment modality.
Results
Between 2003 and 2010, we identified 939 patients with neuroendocrine tumors, of whom 649 patients had NELM. The primary tumor site was the small intestine in 245 patients (38%) and pancreas in 194 patients (30%). With a median follow-up of 44 months, the median, 5 and 10 year OS for each treatment group was as follows: hepatic resection (
n
= 58, 9%), 160 months, 90%, 70%; radiofrequency ablation (
n
= 28, 4%), 123 months, 84%, 55%; chemoembolization (
n
= 130, 20%), 66 months, 55%, 28%; systemic therapy (
n
= 316, 49%), 70 months, 58%, 31%; and observation (
n
= 117, 18%), 38 months, 38%, 20%. Age hazard ratio (HR) 1.0,
p
< 0.001), small bowel primary site (HR 0.5,
p
< 0.001), hepatic resection (HR 0.3,
p
= 0.001), well-differentiated tumors (HR 0.3,
p
< 0.001), alkaline phosphatase within normal limit (WNL) (HR 0.4,
p
< 0.001), and chromogranin A WNL (HR 0.5,
p
< 0.001) were significant independent prognosticators for OS.
Conclusions
This series represents one of the largest single-institution studies of NELM reported. We found that hepatic resection was associated with highly favorable OS. Our observations support hepatic resection in appropriately selected patients.
Pancreatic neuroendocrine tumors (PNETs) are relatively uncommon malignancies, characterized as either functional or nonfunctional secondary to their secretion of biologically active hormones. A wide ...range of clinical behavior can be seen, with the primary prognostic indicator being tumor grade as defined by the Ki67 proliferation index and mitotic index. Surgery is the primary treatment modality for PNETs. While functional PNETs should undergo resection for symptom control as well as potential curative intent, nonfunctional PNETs are increasingly managed nonoperatively. There is increasing data to suggest small, nonfunctional PNETs (less than 2 cm) are appropriate follow with nonoperative active surveillance. Evidence supports surgical management of metastatic disease if possible, and occasionally even surgical management of the primary tumor in the setting of widespread metastases. In this review, we highlight the evolving surgical management of local and metastatic PNETs.
The authors aimed to assess the safety of an enhanced recovery after surgery (ERAS) and early discharge pathway in a robotic pancreatoduodenectomy (PD) program and compared outcomes with an open PD ...control cohort to identify the synergistic effects of robotic surgery and an ERAS pathway on lengths of stay (LOS).
Consecutive patients undergoing open or robotic PD from a single surgeon between March 2020 and July 2022 were identified. Logistic regression models were used for adjusted analyses of postoperative outcomes.
There were 134 consecutive PD patients, of which 40 (30%) were performed robotically. Pancreatic adenocarcinoma was the most common indication in both open (56%) and robotic (55%, p = 0.51) groups, with a similar proportion of them being borderline resectable or locally advanced tumors (78% vs 82% in robotic group, p = 0.82). The LOS was significantly shorter in the robotic PD group (median, 5 IQR 4 to 7 days) when compared with the open PD group (median, 6 IQR 5 to 8 days, p < 0.001). LOS of 4 days or fewer were observed in 40% of the robotic PD group compared with only 3% of patients in the open PD group (p < 0.001). There was no difference in the overall readmission rate (10% vs 12% in the robotic PD group, p = 0.61). On multivariable logistic regression, robotic PD was independently associated with higher odds of LOS of 4 days or fewer (odds ratio 22.4, p = 0.001) when compared with open PD.
An ERAS and early discharge pathway could be safely implemented in a robotic PD program. Patients undergoing robotic PD have significantly shorter length of stay without increased complication or readmission rate compared with open PD, with 40% of patients undergoing robotic PD achieving a LOS of 4 days or fewer.
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