PREDICTORS OF INSUFFICIENT FUTURE LIVER REMNANT HYPERTROPHY AFTER PORTAL VEIN EMBOLIZATION

Background
Sentinel node navigated surgery (SNNS) might offer a less invasive alternative to esophagectomy to tailor the extent of lymphadenectomy in patients with high-risk T1 esophageal adenocarcinoma (EAC). This is the first study to investigate the feasibility and safety of a new treatment strategy, consisting of radical endoscopic resection of the tumor followed by SNNS.

Methods
In this prospective, multicenter pilot study, 10 patients underwent SNNS in two tertiary hospitals after radical endoscopic resection of a high-risk T1 EAC (i.e. deep submucosal invasion ≥500μm, poor differentiation, and/or lymphovascular invasion) without the clinical presence of lymph node or distant metastases (i.e. cN0M0). A hybrid tracer of technetium-99m nanocolloid and indocyanine green (^99mTc-ICG-nanocolloid) was injected endoscopically around the resection scar the day before surgery, followed by preoperative imaging. During thoracoscopy and laparoscopy, sentinel nodes (SNs) were identified using a thoracolaparoscopic gammaprobe and fluorescence-based detection and subsequently resected (Figure 1). Endpoints were surgical morbidity, incidence of gastroesophageal functional disorders, rate of detectable SNs, and number of resected (tumor-positive) SNs per patient.

Results
Localization and dissection of SNs was feasible in all patients (10 male, median age 69), with a median of 3 SNs (range 1-7) on preoperative imaging and a median of 3 SNs (range 1-6) during surgery. The concordance between preoperative imaging and intraoperative detection was high. In one patient (10%), dissection was considered incomplete after two SNs could not be identified due to a lack of ICG fluorescence. In four patients (40%), additional peritumoral SNs were resected after fluorescence-based detection. These SNs were not detected on preoperative imaging or intraoperatively with the laparoscopic gammaprobe as a result of the high background radioactivity of the injection site. Total procedure time was median 125 minutes (range 46-213), and patients were hospitalized for a median of 2 days (range 1-3). One patient (10%) experienced neuropathic thoracic pain related to surgery, while none of the patients developed functional disorders. In two patients (20%), a metastasis was found in one of the resected SNs. Both patients are undergoing strict endoscopic and radiologic follow-up, which was determined in a multidisciplinary meeting based on patient’s older age (n=1) and patient's choice in combination with micrometastasis (n=1).

Conclusion
SNNS with ^99mTc-ICG-nanocolloid appears to be a feasible and safe instrument to tailor lymphadenectomy in patients with high-risk T1 EAC who underwent a prior radical endoscopic resection. The exact position of this new strategy in the treatment algorithm for high-risk T1 esophageal cancer needs to be studied in future research with long-term follow-up.

Background. A wrong diagnosis of nature is common in pancreatic cystic neoplasms (PCNs). The aim of the current study is to reappraise the diagnostic errors for presumed PCNs undergoing surgery.
Methods. All pancreatic resections performed for presumed PCNs at the Verona Pancreas Institute between 2011 and 2020 were analyzed. “Misdiagnosis” was defined as the discrepancy between preoperative diagnosis of nature and final pathology. “Mismatch” was defined as the discrepancy between the preoperative suspect of malignancy (or its absence) and final pathology. Features considered suggestive for malignancy at preoperative work-up and at final pathology are described in Figure 1. Diagnostic errors considered “clinically relevant” implied a potential over- or under-treatment for the patient.
Results. A total of 601 patients were included. Endoscopic Ultrasound (EUS) was performed in 301 (50%) patients. Overall misdiagnosis and mismatch were 19% and 34%, respectively, with no significant benefit for those patients who underwent EUS. The highest rate of misdiagnosis was reached for cystic neuroendocrine tumors (61%) and the lowest for solid pseudopapillary tumors (6%). Several diagnostic errors had clinical relevance, including 7 (13%) presumed serous cystic neoplasms eventually found to be other malignant entities, 50 (24%) intraductal papillary mucinous neoplasms (IPMN) with high-risk stigmata (HRS) revealed to be non-malignant, and 38 (33%) IPMN without HRS revealed to be malignant at final pathology. A preoperative presumption of malignant mucinous cystic neoplasm was correct in only 20 (16%) patients (Table 1).
Conclusions. Despite not always clinically relevant, diagnostic errors are still common among resected PCNs when applying International Guidelines. New diagnostic tools beyond EUS are needed to refine diagnosis of those lesions at higher risk for unnecessary surgery or accidentally observed nevertheless being malignant.

Introduction: Mesenchymal stem cells (MSCs) have been used for the treatment of perianal Crohn’s fistulizing disease by direction injection. However, to date, studies have excluded patients with proctitis, anal canal involvement, vaginal involvement, and an ileal pouch in situ. We sought to assess the safety and efficacy of a direct injection of MSCs for the treatment of perianal, rectovaginal, and peripouch Crohn’s fistula(s).

Methods: Three phase IB/IIA randomized control trials of perianal (n=23), rectovaginal (n=19) and peripouch (n=22) Crohn’s related fistulas were conducted to determine safety and efficacy of MSCs for refractory phenotypes of perianal Crohn’s disease. Crohn’s patients with perianal, rectovaginal, and peripouch Crohn’s fistulizing disease were offered enrollment into a clinical trial. A total of 75 million MSCs were administered with a 22G needle by direct injection after curettage and primary closure of the fistula tract. A repeat injection of 75 million MSCs was administered at 3 months if complete clinical and radiographic healing were not achieved. Adverse and serious adverse events were collected at post procedure day 1, week 2, week 6, month 3, month 6 and month 12. Clinical healing, radiographic healing per magnetic resonance imaging, and patient reported outcomes were assessed at the same time points.

Results: A total of 64 patients were enrolled and treated; 49 were treatment and 15 were control. There were no adverse or serious adverse events reported related to investigational product. At twelve months, overall combined clinical and radiographic healing was achieved in 70% of perianal, 37.5% of rectovaginal, and 46.2% of ileal pouch fistulas, respectfully. In the control cohorts, 12 month healing was 0%, 0%, and 0% in the three clincial trials respectively. The perianal Crohn’s disease activity index and VanAssche score all significantly decreased in treatment patients at six and twelve months, but not in the control groups.

Conclusion: Allogeneic bone marrow derived MSCs offer a safe and effective alternative treatment approach for severe phenotypes of perianal fistulizing Crohn’s disease.

Background: A standardized future liver remnant (sFLR) <30% and a kinetic growth rate (KGR) <2% are associated with increased risk of hepatic insufficiency and death from liver failure after hepatectomy. Here, we sought to identify clinicopathologic factors associated with inadequate sFLR and KGR to help predict which patients may not achieve sufficient hypertrophy with portal vein embolization (PVE) alone and inform selection for liver venous deprivation (LVD).

Methods: A prospectively maintained single institution database was evaluated for patients undergoing PVE between 1998 and 2020. Clinicopathologic variables, including age, sex, BMI, a known diagnosis of liver disease, diabetes, cycles of neoadjuvant chemotherapy, liver function tests, baseline sFLR, and extended PVE (segment 4 embolization) were evaluated for associations with sFLR and KGR.

Results: A total of 474 patients were identified who underwent right PVE and had both pre- and post-PVE volumetric assessments. Median patient age was 58 years (interquartile range [IQR] 49-66) and median BMI was 27kg/m² (IQR 25-30). The most common histology was metastatic colorectal cancer (66%) followed by hepatocellular carcinoma (12%) extrahepatic cholangiocarcinoma (7%), and intrahepatic cholangiocarcinoma (4%). Most patients (77%) received neoadjuvant chemotherapy prior to PVE (median 6 cycles [IQR 4-11]). Median baseline sFLR was 22% (IQR 16-29%). A sFLR >30% was achieved in 60% of patients following PVE, while KGR >2% was noted in 58%. 71% of patients ultimately underwent surgery, which involved right hepatectomy in 58% and extended right hepatectomy in 41%. Multiple logistic regression revealed that baseline sFLR (OR 1.39 [95% CI 1.30-1.50]) was predictive of post-PVE sFLR >30%. Extended PVE (OR 0.44 [95%CI 0.25-0.77]) and planned two-stage hepatectomy (OR 0.51 [95%CI 0.32-0.82]) were predictive of KGR <2%. ROC analysis revealed that a baseline sFLR ≥19 is 90% sensitive and 78% specific for sFLR >30% (AUC 0.92) (Figure).

Conclusions: Patients with a baseline sFLR <19% or those requiring extended hepatectomy may not achieve adequate hypertrophy with PVE alone. In this subset of patients, LVD should be considered to optimize hepatic regeneration.