Background
The impact of lymph node (LN) status and lymphadenectomy (LA) on survival in pancreatic neuroendocrine tumors (pNETs) remains controversial. We evaluated the impact of tumor extension and ...grade on nodal metastasis and survival.
Methods
Surgical pNET patients were queried in the Surveillance Epidemiology and End Results (SEER) database (1998–2012,
N
= 981). Factors associated with LN status were analyzed by logistic regression and by Cox analyses.
Results
For T1–T2 tumors, N status was associated only with tumor size. N status (
p
= 0.001), grade (
p
< 0.001), age (
p
= 0.001), and sex (
p
= 0.007) predicted overall survival (OS). For T3–T4, grade (
p
< 0.001), sex (
p
= 0.004), size (
p
= 0.013), and age (
p
= 0.007) but not N status (
p
= 0.789) predicted OS. For T1–T2, disease-specific survival (DSS;
p
= 0.003) and OS (
p
= 0.008) were longer for N0 vs N1, while N0 vs NX had similar OS (
p
= 0.59) and DSS (
p
= 0.80). While a difference was seen in DSS for NX vs N1 (
p
= 0.04), no significant difference in OS was seen (
p
= 0.08). For T3–T4, N status did not affect DSS (
p
= 0.365) or OS (
p
= 0.454). For all T groups and any N status, extended LA (≥10 nodes resected) was not associated with OS.
Conclusion
While in T1–T2 pNET N1 status is a predictor of negative OS, similar outcome between NX and N0 supports limited LN resection in selected patients. Extended LA is unlikely to be helpful in T3–T4.
Introduction
While preoperative chemotherapy is frequently utilized before resection of non-neuroendocrine liver metastases, patients with resectable neuroendocrine liver metastases typically undergo ...surgery first. FAS is a cytotoxic chemotherapy regimen that is associated with substantial response rates in locally advanced and metastatic pancreatic neuroendocrine tumors.
Methods
All patients who underwent R0/R1 resection of pancreatic neuroendocrine liver metastases at a single institution between 1998 and 2015 were included. The outcomes of patients treated with preoperative FAS were compared with those of patients who were not.
Results
Of the 67 patients included, 27 (40.3%) received preoperative FAS, whereas 40 (59.7%) did not. Despite being associated with higher rates of synchronous disease, lymph node metastases, and larger tumor size, patients who received preoperative FAS had similar overall survival overall survival (OS), 108.2 months (95% confidence interval (CI) 78.0–136.0) vs. 107.0 months (95% CI 78.0–136.0),
p
= 0.64 and recurrence-free survival RFS, 25.1 months (95% CI 23.2–27.0) vs. 18.0 months (95% CI 13.8–22.2),
p
= 0.16 as patients who did not. Among patients who presented with synchronous liver metastases (
n
= 46), the median OS 97.3 months (95% CI 65.9–128.6) vs. 65.0 months (95% CI 28.1–101.9),
p
= 0.001 and RFS 24.8 months (95% CI 22.6–26.9) vs. 12.1 months (2.2–22.0),
p
= 0.003 were significantly greater among patients who received preoperative FAS compared with those who did not.
Conclusions
The use of FAS before liver resection is associated with improved OS compared with surgery alone among patients with advanced synchronous pancreatic neuroendocrine liver metastases.
Background RAS mutations are associated with limited overall survival after resection of colorectal liver metastases. Our aim was to determine criteria for considering hepatectomy for patients with ...RAS mutant colorectal liver metastases. Methods Of 1,163 patients who underwent liver resection for colorectal liver metastases during 2005–2014, all patients operated on with curative intent who had known RAS mutation status were included. Factors associated with overall survival were determined using multivariate analysis. Results A total of 524 patients met the inclusion criteria; 212 (40%) had mutated RAS. Mutations were located on codon 12 in 128 patients (60%) and codon 13 in 29 (14%). At median follow-up of 38 months, median overall survival was 72.6 months for wild-type RAS and 50.9 months for mutated RAS ( P < .001). Median overall survival for patients with codon 12 and 13 mutations was 51.9 and 50.9 months, respectively ( P = .839), significantly worse than for patients with wild-type RAS ( P = .005, and P = .038 for codon 12 and 13, respectively). For patients with RAS mutation, factors associated independently with worse overall survival were node-positive primary tumor, tumor >3 cm, and >7 cycles of preoperative chemotherapy. Major and 2-stage hepatectomy were not associated independently with overall survival. Median overall survival was 57, 41, and 21.5 months for patients with 1, 2, and 3 risk factors, respectively. There were no 4-year survivors in the highest-risk group. Conclusion Patients with multiple risk factors had poor overall survival after curative resection of RAS mutant colorectal liver metastases. For such patients, hepatectomy may be ill advised, and alternative therapies or further systemic therapy should be considered.
Background
Fibrolamellar carcinoma (FLC) and conventional hepatocellular carcinoma (HCC) share the same American Joint Committee on Cancer (AJCC) staging. The worse survival with HCC is attributed to ...the underlying cirrhosis.The aim of this study was to compare stage-matched prognosis after resection of FLC and non-cirrhotic HCC.
Methods
Outcomes after resection of 65 consecutive patients with FLC and 158 non-cirrhotic patients with HCC were compared. Patients were staged according to the 7th edition AJCC staging.
Results
The AJCC stage distributions for FLC and HCC demonstrated a predominance of stage IV disease in FLC and stage I in HCC (FLC stage I—23 %, II—15 %, III—15 %, IV—46 % vs. HCC stage I—42 %, II—32 %, III—20 %, IV—6 %,
p
< 0.001). Among stage IV FLC patients, 81 % had isolated nodal metastases, which did not affect overall survival (OS) or recurrence-free survival (RFS). In FLC, OS was significantly affected by the number of tumors and vascular invasion (
p
< 0.05). Recurrent disease developed in 56 (86 %) FLC patients and was treated with repeat surgical resection in 25 (45 %) patients. Vascular invasion was associated with recurrent FLC, with 3-year RFS rates of 9 % and 35 %, with and without vascular invasion (
p
= 0.034). With respect to RFS, the AJCC staging did not stratify FLC patients, compared to non-cirrhotic HCC.
Conclusions
When compared to non-cirrhotic HCC, patients with FLC are not adequately stratified by AJCC staging with respect to RFS. Our results support classifying lymph node metastases in FLC as regional disease, rather than systemic disease. Important prognostic factors in FLC are the number of tumors and vascular invasion.
The importance and therapeutic value of stem cells in lymphangiogenesis are poorly understood. We evaluated the potential of human and murine mesenchymal stem cells (MSCs) to acquire a lymphatic ...phenotype in vitro and to enhance lymphatic regeneration in vivo.
We assessed the lymphendothelial differentiation of human and murine MSCs after induction with supernatant derived from human dermal microvascular endothelial cells, isolated lymphatic endothelial cells, and purified vascular endothelial growth factor (VEGF)-C in vitro. We used human or murine progenitor MSC lines and then characterized the lymphatic phenotype by morphology, migratory capacity, and the expression of lymphatic markers such as Prox-1, podoplanin, Lyve-1, VEGF receptor-2, and VEGF receptor-3. Using a murine lymphatic edema model, we assessed the potential of these cells to form a functional lymphatic vasculature in vivo after injection of syngeneic MSCs. Incubation with supernatant from lymphatic endothelial cells induced an endothelium-like morphology and the expression of lymphendothelial markers in both human and murine MSCs in vitro. MSCs showed migratory activity along a VEGF-C gradient, which was enhanced by VEGF-C conditioning. In vivo, the local application of MSCs resulted in a significant decrease in edema formation (-20.1%; P<0.01 versus untreated tails) after 3 weekly cell injections and restored the drainage of intradermally injected methylene blue after 7 weekly injections.
MSCs were capable of expressing a lymphatic phenotype when exposed to lymph-inductive media and purified VEGF-C. Migratory activity toward VEGF-C in vitro suggests homing capability in vivo. Restoration of lymphatic drainage after injection of MSCs in a lymphedema model indicates that MSCs play a role in lymphatic regeneration. The potential clinical application of MSC in wound healing and reduction of lymphatic edema warrants further research.
Abstract Background The anatomic resection of Couinaud's segments is one of the key techniques in liver surgery. However, the territories and volumes of the eight segments are not adequately assessed ...based on portal branching. Methods Three-dimensional (3D) perfusion-based volumetry was performed in 107 normal livers. Based on Couinaud classification, the portal branches were identified and the volumes of each segment were calculated. The relationships between branching patterns of the portal veins and segmental volumes were assessed. Results In descending order of volume, median volumes of segments VIII, VII, IV, V, III, VI, II and I were recorded. Segment VIII was the largest, accounting for a median of 26.1% (range: 11.1–38.0%) of total liver volume (TLV), whereas segments II and III each represented <10% of TLV. In 69.2% of subjects, the portal branches of segment V diverged from the trunk of the branches of segment VIII. No relationship was found between branching type and segment volume. Conclusions The territories and volumes of Couinaud's segments vary among segments, as well as among individuals. Detailed 3D volumetry is useful for preoperative evaluations of the dissection line and of future liver remnant volume in anatomic segmentectomy.
Background
Non-gastrointestinal stromal tumor sarcomas (NGSs) have heterogeneous histology, and this heterogeneity may lead to uncertainty regarding the prognosis of patients with liver metastases ...from NGS (NGSLM) and decision regarding their surgical management. Furthermore, the role of preoperative chemotherapy in treatment of NGSLM remains poorly defined. We investigated long-term survival and its correlation to response to preoperative chemotherapy in patients with NGSLM.
Patients and Method
Patients who underwent liver resection for NGSLM during 1998–2015 were identified. Clinical, histopathologic, and survival data were analyzed. Multivariate analysis was performed using a Cox proportional hazards model.
Results
126 patients 62 (49%) with leiomyosarcoma were included. Five-year overall survival (OS) and recurrence-free survival (RFS) rates were 49.3 and 14.9%, respectively. Survival did not differ by histologic subtype, primary tumor location, or use of preoperative or postoperative chemotherapy. NGSLM ≥ 10 cm and extrahepatic metastases at NGSLM diagnosis were the only independent risk factors for OS. In the 83 (66%) patients with metachronous NSGLM, disease-free interval > 6 months was associated with improved OS and RFS. Among the 65 patients (52%) who received preoperative chemotherapy, radiologic response according to Choi criteria specifically was associated with improved OS (
p
= 0.04), but radiologic response according to RECIST 1.1 criteria was not.
Conclusions
Resection of NGSLM led to a 5-year OS rate of 49%, independent of histologic subtype and primary tumor location. Choi criteria (which take into account tumor density) are superior to RECIST 1.1 in assessing radiologic response and should be used to assess response to preoperative chemotherapy.
Background
Portal vein embolization (PVE) reduces the risks of hepatic insufficiency after major hepatectomy for small predicted liver remnant. The extent of liver hypertrophy after PVE depends on ...various clinical factors. We sought to develop a nomogram for predicting the increase in the volume of segments 2 and 3 after right PVE (RPVE).
Method
In 360 patients who underwent RPVE from 1998 through 2013, clinicopathologic data were analyzed, including body mass index (BMI), diabetes, aspirin use, viral hepatitis status, preoperative albumin level, total bilirubin level, prothrombin time, platelet count, type of liver neoplasm, preoperative chemotherapy, previous laparotomy or hepatectomy, segment 4 embolization, two-stage hepatectomy, and liver volumes before and after PVE. Multivariate linear regression analysis was used to identify variables predicting the degree of hypertrophy of segments 2 and 3.
Results
Multivariate regression analysis revealed that BMI (
p
= 0.002), previous hepatectomy (
p
= 0.03), RPVE in the setting of two-stage hepatectomy (
p
< 0.001), and segment 4 embolization (
p
= 0.003) independently predicted the degree of hypertrophy of segments 2 and 3. Based on the fitted model, a nomogram was constructed.
Conclusion
The constructed nomogram predicts the degree of hypertrophy of segments 2 and 3 after RPVE and can be used in clinical decision making for patients undergoing right hepatectomy.
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