No standard adjuvant treatment currently is recommended in localized biliary tract cancer (BTC) after surgical resection. We aimed to assess whether gemcitabine and oxaliplatin chemotherapy (GEMOX) ...would increase relapse-free survival (RFS) while maintaining health-related quality of life (HRQOL) in patients who undergo resection.
We performed a multicenter, open-label, randomized phase III trial in 33 centers. Patients were randomly assigned (1:1) within 3 months after R0 or R1 resection of a localized BTC to receive either GEMOX (gemcitabine 1,000 mg/m
on day 1 and oxaliplatin 85 mg/m
infused on day 2 of a 2-week cycle) for 12 cycles (experimental arm A) or surveillance (standard arm B). Primary end points were RFS and HRQOL.
Between July 2009 and February 2014, 196 patients were included. Baseline characteristics were balanced between the two arms. After a median follow-up of 46.5 months (95% CI, 42.6 to 49.3 months), 126 RFS events and 82 deaths were recorded. There was no significant difference in RFS between the two arms (median, 30.4 months in arm A v 18.5 months in arm B; hazard ratio HR, 0.88; 95% CI, 0.62 to 1.25; P = .48). There was no difference in time to definitive deterioration of global HRQOL (median, 31.8 months in arm A v 32.1 months in arm B; HR, 1.28; 95% CI, 0.73 to 2.26; log-rank P = .39). Overall survival was not different (median, 75.8 months in arm A v 50.8 months in arm B; HR, 1.08; 95% CI, 0.70 to 1.66; log-rank P = .74). Maximal adverse events were grade 3 in 62% (arm A) versus 18% (arm B) and grade 4 in 11% versus 3% ( P < .001).
There was no benefit of adjuvant GEMOX in resected BTC despite adequate tolerance and delivery of the regimen.
Background
Surgical resection remains the best therapeutic option for the long-term survival of patients with perihilar cholangiocarcinoma (PCC).
1
For patients presenting with Bismuth type 3 or 4 ...tumors, left or right extended liver resection has been shown to be feasible.
2
The Achilles heel of the procedure remains biliary reconstruction due to multiple small-diameter remnant liver bile ducts.
3
This study showed how a Kasai-like portoenterostomy allows circumvention of this difficulty.
Methods
A 57-year-old woman with a type 3a PCC invading the main portal vein bifurcation underwent a right hepatectomy with en bloc resection of segment 4b, the caudate lobe, and the extrahepatic common bile duct; hepatic pedicle lymphadenectomy; and main portal vein bifurcation reconstruction.
4
The cross-section of the left biliary plate was tumor-free at frozen section analysis but involved three small biliary ducts originating from segments 2, 3, and 4a. The biliary plate and the distance between each duct were too large to allow unification. A Roux-en-Y portoenterostomy, inspired by the Kasai procedure,
5
was performed between the umbilical plate and the extramucosal wall of an efferent Roux-en-Y jejunal limb. Two temporary external trans-portoenterostomy drains were placed according to the Voelker technique.
Results
The postoperative course was uneventful, and the patient was discharged on postoperative day 8. The two trans-portoenterostomy drains were removed after 6 weeks, and patient was disease-free at the 2-year follow-up evaluation.
Conclusions
In extended PCC, Kasai-like portoenterostomy may facilitate complex biliodigestive reconstructions when multiple biliary ducts are involved.
Objective
The aim of this retrospective study was to compare the outcomes of patients resected for intrahepatic cholangiocarcinoma (ICC) with upfront surgery or after downstaging treatment.
Methods
...All consecutive patients with ICC between January 1997 and November 2017 were included in a single-center database and retrospectively reviewed. Patients were divided into two groups: upfront resection or resection after downstaging using either chemotherapy alone or selective internal radiation therapy (SIRT) combined with chemotherapy. Survival rates of patients who underwent upfront surgery for ICC were compared with those of patients who underwent surgery after downstaging therapy.
Results
A total of 169 patients resected for ICC were included: 137 underwent upfront surgery and 32 received downstaging treatment because their tumor was initially unresectable (13 received chemotherapy, 19 received SIRT). Median OS was not different between the two groups: 32.3 months 95% confidence interval (CI) 23.9–40.7 with primary surgery versus 45.9 months (95% CI 32.3–59.4) with downstaging treatment (
p
= 0.54, log-rank test). In a multivariable Cox regression model, downstaging treatment was not associated with a better or worse prognosis; however, delivery of SIRT as a downstaging treatment was associated with a significant benefit in multivariable analysis (hazard ratio 0.34, 95% CI 0.14–0.84;
p
= 0.019).
Conclusions
Overall survival of patients resected after downstaging treatment was not different compared with the OS of patients resected upfront. Patients should therefore again be discussed with the surgeon following medical treatment. SIRT may be an efficient neoadjuvant therapy in patients with resectable ICC, in order to improve surgical results.
Background
Vascular leiomyosarcomas (LMS) are rare malignant mesenchymal tumors arising from vessel smooth muscle cells. They represent only 2% of soft tissue sarcomas and most commonly (50%) ...originate from the inferior vena cava.
1
–
3
Portal vein LMS are very rare, and their resection combines en bloc negative margin sarcoma surgery principles and complex liver surgery procedures with vascular reconstructions.
3
–
5
Methods
This is the case of a 42-year-old female presenting with a moderate cholestasis. Imaging revealed a 3-cm tumor originating from the main portal vein and its right branch while being in contact with both the right hepatic artery and biliary confluence. No metastases were identified. Core needle biopsy confirmed the diagnosis and tumor board decision was surgical resection.
Results
The procedure included anatomic right hepatectomy with en bloc resection of the portal vein bifurcation, common bile duct, and biliary confluence. Portal venous reconstruction was performed using an autogenous external iliac vein interposition graft, while biliary reconstruction was performed via a Roux-en-Y end-to-side hepatico-jejunostomy. Duration of surgery was 300 min, and blood loss was 300 ml. Postoperative outcomes were uneventful and patient was discharged on postoperative day 8 with a transient right limb edema. Pathology confirmed R0 resection of a T1N0M0 leiomyosarcoma, Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade 2 tumor. Patient was free of disease at 20 months post-surgery.
Conclusions
Portal vein leiomyosarcomas are extremely rare. En bloc extensive surgical resection should be proposed to obtain R0 resection, and achieve prolonged survival.
4
,
6
,
7
Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer worldwide, as a result of a late diagnosis and limited therapeutic options. Tumour microenvironment (or stroma) plays a key role in cancer ...onset and progression and constitutes an intrinsic histological hallmark of PDAC. Thus we hypothesised that relevant prognostic biomarkers and therapeutic targets can be identified in the stroma.
Laser microdissection of the stroma from freshly frozen PDAC was combined to gene expression profiling. Protein expression of candidate biomarkers was evaluated by immunohistochemistry on tissue microarrays (n = 80 tumours) and by ELISA in plasma samples (n = 51 patients).
A signature made of 1256 genes that significantly discriminate the stroma from the non-tumour fibrous tissue was identified. Upregulated genes were associated with inflammation and metastasis processes and linked to NF-Kappa B and TGFβ pathways. TMA analysis validated an increased expression of SFN, ADAMTS12 and CXCL3 proteins in the stroma of PDAC. Stromal expression of SFN was further identified as an independent prognostic factor of overall (p = 0.003) and disease-free survival (DFS) (p = 0.034). SFN plasma expression was significantly associated with reduced DFS (p = 0.006).
We demonstrated that gene expression changes within the stroma of PDAC correlate with tumour progression, and we identified Stratifin as a novel independent prognostic biomarker.
Intrahepatic cholangiocarcinoma (ICC) is the second most common type of primary cancer in the liver. ICC is an aggressive cancer with poor prognosis and limited therapeutic strategies. The ...identification of new drug targets and prognostic biomarkers is an important clinical challenge for ICC. The presence of an abundant stroma is a histological hallmark of ICC. Given the well‐established role of the stromal compartment in the progression of cancer diseases, we hypothesized that relevant biomarkers could be identified by analyzing the stroma of ICC. By combining laser capture microdissection and gene expression profiling, we demonstrate that ICC stromal cells exhibit dramatic genomic changes. We identified a signature of 1,073 nonredundant genes that significantly discriminate the tumor stroma from nontumor fibrous tissue. Functional analysis of differentially expressed genes demonstrated that up‐regulated genes in the stroma of ICC were related to cell cycle, extracellular matrix, and transforming growth factor beta (TGFβ) pathways. Tissue microarray analysis using an independent cohort of 40 ICC patients validated at a protein level the increased expression of collagen 4A1/COL4A1, laminin gamma 2/LAMC2, osteopontin/SPP1, KIAA0101, and TGFβ2 genes in the stroma of ICC. Statistical analysis of clinical and pathological features demonstrated that the expression of osteopontin, TGFβ2, and laminin in the stroma of ICC was significantly correlated with overall patient survival. More important, multivariate analysis demonstrated that the stromal expression of osteopontin was an independent prognostic marker for overall and disease‐free survival. Conclusion: The study identifies clinically relevant genomic alterations in the stroma of ICC, including candidate biomarkers for prognosis, supporting the idea that tumor stroma is an important factor for ICC onset and progression. (Hepatology 2013; 58:1992–2000)
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