Background
To describe the technical details and efficacy of distal pancreatectomy with celiac axis resection (DP-CAR) and left gastric artery (LGA) flow preservation for pancreatic ductal ...adenocarcinoma (PDAC).
Method
This single-center, retrospective analysis investigated short- and long-term outcomes of DP-CAR performed on 55 patients with PDAC from 2011 to 2019. Our method included LGA reconstruction after total resection of the CA (rDP-CAR group; 24 patients) or LGA preservation if the tumor invasion was away from its root (pDP-CAR group; 31 patients), a CA-first approach to reduce blood loss during dissection, and conservative drain management with or without jejunal serosal patching at the pancreatic stump.
Results
Among the study patients, 23 had locally advanced PDAC and 22 had borderline resectable PDAC. Median operation duration was 443 min (248–810), estimated blood loss was 600 mL (150–2280), and incidence of transfusion was 2%. Ischemic complications occurred exclusively in the rDP-CAR group, including two patients with ischemic gastropathy (8%) and three patients with findings of liver ischemia on computed tomography (13%). One patient underwent relaparotomy for stomach perforations, and 19 patients (35%) had pancreatic fistula, including 8 patients who underwent conservative drain placement for more than 3 weeks without specific symptoms. There were no Clavien–Dindo grade 4 or higher postoperative complications. Preoperative therapy showed improved 3-year overall survival rates than without (54% vs. 37%,
p
= 0.027).
Conclusions
Using the standardized technique, DP-CAR was safely performed with no mortality and acceptable long-term survival.
Background
We describe the short- and long-term outcomes for PDAC patients after tailored mesopancreas dissection using supracolic artery-first approach followed by adjuvant therapy.
Methods
This ...study analyzed 233 consecutive patients who underwent artery-first pancreaticoduodenectomy for PDAC. Dissection extent for the superior mesenteric artery (SMA) was categorized into three levels: level 2 (LV2) including regional lymph nodes, level 3 (LV3) with hemicircumferential nerve plexus dissection, and extended-level 3 (E-LV3) including borderline resectable cases for the SMA. All clinical, pathological, and survival outcomes were reviewed.
Results
LV2/3/E-LV3 dissection was performed in 77/115/41 patients. The short-term outcomes were similar among groups without mortality. Although postoperative diarrhea requiring opioids was significantly more frequent in the E-LV3 group (76%) than other groups (vs. LV2 (21%),
P
< .0001; vs. LV3 (34%),
P
< .0001; LV2 vs. LV3,
P
= 0.20), most cases of diarrhea were well controlled. Adjuvant chemotherapy was introduced similarly among groups (LV2, 76%; LV3, 81%; E-LV3, 88%,
P
= 0.29). The 3- and 5-year overall survival rates in the LV2/3/E-LV3 groups were 42/33/42% and 27/22/26%, respectively, showing no significant difference among groups.
Discussion
Our tailored dissection and preemptive use of opioid antidiarrheal effectively prevents intractable diarrhea, increasing the success of adjuvant chemotherapy.
Immunotherapy has become the standard-of-care treatment for hepatocellular carcinoma (HCC), but its efficacy remains limited. To identify immunotherapy-susceptible HCC, we profiled the molecular ...abnormalities and tumor immune microenvironment (TIME) of rapidly increasing nonviral HCC.
We performed RNA-seq of tumor tissues in 113 patients with nonviral HCC and cancer genome sequencing of 69 genes with recurrent genetic alterations reported in HCC. Unsupervised hierarchical clustering classified nonviral HCCs into three molecular classes (Class I, II, III), which stratified patient prognosis. Class I, with the poorest prognosis, was associated with TP53 mutations, whereas class III, with the best prognosis, was associated with cadherin-associated protein beta 1 (CTNNB1) mutations. Thirty-eight percent of nonviral HCC was defined as an immune class characterized by a high frequency of intratumoral steatosis and a low frequency of CTNNB1 mutations. Steatotic HCC, which accounts for 23% of nonviral HCC cases, presented an immune-enriched but immune-exhausted TIME characterized by T cell exhaustion, M2 macrophage and cancer-associated fibroblast (CAF) infiltration, high PD-L1 expression, and TGF-β signaling activation. Spatial transcriptome analysis suggested that M2 macrophages and CAFs may be in close proximity to exhausted CD8+ T cells in steatotic HCC. An in vitro study showed that palmitic acid-induced lipid accumulation in HCC cells upregulated PD-L1 expression and promoted immunosuppressive phenotypes of cocultured macrophages and fibroblasts. Patients with steatotic HCC, confirmed by chemical-shift MR imaging, had significantly longer PFS with combined immunotherapy using anti-PD-L1 and anti-VEGF antibodies.
Multiomics stratified nonviral HCCs according to prognosis or TIME. We identified the link between intratumoral steatosis and immune-exhausted immunotherapy-susceptible TIME.
The degree of peritoneal dissemination and chemotherapy-resistant tumors is related to the prognosis in patients with advanced-stage ovarian cancer. The epithelial-mesenchymal-transition (EMT) is a ...multifaceted pathological program that endows cancer cells with the ability to invade and disseminate. CD24 is frequently overexpressed in various human cancers and is correlated with a poor prognosis. We herein examined the functions of CD24 in human ovarian cancer cell lines and evaluated how it contributes to the molecular mechanism underlying the regeneration of cancer stem-like cells (CSCs) through the EMT mechanism in ovarian carcinoma. We demonstrated that CD24 was expressed in 70.1% of primary ovarian carcinoma tissues, which were obtained from 174 patients, and that the expression of CD24 was an independent predictor of survival in patients with ovarian cancer. The expression of CD24 has been found to be correlated with the FIGO stage, presence of peritoneal and lymph node metastasis. CD24 induces the EMT phenomenon, which is involved in cell invasion, the highly proliferative phenotype, colony formation and which is associated with cisplatin resistance and the properties of CSCs, via the activation of PI3K/Akt, NF-κB and ERK in Caov-3 cisplatin-resistant cell lines. CD24-positive ovarian carcinomas have been shown to have a greater potential for intra-abdominal tumor cell dissemination in in vivo models. Our findings suggest that CD24 induced the EMT phenomenon in ovarian cancer, and that CD24 amplified cell growth-related intracellular signaling via the PI3K/Akt and MAPK pathways by affecting the EMT signal pathways. We believe that CD24 is a key molecule of metastatic progression in the EMT phenomenon and a promising therapeutic target for advanced ovarian cancer.
Background
For pancreatic ductal adenocarcinoma (PDAC) surgery, extended dissection of the nerve plexus (pl) around the superior mesenteric artery (SMA) or celiac artery (CA) is sometimes necessary. ...This consequently results in postoperative refractory diarrhea. This study aimed to evaluate the clinical impact of extended nerve plexus dissection around major arteries on postoperative diarrhea.
Methods
Patients who underwent pancreatoduodenectomy (PD) for PDAC between January 2013 and December 2016 were included. The frequency of diarrhea (defined as a condition requiring opioid antidiarrheal drug for at least 6 months after surgery) and its short- and long-term outcomes were reviewed.
Results
Of 200 consecutive patients who underwent PD, 78 (39.0%) developed postoperative refractory diarrhea (diarrhea group), and 73 of them (93.6%) underwent hemi-circumferential or more nerve dissection for SMA or CA; both plSMA and plCA dissection were associated with diarrhea. Borderline resectable artery (BR-A) PDAC was included more in the diarrhea group (32.0% vs. 13.1%,
P
= 0.001); however, the local recurrence rate in the diarrhea group was significantly lower than that in the non-diarrhea group (14.1% vs. 26.2%,
P
= 0.036). The completion of adjuvant chemotherapy and overall survival were comparable between the two groups. The pre-albumin level improved in 2 years, and 61.3% of patients with diarrhea could stop opioid antidiarrheal drugs within 3 years of surgery.
Conclusions
Although the frequency of diarrhea increased following nerve plexus dissection around arteries, diarrhea was controllable and resulted in a reduced local recurrence rate. Aggressive dissection of the nerve plexus may be justified for local disease control in BR-A PDAC.
Purpose
Although endoscopic naso-biliary drainage (ENBD) is a popular preoperative biliary drainage (PBD) method for patients with perihilar biliary malignancy (PHBM), patient discomfort caused by ...the nasal tube remains a problem. This study aimed to analyze the safety and efficacy of PBD with the placement of a plastic stent above the papilla inside-stent (IS) as a bridging therapy.
Methods
The outcomes of 78 patients with potentially resectable PHBM, of whom 29 underwent IS placement and 49 underwent ENBD were evaluated.
Results
The stent-associated complication rates were not different between the two groups (7% in the IS group and 10% in the ENBD group,
P
= 0.621). Catheter dislocation occurred less frequently (0% vs. 22%,
P
= 0.016), and the median time to recurrent biliary obstruction was longer (not reached vs. 32 days,
P
= 0.039) in the IS group than in the ENBD group. Among the patients who underwent resection, their postoperative severe complication rates were not substantially different (26% vs. 25%,
P
= 0.923).
Conclusion
IS placement is a possible alternative to ENBD as a bridge to a definitive operation for patients with resectable PHBM and a prospective trial to prove its feasibility and safety is therefore warranted.
Background/Purpose
We evaluated efficacy of neoadjuvant therapy with gemcitabine and nab‐paclitaxel (GNP‐NAT) in borderline resectable pancreatic cancer (BR‐PC) patients compared to conventional ...upfront surgery (UPS).
Methods
This single‐center retrospective study assessed 151 consecutive patients: 96 diagnosed in 2008‐2014 underwent UPS (UPS group) and 55 diagnosed in 2015‐2017 underwent GNP‐NAT (GN group). Patient background, surgical, pathological, and survival outcomes were compared between groups.
Results
Age, sex, and pretreatment carbohydrate antigen 19‐9 were similar between groups. After four courses of NAT‐GNP, 46 GN patients (84%) underwent surgery while all UPS patients underwent surgery. Only three GN patients (5%) underwent non‐therapeutic procedures, compared to 23 (24%) in the UPS group (P = .004). In the whole cohort, R0‐resection was achieved in 40 GN patients (73%) vs 46 UPS patients (48%; P = .004) and the 3‐year overall survival was significantly higher in the GN group (median survival time, 31.9 vs 18.1 months, P = .014). In the resection cohort, the R0‐resection rate was 93% (GN) vs 63% (UPS; P = .0007). There was no 90‐day mortalities in either group.
Conclusions
Intention‐to‐treat‐based analysis indicated considerable benefits of GNP‐NAT in BR‐PCs for long‐term survival, contributing to improved tumor suppression and patient selection.
Highlight
Inoue and colleagues compared the short‐ and long‐term outcomes of neoadjuvant gemcitabine and nab‐paclitaxel therapy with those of conventional upfront surgery for borderline pancreatic cancers. Intention‐to‐treat‐based analysis revealed significant benefits of neoadjuvant therapy for long‐term survival, providing improved tumor suppression and patient selection, allowing aggressive surgical procedures with similar safety.
To investigate the feasibility and efficacy of anatomical liver resection (ALR) guided by fused images comprising a macroscopic view and indocyanine green fluorescence imaging (fusion IGFI).
ALR is ...established in treating hepatocellular carcinoma or other malignancies to achieve curability and functional preservation. However, the conventional demarcation technique (CDT) marks only the organ surface and sometimes fails to execute a completely valid demarcation.
Twenty-four consecutive ALRs for focal liver malignancy were studied using fusion IGFI. Indocyanine green was administered systemically after selective inflow clamping in 12 patients or by portal puncture and direct injection in 12 patients, and we compared demarcation findings between fusion IGFI and CDT. The strength of contrast between target and nontarget areas was quantitatively calculated as contrast index and compared between IGFI and CDT according to injection technique or state of the liver surface.
Fusion IGFI achieved valid demarcation in 23 of 24 patients (95.8%), whereas CDT achieved valid demarcation in only 10 patients (41.7%) (P < 0.0001). The contrast index of fusion IGFI was 0.81 (0.18-2.51), which was significantly higher than that of CDT at 0.12 (0.01-0.42) (P < 0.0001), and the same result was obtained regardless of the injection method or liver surface state used. ALR was conducted referring to 3-dimensional staining of target parenchyma, with no related perioperative adverse events.
Fusion IGFI is a safe imaging technique for ALR that attained valid 3-dimensional parenchymal demarcation with better feasibility and clearer demarcation than CDT.
Background
RAS mutation status is considered a powerful prognostic factor in patients undergoing hepatectomy for colorectal liver metastases (CLM). However, whether its prognostic power is robust ...regardless of administration of preoperative chemotherapy or tumor burden remains unclear.
Methods
Consecutive patients who underwent initial hepatectomy for CLM from April 2010 through March 2017 in two hospitals were included. The prognostic value of KRAS was compared based on whether patients received preoperative chemotherapy and their tumor burden score (TBS).
Results
We included 409 patients (median follow-up 38 months). In the preoperative chemotherapy group, patients with mutant KRAS (mt-KRAS) CLM had poorer overall survival (OS) than those with wild KRAS (wt-KRAS; 5-year OS: 37.7% vs 53.8%,
p
= 0.024), although their OS was not different from patients undergoing upfront surgery. Similarly, patients with mt-KRAS had poorer OS than those with wt-KRAS in TBS of 3–9 (5-year OS: 33.1% vs 63.2%,
p
= 0.001), although their OS was not different from patients with TBS < 3 or ≥ 9. In multivariate analysis, mt-KRAS was an independent prognostic factor of OS among patients receiving preoperative chemotherapy (hazard ratio HR 1.61, 95% confidence interval CI: 1.034–2.491;
p
= 0.035) and patients with TBS of 3–9 (HR 1.836, 95% CI 1.176–2.866;
p
= 0.008). However, it was not a prognostic factor in patients who underwent upfront surgery or with TBS > 3 or ≥ 9.
Conclusions
In patients undergoing hepatectomy for CLM, the prognostic value of KRAS depends on their history of preoperative chemotherapy or tumor burden.
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