Background
Unresectable pancreatic cancer (UR-PC) has a poor prognosis. Although conversion surgery has been considered a promising strategy for improving prognosis in UR-PC, the clinical benefit ...offered to patients with UR-PC remains controversial. This study aimed to investigate the clinical benefits of conversion surgery in patients with UR-PC.
Methods
We evaluated patients with UR-PC referred to our department for possible surgical resection between January 2008 and June 2017. Resectability was evaluated using multimodal imaging in patients who underwent chemotherapy for more than 6 months. Conversion surgery was performed only in patients who were judged eligible for R0 resection.
Results
In total, 90 patients were evaluated. Among them, only 22 (24.4%) could actually undergo conversion surgery, and the R0 resection rate was 72.7% (16/22). Although Evans grade ≥ IIB was noted in six patients (27.3%), none achieved complete response (CR). The median survival time was significantly longer among patients who underwent conversion surgery than in the unresected patients who underwent chemotherapy (21.3 months vs. 12.6 months;
p
< 0.001). Multivariate and Kaplan–Meier analyses revealed microvascular invasion to have a significant adverse effect on recurrence-free survival (RFS: 7 months vs. not reached,
p
= 0.004) and overall survival (OS: 21 months vs. 85 months,
p
= 0.047).
Conclusions
After long-term chemotherapy, conversion surgery for UR-PC is associated with long-term survival. Microvascular invasion is predictive of poor prognosis in these patients; adjuvant protocols are therefore needed for patients with microvascular invasion.
Methionine addiction is a fundamental and general hallmark of cancer. Methionine addiction prevents cancer cells, but not normal cells from proliferation under methionine restriction (MR). Previous ...studies reported that MR altered the histone methylation levels in methionine-addicted cancer cells. However, no study has yet compared the status of histone methylation status, under MR, between cancer cells and normal cells. In the present study, we compared the histone methylation status between cancer cells and normal fibroblasts of H3K4me3 and H3K9me3, using recombinant methioninase (rMETase) to effect MR. Human lung and colon cancer cell lines and human normal foreskin fibroblasts were cultured in control medium or medium with rMETase. The viability of foreskin fibroblasts was approximately 10 times more resistant to rMETase than the cancer cells in vitro. Proliferation only of the cancer cells ceased under MR. The histone methylation status of H3K4me3 and H3K9me3 under MR was evaluated by immunoblotting. The levels of the H3K4me3 and H3K9me3 were strongly decreased by MR in the cancer cells. In contrast, the levels of H3K4me3 and H3K9me3 were not altered by MR in normal fibroblasts. The present results suggest that histone methylation status of H3K4me3 and H3K9me3 under MR was unstable in cancer cells but stable in normal cells and the instability of histone methylation status under MR may determine the high methionine dependency of cancer cells to survive and proliferate.
•Methionine addiction is a fundamental and general hallmark of cancer.•H3K4me3 and H3K9me3 are unstable in cancer but not normal cells under methionine restriction (MR).•These results help explain why cancer cells and not normal cells cease proliferation under MR.•MR is efficiently effected by recombinant methioninase.
Background
The inflammation-based Glasgow prognostic score (GPS) has been demonstrated to be prognostic for various tumors. We investigated the value of the modified GPS (mGPS) for the prognosis of ...patients undergoing curative resection for colorectal liver metastases (CRLM).
Methods
A total of 343 patients were enrolled onto this study. The mGPS was calculated as follows: mGPS-0, C-reactive protein (CRP) ≤10 mg/L; mGPS-1, CRP >10 mg/L and albumin ≥35 g/L; and mGPS-2, CRP >10 mg/L and albumin <35 g/L. Prognostic significance was retrospectively analyzed by univariate and multivariate analyses.
Results
Of the 343 patients, 295 (86.0 %) were assigned to mGPS-0, 33 (9.6 %) to mGPS-1, and 15 (4.4 %) to mGPS-2. The median disease-free survival of patients with mGPS-0, -1, and -2 was 18.3, 15.5, and 5.2 months, respectively. The median cancer-specific survival (CSS) of patients with mGPS-0, -1, and -2 was 89.5, 62.2, and 25.8 months, respectively. The CSS of patients with mGPS-0 was significantly longer than that of patients with mGPS-2. Multivariate analysis revealed a significant association between cancer-related postoperative mortality and mGPS and carcinoembryonic antigen level.
Conclusions
The preoperative mGPS is a useful prognostic factor for postoperative survival in patients undergoing curative resection for CRLM.
Purpose
Although many studies have concluded that prophylactic drain insertion during elective liver resection offers few advantages, we reassessed the clinical value and appropriate management of ...drain insertion.
Methods
We retrospectively studied the clinical value of abdominal drainage in 167 consecutive patients who underwent hepatectomy, focusing on drainage volumes, bilirubin concentrations, drainage fluid bacterial culture results and short-term postoperative outcomes. The results were then validated prospectively in the next 50 consecutive patients to undergo hepatectomy.
Results
Most of the patients with morbidities such as biliary fistulas, ascites, fluid collection or duodenal perforation (20/24 or 83 %) were treated using operative drainage tubes, avoiding the use of percutaneous drainage procedures. The values obtained with the formula (drainage fluid bilirubin concentration/serum bilirubin concentration) × drainage fluid volume, were greater on both postoperative days (POD) 2 and 3 (
P
= 0.03 and
P
< 0.01) in patients with biliary leakage compared with those observed in the patients without leakage. The bacteriologic cultures of drainage fluid were positive less frequently on POD 4 or earlier (7/203) than on POD 5 or later (24/74,
P
< 0.01). In the validation cohort, new drain removal criteria based on the retrospective results led to successful drain management without additional treatment in 96 % of patients.
Conclusions
Abdominal drainage is effective for both postoperative monitoring and morbidity treatment.
Background
Surgical resection is the only curative strategy for perihilar cholangiocarcinoma (PHC), but recurrence rates are high even after purported curative resection. This study aimed to evaluate ...the efficacy and safety of gemcitabine/S-1 (GS) combination chemotherapy in the neoadjuvant setting.
Methods
In an open-label, single-arm, phase 2 study, neoadjuvant chemotherapy (NAC) with GS, repeated every 21 days, was administered for three cycles to patients with histologic or cytologically confirmed borderline resectable (BR) PHC who were eligible for inclusion in the study. In this study, BR PHC was defined as positive for lymph node metastasis and for cancerous vascular invasion or Bismuth type 4 on preoperative imaging. The primary end point consisted of the 3- and 5-year survival rates. The secondary end points were feasibility, resection rate, and pathologic effect.
Results
The study enrolled 60 patients between January 2011 and December 2016. With respect to toxicity, the major adverse effect was neutropenia, which reached grade 3 or 4 in 53.3% of cases. The overall disease control rate was 91.3%. The median survival time for the entire cohort was 30.3 months. For all the patients, the estimated 3-year survival rate was 44.1%, and the 5-year survival rate was 30.0%. Resection with curative intent was performed for 43 (71%) of the 60 patients. For 81% of the resected patients, R0 resection was performed, and Clavien-Dindo grade 3 complications or a higher morbidity rate was seen in 41% of the patients. The median survival time was 50.1 months for the resected and 14.8 months for the unresected patients. For the resected patients, the estimated 3-year survival rate was 55.8%, and the estimated 5-year survival rate was 36.4%.
Conclusions
Gemcitabine/S-1 combination NAC has promising efficacy and good tolerability for patients with BR PHC.
Background
Pancreatectomy is the main curative therapeutic option for pancreatic neuroendocrine tumors (pNETs). Given the indolent behavior of pNETs and the relatively limited lifetime of elderly ...patients, the impact of primary site surgery (PSS) of pNETs on long-term outcomes among older patients has been a topic of debate.
Methods
Patients aged 70 or older with pNETs were identified in the Surveillance, Epidemiology and the End Results (SEER) database from 1998 to 2016. Propensity score matching was used to compare overall (OS) and cancer-specific survival (CSS) of patients who did versus did not undergo PSS.
Results
Among 2,319 elderly patients with pNETs, 942 patients (40.6%) underwent PSS, while 1,377 (59.4%) did not undergo PSS (non-PSS: NPSS). After propensity score matching (
n
= 433 in each group), PSS group had improved survival compared with the NPSS group (5-year OS: 53.4% vs. 37.3%; 5-year CSS: 77.2% vs. 58.1%, both
p
< 0.001). In contrast, subgroup analysis of individuals aged ≥ 80 revealed no difference in 5-year CSS (PSS: 69.2% vs. NPSS: 67.4%,
p
= 0.27). A subgroup analysis among patients who had small (≤ 2 cm) non-functional (NF) pNETs noted comparable long-term outcomes among patients who underwent PSS versus NPSS patients (5-year OS: 73.1% vs. 66.5%,
p
= 0.19; 5-year CSS: 98.5% vs. 95.2%,
p
= 0.14).
Conclusions
Approximately 2 in 5 elderly patients with pNETs underwent PSS. While PSS was generally associated with prolonged OS and CSS among older patients, PSS was not associated with improved CSS among a subset of patients aged 80 or older, as well as among patients age ≥ 70 years with NF-pNET less than 2 cm.
Background
The high operative mortality rate after hepatopancreatoduodenectomy (HPD) is still a major issue. The present study explored why operative mortality differs significantly due to hospital ...volume.
Method
Surgical case data were extracted from the National Clinical Database (NCD) in Japan from 2011 to 2014. Surgical procedures were categorized as major (≥2 sections) and minor (<2 sections) hepatectomy. Hospitals were categorized according to the certification system by the Japanese Society of Hepato‐Biliary‐Pancreatic Surgery (JSHBPS) based on the number of major hepato‐biliary‐pancreatic surgeries performed per year. The FTR rate was defined as death in a patient with at least one postoperative complication.
Results
A total of 422 patients who underwent HPD were analyzed. The operative mortality rates in board‐certified A training institutions, board‐certified B training institutions, and non‐certified institution were 7.2%, 11.6%, and 21.4%, respectively. Multiple logistic regression showed that certified A institutions, major hepatectomy, and blood transfusion were the predictors of operative mortality. Failure to rescue rates were lowest in certified A institutions (9.3%, 17.0%, and 33.3% in certified A, certified B, and non‐certified, respectively).
Conclusions
To reduce operative mortality after HPD, further centralization of this procedure is desirable. Future studies should clarify specific ways to improve the failure‐to‐rescue rates in certified institutions.
Highlight
Endo and colleagues analyzed hepatopancreatoduodenectomy data from 422 patients in Japan. Operative mortality rates in board‐certified A, board‐certified B, and non‐certified institutions were 7.2%, 11.6%, and 21.4%, respectively. Failure‐to‐rescue rates were lowest in board‐certified A institutions. The incidence of complications after hepatopancreatoduodenectomy approximated the sum of that after hepatectomy and that after pancreatectomy in non‐certified institutions.
To establish clinical prediction models of vessels encapsulating tumor clusters (VETC) pattern using preoperative contrast-enhanced ultrasound (CEUS) and gadolinium-ethoxybenzyl-diethylenetriamine ...pentaacetic acid magnetic resonance imaging (EOB-MRI) in patients with hepatocellular carcinoma (HCC). A total of 111 resected HCC lesions from 101 patients were included. Preoperative imaging features of CEUS and EOB-MRI, postoperative recurrence, and survival information were collected from medical records. The best subset regression and multivariable Cox regression were used to select variables to establish the prediction model. The VETC-positive group had a statistically lower survival rate than the VETC-negative group. The selected variables were peritumoral enhancement in the arterial phase (AP), hepatobiliary phase (HBP) on EOB-MRI, intratumoral branching enhancement in the AP of CEUS, intratumoral hypoenhancement in the portal phase of CEUS, incomplete capsule, and tumor size. A nomogram was developed. High and low nomogram scores with a cutoff value of 168 points showed different recurrence-free survival rates and overall survival rates. The area under the curve (AUC) and accuracy were 0.804 and 0.820, respectively, indicating good discrimination. Decision curve analysis showed a good clinical net benefit (threshold probability > 5%), while the Hosmer-Lemeshow test yielded excellent calibration (P = 0.6759). The AUC of the nomogram model combining EOB-MRI and CEUS was higher than that of the models with EOB-MRI factors only (0.767) and CEUS factors only (0.7). The nomogram verified by bootstrapping showed AUC and calibration curves similar to those of the nomogram model. The Prediction model based on CEUS and EOB-MRI is effective for preoperative noninvasive diagnosis of VETC.
Gallbladder cancer is a biliary tract cancer that originates in the gallbladder and cystic ducts and is recognized worldwide as a refractory cancer with early involvement of the surrounding area ...because of its anatomical characteristics. Although the number of cases is increasing steadily worldwide, the frequency of this disease remains low, making it difficult to plan large‐scale clinical studies, and there is still much discussion about the indications for surgical resection and the introduction of multidisciplinary treatment. Articles published between 2019 and 2020 were reviewed, focusing mainly on the indications for surgical resection for each tumor stage, the treatment of incidental gallbladder cancer, and current trends in minimally invasive surgery for gallbladder cancer.
PDF
