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Colorectal cancer with liver metastasis (CLM) has high postoperative recurrence rates; therefore, optimizing perioperative treatment is imperative. Postoperative carcinoembryonic antigen (CEA) can aid in detecting minimal residual disease in colon cancer following curative resection. This study aimed to identify the potential role of serum CEA following liver resection in patients with CLM.This retrospective study was conducted at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research from 2004 to 2018 and enrolled patients with CLM who underwent complete resection of primary tumors and CLM. Associations between perioperative CEA levels and characteristics of recurrence were investigated.Recurrence was detected during a median follow-up period of 90.1 months in 343 (54.2%) out of 633 analyzed patients. Patients in the postoperative CEA level5 ng/ml group had a significantly higher recurrence rate (75.7% versus 50.0%, p0.01) and shorter time until recurrence (4.4 versus 36.9 months, p0.01) than those in the postoperative CEA level ≤ 5 ng/ml group. Multivariate analysis revealed that postoperative CEA level5 ng/ml was an independent predictor, with hazard ratios of 2.77 (p0.01) for recurrence-free survival (RFS) and 3.18 (p0.01) for overall survival (OS). Additionally, RFS was significantly shorter among patients in the postoperative CEA level5 ng/ml group who did not have normalized CEA levels following adjuvant chemotherapy than among those in the normalized CEA group.The postoperative and post-adjuvant chemotherapy CEA levels in the CEA level5 ng/ml group may be predictors of RFS and OS.

The prognosis of initially unresectable pancreatic cancer (UR-PC) has improved since the introduction of FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel (GNP) treatment. Nonetheless, the indications and optimal timing for conversion to resection remain unclear for UR-PC. The aim of this study is to evaluate the characteristics of cases with initially UR-PC who received modified FFX or GNP treatment.This retrospective study reviewed 454 consecutive Japanese UR-PC cases who received modified FFX/GNP treatment. Cases were categorized according to resection status, and overall survival (OS) was evaluated using a multivariable prognostic scoring model (0-4 points, higher score indicating more favorable prognostic factors).The overall resection rate was 16% for locally advanced UR-PC (UR-LA) and 5% for metastatic UR-PC (UR-M). The resection group had better OS than the nonresection group (median OS time: not reached versus 13.0 months, P0.001). The independent prognostic factors were normalized CA19-9 concentration, modified Glasgow prognostic score of 0, tumor shrinkage after chemotherapy, chemotherapy duration ≥ 8 months, and resection. Cases were grouped according to their prognostic score, and the results suggested that candidates for resection might have prognostic scores of 4 points in UR-M cases or 2-4 points in UR-LA cases.Stratification according to prognostic score was useful in predicting the outcomes of UR-PC cases and may aid in identifying cases who might benefit from surgical treatment after responding to chemotherapy.

Laparoscopic radical antegrade modular pancreatosplenectomy (Lap-RAMPS) for left-sided pancreatic cancer remains a technically challenging procedure. How to approach the splenic artery in laparoscopic surgery has not been discussed in adequate detail, and the implications of an artery-first approach in left-sided pancreatic cancer remain unclear.Forty-five consecutive patients with left-sided resectable pancreatic cancer underwent Lap-RAMPS between July 2018 and September 2020. They were divided according to whether Lap-RAMPS was performed using an anterocranial splenic artery-first (ASF) approach (ASF group, n = 23) or via another approach (non-ASF group, n = 22). Clinical, pathological, and short-term outcomes were reviewed and compared between the groups.The ASF approach was performed safely in all patients with resectable left-sided pancreatic cancer, and none required conversion to laparotomy. The ASF group had better outcomes in terms of conspicuous bleeding from the spleen during splenic mobilization (P = 0.016) and blood pooling during posterior dissection (P = 0.035). Consequently, blood loss was significantly less and operation time was significantly shorter in the ASF group than in the non-ASF group. There was no significant between-group difference in other short-term outcomes, including mortality, length of hospital stay, or Clavien-Dindo classification.The ASF approach was safe when performed for resectable left-sided pancreatic cancer and may help to prevent congestion of the pancreas and lessen intraoperative blood loss.

Hepatic resection combined with perioperative chemotherapy is the standard of care for patients with multiple colorectal liver metastases (CLMs). However, the optimal surgical strategy for treating advanced CLMs remains unclear. The role of the two-stage hepatectomy (TSH) strategy in the management of multiple CLMs remains challenging. This study aimed to compare the outcomes of one-step hepatectomy (OSH)-treated and TSH-treated patients with multiple CLMs.This single-institution study included 742 consecutive patients who underwent initial liver resection for histologically confirmed CLMs. The study enrolled patients with 10 or more tumors (n = 106). Clinicopathologic characteristics and long-term outcomes were compared between patients who underwent OSH and those who underwent TSH for 10 or more CLMs.The study planned OSH for 67 patients (63%) and TSH for 39 patients (37%). One of the OSH-planned patients and two of the TSH-planned patients underwent a trial laparotomy because of non-curative factors. Five patients (13%) did not progress to the second stage of TSH. In the entire cohort, the cumulative 3-year overall survival rate was 58.4% for the patients who had 10 or more CLMs treated with OSH compared with 61.1% for the patients treated with TSH (P = 0.746). In the curative resection cohort, the cumulative 1-year recurrence-free survival rate was 18.2% for the patients treated with OSH and 17.9% for the patients treated with TSH (P = 0.640).Hepatectomy with perioperative chemotherapy for advanced CLMs with 10 or more tumors is feasible and effective. To prolong survival, TSH is a promising option when curative resection with OSH is impossible.

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. Conclusions In patients undergoing hepatectomy for CLM, the prognostic value of KRAS depends on their history of preoperative chemotherapy or tumor burden.

The oncologic advantage of anatomic resection (AR) for primary hepatocellular carcinoma (HCC) remains controversial. This study aimed to evaluate the clinical advantages of AR for primary HCC by using propensity score-matching and by assessing treatment strategies for recurrence after surgery. The study reviewed data of patients who underwent AR or non-anatomic resection (NAR) for solitary HCC (≤ 5 cm) in two institutions between 2004 and 2017. Surgical outcomes were compared between the two groups in a propensity score-adjusted cohort. The time-to-interventional failure (TIF), defined as the elapsed time from resection to unresectable/unablatable recurrence, also was evaluated. The inclusion criteria were met by 250 patients: 77 patients (31%) with AR and 173 patients (69%) with NAR. In the propensity score-matched populations (AR, 67; NAR, 67), the 5-year recurrence-free survival (RFS) for AR was better than for NAR (62% vs 35%; P = 0.005). No differences, however, were found in the 5-year overall survival between the two groups (72% vs 78%; P = 0.666). The 5-year TIF rates for the NAR group (60%) also were similar to those for the AR group (66%) (P = 0.413). In the cohort of 67 patients, curative repeat resection or ablation therapy was performed more frequently for the NAR patients (42%) than for the AR patients (10%) (P

Neoadjuvant therapy is used for borderline resectable pancreatic ductal adenocarcinoma (PDAC) with high risk of incomplete resection and early recurrence. Because distal PDAC is rare, the optimal criteria for neoadjuvant therapy specific for distal PDAC remain unclear. We hypothesized large distal PDAC would recur earlier than small distal PDAC. The aim of this study was to identify the risk factors for failure of upfront resection for resectable distal PDAC. The study cohort comprised 158 patients with resectable distal PDAC who underwent radical resection. The long-term outcomes were recurrence-free survival (RFS), disease-specific survival (DSS), and post-recurrence survival (PRS). R0 resection was achieved in 92% of patients, and median DSS for the entire cohort was 31 months. Among 103 patients who developed recurrence, 32 (31%) developed recurrence within 6 months. The median PRS and DSS for those with early recurrence was 6 and 10 months, respectively, compared with 11 and 30 months, respectively, for those with late recurrence (p = 0.017 and p 4 cm had higher rates of R1 resection (16%) and concomitant resection of another organ (19%) than those with smaller tumors (4% and 2%, p = 0.009 and p 4 cm remained a significant predictor of early recurrence (p 4 cm is a reliable predictor of early recurrence after resection of distal PDAC, and neoadjuvant therapy may help select patients who can benefit from radical resection.

Patients with pancreatic cancer (PC) have poor prognosis and a high incidence of recurrence. Since further treatment is applicable for specific recurrent events, it is important to predict recurrence patterns after surgery. This study aimed to identify and predict early and late recurrence patterns of PC using a histology-based machine learning model.Patients who underwent upfront curative surgery for PC between 2001 and 2014 were included. The timing of recurrence and prognosis of each first recurrence site were examined. A histology-based supervised machine learning method, which combined convolutional neural networks and random forest, was used to predict the recurrence and respective sites of metastasis. Accuracy was evaluated using area under the receiver operating characteristic curve (AUC).In total, 524 patients were included. Recurrence in the liver accounted for 47.8% of all recurrence events in the first year after surgery. Meanwhile, recurrence in the lung occurred later and could become apparent more than 5 years post-surgery, with indications for further surgery. In terms of substantial distant organ metastases, liver and lung metastases were identified as representative early and late recurrence events. The predictive AUCs of the machine learning model for training and test data were 1.000 and 0.861, respectively, and for predicting nonrecurrence were 1.000 for both.We identified the liver and lung as early and late recurrence sites, which could be distinguished with high probability using a machine learning model. Prediction of recurrence sites using this model may be useful for further treatment of patients with PC.

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.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).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 TBS3 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 TBS3 or ≥ 9.In patients undergoing hepatectomy for CLM, the prognostic value of KRAS depends on their history of preoperative chemotherapy or tumor burden.

The oncologic advantage of anatomic resection (AR) for primary hepatocellular carcinoma (HCC) remains controversial. This study aimed to evaluate the clinical advantages of AR for primary HCC by using propensity score-matching and by assessing treatment strategies for recurrence after surgery.The study reviewed data of patients who underwent AR or non-anatomic resection (NAR) for solitary HCC (≤ 5 cm) in two institutions between 2004 and 2017. Surgical outcomes were compared between the two groups in a propensity score-adjusted cohort. The time-to-interventional failure (TIF), defined as the elapsed time from resection to unresectable/unablatable recurrence, also was evaluated.The inclusion criteria were met by 250 patients: 77 patients (31%) with AR and 173 patients (69%) with NAR. In the propensity score-matched populations (AR, 67; NAR, 67), the 5-year recurrence-free survival (RFS) for AR was better than for NAR (62% vs 35%; P = 0.005). No differences, however, were found in the 5-year overall survival between the two groups (72% vs 78%; P = 0.666). The 5-year TIF rates for the NAR group (60%) also were similar to those for the AR group (66%) (P = 0.413). In the cohort of 67 patients, curative repeat resection or ablation therapy was performed more frequently for the NAR patients (42%) than for the AR patients (10%) (P 0.001).For solitary HCC, AR decreases recurrence after the initial hepatectomy. However, aggressive curative-intent interventions for recurrence compensate for the impaired RFS, even for patients undergoing NAR.

Neoadjuvant therapy is used for borderline resectable pancreatic ductal adenocarcinoma (PDAC) with high risk of incomplete resection and early recurrence. Because distal PDAC is rare, the optimal criteria for neoadjuvant therapy specific for distal PDAC remain unclear. We hypothesized large distal PDAC would recur earlier than small distal PDAC.The aim of this study was to identify the risk factors for failure of upfront resection for resectable distal PDAC.The study cohort comprised 158 patients with resectable distal PDAC who underwent radical resection. The long-term outcomes were recurrence-free survival (RFS), disease-specific survival (DSS), and post-recurrence survival (PRS).R0 resection was achieved in 92% of patients, and median DSS for the entire cohort was 31 months. Among 103 patients who developed recurrence, 32 (31%) developed recurrence within 6 months. The median PRS and DSS for those with early recurrence was 6 and 10 months, respectively, compared with 11 and 30 months, respectively, for those with late recurrence (p = 0.017 and p 0.001, respectively). Patients with tumors 4 cm had higher rates of R1 resection (16%) and concomitant resection of another organ (19%) than those with smaller tumors (4% and 2%, p = 0.009 and p 0.001, respectively). In multivariate analysis, tumor 4 cm remained a significant predictor of early recurrence (p 0.001, hazard ratio [HR] 6.51), shorter RFS (p = 0.018, HR 1.71), and shorter DSS (p = 0.002, HR 2.07).Tumor size 4 cm is a reliable predictor of early recurrence after resection of distal PDAC, and neoadjuvant therapy may help select patients who can benefit from radical resection.

Duodenal adenocarcinoma (DA) is a rare disease, and the optimal extent of lymphadenectomy and the role of limited resection remain controversial. The aim of our study was to assess the pattern of regional lymph node spread of DA and to determine the optimal extent of resection. A total of 65 patients who underwent curative resection for DA at our institution from 1989 through 2015 were included in this study. Clinicopathologic factors associated with long-term outcomes and the patterns of regional node spread per primary tumor location were evaluated. Fifty-one patients (78%) underwent pancreaticoduodenectomy (PD), with the remainder undergoing limited resection. The median number of retrieved lymph nodes was 24 (range 1–63) and 48% of patients had regional node metastasis. The 5-year overall survival (OS) rate was 67%. In the multivariate analysis, regional node and para-aortic lymph node metastasis were risk factors associated with poorer OS (hazard ratio [HR] 12.1 [p = 0.025], and HR 3.2 [p = 0.045], respectively). While pancreaticoduodenal (#13) and superior mesenteric (#14) lymph node stations were commonly involved by both distal and proximal DA (33 vs. 39% for #13, p = 0.39; and 33 vs. 22% for #14, p = 0.27), the pyloric lymph node station was much less involved by distal DA than proximal DA (0 vs. 37%, p = 0.036). The pancreaticoduodenal lymph node station was the most commonly involved lymph node in DA, and PD should be the standard operation for DA. Segmental resection should only be reserved for patients with distal DA who are physically unfit for PD.

Prophylactic impact of major hepatectomy (MH) on liver recurrence has yet to be clarified in patients with advanced colorectal liver metastases (CLMs). In our institute, parenchymal-sparing hepatectomy (PSH) is a standard procedure for CLMs consistently throughout initial and repeat resection, and MH is selected only in cases in which CLMs are close to major Glisson’s pedicles. We reviewed 145 patients who underwent curative hepatectomy for advanced CLMs (≥4 nodules and ≤50 mm in size) from 1999 to 2012. Surgical outcomes and survival were compared between patients who underwent PSH and MH. PSH was performed in 113 patients (77.9 %) and MH in 32 (22.1 %) patients with advanced CLMs. Tumor characteristics and short-term outcomes did not differ between the 2 groups. Incidence of positive tumor margin (8.8 % in PSH vs 9.4 % in MH; p = .927) and rates of liver-only recurrence (43.4 % in PSH and 50.0 % in MH; p = .505) did not differ. No significant differences were found in 5-year overall survival (37.0 % in PSH vs 29.4 % in MH, p = .473), recurrence-free survival (7.6 vs 6.8 %, p = .597), and liver recurrence-free survival (21.0 vs 21.3 %, p = .691). A total of 65 patients had liver-only recurrence, for which repeat hepatectomy was performed in 81.5 % (53 of 65) following our parenchymal-sparing approach. In patients with advanced CLM, PSH does not increase positive surgical margin or liver recurrence in comparison with MH. A parenchymal-sparing approach offers a high rate of repeat resection for liver recurrence (salvageability).

Preoperative chemotherapy sometimes makes colorectal liver metastases disappear or diminish. Contrast-enhanced intraoperative ultrasound (CE-IOUS) using perflubutane may identify such metastases.Among 131 consecutive patients who underwent hepatic resection, 86 had received preoperative chemotherapy. Of these patients, 72 were examined using contrast-enhanced computed tomography (CE-CT), gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI), contrast-enhanced ultrasound (CEUS), intraoperative ultrasound (IOUS), and CE-IOUS; these patients were the subject of the present study. Effects of IOUS and CE-IOUS to search for disappearing liver metastases (DLM) and tumors with a diameter of 1 cm or less based on the preoperative imaging were assessed.A total of 32 DLMs were noted in 11 patients. Four DLMs were identified using IOUS, and 16 DLMs (including the four DLMs identified using IOUS) were identified using CE-IOUS. Of the 16 DLMs that were missed using both IOUS and CE-IOUS, nine were resected using anatomical resection and seven were not resected. One of the nine resected DLMs was histologically proven to be adenocarcinoma. Three of the seven unresected DLMs showed tumor regrowth during a postoperative follow-up examination. CE-IOUS identified 79 % of the 19 DLMs that were ultimately confirmed as liver metastases, whereas IOUS identified 21 % of them (p0.004). Among the 202 tumors that were identified using preoperative imaging, 54 were 1 cm or less in diameter. The sensitivity of CE-IOUS for these tumors were superior to CE-CT (p0.04) and IOUS (p0.04), respectively.CE-IOUS might be necessary after preoperative chemotherapy for colorectal liver metastasis.

This phase II trial was designed to evaluate the safety and efficacy of adjuvant chemotherapy with S-1 in patients with curatively resected liver metastasis from colorectal cancer. Results of an interim analysis of safety and short-term outcomes are reported. Patients who underwent curative resection of liver metastasis from colorectal cancer received S-1 monotherapy (on days 1–28, followed by 14 days’ rest, 8 cycles) as adjuvant chemotherapy. Among 62 patients enrolled between October 2008 and August 2010, a total of 60 patients were eligible for analysis. The most frequent grade 3 or higher hematologic toxicity involved neutropenia in three patients (5.0 %). Nonhematologic toxicities of grade 3 or higher were fatigue in 6.7 % of patients. Grade 4 enteritis occurred in one patient, but resolved promptly after withdrawal of S-1 therapy. The completion rate of the eight scheduled cycles of chemotherapy was 58.3 %. The most common reasons for withdrawal of treatment was the detection of early relapse in 16 patients (64 %). When the 16 patients who had recurrence during adjuvant treatment were excluded from analysis, 79.5 % of the remaining 44 patients completed the scheduled treatment. Early recurrence within 1 year after curative liver resection occurred in 21 patients (35 %). The most common site was the remnant liver in 14 patients. Orally administered S-1 after curative liver resection has an acceptable toxicity profile and a high rate of completion of the therapy. S-1 can be safely used and might be a viable treatment option in an adjuvant setting.

The rate of recurrence after liver resection for colorectal liver metastases (CLM) is high, and repeat resection (RR) is reserved with curative intent in selected patients. This study evaluated the benefit of RR for recurrence after liver resection for CLM. Data were collected on 287 consecutive patients who underwent primary curative hepatectomy between January 1999 and October 2008 for CLM at our institution. After median follow-up of 63 months, 211 patients (73 %) developed recurrence and RR was conducted in 102 (48 %) patients. Five-year overall survival (OS) was significantly higher in the RR group than in those patients not selected for RR (70 vs. 45 %, P = 0.002). On multivariate analyses, RR was identified as an independent factor for good prognosis. According to the first recurrence sites, 5-year OS after recurrence was significantly better in patients with liver or lung only recurrence (55, 51 %, respectively) than in locoregional/lymph node metastases and other/multiple sites recurrence (33, 9.0 %, respectively). In patients with liver- or lung-only recurrence, 5-year OS after recurrence was significantly higher in RR patients than in those without RR (liver; 67 and 0 %, lung; 88 and 24 %, respectively; P