Clinical Significance of Primary Tumor Resection in Perihilar Cholangiocarcinoma with Positive Peritoneal Lavage Cytology.

BACKGROUND: The prognostic impact of positive peritoneal lavage cytology (CY+) in patients with perihilar cholangiocarcinoma (PHC) remains unclear. The present study investigated the clinical significance of primary tumor resection of CY+ PHC. METHODS: We retrospectively evaluated 282 patients who underwent surgery for PHC between September 2002 and March 2022. The patients' clinicopathological characteristics and survival outcomes were compared between the CY negative (CY-) resected (n = 262), CY+ resected (n = 12), and CY+ unresected (n = 8) groups. Univariate and multivariate analyses were performed to identify prognostic factors for overall survival. RESULTS: The expected residual liver volume was significantly higher in the CY+ resected group (61%) than in the CY- resected (47%) and CY+ unresected (37%) groups (p = 0.004 and 0.007, respectively). The CY+ resected group had a higher administration rate of postoperative therapy than the CY- resected group (58% vs. 16%, p = 0.002). Overall survival of the CY+ resected group was similar to that of the CY- resected group (median survival time [MST] 44.5 vs. 44.6, p = 0.404) and was significantly better than that of the CY+ unresected group (MST 44.5 vs. 17.1, p = 0.006). CY positivity was not a prognostic factor according to a multivariate analysis in patients with primary tumor resection. CONCLUSIONS: The CY+ resected group showed better survival than the CY+ unresected group and a similar survival to that of the CY- resected group. Resection of the primary tumor with CY+ PHC may improve the prognosis in selected patients.

Acute adverse events of ultra-hypofractionated whole-breast irradiation after breast-conserving surgery for early breast cancer in Japan: an interim analysis of the multi-institutional phase II UPBEAT study.

BACKGROUND: The applicability of ultra-hypofractionated (ultra-HF) whole-breast irradiation (WBI) remains unknown in Japanese women. This study aimed to evaluate the safety and efficacy of this approach among Japanese women and report the results of an interim analysis performed to assess acute adverse events (AEs) and determine whether it was safe to continue this study. METHODS: We enrolled Japanese women with invasive breast cancer or ductal carcinoma in situ who had undergone breast-conserving surgery, were aged ≥ 40 years, had pathological stages of Tis-T3 N0-N1, and had negative surgical margins. Ultra-HF-WBI was delivered at 26 Gy in five fractions over one week. When the number of enrolled patients reached 28, patient registration was paused for three months. The endpoint of the interim analysis was the proportion of acute AEs of grade ≥ 2 (Common Terminology Criteria for Adverse Events v5.0) within three months. RESULTS: Of the 28 patients enrolled from seven institutes, 26 received ultra-HF-WBI, and 2 were excluded due to postoperative infections. No AEs of grade ≥ 3 occurred. One patient (4%) experienced grade 2 radiation dermatitis, and 18 (69%) had grade 1 radiation dermatitis. The other acute grade 1 AEs experienced were skin hyperpigmentation (n = 10, 38%); breast pain (n = 4, 15%); superficial soft tissue fibrosis (n = 3, 12%); and fatigue (n = 1, 4%). No other acute AEs of grade ≥ 2 were detected. CONCLUSIONS: Acute AEs following ultra-HF-WBI were within acceptable limits among Japanese women, indicating that the continuation of the study was appropriate.

Predictive score for identifying intrahepatic cholangiocarcinoma patients without lymph node metastasis: a basis for omitting lymph node dissection.

BACKGROUND: This study aimed to develop a predictive score for intrahepatic cholangiocarcinoma (ICC) in patients without lymph node metastasis (LNM) using preoperative factors. METHODS: A retrospective analysis of 113 ICC patients who underwent liver resection with systemic lymph node dissection between 2002 and 2021 was conducted. A multivariate logistic regression analysis was used as a predictive scoring system for node-negative patients based on the ß coefficients of preoperatively available factors. RESULTS: LNM was observed in 36 patients (31.9%). Four factors were associated with LNM: suspicion of LNM on MDCT (odds ratio [OR] 13.40, p < 0.001), low-vascularity tumor (OR 6.28, p = 0.005), CA19-9 ≥500 U/mL (OR 5.90, p = 0.010), and tumor location in the left lobe (OR 3.67, p = 0.057). The predictive scoring system was created using these factors (assigning 3 points for suspected LNM on MDCT, 2 points for CA19-9 ≥500 U/mL, 2 points for low vascularity tumor, and 1 point for tumor location in the left lobe). A score cutoff value of 4 resulted in 0.861 sensitivity and a negative predictive value of 0.922 for detecting LNM. Notably, no patients with peripheral tumors and a score of ≤3 had LNM. CONCLUSION: The developed scoring system may effectively help identify ICC patients without LNM.

Industrially produced trans-fatty acids are potent promoters of DNA damage-induced apoptosis.

trans-Fatty acids (TFAs) are unsaturated fatty acids harboring at least one carbon-carbon double bond in trans configuration, which are categorized into two groups according to their origin: industrial and ruminant TFAs, hereafter called iTFAs and rTFAs, respectively. Numerous epidemiological studies have shown a specific link of iTFAs to various diseases, such as cardiovascular and neurodegenerative diseases. However, there is little evidence for underlying mechanisms that can explain the specific toxicity of iTFAs, and how to mitigate their toxicity. Herein, we show that iTFAs, including elaidic acid (EA) and linoelaidic acid, but not rTFAs, facilitate apoptosis induced by doxorubicin (Dox), triggering DNA double-strand breaks. We previously established that EA promotes Dox-induced apoptosis by accelerating c-Jun N-terminal kinase (JNK) activation through mitochondrial reactive oxygen species (ROS) overproduction. Consistently, iTFAs specifically enhanced Dox-induced JNK activation. Furthermore, Dox-induced pro-apoptotic signaling by iTFAs was blocked in the presence of oleic acid (OA), the geometrical cis isomer of EA. These results demonstrate that iTFAs specifically exert their toxicity during DNA damage-induced apoptosis, which could be effectively suppressed by OA. Our study provides evidence for understanding the difference in toxic actions between TFA species, and for new strategies to prevent and combat TFA-related diseases.

Efficacy of lymph node dissection for duodenal cancer according to the lymph node station.

Background: Lymph node metastasis (LNM) is associated with poor prognosis in patients with duodenal cancer (DC). However, the efficacy and optimal extent of lymph node (LN) dissection have not been thoroughly discussed. Methods: A total of 98 consecutive patients with DC who underwent surgical resection (pancreatoduodenectomy, n = 55; partial resection, n = 32; pancreas-sparing total duodenectomy, n = 9) were retrospectively analyzed. The LN stations located upstream of the lymphatic flow were defined as Np stations according to tumor location, whereas the others were defined as Nd stations. The association between the dissection of each LN station and survival outcome was investigated using the efficacy index (EI; percentage of metastases to lymph nodes in each station multiplied by the 5-year survival rate of metastatic cases). Results: The survival of patients with LNM at the Nd stations (n = 6) was significantly worse than that of patients with LNM only at the Np stations (n = 20) (relapse-free survival, median survival time [MST], 6.0 vs. 48.4 months, p < 0.001; overall survival, MST, 15.1 vs. 96.0 months, p < 0.001). Multivariate analysis identified LNM at Nd stations as an independent prognostic factor for overall survival (hazard ratio 9.92; p = 0.015). The Np stations had a high EI (range, 8.34-20.88), whereas the Nd stations had an EI of 0, regardless of the tumor location. Conclusions: LN dissection of the Np stations contributed to acceptable survival, whereas LNM of the Nd stations led to poor survival, possibly reflecting advanced tumor progression to systemic disease in patients with DC.

Tumor vascularity on contrast-enhanced computed tomography as a predictive marker of metastatic potential for small nonfunctioning pancreatic neuroendocrine tumors.

BACKGROUND: Although surgical resection is generally suggested for nonfunctioning pancreatic neuroendocrine tumors, observation can be proposed for carefully selected patients with small tumors. However, the indications for observation remain unclear. METHODS: This retrospective study included 77 patients with nonfunctioning pancreatic neuroendocrine tumors, including small tumors (≤2.0 cm, n = 41), who received pancreatectomy. The ratio of the mean computed tomography value of a tumor in the late arterial/equilibrium phase (computed tomography a/e ratio) was used to evaluate tumor vascularity. Pathologic examinations of small tumors were conducted. The associations among the computed tomography a/e ratio, pathologic findings, and survival outcomes were investigated. RESULTS: Small tumors were pathologically categorized by the degree of fibrosis as follows: medullary (n = 20), intermediate (n = 11), and fibrotic (n = 10). The fibrotic type had significantly lower computed tomography a/e ratios than the medullary type (median, 1.42 vs 2.03, P < .001). The median number of vessels with microscopic venous invasion was significantly higher in the fibrotic type than in the medullary type (4.5 vs 0.0, P < .001). The cutoff value of the computed tomography a/e ratio for predicting microscopic venous invasion was determined to be 1.54 by the receiver operating characteristic curve (area under the curve, 0.832; sensitivity, 80.0%; specificity, 83.9%; accuracy, 82.9%). Microscopic venous invasion was an independent prognostic factor for relapse-free survival in overall patients (hazard ratio 5.18, P = .017). CONCLUSION: The computed tomography a/e ratio may be a useful predictor of the metastatic potential of nonfunctioning pancreatic neuroendocrine tumors and may help decide the indications of observation for small nonfunctioning pancreatic neuroendocrine tumors.

Clinical outcomes of scalp or face angiosarcoma treatment with intensity-modulated radiotherapy: a multicenter study.

Combined modality therapy, including radiotherapy (RT), is a common treatment for scalp or face angiosarcoma. Although intensity-modulated radiotherapy (IMRT) can deliver homogeneous doses to the scalp or face, clinical data are limited. This multicenter study aimed to evaluate scalp or face angiosarcoma treated with definitive or post-operative IMRT. We retrospectively analyzed data from patients who received IMRT for scalp or face angiosarcoma at three institutions between January 2015 and March 2020. Local control (LC) rate, overall survival (OS), progression-free survival (PFS), recurrence patterns and toxicity were evaluated. Fifteen patients underwent IMRT during the study period. Definitive RT was performed on 10 patients and post-operative RT was performed on 5 patients. The 1-year LC rate was 85.7% (95% confidence interval [CI], 53.9-96.2%). The 1-year OS and PFS rates were 66.7% (95% CI, 37.5-84.6%) and 53.3% (95% CI, 26.3%-74.4%), respectively. Univariate analysis revealed that a clinical target volume over 500 cm3 was associated with poor LC. Distant metastasis was the most common recurrence pattern. All patients experienced Grade 2 or 3 radiation dermatitis, and five patients experienced grade ≥ 3 skin ulceration. One patient who underwent maintenance therapy with pazopanib developed Grade 5 skin ulceration. Fisher's exact test showed that post-operative RT was significantly associated with an increased risk of skin ulceration of grade ≥ 3. These results demonstrate that IMRT is a feasible and effective treatment for scalp or face angiosarcoma, although skin ulceration of grade ≥ 3 is a common adverse event in patients who receive post-operative RT.

Prognostic impact of the distance from the root of splenic artery to tumor in the patients with pancreatic body or tail cancer.

BACKGROUND: The impact of the distance from the root of splenic artery to tumor (DST) on the prognosis and optimal surgical procedures in the patients with pancreatic body/tail cancer has been unclear. METHODS: We retrospectively analyzed 94 patients who underwent distal pancreatectomy (DP) and 17 patients who underwent DP with celiac axis resection (DP-CAR) between 2008 and 2018. RESULTS: The 111 patients were assigned by DST length (in mm) as DST = 0: n = 14, 0

Benefit of lymph node dissection for perihilar and distal cholangiocarcinoma according to lymph node stations.

BACKGROUND: The benefits of lymph node (LN) dissection at each station have not previously been fully investigated in perihilar cholangiocarcinoma (PHCC) and distal cholangiocarcinoma (DCC). METHODS: The efficacy index (EI) was calculated in patients who underwent surgery for PHCC (n = 134) and DCC (n = 135) by multiplying the frequency of metastasis to the LN station and the 5-year overall survival (OS) rate of patients with metastasis to that station. RESULTS: In PHCC, the frequency of metastasis, 5-year OS rates, and the EI in para-aortic LNs (4.7%, 0%, and 0, respectively) and posterior pancreaticoduodenal LNs (8.1%, 0%, and 0, respectively) were lower than those in hepatoduodenal ligament LNs (30.1%, 24.1%, and 7.25, respectively) and LNs along the common hepatic artery (CHA) (16.2%, 15.0%, and 2.43, respectively). In DCC, these values were lower in LNs along the CHA (6.4%, 0%, and 0, respectively) than in the posterior pancreaticoduodenal LNs (31.2%, 34.5%, and 10.8, respectively), the hepatoduodenal ligament LNs (14.8%, 15.2%, and 2.25, respectively), and para-aortic (4.0%, 25.0%, and 0.99, respectively) LNs. CONCLUSIONS: According to the EI, this study raises concerns about the effectiveness of dissection in the posterior pancreaticoduodenal LNs in PHCC and LNs along the CHA in DCC.

Comparison of Cefazolin and Ceftriaxone as Antimicrobial Prophylaxis in Pancreatoduodenectomy with Preoperative Drainage: Incidence of Surgical Site Infection and Susceptibility of Bacteria in Bile.

BACKGROUND: The optimal perioperative antimicrobial agent for preventing surgical site infection (SSI) in pancreatoduodenectomy (PD) with preoperative biliary drainage (PBD) remains unclear. METHODS: We retrospectively reviewed 288 patients who underwent PD after PBD between 2010 and 2020 at our institution. Patients were classified into two groups according to the perioperative antimicrobial agent used (cefazoline [CEZ] group [n = 108] and ceftriaxone [CTRX] group [n = 180]). The incidence of SSI, type of bacteria in intraoperative bile culture (IBC), and antimicrobial susceptibility to prophylactic antimicrobial agents were analyzed. RESULTS: The incidence of incisional SSI was significantly lower in the CTRX group than in the CEZ group (18% vs. 31%, P = 0.021), whereas the incidence of organ/space SSI in the two groups did not differ to a statistically significant extent (35% vs. 44%, P = 0.133). Gram-negative rod (GNR) bacteria in the IBC showed better antimicrobial susceptibility in the CTRX group than in the CEZ group. In multivariate analysis, antimicrobial resistance due to GNR was a significant risk factor for incisional SSI (odds ratio, 3.50; P < 0.001). CONCLUSIONS: CTRX had better antimicrobial coverage than CEZ for GNR cultured from intraoperative bile samples. In addition, CTRX provides better antimicrobial prophylaxis than CEZ against superficial SSI in patients with PD after PBD. TRIAL REGISTRATION NUMBER: This study was not a clinical trial and had no registration numbers.

Conversion surgery for advanced jejunal adenocarcinoma with multiple peritoneal metastases: a case report.

BACKGROUND: Small bowel cancer (SBC) is a rare malignancy that is often diagnosed at an advanced stage. Palliative chemotherapy is the standard treatment for patients with metastatic SBC. The relevant literature on conversion surgery in patients who have responded favorably to chemotherapy is limited. CASE PRESENTATION: A 64-year-old man was diagnosed with jejunal carcinoma with multiple peritoneal metastases. After implanting an expandable metallic stent at the primary site, the patient underwent 6 months of FOLFOX therapy, resulting in a clinical complete response. Chemotherapy was continued, and four years after the initiation of therapy, the patient showed no evidence of disease progression. Nevertheless, anemia of continuous minor hemorrhages from the stent site and general malaise of chemotherapy got progressively worse during treatment. After confirming negative ascites cytology and the absence of peritoneal metastasis via staging laparoscopy, the patient underwent partial jejunectomy. Pathologically, no residual tumor was detected in the resected specimen. The postoperative course was uneventful, and the patient remained free of recurrence for 30 months after surgery without chemotherapy. CONCLUSION: Although infrequent, conversion surgery may be a valid therapeutic option for selected cases of SBC with peritoneal metastasis.

Surrogacy of Recurrence-free Survival for Overall Survival as an Endpoint of Clinical Trials of Perioperative Adjuvant Therapy in Hepatobiliary-pancreatic Cancers: A Retrospective Study and Meta-analysis.

OBJECTIVE: To assess the correlation between recurrence-free survival (RFS) and overall survival (OS) in the hepato-biliary-pancreatic (HBP) surgical setting in order to validate RFS as a surrogate endpoint. SUMMARY BACKGROUND DATA: Reliable surrogate endpoints for OS are still limited in the field of HBP surgery. METHODS: We analyzed patients who underwent curative resection for HBP disease (986 patients with pancreatic ductal adenocarcinoma [PDAC], 1168 with biliary tract cancer [BTC], 1043 with hepatocellular carcinoma [HCC], and 1071 with colorectal liver metastasis [CRLM]) from September 2002 to June 2022. We also conducted meta-analyses of randomized controlled trials of neoadjuvant or adjuvant therapy to validate the surrogacy in PDAC and BTC. RESULTS: Correlation coefficients between RFS and OS were low for HCC (ρ = 0.67) and CRLM (ρ = 0.53) but strong for PDAC (ρ = 0.80) and BTC (ρ = 0.75). In a landmark analysis, the concordance rates between survival or death at 5 years postoperatively and the presence or absence of recurrence at each time point (1, 2, 3, and 4 y) were 50%, 70%, 74%, and 77% for PDAC and 54%, 67%, 73%, and 78% for BTC, respectively, both increasing and reaching a plateau at 3 years. In a meta-analysis, the correlation coefficients for the RFS hazard ratio and OS hazard ratio in PDAC and BTC were ρ = 0.88 (P < 0.001) and ρ = 0.87 (P < 0.001), respectively. CONCLUSION: Three-year RFS can be a reliable surrogate endpoint for OS in clinical trials of neoadjuvant or adjuvant therapy for PDAC and BTC.

Assessing target localization accuracy across different soft-tissue matching protocols using end-exhalation breath-hold cone-beam computed tomography in patients with pancreatic cancer.

The purpose of this study was to retrospectively assess target localization accuracy across different soft-tissue matching protocols using cone-beam computed tomography (CBCT) in a large sample of patients with pancreatic cancer and to estimate the optimal margin size for each protocol. Fifty-four consecutive patients with pancreatic cancer who underwent 15-fraction volumetric modulated arc therapy under the end-exhalation breath-hold condition were enrolled. Two soft-tissue matching protocols were used according to the resectability classification, including gross tumor volume (GTV) matching for potentially resectable tumors and planning target volume (PTV) matching for borderline resectable or unresectable tumors. The tolerance of the target localization error in both matching protocols was set to 5 mm in any direction. The optimal margin size for each soft-tissue matching protocol was calculated from the systematic and random errors of the inter- and intrafraction positional variations using the van Herk formula. The inter- and intrafraction positional variations of PTV matching were smaller than those of GTV matching. The percentage of target localization errors exceeding 5 mm in the first CBCT scan of each fraction in the superior-inferior direction was 12.6 and 4.8% for GTV and PTV matching, respectively. The optimal margin sizes for GTV and PTV matching were 3.7 and 2.7, 5.4 and 4.1 and 3.9 and 3.0 mm in the anterior-posterior, superior-inferior and left-right directions, respectively. Target localization accuracy in PTV matching was higher than that in GTV matching. By setting the tolerance of the target localization error, treatment can be successful within the planned margin size.

Impact of planning organ at risk volume margins and matching method on late gastrointestinal toxicity in moderately hypofractionated IMRT for locally advanced pancreatic ductal adenocarcinoma.

BACKGROUND: This study examined the differences in late gastrointestinal (GI) toxicities in moderately hypofractionated intensity-modulated radiation therapy (IMRT) for locally advanced pancreatic ductal adenocarcinoma (LA-PDAC) by changing the planning organs at risk volume (PRV) margin and the target matching method and assessed the causes of adverse events. METHODS: We examined 37 patients with LA-PDAC who underwent moderately hypofractionated IMRT between 2016 and 2020 at our institution; 23 patients were treated with wide PRV margins and soft tissue matching (Protocol A) and 14 with narrow PRV margins and fiducial marker matching (Protocol B). The GI toxicities, local control (LC) rate, and overall survival (OS) were assessed for each protocol. The initially planned and daily doses to the gross tumor volume (GTV), stomach, and duodenum, reproduced from cone-beam computed tomography, were evaluated. RESULTS: The late GI toxicity rate of grades 3-4 was higher in Protocol B (42.9%) than in Protocol A (4.3%). Although the 2-year LC rates were significantly higher in Protocol B (90.0%) than in Protocol A (33.3%), no significant difference was observed in OS rates. In the initial plan, no deviations were found for the stomach and duodenum from the dose constraints in either protocol. In contrast, daily dose evaluation for the stomach to duodenal bulb revealed that the frequency of deviation of V3 Gy per session was 44.8% in Protocol B, which was significantly higher than the 24.3% in Protocol A. CONCLUSIONS: Reducing PRV margins with fiducial marker matching increased GI toxicities in exchange for improved LC. Daily dose analysis indicated the trade-off between the GTV dose coverage and the irradiated doses to the GI. This study showed that even with strict matching methods, the PRV margin could not be reduced safely because of GI inter-fractional error, which is expected to be resolved with online adaptive radiotherapy.

Liver abscess caused by Clostridium perfringens after left hepatic trisectionectomy for perihilar cholangiocarcinoma: a case report.

BACKGROUND: Clostridium perfringens sepsis has been reported to have a rapid onset and severe clinical outcome. We herein report a case of C. perfringens sepsis associated with massive intravascular hemolysis after left hepatic trisectionectomy for perihilar cholangiocarcinoma. CASE PRESENTATION: A 72-year-old woman underwent left hepatic trisectionectomy for perihilar cholangiocarcinoma. Her postoperative course was uneventful except for bile leakage. She was discharged on postoperative day (POD) 35. On POD 54, she was readmitted because of abdominal pain with a high fever. Although her vital signs were stable on arrival at the hospital, a laboratory examination showed a severe inflammatory reaction and hemolysis, and she had developed disseminated intravascular coagulation. Abdominal contrast-enhanced computed tomography showed a 70-mm irregular shape and low-density containing air in liver segment 6, which suggested a liver abscess. The abscess was immediately drained of pus containing air. The pus showed multiple Gram-positive bacilli, and two blood cultures showed Gram-positive bacilli and hemolysis. Empirical antibiotic therapy with vancomycin and meropenem was started because C. perfringens was detected from the preoperative bile culture. Four hours after arrival, tachypnea and decreased oxygen saturation were observed. Her general condition deteriorated rapidly with significant hypoglycemia, progressive acidosis, anemia, and thrombocytopenia. Despite rapid drainage and empiric therapy, she died six hours after her arrival. At autopsy, the abscess consisted of coagulation necrosis of liver cells with inflammatory cell infiltration, and clusters of Gram-positive large bacilli were observed in the necrotic debris. C. perfringens was detected in the drainage fluid and blood culture. She was diagnosed with a liver abscess and severe sepsis caused by C. perfringens and treated promptly, but the disease progressed rapidly and led to her death. CONCLUSIONS: Sepsis caused by C. perfringens can progress rapidly and lead to death in a few hours, so prompt treatment is needed. When patients who have undergone highly invasive hepatobiliary-pancreatic surgery show hemolysis and hepatic abscesses with gas, C. perfringens should be considered the most likely bacterium.

ASO Author Reflections: Prognostic Role of Preoperative Duke Pancreatic Monoclonal Antigen Type 2 Values in Patients with Pancreatic Cancer: Focusing on the Usefulness in Patients with Normal CA19-9.

Pancreatic cancer (PC) is one of the most aggressive cancer types, and carbohydrate antigen (CA) 19-9 has been the most useful biomarker for its surveillance and prognosis prediction. However, CA19-9 may not be sufficiently prognostic in some patients, such as Lewis antigen-negative phenotype (Le[a-b-]) patients who secrete little or no CA19-9. Duke pancreatic monoclonal antigen type 2 (DUPAN-2) has been proposed as a complementary marker to CA19-9 in PC patients, but its utility in Le(a-b-) patients has only been reported in a limited number of cases. In a retrospective analysis of 224 PC patients who underwent surgery, the present study investigated the utility of DUPAN-2 in combination with CA19-9. The study subjects were divided into three groups based on their CA19-9 and DUPAN-2 levels. The normal CA19-9/high DUPAN-2 group had significantly larger tumors and a higher frequency of microscopic vascular invasion, perineural invasion, and recurrence than the normal CA19-9/normal DUPAN-2 group. Both the disease-free survival and disease-specific survival (DSS) of patients in the normal CA19-9/high DUPAN-2 group were significantly shorter than those in the normal CA19-9/normal DUPAN-2 group, and comparable with those in the high CA19-9 group. The results suggest that DUPAN-2 may be useful as a complementary biomarker to CA19-9 in PC, especially in patients who have normal CA19-9 levels. However, since this was a single-center, retrospective study, multicenter studies are needed to confirm the findings and determine the optimal cut-off value for patients with normal CA19-9 levels.

Genomic landscape of pancreatic cancer in the Japanese version of the Cancer Genome Atlas.

Background: Pancreatic cancer (PC) is one of the most aggressive cancers worldwide. Although many studies have investigated genomic alterations, the genomic landscape of Japanese PC patients has not been fully elucidated. Methods: We used whole-exome sequencing, cancer gene panel deep-sequencing, and microarray gene expression profiling data derived from the Japanese version of the Cancer Genome Atlas (JCGA) in 93 PC cases. Results: Somatic driver mutations were identified in 65.6% of samples in 19 genes. The median tumor mutation burden (TMB) value was 0.24 Muts/Mb (interquartile range, 0.15-0.64 Muts/Mb). The commonly mutated genes were KRAS (58%), TP53 (40%), CDKN2A (10%), SMAD4 (10%), FGFR2 (9%), and PKHD1 (9%). Frequent germline variation genes were BRCA1 (8%), CDH1 (5%), MET (5%), MSH6 (5%), and TEK (5%). Frequent chromosomal arm alterations included copy number gains in 2q (42%), 7q (24%), and 3q (24%), and copy number losses in 19p (62%), 19q (47%), 12q (34%), and 7q (30%). A prognostic analysis according to the presence of driver mutations showed that overall survival (OS) in the driver mutation-positive group was significantly worse in comparison to that of the driver mutation-negative group (median, 23.1 vs 46.7 mo; P = .010). A Cox proportional hazards analysis for OS identified driver mutation (hazard ratio [HR], 1.89; P = .025) and lymph node metastasis (HR, 3.27; P = .002) as independent prognostic factors. Conclusion: The present results from the JCGA dataset constitute a fundamental resource for genomic medicine for PC patients, especially in Japan.