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.

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

Evaluation of ventral branches of segment VI portal vein relative to the right hepatic vein in laparoscopic right anterior sectionectomy.

INTRODUCTION: The right intersectional plane and the right hepatic hilum were noted too often exhibit anatomical variations, making difficult the laparoscopic right anterior sectionectomy (LRAS). METHODS: We analyzed the anatomical features employing 3D-CT images of 55 patients, and evaluated these features according to the course of ventral branches of segment VI of the portal vein (PV, P6a) relative to the right hepatic vein (RHV). RESULTS: P6a run on the dorsal side of RHV in 32 patients (58%, Dorsal-P6a) and the ventral side of RHV in 23 (42%, Ventral-P6a). Ventral-P6a had more patients with S6 partially drained by middle hepatic vein (MHV, 39% vs. 0%, P < 0001), the narrower angle between the anterior and posterior branches of PV (73.1° vs. 93.8°, P = 0.006), the wider angle between the RHV and inferior vena cava  (54.3° vs. 44.3°, P < 0.001), and more steeply pitched angle between S6 and S7 along the RHV (140.6° vs. 162.0°, P < 0.001) compared to Dorsal-P6a. CONCLUSION: In LRAS for Dorsal-P6a patients, the transection surface was relatively flat. In LRAS for Ventral-P6a patients, the narrow space between anterior and posterior glissons makes difficult the glissonean approach. The transection plane was steeply pitched, and RHV was partially exposed. S6 was often partially drained to MHV in 39% of the Ventral-P6a patients, which triggers congestion during liver transection of a right intersectional plane after first splitting the confluence of this branch.

Two Japanese families with familial pancreatic cancer with suspected pathogenic variants of CDKN2A: a case report.

BACKGROUND: Germline mutations in CDKN2A result in Familial Atypical Multiple Mole Melanoma Syndrome (FAMMM) (OMIM #155,601), which is associated with an increased risk of pancreatic ductal adenocarcinoma and melanoma. FAMMM has been reported globally, but it is quite rare in Japan. We report two families with familial pancreatic cancer with suspected pathogenic variants of CDKN2A that were incidentally identified through comprehensive genomic profiling. CASE PRESENTATION: The first case is a 74-year-old woman with a diagnosis of pancreatic carcinoma with multiple liver metastases. She had family histories of pancreatic cancer, but no personal or family history of malignant melanoma. Whole exon sequencing detected a germline CDKN2A variant evaluated as likely pathogenic. The results were disclosed to her daughters after she died, and the same CDKN2A variant was detected in one of the daughter. The daughter was referred to a nearby hospital for her clinical management. The second case is a 65-year-old man with pancreatic ductal adenocarcinoma. He had family histories of pancreatic cancer, but no personal or family history of malignant melanoma. He underwent a comprehensive genomic profiling test using pancreatic cancer tissue, and detected a presumed germline pathogenic variant of CDKN2A. Germline testing confirmed the same CDKN2A variant. Genetic analysis of his relatives produced negative results. Other blood relatives are scheduled for genetic analysis in the future. We report two families with familial pancreatic cancer with suspected pathogenic variants of CDKN2A that were incidentally identified through comprehensive genomic profiling. CONCLUSIONS: In current Japanese precision medicine, comprehensive genetic analysis can reveal rare genetic syndromes and offer us the opportunity to provide health management for patients and their relatives. However, gene-specific issues are raised in terms of the evaluation of a variant's pathogenicity and the extent of surveillance of the at-risk organs due to a lack of genetic and clinical data concerning CDKN2A variant carriers in Japan.

Positive impact of laparoscopic hepatectomy versus open hepatectomy on body size-corrected bleeding in obese patients.

PURPOSE: Laparoscopic hepatectomy (LH) is reported to cause less bleeding than open hepatectomy (OH) in obese patients; however, there are no reports addressing this issue in terms of body size-corrected bleeding. METHODS: The subjects of this study were 31 obese and 149 non-obese patients who underwent LH and 32 obese and 245 non-obese patients who underwent OH. Bleeding corrected for body surface area (C-BL) was compared between the obese and non-obese patients who underwent each procedure. A multivariate analysis for increased C-BL was performed using the median C-BL for each procedure. RESULTS: The median C-BL tended to be higher in the obese patients than in the non-obese patients who underwent LH, but there was no significant difference (72 vs. 42 mL/m2, P = 0.050). However, it was significantly higher in the obese patients than in the non-obese patients who underwent OH (542 vs. 333 mL/m2, P = 0.002). In a multivariate analysis, for OH, sectionectomy or more (OR 3.20, P < 0.001) and a high BMI (OR 2.76, P = 0.018) were found to be independent risk factors, whereas for LH, a high BMI was not (OR 1.58, P = 0.301). CONCLUSIONS: Obesity was identified as a risk factor for increased bleeding with body size correction for OH, but the risk was reduced for LH.

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.

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.

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.

Prognostic Role of Preoperative Duke Pancreatic Monoclonal Antigen Type 2 Levels in Patients with Pancreatic Cancer.

BACKGROUND: This study aimed to evaluate the clinical implication of Duke pancreatic monoclonal antigen type 2 (DUPAN-2) for patients with pancreatic cancer (PC), especially those with normal carbohydrate antigen (CA) 19-9 levels. METHODS: The study reviewed 224 patients who underwent surgery for PC from January 2003 through December 2019 at the Shizuoka Cancer Center. The patients were divided into three groups according to the following CA19-9 and DUPAN-2 levels: normal CA19-9/normal DUPAN-2, normal CA19-9/high DUPAN-2, and high CA19-9. The prognostic utility of the DUPAN-2 levels in the normal CA19-9 patients was investigated. RESULTS: Elevated serum levels of DUPAN-2 were observed in 29 (25.2%) of the normal CA19-9 patients. The cutoff value for serum DUPAN-2 level was set at 250 U/ml. Both disease-free survival and disease-specific survival (DSS) in the normal CA19-9/high DUPAN-2 group were significantly shorter than in the normal CA19-9/normal DUPAN-2 group and comparable with those in the high CA19-9 group. In the normal CA19-9 group, DUPAN-2 was identified as an independent prognostic factor for DSS. The patients with normal CA19-9/high DUPAN-2 had higher pathologic malignancy than the patients with normal CA19-9/normal DUPAN-2, which was comparable with that in the patients with high CA19-9. CONCLUSION: In PC, DUPAN-2 may be useful as a biomarker complementary with CA19-9. The combination of these two markers may aid in the preoperative prediction of prognosis for patients with PC.

Multi-institutional phase II study of ultra-hypofractionated whole-breast irradiation after breast-conserving surgery for breast cancer in Japan: Kyoto Radiation Oncology Study Group (UPBEAT study).

PURPOSE: The UK-FAST-Forward study showed that ultra-hypofractionated whole-breast irradiation (ultra-HF-WBI) involving five fractions of 26 Gy radiation over 1 week was not inferior to HF-WBI. However, it is not used in Japan due to safety concerns. In April 2022, we commenced a multi-institutional, single-arm, phase II trial. Our aim is to confirm the safety of ultra-HF-WBI after breast-conserving surgery (BCS) for breast cancer in Japanese women. METHOD: We plan to enroll 98 patients from 13 institutions. The primary endpoint is the proportion of late adverse events of grades ≥2 within 3 years. DISCUSSION: We believe that this highly promising clinical study can positively impact the Japanese guidelines for breast cancer treatment. The results will help us decide whether or not ultra-HF-WBI can be used as a more convenient alternative to WBI. REGISTRATION NUMBER AND DATE: This trial was registered in the UMIN Clinical Trials Registry (UMIN000047080) on March 4, 2022.

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.

Long-term adjuvant chemotherapy after resection for pancreatic cancer patients with positive peritoneal lavage cytology.

PURPOSE: The significance of resection for pancreatic cancer with positive peritoneal lavage cytology (CY +) remains controversial, and the lack of evidence concerning adjuvant chemotherapy (AC) in these patients remains an issue. The aim of the present study was to investigate the prognostic impacts of AC and its duration on the survival outcome in patients with CY + pancreatic cancer. METHODS: A total of 482 patients with pancreatic cancer who underwent pancreatectomy between 2006 and 2017 were retrospectively analyzed. The overall survival (OS) was compared among the patients with CY + tumors according to the duration of AC. RESULTS: Among the resected patients, 37 (7.7%) had CY + tumors: 13 received AC for > 6 months, 15 received AC for ≤ 6 months and 9 did not receive AC. The OS of 13 patients with resected CY + tumors who received AC for > 6 months was comparable to that of 445 patients with resected CY- tumors (median survival time 43.0 vs. 33.6 months, P = 0.791), and was significantly better than that of 15 patients with resected CY + tumors who received AC for ≤ 6 months (vs. 16.6 months, P = 0.017). The duration of AC (> 6 months) was an independent prognostic factor in patients with resected CY + tumors (hazard ratio 3.29, P = 0.005). CONCLUSION: Long-term AC (> 6 months) may improve postoperative survival in pancreatic cancer patients with CY + tumors.

Impact of obstructive ventilatory impairment on intraoperative bleeding during laparoscopic hepatectomy.

PURPOSE: An animal model of laparoscopic hepatectomy showed that bleeding from the hepatic vein is influenced by airway pressure. However, there are little research reports on how airway pressure leads to risks in clinical practice. The main objective of this study was to investigate the impact of preoperative forced expiratory volume % in 1 s (FEV1.0%) on intraoperative blood loss in laparoscopic hepatectomy. METHODS: All patients who underwent pure laparoscopic or open hepatectomy from April 2011 to July 2020 were classified into two groups by preoperative spirometry: those with obstructive ventilatory impairment (obstructive group; FEV1.0% < 70%) and those with normal respiratory function (ormal group; FEV1.0% ≥ 70%). Massive blood loss was defined as 400 mL for laparoscopic hepatectomy. RESULTS: In total, 247 and 445 patients underwent pure laparoscopic and open hepatectomy, respectively. Regarding laparoscopic hepatectomy group, blood loss was significantly greater in the obstructive group (122 vs. 100 mL, P = 0.042). Multivariate analysis revealed that high IWATE criteria which classify the surgical difficulty of laparoscopic hepatectomy (≥ 7, odds ratio (OR): 4.50, P = 0.004) and low preoperative FEV1.0% (< 70%, OR: 2.28, P = 0.043) were independent risk factors for blood loss during laparoscopic hepatectomy. In contrast, FEV1.0% did not affect the blood loss (522 vs. 605 mL, P = 0.113) during open hepatectomy. CONCLUSION: Obstructive ventilatory impairment (low FEV1.0%) may affect the amount of bleeding during laparoscopic hepatectomy.

Secondary Budd-Chiari syndrome occurred after adjuvant radiotherapy for perihilar cholangiocarcinoma: a case report.

BACKGROUND: Budd-Chiari syndrome (BCS) is a rare vascular disorder of the liver, and acute and secondary BCS is even rarer. CASE PRESENTATION: A 62-year-old man with perihilar cholangiocarcinoma of Bismuth type IIIa underwent right hemi-hepatectomy with caudate lobectomy and pancreatoduodenectomy. Adjuvant chemoradiotherapy was performed due to a positive hepatic ductal margin. Subsequently, the disease passed without recurrence. The patient visited for acute onset abdominal pain at the 32nd postoperative month. Multidetector-row computed tomography (MDCT) showed stenosis of the left hepatic vein (LHV) root, which was the irradiated field, and thrombotic occlusion of the LHV. The patient was diagnosed with acute BCS caused by adjuvant radiotherapy. Although anticoagulation therapy was performed, the patient complained of sudden upper abdominal pain again. MDCT showed an enlarged LHV thrombus and hepatomegaly. The patient was diagnosed with exacerbated acute BCS, and stenting for the stenotic LHV root was performed with a bare stent. Although stenting for the LHV root was very effective, restenosis occurred twice due to thrombus in the existing stent, so re-stenting was performed twice. The subsequent clinical course was acceptable without recurrence or restenosis of the LHV root as of 6 months after the last stenting using a stent graft. CONCLUSION: Although no case of BCS caused by radiotherapy has yet been reported, the present case showed that late side effect of radiotherapy can cause hepatic vein stenosis and secondary BCS.

Vascular resection for distal cholangiocarcinoma.

PURPOSE: Vascular resection (VR) is extended surgery to attain a negative radial margin (RM) for distal cholangiocarcinoma (DCC). The present study explored the significance of VR for DCC, focusing on VR, RM, and findings suggestive of vascular invasion on multidetector-row computed tomography (MDCT). METHODS: Patients with DCC who underwent resection between 2002 and 2019 were reviewed. RESULTS: Among 230 patients, 25 received VR. The overall survival (OS) in the VR group was significantly worse than in the non-VR group (16.7% vs. 50.7% at 5 years, P < 0.001). Patients who underwent VR with a negative RM failed to show a better OS than those who did not undergo VR with a positive RM (19.7% vs. 35.7% at 5 years, P = 0.178). Of the 30 patients who were suspected of having vascular invasion on MDCT, 11 did not receive VR because the vessels were freed from the tumor; these patients had a significantly better OS (57.9% at 5 years) than those who underwent VR. CONCLUSIONS: VR for DCC was associated with a poor prognosis, even if a negative RM was obtained. VR is not necessary for DCC when the vessels are detachable from the tumor.

The proximity of the middle hepatic vein to the hepatic hilus: a retrospective radiological study.

PURPOSE: The middle hepatic vein (MHV) is an important landmark in anatomical hemihepatectomy. The proximity between the MHV and the hilar plate was suspected to be associated with tumor exposure during left hemihepatectomy for advanced perihilar cholangiocarcinoma and is reported to facilitate a dorsal approach to the MHV during laparoscopic hemihepatectomy. However, the precise distance between these locations is unknown. METHODS: To investigate the "accurate and normal" distance between the MHV and the hilar plate, the present study focused on patients who presented without perihilar tumor. One hundred and sixty-eight consecutive patients who underwent pancreatoduodenectomy were included. Retrospective radiological measurement was performed using preoperative multi-detector row CT. The optimized CT slices perpendicular to the MHV were made using the multiplanar reconstruction technique. The shortest distance between the MHV and the hilar plate was measured on the left and right sides on the perpendicular slices. The diameters of the left and right hepatic ducts were also measured. RESULTS: The distance was 9.0 mm (1.9-20.0 mm) on the left side and 11.3 mm (2.3-21.8) on the right side (p < 0.001). The distance on the left side was < 10 mm in 60% of patients (n = 100). Only one-third of patients (n = 55) had a distance of ≥ 10 mm on both sides. As the hepatic ducts became more dilated, the distance from the MHV to the hilar plate became shorter. CONCLUSION: The MHV was located in close proximity to the hepatic hilus, especially on the left side.

Early Recurrence in Resected Gallbladder Carcinoma: Clinical Impact and Its Preoperative Predictive Score.

BACKGROUND: Surgical resection is the only potentially curative therapy for gallbladder carcinoma (GBC). However, the postoperative recurrence rate is high (approximately 50%), and recurrence occasionally develops early after surgery. PATIENTS AND METHODS: A total of 139 patients who underwent macroscopically curative resection for GBC between 2002 and 2018 were retrospectively reviewed. Early recurrence (ER) was defined as recurrence within 6 months after surgery. Univariate and multivariate logistic regression analysis was performed using preoperative factors that may influence early recurrence, namely patient background factors, tumor markers, imaging findings, and body composition parameters obtained preoperatively, to create a predictive score for ER. RESULTS: The median follow-up period was 21.9 months (range, 6.2-195.7 months). Postoperative recurrence was observed in 55 (39.6%) patients, of whom 14 (25.5%) developed ER. The median overall survival after surgery was 104.7 months for the non-ER group and 15.7 months for the ER group. On multivariate analysis, high carbohydrate antigen 19-9, low muscle attenuation, high visceral fat attenuation, liver invasion, and other organ invasion on preoperative computed tomography were identified as independent risk factors for ER. A preoperatively predictive scoring system for ER was constructed by weighting the above five factors. The nomogram showed an area under the curve of 0.881, indicating good predictive potential for ER. CONCLUSIONS: ER in resected GBC indicates a very poor prognosis. The present preoperative scoring system can sufficiently predict ER and may be helpful in determining the optimal treatment strategies.

The Association Between Neoadjuvant Therapy and Pathological Outcomes in Pancreatic Cancer Patients After Resection: Prognostic Significance of Microscopic Venous Invasion.

BACKGROUND: The impact of neoadjuvant therapy (NAT) on pathological outcomes, including microscopic venous invasion (MVI), remains unclear in pancreatic cancer. METHODS: A total of 456 patients who underwent pancreatectomy for resectable and borderline resectable pancreatic cancer between July 2012 and February 2020 were retrospectively reviewed. Patients were divided into two groups: patients with NAT (n = 120, 26%) and those without NAT (n = 336, 74%). Clinicopathological factors, survival outcomes and recurrence patterns were analyzed. RESULTS: Regarding pathological findings, the proportion of MVI was significantly lower in patients with NAT than in those without NAT (43% vs 62%, P = 0.001). The 5-year survival rate in patients with NAT was significantly better than that in those without NAT (54% vs 45%, P = 0.030). A multivariate analysis showed that MVI was an independent prognostic factor for the overall survival (OS) (hazard ratio 2.86, P = 0.003) in patients who underwent NAT. MVI was an independent risk factor for liver recurrence (odds ratio [OR] 2.38, P = 0.016) and multiple-site recurrence (OR 1.92, P = 0.027) according to a multivariate analysis. The OS in patients with liver recurrence was significantly worse than that in patients with other recurrence patterns (vs lymph node, P = 0.047; vs local, P < 0.001; vs lung, P < 0.001). The absence of NAT was a significant risk factor for MVI (OR 1.93, P = 0.007). CONCLUSION: MVI was a crucial prognostic factor associated with liver and multiple-site recurrence in pancreatic cancer patients with NAT. MVI may be reduced by NAT, which may contribute to the improvement of survival in pancreatic cancer patients.

Resectability Status of Pancreatic Cancer Having Tumor Contact with an Aberrant Right Hepatic Artery: Is Upfront Surgery Justified?

BACKGROUND: The NCCN guidelines define pancreatic cancer that has contact with an aberrant right hepatic artery (A-RHA) as a borderline-resectable tumor. However, the impact of tumor contact with an A-RHA on surgical and survival outcomes has not been well discussed. METHODS: A total of 541 patients who underwent pancreatoduodenectomy for resectable and borderline-resectable pancreatic cancer between 2002 and 2019 were retrospectively analyzed. The presence of an A-RHA and tumor contact with an A-RHA were evaluated based on the preoperative computed tomography findings. Patients with resectable tumors and tumors with A-RHA-contact (having contact with an A-RHA without involvement of the major arteries) were generally treated by upfront surgery, whereas those with borderline-resectable tumors generally underwent neoadjuvant therapy and subsequent resection. RESULTS: Among the 541 patients, 116 (21.4%) had an A-RHA and 15 (2.8%) had tumor with A-RHA-contact. The A-RHA was resected in 12, and arterial reconstruction was performed in 8. The rates of morbidity and R1 resection in patients with an A-RHA (32.8 and 10.3%, respectively) were comparable to those without an A-RHA (27.3 and 11.3%, respectively). The overall survival in patients with A-RHA-contact was significantly worse than that in patients with borderline-resectable tumors (median survival time, 14.6 vs. 35.3 months, p = 0.048). CONCLUSIONS: Although upfront resection was safely performed and led to a high R0 resection rate in patients with A-RHA-contact, the survival outcome was dismal. A tumor with A-RHA-contact should be regarded as technically resectable but oncologically borderline-resectable. Upfront surgery may not be appropriate for patients with A-RHA-contact.

Overview and clinical significance of multiple mutations in individual genes in hepatocellular carcinoma.

BACKGROUND: Multiple mutation (MM) within a single gene has recently been reported as a mechanism involved in carcinogenesis. The present study investigated the clinical significance of MMs in hepatocellular carcinoma (HCC). METHODS: Two hundred twenty-three surgically resected HCCs were subjected to gene expression profiling and whole-exome sequencing. RESULTS: MMs in individual genes were detected in 178 samples (MM tumors: 79.8%). The remaining samples all carried a single mutation (SM tumors: 20.2%). Recurrence-free survival in the MM group was significantly worse in comparison to the SM group (P = 0.012). A Cox proportional hazard analysis revealed that MM tumor was an independent predictor for worse a prognosis (hazard ratio, 1.72; 95% confidence interval, 1.01-3.17; P = 0.045). MMs were frequently observed across in various genes, especially MUC16 (15% of samples had at least one mutation in the gene) and CTNNB1 (14%). Although the MUC16 mRNA expression of MUC16 wild-type and MUC16 SM tumors did not differ to a statistically significant extent, the expression in MUC16 MM tumors was significantly enhanced in comparison to MUC16 SM tumors (P < 0.001). In MUC16, MMs were associated with viral hepatitis, higher tumor marker levels and vascular invasion. The MUC16 MMs group showed significantly worse recurrence-free survival in comparison to the MUC16 SM group (P = 0.022), while no significant difference was observed between the MUC16 SM group and the MUC16 wild-type group (P = 0.324). CONCLUSIONS: MM was a relatively common event that may occur selectively in specific oncogenes and is involved in aggressive malignant behavior.