Relationships between postoperative recurrences and standardized uptake value on 18F-fluorodeoxyglucose-positron emission tomography in patients with resectable and borderline resectable pancreatic ductal adenocarcinoma who underwent curative pancreatic resection after neoadjuvant chemoradiotherapy.

BACKGROUND: This study aimed to examine postoperative recurrence after curative pancreatic resection following neoadjuvant chemoradiotherapy (NACRT) in patients with resectable (R-) and borderline resectable (BR-) pancreatic ductal adenocarcinoma (PDAC), focusing on its relationship with the standardized uptake value (SUV) on 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET). METHOD: The postoperative initial recurrence patterns were examined in patients with R- and BR-PDAC who underwent NACRT followed by curative pancreatic resection. Data collected from three prospective clinical trials were retrospectively analysed. RESULTS: After a median follow-up of 29 months, 91 (60 %) of 151 patients experienced postoperative recurrence. The median recurrence-free survival (RFS) for all patients was 18 months. The sites of first recurrence were lung-only in 24 (26 %) patients, liver-only in 23 (25 %), local-only in 11 (12 %), peritoneum-only in 10 (11 %), other single site in 5 (5 %), and multiple sites in 19 (21 %) patients. Multivariate analysis identified the maximum standardized uptake value (SUVmax) on FDG-PET at diagnoses ≥5.40 (hazard ratio [HR], 1.62; 95 % confidence interval [CI], 1.01-2.61; p = 0.045) and node-positive pathology (HR, 2.01; 95 % CI, 1.32-3.08; p = 0.001) as significant predictors of RFS. Furthermore, the SUVmax at initial diagnosis and after NACRT correlated with liver metastasis. CONCLUSION: R- and BR-PDACs with high SUV on FDG-PET at diagnosis are risk factors for postoperative recurrence. Among patients who undergo surgery after NACRT, those with a high SUVmax at diagnosis or post-NACRT require careful attention for postoperative liver recurrence.

[A Case of Intrahepatic Cholangiocarcinoma and Early Postoperative Recurrences Using Comprehensive Genome Profiling to Implement Effective Treatment].

Subsequent to a medical examination, a 61-year-old male was referred to our hospital with jaundice. He was diagnosed with intrahepatic cholangiocarcinoma involving the hepatic hilum and was referred to our department to undergo a left trisectionectomy of the liver, extrahepatic bile duct resection, and regional lymphadenectomy. He was discharged on postoperative day 39 without liver failure. Two months postoperatively, positron-emission tomography/computed tomography(PET/ CT)indicated recurrences in the bone, and paraaortic lymph node. Gemcitabine and cisplatin combination first-line therapy was administered. Disease progression occurred after 4 courses of therapy. Gene panel testing was performed and the patient was switched to pembrolizumab owing to high microsatellite instability. After 2 courses of pembrolizumab, notable shrinkage of the paraaortic lymph node recurrence was confirmed on computed tomography as well as a partial response. PET-CT revealed disappearance of abnormal accumulation in all lesions at 20 months postoperatively. This has been sustained for 24 months following surgery without remarkable immune-related side-effects.

Prognostic Significance of 18F-FDG PET/CT and Tumor Metabolic Changes in Patients With Pancreatic Ductal Adenocarcinoma.

BACKGROUND/AIM: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is reportedly associated with the malignant potential of cancer. This study aimed to evaluate the association between FDG accumulation and tumor metabolism in pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: A prognostic analysis of data from 131 patients with PDAC who underwent FDG-PET/CT before curative-intent pancreatic surgery was performed. Capillary electrophoresis-mass spectrometry (CE-MS) was used to analyze the metabolome of tumor and non-neoplastic pancreas from 80 patients. These patients were divided into two groups: low SUVmax group (SUVmax <6.09) and high SUVmax group (SUVmax ≥6.09). RESULTS: Carbohydrate antigen 19-9 (CA19-9), maximum standardized uptake value (SUVmax) of PET, N stage, and postoperative chemotherapy were identified as significant prognostic factors by univariate analysis. SUVmax emerged as an independent prognostic factor for overall survival [hazard ratio (HR)=1.88, p<0.05] and disease-free survival (HR=2.01, p<0.05) in multivariate analysis. Metabolic analyses confirmed that 43 metabolites significantly differed depending on the accumulation of SUV in tumors. Metabolites involved in the removal of reactive oxygen species (e.g., hypotaurine, glutathione, Met), treatment resistance (UDP-N-acetylglucosamine), and proliferation (e.g., choline, leucine, isoleucine) were increased in the high SUVmax group. CONCLUSION: FDG accumulation is an important independent prognostic factor reflecting tumor activity associated with metabolic changes in cancer cells.

A rare case of hypervirulent Klebsiella pneumoniae liver abscess and bacterial endophthalmitis associated with distal bile duct cancer.

We report a case of a patient with distal bile duct cancer who presented with ocular pain and eye redness due to a liver abscess. The patient developed a liver abscess while waiting for surgery. Since Klebsiella pneumoniae with high viscosity was identified and imaging studies showed systemic infection, a diagnosis of klebsiella invasive syndrome was made. In addition, infectious intraocular inflammation was also observed at the same time. In addition to antibiotic therapy, vitrectomy and percutaneous transhepatic abscess drainage successfully normalized the inflammatory response and negative blood cultures were obtained. Thirty-four days after the start of treatment, surgery was performed and the postoperative course was uneventful, and the patient was discharged from the hospital on the 39th postoperative day. Forty-six months after that surgery, there has been no evidence of recurrence of cholangiocarcinoma or recurrence of infection, but unfortunately, vision loss in the right eye remains. Some Klebsiella pneumoniae are highly pathogenic and are often reported from Southeast Asia, and ocular pain and hyperemic symptoms are important physical findings.

A case of chronic expanding hematoma mimicking a cystic pancreatic tumor.

BACKGROUND: A chronic expanding hematoma is an uncommon entity described as an organized blood collection that increases in size after the initial hemorrhagic event without histological neoplastic features. The standard treatment is complete resection. To our knowledge, this is the first report of a chronic expanding hematoma mimicking a pancreatic cystic tumor that has been successfully resected utilizing a laparoscopic approach. CASE PRESENTATION: We report the case of a 32-year-old man with a 10-cm chronic expanding hematoma that was preoperatively diagnosed as a cystic pancreatic tumor. Dynamic computed tomography revealed a cyst at the inferior part of the uncinate process of the pancreas without contrast enhancement. His blood biochemical data were within normal limits. The operation initially utilized a laparoscopic approach; however, the procedure was converted to hand-assisted laparoscopic surgery due to capsule adherence to surrounding organs and finally, enucleation of the tumor was performed. Pathological findings revealed a chronic expanding hematoma in the retroperitoneal space. CONCLUSION: Chronic expanding hematoma in the retroperitoneal space is so rare and sometimes adheres to the surrounding tissue. It is difficult to distinguish hematoma attaching pancreas and pancreatic cyst preoperatively. In rare cases such as this, hand-assisted laparoscopic surgery is a feasible, less invasive procedure for facilitating complete resection and preventing recurrence.

Short- and Long-Term Outcomes of Neoadjuvant Chemoradiotherapy Followed by Pancreatoduodenectomy in Elderly Patients with Resectable and Borderline Resectable Pancreatic Cancer: A Retrospective Study.

Background: The efficacy of neoadjuvant chemoradiotherapy (NACRT) followed by pancreatoduodenectomy (PD) in elderly patients with pancreatic ductal adenocarcinoma (PDAC) remains unclear. Methods: This retrospective analysis of prospectively collected data examined the effect of NACRT followed by PD in elderly patients with PDAC. A total of 112 patients with resectable (R-) and borderline resectable (BR-) PDAC, who were planned for PD and received NACRT between 2009 and 2022, were assessed. Changes induced by NACRT, surgical outcomes, nutritional status, renal and endocrine functions, and prognosis were compared between elderly (≥75 years, n = 43) and non-elderly (<75 years, n = 69) patients over two years following PD. Results: Completion and adverse event rates during NACRT, nutritional status, renal function, endocrine function over two years postoperatively, and prognosis did not significantly differ between the two groups. Low prognostic index after NACRT and the absence of postoperative adjuvant chemotherapy may be adverse prognostic indicators for elderly patients undergoing NACRT for R- and BR-PDAC. Conclusions: Despite a higher incidence of postoperative complications, NACRT followed by PD can be safely performed in elderly patients, resulting in a prognosis similar to that in non-elderly patients.

A combined score for predicting clinically relevant postoperative pancreatic fistula based on inflammatory parameters and drainage fluid culture results on postoperative day 3.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreatic resection can lead to severe postoperative complications. POPF is defined based on postoperative day (POD) 3 drainage fluid amylase level. POPF correlates with inflammatory parameters as well as drainage fluid bacterial infection. However, a standardized model based on these factors for predicting CR-POPF remains elusive. We aimed to identify inflammatory parameter- and drainage fluid culture-related risk factors for CR-POPF on POD 3 after pancreatoduodenectomy (PD) and distal pancreatectomy (DP). METHODS: Data from 351 patients who underwent PD or DP between 2013 and 2022 at a single institution were retrospectively analyzed. Risk factors for CR-POPF were investigated using multivariate analyses, and a prediction model combining the risk factors for CR-POPF was developed. RESULTS: Of the 351 patients, 254 and 97 underwent PD and DP, respectively. Multivariate analyses revealed that drainage fluid amylase level ≥722 IU/L, culture positivity, as well as neutrophil count ≥5473/mm3 on POD 3 were independent risk factors for CR-POPF in PD group. Similarly, drainage fluid, amylase level ≥500 IU/L, and culture positivity on POD 3 as well as pancreatic thickness ≥11.1 mm were independent risk factors in the DP group. The model for predicting CR-POPF achieved the maximum overall accuracy rate when the number of risk factors was ≥2 in both the PD and DP groups. CONCLUSIONS: Inflammatory parameters on POD 3 significantly influence the risk of CR-POPF onset after pancreatectomy. The combined models based on these values can accurately predict the risk of CR-POPF after pancreatectomy.

Predictive role of the prognostic nutritional index in patients with pancreatic ductal adenocarcinoma who underwent neoadjuvant chemoradiotherapy followed by curative pancreatic resection: A retrospective study using prospectively collected data.

BACKGROUND: Despite a strong association between nutritional indices and disease prognosis, evidence regarding the evaluation of nutritional indices after preoperative treatment for pancreatic ductal adenocarcinoma (PDAC) is insufficient. We evaluated the clinical significance of the prognostic nutritional index (PNI) in patients with resectable (R-) and borderline resectable (BR-) PDAC who received neoadjuvant chemoradiotherapy (NACRT) followed by pancreatic resection. METHODS: We assessed 153 patients with R- and BR-PDAC who underwent NACRT followed by curative resection between 2009 and 2022. We evaluated the association between preoperative PNI after NACRT and short- and long-term outcomes. RESULTS: The median preoperative PNI value after NACRT was 42.1, and the optimal cutoff value from the time-dependent receiver operating characteristic curve was 38.6. The low PNI group (PNI < 38.6, n = 44) exhibited significantly worse inflammatory parameters, surgical outcomes, and prognoses than the high PNI group (PNI ≥ 38.6, n = 109). Multivariate analysis identified preoperative PNI ≤ 38.6 (hazard ratio [HR]: 2.32, 95% confidence interval [CI]: 1.00-5.38, p = .049), blood loss ≥1642 mL (HR: 3.05, 95% CI: 1.65-5.64, p < .001), node positive pathology (HR: 2.10, 95% CI: 1.32-3.34, p = .002), and lack of postoperative adjuvant chemotherapy (HR: 3.55, 95% CI: 2.05-6.15, p < .001) as significant predictors of overall survival. CONCLUSIONS: For patients with R- and BR-PDAC receiving preoperative treatment, it is imperative to closely monitor their nutritional status when determining the optimal surgical procedure timing.

Serum Carbohydrate Antigen 19-9 and Metabolite Hypotaurine Are Predictive Markers for Early Recurrence of Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: A significant number of patients experience early recurrence after surgical resection for pancreatic ductal adenocarcinoma (PDAC), negating the benefit of surgery. The present study conducted clinicopathologic and metabolomic analyses to explore the factors associated with the early recurrence of PDAC. MATERIALS AND METHODS: Patients who underwent pancreatectomy for PDAC at Kagawa University Hospital between 2011 and 2020 were enrolled. Tissue samples of PDAC and nonneoplastic pancreas were collected and frozen immediately after resection. Charged metabolites were quantified by capillary electrophoresis-mass spectrometry. Patients who relapsed within 1 year were defined as the early recurrence group. RESULTS: Frozen tumor tissue and nonneoplastic pancreas were collected from 79 patients. The clinicopathologic analysis identified 11 predictive factors, including preoperative carbohydrate antigen 19-9 levels. The metabolomic analysis revealed that only hypotaurine was a significant risk factor for early recurrence. A multivariate analysis, including clinical and metabolic factors, showed that carbohydrate antigen 19-9 and hypotaurine were independent risk factors for early recurrence ( P = 0.045 and P = 0.049, respectively). The recurrence-free survival rate 1 year after surgery with both risk factors was only 25%. CONCLUSIONS: Our results suggested that tumor hypotaurine is a potential metabolite associated with early recurrence. Carbohydrate antigen 19-9 and hypotaurine showed a vital utility for predicting early recurrence.

Tumor location, clinicopathological features, and perioperative and prognostic outcomes in patients who underwent pancreatic resection following neoadjuvant chemoradiotherapy for resectable pancreatic cancer: A retrospective study.

BACKGROUND: /Objective: Preoperative treatment of resectable pancreatic ductal adenocarcinoma (PDAC) is gaining popularity worldwide. However, the characteristics of tumors located in the pancreatic head (Ph), or those in the body or tail (Pbt), after surgery following neoadjuvant chemoradiotherapy (NACRT) remain unclear. This study aimed to evaluate and compare the clinicopathological features, perioperative outcomes, and prognosis of patients with resectable PDAC who underwent NACRT followed by curative pancreatic resection, focusing on distinguishing between Ph and Pbt PDACs. METHODS: We included 107 patients with resectable PDAC who underwent curative resection following NACRT between 2009 and 2023. Clinicopathological features, perioperative and prognostic outcomes, recurrence patterns, and prognoses were compared between Ph and Pbt PDAC groups. RESULTS: Tumors were found in the Ph and Pbt in 64 and 43 patients, respectively. Albumin levels and lymphocyte-to-monocyte ratios after NACRT were significantly lower in the Ph group than in the Pbt group. The Pbt group showed significantly higher rates of positive peritoneal lavage cytology and serosal, arterial, and portal vein invasion than the Ph group did. Overall and recurrence-free survival were similar between the two groups. The most common site of initial postoperative recurrence was the lung only in both groups; however, the rate of peritoneal dissemination only was significantly higher in the Pbt group than in the Ph group. CONCLUSIONS: The prognoses based on tumor locations in the Ph and Pbt after surgery following NACRT are similar. Following the resection of resectable Pbt PDAC, the possibility of peritoneal dissemination recurrence should be considered.

Tumor-to-blood pool ratio of 18F-fluorodeoxyglucose-positron emission tomography's standardized uptake value as a useful parameter indicating malignant transformation in pancreatic branch-duct intraductal papillary mucinous neoplasm compared to the international Fukuoka guidelines: a retrospective cohort study from surgical resections.

BACKGROUND: Identifying malignant transformation in pancreatic branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) remains challenging, but the standardized uptake value (SUV) obtained from 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT has the potential to become a valuable parameter for differentiation. This study aimed to assess the effectiveness of SUV of FDG-PET/CT in distinguishing low-grade dysplasia (LGD), high-grade dysplasia (HGD), and intraductal papillary mucinous carcinoma (IPMC) within BD-IPMNs. METHODS: We assessed 58 patients with confirmed BD-IPMN undergoing surgery between 2008 and 2022. Receiver operating characteristic curves were plotted using the tumor-to-blood pool ratio (TBR) of FDG-PET/CT in two scenarios: one considering HGD + IPMC as positive and the other considering only IPMC as positive. RESULTS: In the cohort of 58 cases, there were 39 females, and the median age was 71 years. The median TBR value was 1.45 (range, 0.35-25.44). The TBRs exhibited a significant correlation with each histopathology (p < 0.001). Furthermore, in the multivariate analysis, TBR was independently significant in both scenarios, with HGD + IPMC defined as malignant (p = 0.001) and with only IPMC defined as malignant (p = 0.024). CONCLUSIONS: TBR might have the potential to serve as a valuable parameter for indicating malignant transformation in pancreatic BD-IPMNs.

Internal hernia after laparoscopic sigmoidectomy with splenic flexural mobilization and high ligation of the inferior mesenteric vein: A case report.

Several studies have recently reported the rare occurrence of internal herniation of the small bowel after laparoscopic colorectal surgery. Most cases of internal herniation after laparoscopic colorectal surgery occur due to a mesenteric defect. However, there have been no reports on the indications for closing mesenteric defects to prevent the development of an internal hernia. This study reports a case of an internal hernia of the proximal jejunum near the ligament of Treitz in a patient who underwent laparoscopic sigmoidectomy with splenic flexural mobilization and high ligation of the inferior mesenteric vein. Assessing the risk for internal herniation before completing the initial surgery is crucial. Additionally, mesenteric defect closure should be performed to prevent the development of internal hernias among patients with a potential risk.

P53 immunolabeling in EUS-FNA biopsy can predict low resection rate and early recurrence in resectable or borderline resectable pancreatic cancer treated with neoadjuvant therapy.

PURPOSE: KRAS, P16, TP53, and SMAD4/DPC4 mutations are common in pancreatic ductal adenocarcinoma (PDAC). The study aimed to evaluate the association between gene mutations in pre-treatment endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) samples and clinical outcomes of patients with PDAC. METHODS: There were 43 patients with resectable (R) PDAC and 41 patients with borderline resectable (BR) PDAC. CDKN2A/p16, TP53, and SMAD4/DPC4 were evaluated through immunohistochemistry (IHC) of pretreatment EUS-FNA (n = 84) and resected specimens (n = 71). All patients received neoadjuvant therapy. RESULTS: IHC of EUS-FNA specimens revealed p16 loss in 61 (73%), abnormal p53 in 61 (73%), and Smad4 loss in 38 (45%) patients. Abnormal p53 was associated with a lower resection rate (p = .017). Abnormal p53 and Smad4 loss were associated with recurrence within 6 months post-pancreatectomy (p = .03, p = .03, respectively). Univariate Cox regression analysis was conducted to reveal that abnormal p53 (p = .07), p16 loss and abnormal p53 (p = .04), and Smad4 and p16 loss (p = .03) were associated with poor prognosis. CONCLUSIONS: Pre-treatment abnormal labeling of p53 in EUS-FNA specimen was associated with a lower resection rate and an early recurrence in R or BR PDAC cases.

Efficacy of neoadjuvant chemoradiotherapy followed by pancreatic resection for older patients with resectable and borderline resectable pancreatic ductal adenocarcinoma.

BACKGROUND: The benefit of preoperative treatment followed by pancreatic resection in older patients with pancreatic ductal adenocarcinoma (PDAC) remains unclear. In this retrospective analysis of prospectively collected data, we evaluated the significance and safety of preoperative treatment followed by curative resection for older PDAC patients. METHODS: We evaluated 122 patients with resectable and borderline resectable PDAC who received neoadjuvant chemoradiotherapy (NACRT) followed by curative resection between 2009 and 2019. Changes in the prognostic nutritional indices during NACRT, surgical outcomes, and prognosis were compared between older (≥75 years, n = 44) and younger patients (<75 years, n = 78). RESULTS: The completion rate, adverse event rate, changes in prognostic nutritional indices during NACRT, and prognosis were similar between the groups. In multivariate analysis, an elevated C-reactive protein/albumin ratio (CRP/Alb) ≥ 33.1% during NACRT (p = 0.035) and no postoperative adjuvant chemotherapy (p = 0.041) were identified as significant predictors of overall survival. CONCLUSIONS: NACRT followed by pancreatic resection could be safely performed in older patients, with a similar prognosis as that of younger patients, despite an increased frequency of postoperative complications. Elevated CRP/Alb during NACRT and no postoperative adjuvant chemotherapy were poor prognostic factors for older patients.

Risk factors associated with hypoglycemic events after total pancreatectomy: A nationwide multicenter prospective study in Japan.

BACKGROUND: The number of total pancreatectomy cases have increased worldwide, expanding the need for new insulin products and high-titer pancrelipases. However, the current data that is focused on hypoglycemic events after a total pancreatectomy from large nationwide series are still lacking. This study is aimed to assess the risk factors associated with hypoglycemic events after a total pancreatectomy. METHODS: Data were prospectively collected from 216 consecutive patients who underwent total pancreatectomies between August 2015 and December 2017 from 68 Japanese centers. Of the 216 patients, 166 with a follow-up period of 1 year were analyzed. The risk factors for hypoglycemic events at 6 and 12 months (postoperative months 6 and 12) were investigated based on the results of a nationwide multicenter prospective study. RESULTS: Of the 166 patients, 57 (34%) and 70 (42%) experienced moderate or severe hypoglycemic events or hypoglycemia unawareness on a monthly basis at postoperative months 6 and 12, respectively. Multivariate analysis revealed that body weight loss after surgery ≥0.3 kg and total cholesterol level ≤136 mg/dL at postoperative month 6, and glycated hemoglobin level ≤8.9% and rapid-acting insulin use at postoperative month 12 were independent risk factors for hypoglycemic events after a total pancreatectomy. There were different independent risk factors depending on the postoperative period. CONCLUSION: Patients with body weight loss after surgery, low total cholesterol level, strict glycemic control, and using rapid-acting insulin should be aware of the occurrence of hypoglycemic events after their total pancreatectomy. In order to prevent hypoglycemic events after a total pancreatectomy, we need to consider optimal nutritional and glycemic control according to the postoperative period.

Constrictive pericarditis caused by pericardial metastasis from esophageal squamous cell carcinoma: a case report.

Constrictive pericarditis is a rare condition characterized by clinical signs of right heart failure subsequent to the loss of pericardial compliance. We report a case of constrictive pericarditis due to pericardial metastasis in a patient with a history of esophageal squamous cell carcinoma that had a pathological complete response (pCR) to preoperative chemoradiotherapy. A 66-year-old woman was referred to our division for the treatment of advanced esophageal cancer. Video-assisted thoracoscopic surgery esophagectomy (VATSE) with 3-field lymphadenectomy was performed after neoadjuvant chemoradiotherapy (NAC-CRT). Pathological examination revealed no residual tumor, lymph node metastasis, lymphatic invasion, or vessel invasion. The histological treatment effect of the chemoradiotherapy was pathological complete response (pCR). Five months after surgery, the patient was admitted to a nearby hospital for the treatment of acute pericarditis. However, a month after admission, acute pericarditis progressed to constrictive pericarditis, and she was referred to our hospital for further management. Subsequently, urgent pericardiectomy was performed through a lower half sternotomy incision. After surgery, heart failure improved for a while but worsened again. The patient died 7 days after the surgery. Pathological examination of the resected pericardium revealed evidence of metastasis from squamous cell carcinoma of the esophagus. An autopsy revealed the spread of esophageal cancer to the bilateral pleura, right lung, pericardium, diaphragm, soft tissue surrounding the tracheal bifurcation, and bilateral hilar lymph nodes. Similarly, tumor cells were found in the lymphatic vessels of the pericardium and pleura. Even if pCR is achieved with NAC-CRT, as in our case, esophageal cancer may metastasize and present as constrictive pericarditis within a short period; therefore, careful patient follow-up is essential.

Efficacy and Safety of Neoadjuvant Chemoradiation Therapy Administered for 5 Versus 2 Weeks for Resectable and Borderline Resectable Pancreatic Cancer.

OBJECTIVES: Indications of preoperative treatment for resectable (R-) or borderline resectable (BR-) pancreatic ductal adenocarcinoma (PDAC) are unclear, and the protocol remains to be standardized. METHODS: Included 65 patients with R- and BR-PDAC with venous involvement (V-) received neoadjuvant chemoradiotherapy with S-1 and 50 Gy of radiation as the 5-week regimen. The outcomes of this group were compared with those of 52 patients who underwent S-1 and 30 Gy of radiation as the 2-week regimen, previously collected as our prospective phase II study. RESULTS: Compared with the 2-week regimen, there were no significant differences in the rate of protocol completion, adverse events, mortality and morbidity, or R0 resection in the 5-week regimen. In subgroup analyses of R-PDAC, there were no significant differences in overall survival and recurrence-free survival between the groups. In contrast, the 5-week regimen had significantly better overall survival and recurrence-free survival than the 2-week regimen for BRV-PDAC. Similar results were observed after propensity score matching analysis. CONCLUSIONS: The 5-week regimen of neoadjuvant chemoradiotherapy has good clinical efficacy and safety for R- and BRV-PDAC. The 5-week regimen could achieve better outcomes than the 2-week regimen for BRV-PDAC. In contrast, both regimens achieved similar outcomes for R-PDAC.

Tumor metabolic alterations after neoadjuvant chemoradiotherapy predict postoperative recurrence in patients with pancreatic cancer.

OBJECTIVE: We investigated the metabolic changes in pancreatic ductal adenocarcinoma to identify the mechanisms of treatment response of neoadjuvant chemoradiation therapy. METHODS: Frozen tumor and non-neoplastic pancreas tissues were prospectively obtained from 88 patients with pancreatic ductal adenocarcinoma who underwent curative-intent surgery. Sixty-two patients received neoadjuvant chemoradiation therapy and 26 patients did not receive neoadjuvant therapy (control group). Comprehensive analysis of metabolites in tumor and non-neoplastic pancreatic tissue was performed by capillary electrophoresis-mass spectrometry. RESULTS: Capillary electrophoresis-mass spectrometry detected 90 metabolites for analysis among more than 500 ionic metabolites quantified. There were significant differences in 27 tumor metabolites between the neoadjuvant chemoradiation therapy and control groups. There were significant differences in eight metabolites [1-MethylnNicotinamide, Carnitine, Glucose, Glutathione (red), N-acetylglucosamine 6-phosphate, N-acetylglucosamine 1-phosphate, UMP, Phosphocholine] between good responder and poor responder for neoadjuvant chemoradiation therapy. Among these metabolites, phosphocholine, Carnitine and Glutathione were associated with recurrence-free survival only in the neoadjuvant chemoradiation therapy group. Microarray confirmed marked gene suppression of choline transporters [CTL1-4 (SLC44A1-44A4)] in pancreatic ductal adenocarcinoma tissue of neoadjuvant chemoradiation therapy group. CONCLUSION: The present study identifies several important metabolic consequences and potential neoadjuvant chemoradiation therapy targets in pancreatic ductal adenocarcinoma. Choline metabolism is one of the key pathways involved in recurrence of the patients with pancreatic ductal adenocarcinoma who received neoadjuvant chemoradiation therapy.

Prediction of local tumor control and recurrence-free survival in patients with pancreatic cancer undergoing curative resection after neoadjuvant chemoradiotherapy.

BACKGROUND AND OBJECTIVES: There is little data on the correlation between the reduction in fluorodeoxyglucose positron emission tomography (FDG-PET) radioactive accumulation and carbohydrate antigen 19-9 (CA19-9) levels with pathological tumor responses (PTRs) and prognosis after neoadjuvant chemoradiotherapy (NACRT) for patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: This study was a retrospective analysis of prospectively collected data from 102 patients with resectable (R-) and borderline resectable (BR-) PDAC who received NACRT, followed by curative resection. Data were prospectively collected and compared between the responders and nonresponders to NACRT. RESULTS: Patients with 60% or more reduction in maximum standardized uptake value (SUVmax) on FDG-PET, with 75% or more reduction in CA19-9 levels, or with 50%-100% of tumor cells destroyed due to NACRT had significantly better recurrence-free survival (RFS) than each of the nonresponders (p = 0.028, <0.001, and 0.022, respectively). The reduction rates of SUVmax and CA19-9 levels were correlated with PTR. The combined evaluation of these biomarkers reflected RFS. CONCLUSIONS: Reduction rates of FDG uptake and CA19-9 levels were preoperative predictors of pathological response to NACRT. These biomarkers of local response had prognostic value in R-PDAC and BR-PDAC. The combined evaluation of these biomarkers allowed for reliable prediction of RFS after surgery.

[Case of Solitary Liver Metastasis of Breast Cancer Showing Minimal Differentiation from Intrahepatic Cholangiocarcinoma].

A 75-year-old woman presented to our department with a liver tumor. She had undergone left total mastectomy and axillary lymph node dissection for left breast cancer at the age of 67 years. Subsequently, she had taken an aromatase inhibitor. A follow-up abdominal echo revealed a 50 mm tumor in the liver. Based on examinations, she was diagnosed with an intrahepatic cholangiocarcinoma. She underwent laparoscopic lateral segment hepatectomy. Pathological diagnosis showed liver metastasis of the breast cancer. After surgery, she received hormonal therapy. After 5 months, multiple brain metastases appeared. She died 15 months after the liver operation.