Clinical Utility of the Combined Use of CA19-9 and DUPAN-2 in Pancreatic Adenocarcinoma.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) patients with normal carbohydrate antigen (CA) 19-9 levels can have early-stage cancer or advanced cancer without elevation of CA19-9 level; estimating their malignant potential is difficult. This study investigated the clinical utility of the combined use of preoperative CA 19-9 and Duke pancreatic monoclonal antigen type 2 (DUPAN-2) levels in patients with PDAC. METHODS: Patients who underwent curative-intent surgery for PDAC between November 2005 and December 2021 were investigated. Eligible patients were classified into four groups based on these two markers. Among patients with normal CA19-9 levels, those with normal and high DUPAN-2 levels were classified into normal/normal (N/N) and normal/high (N/H) groups, respectively. Among patients with high CA19-9 levels, those with normal and high DUPAN-2 levels were classified into high/normal (H/N) and high/high (H/H) groups, respectively. Survival rates were compared between the groups. RESULTS: Among 521 patients, the N/N, N/H, H/N, and H/H groups accounted for 25.0%, 10.6%, 35.1%, and 29.4% of patients, respectively. The proportions of resectable PDAC in the N/N and H/N groups (71.5% and 66.7%) were significantly higher than those in the N/H and H/H groups (49.1% and 54.9%) (P < 0.01). The 5-year survival rates in the N/N, N/H, H/N, and H/H groups were 66.0%, 31.1%, 34.9%, and 29.7%, respectively; the rate in the N/N group was significantly better than those in the other three groups (P < 0.0001, P < 0.0001, and P < 0.0001, respectively). CONCLUSIONS: Only patients with normal CA19-9 and DUPNA-2 values should be diagnosed with early-stage PDAC.

Prognostic impact of peritoneal washing cytology in patients with biliary tract cancer.

PURPOSE: To elucidate the clinical significance of peritoneal washing cytology (PWC) in patients with resectable biliary tract cancer (BTC). METHODS: Clinical data of patients with BTC, who received PWC at curative intent surgery from March 2009 to December 2021, were retrospectively analyzed. Eligible patients were stratified into two groups according to positive or negative PWC. Recurrence-free survival and overall survival were compared between the two groups. Independent factors associated with positive PWC were investigated using multivariate analysis. RESULTS: Among the 284 patients analyzed, all 53 patients with ampullary carcinoma showed negative PWC and these patients were excluded. Among the remaining eligible 231 patients, 41 patients had intrahepatic cholangiocarcinoma, 55 had gall bladder carcinoma, 72 had hilar cholangiocarcinoma, and 63 had distal cholangiocarcinoma. Eleven (4.8%) patients had positive PWC, and 220 (95.2%) had negative PWC. The median recurrence-free survival in the positive and negative PWC groups were 12.0 vs. 60.7 months (p = 0.005); the median overall survival times were 17.0 vs. 60.6 months (p = 0.008), respectively. Multivariate analysis revealed that serum carbohydrate antigen 19-9 level over 80 U/mL and multiple lymph node metastasis were independently associated with positive PWC (odds ratio [OR]: 5.84, p = 0.031; OR: 5.28, p = 0.021, respectively). CONCLUSION: Patients with positive PWC exhibited earlier recurrence and shorter survival times compared with those with negative PWC.

Δ3-tubulin impairs mitotic spindle morphology and increases nuclear size in pancreatic cancer cells.

Cancer cell proliferation is affected by post-translational modifications of tubulin. Especially, overexpression or depletion of enzymes for modifications on the tubulin C-terminal region perturbs dynamic instability of the spindle body. Those modifications include processing of C-terminal amino acids of α-tubulin; detyrosination, and a removal of penultimate glutamic acid (Δ2). We previously found a further removal of the third last glutamic acid, which generates so-called Δ3-tubulin. The effects of Δ3-tubulin on spindle integrities and cell proliferation remain to be elucidated. In this study, we investigated the impacts of forced expression of Δ3-tubulin on the structure of spindle bodies and cell division in a pancreatic cancer cell line, PANC-1. Overexpression of HA-tagged Δ3-tubulin impaired the morphology and orientation of spindle bodies during cell division in PANC-1 cells. In particular, spindle bending was most significantly increased. Expression of EGFP-tagged Δ3-tubulin driven by the endogenous promoter of human TUBA1B also deformed and misoriented spindle bodies. Spindle bending and condensation defects were significantly observed by EGFP-Δ3-tubulin expression. Furthermore, EGFP-Δ3-tubulin expression increased the nuclear size in a dose-dependent manner of EGFP-Δ3-tubulin expression. The expression of EGFP-Δ3-tubulin tended to slow down cell proliferation. Taken together, our results demonstrate that Δ3-tubulin affects the spindle integrity and cell division.

Long-term outcomes of neoadjuvant gemcitabine, nab-paclitaxel, and S1 (GAS) in borderline resectable pancreatic cancer with arterial contact: Results from a phase II trial.

BACKGROUND/PURPOSE: This study reports the long-term results of a phase II trial evaluating the clinical efficacy of neoadjuvant gemcitabine, nab-paclitaxel, and S1 (GAS) in borderline resectable pancreatic cancer with arterial contact (BRPC-A). METHODS: A multicenter, single-arm, phase II trial was conducted. Patients received six cycles of GAS and patients without progressive disease were intended for R0 resection. RESULTS: Of the 47 patients, 45 (96%) underwent pancreatectomy. At the time of this analysis, all patients were updated with no loss to follow-up. A total of 30 patients died, while the remaining 17 patients were followed for a median of 68.1 months. The updated median overall survival (OS) was 41.0 months, with 2- and 5-year OS rates of 68.0% and 44.6%, respectively. Multivariate analysis in the preoperative model showed that a tumor diameter reduction rate ≥10% and a CA19-9 reduction rate ≥95% after neoadjuvant chemotherapy remained independently associated with favorable survival. In the postoperative multivariate model, no lymph node metastasis, no major surgical complications, and completion of adjuvant chemotherapy were independently associated with improved OS. CONCLUSIONS: This long-term evaluation of the neoadjuvant GAS trial demonstrated the high efficacy of the regimen, suggesting that it is a promising treatment option for patients with BRPC-A.

Optimal Lymphadenectomy in Patients with Well-Differentiated Nonfunctioning Pancreatic Neuroendocrine Neoplasms.

This study aimed to evaluate the optimal extent of lymphadenectomy in patients with nonfunctioning pancreatic neuroendocrine neoplasms. We retrospectively analyzed the clinicopathological data of patients with nonfunctioning pancreatic neuroendocrine neoplasms who underwent surgical resection. We investigated the frequency of metastases at each lymph node station according to tumor location and analyzed the factors contributing to poor overall survival (OS) and disease-free survival (DFS). Overall, data of 84 patients were analyzed. Among patients with pancreatic head tumors, metastases at stations 8, 13, and 17 were found in one (3.1%), four (12.5%), and three (9.3%) patients, respectively. However, none of the other stations showed metastases. For pancreatic body and tail tumors, metastases only at station 11 were found in two (5.1%) patients. Additionally, multivariate DFS and OS analyses showed that lymph node metastasis was the only independent prognostic factor. In conclusion, lymph node metastasis near the primary tumor was the only independent factor of poor prognosis in patients with nonfunctioning pancreatic neuroendocrine neoplasms after undergoing curative surgery. Peri-pancreatic lymphadenectomy might be recommended for nonfunctioning pancreatic neuroendocrine neoplasms.

Difficulty of adjuvant chemotherapy administration in patients with biliary tract cancer.

PURPOSE: This study aimed to elucidate the difficulty of adjuvant chemotherapy administration in patients with biliary tract carcinoma (BTC). METHODS: Clinical data of patients with BTC who underwent curative-intent surgery were retrospectively analyzed. The eligible patients were stratified into two groups according to the presence or absence of adjuvant chemotherapy administration (adjuvant and non-adjuvant groups), and the clinicopathological features were compared between the two groups. The ratios of adjuvant chemotherapy administration were investigated in each surgical procedure. Independent factors associated with no administration of adjuvant chemotherapy were analyzed using multivariate analyses. RESULTS: Among 168 eligible patients, 141 (83.9%) received adjuvant chemotherapy (adjuvant group), while 27 (16.1%) did not (non-adjuvant group). The most common surgical procedure was pancreaticoduodenectomy in the adjuvant group, and it was hepatectomy with extrahepatic bile duct resection (BDR) in the non-adjuvant group, respectively. The rate of no adjuvant chemotherapy was significantly higher in patients who underwent hepatectomy with BDR than in those who underwent other surgeries (p < 0.001). The most common cause of no adjuvant chemotherapy was bile leak in 12 patients, which occurred after hepatectomy with BDR in ten patients. Multivariate analyses revealed that hepatectomy with BDR and preoperative anemia were independently associated with no adjuvant chemotherapy (p < 0.001 and p < 0.001, respectively). CONCLUSIONS: Hepatectomy with BDR and subsequent refractory bile leak can be the obstacle to adjuvant chemotherapy administration in patients with BTC.

Prognostic factor in patient with recurrent pancreatic adenocarcinoma.

PURPOSE: To elucidate prognostic factors for post-recurrence survival in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Patients who underwent curative-intent surgery for PDAC between January 2014 and May 2020 were identified. Among them, patients who had postoperative recurrences and received chemotherapy were retrospectively investigated. Independent prognostic factors for survival after recurrence were investigated using multivariate analyses. Eligible patients were divided into two groups according to the presence or absence of the identified prognostic factors, and survival times after recurrence were compared. RESULTS: Eighty-four patients with recurrent PDAC were included. Multivariate analysis showed that red blood cell (RBC) transfusion (HR, 2.80; p = 0.0051), low albumin level (HR, 1.84; p = 0.0402), and high carbohydrate antigen 19-9 (CA19-9) level at recurrence (HR, 2.11; p = 0.0258) were significant predictors of shorter survival after recurrence. The median survival times after recurrence in the transfusion and non-transfusion groups were 5.5 vs. 18.1 months (p < 0.0001), respectively; those in the low and normal albumin groups were 10.1 vs. 18.7 months (p = 0.0049), and those in the high and normal CA19-9 groups were 11.5 vs. 22.6 months (p = 0.0023), respectively. CONCLUSIONS: RBC transfusion, low albumin, and high CA19-9 levels at recurrence negatively affected survival after recurrence in patients with PDAC.

The prognostic impact of peritoneal washing cytology for otherwise resectable extrahepatic cholangiocarcinoma patients.

The clinical importance of peritoneal washing cytology (PWC) for cholangiocarcinoma patients remains unclear. The clinical data of 137 extrahepatic cholangiocarcinoma patients who received PWC and curative surgery were retrospectively analyzed. Among the 137 patients analyzed, five (3.6%) had positive PWC, and 132 (96.4%) had negative PWC. The median survival time in patients with negative PWC was 6.45 years, and the overall 1-, 2-, and 5-year survival rates were 86.5%, 75.3%, and 51.6%, respectively. The median survival time in patients with positive PWC was 2.56 years, and the overall 1-, 2-, and 5-year survival rates were 60.0%, 60.0%, and 40.0%, respectively. A multivariate analysis revealed that positive lymph node metastasis (P < 0.001), positive perineural invasion (P = 0.014) and no use of adjuvant chemotherapy (P < 0.001), but not positive PWC were independently associated with a worse overall survival. In conclusion, surgery and subsequent chemotherapy might be a therapeutic option for cholangiocarcinoma patients with positive PWC.

Falciform ligament hernia with specific abdominal symptom.

Falciform ligament hernia is a very rare internal hernia and is difficult to diagnose before surgery. We report a case of falciform ligament hernia with a specific symptom and image findings, which led to an accurate diagnosis and subsequent laparoscopic surgery. A 15-year-old adolescent boy with no previous medical history showed epigastric pain and was referred to our hospital. The abdominal pain was strong in the supine position and was alleviated in the knee-chest position. Contrast-enhanced computed tomography showed that the round ligament was recognized as a cord-like structure, and the mesentery of the small intestine was located at the cranioventral side of the ligament. He was diagnosed as having falciform ligament hernia, and emergency laparoscopic surgery was performed. The small intestine passed through the falciform ligament; however, it showed no sign of ischemia, and bowel resection was not required. The malposed intestine was repositioned, and the falciform ligament was cut to prevent hernia recurrence. The specific abdominal symptom and computed tomography image finding were useful to make the correct diagnosis in this case.

[Lung Metastasis from Alpha-Fetoprotein Resulting in Esophagogastric Junction Cancer-A Case Report].

A 51-year-old male underwent total gastrectomy for esophagogastric junction cancer(T3N0M0, Stage ⅡA). He was diagnosed with an alpha-fetoprotein(AFP) producing tumor and hepatoid adenocarcinoma. One month after radical surgery, computed tomography(CT) showed lung metastasis, and the patient's serum AFP level was high. He underwent chemotherapy( S-1 and wPTX/RAM)and eventually died 4 months after surgery.

Successful treatment of conversion chemotherapy for initially unresectable synchronous colorectal liver metastasis.

A 72-year-old woman with a sigmoid colon cancer and a synchronous colorectal liver metastasis (CRLM), which involved the right hepatic vein (RHV) and the inferior vena cava (IVC), was referred to our hospital. The metastatic lesion was diagnosed as initially unresectable because of its invasion into the confluence of the RHV and IVC. After she had undergone laparoscopic sigmoidectomy for the original tumor, she consequently had 3 courses of modified 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus cetuximab. Computed tomography revealed a partial response, and the confluence of the RHV and IVC got free from cancer invasion. After 3 additional courses of mFOLFOX6 plus cetuximab, preoperative percutaneous transhepatic portal vein embolization (PTPE) was performed to secure the future remnant liver volume. Finally, a right hemihepatectomy was performed. The postoperative course was uneventful. The patient was discharged from the hospital on postoperative day 13. She had neither local recurrence nor distant metastasis 18 mo after the last surgical intervention. This multidisciplinary strategy, consisting of conversion chemotherapy using FOLFOX plus cetuximab and PTPE, could contribute in facilitating curative hepatic resection for initially unresectable CRLM.