Pathological complete response following neoadjuvant chemotherapy for locally advanced intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer. Cases when found are often advanced with vascular invasion, and radical resection is often difficult. Despite curative resection, the postoperative recurrence rate of patients with histological lymph node metastasis is high, and their prognosis is poor. Therefore, there is an urgent need to establish multidisciplinary treatment that combines chemotherapy and surgical resection. The efficacy of neoadjuvant chemotherapy (NAC) for locally advanced ICC is unclear. In this report, a case of locally advanced ICC in which pathological complete response (pCR) was achieved after NAC is described. CASE PRESENTATION: A 79-year-old woman was admitted to a local hospital with appetite loss. Computed tomography showed a 100 × 90 mm low-contrast tumor in the left hepatic lobe and segment 1 with invasion to the inferior vena cava (IVC), and several lymph nodes along the left gastric artery and lesser curvature were enlarged. Therefore, she was treated with a combined chemotherapy regimen of gemcitabine and cisplatin. After four courses, the tumor size decreased to 30 × 60 mm without invasion to the IVC. Left hepatectomy extending to segment 1 with bile duct resection combined with middle hepatic vein resection (H1234-B-MHV), dissection of regional lymph nodes and pyloroplasty were performed. After radical resection, pCR was achieved. She is alive with no evidence of disease, 2 years after surgery. CONCLUSIONS: In this case, a patient with locally advanced ICC achieved pCR to NAC. NAC may be effective for ICC. Patients who achieve pCR may have a better prognosis.

Impact of the course of the segment 4 hepatic artery on proximal ductal margin status in right hepatectomy for perihilar cholangiocarcinoma.

BACKGROUND: The relationship between the course of the segment 4 hepatic artery and proximal ductal margin status in the right hepatectomy (H15678-B) for perihilar cholangiocarcinoma is unclear. This study aimed to evaluate proximal ductal margin status according to the course of the segment 4 hepatic artery in patients with perihilar cholangiocarcinoma treated with right hepatectomy. METHODS: Consecutive patients with perihilar cholangiocarcinoma who underwent a right hepatectomy between January 2006 and August 2021 were retrospectively reviewed. The course of the segment 4 hepatic artery was classified based on the positional relationship with the umbilical portion of the left portal vein into R-UP and L-UP types. The R-UP type had the segment 4 hepatic artery running along the right caudal position of the umbilical portion of the left portal vein, whereas the L-UP type had the segment 4 hepatic artery running along the left cranial position of the umbilical portion of the left portal vein, with or without another branch running along the right caudal position of the umbilical portion of the left portal vein. Proximal ductal margin status after the right hepatectomy was compared between types. RESULTS: Among 102 patients, 72 (70.5%) were R-UP type, and 30 (29.5%) were L-UP type. Rates of negative proximal ductal margin were higher with the L-UP type (27/30, 90.0%) than with the R-UP type (51/72, 70.8%; P = .04). On multivariate analysis, Bismuth-Corlette type II and IIIa (risk ratio 4.13, 95% confidence interval 1.52-11.5; P = .005) and L-UP type (risk ratio 4.03, 95% confidence interval 1.18-18.8; P = .04) were independent predictors of negative proximal ductal margin after a right hepatectomy for perihilar cholangiocarcinoma. CONCLUSION: For the course of the segment 4 hepatic artery, L-UP type rather than R-UP type might be anatomically advantageous for achieving negative proximal ductal margin in a right hepatectomy for perihilar cholangiocarcinoma.

Serum elastase-1 predicts malignancy in intraductal papillary mucinous neoplasm of the pancreas.

BACKGROUND: The indication for surgical resection of intraductal papillary mucinous neoplasms (IPMNs) is defined by imaging features, such as mural nodules. Although carbohydrate antigen (CA) 19-9 was selected as a parameter for worrisome features, no serum biomarkers were considered when deciding on surgical indications in the latest international consensus guideline. In this study, we assessed whether clinical factors, imaging findings, and serum biomarkers are useful in predicting malignant IPMNs. METHODS: A total of 234 resected IPMN cases in Chiba University Hospital from July 2005 to December 2021 were retrospectively analyzed. RESULTS: Among the 234 patients with resected IPMNs diagnosed by preoperative imaging, 117 were diagnosed with malignant pathologies (high-grade dysplasia and invasive IPMNs) according to the histological classification. In the multivariate analysis, cyst diameter ≥30 mm; p = 0.035), enhancing mural nodules on multidetector computed tomography (≥5 mm; p = 0.018), and high serum elastase-1 (≥230 ng/dl; p = 0.0007) were identified as independent malignant predictors, while CA19-9 was not. Furthermore, based on the receiver operator characteristic curve analyses, elastase-1 was superior to CA19-9 for predicting malignant IPMNs. Additionally, high serum elastase-1 levels (≥230 ng/dl; p = 0.0093) were identified as independent predictors of malignant IPMNs in patients without mural nodules on multidetector computed tomography (MDCT) in multivariate analysis. CONCLUSION: The serum elastase-1 level was found to be a potentially useful biomarker for predicting malignant IPMNs.

Clinical benefits of pulmonary resection for lung metastases from pancreatic cancer.

PURPOSE: Systemic chemotherapy is generally used for metastatic pancreatic cancer; however, pulmonary resection may be a treatment option for lung oligometastases from pancreatic cancer. The current study aimed to clarify the oncological outcomes and clinical benefits of pulmonary resection for lung metastases. METHODS: Of 510 patients who underwent pancreatic resection for pancreatic cancer, 44 patients with recurrence of isolated lung metastases and one patient with simultaneous lung metastases were evaluated. RESULTS: Of the 45 patients, 20 patients were selected as candidates for pulmonary resection based on clinical factors such as recurrence-free interval (RFI) from pancreatectomy to lung metastases, number of lung metastases, and serum CA19-9 level. The post-recurrent survival of patients with pulmonary resection was significantly better than that of patients without pulmonary resection. Fourteen of the 20 patients with pulmonary resection developed tumor recurrence with a median disease-free survival (DFS) of 15 months. Univariate analyses revealed that an RFI from pancreatectomy to lung metastases of ≥28 months was associated with better DFS after pulmonary resection. Of the 14 patients with an RFI of ≥28 months, pulmonary resection resulted in prolonged chemotherapy-free interval in 12 patients. Furthermore, repeat pulmonary resection for recurrent tumors after pulmonary resection led to further cancer-free interval in some cases. CONCLUSIONS: Although many patients had tumor recurrence after pulmonary resection, pulmonary resection for lung metastases from pancreatic cancer may provide prolonged cancer-free interval without the need for chemotherapy. Pulmonary resection should be performed for the patients with a long RFI from pancreatectomy to lung metastases.

Prognostic impact of proximal ductal margin status in perihilar cholangiocarcinoma according to the presence or absence of lymph node metastasis.

BACKGROUND: Although both proximal ductal margin status and lymph node metastasis status influence the survival of patients with perihilar cholangiocarcinoma, the effect of proximal ductal margin status on survival according to lymph node metastasis status is unclear. The aim of this study was, thus, to evaluate the prognostic impact of proximal ductal margin status in perihilar cholangiocarcinoma according to the presence or absence of lymph node metastasis. METHODS: Consecutive patients with perihilar cholangiocarcinoma who underwent major hepatectomy between June 2000 and August 2021 were retrospectively reviewed. Patients with Clavien-Dindo grade V complications were excluded from the analysis. Overall survival was assessed according to the combination of lymph node metastasis and proximal ductal margin status. RESULTS: Of the 230 eligible patients, 128 (56%) were lymph node metastasis negative, and 102 (44%) were lymph node metastasis positive. Overall survival was significantly better in lymph node metastasis negative than lymph node metastasis positive patients (P < .0001). Of the 128 lymph node metastasis-negative patients, 104 (81%) were proximal ductal margin negative, and 24 (19%) were proximal ductal margin positive. In lymph node metastasis-negative patients, overall survival was worse in the proximal ductal margin positive than the proximal ductal margin negative group (P = .01). Of the 102 lymph node metastasis-positive patients, 72 (71%) were proximal ductal margin negative and 30 (29%) were proximal ductal margin positive. In these patients, overall survival was similar between the 2 groups (P = .10). CONCLUSION: In patients with perihilar cholangiocarcinoma, the prognostic impact of proximal ductal margin positivity on survival might differ according to the presence or absence of lymph node metastasis.

[A Case of Perihilar Cholangiocarcinoma with Postoperative Hepatic Encephalopathy Due to Portosystemic Shunt Treated by Percutaneous Embolization].

An 83-year-old woman developed jaundice, and was diagnosed as perihilar cholangiocarcinoma. Abdominal contrast- enhanced CT revealed coexisting portosystemic shunt between portal vein and inferior vena cava, however, her blood ammonia level was normal. She underwent right hemihepatectomy and caudate lobectomy combined with extrahepatic bile duct resection and portal vein resection. Postoperatively, hyperammonemia refractory to conservative treatment was observed. The blood ammonia level increased to 180µg/dL and she was suffered from grade Ⅲ hepatic encephalopathy on the 20th postoperative day. CT showed an increase in the diameter of the portosystemic shunt, while there was only a slight increase in the remnant left lobe of the liver. These findings indicated that hepatic encephalopathy was caused by increased portosystemic shunt blood flow and decreased portal venous flow. Hepatic encephalopathy was rapidly improved by percutaneous transhepatic portosystemic shunt obliteration.

[Intraoperative Blood Flow Assessment of Gastric Tube Using Indocyanine Green fluorography during Pancreaticoduodenectomy Following Esophagectomy-Case Reports].

Case 1: A 73-year-old male, who had an intraductal papillary mucinous adenocarcinoma or resectable pancreatic cancer at the uncinate process of the pancreas five years after subtotal esophagectomy for esophageal cancer, underwent pylorus preserving pancreaticoduodenectomy(PPPD). Case 2: A 68-year-old male, who also had a resectable pancreatic cancer at the uncinate process of the pancreas 3 years after subtotal esophagectomy for esophageal cancer, underwent PPPD following neoadjuvant chemotherapy. In both cases, right gastroepiploic artery and vein were preserved to maintain the perfusion of the gastric tube during surgery. Indocyanine Green(ICG)fluorography was performed just before duodenal-jejunal anastomosis, which visually showed the well-perfused gastric tube. Both patients had no necrosis of the gastric tube, nor gastrointestinal obstruction after surgery. Intraoperative ICG fluorography was useful to evaluate the blood flow of the remaining gastric tube visually during PPPD for post-esophagectomy patients.

[Conversion Surgery Following Systemic Chemotherapy for Advanced Gallbladder Cancer with Peritoneal Dissemination-A Case Report].

A 73-year-old female was diagnosed with gallbladder cancer, but the future liver remnant volume was deemed insufficient for curative resection. Consequently, transileocolic portal vein embolization was performed. During laparotomy, multiple nodules were palpable on the peritoneal surface of the pelvic floor. Subsequently, staging laparoscopy confirmed the pathological diagnosis of adenocarcinoma in the resected nodules, indicating peritoneal dissemination of gall bladder cancer. Due to this peritoneal dissemination, surgical resection was deemed inappropriate, and the patient was initiated on systemic chemotherapy consisting of gemcitabine and cisplatin. Following 22 courses of chemotherapy, contrast-enhanced computed tomography demonstrated no significant changes in the size of the primary tumor or its location relative to the main vessels, although a small metastatic lesion was identified in the gallbladder bed. At the second staging laparoscopy, any nodules suggesting peritoneal dissemination were observed. Based on these findings, we decided to perform curative resection. The surgical procedure involved right hepatectomy plus segment 4a resection, extrahepatic bile duct resection, and hepaticojejunostomy. Pathological examination revealed ypT3bN0M1(HEP), ypStage ⅣB, with the achievement of R0 resection. The patient survived with no recurrences for 40 months after surgery. These results suggest that aggressive therapeutic strategies, including conversion surgery following systemic chemotherapy, may be beneficial for patients initially deemed unresectable due to gallbladder cancer.

[Retrospective Study of Preoperative Serial Pancreatic Juice Aspiration Cytological Examination(SPACE)for Early Preoperative Detection of Pancreatic Cancer].

Serial pancreatic juice aspiration cytological examination(SPACE)has been reported as a reliable preoperative diagnostic method for early pancreatic cancer, when combined with imaging findings suspecting early pancreatic cancer. Among 259 patients with suspected pancreatic cancer who underwent pancreatic resection at our hospital, SPACE was preoperatively performed in 14 cases(5.4%). Of these 14 cases, final pathological diagnosis was pancreatic cancer in 12 patients (86%), including 5 patients with Stage ⅠA pancreatic cancer(35.7%), all of whom had a mass on preoperative CT or EUS. On the other hand, in the other 2 cases(14.3%), CT/EUS detected no mass but focal pancreatic parenchymal atrophy and main pancreatic duct stenosis which were the imaging findings suspecting very early pancreatic cancer such as cancer in situ. Although preoperative SPACE results of these 2 cases were class Ⅳ, final pathological results of resected specimen were low-grade PanIN in both cases. SPACE was considered useful for preoperative diagnosis of pancreatic cancer in our study, however further study is needed to examine its diagnostic accuracy for early pancreatic cancer which does not appear as a mass in any imaging modality.

Impact of resection margin status on survival after operation for pancreatic head cancer with extrapancreatic nerve plexus invasion.

BACKGROUND: Extrapancreatic nerve plexus (PL) invasion of pancreatic ductal adenocarcinoma (PDAC) is an important factor for determining resectability and surgical method. We sought to clarify the characteristics of PDAC with PL invasion and clinical impact of the resection margin status on prognosis for PDAC with PL invasion. METHODS: A total of 242 patients with pancreatic head cancer who underwent pancreatectomy were evaluated. Clinicopathological data and patient survival were analyzed. RESULTS: Pathological PL invasion was observed in 68 patients (28.1%). Patients with PL invasion had significantly shorter disease-free survival (DFS) and showed trends toward worse overall survival (OS) than those without PL invasion. While multivariate analysis revealed that PL invasion was not an independent prognostic factor, PL invasion was associated with extensive venous invasion and a high percentage of lymph node metastases, both of which were independent factors affecting DFS and OS. Among patients with PL invasion, there was no significant difference in DFS and OS between the R0 and R1 resection groups. CONCLUSIONS: PL invasion is a common pathological feature of aggressive PDAC with high propensity for invasiveness and metastatic potential. The microscopic resection margin status may not affect the survival of pancreatic head cancer patients with PL invasion.

Preoperative Diagnosis of Lymph Node Metastasis of Perihilar Cholangiocarcinoma Using Diffusion-Weighted Magnetic Resonance Imaging.

INTRODUCTION: Although the prognosis of patients with resected perihilar cholangiocarcinoma (PHC) with histological lymph node metastasis (LNM) is poor, preoperative prediction of LNM is difficult. This study aimed to evaluate the diagnostic performance of diffusion-weighted magnetic resonance imaging (DWI) for LNM of PHC. METHOD: Consecutive patients who underwent surgical resection of PHC between January 2012 and May 2020 were retrospectively reviewed. The lymph node (LN) area (mm2) and apparent diffusion coefficient (ADC) value ( × 10-3 mm2/s) of pericholedochal LNs were measured by DWI. The characteristics of the patients and the LNs were evaluated according to the histological presence or absence of regional LNM. Univariate and multivariate analyses were performed to identify the predictors of LNM of PHC. RESULTS: Of the 93 eligible patients, 49 (53%) were LNM positive and 44 (47%) were LNM negative. Although the characteristics of the patients were similar between the two groups, the mean ADC value was significantly lower in the LNM positive group than in the LNM negative group. On multivariate analysis, mean ADC value ≤1.80 × 10-3 mm2/s was independently associated with LNM of PHC (risk ratio: 12.5, 95% confidence interval: 3.05-51.4; p = 0.0004). The sensitivity, specificity and accuracy of mean ADC values ≤ 1.80 × 10-3 mm2/s for predicting LNM of PHC were 94%, 55% and 75%, respectively. CONCLUSIONS: DWI might be useful for the preoperative diagnosis of LNM of PHC.

Surgical implications of the confluence patterns of the left intrahepatic bile ducts in right hepatectomy for perihilar cholangiocarcinoma.

BACKGROUND: Although the most important goal in surgery for perihilar cholangiocarcinoma (PHC) is to achieve tumor-free proximal ductal margins, little is known about the implications of confluence patterns of the left intrahepatic bile ducts for the proximal ductal margin status in right hepatectomy (RH) for PHC. METHODS: Of 203 patients who underwent surgical resection for PHC with curative intent, confluence patterns of the left intrahepatic bile duct were evaluated in 94 consecutive patients who underwent RH, and they were classified into the following two types: normal type: the bile duct of segment 4 (B4) drained into the common trunk of the bile ducts of segment 2 (B2) and segment 3 (B3) at the right side of the umbilical portion of the left portal vein to form the left hepatic duct; and hepatic confluence type: B2 entered the common trunk of B3 and B4 at the hepatic confluence or B4 entered the common trunk of B2 and B3 at the hepatic confluence. The proximal ductal margin status following RH was compared between the two types of confluence patterns. RESULTS: Of 94 consecutive patients, 69 (73%) were the normal type, and 25 (27%) were the hepatic confluence type. There were no significant differences in patients' characteristics, surgical characteristics, surgical outcomes, and histopathological features between the two groups. However, in patients with Bismuth-Corlette type II and IIIa PHC, the achievement rates of negative proximal ductal margins at the first dividing line were significantly higher in the hepatic confluence type group than in the normal type group (16/16 [100%] vs 34/52 [65%], respectively; P = .007). CONCLUSIONS: Confluence patterns of the left intrahepatic bile ducts might affect proximal ductal margin status in RH for PHC.

Simultaneous brain and lung metastases of pancreatic ductal adenocarcinoma after curative pancreatectomy: a case report and literature review.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) rarely metastasizes to the brain; therefore, the features of brain metastasis of PDAC are still unknown. We encountered simultaneous metastases to the brain and lung in a PDAC patient after curative surgery. Case presentation A 68-year-old man with PDAC in the tail of the pancreas underwent distal pancreato-splenectomy. He received gemcitabine as adjuvant chemotherapy for 6 months. Two months later, brain and lung metastases occurred simultaneously. Considering the systemic condition, the patient received gamma knife treatment and an Ommaya reservoir was inserted for drainage. The patient's condition gradually worsened and he received the best supportive care. To the best of our knowledge, only 28 cases in which brain metastases of PDAC were identified at the time of ante-mortem have been reported to date, including the present case. Notably, the percentage of simultaneous brain and lung metastases was higher (32%) in a series of reviewed cohorts. Thus, lung metastasis might be one of the risk factors for the development of brain metastasis in patients with PDAC. As a systemic disease, it can be inferred that neoplastic cells will develop brain metastasis via hematogenous dissemination beyond the blood-brain barrier, even if local recurrence is controlled. In our case, immunohistochemical staining showed that the neoplastic cells were positive for carbonic anhydrase 9 (CAIX), mucin core protein 1 (MUC1), and MUC5AC in the resected primary PDAC. CONCLUSION: We describe a case of simultaneous brain and lung metastases of PDAC after curative pancreatectomy, review previous literature, and discuss the clinical features of brain metastasis of PDAC.