Successful management of splenic artery dissection after sigmoid colon perforation in vascular Ehlers-Danlos syndrome.

BACKGROUND: Ehlers-Danlos syndrome (EDS) is a genetic disorder that causes fragility of the systemic connective tissues. Of the 13 subtypes, vascular EDS (vEDS) is associated with abnormalities in collagen production, resulting in arterial rupture and intestinal perforation. Herein, we report the case of a man with confirmed vEDS who survived a ruptured dissected splenic artery aneurysm triggered by perforation of the sigmoid colon. CASE PRESENTATION: A 48-year-old man presented to our hospital with sudden severe lower abdominal pain. The patient was genetically diagnosed with vEDS at the age of 43 years. Abdominal computed tomography (CT) showed fluid and free air surrounding the sigmoid colon. These findings suggested sigmoid colon perforation, and emergency surgery was needed. Hartmann's procedure was performed. The resected specimen showed a 2-cm-sized depression around the perforation. Histopathological findings showed an abscess and exudate in the serosa of the perforation and thinning of the intrinsic muscular layer in the depressed area. The patient was doing well postoperatively; however, on the ninth postoperative day, sudden upper abdominal pain developed. CT revealed an intra-abdominal hemorrhage due to rupture of a dissecting splenic artery aneurysm. The aneurysm was not observed on preoperative CT and was distant from the surgical site. Urgent transcatheter arterial embolization was performed. Although embolization of the splenic artery was attempted during the procedure, the arterial dissection spread to the common hepatic artery. Moreover, the proper hepatic and gastroduodenal arteries were poorly visualized, probably due to vasospasm. Although complications associated with extensive embolization were a concern, embolization of the splenic and common hepatic arteries was necessary to save the patient's life. After embolization, angiography showed that the left hepatic blood flow was maintained from the inferior phrenic artery, and the right hepatic inflow was maintained from the superior mesenteric artery via the peribiliary vascular plexus in the hilar area. The patient recovered well and was discharged on the 19th postoperative day. CONCLUSIONS: vEDS can cause arterial rupture after intestinal surgery. Therefore, careful post-operative management is necessary. Moreover, cooperation with interventional radiologists is important for prompt treatment of vascular complications.

Total neoadjuvant therapy improves survival of patients with borderline resectable pancreatic cancer with arterial involvement.

Aim: This study aimed to evaluate the prognostic impact of total neoadjuvant therapy (TNT) for borderline resectable pancreatic cancer with arterial involvement (BR-A) pancreatic cancer. Methods: We analyzed 81 patients initially diagnosed as BR-A who received initial treatments between 2007 and 2021. Among them, 18 patients who received upfront surgery were classified as the UFS group, while 30 patients who were treated with neoadjuvant chemoradiotherapy were classified as the NACRT group. Furthermore, 33 patients who planned to receive a combination treatment of over 6 months of systemic chemotherapies followed by chemoradiotherapy before surgery were classified as the TNT group. Results: There were no significant differences in the patients' backgrounds between the three groups at the time of initial treatment. The resection rates of the UFS, NACRT, and TNT groups were 89%, 77%, and 67%, respectively. NACRT had no impact on the prognosis compared to upfront surgery. In sharp contrast, the TNT group had a significantly better prognosis compared to the other groups, especially after pancreatic resection. Multivariate analysis demonstrated that TNT and resection were independent prognostic factors for the patients of BR-A. Conclusion: TNT can be a promising therapeutic strategy for patients with BR-A.

Clinical impact of sarcopenia in early-stage intrahepatic recurrent hepatocellular carcinoma: an association with impaired host immunity.

PURPOSE: This study investigated the role of sarcopenia in the long-term outcomes of patients with early-stage intrahepatic recurrent hepatocellular carcinoma (HCC). METHODS: The study included 136 patients with intrahepatic recurrent Barcelona Clinic Liver Cancer (BCLC) stage 0/A HCC following liver resection diagnosed between 2006 and 2020 and underwent surgery, radiofrequency ablation (RFA), or transcatheter arterial chemoembolization (TACE). Sarcopenia was defined based on the skeletal muscle index using computed tomography at the time of recurrence, and its association with long-term outcomes was evaluated. Tumor-infiltrating lymphocytes (CD4 + , CD8 + , and CD45RO + T cells) were assayed using immunohistochemistry on specimens obtained from repeat hepatectomies, and their association with sarcopenia was evaluated. RESULTS: The overall survival (OS) and recurrence-free survival (RFS) rates after initial recurrence of patients with sarcopenia were significantly lower than those without sarcopenia (p < 0.001 and p < 0.001, respectively). Multivariate analysis identified sarcopenia as an independent prognostic factor for RFS (p < 0.001). In patients without sarcopenia, surgery resulted in better RFS than RFA or TACE. Contrastingly, in patients with sarcopenia, the RFS was extremely poor regardless of the treatment type: surgery, RFA, or TACE (median RFS, 11.7, 12.7, and 10.1 months). Significantly low levels of tumor-infiltrating CD4 + , CD8 + , and CD45RO + lymphocytes were observed in patients with sarcopenia (p = 0.001, p = 0.001, and p = 0.001, respectively). CONCLUSIONS: This study suggests that patients with sarcopenia have poor RFS regardless of the treatment type for early-stage intrahepatic recurrent HCC. Impaired host immunity might be one of the underlying mechanisms.

Combination of carbohydrate antigen 19-9 level and tumor size after neoadjuvant chemoradiation therapy may predict early recurrence of resectable pancreatic ductal adenocarcinoma.

BACKGROUND: Although the overall survival rate of patients with resectable pancreatic cancer has gradually improved, some patients relapse early and have a poor prognosis. This study aimed to identify the preoperative risk factors for early recurrence after neoadjuvant chemoradiotherapy in patients with resectable pancreatic cancer. METHODS: This study analyzed patients who underwent pancreatectomy after receiving neoadjuvant chemoradiotherapy for resectable pancreatic cancer between January 2009 and June 2021 and excluded those with borderline resectable and unresectable pancreatic cancers. Early recurrence was defined as recurrence within 6 months after surgery. RESULTS: This study included 203 patients, of whom 22 experienced early recurrence. The median survival time of patients with early recurrence was 18.3 months, which was significantly worse than that of patients with late recurrence (44.0 months, p < 0.001) or no recurrence (not reached, p < 0.001). Logistic regression analysis revealed that a carbohydrate antigen 19-9 level of >100 units/mL and a T status of ≥T2 after neoadjuvant chemoradiotherapy were independent predictive risk factors for early recurrence. The median recurrence-free survival time of patients with two risk factors was 9.7 months and significantly worse than that of those with either risk factors (20.5 months, p = 0.024) and those with no risk factor (26.2 months, p < 0.001). CONCLUSIONS: A combination of a high-level carbohydrate antigen 19-9 and a T status of ≥T2 after neoadjuvant chemoradiotherapy are predictors of early recurrence and may be helpful for selecting patients who require a stronger preoperative treatment.

Impact of the Prolonged Intermittent Pringle Maneuver on Post-Hepatectomy Liver Failure: Comparison of Open and Laparoscopic Approaches.

BACKGROUND: The influence of prolonged intermittent Pringle maneuver (IPM) on post-hepatectomy liver failure (PHLF) remains unclear. We evaluated the impact of the prolonged IPM on PHLF in patients undergoing open and laparoscopic hepatectomy. METHODS: We retrospectively included 546 patients who underwent hepatectomy using IPM. The patients were divided into open (n = 294) and laparoscopic (n = 252) groups. Odds ratios for PHLF occurrence were estimated in each group according to cumulative Pringle time (CPT). The cut-off value was set at CPT of 120 min. Risk factors for PHLF were evaluated in the open and laparoscopic groups. Additionally, we analyzed the post-operative outcomes in the open and laparoscopic groups with CPT ≥ 120 min and performed propensity score matching analysis based on PFLF-associated factors. RESULTS: In the open group, the risk of PHLF increased as CPT increased, particularly after 120 min. However, in the laparoscopic group, PHLF did not occur at less than 60 min, and the risk of PHLF was not significantly different at more than 60 min. Multivariate analysis identified CPT ≥ 120 min as an independent risk factor for PHLF in the open group (p < 0.001), but not in the laparoscopic group. Propensity score matching analysis showed that the PHLF rate was significantly lower in the laparoscopic group with CPT ≥ 120 min (p = 0.027). The post-operative transaminase levels were significantly lower in the laparoscopic group with CPT ≥ 120 min. CONCLUSIONS: Laparoscopic hepatectomy may cause less PHLF with prolonged IPM compared with open hepatectomy.

Pancreatic ductal adenocarcinoma arising from the pancreatic parenchyma compressed by a huge pancreatic lipoma: a case report.

BACKGROUND: Pancreatic lipomas (PLs) arising from the adipose tissue in the pancreatic parenchyma are rare among pancreatic tumors. Coexisting pancreatic ductal adenocarcinoma (PDAC) and PLs have not been previously reported. Herein, we report a case of PDAC arising from the pancreatic parenchyma with chronic pancreatitis compressed by a large PL. CASE PRESENTATION: The patient was a 69-year-old male. He had been diagnosed with a PL using computed tomography (CT) 12 years previously. The tumor had been slowly growing and was followed up carefully because of the possibility of well-differentiated liposarcoma. During follow-up, laboratory data revealed liver damage and slightly elevated levels of inflammatory markers. Contrast-enhanced CT revealed the previously diagnosed 12 cm pancreatic head tumor and an irregular isodensity mass at the upper margin of the tumor that invaded and obstructed the distal common bile duct. Magnetic resonance cholangiopancreatography demonstrated no specific findings in the main pancreatic duct. Based on these imaging findings, the patient underwent endoscopic retrograde biliary drainage and bile duct brushing cytology, which revealed indeterminate findings. The differential diagnosis of the tumor at that time was as follows: (1) pancreatic liposarcoma (focal change from well-differentiated to dedifferentiated, not lipoma), (2) distal cholangiocarcinoma, and (3) pancreatic cancer. After the cholangitis improved, a pancreatoduodenectomy was performed. Histologically, hematoxylin-eosin staining revealed moderately differentiated PDAC compressed by proliferating adipose tissue. The adipose lesion showed homogeneous adipose tissue with no evidence of sarcoma, which led to a diagnosis of lipoma. Additionally, extensive fibrosis of the pancreatic parenchyma and atrophy of the acinar cells around the lipoma was suggestive of chronic pancreatitis. The pathological diagnosis was PDAC (pT2N0M0 pStage Ib) with chronic pancreatitis and PL. The postoperative course was uneventful, and the patient was discharged on the 15th day after surgery. The patient received adjuvant chemotherapy and has remained recurrence-free for more than 6 months. CONCLUSIONS: PL may be associated with the development of PDAC in the surrounding inflammatory microenvironment of chronic pancreatitis. In cases of growing lipomas, careful radiologic surveillance may be needed not only for the possibility of liposarcoma but also for the coincidental occurrence of PDAC.

Identification of Nectin Family Interactive Gene Panel and Stratification of Clinical Outcomes in Patients with Pancreatic Cancer.

BACKGROUND: Although patient-risk stratification is important for selecting individualized treatment for pancreatic ductal adenocarcinoma (PDAC), predicting the oncologic outcomes after surgery remains a challenge. In this study, we identified a nectin family gene panel (NFGP) that can accurately stratify oncologic outcomes in patients with PDAC. STUDY DESIGN: Comprehensive analysis of the expression of 9 nectin family genes identified the NFGP, which was assessed for predictive performance in 2 independent public cohorts (The Cancer Genome Atlas [TCGA] n = 176; International Cancer Genome Consortium [ICGC] n = 89). It was subsequently trained and validated for the in-house training cohort without neo-adjuvant therapy (NAT, n = 213) and the validation cohort with NAT (n = 307). RESULTS: Using the Cox regression model, NFGP derived from 9 nectin family genes accurately stratified overall survival (OS) in TCGA (p = 0.038) and ICGC (p = 0.005). We subsequently optimized NFGP, which robustly discriminated postoperative prognosis, OS (p = 0.014) and relapse-free survival ([RFS] p = 0.006) in the training cohort. The NFGP was successfully validated in an independent validation cohort (OS: p < 0.001; RFS: p = 0.004). Multivariate analysis demonstrated the NFGP was an independent prognostic factor for OS and RFS in the training (p = 0.028 and 0.008, respectively) and validation (p < 0.001 and 0.013, respectively) cohorts. The subcohort analyses showed that the predictive performance of NFGP is applicable to the patients' subcohort according to resectability or adjuvant therapy status. Additionally, a combination model of NFGP score and CA19-9 level emerged with improved accuracy for predicting prognosis. CONCLUSIONS: This study established the predictive significance of NFGP for oncologic outcomes after surgery in PDAC. Our data demonstrate its clinical impact as a potent biomarker for optimal patient selection for individualized treatment strategies.

Significance of multiple tumor markers measurements in conversion surgery for unresectable locally advanced pancreatic cancer.

BACKGROUND: This study aimed to evaluate the significance of multiple tumor markers (TMs) measurements in determining the indications for conversion surgery (CS) in the management of unresectable locally advanced pancreatic cancer (UR-LAPC). METHODS: A total of 103 patients with UR-LAPC, treated between 2008 and June 2021, were enrolled in this study. Three TMs, including carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and Duke pancreatic monoclonal antigen type 2 (DUPAN-2), were measured. RESULTS: Twenty-five patients (24%) underwent CS. The median preoperative treatment period was 9.5 months. The median survival time (MST) from the initial treatment for patients with CS was significantly longer than that for patients without surgery (34.6 vs. 18.9 months, P < 0.001). The number of elevated TMs before CS was one in five patients and two in five patients, while 15 patients had normal levels of all three TMs. Notably, the MST from the initial treatment for patients with all three preoperative normal TMs levels was favorable for 70.5 months. In contrast, patients with one or two preoperatively elevated TMs levels had a significantly worse prognosis (25.4 and 21.0 months, respectively, P < 0.001). Furthermore, the relapse-free survival of patients with three preoperative normal TMs levels was significantly longer than those with one or two elevated TMs levels (21.9 vs. 11.3 or 3.0 months, respectively, P < 0.001). Non-normal values of all TMs before CS were identified as independent poor prognostic factors. CONCLUSIONS: Simultaneous measurement and assessment of the three TMs levels may help determine the surgical indications for UR-LAPC after systemic anticancer treatment.

Essential updates 2021/2022: Surgical outcomes of oligometastasis in pancreatic ductal adenocarcinoma.

Oligometastatic disease has been proposed as an intermediate state between localized and polymetastatic disease that can benefit from multimodal treatment, including surgery. There is a growing concern about performing surgery for oligometastatic pancreatic ductal adenocarcinoma, although there is still little evidence. We reviewed articles published between 2021 and 2022, focusing mainly on surgical outcomes. Furthermore, we summarized the current status of surgery in the multidisciplinary treatment of oligometastatic pancreatic cancer and discuss future perspectives. In liver oligometastasis, multimodal treatment including surgery achieved favorable long-term survival, especially in patients with good responses to preoperative chemotherapy, with a median survival time from 25.5 to 54.6 months. In addition, the data from the National Cancer Database in the United States showed that patients who underwent surgery for oligometastatic liver metastases had a significantly longer overall survival than those who received chemotherapy alone. Prognostic biomarkers were identified, including carbohydrate antigen 19-9 (CA19-9) levels at diagnosis and preoperative chemotherapy with normalization of CA19-9 levels or favorable radiological response. Patients with lung oligometastasis had a more favorable long-term prognosis than those with other recurrence sites, and the updated literature further confirmed the previous studies. Overall survival was favorable, with 84 months after initial surgery and 29.2 months after metastasectomy, and a 5-year survival rate of 60.6% was also reported. In peritoneal oligometastasis, the results of conversion surgery after good responses to preoperative treatment with intraperitoneal therapy or systematic chemotherapy were reported, and the conversion rate and long-term prognosis were favorable. There is a growing concern about performing surgery for oligometastatic pancreatic ductal adenocarcinoma. We reviewed articles published between 2021 and 2022, focusing mainly on surgical outcomes. Furthermore, we summarize the current status of surgery in multidisciplinary treatment of oligometastatic pancreatic cancer and discuss future perspectives.

Importance of triple tumor markers as biomarkers in patients with pancreatic ductal adenocarcinoma.

Aim: There is an urgent need to establish biomarkers for the treatment of pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to investigate the usefulness of the combined assessment of carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and duke pancreatic monoclonal antigen type 2 (DUPAN-2) in PDAC. Methods: We retrospectively investigated the impact of three tumor markers on overall survival (OS) and recurrence-free survival (RFS). Patients were classified into two groups: upfront surgery (US) and neoadjuvant chemoradiation (NACRT) groups. Results: In total, 310 patients were evaluated. In the US group, patients who had all three elevated markers showed a significantly worse prognosis than the others (median: 16.4 months, P = .005). In the NACRT group, patients who had elevated CA 19-9 and CEA levels after NACRT had significantly worse prognosis than the others (median: 26.2 months, P < .001). The elevated DUPAN-2 levels before NACRT were associated with significantly worse prognosis than normal levels (median: 44.0 vs 59.2 months, P = .030). Patients who had elevated DUPAN-2 levels before NACRT with elevated CA 19-9 and CEA levels after NACRT showed extremely poor RFS (median: 5.9 months). Multivariate analysis revealed that a modified triple-positive tumor marker indicating elevated DUPAN-2 levels before NACRT and elevated CA19-9 and CEA levels after NACRT was an independent prognostic factor of OS (hazard ratio: 2.49, P = .007) and RFS (hazard ration: 2.47, P = .007). Conclusions: The combined evaluation of three tumor markers may provide useful information for the treatment of patients with PDAC.

Laparoscopic mucosectomy for gastric duplication cysts that communicated with the spleen in a 10-year-old girl: A case report.

We report a case of laparoscopic mucosectomy for gastric duplication cysts that communicated with the spleen. A 10-year-old girl visited a local hospital with a chief complaint of intermittent left abdominal pain that had lasted for about 2 months. We diagnosed two gastric duplication cysts by ultrasonography and planned a laparoscopic extirpation. The elliptical masses were found in the splenic hilum and were 5 and 3 cm in diameter. The bigger one communicated with the spleen, so cystectomy could not be performed. Considering the risk of hemorrhage and the patient's age, we performed a mucosectomy rather than a partial splenectomy. The patient had an uneventful postoperative course. We histologically diagnosed gastric duplication cysts. Laparoscopic mucosectomy is a useful procedure for gastric duplication cysts that communicate with the spleen.

Biphasic clinical course of a ruptured right gastric artery aneurysm caused by segmental arterial mediolysis: a case report.

BACKGROUND: Gastric artery aneurysms are rarely caused by segmental arterial mediolysis (SAM), a condition that often involves multiple vessels. The clinical course of SAM after vessel rupture may vary depending on the involved vessels. For example, the "double-rupture phenomenon" observed following the rupture of the splenic artery aneurysm manifests as a biphasic and relatively slow clinical course. Even in cases of rupture of gastric artery aneurysm, the double-rupture phenomenon has only been reported in two cases so far. However, the rupture was not caused by SAM in either case. Herein, we present the apparent first case of a right gastric artery (RGA) aneurysm rupture caused by SAM that presented with a biphasic clinical course, possibly due to the double-rupture phenomenon. CASE PRESENTATION: A 54-year-old woman was transferred to the emergency department with severe abdominal pain and a cold sweat for a duration of 3 h. She had developed mild abdominal pain and nausea 3 days earlier. Her vital signs were stable. Physical examination revealed tenderness in the epigastric area. Abdominal contrast-enhanced computed tomography revealed an RGA aneurysm with contrast media extravasation. A diagnosis of hemoperitoneum following a ruptured RGA aneurysm was made, and the patient underwent angiography. However, this modality did not reveal any extravasation from the RGA due to an interruption in the peripheral branch of the artery. Nevertheless, to prevent major bleeding, we performed coil embolization at the point of interruption in the RGA, which we suspected to be a ruptured aneurysm. A distal gastrectomy with Roux-en-Y reconstruction for aneurysm resection was performed the following day. There were no postoperative complications, and the patient was discharged 17 days after surgery. Histologically, the RGA demonstrated multiple vacuoles in the medial muscle layer, which were characteristic of SAM. CONCLUSIONS: An RGA aneurysm rupture should be considered a differential diagnosis in patients presenting with hemoperitoneum with a slow or biphasic clinical course.