IQ Motif Containing GTPase-Activating Protein 3 Is Associated with Cancer Stemness and Survival in Pancreatic Ductal Adenocarcinoma.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of malignancy, with poor prognosis and rising incidence. IQ motif containing GTPase-activating protein 3 (IQGAP3) is a member of the IQGAPs family of scaffolding proteins that govern multiple cellular activities like cytoskeletal remodeling and cellular signal transduction. This study aimed to analyze the expression and biological function of IQGAP3 in PDAC. METHODS: We analyzed IQGAP3 expression in 81 PDAC samples by immunohistochemistry. RNA interference was used to inhibit IQGAP3 expression in PDAC cell lines. RESULTS: Immunohistochemical analysis of IQGAP3 showed that 54.3% of PDACs were positive for cytoplasmic expression of IQGAP3, with no expression found in non-neoplastic tissue. Furthermore, IQGAP3 expression was an independent poor prognostic factor in our immunostaining-based studies and analyses of public databases. Our cohort and the Cancer Genome Atlas database indicated that IQGAP3 is co-localized with kinesin family member C1 (KIFC1), which we previously reported as a cancer stem cell-associated protein. IQGAP3 small interfering RNA treatment decreased PDAC cell proliferation and spheroid colony formation via ERK and AKT pathways. DISCUSSION/CONCLUSION: These results suggest that IQGAP3, a transmembrane protein, is involved in survival and stemness and may be a promising new therapeutic target for PDAC.

Effects of transmembrane serine protease 4 on the survival in patients with pancreatic ductal adenocarcinoma undergoing surgery followed by adjuvant chemotherapy.

PURPOSE: The transmembrane serine protease 4 (TMPRSS4) gene is upregulated in various human cancers. However, its biological functions in pancreatic ductal adenocarcinoma remain unclear. We examined the expression of TMPRSS4 in pancreatic ductal adenocarcinoma tissues and its correlation with clinicopathological parameters in patients with pancreatic ductal adenocarcinoma who underwent surgery. METHODS: The TMPRSS4 expression was immunohistochemically examined in 81 PDAC patients with pancreatic ductal adenocarcinoma. We analyzed the association between the TMPRSS4 expression and clinicopathological factors, the recurrence-free survival (RFS), and the overall survival (OS) and examined the effect of TMPRSS4 expression on cell migration and sensitivity to 5-fluorouracil. RESULTS: The expression rate of TMPRSS4 in the samples was 62.9% (51/81). The TMPRSS4 expression was not correlated with any clinicopathological feature. The five-year overall and recurrence-free survival rates were significantly lower in the TMPRSS4-positive group than in the TMPRSS4-negative group. On a multivariate analysis, TMPRSS4 positivity, poorly differentiated histology, and non-adjuvant chemotherapy predicted a poor OS, while TMPRSS4 positivity and poorly differentiated histology predicted a poor RFS. TMPRSS4-silenced pancreatic ductal adenocarcinoma cells showed higher sensitivity to 5- fluorouracil than did the control siRNA-transfected cells. CONCLUSIONS: TMPRSS4 can be considered a prognostic factor and therapeutic target for pancreatic ductal adenocarcinoma.

Effect of body fat mass loss on prognosis of radical resection for pancreatic ductal adenocarcinoma based on bioelectrical impedance analysis.

BACKGROUND: Few reports have performed a prognostic analysis based on bioelectrical impedance analysis in patients with radical resection of pancreatic ductal adenocarcinoma (PDAC), and its usefulness in prognostic analysis remains unclear. This study aimed to evaluate body composition changes in patients undergoing radical resection for PDAC and analyze its impact on prognosis. METHODS: The medical records of radical resection for patients with PDAC were retrospectively reviewed, and the parameters of body composition, including body weight, skeletal muscle mass, body fat mass (BFM), and extracellular water-total body water ratio, from preoperatively to 12 months postoperatively, for each surgical procedure were measured based on direct segmental multifrequency bioelectrical impedance analysis with an InBody 770 (InBody Inc., Tokyo, Japan) device. The clinicopathological and prognostic factors were analyzed. RESULTS: Among 79 patients who underwent radical resection for PDAC, 36 (46%), 7 (8%), and 36 (46%) underwent pancreatoduodenectomy, total pancreatectomy, and distal pancreatectomy, respectively. The multivariate overall survival analysis demonstrated that BFM loss percentage at 1 month postoperatively ≧14% (p = 0.021), lymph node metastasis (p = 0.014), and non-adjuvant chemotherapy (p <  0.001) were independent poor prognostic factors. Multivariate analysis revealed that preoperative BFM < 12 kg and preoperative albumin < 3.5 g/dL were independently associated with BFM loss percentage at 1 month postoperatively ≧14% (p = 0.021 and p = 0.047, respectively). CONCLUSIONS: Loss of BFM in the early postoperative period may have a poor prognosis in radical resection of PDAC.

Clinical features and images of malignant lymphoma localized in the pancreatic head to differentiate from pancreatic ductal adenocarcinoma: a case series study.

BACKGROUND: Pathological examination by endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has been reported to be useful in diagnosing pancreatic malignant lymphoma (ML), but some ML cases are difficult to be differentiated from pancreatic ductal adenocarcinoma (PDAC). METHODS: This retrospective study included 8 patients diagnosed with ML that had a pancreatic-head lesion at initial diagnosis and 46 patients with resected PDAC in the pancreatic head between April 2006 and October 2021 at our institute. ML and PDAC were compared in terms of patients' clinical features and imaging examinations. RESULTS: The median tumor size was larger in ML than in PDAC (45.8 [24-64] vs. 23.9 [8-44] mm), but the median diameter of the caudal main pancreatic duct (MPD) was larger in PDAC (2.5 [1.0-3.5] vs. 7.1 [2.5-11.8] mm), both showing significant differences between these malignancies (both, P < 0.001). In the analysis of covariance, MLs showed a smaller caudal MPD per tumor size than PDACs, with a statistical difference (P = 0.042). Sensitivity and specificity using sIL-2R ≥ 658 U/mL plus CA19-9 < 37 U/mL for the differentiation of ML from PDAC were 80.0% and 95.6%, respectively. CONCLUSIONS: Diagnosing pancreatic ML using cytohistological examination through EUS-FNA can be difficult in some cases. Thus, ML should be suspected if a patient with a pancreatic tumor has a small MPD diameter per tumor size, high serum sIL-2R level, normal CA19-9 level. If the abovementioned features are present and still cannot be confirmed as PDAC, re-examination should be considered.

Psychosocial factors predicting symptoms of depression and anxiety in allogeneic hematopoietic stem cell transplant recipients in Japan.

OBJECTIVE: We explored whether a patient's psychosocial background before allogeneic hematopoietic stem cell transplantation (allo-HSCT) could predict the occurrence of psychiatric symptoms during treatment and after hospital discharge. METHOD: Logistic regression analysis was performed using INTERMED, a scale that comprehensively evaluates psychological factors such as psychiatric history, current mental status, and coping skills, and social factors such as social participation status, relationships with others, and living environment, which were used as independent variables. The Center for Epidemiologic Studies Depression Scale was used to measure depression, while the Profile of Mood States was used to measure anxiety and other symptoms. Both measures were used as dependent variables and were administered upon clean room admission, during clean room stay, at clean room discharge, and at 3, 6, and 12 months after hospital discharge. RESULTS: Participants included 70 patients (45 males and 25 females, mean age 53.3 ± 12.3 years). Thirty-eight patients participated in the program for the entire period, up to 12 months after hospital discharge. The total score on the Japanese version of the INTERMED and psychological factor scores assessed at baseline were significant predictors of depressed mood on discharge; however, there were no significant predictors of scores on the Profile of Mood States. CONCLUSIONS: A comprehensive pretransplant evaluation of psychosocial background can help predict the appearance of psychiatric symptoms after allo-HSCT. In patients who are expected to develop psychiatric symptoms after allo-HSCT, it is important to consider early intervention by a specialist and close monitoring by a medical team.

[Surgical Resection and Adjuvant Chemotherapy for Early Multiple Peritoneal Recurrence after Rejection of Hepatocellular Carcinoma-A Case Report].

Thus far, no consensus has been reached regarding the treatment of peritoneal dissemination of hepatocellular carcinoma (HCC). Here, we report a case of surgical resection and postoperative adjuvant chemotherapy for early multiple peritoneal recurrences of HCC. A 74-year-old man was found to have hepatic mass of 80 mm in size in S7 and 57 mm in S8, and was diagnosed with HCC. The patient underwent an open anterior segmentectomy and S7 subsegmentectomy of the liver. Peritoneal washing cytology revealed the presence of malignant cells. The tumor strongly adhered to the diaphragm, necessitating partial resection of the diaphragm. Six months after surgery, multiple disseminated recurrences were found on the CT scan. Atezolizumab plus bevacizumab combination therapy was initiated, but tumor size enlargement and elevation of tumor markers were observed after 3 courses. Resection of the dissemination(2 on the surface of the lung right lower lobe, 1 on the right renal superior retroperitoneum, 1 on the omentum, and 1 invading the jejunum)was performed. Considering the high risk of recurrence, postoperative adjuvant chemotherapy with lenvatinib was administered for 1 year. No recurrence has been found for 16 months after the resection. Although more cases are needed to conclude, this case report suggests that surgical resection and postoperative administration of lenvatinib may be effective in the treatment of disseminated HCC lesions at a high risk of recurrence.

[Unresectable Esophageal Cancer on the Elderly Woman Which Was Treated Effectively with Ipilimumab plus Nivolumab-A Case Report].

Until now, the standard treatment regimen was cisplatin plus 5-FU as the chemotherapy for unresectable advanced esophageal cancer. Immune checkpoint inhibitors have brought about changes to the cancer treatment. Ipilimumab plus nivolumab was approved in June 2022 for unresectable advanced esophageal cancer. An 86-year-old woman who was normal ADL and cognitive function was diagnosed with unresectable esophageal cancer with multiple lymph node metastasis. We thought surgery or chemotherapy is impossible because of her age and health status, so we treated with ipilimumab plus nivolumab. After 2 cycles, tumor became reduced in size on endoscopic examination and accumulation in primary lesion and lymph node metastases was decreased considerably on positron emission tomography/computed tomography(PET-CT). Though the cycle after initiation of chemotherapy was uneventful, tumor regrowth on the examinations at 5 months. The patient's condition of the disease was improved temporarily after change chemotherapy to paclitaxel as the second-line therapy, but she died due to disease progression at 11.4 months from initiation of treatment. Ipilimumab plus nivolumab can become one of the effective treatments for patients who are impossible to treat with conventional chemotherapy.

Long-standing diabetes mellitus increases concomitant pancreatic cancer risk in patients with intraductal papillary mucinous neoplasms.

BACKGROUND: When monitoring patients with an intraductal papillary mucinous neoplasm (IPMN), it is important to consider both IPMN-derived carcinoma and concomitant ductal adenocarcinoma (PDAC). The latter is thought to have a poorer prognosis. We retrospectively analyzed the risk factors for concomitant PDAC in IPMN. METHODS: In total, 547 patients with pancreatic cysts, including IPMNs inappropriate for surgery on initial diagnosis, encountered from April 2005 to June 2019, were reviewed. We performed surveillance by imaging examination once or twice a year. RESULTS: Five IPMNs with high-grade dysplasia and one IPMN associated with invasive carcinoma were encountered. In comparison, 14 concomitant PDACs were encountered. The prognosis was very poor for concomitant PDACs. All 14 PDAC patients had IPMNs. In patients with IPMNs, long-standing diabetes mellitus was the only significant risk factor for concomitant PDAC in both univariate and multivariate analyses (P < 0.001 and P < 0.01, respectively). Furthermore, patients with IPMNs and diabetes mellitus had a high frequency of concomitant PDACs (9.5%, 9/95) in a median 48-month surveillance period. CONCLUSIONS: When monitoring IPMNs, the development of not only IPMN-derived carcinomas but also concomitant PDACs should be considered. During this period, it may be prudent to concentrate on patients with other risk factors for PDAC, such as long-standing diabetes mellitus.

[A Case of Pancreatoduodenectomy for Multiple Nonfunctioning Neuroendocrine Tumors of the Duodenum].

A 42-year-old woman was referred to our hospital because of incidentally discovered multiple neoplastic lesions of the duodenum. Upper gastrointestinal endoscopy showed there were more than 10 submucosal tumors and less than 10 mm in diameter. Histological examination of the biopsy specimen revealed nonfunctioning neuroendocrine tumor(NET). Enhanced computed tomography(CT)showed neither regional lymph node nor distant metastasis, so we performed pancreatoduodenectomy with regional lymph node dissection. Pathological examination showed multiple NET G2 less than 5 mm in size with invasion to muscularis propria and 3 lymph node metastases, so diagnosed as pT2(m)N1M0, Stage Ⅲ. She is alive without tumor recurrence for 14 months after surgery. In general, sporadic nonfunctioning NET of the duodenum less than 10 mm in diameter has low possibility of lymph node metastasis. However, our case suggested the possibility of lymph node metastasis in patients with multiple NETs of the duodenum, in spite of small size. Therefore, pancreatoduodenectomy with regional lymph node dissection should be considered for multiple nonfunctioning NETs of the duodenum.

[A Case of Sclerosing Angiomatoid Nodular Transformation Resected for Suspected Relapse of Diffuse Large B-cell Lymphoma].

We report a case of sclerosing angiomatoid nodular transformation(SANT)5 years after remission of diffuse large B-cell lymphoma(DLBCL). A 64-year-old woman was diagnosed a nodular mass at the spleen by a contrast-enhanced CT scan 5 years after the relief for DLBCL. The mass showed accumulation of FDG. Because the possibility of the recurrence of malignant lymphoma could not be ruled out, laparoscopic splenectomy was performed for diagnosis and treatment. Immunohistologically, the resected mass revealed 3 different vascular components pattern(CD31, CD34 and CD8), so we diagnosed SANT. It is difficult to distinguish from malignant lymphoma or cancer even with various examination, so laparoscopic splenectomy is useful for diagnosis and treatment.