Presence of CD44v9-Expressing Cancer Stem Cells in Circulating Tumor Cells and Effects of Carcinoembryonic Antigen Levels on the Prognosis of Colorectal Cancer.

Circulating tumor cells (CTCs) are cancer cells released from the primary tumor into the bloodstream, and contain cancer stem cells that influence tumor survival, recurrence, and metastasis. Here, we investigated CD44v9 expression in CTCs and impact of preoperative carcinoembryonic antigen (CEA) levels on colorectal cancer (CRC) prognosis. We analyzed the expression of CD44v9 mRNA in CTCs using reverse transcription-polymerase chain reaction and preoperative CEA levels in blood samples obtained from 300 patients with CRC. Subsequently, we evaluated the association of CD44v9 expression and CEA levels with clinicopathological factors. CD44v9 mRNA was expressed in 31.3% of the patients, and was significantly associated with liver metastasis. Patients with positive CD44v9 expression had a lower 5-year survival rate (62.3%) than those with negative CD44v9 expression (82.8%, p < 0.001). Cox regression analysis identified CD44v9 expression and high CEA levels (≥5 ng/mL) as poor prognostic factors, while negative CD44v9 expression and low CEA levels (<5 ng/mL) were associated with favorable prognosis (hazard ratio = 0.285, p = 0.006). These results suggest that a combination of CD44v9 mRNA expression in CTCs and serum CEA levels could serve as a valuable prognostic marker for CRC, potentially enhancing the accuracy of prognosis predictions.

Monitoring Metastatic Colorectal Cancer Progression According to Reactive Oxygen Metabolite Derivative Levels.

Oxidative stress has been implicated in the development, proliferation, and metastasis of colorectal cancer, but few studies have considered how oxidative stress changes in relation to treatment response. In this study, we investigated whether the rate of change in reactive oxygen metabolite derivatives (d-ROM)-serum markers of oxidative stress-could predict treatment response in metastatic colorectal cancer. We enrolled 53 patients with metastatic colorectal cancer who were treated with 3 months of chemotherapy. We measured d-ROM levels and performed computed tomography before and after chemotherapy, and we examined the change in d-ROM levels for each anticancer treatment. Factors influencing the d-ROM ratio (post-treatment: pre-treatment levels) were examined using linear regression analysis. d-ROM levels decreased in patients showing a partial response (p < 0.001) and increased in those showing disease progression (p = 0.042). An increasing d-ROM ratio was associated with disease progression (regression coefficient: 0.416, 95% confidence interval: 0.279-0.555, p < 0.001). Our study indicates that d-ROM levels are useful markers of tumor progression and that the d-ROM ratio is useful for predicting treatment response in patients with metastatic colorectal cancer.

Follicular cholangitis mimicking a common bile duct cancer: a case report.

BACKGROUND: Follicular cholangitis (FC) is a benign bile duct disease that was first reported 2003. Pathologically, it is characterized by lymphoplasmacytic infiltration with multiple lymphoid follicle formations under the mucosal layer of the biliary tract. However, as this disease is extremely rare, little is known about its etiology and pathogenesis. CASE PRESENTATION: A 77-year-old woman was diagnosed with middle bile duct stenosis and potential increases in alkaline phosphatase (ALP) and γ-glutamyl transpeptidase levels (γ-GTP). Carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and IgG4 levels were all within the normal limits. Contrast-enhanced computed tomography (CE-CT) and magnetic resonance imaging (MRI) revealed bile duct dilation from intrahepatic to upper common bile duct and an irregular mass lesion in distal bile duct. Additionally, multiple overlapping leaf-like folds were detected. 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET/CT) did not demonstrate fluorodeoxyglucose uptake. Subtotal stomach-preserving pancreaticoduodenectomy with regional lymph node dissection was performed because common bile duct cancer could not be ruled out. The resected specimen showed diffuse homogeneous middle bile duct wall thickening. Microscopically, the lesion exhibited thick fibrosis with several invaded lymphoplasmacytic cells, and lymphoid follicle formations were detected under the mucosal layer. Immunohistochemical staining (IHC) revealed positive for CD3, CD4, CD20 and CD79a, and these findings led to a final diagnosis of FC. The patient has not experienced recurrence to date (42 months postoperatively). CONCLUSIONS: Currently, accurate preoperative diagnosis of FC is difficult. More cases must be accumulated to generate additional knowledge on its precise diagnosis and proper treatment.

[Short-Term Outcomes of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer].

In recent years, an increasing number of reports have demonstrated the usefulness of neoadjuvant chemoradiotherapy (NACRT). In our department, we consider cT3-4 and/or cN-positive locally advanced rectal cancer as an indication for NACRT. We have retrospectively evaluated the efficacy and safety of NACRT in 11 patients who underwent NACRT from November 2018 to July 2022. All patients were male, with a median age of 69 years, and cStage was Ⅱa: 1, Ⅱc: 1, Ⅲb: 5, Ⅲc: 3, and Ⅳa: 1. All patients completed NACRT, and there were no cases of CTCAE Grade 3 or higher adverse events or treatment interruptions. The response rate was 72.7%, and histological response grade were Grade 3: 1(9.1%), 2: 4 (36.4%), 1b: 6(54.5%), and surgical margin was negative in all cases. Pathological down stage was obtained in 45.5% of cases, and pCR was obtained in 1 case(9.1%). The median observation period was 17 months, and during the period, 2 cases(18.2%)developed recurrence, both of which were pulmonary metastases, and no local recurrence including pelvic lymph node recurrence was observed. NACRT for locally advanced rectal cancer is considered a relatively safe and highly locally controllable preoperative treatment.

Anti-Prokineticin1 Suppresses Liver Metastatic Tumors in a Mouse Model of Colorectal Cancer with Liver Metastasis.

Multidisciplinary treatment for colorectal cancer (CRC) has undergone significant advances, and molecularly targeted drugs have substantially improved patient prognosis. However, one problem with current molecularly targeted therapeutics is that they must be used in combination with anticancer agents. New molecular targeted therapies that can be used alone are needed. We have previously identified prokineticin1 (PROK1) factor as a therapeutic potential target for CRC. PROK1 factor is involved in the angiogenesis of tissues surrounding CRC tumors. Additionally, PROK1 receptors 1 and 2 are expressed in CRC cell lines, playing roles in cell proliferation via an autocrine mechanism and in the signaling system. In this study, a liver metastasis mouse model was developed using human colorectal cancer cell lines, and mice were divided into anti-PROK1 antibody administration and control groups. Mice were treated intraperitoneally with antibodies or phosphate-buffered saline (control) every three days. The number, size, and cell proliferation ability of metastatic lesions were analyzed. Our results suggested that the number, size, and cancer cell proliferation ability of metastatic lesions decreased, and the survival time significantly increased in the antibody-treated group compared to those in the control group. Thus, the anti-PROK1 antibody therapy suppressed the cell proliferation ability of liver metastatic lesions in a CRC mouse model, suggesting its potential as a novel treatment strategy.

[A Case of BRAF V600E-Mutant Colorectal Cancer Treated Effectively by Encorafenib, Binimetinib, and Cetuximab Triple Therapy].

A 76-year-old woman was diagnosed with left-sided transverse colon cancer invading the pancreatic tail with multiple liver metastases and peritoneal dissemination. Preoperative diagnosis was cT4b(SI)N2aM1c(H3, P1), cStage Ⅳc, harboring BRAF V600E mutation. Transverse colostomy was performed, and FOLFOXIRI plus bevacizumab(BEV)was administered. After 12 chemotherapy cycles, the primary tumor and metastatic lesions showed partial response. Because of CEA elevating after 5-FU plus LV plus BEV as maintenance therapy was changed, the regimen was switched to encorafenib plus binimetinib plus cetuximab as the second-line chemotherapy. The patient developed dermatitis around the colostomy after the start of the second-line chemotherapy, resulting in temporally cetuximab monotherapy. After improvement of dermatitis, the patient resumed encorafenib plus binimetinib, improving liver metastases. Eight months after the start of the second- line, the patient has been administered with triple therapy and had stable disease status.

Oxidative Stress as a Biomarker for Predicting the Prognosis of Patients with Colorectal Cancer.

INTRODUCTION: Excess oxidative stress is generated by inflammation and cancer, and it is involved in the development and metastasis of colorectal cancer. However, there are few reports on the relationship between blood oxidative stress and prognosis. This study examined the usefulness of derivatives of reactive oxygen metabolites (d-ROMs), a measure of oxidative stress, and the neutrophil-to-lymphocyte ratio (NLR), an inflammatory marker, as prognostic markers in colorectal cancer. METHODS: The study enrolled 163 patients who underwent colorectal cancer resection at our institution between 2013 and 2018. Blood samples were taken preoperatively to measure d-ROMs and NLR. Spearman's correlation analysis was used to examine the relationships between d-ROMs and NLR, and Cox regression analysis was performed to identify factors associated with d-ROMs and NLR. The Kaplan-Meier method was used to calculate disease-specific survival (DSS). RESULTS: There was no correlation between d-ROMs and NLR. Tumor size was significantly associated with d-ROMs and NLR. DSS was significantly worse among patients with high d-ROMs or high NLR, although patients with high d-ROMs and high NLR had the worst DSS. In the multivariate analysis, distant metastasis and the high d-ROM/NLR combination were significant factors associated with DSS (p < 0.001, hazard ratio [HR] = 22.880 and p = 0.049, HR = 2.391, respectively). CONCLUSION: Preoperative d-ROMs and NLR reflect the tumor size among patients with colorectal cancer. The combination of d-ROMs and NLR may effectively predict prognosis in patients with colorectal cancer.

Stage IV anal canal squamous cell carcinoma with long-term survival: a case report.

BACKGROUND: Currently, no established standard treatment exists for metastatic anal squamous cell carcinoma. We report a case of complete response in a patient with stage IV anal squamous cell carcinoma after undergoing multidisciplinary treatment. CASE PRESENTATION: A 62-year-old woman visited a nearby doctor with a chief concern of severe pain associated with a firm mass in the anus. The patient was diagnosed with anal canal squamous cell carcinoma and liver metastases and referred to First Department of Surgery Faculty of Medicine University of Fukui for treatment. The patient received a TNM classification of T4N0M1 and stage IV. Rectal amputation was performed; however, postoperative complications hindered immediate anticancer therapy and the liver metastases exacerbated. Radiofrequency hyperthermia and systemic chemotherapy were performed 3 months postoperatively. A prominent reduction in the liver metastasis was observed. Lung metastases appeared during the course of systemic chemotherapy. Radiotherapy was performed to treat the lung lesion and resolved. Radiotherapy was also performed for liver metastasis. The lesion in the liver showed resolution after 54 months postoperatively, and treatment with the anticancer drug was discontinued. Ten-year follow-up findings suggested complete resolution of the lesion in response to the treatment protocol followed in this case. This long-term survival was achieved through a multidisciplinary treatment. CONCLUSIONS: The present case suggests that multidisciplinary treatment approach is effective for resolving stage IV anal squamous cell carcinoma, and addition of new anticancer drug therapy may improve the overall prognosis of squamous cell carcinoma.

Fructan Improves Survival and Function of Cryopreserved Rat Islets.

Cryopreservation of pancreatic islets enables their long-term storage and subsequent transplantation; however, post-cryopreservation, islets viability, and functions are reduced to a significant extent. Islet is composed of five cells (α cell, ß cell, δ cell, ε cell, and PP cell), and blood vessels that carry the nutrition. Freezing technology of the organization has not developed a good method. This paper is studied using a fructan which has been found to effectively freeze protect a material of the cell. Islet transplantation has been established as an effective means of treating patients with type 1 diabetes. In this study, we demonstrated the effectiveness of using a fructan on the cryopreserved islets by showing valid results for diabetes. Isolated rat islets were cryopreserved using phosphate-buffered saline (PBS) supplemented with different concentrations of fructan and/or dimethyl sulfoxide (DMSO) in FBS. The survival rates of the islets were estimated at different time intervals, and insulin secretion function was tested in vitro. Furthermore, the in vivo function was tested by syngeneic transplantation into streptozotocin-induced diabetic rats, and the grafts were analyzed histologically and immunohistochemically. Fructan significantly increased islet survival; 30% fructan led to survival rates of more than 90% on day 3, which was significantly higher than those of the DMSO groups (p < 0.05). For both fructan and DMSO, the survival showed dose dependence, with the highest rates observed for 30% fructan and 10% DMSO, respectively (p < 0.05). The fructan groups showed a significantly increased insulin secretion volume in comparison to the DMSO groups (p < 0.05). Furthermore, cell clusters of pancreatic islets were well maintained in the fructan group, whereas margin collapse and vacuolation were observed in the DMSO group. Three days after transplantation of pancreatic islets preserved with 30% fructan, the blood glucose levels of diabetic rats were restored to the normal range, and removal of transplanted pancreatic islets from the kidney led to a profound increase in blood glucose levels. Together, these results show that a fructan is effective at cryopreserving rat pancreatic islets for subsequent transplantation.

[A Long Term Survival Case of Gastric Cancer with Peritoneal Dissemination Responding to Intraperitoneal Chemotherapy].

A 32-year-old woman was admitted our hospital due to epigastric discomfort. The patient diagnosed as having scirrhous carcinoma of the stomach by upper gastrointestinal scope. Peritoneal dissemination and ovarian metastasis were confirmed by the diagnostic laparoscopy. Therefore, combination chemotherapy with S-1 and intraperitoneal chemotherapy(ip)with docetaxel (DTX) was started. After 2 courses chemotherapy, laparoscopy was performed again. Peritoneal dissemination was scarred, but biopsy showed altered AE1/AE3 positive cells, and increased left ovarian metastasis, so systemic chemotherapy was changed to DCS chemotherapy and added DTX ip. After 4 courses chemotherapy and 7 months after the first diagnosis, subtotal gastrectomy, hysterectomy and bilateral adnexectomy were performed because the cytology and tumor marker remained within normal range. In histopathological diagnosis, the effect of chemotherapy was Grade 2 at the primary site and Grade 3 at the metastatic site. Nine years have passed since the initial diagnosis and she has no relapse with postoperative adjuvant chemotherapy.

[Examination of Prognosis and Adjuvant Chemotherapy in Stage â ¡ and Stage â ¢ Resected Colorectal Cancer in the 9th Edition Japanese Classification of Colorectal Carcinoma].

In the 9th edition Japanese Classification of Colorectal Carcinoma, Stage Ⅱ and Stage Ⅲ colorectal cancer(CRC)were subdivided by TNM classification on invasion and number of lymph node metastases. We studied prognostic comparison and relation of adjuvant chemotherapy at the new classification. We included 400 cases with resected Ⅱ and Ⅲ CRC from 2007 to 2014. Ⅱa/Ⅱb/Ⅱc/Ⅲa/Ⅲb/Ⅲc were 97/68/20/24/124/67 cases. Adjuvant chemotherapy was performed at 19/32/45/66/59/70% in Ⅱa/Ⅱb/Ⅱc/Ⅲa/Ⅲb/Ⅲc, with or without adjuvant chemotherapy at each stage survival rates were compared. In Ⅱa/Ⅱb/Ⅱc, DSS was 97/97/82% and DFS was 89/88/76%, and the prognosis of Ⅱc was significantly worse. In Ⅲa/Ⅲb/Ⅲc, DSS was 95/86/57% and DFS was 82/77/41%. By the presence or absence of adjuvant chemotherapy, significantly differences were obtained at Ⅲb and Ⅲc. Prognosis of Ⅱc was almost same as Ⅲb, and prognosis of Ⅲa was almost same as Ⅱb. Therefore, we considered adjuvant chemotherapy with oxaliplatin should be performed to Ⅱc, Ⅲb, and Ⅲc.

Primary hepatic diffuse large B-cell lymphoma presenting unusual imaging features.

Primary hepatic lymphomas are frequently misdiagnosed, due to their rarity and non-specific clinical manifestations. As these tumors can be successfully treated with chemotherapy and/or radiotherapy, early recognition on imaging is essential to avoid unnecessary surgery. We report a case of primary hepatic lymphoma in a 73-year-old woman presenting with a 1-week history of persistent fever and elevated hepatobiliary enzymes. Ultrasound showed a hypoechoic hepatic mass in the anterior segment. Dynamic contrast-enhanced computed tomography (CT) revealed an ill-defined solitary mass showing peripherally dominant slight-to-moderate enhancement contrasting with a hypovascular central area. On magnetic resonance imaging, the mass showed moderate hyperintensity on T2-weighted imaging, hypointensity on T1-weighted imaging, doughnut-like hyperintensity on diffusion-weighted imaging, and an obviously low apparent diffusion coefficient (ADC). The pattern of enhancement resembled that of CT. Neither calcification nor any fat component was observed. Doughnut-like accumulation was seen on 18F-fluorodeoxyglucose (FDG)-positron emission tomography/CT without other FDG-avid lesions. Imaging findings suggested the possibility of cholangiocellular carcinoma, but the low ADC and extremely high FDG accumulation were suggestive of malignant lymphoma, and diffuse large B-cell lymphoma was pathologically confirmed from percutaneous biopsy. The mass disappeared after radiochemotherapy, and no recurrence has been observed for 3 years.

A typical case of resected pancreatic hamartoma: a case report and literature review on imaging and pathology.

BACKGROUND: Pancreatic hamartomas are rare entities and difficult to diagnose before resection. We report a case of resected pancreatic hamartoma and literature review of typical characteristics of the lesion. CASE PRESENTATION: A 78-year-old man presented with a mass in his pancreas, which was incidentally identified when he experienced pneumonia. No remarkable symptoms were observed, and laboratory tests showed no abnormalities, except a slight carcinoembryonic antigen elevation. Enhanced computed tomography and magnetic resonance imaging showed a well-demarcated solid mass with heterogeneous contrast that was 2 cm in size. A gradual enhancement pattern was also observed. The biopsy revealed no specific findings; therefore, surgical resection was necessitated to confirm the diagnosis. Histopathologically, ducts, acinar cells, and adipose cells without atypia were observed among abundant fibrous stroma, but islets of Langerhans and peripheral nerves were absent. An immunohistochemical examination demonstrated CD34 and c-kit positive staining in the stromal cells, S-100 positivity in the adipose cells, and a lack of elastic fibers in the duct walls. The lesion was diagnosed as a pancreatic hamartoma. CONCLUSION: Asymptomatic pancreatic hamartomas can avoid resection. A careful consideration of imaging and appropriate immunohistochemistry of biopsy specimen may facilitate accurate diagnosis before resection. Therefore, sufficient recognition of the characteristics of pancreatic hamartomas is desirable.

RPN2 is effective biomarker to predict the outcome of combined chemotherapy docetaxel and cisplatin for advanced gastric cancer.

Preoperative chemotherapy, often using docetaxel and cisplatin, is a famous treatment option for advanced gastric cancer in Japan. But, there are no effective biomarkers that predict the therapeutic outcome on gastric cancer. Ribophorin II (RPN2) silencing, which decreases glycosylation of P-glycoprotein (P-gp) and membrane localization, restores the sensitivity to docetaxel and cisplatin. We inquired whether RPN2 expression in advanced gastric cancer biopsy tissues may be a predictive biomarker for docetaxel and cisplatin combination preoperative chemotherapy. We judged RPN2 expression immunohistochemically in upper endoscopic biopsy tissues from 40 advanced gastric cancer patients, who received the combination preoperative chemotherapy of docetaxel and cisplatin and gastrectomy with D2 resection during 2008-2014, and compared clinicopathological effects between RPN2-positive and RPN2-negative groups. We also examined sensitivity of RPN2-knockout gastric cancer cells by genome editing to docetaxel and cisplatin. RPN2 expression was observed in 19 of 40 gastric cancer cases. The RPN2-negative group had better clinicopathological responses to docetaxel and cisplatin combination chemotherapy than the RPN2-positive group, especially, in assessment of the histopathological criteria to preoperative chemotherapy. And RPN2-negative group had a significantly higher overall survival and progression-free survival compared to the RPN2-positive group. We also found RPN2-knockout to change docetaxel and cisplatin sensitivity in vitro. RPN2 expression in upper endoscopic biopsy tissues can be an effective predictive biomarker for the treatment outcome to docetaxel and cisplatin combination preoperative chemotherapy in advanced gastric cancer.

Long-term survival in a patient with Virchow's lymph node metastasis of cecal cancer.

The patient was a 53-year-old male with a chief complaint of bloody stool. To treat the cecal colon cancer, right hemicolectomy was performed. Histological examination showed moderately differentiated adenocaricinoma, SE, N3, H0, P0, M0 Stage IIIb by Japanese Classification of the Colorectal Carcinoma. After the operation, the patient received a chemotherapy with 6 cycles of Capecitabine regimen. After 1 year later, computed tomography detected swelling of Virchow's lymph node and tumor in the thyroid gland. By fine-needle aspiration cytology, thyroid gland tumor was diagnosed as papillary cancer and Virchow's lymph node was detected adenocarcinoma which was metastasis of cecal cancer. Total thyroidectomy and cervical lymph node dissection were performed. After the operation, the patient received chemotherapy with 6 cycles of FOLFOX regimen. And the patient had taken UFT/LV for 30 months. Now he has no recurrence and keeps his quality of life high. He has been alive for 80 months since the first operation. Virchow lymph node dissection can be one of the options of treatment of metastasis.

Favorable response of colonic mixed adenoneuroendocrine carcinoma to streptozocin monotherapy.

Mixed adenoneuroendocrine carcinoma (MANEC) of the colon is rare and has a poor prognosis. Here, we report a case of MANEC in the ascending colon, in which streptozocin monotherapy achieved a partial response. A 36-year-old woman underwent right hemicolectomy for colonic polyposis, which included ascending colon cancer. Pathological examination revealed that some mucosal polyps were adenocarcinoma while one submucosal polyp was neuroendocrine carcinoma. Adjuvant chemotherapy was not administered, and 5 months after the operation, multiple liver metastases were identified. She was started on modified (5-FU, leucovorin, oxaliplatin) followed by XELOX (capecitabine, oxaliplatin) plus bevacizumab. Although these regimens helped achieve stable disease, computed tomography showed that the hepatic metastatic lesions had enlarged 4 months later. Subsequently, the regimen was changed to streptozocin monotherapy (1000 mg/m2, weekly). After 5 cycles, the regimen achieved partial response and was continued for a total of 17 courses without significant adverse events until progressive disease. As a third-line chemotherapy regimen, cisplatin plus etoposide (EP) was administered. The EP regimen reduced the size of the hepatic and ovarian metastatic lesions but severe neutropenia and anemia was observed. Amrubicin monotherapy was also administered as fourth-line chemotherapy but a good clinical response was not detected, and the patient died 20 months after the operation. Streptozocin monotherapy has the potential to be a therapeutic option for mixed adenoneuroendocrine carcinoma of the colon.

Clinical influence of anastomotic stricture caused by pancreatogastrointestinalstomy following pancreatoduodenectomy.

BACKGROUND AND PURPOSE: Pancreatic fistula after pancreatoduodenectomy (PD) is not uncommon, but few reports describe a stricture after pancreatogastrointestinalstomy. We investigated the clinical influence of anastomotic stricture caused by pancreatogastrointestinalstomy after PD. METHODS: The subjects of this prospective cohort study were 132 patients who underwent PD or pylorus-preserving PD. We reviewed the relationships between pancreatic duct dilatation of the remnant pancreas and several risk factors. We also compared pancreatic duct dilatation with pancreatic atrophy and analyzed nutrient parameters in the first postoperative year. RESULTS: Patients with a preoperative pancreatic duct diameter less than 3 mm had a significantly dilated postoperative pancreatic duct diameter (p = 0.0001). The average atrophy rate of the remnant pancreas was 26.3 %, with the lowest atrophy rate (7.3 %) seen in patients without pre- or postoperative pancreatic duct dilation. A normal pancreas in which pancreatic duct dilatation developed postoperatively had a high atrophy rate (34.9 %). Moreover, only patients without pre- or postoperative pancreatic dilatation gained body weight (3.9 %). CONCLUSION: This study shows a significant correlation between pancreatic atrophy rate and weight loss. Atrophy of the remnant pancreas caused by anastomotic stricture influences the exocrine function of patients after PD. The anastomotic method must be improved to prevent pancreatic duct dilatation and allow for early diagnosis and management of stenotic lesions.

Large-cell neuroendocrine carcinoma of the common bile duct: a case report and a review of literature.

BACKGROUND: Large-cell neuroendocrine carcinoma (LCNEC) of the bile duct is extremely rare and is a high-grade type of neuroendocrine tumor with an aggressive clinical course. Here, we report a case of LCNEC of the extrahepatic bile duct. CASE PRESENTATION: An 80-year-old man presented with severe jaundice. Endoscopic retrograde cholangiography and enhanced computed tomography revealed complete obstruction of the common bile duct (CBD) by a dense tumor measuring 1.5 cm in diameter. Although there were no malignant cells in the biliary brush cytology, we suspected a cholangiocarcinoma and performed extrahepatic bile duct resection. Histologically, the LCNEC occupied most of the places deeper than the stratum submucosum and an adenocarcinoma component, approximately 15%, was present in the mucosa. There were no transitional areas between the two components. Immunohistochemically, the LCNEC cells were reactive for CD56 and synaptophysin and had a high MIB-1 index (72%). The patient died of multiple liver, lung, and peritoneal metastases 3 months after surgery. CONCLUSIONS: LCNEC of the CBD is particularly rare and has a very poor prognosis. Only five cases have been reported in the literature; therefore, there is no established effective therapy, including surgery, for LCNEC of the CBD at present. An accumulation of additional cases and further studies of multimodal treatment are required in the future to improve the prognosis.

Acinar cell carcinoma of the pancreas in childhood.

A 12-year-old Japanese girl with pancreatic acinar cell carcinoma is presented. She was referred to our hospital with upper abdominal pain on exercise. Computed tomography scan showed a 17 × 17 × 12 cm heterogeneous mass in the right abdominal cavity centering around the pancreatic head to the anterior pararenal space. We performed pylorus-preserving pancreatoduodenectomy, because the tumor invaded the pancreatic head. Macroscopically, the tumor was a 19 × 18 cm, encapsulated mass derived from the pancreatic head without invasion to the surrounding organs, and consisted of solid and cystic portions. Histological examination showed tumor cells proliferating in an acinar pattern and invading the duodenal muscle layer. Immunohistochemically, tumor cells were positive for α1 trypsin and α1 chymotrypsin. From these histological findings, we diagnosed the lesion as an acinar cell carcinoma of the pancreas. We report this case of childhood acinar cell carcinoma, which is extremely rare, with a review of the literature.

Hepatic artery infusion therapy is effective for chemotherapy-resistant liver metastatic colorectal cancer.

BACKGROUND: Systemic FOLFOX (folinic acid (leucovorin (LV)), 5-fluorouracil (5-FU), and oxaliplatin), FOLFIRI (LV, 5-FU, and irinotecan), or FOLFOXIRI (5-FU, leucovorin, oxaliplatin, and irinotecan) chemotherapy regimens and additional molecular-target treatments, including anti-vascular endothelial growth factor, anti-epidermal growth factor receptor, and anti-multi-kinase antibodies, have been recommended for unresectable recurrent colorectal cancers. However, no effective treatments are currently available for cases refractory to these therapies. Therefore, the development of alternative therapies is desired. In the present study, we administered and observed the effectiveness of hepatic artery infusion therapy (HAIC) in patients with unresectable liver metastatic colorectal cancers refractory to systemic chemotherapy. In addition, we observed that in an experimental system with anticancer drug-resistant colorectal cancer lines, apoptosis and cell death could be induced by increasing anticancer drug concentrations. METHODS: The subjects had liver metastatic colorectal cancers that were unresponsive to systemic chemotherapy (FOLFOX/FOLFIRI) or to additional molecular-target therapies for progressive disease. Hepatic infusion tube placement was conducted according to the Seldinger method to insert a catheter with a side hole via the right femoral artery. A coiling procedure was performed to prevent drug influx into the gastroduodenal artery. Ten subjects were selected, and the results were evaluated after HAIC (5-FU and LV administered once weekly). Moreover, anticancer drug-resistant colorectal cancer lines were subsequently prepared to investigate whether increased anticancer drug concentrations could induce apoptosis or cell death. RESULTS: Of the 10 subjects, 3 (30 %) showed partial response and 4 (40 %) showed no change according to computed tomography imaging findings obtained after hepatic artery infusion. The disease control rate was 70 %. Eight subjects had improved quality of life. Survival time ranged from 2 to 16 months (median, 9 months). Meanwhile, we found that higher anticancer drug concentrations induced apoptosis and cell death in an anticancer drug-resistant colorectal cancer cell line. CONCLUSIONS: HAIC was effective in some systemic chemotherapy-resistant colorectal cancers with liver metastases and should be considered as an effective palliative therapy. This supports the finding that apoptosis and cell death could be induced in anticancer drug-resistant colorectal cancer cells in a drug concentration-dependent manner.