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In this study, we aimed to develop and validate a nomogram to predict overall survival (OS) and recurrence-free survival (RFS) in patients who underwent curative resection of ampulla of Vater (AOV) cancer. This is the first study for nomograms in AOV cancer patients using retrospective data based on an international multicenter study.A total of 2007 patients with AOV adenocarcinoma who received operative therapy between 2002 January and 2015 December in Korea and Japan were retrospectively assessed to develop a prediction model. Nomograms for 5-year OS and 3-year RFS were constructed by dividing the patients who received and who did not receive adjuvant therapy after surgery, respectively. Significant risk factors were identified by univariate and multivariate Cox analyses. Performance assessment of the four prediction models was conducted by the Harrell's concordance index (C-index) and calibration curves using bootstrapping.A total of 2007 and 1873 patients were collected for nomogram construction to predict 5-year OS and 3-year RFS. We developed four types of nomograms, including models for 5-year OS and 3-year RFS in patients who did not receive postoperative adjuvant therapy, and 5-year OS and 3-year RFS in patients who received postoperative adjuvant therapy. The C-indices of these nomograms were 0.795 (95% confidence interval [CI]: 0.766-0.823), 0.712 (95% CI: 0.674-0.750), 0.804 (95% CI: 0.7778-0.829), and 0.703 (95% CI: 0.669-0.737), respectively.This predictive model could help clinicians to choose optimal treatment and precisely predict prognosis in AOV cancer patients.

Introduction Pancreatic acinar cell carcinoma (ACC) is a relatively rare neoplasm. Furthermore, tumor rupture is extremely rare. Only 1 case of ruptured pancreatic ACC has been reported, and the long-term outcome of the case is unknown. Here, we present a case of spontaneously ruptured ACC with long-term survival after successful resection. Case Presentation A 67-year-old man was brought to our hospital by ambulance, presenting with progressive left abdominal pain. Laboratory data showed an increased inflammatory response, and contrast-enhanced computed tomography showed a mass in the pancreas tail with nonuniform enhancement in the early phase. Fluid collection was detected around the spleen to the left kidney. Spontaneous rupture of a pancreatic tumor was strongly suspected. After improvement of his general condition, the patient underwent resection of the pancreas and adjacent organs. The resected tumor was surrounded by organs and adipose tissue, so obvious exposure was not observed in the surgical margins. Pathologically, neither exposure of tumor cells at the surgical margins nor lymph node involvement was detected. The patient has survived 80 months since initial diagnosis without any evidence of recurrence. Conclusion Although ruptured pancreatic ACC has the potential for dissemination, surgical resection including adjacent organs remains an option for curative treatment.

Background/aim There is rapid progression and widespread use of patient-derived tumor xenografts (PDX) in translational pancreatic cancer research. This study aimed to establish a liver transplant PDX model using cryopreserved primary pancreatic ductal adenocarcinoma (PDAC). Patients and methods Primary PDAC from 10 patients were cryopreserved and transplanted into immunodeficient mice using the liver pocket method. H&E staining and immunohistochemical staining, such as Ki-67, p53, Smad4, and MUC1 were used to evaluate engraftment and histological similarities. Results Patient-derived xenograft placement was successful in six cases (60%), and 10 mice (33.3%). The Ki-67 index of primary PDAC and the cryopreservation duration were significantly related to successful engraftment (p=0.003 and p=0.007, respectively). Conclusion In this study, we succeeded in establishing a liver transplant PDX mouse model as a preclinical platform. The successful engraftment was affected by the cryopreservation duration and could be detected by the Ki-67 index.

Background/aim This study evaluated the prognostic significance of preoperative neutrophil-to-lymphocyte ratio (NLR) and CD8+ tumor-infiltrating lymphocytes (TILs), and whether preoperative NLR was associated with CD8+ TILs in biliary tract cancers (BTCs). Patients and methods A total of 154 patients with BTCs who underwent surgery were enrolled in this study. We obtained neutrophil and lymphocyte counts, and calculated NLR from preoperative peripheral blood samples. CD8+ TILs were identified by immunohistochemical staining. Results The overall survival (OS) and recurrence-free survival (RFS) of patients with high NLR were shorter than those with low NLR. The OS and RFS of patients with high CD8+ TILs were longer than those with low CD8+ TILs. Preoperative NLR and CD8+ TILs were negatively correlated. Conclusion NLR and CD8+ TILs were associated with OS and RFS in BTCs. NLR can predict CD8+ TILs infiltrating the cancer microenvironment.

A 75-year-old woman underwent transcatheter chemoembolization(TACE)for 2 small hepatocellular carcinoma(HCC) lesions associated with severe alcoholic liver cirrhosis that necessitated management for ascites. Over 5 years after the initial TACE, she received multidisciplinary therapies with TACE, transcatheter arterial infusion of anticancer agents, percutaneous ethanol injections, or percutaneous radiofrequency ablation performed on 5 occasions for small recurrent HCC lesions. Computed tomography performed after the last therapy for HCC revealed a solitary lymph node swelling(39 mm in diameter) around the common hepatic artery. Magnetic resonance imaging performed 3 months later revealed that the lymph node had enlarged to 45 mm, without recurrence of the primary HCC, and after 4 months, to 60 mm; she then underwent laparoscopic lymph node resection. Histopathological examination of the resected specimen showed HCC metastasis. A recurrent metastatic lymph node(30 mm in diameter)was detected around the common hepatic artery and was resected laparoscopically 17 months postoperatively. Pancreatic head cancer was diagnosed 22 months after the second surgery; however, the patient refused cancer therapy and died 16 months after this diagnosis. No recurrence of the primary HCC or lymph node metastasis was observed over the 38 months after the second surgery.

Aim Pancreaticobiliary maljunction (PBM) with or without congenital biliary dilatation (CBD) is a risk factor for biliary tract cancer. We investigated long‐term outcomes after biliary diversion operation with special reference to types of CBD. Methods Subjects comprised 40 adult patients who underwent biliary diversion operation for PBM without biliary tract cancer. Group A comprised 20 patients with type Ia or Ic CBD, or non‐dilated bile ducts, while group B comprised 20 patients with type IV‐A CBD. The clinical findings and postoperative outcomes were compared between groups. Results Of 40 patients, nine patients suffered from repeated cholangitis and eight of these nine patients suffered from hepatolithiasis after biliary diversion operation. Biliary tract cancer or pancreatic cancer was detected in four patients at 3 years and 2 months to 24 years after the operation. In three of these four patients, the serum concentration of carbohydrate antigen 19‐9 increased before detection of carcinoma. One patient died of hepatic failure due to repeated cholangitis. The proportions of patients with repeated cholangitis, hepatolithiasis, and re‐operation, and patients who died of biliary tract cancer, pancreatic cancer, or hepatic failure, were significantly higher in group B than in group A. The survival rate was significantly worse in group B than in group A. Conclusions Careful long‐term follow‐up with measurement of serum tumor markers is necessary after biliary diversion operation for PBM, especially in patients with type IV‐A CBD or repeated cholangitis., This study showed that careful long‐term follow‐up with measurement of serum tumor markers is necessary after biliary diversion operation for PBM, especially in patients with type IV‐A CBD who were found to have significantly less favorable outcomes.

To safely carry out outpatient chemotherapy, it is important that patients participate in their treatment while maintaining their physical condition, and the medical staff have a role in assisting patients in managing themselves. Therefore, we introduced a self-administered chemotherapy treatment diary(hereinafter referred to as a treatment diary). This helped patients in managing themselves and motivated them to participate in their treatment.

Introduction: The anterior approach to the inferior vena cava (IVC) by the liver hanging maneuver is effective in resecting large retrohepatic tumors without mobilizing the right lobe. Case presentation: A 50-year-old man was referred to our hospital with a diagnosis of pheochromocytoma. He had severe congestive heart failure and cardiac ejection fraction was 15%. Abdominal magnetic resonance imaging (MRI) and ultrasonography (US) showed an adrenal mass about 80 mm in diameter. The tumor-infiltrated posterior segment of the right hepatic lobe and tumor were widely attached to the IVC. After treatment of congestive heart failure with conservative therapy, surgery was planned. Right adrenectomy and right hepatectomy were performed, the latter using the liver hanging maneuver to avoid mobilizing the right lobe, and we were able to minimize blood pressure fluctuations and perform the operation safely. The histopathologic diagnosis was malignant pheochromocytoma. Conclusions: We performed right hepatectomy without mobilizing the right lobe by the liver hanging maneuver and minimized stimulation of the tumor. We could perform the operation safely using the liver hanging maneuver, which seems effective in such cases.

This study evaluated the prognostic significance of preoperative neutrophil-to-lymphocyte ratio (NLR) and CD8A total of 154 patients with BTCs who underwent surgery were enrolled in this study. We obtained neutrophil and lymphocyte counts, and calculated NLR from preoperative peripheral blood samples. CD8The overall survival (OS) and recurrence-free survival (RFS) of patients with high NLR were shorter than those with low NLR. The OS and RFS of patients with high CD8NLR and CD8

The RAINBOW trial showed that paclitaxel(PTX)plus ramucirumab(RAM)therapy improved the survival of patients with advanced gastric cancer, previously treated with chemotherapy. We retrospectively investigated 33 patients with unresectable or recurrent gastric cancer who underwent PTX plus RAM treatment as second- or third-line chemotherapy between September 2015 and December 2017. The median age was 68(45-84)years with 22 patients(67%)aged 65 years or older. Seventeen patients had unresectable and 16 patients had recurrent gastric cancer. ECOG PS was 2 in 5 patients(16%). PTX plus RAM was administered as second-line therapy for 24 patients, and as third-line therapy for 9 patients. Best overall response was partial response(PR)in 4 patients, stable disease(SD)in 14 patients, and progressive disease(PD)in 9 patients. Response rate(RR)and disease control rate(DCR)were 14.8% and 66.7%, respectively. Grade 3/4 adverse events were observed in 28(85%)of(leucopenia·neutropenia[64%], neuropathy[9%], etc). Median follow-up period was 7.3(0.4- 22.4)months. Median OS and PFS were 9.3(0.4-22.4)months and 4.7(0.4-22.4)months, respectively. We conclude that PTX plus RAM therapy is useful for treating unresectable or recurrent gastric cancer. In clinical practice, we have many opportunities to provide PTX plus RAM therapy for patients of older age and poorer PS; careful attention to adverse events is essential in such cases.

Hepatic infarction is a relatively rare life-threatening complication after pancreatoduodenectomy (PD). Computed tomography (CT) findings and risk factors for hepatic infarctions after PD were investigated. One hundred-fifty three patients who underwent contrast-enhanced CT (CECT) after PD between January 2011 and August 2016 were retrospectively analyzed. Hepatic infarction was defined as the non-contrast enhanced area expanding to the liver surface without mass effect on CECT. The relationships between infarctions and preoperative laboratory data or surgical procedures using uni- and multivariate analyses were examined. Twenty-nine patients showed 47 hepatic infarctions on CT. Infarctions most commonly appeared in segment 7 (S7) (17 lesions, 36.2%). Lesions were wedge-shaped in 12 patients and spread over multiple hepatic segments in 11 patients. Univariate analysis identified celiac artery (CA) or common hepatic artery (CHA) resection (p = 0.0029) and portal vein (PV) resection (p = 0.013) as risk factors for infarctions. CA or CHA resection (p = 0.038) remained as a significant factor after multivariate logistic analysis. Hepatic infarctions after PD were most frequently seen in S7 and PV penetrating sign was characteristic CT findings. CA or CHA resection or PV resection were revealed as risk factors for hepatic infarctions.

Synchronous double cancers in the biliary system are rare. Double cancer of the common bile duct (CBD) and the ampulla of Vater without pancreaticobiliary maljunction (PBM) is extremely rare. To our knowledge, only 7 cases have been reported previously. Here we report a case of synchronous double cancer of the CBD and the ampulla of Vater without PBM. A 63-year-old man was referred to our hospital with epigastric pain and jaundice. Computed tomography (CT) showed dilatation of both intrahepatic and intrapancreatic bile ducts, and slightly enhanced tumor in the middle part of the CBD and the ampulla of Vater. Endoscopic retrograde cholangiopancreatography (ERCP) showed a tuberous filling defect in the middle part of the CBD and an exposed tumor of the ampulla of Vater. Under a diagnosis of synchronous double cancer of the middle bile duct and the ampulla of Vater, pancreaticoduodenectomy was performed. Histopathologically, the ampulla of Vater tumor was well-differentiated tubular adenocarcinoma while the middle bile duct tumor was moderately-differentiated tubular adenocarcinoma. Normal mucosa was interposed between both tumors. These findings suggest that they were 2 primary tumors. Double cancer of the CBD and the ampulla of Vater without PBM is extremely rare. We report a case of synchronous double cancer of the CBD and the ampulla of Vater without PBM.

A 73-year-old woman presented to her doctor because of lower abdominal pain and distension. A neoplastic lesion in the lower abdomen was revealed, and she was referred to our department. Enhanced CT showed wall thickening in the urinary bladder and a 6 cm mass that extended to the appendix. An appendiceal tumor invading the urinary bladder or a urinary bladder tumor invading the appendix was suspected, and we planned surgical treatment. One month later, we repeated enhanced CT scanning on admission. The mass had shrunk, but the thickening of the urinary bladder wall remained, and an enhanced appendiceal tumor was visible. Surgery was performed and we found a 1 cm appendiceal tumor. Intraoperative pathological examination revealed appendiceal cancer. Therefore, we performed ileocecal resection, D2 lymph node dissection, and partial cystectomy. Final histopathological examination revealed appendiceal cancer with pT2N0M0, pStage Ⅰ. Taking into account the patient's clinical course, we diagnosed obstructive appendicitis with an abscess due to appendiceal cancer rupture into the urinary bladder.

History of male breast cancer and pancreatic cancer are important for diagnosis of hereditary breast and ovarian cancer syndrome(HBOC), while advanced pancreatic cancer is reported to have metastasis to mammary gland tissue. A 67-year-old man visited a local hospital because fever and right hypochondrial pain. Computed tomography scan revealed pancreatic cancer with multiple liver metastasis and peritoneal metastasis. He was referred to our hospital for further evaluation and treatment. No particular family history of malignancy was formed. A palpable lump was found in his left breast. Ultrasonography revealed 2.8 cm sized mass that had heterogenous internal echo and rough border. The background mammary gland showed gynecomastia. Since it was difficult primary breast cancer with metastatic tumor originated from pancreas cancer a core needle biopsy was performed. The finding of pathological examination showed invasive carcinoma with hormonal receptor negative and HER2 negative feature. CK7 and CK19 were both positive. Although it was difficult to male differentiation whether the tumor was primary a metastatic, we diagnosed as synchronous duplicated cancer of pancreas and breast due to existence of gynecomastia. Since hepatic failure due to tumor growth advanced prior to treatment start, the treatment policy became best supportive care.

We studied 14 patients with anal squamous cell carcinoma(ASCC)who were treated in our hospital between 1994 and 2016. As initial therapies, surgeries were performed in 5 patients. Of these, disease recurrence appeared in 4 patients, and 3 patients died within 1 year after operation. Other 9 patients were treated with chemoradiotherapy. As a result, 9 of 6 patients were considered as complete response(CR), and 4 patients are still alive without recurrence. Although other 2 patients were recurred, recurrent lesions were removed and then, they are still alive. Of 3 patients who were considered as partial response (PR), 1 patient who was treated with local excision is still alive without recurrence, however, 2 patients were died for distant metastases. Chemoradiotherapy is considered to be effective and expected to cure without surgery, however, a careful surveillance should be needed for distant metastases.

Background Common complications of pelvic fractures include visceral injury, large-volume hemorrhage, genitourinary injury, rectal injury, and pulmonary embolism. On the other hand, traumatic hernia is a rare complication, especially in association with pelvic fractures. We report a case of bowel perforation due to traumatic hernia at a pelvic fracture site. Case presentation A 65-year-old female was presented at our hospital for further examination and treatment of ileus. She was diagnosed with bowel perforation due to traumatic hernia at a pelvic fracture site, and an emergency operation was thus immediately performed. We performed segmental jejunum resection and constructed jejunostomy, and the iliac bone fracture was fixed with four pins. In the postoperative course, she received antibiotics and vasopressors for septic shock. However, there was no need for either a ventilator, dialysis or admission to the ICU. At seven days after the operation, a residual abscess was detected in the pouch of Douglas. We performed percutaneous drainage (Clavien-Dindo IIIa) and jejunostomy closedown 35 days after the first operation. The postoperative course was without complication, but she received rehabilitation until she was able to walk unaided. She was discharged 64 days after the first operation. Conclusion The occurrence of traumatic hernia is rare, especially in association with pelvic fractures. Although its rarity, traumatic hernia follows a severe course. Thus, proper diagnosis and effective treatment are necessary. Surgeons treating patients with pelvic injuries should consider the possibility of any complications and perform a work-up examination in order to achieve an accurate diagnosis at an earlier time point.

We retrospectively investigated the efficacy and safety of S-1 and oxaliplatin(SOX)as the first-line chemotherapy in patients with metastatic/recurrent gastric cancer. A total of 27 patients who received SOX as the first-line chemotherapy in our hospital were considered for the study. The SOX chemotherapy schedule consisted of 1 course every 3 weeks. S-1 was administered orally, at 80-120mg-body, every day for 14 days. Oxaliplatin was infused at 100mg/m2 on day 1 of each course. The median number of treatment courses was 7. The response rate and disease control rate were 47.6% and 76.2%, respectively. The observed adverse events of Grade 3 or more included neutropenia(33.3%); peripheral neuropathy and anorexia(11.1%); thrombocytopenia(7.4%); and anemia, diarrhea, fatigue, and hypercalcemia(3.7%). The median overall survival was not achieved, and the 1-year survival rate was 63.2%. Therefore, SOX is an effective and feasible first-line chemotherapy that is easily available for ambulatory treatment of patients with metastatic/recurrent gastric cancer.

Patients with overweight reportedly have more comorbidities, including diabetes mellitus and cardiovascular disease, and longer operating times as well as more blood loss during surgery compared with those with normal weight. However, the impact of overweight on the short-term outcome after transthoracic esophagectomy for patients with esophageal squamous cell carcinoma (ESCC) remains unclear. We hypothesized that overweight has a negative impact on short-term surgical outcomes after esophagectomy for patients with ESCC.A total of 304 patients who underwent transthoracic esophagectomy for ESCC were included in this study. Body mass index (BMI) was classified into three categories,18.49, 18.50-24.99, and25.00 (kg/m(2)), defined as low, normal, and high BMI, respectively, according to the World Health Organization criteria. We investigated the association of BMI status with patient demographics and surgical outcomes after esophagectomy for patients with ESCC. In addition, overall survival and relapse-free survival stratified by BMI were compared.Fifty-nine (19.4 %) and 41 (13.4 %) patients were classified to low BMI and high BMI, respectively. The high-BMI group had significantly higher comorbidity rates of diabetes mellitus (p 0.01) and anastomotic leakage (p = 0.011) than the normal-BMI group. There were no significant association between high BMI and another various complications except for an anastomotic leakage, severe complications defined by Clavien-Dindo classification and in-hospital mortality. In multivariate analysis, high BMI was a significant risk factor for anastomotic leakage (p = 0.030, hazard ratio; 3.423, 95%CI; 1.128-10.38). On the other hand, no significant association was observed between low BMI and short surgical outcomes. There were no significant differences in overall and relapse-free survival among the three BMI groups in univariate and multivariate analysis (p = 0.128 and p = 0.584, respectively).The surgical treatment should not be denied for patients with ESCC due to overweight and underweight. However, intraoperative prevention and postoperative careful monitoring for anastomotic leakage might be required after esophagectomy for overweight patients with ESCC.

A 66-year-old woman underwent sigmoidectomy for colon cancer. The final diagnosis was early cancer of pT2 pN0 and M0 (fStage I ). A chest CT revealed lung metastasis and lymph node metastasis 6 years after surgery. The patient was treated sequentially with FOLFOX, FOLFIRI, and XELOX regimens. Since these regimens resulted in progressive disease, regorafenib was started as the fourth regimen. After 8 courses, she was evaluated as having a partial response. Her partial response has continued for 18 months of regorafenib treatment.

Background We researched the origin and progression of anaplastic pancreatic cancer (APC) from the viewpoints of cell lineage, epithelial-mesenchymal transition (EMT) and cancer stem like cells (CSC). Methods Using specimens from patients with APC and differentiated pancreatic ductal adenocarcinoma (PDAC), expression of sex-determining region Y box 9 (SOX9), E-cadherin, vimentin, ZEB-1, Snail, N-cadherin, CD24 and CD44 was estimated using immunohistochemistry. Results Almost all cases were positive for SOX9 expression. APC cases were negative, but many PDAC cases were positive for the expression of E-cadherin. A much higher number of APC cases than PDAC cases were positive for the expression of other EMT related proteins and for the expression of CSC related proteins. The ductal cancerous component of APC accounted for an average of 12% of the cancerous lesion and the expression of each marker in this component was similar to that of PDAC cases. Conclusions APC had pancreatic duct cell like features and might gain dedifferentiate components through EMT and the acquisition of CSC properties. This article is protected by copyright. All rights reserved.

Background Despite the efficacy of pharmacotherapy for gastrointestinal ulcers, severe cases of bleeding or perforation due to gastrointestinal ulcers still occur. Giant duodenal ulcer perforation is an uncommon but difficult-to-manage pathology with a high mortality rate. We report two cases of giant duodenal ulcer perforation after neurosurgery for brainstem tumors that needed reoperation for gastric disconnection because of postoperative leakage and bleeding. Case presentation Both cases had undergone neurosurgery for brainstem tumors, and the patients were in a shock state for several days with peritonitis due to giant duodenal perforation. In Case 1, antrectomy with Billroth II reconstruction was performed. However, reoperation for gastric disconnection was needed because of major leakage of gastrojejunostomy and jejunojejunostomy. In Case 2, an omental patch, cholecystectomy, and insertion of a bile drainage tube from the cystic duct were performed for the giant duodenal ulcer, but leakage and bleeding from the ulcer edge required reoperation for gastric disconnection. Conclusions Brainstem tumors in these cases might have been related to duodenal ulcer perforation with late diagnosis that progressed to severe sepsis. For giant duodenal ulcer perforation with poor general condition, simple closure including omental patch or antrectomy with reconstruction is hazardous. Antrectomy with gastric disconnection, meaning gastrostomy, duodenostomy, feeding jejunostomy and cholecystectomy, is recommended.

We evaluated the prognostic significance of the peripheral lymphocyte count and lymphocyte percentage, which reflect the preoperative immune status, in patients with colorectal cancer (CRC) and then compared their accuracy as predictors of the survival. We retrospectively reviewed a database of 362 patients. We classified the patients into high lymphocyte count and low lymphocyte count groups. We also classified the patients into high lymphocyte percentage and low lymphocyte percentage groups. The 5-year relapse-free survival (RFS) rate in the high lymphocyte count group tended to be higher than that in the low lymphocyte count group. The 5-year overall survival (OS) rate in the high lymphocyte count group was significantly higher than that in the low lymphocyte count group. In contrast, the 5-year RFS and OS rates in the high lymphocyte percentage group were both significantly higher than those in the low lymphocyte percentage group. A multivariate analysis showed that the lymphocyte percentage was independently associated with the OS. These findings suggest that the lymphocyte percentage is a good predictor of the OS and may be a stronger predictor of survival than the lymphocyte count in CRC patients.

Background Anaplastic pancreatic cancer (APC) cell lines have been scarcely established. Methods The morphology, gene expressions, karyotyping and epithelial-mesenchymal transition markers of newly established APC cell lines OCUP-A1 and OCUP-A2 were analyzed. Their abilities of proliferation under normoxia and hypoxia, migration and invasion were compared to 4 commercially available pancreatic ductal adenocarcinoma (PDA) cell lines. Their induction of angiogenesis, stem-like cell population and subcutaneous tumor growth in nude mice were estimated, comparing 2 PDA cell lines examined here. Results OCUP-A1 and OCUP-A2 cells continuously grew with spindle and polygonal shapes, respectively. Gene analysis revealed 9 gene mutations including KRAS and TP53. Karyotyping clarified numerical structural abnormalities in both cells. Loss of E-cadherin and expression of vimentin in both cell lines were observed. The doubling time of both cell lines was approximately 20 h. Proliferation, migration and invasion abilities were not notable compared to other PDA cell lines. However stem-like cell population of both cell lines was superior to a part of PDA cell lines. Moreover OCUP-A1 showed stronger hypoxia tolerance and induction of angiogenesis than other PDA cell lines. The tumorigenicity in vivo of OCUP-A2 was stronger than conventional PDA cell lines. Conclusions The OCUP-A1 and OCUP-A2 cell lines of rare malignancies might be useful for investigating the biology of pancreatic cancer.

ERas is a recently identified oncogene involved in the tumorgenic growth of embryonic stem cells. We examined the significance of ERas expression in scirrhous gastric carcinoma, and the possibility of ERas as a tumor-associated antigen of gastric cancer for developing a cancer vaccine. ERas expression was determined in scirrhous gastric carcinoma specimens by immunohistochemical staining. To assess the possibility of the ERas protein as an anticancer vaccine target, we examined whether ERas for HLA-A-restricted epitope peptides were capable of eliciting cytotoxic T lymphocyte activity. Immunohistochemical analysis identified ERas protein in the nucleus and cytoplasm of cancer cells, yet ERas was not expressed in normal gastric epithelium. By western blotting, lysates of the scirrhous gastric cancer cell lines, OCUM-8, OCUM-2MD3 and OCUM-2M were shown to contain a 25-kDa band of ERas protein. ERas mRNA was detected in these cell lines by RT-PCR. To investigate cytotoxicity, we successfully established cytotoxic T lymphocyte clones stimulated by HLA-A*2402-restricted ERas peptides (FALDDPSSL). These peptides have specific cytotoxicity against corresponding HLA-A*2402-positive target cells pulsed with the candidate peptide. We found that the cytotoxic T lymphocyte clones demonstrated cytotoxic activity against OCUM-8 cells that endogenously express ERas. Our results suggest that ERas is a novel tumor-associated antigen with the potential application to be a vaccine against scirrhous gastric cancer. (Cancer Sci 2011; 102: 683–689)

Background: The density of tumor-infiltrating lymphocytes (TILs) have been reported to reflect antitumor immune response and correlate with prognosis in malignancy. However, the methodology for evaluating the density of TILs by an immunohistochemical analysis differs among reports. The aim of this study was to verify the methodology for evaluating the density of TILs by immunohistochemical analysis and thereby identify the optimum methodology in clinical setting. Methods: Three-hundred-thirteen patients who underwent curative operation for stage II/III colorectal cancer were enrolled. We retrospectively examined the density of TILs using immunohistochemical staining according to each method as follows: 1) subset of lymphocytes (i.e. CD4+/CD8+), 2) selected fields (i.e. at random or focusing on hot spots), 3) location in low-power field (i.e. the invasive margin [TILsIM] or the center of the tumor [TILsCT] or the surface of the tumor [TILsST]), and 4) location in high-power field (i.e. in tumor stroma [sTILs] or intra-tumor cells [iTILs] or total TILs [tTILs: sTILs+iTILs]). We then assessed the prognostic value of the density of TILsIM evaluated as described above. We also evaluated the correlation between the density of TILsIM and that of TILsCT/TILsST. Results: In randomly selected fields, the densities of CD8+sTILsIM and CD8+tTILsIM were significantly associated with the survival. However, the densities of TILs evaluated via other methods were not associated with the survival. Furthermore, the density of CD8+TILsIM was significantly associated with that of CD8+TILsCT and CD8+TILsST. Conclusions: We concluded that best and easiest way to evaluate the density of TILs in the clinical setting may be to assess the density of total CD8+TILs at the invasive margin in randomly selected fields. Citation Format: Shinji Matsutani, Masatsune Shibutani, Kiyoshi Maeda, Hisashi Nagahara, Tatsunari Fukuoka, Tatsuro Tamura, Go Ohira, Sadaaki Yamazoe, Kenjiro Kimura, Takahiro Toyokawa, Ryosuke Amano, Hiroaki Tanaka, Kazuya Muguruma, Kosei Hirakawa, Masaichi Ohira. Verification of the methodology for evaluating tumor-infiltrating lymphocytes in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5701.

A 66-year-old man underwent laparoscopic right nephrectomy for renal cell carcinoma (T2b, N0, M1, clear cell, Grade 3). He was treated with targeted therapy for lung metastases after nephrectomy. Despite the targeted therapy, he was paralyzed in the lower half of the body due to the spinal metastases. Therefore, an osteoplastic laminectomy and domelaminectomy for the spinal metastases was performed. The FDG-PET examination, which was performed after the operation, revealed lung, liver, bone, and small intestinal metastases. After a while, he suffered from continuous massive melena. Double balloon enteroscopy revealed a hemorrhagic tumor in the small intestine, and an emergency operation was performed. A partial resection of the small intestine was performed for the 3 tumors. The histopathological diagnosis was small intestinal metastasis from renal cell carcinoma. It is well known that renal cell carcinoma often develops metastases to the lung, bone, and liver. However, small intestinal metastasis from renal cell carcinoma is rare. Although small intestinal metastasis from renal cell carcinoma often accompanies metastases to other organs, a palliative operation might improve the quality of life in patients with symptomatic tumors.

A 60-year-old man underwent laparoscopic total proctocolectomy with ileostomy for advanced ulcerative colitis-associated rectal cancer. The final diagnosis was advanced cancer pT3, pN2 and M0 (pStage Ⅲb). Adjuvant therapy with XELOX was performed. However, abdominal CT revealed a liver metastasis and lymph node metastases in the pelvis 6 months after surgery. The patient was treated with FOLFIRI plus bevacizumab. After 20 courses of chemotherapy, the patient was considered to have experienced a clinical CR, which has been maintained for 3 years 5 months.

It is important in the clinical setting to integrate all of the findings when diagnosing and making treatment decisions. We report a case of particular interest for managing cancer patients. A 69-year-old man underwent endoscopic resection for an Rb rectal tumor. The tumor showed a positive vertical margin and required laparoscopy-assisted super low anterior resection with ileostomy for histopathological stage Ⅰrectal cancer. His postoperative course was uneventful. The follow-up computed tomography (CT) scan revealed a tumor locating close to the left common iliac artery. Although positron emission tomography (PET) showed 18F-fluorodeoxyglucose (FDG) accumulation in the tumor, none of the other clinical findings indicated a recurrence of rectal cancer. FDG is not specific to malignant neoplasias, but the location of the tumor and the FDG uptake suggested the possibility of malignancy. No other tests found any evidence of a recurrence. Tumor resection was performed concurrently with ileostomy closure. Histopathology demonstrated it was an asymptomatic abscess in a lymph node. Tumor recurrence and metastases have to be kept in mind even if the primary lesion is in an early stage. This case shows the difficulty in deciding how to manage patients when clinical results are not consistent, especially in cases needing surgical procedures.

Background Pheochromocytoma is a disease where catecholamines are secreted. If pheochromocytoma occurs during pregnancy, it can be difficult to diagnose because it is similar to pregnancy-induced hypertension. Furthermore, bilateral pheochromocytoma during pregnancy is even rarer than unilateral pheochromocytoma. Case presentation A 32-year-old primigravida, who was 12 weeks’ pregnant, was aware of right abdominal discomfort. Masses in both adrenal glands were observed by abdominal ultrasonography. She was diagnosed with pheochromocytoma. Bilateral adrenalectomy was undertaken at 15 weeks’ gestation and she continued pregnancy. At 39 weeks’ gestation, a healthy male neonate was delivered. She was discharged on the 4th postpartum day. Conclusions We present a case of bilateral pheochromocytoma during pregnancy that was diagnosed in the first trimester. Differentiating pheochromocytoma from pregnancy-induced hypertension is important. Early diagnosis and appropriate blood pressure management with medical treatment followed by surgical removal of the tumor results in good maternal and fetal outcomes.

Background Acute adrenal hemorrhage is an uncommon entity. Although trauma is the most common cause of adrenal hemorrhage, non-traumatic etiologies have also been reported. We report an unusual case of a spontaneously ruptured adrenocortical carcinoma that initially presented as a critical massive retroperitoneal hemorrhage. The case was treated successfully using a combination of emergency interventional radiology and elective surgery. Case presentation A 47-year-old woman was transported to our hospital because of the sudden onset of severe pain in her left lower back. The shadow of a tumor-like soft mass accompanied by bleeding was observed in the upper pole of the left kidney, together with vascular leakage from the middle suprarenal artery on computed tomography. Transcatheter embolization of the left middle adrenal artery was administered based on a diagnosis of acute adrenal hemorrhage. Further observation indicated that the bleeding was caused by rupture of an adrenocortical carcinoma. Left adrenalectomy was subsequently carried out via laparotomy. Conclusions We experienced an unusual case of acute massive adrenal hemorrhage caused by the rupture of a non-functional adrenocortical carcinoma, which was treated successfully by ambulatory transcatheter embolization therapy and elective surgery.

症例は67歳の女性,下腹部痛と血便を主訴に受診し入院となった. CT検査にて骨盤腔内にガスと液体貯留を有する嚢腫様病変と,それに接するS状結腸壁の壁肥厚を認めた.入院翌日に下腹部激痛を訴え, X線写真で両横隔膜下に遊離ガス像を認めた. S状結腸膀胱痩とそれに起因する汎発性腹膜炎を疑い手術を行った.術中所見では多量の膿性腹水を認めたが膀胱は正常であり子宮体部に穿孔を認めた. S状結腸に腫瘍を認め子宮体部背側に癒着していたが浸潤の有無は不明であった. S状結腸癌に伴った子宮留膿腫破裂による汎発性腹膜炎と診断し,単純子宮全摘術・S状結腸切除術を施行した.病理組織学的には,子宮は炎症著明であったが子宮内膜・筋層にS状結腸癌の腫瘍細胞を認めなかった.本症例はS状結腸癌に伴った子宮留膿腫破裂による汎発性腹膜炎をきたした稀な症例であった.

62 Background: Conversion surgery after chemotherapy responds to unresectable gastric cancer has long-term prognosis, however, chemotherapy after surgery should also be considered to improve treatment outcome. The effectiveness of immune checkpoint inhibitors for gastric cancer has been proved. In this study, we investigated the association between PDL-1 expression and CD8+ T cell infiltration in the primary tumor and prognosis of patients who underwent conversion surgery after S-1-based multidrug chemotherapy in unresectable gastric cancer. Methods: We evaluated PDL-1 expression and CD8 T cell infiltration by immunohistochemical staining and examined the relationship with prognosis in 90 patients with Stage IV gastric cancer who underwent gastrectomy in our department from 2007 to 2015. Results: 90 cases included 47 cases of palliative resection, 26 cases of CY1P 0cases and 17 cases of conversion surgery. Among Conversion Surgery cases, 11 (65%) patients underwent R0 surgery, and the 5-year survival rate was 66%. The 5-year survival rate of non-curative resected cases was 16%. In immunohistochemical examination, PDL-1 high expression was a poor prognostic factor in palliative surgery and CY1P0 cases. Meanwhile, in the case of Conversion Surgery, the 5-year survival rate was 58%, 32%, 61%, and 30% in the order of PDL-1 high expression group, low expression group, CD8 T cell high infiltration, and low infiltration group, respectively. Prognosis of PDL-1 high expression group and CD8 T cell infiltration group was good. There was no association between curative resection and neither of CD8 T cell infiltration or PDL-1 expression. Conclusions: We found that the prognosis was relatively good in patients where local immune response was enhanced, regardless of R0 excision. Our results suggested that infiltration of CD8 T cells in the primary tumor may be a prognostic predictor, and it is expected to use an immune check point inhibitor after conversion surgery for unresectable gastric cancer.

We report on a 30-year-old man with familial adenomatous polyposis (FAP ) who developed advanced sigmoid colon cancer with desmoid tumors. The patient initially presented with melena. FAP advanced sigmoid colon cancer was diagnosed following a laparoscopy-assisted proctocolectomy in 2007. A computed tomography (CT) scan, conducted 7 months later, revealed a tumor around the branch of the common iliac artery. We diagnosed sigmoid colon cancer recurrence and attempted treatment by surgical removal. However, there were many smooth tumors within the patient's abdomen, which were diagnosed as desmoid tumors using rapid intraoperative pathological diagnosis. Although the patient was administered a COX-2 inhibitor and tamoxifen after surgery, the tumor grew. Dacarbazine (DTIC) and doxorubicin (DOX) were subsequently administered to the patient, and after 4 courses, the tumor was reduced by 60% and stable disease (SD) was achieved. In 2009, a CT scan indicated sigmoid colon cancer recurrence in the liver. The patient underwent a left hepatic lobectomy by laparoscopy-assisted surgery. To date, 4 years and 6 months after surgery, we have been unable to find new disease or desmoid tumor growth.

There are only a few reports in the literature about the effect of recombinant human soluble thrombomodulin (rTM) in patients with solid carcinoma with disseminated intravascular coagulation (DIC). A retrospective study of 40 patients with solid carcinoma with DIC was performed between February 2009 and April 2013. The withdrawal rate was 32.5% (13/40 patients), and the 28-day survival rate was 40.0% (16/40 patients). Patients with successful withdrawal of DIC had significantly better outcomes (p.001). Therapy with rTM is one of the treatment options for patients with solid carcinoma with DIC.

Small cell carcinoma of the esophagus is reported to be both rare and aggressive, and is commonly associated with a short post-diagnosis survival period. We report a case of Stage IV small cell carcinoma of the esophagus involving a relatively long survival period of 2 years. The patient was a 70-year-old man with a chief complaint of epigastric discomfort. Upper gastrointestinal endoscopy by a local physician showed a protruding tumor at the mid-thoracic esophagus. Tumor biopsy revealed small cell carcinoma. Chest-abdominal computed tomography revealed multiple liver metastases, and swelling of a number of regional lymph nodes. The diagnosis was cT3N4M1, cStage IVb esophageal small cell carcinoma. According to the regimen used for lung small cell carcinoma, we administered CDDP/CPT-11. After administration of four courses, the primary lesion, liver metastases, and lymph node metastases significantly reduced, indicating a partial response. However, after completion of eight courses, liver metastasis and lymph node swelling recurred. The patient subsequently received other therapeutic regimens such as CBDCA/VP-16, AMR, NGT, and CDGP/5-FU. However, the tumor gradually progressed, and the patient died approximately 2 years after the first treatment.

A 64-year-old man underwent sigmoidectomy for sigmoid colon cancer 9 years ago. We attempted to discontinue surveillance, as the postoperative course was event free for 5 years; however, we continued the follow-up on the patient's request. Nine years after the operation, elevation of the serum carcinoembryonic antigen (CEA) level was detected, and positron emission tomography-computed tomography (PET-CT) showed a 35-mm mass with an abnormal signal (SUVmax 18.6 Bq/ mL). We performed an abdominal CT and magnetic resonance imaging and found the mass invading the sigmoid colon. We suspected lymph node recurrence of the sigmoid colon cancer and considered curative surgery to be appropriate as there were no other signs of recurrence. We therefore excised the tumor by sigmoidectomy. A histopathological examination revealed metastatic adenocarcinoma in the lymph node. One year after the second operation, there was no evidence of recurrence on imaging and the levels of tumor markers were within the normal limits. Few reports have documented recurrence over 5 years after surgery. We herein describe our case and report the characteristics of a recurrent lesion and also suggest a protocol for surveillance, taking into consideration the previous literature.

Study Background: In the International Consensus Guidelines 2012 for intraductal papillary mucinous neoplasm (IPMN), 'high-risk stigmata' (HRS) were described as indications for resection. The purpose of this study was to evaluate the prognostic meaning of HRS in the 2012 guidelines. Method: Clinical and pathological data from 98 patients who underwent pancreatic resection for IPMN at our institution between 1994 and 2014 were retrospectively analyzed. Results: The 98 resected IPMNs were categorized as demonstrating no criteria (NC) (n=18), worrisome features (WF) (n=39), or HRS (n=46) according to the guidelines. By multivariate analysis, positive lymph node metastasis and HRS were significantly identified as independent prognostic factors. Five-year disease-specific survival rates for NC and WF were both 100%, whereas that for HRS was significantly poorer at 49.5% (p

[Background] Promising efficacy of the immunotherapy with anti-PD-1 antibody for esophageal squamous cell carcinoma (ESCC) is expected. Tumor-infiltrating lymphocytes (TILs)have been found to be associated with favorable outcome of patients in many cancers including ESCC. However, the contributing factor of TILs in the primary tumor remains unclear. Dendritic cells (DCs) are the most potent antigen-presenting cells to induce cytotoxic T lymphocytes. [Purpose] The aim of this study was to examine the correlation of mature dendritic cells with CD8+ cells in the tumor in order to clarify the impact of DCs on locally infiltrated lymphocytes in ESCC. [Object and Methods] Formalin-fixed, paraffin-embedded blocks of primary lesions were collected from 80 patients with ESCC who underwent surgical treatment at Osaka City University Hospital. Immunohistochemical analysis using anti-LAMP-3 antibody and CD8 antibody was used to evaluate intratumoral DCs and TILs. The number of LAMP-3+DCs and TILs were counted at ×400 magnification. We divided the 80 cases into two groups according to the median number of intratumoral DCs and TILs to examine the clinicopathological features. [Results] LAMP-3+DCs were predominantly observed in peritumoral area and sparsely found in intratumoral area, whereas CD8+T cells distributed between both peritumoral and intratumoral areas. The number of DCs was significantly associated with increasing TNM stage. For example, the median number of DCs was 59.9 in pathological T1, 34.2 in T2/3, 62.4 in pN1, 34.1 in pN1/2/3. In addition, many patients with high infiltaraion of DCs had positive lymphatic invasion (Ly). The number of intratumoral DCs was significantly correlated with the number of TILs which were observed in intratumoral regions. Patients in the high infiltration of DCs group showed a significant better prognosis than patients in the low infiltration group. Double staining showed that LAMP3+DC-CD8+T cell clusters were seen in peritumoral area. Citation Format: Junya Nishimura, Hiroaki Tanaka, Yuichiro Miki, Tatsuro Tamura, Tatsunari Fukuoka, Go Ohira, Masatsune Shibutani, Sadaaki Yamazoe, Kenjiro Kimura, Takahiro Toyokawa, Hisashi Nagahara, Ryosuke Amano, Kazuya Muguruma, Kiyoshi Maeda, Kosei Hirakawa, Masaichi Ohira. Impact of intratumoral mature dendritic cells on prognosis of the patients with esophageal squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2945. doi:10.1158/1538-7445.AM2017-2945