[A Case of Conversion Surgery after SOX plus Nivolumab for Unresectable Advanced Gastric Cancer].

A 63-year-old woman came to our hospital complaining of anemia and weight loss. The abdominal CT showed wall thickening from the upper to lower the body of stomach, and peritoneal dissemination. The EGD revealed a type 3 large tumor extending about 2/3 of the circumference. Adenocarcinoma was detected as a result of biopsy. The patient was diagnosed with unresected gastric cancer(cT4aN+M1, cStage Ⅳ). SOX plus nivolumab was selected as a first-line chemotherapy because of HER2 expression negative. Symptoms such as diarrhea developed, and the treatment was completed until 5 courses. Laparoscopic distal gastrectomy was performed after the disappearance of abdominal dissemination by CT scan and PET. Pathological examination revealed cancer cells were completely disappeared in the tumor, regional lymph nodes and white nodules in the peritoneum, and final diagnosis was ypT0N0M0, ypStage 0(histological effect determination is Grade 3). Six months after the operation, the patient has been free of recurrence.

[A Case of Giant Abdominal Desmoid Tumor in a Young Man].

Desmoid tumor is a rare tumor of the soft tissue. The frequency of occurrence is 2.4 to 4.3 cases per year per million people, which is a very rare disease. We experienced a huge intra-abdominal desmoid tumor which is thought to be the primary mesentery. The case was a male in his 20s. He visited a nearby doctor with a complaint of abdominal bloating and abdominal pain. Abdominal contrast CT revealed a huge abdominal mass with a clear boundary of 35×25 cm in size extending from the upper right abdomen to the pelvis. Surgery was performed with a diagnosis of an intra-abdominal mass. Open abdominal tumor resection. Due to infiltration into the duodenum, transverse colon, and pancreas, right hemicolectomy and duodenal combined resection were performed. The pathological diagnosis was a diagnosis of desmoid tumor.

[A Case of Early Pancreatic Cancer Diagnosed from the Finding of Partial Pancreatic Parenchymal Atrophy].

A man in his 80s was referred to our hospital for further examination of partial pancreatic atrophy that was detected incidentally. Various imaging examinations including CT, MRI, and EUS did not reveal any obvious abnormal findings other than the partial pancreatic atrophy. However, cytological examination of serial pancreatic juice aspiration showed atypical cells. The presence of pancreatic intraepithelial carcinoma in the atrophy site was considered, and the patient underwent laparoscopic distal pancreatectomy. Pathological examination of the excised specimen confirmed the presence of high-grade pancreatic intraepithelial neoplasia consistent with the atrophy site, and the patient was diagnosed with pTisN0M0, Stage 0 pancreatic cancer. For the detection of early pancreatic cancer, it is important to be aware of partial pancreatic atrophy on imaging studies.

[Invasive Ductal Carcinoma within a Borderline Malignancy Phyllodes Tumor-A Case Report].

Phyllodes tumors are uncommon breast neoplasms that constitute 1-2% of breast malignancies. Invasive ductal carcinoma in the epithelial component of phyllodes tumor is very rare. When carcinoma is detected within the specimen, the management of treatment changes completely. We report a rare case of invasive ductal carcinoma arising in a giant borderline malignancy phyllodes tumor in a 51-year-old female patient. A painful 20 cm mass was found in her right breast, and a needle biopsy revealed fibroadenoma or benign phyllodes tumor, and a total mastectomy was performed. Pathological results showed that a borderline malignant phyllodes tumor coexisted with invasive ductal carcinoma. We explained that axillary surgery was necessary because invasive cancer was diagnosed after surgery, but the patient requested follow-up using images. Endocrine therapy was performed as postoperative adjuvant therapy, and the follow-up is underway without recurrence.

[A Case of Primary Hepatic Mucosa-Associated Lymphoid Tissue Lymphoma].

A 74-year-old man with no chronic liver disease was admitted for an incidental liver tumor by computed tomography. Serological examinations for hepatitis B and C virus were negative and tumor markers, including carcinoembryonic antigen, α-fetoprotein, carbohydrate antigen 19-9, and des-gamma-carboxy prothrombin, were within the normal range. The contrast- enhanced magnetic resonance imaging revealed that the 26 mm in diameter patchy tumor occupied the S7 in the liver. The tumor boundary was enhanced slightly in the arterial phase and inside gradually in the portal phase, and the enhancement was faded in the late phase. As a characteristic finding, vessels penetrated the tumor. The tumor was diagnosed as cholangiocarcinoma, and the patient underwent right lateral sectionectomy. After 19 days postoperatively, the patient was discharged. The diagnosis of hepatic mucosa-associated lymphoid tissue(MALT)lymphoma was made by pathological examination. Currently, the patient has no recurrence for 5 months without adjuvant chemotherapy. The primary hepatic MALT lymphoma is a rare disease among primary hepatic malignant lymphomas. The patient must be followed up carefully because 2 cases were reported as recurrent cases after several years postoperatively although the disease has a good prognosis.

[A Case of Laparoscopically Resected Sigmoid Colon Cancer and Transverse Colon Mesentery Primary Solitary Fibrous Tumor].

The patient is a 52-year-old woman who visited the general practitioner because of positive fecal occult blood test by medical examination. The patient underwent colonoscopy at the hospital, which revealed sigmoid colon cancer. Therefore, the patient was referred to our hospital for surgery. Preoperative CT scan revealed a well-defined and lobulated 54 mm tumor on the caudal side of the duodenal third portion. On MRI, the tumor showed low T1-weighted image signal and high T2-weighted and diffusion-weighted images signal, with low ADC. For preoperative diagnosis, we diagnosed sigmoid colon cancer and transverse colon mesenteric and performed laparoscopic sigmoid colon and transverse colon mesenteric tumor resections. The histopathological tumor diagnoses were sigmoid colon cancer(S, type 2, 30×30 mm, 1/2 circumference, moderately differentiated adenocarcinoma, pT3[SS], INF b, Ly1a, V1a, pN1b[#252: 2/4], sM0, fStage Ⅲb)and transverse colon mesentery primary solitary fibrous tumor. The patient was treated with XELOX as the adjuvant chemotherapy and survived without recurrence until present.

[A Case of Giant Pancreatic Mucinous Cystic Neoplasm That Was Difficult to Preoperative Diagnosis].

A 43-year-old woman with about abdominal distension was referred to our hospital for a more detailed examination. Abdominal CT showed 27 cm-sized cystic lesion with the calcification along the partition wall and a nodular hyperplasia. We suspected pancreatic pseudocyst, primary retroperitoneal tumor and we performed tumorectomy. The resected specimen had a maximum diameter of 27 cm. The histopathological diagnosis was mucinous cystadenocarcinoma of the pancreas with ovarian-type stroma. The adjuvant chemotherapy treated with gemcitabine was selected for 3 courses. She continues to do well without any recurrences 7 months later.

[Questionnaire Survey of Treatment for Elderly Breast Cancer in Yamaguchi Prefecture].

A questionnaire survey was conducted by 17 doctors from 14 hospitals regarding treating elderly breast cancer in Yamaguchi Prefecture. The survey items are the implementation status of the geriatric assessment(GA)for the elderly, the state at the start of treatment(fit/vulnerable/frail), and the setting of restrictions on the indication of surgery and drug treatment (endocrine therapy/chemotherapy/molecular targeted therapy). Only one institution(6%)was used for GA; the tools used were the G8 and Charlson comorbidity index. Regarding surgical treatment, most facilities did not set restrictions according to age or condition. Endocrine and molecular-targeted therapies(anti-HER drugs)are highly tolerated, and most facilities do not have age restrictions. On the other hand, 40% of the respondents set age restrictions on chemotherapy. Four(24%) therapists said they would limit their age to 70 to 75 if the patient had a frail condition. These results tended to be similar to the reports of NCD-registered elderly breast cancer treatment.

[A Case of Gastric Cancer Performed Curative Operation after Nivolumab].

A 69-year-old man was admitted for the severe anemia. Upper gastrointestinal endoscopy revealed type 3 gastric cancer (por1, HER2 negative)that spread from EG junction to the lesser curvature of lower gastric body. CT revealed LNs metastasis and the direct invasion to the diaphragm. We diagnosed the locally advanced gastric cancer(T4bN[+]M0, Stage ⅣA) and planed neoadjuvant chemotherapy. After 3 courses of S-1 plus CDDP therapy, serum CEA level increased. And the invasion to diaphragm was unclear although the tumor shrunk. After 3 courses of nab-PTX plus RAM therapy as the second- line, the tumor was PD. As the third-line chemotherapy, nivolumab therapy was repeated up to a total of 15 courses. As the tumor was PR, the patient underwent total gastrectomy with D2 lymphadenectomy. The histopathological examination revealed that the cancer invaded into the muscle layer without lymph nodes metastasis. The cancer was diagnosed as pT2 (MP)N0M0, Stage ⅠB. The cancer cells were EB virus positive and MSI-high. CD 8 positive T lymphocytes infiltrated into the stroma. The patient is alive 26 months without adjuvant chemotherapy. The curative operation was able to perform because the infiltrative CD8 positive T lymphocytes reactivated with nivolumab responded remarkably.

[A Case of Laparoscopic Resection for a Primary Malignant Lymphoma of the Small Intestine Strongly Adhered to the Sigmoid Colon].

An 85-year-old man presented to our hospital for loss of consciousness. Blood test revealed anemia, and the fecal occult blood test was positive. Colonoscopy revealed an ileal ulcer located 10-14 cm from the ileal end on the proximal side. Pathological examination was indicative of diffuse large B-cell lymphoma(DLBCL), and laparoscopic resection was selected as the technique of choice. The ileal tumor was strongly adhered to the sigmoid colon, and laparoscopic partial resection of the ileum and sigmoid colon was performed. In general, primary gastrointestinal lymphomas may occur, for which perforate and surgical resection is recommended. It is rare for malignant lymphomas to involve other intestinal areas, and laparoscopic surgery is useful in such cases.

A phase I study of multi-HLA-binding peptides derived from heat shock protein 70/glypican-3 and a novel combination adjuvant of hLAG-3Ig and Poly-ICLC for patients with metastatic gastrointestinal cancers: YNP01 trial.

BACKGROUND: This phase I study aimed to evaluate the safety, peptide-specific immune responses, and anti-tumor effects of a novel vaccination therapy comprising multi-HLA-binding heat shock protein (HSP) 70/glypican-3 (GPC3) peptides and a novel adjuvant combination of hLAG-3Ig and Poly-ICLC against metastatic gastrointestinal cancers. METHODS: HSP70/GPC3 peptides with high binding affinities for three HLA types (A*24:02, A*02:01, and A*02:06) were identified with our peptide prediction system. The peptides were intradermally administered with combined adjuvants on a weekly basis. This study was a phase I dose escalation clinical trial, which was carried out in a three patients' cohort; in total, 11 patients were enrolled for the recommended dose. RESULTS: Seventeen patients received this vaccination therapy without dose-limiting toxicity. All treatment-related adverse events were of grades 1 to 2. Peptide-specific CTL induction by HSP70 and GPC3 proteins was observed in 11 (64.7%) and 13 (76.5%) cases, respectively, regardless of the HLA type. Serum tumor marker levels were decreased in 10 cases (58.8%). Immunological analysis using PBMCs indicated that patients receiving dose level 3 presented with significantly reduced T cell immunoglobulin and mucin-domain containing-3 (TIM3)-expressing CD4 + T cells after one course of treatment. PD-1 or TIM3-expressing CD4 + T cells and T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT)-expressing CD8 + T cells in PBMCs before vaccination were negative predictive factors for survival. CONCLUSIONS: This novel peptide vaccination therapy was safe for patients with metastatic gastrointestinal cancers.

The kinetic analysis of breast cancer: An investigation of the optimal temporal resolution for dynamic contrast-enhanced MR imaging.

INTRODUCTION: There is wide agreement that morphologic features and enhancement kinetics should be evaluated for MRI of the breast, although there has been no clear consensus concerning optimal temporal resolutions. The objective of this study was to investigate the optimal temporal resolution for the kinetic analysis of breast cancers. METHODS: Thirty-four patients with 34 enhancing lesions of breast cancer who underwent dynamic contrast-enhanced MRI (DCE-MRI) on a 3.0-T scanner were included in this retrospective study. DCE-MRI was performed with an original temporal resolution of 10-s, and the values of pharmacokinetic parameters (Ktrans, Ve, Kep, and area under the curve (AUC)) were compared with selected data of 30-s and 60-s time intervals. RESULTS: Among the 34 lesions, 10 showed a wash out pattern, 16 showed a plateau pattern, and 8 showed a persistent enhancement pattern. The Ktrans value in the wash-out pattern was significantly higher than that of other time-intensity curve patterns (p < 0.01). The Kep and AUC also showed significant differences between the wash-out pattern and other types (p < 0.01). On comparing the perfusion parameters among different temporal resolutions, simulations showed that only the AUC differed significantly between the data acquired at a 10-s temporal resolution and that acquired at a 60-s time interval (p < 0.01). Although the comparison of the AUC between the 30-s and 60-s data also showed significant differences (p = 0.01), there was no significant difference between the 10-s and 30-s data (p = 0.17). CONCLUSIONS: DCE-MRI with a temporal resolution of 30-s preserves the kinetic information. Further prospective studies will be needed to investigate the trade-off between temporal and spatial resolution in DCE-MRI.

[A Case of Local Recurrence in the Reconstructed Breast Three Years after Reconstructive Surgery and Seven Years after Breast Cancer Surgery].

In recent years, breast reconstruction has been increasingly performed in breast cancer surgery with improving the appearance of the breast. We report a case of local breast cancer recurrence after artificial breast reconstruction. The patient was a 52-year-old woman. She had undergone total mastectomy for left breast cancer 11 years ago, and reconstruction with breast implant 3 years ago. She presented to our hospital with the chief complaint of skin redness and induration of the reconstructed breast. A core needle biopsy was performed, and its results showed in the invasive ductal carcinoma. She had an operation of resection of tumor and reconstruction implant. As a result of histopathological diagnosis, it was a local recurrence of breast cancer 11 years ago. After the surgery, she underwent endocrine therapy and there is no recurrence. As the increase in the number of cases of breast reconstruction, the number of recurrences in the reconstructed breast is expected to increase the future. The treatment strategy for cases of local recurrence after breast reconstruction is currently under review, the accumulation of evidence is necessary.

Identification of a Promiscuous Epitope Peptide Derived From HSP70.

We previously found that heat-shock protein 70 (HSP70) is expressed on hepatocellular carcinoma cells and developed an HSP70 mRNA-transfected dendritic cell therapy for treating unresectable or recurrent hepatocellular carcinoma. The phase I trial was completed successfully. The purpose of this study is to identify a promiscuous epitope peptide derived from HSP70 for the purpose of developing a novel cancer peptide vaccine. Using a computational algorithm to analyze the specificity of previously reported major histocompatibility complex class I-binding peptides, we selected candidates that bound to >2 of the 3 HLA types. Twenty-nine HSP70-derived peptides (9-mers) that bound to HLA-class I was selected. The peptides were prioritized based on the results of peptide binding experiments. Using dendritic cells stimulated with the candidate peptide described previously as stimulators and CD8 T cells as effectors, an ELISPOT assay was performed. Cytotoxicity of CD8 lymphocytes stimulated with the candidate peptides toward HSP70-expressing cancer cells was analyzed using an xCELLigence System. Peptides were administered to HLA-A 24 transgenic mice as vaccines, and peptide-specific T-cell induction was measured in vivo. We identified a multi-HLA-class I-binding epitope peptide that bound to HLA-A*02:01, *02:06, and *24:02 in vitro using an interferon-γ ELISPOT immune response induction assay. Cytotoxicity was confirmed in vitro, and safety and immune response induction were confirmed in vivo using HLA-A 24 transgenic mice. Our study demonstrated that the promiscuous HSP70-derived peptide is applicable to cancer immunotherapy in patients with HLA-A*24:02-positive, *02:01-positive, and *02:06-positive HSP70-expressing cancers.

Perioperative variations in indices derived from noninvasive assessments to detect postmastectomy lymphedema.

OBJECTIVE: This study aimed to clarify the variations in indices derived from noninvasive assessments for the early detection of postmastectomy lymphedema (LE) from 1 month preoperatively until 2 years postoperatively. METHODS: In total, 120 patients who underwent surgery for breast cancer in our institution were prospectively followed up with a questionnaire for arm swelling as well as with tape measurements, bioimpedance analysis (BIA), and skin and subcutaneous tissue ultrasound at 1 month before and 3, 6, 12, 18, and 24 months after surgery. RESULTS: Ninety-seven patients completed the study. Among 93 patients who did not present with LE, 9% complained of arm swelling even before surgery, and the incidence peaked at 17% at 6 months after surgery. There were no differences in the circumferences of the upper arm, forearm, and hand between sides throughout the study period. However, the postoperative circumference values of the upper arm only on the operation side were slightly increased compared with the preoperative values. The mean excess fluid in the arm on the operation side compared with the contralateral side, as assessed by BIA, was nearly zero throughout the study period. There were no differences in subcutaneous echogenicity or skin and subcutaneous thicknesses between the sides throughout the study period. However, time-dependent increases in subcutaneous thicknesses were noticed on both sides. Four patients (4.1%) developed LE. In three of these patients, abnormality in the BIA was recorded 6 to 12 months before presentation. Immediately after presentation, the common findings included BIA abnormality and increased subcutaneous echogenicity and skin thickness in the medial forearm. CONCLUSIONS: In this study, a complaint of arm swelling was not sensitive enough for detection of the early onset of LE because a certain number of patients constantly complained of this symptom. Measurements of circumference might help in the diagnosis of LE onset, but this method is not specific enough because these measurements are also affected by various factors. However, BIA and skin and subcutaneous ultrasound were identified as potential tools for the early detection of LE.

[Combination Therapy of Hepatic Arterial Infusion Chemotherapy and Surgical Resection against Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis].

We have performed a combination therapy of hepatic arterial infusion chemotherapy(HAIC), radiation therapy(RT), and surgical resection for the treatment of hepatocellular carcinoma(HCC)with portal vein tumor thrombosis(PVTT)since 2013. We retrospectively analyzed 36 patients with HCC with PVTT who underwent hepatectomy between 1995 and 2016 to evaluate the clinical outcomes. Ten patients received preoperative HAIC, 7 underwent RT, and 14 received postoperative HAIC. The median survival time(MST)was 19.3 months, and the MST was significantly longer in the patients who underwent curative resection than those in patients who did not. In the non-curative resection group, postoperative HAIC prolonged the survival.

[Investigation of Patients with Stage â £ Breast Cancer Who Underwent Primary Tumor Resection].

We investigated whether primary tumor resection performed at our department for the purpose of local control affects the disease progression of Stage Ⅳ breast cancer. Fifteen patients who underwent primary tumor resection between 2009 and 2017 were investigated. The median age at the time of surgery was 63 years. There were two postoperative deaths(1 at<1 year postoperatively and 1 at<2 years postoperatively). The median postoperative stable disease(SD)period was 11 months overall and was 12 months or longer in 7 patients. SD was attained by all patients with the first drug treatment after primary tumor resection. Patients who tended to have a longer postoperative SD period did not receive preoperative drug treatment, were luminal HER2-positive, and had one metastatic organ. Regardless of surgery timing and reason, there were no cases of rapid postoperative disease progression. In all patients, postoperative local control was satisfactory, and continuation of medical treatment was feasible for distant metastatic tumors. These data signify that primary tumor resection can be considered to treat Stage Ⅳ breast cancer for the purpose of local control.

[A Case of Gastric Endocrine Carcinoma with a Huge Liver Metastasis].

A-67-year old man was diagnosed with gastric cancer and a liver tumor. Extended left hemihepatectomy combined with caudate lobectomy and distal gastrectomy with lymph node dissection were performed. Histological examination revealed synaptophysin and CD56positive tumor cells with a solid and rosette structure, which was diagnosed as endocrine carcinoma (EC). Additionally, a tubular adenocarcinoma was present in the stomach. The liver tumor presented as EC with tumor thrombus in the left portal vein. Finally, the patient was diagnosed with gastric EC(pT3[SS], pN0, P0, CY0, M1[HEP], Stage Ⅳ, R0). He received 6courses of the adjuvant chemotherapy with cisplatin(CDDP)plus irinotecan(CPT-11), and has been alive without recurrence for 21 months post-operation. Gastric EC is a rare subtype of gastric cancer. The resection of liver metastasis of gastric EC may improve patients' prognosis and QOL. CDDP-based chemotherapy is recommended, due to the regimen for small cell lung cancer.

[A Case of Pancreatic Head Cancer Resected after Neoadjuvant Chemotherapy Followed by Pseudocyst].

A 41-year-old man with upper abdominal and back pain was admitted to another hospital. He had a history of recurring acute pancreatitis and pseudocyst. Six months later, abdominal CT revealed a pancreatic head tumor arising from the pseudocyst, and adenocarcinoma was suspected based on endoscopic ultrasound fine needle aspiration(EUS-FNA)findings. We selected neoadjuvant chemotherapy because resection was difficult due to severe inflammation and edema around the tumor. Chemotherapy(FOLFIRINOX followed by gemcitabine plus nab-paclitaxel)was effective, and the tumor almost disappeared on CT. Subtotal stomach-preserving pancreatoduodenectomy(SSPPD)was performed 12 months after starting chemotherapy, and curative resection was successful. The final Stage was ⅡA(T3[CH1]N0M0). Histopathological examination revealed no viable tumor cells. S-1 adjuvant chemotherapy was administered for 6 months. He was still alive 22 months postoperation without any recurrence. Neoadjuvant chemotherapy is effective in cases involving pancreatic cancer with severe inflammation, because pre-operative chemotherapy can reduce tumor size and alleviate the inflammation caused by acute pancreatitis and pseudocysts.

Thymidine phosphorylase affects clinical outcome following surgery and mRNA expression levels of four key enzymes for 5-fluorouracil metabolism in patients with stage I and II non-small cell lung cancer.

The expression levels of thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), thymidylate synthase (TS) and orotate phosphoribosyltransferase (OPRT) may predict the clinical efficacy of 5-fluorouracil-based chemotherapy in patients with cancer. We herein investigated the differences in the mRNA levels of these enzymes in non-small-cell lung cancer (NSCLC) and evaluated their prognostic value for NSCLC treated by surgical resection. The intratumoral mRNA levels of TP, DPD, TS, and OPRT were quantified in 66 patients with pathological stage I and II NSCLC (adenocarcinoma or squamous cell carcinoma) following complete resection according to the Danenberg Tumor Profile method. The TP level was the only significant prognostic factor for disease-specific survival (DSS) following complete resection; the mean TP mRNA level differed significantly between the high and low mRNA expression groups. The DSS at 5 years was significantly higher in the low TP mRNA compared with that in the high TP mRNA expression group (83.4 vs. 58.6%, respectively; P=0.005). A Cox proportional hazards model revealed that pathological stage, sex, and TP expression were independent prognostic factors for DSS in patients with stage I and II NSCLC following complete resection. Thus, TP level may be used to monitor treatment efficacy and predict the outcome of NSCLC patients.