Multiple developmental pathways lead to the generation of CD4 T-cell memory.

Long-term immunological memory mediated by CD4 T cells provides a rapid protection against previously encountered pathogens or antigens. However, it is still controversial how memory CD4 T cells are generated and maintained. Unclear definitions of T-cell memory may be partially responsible for this controversy. It is becoming clear that diverse pathways are responsible for the differentiation and long-term persistence of memory T cells. We herein discuss the diversity of memory cell generation, describing a novel population of resting memory CD4 T cells and their precursors.

[Two Cases in Which Simultaneous Laparoscopic Surgery and Breast Cancer Surgery Using a Head-Mounted Monitor Were Useful].

Herein, we report on how we were able to reduce the operation time by simultaneously performing laparoscopic surgery and breast cancer surgery using a head-mounted monitor(HMS-3000MT, Sony corporation). Case 1: 60s, female. A 5.5 cm leiomyoma was found in the central thoracic esophagus, and a 1 cm breast cancer was found in the C region of the left mammary gland. Subtotal esophagectomy with right thoracotomy and laparoscopy and a left partial mastectomy were performed. For the abdominal surgery, HMS-3000MT was used under hand-assisted laparoscopy, and a left partial mastectomy was performed concurrently. Operation time was 367 minutes(simultaneous surgery for 56 minutes). Esophagus: leiomyoma, 50×45 mm; and mammary gland: 16×15 mm, pTis(DCIS), pN0(sn), cM0, and pStage 0. Case 2: 70s, female. A 3 cm sized GIST was found on the posterior wall of the middle gastric body, and a breast cancer of 1.3 cm was also found in the B region of the right mammary gland. Using HMS-3000MT, laparoscopic local resection of the stomach and right total glandectomy were performed concurrently. Operation time was 114 minutes(simultaneous surgery for 58 minutes). Stomach: GIST, 25×22 mm, and modified Flecher classification low risk; and mammary gland: invasive ductal carcinoma, 15×15 mm, pT1c, pN0(sn), cM0, and pStage Ⅰ. Conclusion: In 2 fields of surgery, simultaneous surgery using HMS-3000MT was considered to be a useful method to shorten the operation time.

[A Case of Ectopic Pheochromocytoma between the Abdominal Aorta and Inferior Vena Cava].

We report a case of ectopic pheochromocytoma which is relatively rare. A 50-year-old man was found to have an abdominal tumor on a medical examination, and contrast-enhanced computed tomography showed a retroperitoneal tumor between the abdominal aorta and the inferior vena cava. As a result of close examinations, an ectopic pheochromocytoma was suspected. He was asymptomatic and suspected infiltrating into great vessels, but possibility of a malignant neoplasm could not be ruled out for the tumor had a tendency to enlarge, the resection of the tumor was performed. During the operation, the invasion of the tumor into the great vessels was denied and the tumor was completely resected. Large fluctuation of the blood pressure was not observed during the operation. Histopathological evaluations of the resected specimen revealed the ectopic pheochromocytoma. A pheochromocytoma was newly defined as a tumor with malignant potential for metastasis in all cases by the WHO classification published in 2017. He was diagnosed as moderately malignant by GAPP score, therefore the careful follow-up was considered necessary in the future.

[A Case of Metastatic Breast Cancer with BRCA1 Mutation after Breast Reconstruction and Pregnancy].

We present the case of a 31-year-old woman with a chief complaint of a left breast mass. The patient visited our department for an evaluation of this left breast mass. Left breast cancer(cT1cN0M0, cStage Ⅰ, triple negative type)was diagnosed, and left partial mastectomy and sentinel node biopsy were performed. Although the pStage was the same prior to surgery, a BRCA1 mutation was identified on genetic testing. After administration of postoperative adjuvant chemotherapy (epirubicin, cyclophosphamide, and paclitaxel), consorted mastectomy, tissue expander insertion, and breast reconstruction with silicone implant were performed. Spontaneous pregnancy occurred 1 year and 10 months after the first operation. She had an uneventful delivery with a normal course of labor 2 years and 6 months after the surgery. Two years and 11 months after the first operation, she visited our institution with complaints of headache, dizziness, and difficulty eating. Upon assessment, brain, lung, liver, and bone metastases were identified on contrast-enhanced computed tomography. Concentrated glycerin and fructose, steroid administration, and whole-brain irradiation improved the symptoms due to cerebral edema. Thereafter, olaparib was started, and treatment was continued while maintaining partial response(PR).

Kit-independent mast cell adhesion mediated by Notch.

Kit/CD117 plays a crucial role in the cell-cell and cell-matrix adhesion of mammalian mast cells (MCs); however, it is unclear whether other adhesion molecule(s) perform important roles in the adhesion of MCs. In the present study, we show a novel Kit-independent adhesion mechanism of mouse cultured MCs mediated by Notch family members. On stromal cells transduced with each Notch ligand gene, Kit and its signaling become dispensable for the entire adhesion process of MCs from tethering to spreading. The Notch-mediated spreading of adherent MCs involves the activation of signaling via phosphatidylinositol 3-kinases and mitogen-activated protein kinases, similar to Kit-mediated spreading. Despite the activation of the same signaling pathways, while Kit supports the adhesion and survival of MCs, Notch only supports adhesion. Thus, Notch family members are specialized adhesion molecules for MCs that effectively replace the adhesion function of Kit in order to support the interaction of MCs with the surrounding cellular microenvironments.

Global Ocean Spectrophotometric pH Assessment: Consistent Inconsistencies.

Ocean acidification (OA)-or the decrease in seawater pH resulting from ocean uptake of CO2 released by human activities-stresses ocean ecosystems and is recognized as a Climate and Sustainable Development Goal Indicator that needs to be evaluated and monitored. Monitoring OA-related pH changes requires a high level of precision and accuracy. The two most common ways to quantify seawater pH are to measure it spectrophotometrically or to calculate it from total alkalinity (TA) and dissolved inorganic carbon (DIC). However, despite decades of research, small but important inconsistencies remain between measured and calculated pH. To date, this issue has been circumvented by examining changes only in consistently measured properties. Currently, the oceanographic community is defining new observational strategies for OA and other key aspects of the ocean carbon cycle based on novel sensors and technologies that rely on validation against data records and/or synthesis products. Comparison of measured spectrophotometric pH to calculated pH from TA and DIC measured during the 2000s and 2010s eras reveals that (1) there is an evolution toward a better agreement between measured and calculated pH over time from 0.02 pH units in the 2000s to 0.01 pH units in the 2010s at pH > 7.6; (2) a disagreement greater than 0.01 pH units persists in waters with pH < 7.6, and (3) inconsistencies likely stem from variations in the spectrophotometric pH standard operating procedure (SOP). A reassessment of pH measurement and calculation SOPs and metrology is urgently needed.

[A Case of Laparoscopic Distal Gastrectomy for Gastric Cancer with an Adachi Type â ¥ Group 24 Vascular Anomaly].

We report a case of successful laparoscopic distal gastrectomy for gastric cancer with an Adachi type Ⅵ group 24 vascular anomaly. A male in his 60s exhibited a type 0-Ⅱa plus Ⅱc lesion at the lesser curvature of the gastric angle by esophagogastroduodenoscopy and was diagnosed with tub2. He was referred to us for surgical treatment. The clinical diagnosis was cT1bN0M0, and cStage Ⅰ. Preoperative multidetector-row computed tomography(MDCT)showed an Adachi type Ⅵ group 24 vascular anomaly. At laparoscopic surgery, we dissected No. 8a lymph nodes with exposure of the surface of the portal vein because the common hepatic artery was absent. The left gastric artery and splenic artery formed a common trunk. As there are various kinds of vascular anomalies of the celiac artery branch, we must understand the arterial running pattern prior to gastric surgery. This technique is more useful in laparoscopic surgeries where tactile sensation is limited. To prevent perioperative and postoperative complications, we must recognize the anomaly pattern prior to surgery using MDCT.

[A Case in Which Trastuzumab Combined Chemotherapy Was Effective for Recurrence of Post-Operative Gastric Cancer with Partial HER2 Overexpression].

We report a case in which recurrent partial HER2-positive gastric cancer showed complete clinical response to capecitabine (Cape)/oxaliplatin(L-OHP/OX)(CapeOX)plus trastuzumab(Tmab)combined chemotherapy for 32months. A 65-yearold man underwent distal gastrectomy, D2 lymph node dissection, and Roux-en-Y reconstruction for type 2 gastric cancer of the prepyloric anterior wall in December 2014. Pathological stage was as follows: L, ant, Type 2, 32×22 mm, tub1>tub2> por1, pT2(MP), int>med, INF c>a, Ly1a, V0, pN0, cM0, cH0, cP0, pCY0, pStage I B, pPM0(60mm), pDM0(75mm), pR0. Immunostaining of the tumor indicated overexpression of the HER2 gene in more than 10% of the well differentiated tubular adenocarcinoma(tub1). Nineteen months post-surgery, pancreatic head lymph node metastasis was diagnosed, and we started CapeOX plus Tmab combined chemotherapy. After 19 courses, the metastatic lymph node reduced its size until we could not detect it on CT. We continued treatment for 45 courses(about 32 months). During the courses, there were adverse events such as peripheral neuropathy(Grade 3, CTCAE v5.0), which required interruption of L-OHP, and oral mucosal ulcer (Grade 2).

[A Case of Laparoscopic Low Anterior Resection and Adrenalectomy for Rectal Cancer and Adrenal Tumor].

A 70-year-old woman had consulted a doctor at a former clinic because of bloody stool and colonoscopy revealed a type 2 tumor of the rectum. She was referred to our hospital for further examinations and treatment. Preoperative blood examination showed an elevated HbA1c level of 10.2%. Abdominal CT showed a 25mm tumor in the left adrenal gland. The patient was diagnosed with adrenal Cushing's syndrome based on low ACTH levels, disappearance of circadian variation in blood cortisol levels, lack of inhibition by dexamethasone loading, and high urinary cortisol levels. Laparoscopic adrenalectomy for left adrenal tumor and low anterior resection for rectal cancer were performed. The pathological findings were rectal cancer, pap, pT1b(SM), pN0, cM0, fStageⅠof rectal cancer, and adrenal cortical adenoma. The postoperative course was uneventful with steroid replacement therapy. The ileal stoma was closed 4 months after surgery. Surgery in hyperadrenalism requires perioperative steroid replacement therapy because of the risk of postoperative acute adrenal failure. In addition, when diabetes is poorly controlled, we should be careful about risk of leakage and susceptibility to infection.

[A Case of Effective Neoadjuvant Chemotherapy for Transverse Colon Cancer with Extensive Abdominal Wall Invasion].

A 68-year-old man with abdominal mass and anorexia was diagnosed with transvers colon cancer invading the abdominal wall. Considering the difficulty of curative resection, we first performed ileostomy. After surgery, the patient received mFOL FOX6 with bevacizumab as neoadjuvant chemotherapy. After 10 course of the regimen, computed tomography revealed shrinkage of the lesion, with the efficacy evaluated as a partial response. The patient underwent right hemicolectomy and partial resection of the abdominal wall. The pathological findings was ypT3(SS), ypN3, ly0, v1, ypPM0, ypDM0, ypRM0, ypStage III b. On histopathological examination, the efficacy of the chemotherapy was evaluated as Grade 1b. The patient received adjuvant chemotherapy with mFOLFOX6 and remains well without any evidence of recurrence more than 7 months after surgery.

[A Case of Appendiceal Mucinous Adenocarcinoma Detected with a Bladder Tumor].

A 74-year-oldwoman hadconsultedthe department of urology in our hospital because of microscopic hematuria. Cystoscopy revealeda urinary bladder tumor, suspectedas an adenocarcinoma basedon biopsy. MRI showeda cystic tumor of the appendix with vesical fistula; therefore, she underwent an operation with a diagnosis of appendiceal cancer invading the urinary bladder. During the operation, we found that the appendix sunk into the urinary bladder with right adnexa. Therefore, we performed ileocecal resection, partial resection of the urinary bladder, and right adnexectomy. Macroscopically, the bladder was filled with a large number of mucus lumps. A papillary tumor, 4 cm in size, growing in the lumen of the bladder was detectedat the invasion site. Microscopically, proliferating carcinoma cells in a papillary form were observedin the lumen of the appendix with mucus production, invading the wall of the urinary bladder at the fundus of the appendix. Thus, the patient was diagnosed with mucinous adenocarcinoma of the appendix(V, type 1, 45×30 mm, muc, pT4b[SI, urinary bladder], int, INF c, ly0, v0, pN0, cM0, pStage II ). Primary appendiceal cancer invading the urinary bladder is very rare; herein, we report a rare case of appendiceal mucinous adenocarcinoma detected with a bladder tumor and present a literature review.

Risk Factors for Anastomotic Leakage After Intersphincteric Resection Without a Protective Defunctioning Stoma for Lower Rectal Cancer.

BACKGROUND: Intersphincteric resection (ISR) is performed as an alternative to abdominoperineal resection for super-low rectal cancer. The purpose of this study was to evaluate risk factors for anastomotic leakage (AL) after ISR without a defunctioning stoma for lower rectal cancer. METHODS: Between 1995 and 2012, 135 consecutive patients with lower rectal cancer underwent curative ISR without a protective defunctioning stoma. Univariate and multivariate analyses were performed to determine the risk factors for AL. RESULTS: The radiological and symptomatic AL rate was 17.0 % (23/135). Univariate analysis demonstrated that male sex (P = 0.030), preoperative chemotherapy (P = 0.016), partial ISR (P < 0.001), lateral lymph-node dissection (P = 0.042), distal tumor distance from the dentate line (P = 0.007), and straight reconstruction (P < 0.001) were significantly associated with AL. Severe AL requiring re-laparotomy developed in 13 (9.6 %) patients. Univariate analysis demonstrated that male sex (P = 0.006), partial ISR (P < 0.001), distal tumor distance from the dentate line (P = 0.002), and straight reconstruction (P < 0.001) were significantly associated with AL requiring relaparotomy. Multivariate analysis demonstrated that partial ISR [odds ratio (OR) 6.701; P = 0.001] and straight reconstruction (OR 5.552; P = 0.002) were independently predictive of AL. CONCLUSIONS: Partial ISR and straight reconstruction increased the risk of AL after ISR without a protective defunctioning stoma. A defunctioning stoma might be mandatory in patients with the risk factors identified in this analysis.

[A Case of Retroperitoneal Liposarcoma].

A 52-year-old man visited a local hospital complaining of abdominal distension. Enhanced computed tomography scan revealed a giant retroperitoneal tumor surrounding the left internal iliac artery and left kidney. We performed en bloc tumor resection with left internal iliac artery resection. The tumor was 35 cm in size and weighed 6,860 g. The histological diagnosis was a dedifferentiated liposarcoma. After surgery, the patient experienced left lower limb paralysis. Clinical examination and neurological findings suggested a lumbosacral problem. After 6 months, the patient's lower limb paralysis had not improved. It is important to note that ischemic neuropathy may be related to internal iliac artery resection.

[A Case of Curatively Resected Ascending Colon Cancer Invading the Duodenum after Neoadjuvant Chemotherapy].

A 64-year-old woman with anorexia and anemia was diagnosed with ascending colon cancer invading the duodenum. Considering the difficulty of curative resection, we first performed gastrojejunostomy and ileostomy. After surgery, the patient received FOLFIRI with cetuximab as neoadjuvant chemotherapy. After 9 courses of the regimen, enhanced computed tomography revealed shrinkage of the lesion, with the efficacy evaluated as a partial response. The patient underwent right hemico- lectomy and partial resection of the duodenum. The pathological diagnosis was pT3(SS), pN0(0/30), ly1, v1, pPM0, pDM0, pRM0, fStage II . On histopathological examination, the efficacy of chemotherapy was evaluated as Grade 1a. The patient received adjuvant chemotherapy with FOLFIRI and remains well without any evidence of recurrence more than 6 months after surgery.

[A Case of MALT Lymphoma of the Rectum Treated with Intersphincteric Resection (ISR)].

A 60-year-old woman visited a local hospital complaining of melena. On colonoscopy, she was found to have 2 tumors in the lower rectum, each of approximately 10 mm in diameter. A biopsy of the tumors indicated MALT lymphoma, and the patient was referred to our hospital. We performed intersphincteric resection (ISR) with lymph node dissection according to the guidelines for the treatment of rectal cancer for 2 reasons. One reason was that eradication therapy for Helicobacter pylori was not effective in this case, and we needed to obtain an accurate histopathological diagnosis as to whether the patient had diffuse large B cell lymphoma (DLBCL). The other reason was that it was localized disease in the rectum, and that curative resection could be performed. MALT lymphoma of the rectum occurs frequently in the lower rectum and has a relatively good prognosis. It is important to consider the quality of life when selecting an operative method. ISR is thought to be a good option.

[Preoperative Chemotherapy and Risk Factors for Colorectal Liver Metastases].

Between February 2007 and December 2013, 65 liver resections for colorectal metastases were performed in our institution. Preoperative chemotherapy was conducted in 47 patients, of whom 42 were treated with modified FOLFOX6 (mFOLFOX6)-based preoperative chemotherapy. For cases of solitary tumors smaller than 2 cm that are located in the liver surface area, we selected upfront surgery. In the patients who underwent preoperative chemotherapy and upfront surgery, the 3-year OS was 73.9% (Grade A: 81.8%, Grade B: 77.8%, and Grade C: 0%) and the 5-year OS was 62.5%. The 3-year OS in the preoperative chemotherapy group was 63.3%. OS did not differ significantly between the patients who were grouped according to the time of metastasis onset or the extent of metastasis according to the Japanese classification. In the multivariate analysis, no statistical differences were found between the risk factors for recurrence. However, further follow up is needed. Moreover, we believe that the relationships of morphological response to chemotherapy, pathological response, and clinical prognosis should be assessed in the future.

[A Case of Extranodal Nasal Type, NK／T Cell Lymphoma in the Ileum with Perforated Peritonitis during Chemotherapy].

A 65-year-old woman complaining of melena and a high fever was admitted to our hospital. Colonoscopy revealed a large tumor with a wide ulcer in the terminal ileum, and nasal type, extranodal NK/T cell lymphoma was suspected via biopsy. Owing to rapid progression of hepatocellular damage with hepatomegaly and splenomegaly, chemotherapy with CHOP was initiated immediately. Two days later, the patient developed panperitonitis, and emergency laparotomy was performed. The tumor in the terminal ileum widely adhered to the bladder, where a deep perforated ulcer was found, for which palliative ileocecal resection was performed. Enlargement of the residual tumor caused an abdominal abscess, intestinal obstruction, and hepatic failure, and the patient died 75 days after surgery. In summary, we initiated chemotherapy to control the deteriorating systemic condition of the patient. However, nasal type, extranodal NK/T cell lymphoma is a rapidly progressing lymphoma occasionally accompanied by perforation of the tumor. Surgery preceding chemotherapy should be considered an alternative treatment.

[Treatment Strategy for Stage â £ Rectal Cancer].

Eighteen consecutive patients who underwent rectal resection following preoperative chemotherapy for cStage Ⅳ rectal cancer at our institute, between 2009 and 2014, were retrospectively assessed. Preoperative chemotherapy with mFOLFOX6, SOX, XELOX, and other anticancer agents was administered to 8, 5, 3, and 2 patients, respectively. Combined molecular targeted therapy was administered to 12 patients. The response evaluation showed that an antitumor effect was observed in 10 and 8 patients with local tumors who achieved a partial response (PR) and stable disease (SD), respectively, and in 9 and 9 patients with distant metastases who achieved a PR and SD, respectively. The operative procedures included high/low anterior resection (n=12), intersphincteric resection (n=2), and abdominoperineal resection/Hartmann's operation (n=4). An ileostomy was performed in 6 patients before chemotherapy. Postoperative complications occurred in 6 patients. Two patients with an ileostomy had anastomotic insufficiency, but recovered without reoperation. There was no significant difference in overall survival (p=0.382) when these patients were compared with 45 cStage Ⅳ rectal cancer patients who underwent surgery without preoperative chemotherapy. However, the rate of curability B was higher in patients who received preoperative chemotherapy (44.4%) compared to those who did not (26.7%). The results of this study are inconclusive and have not determined whether preoperative chemotherapy results in better long-term survival for cStage Ⅳ rectal cancer patients. However, preoperative chemotherapy might contribute to higher operative curability.

[A Case of Pseudo-Meigs Syndrome Associated with Metachronous Ovarian Metastasis from Ascending Colon Cancer].

We experienced a case of pseudo-Meigs syndrome associated with metachronous metastasis to the ovary from ascending colon cancer. A 65-year-old woman underwent curative surgery for ascending colon cancer at another hospital. A follow-up CT carried out 3 months after the surgery revealed a right ovarian tumor and a large amount of ascites. The patient was diagnosed with ovarian metastasis from ascending colon cancer with carcinomatous peritonitis. Palliative care was recommended, and she presented at our department for a second opinion. In spite of a large amount of ascites and pleural effusion, no disseminating tumor was detected on contrast-enhanced CT at our hospital, and we recommended that she undergo a diagnostic laparotomy. The laparotomy was negative for carcinomatous peritonitis and a right oophorectomy was performed. The histopathological findings indicated that the ovarian tumor was consistent with metastasis from ascending colon cancer. After the surgery, we initiated chemotherapy with mFOLFOX6+bevacizumab and the symptoms were well controlled. A follow-up CT carried out 11 months after the surgery revealed a left ovarian tumor and increased ascites, and the patient underwent a left oophorectomy. Then, chemotherapy with the same regimen was administered for 12 months, and she did not develop any signs of recurrence for 27 months after the surgery. Ovarian metastasis from colon cancer may occasionally cause pseudo-Meigs syndrome, and it is important to be aware of the usefulness of oophorectomy for the control of ascites and pleural effusion.

[A review of stereotactic radiotherapy (SRT) for lung metastasis of colon cancer].

We retrospectively analyzed the efficacy of stereotactic radiotherapy (SRT) for lung metastasis of colon cancer, with particular emphasis on local tumor control. Seven patients with 8 lesions underwent SRT for lung metastasis of colon cancer in our institution between February 2012 and February 2014. We judged the curative effect of SRT on the basis of tumor shrinkage observed on computed tomography (CT) scans. All lung metastases decreased in size, and local recurrence was not observed. SRT is a technique involving three-dimensional radiation, which decreases radiation exposure to neighboring normal tissues. The 2-year local tumor control rate for lung metastasis of colon cancer with SRT is 77.9%, and the 2-year survival rate is 53.7%. Our results, in which all patients achieved local control, suggest that SRT is a minimally aggressive treatment option for lung metastasis of colon cancer in cases where a pneumonectomy is difficult to perform. In the future, results from long-term studies are needed to validate our findings.