[A Case of Double Cancer of Squamous Cell Carcinoma of the Rectum and Adenocarcinoma of the Sigmoid Colon].

A 72-year-old male was transported to our hospital with complaints of heart palpitations and dyspnea since a month earlier and was immobile. Blood examination showed severe anemia, and colonoscopy revealed circumferential tumors in the rectum and the sigmoid colon. Histopathologic examination revealed the tumors as squamous cell carcinoma of the rectum and adenocarcinoma of the sigmoid colon. Therefore, they were diagnosed as double colorectal cancers. CT and MRI showed that rectal cancer invaded the seminal vesicles and the prostate; therefore, the patient underwent neoadjuvant chemoradiotherapy(oral capecitabine and concomitant radiation therapy: a total dose of 50.4 Gy/28 Fr)followed by total pelvic exenteration. Subsequent specimen pathology revealed a tumor regression grading of Grade 2 for the rectal and sigmoid colon cancers, and both were staged as ypT3N0M0, ypStage Ⅱa. Herein, we report a rare case of double cancer of adenocarcinoma of the sigmoid colon and squamous cell carcinoma of the rectum with a literature review.

Diabetes in Humans Activates Pancreatic Stellate Cells via RAGE in Pancreatic Ductal Adenocarcinoma.

Pancreatic stellate cells (PSCs) mainly consist of cancer-associating fibroblasts in pancreatic ductal adenocarcinoma (PDAC). The receptor for advanced glycation end products (RAGE) is implicated in the pathophysiology of diabetic complications. Here, we studied the implication of RAGE in PSC activation in PDAC. The activation of cultured mouse PSCs was evaluated by qPCR. The induction of epithelial mesenchymal transition (EMT) in PDAC cell lines was assessed under stimulation with culture supernatant from activated PSCs. A total of 155 surgically resected PDAC subjects (83 nondiabetic, 18 with ≦3-years and 54 with >3-years history of diabetes) were clinicopathologically evaluated. A high-fat diet increased the expression of activated markers in cultured PSCs, which was abrogated by RAGE deletion. Culture supernatant from activated PSCs facilitated EMT of PDAC cells with elevation of TGF-ß and IL-6, but not from RAGE-deleted PSCs. Diabetic subjects complicated with metabolic syndrome, divided by cluster analysis, showed higher PSC activation and RAGE expression. In such groups, PDAC cells exhibited an EMT nature. The complication of metabolic syndrome with diabetes significantly worsened disease-free survival of PDAC subjects. Thus, RAGE in PSCs can be viewed as a new promoter and a future therapeutic target of PDAC in diabetic subjects with metabolic syndrome.

[A Case of Stage â £ Gastric Cancer with Para-Aortic Lymph Node Metastasis, and Multiple Liver, Lung, and Bone Metastases Leading to Conversion Therapy].

We report a case of unresectable gastric cancer with para-aortic lymph node metastasis, and multiple liver, lung, and bone metastases leading to conversion therapy. A 70s-year-old man visited previous doctor with epigastralgia. He was diagnosed as stage Ⅳ gastric cancer with para-aortic lymph node metastasis, and multiple liver, lung, and bone metastases by upper gastrointestinal endoscopy, contrast enhanced computer tomography(CT), and positron emission tomography(PET). After a regimen consisting of 6 courses of capecitabine plus cisplatin plus trastuzumab, para-aortic lymph node metastasis and liver, lung, and bone metastases were absent in CT and PET images. So, he visited our department for surgery treatment. We judged curative resection could be achieved for gastric cancer. Total gastrectomy, D2 and paraaortic lymphadenectomy, and cholecystectomy were performed. The histopathological examination of the resected specimen revealed the efficacy of chemotherapy was Grade 2b. The patient was discharge 14 days after the operation, and capecitabine plus trastuzumab was started as adjuvant chemotherapy, and the patient remains alive without recurrence 11 months after surgical treatment.

[Improvement of QOL by Surgery in Two Patients for Brain Metastasis from Esophageal Carcinoma with Paralysis-A Report of Two Cases].

Brain metastasis from esophageal cancer is rare. Symptoms such as paralysis caused a decline in quality of life(QOL)and activity of daily life(ADL)and required emergency treatment. We report 2 cases in which QOL was improved by emergency resection for brain metastasis from esophageal carcinoma with paralysis. Case 1: A 50's male was diagnosed esophageal carcinoma and underwent esophagectomy(pT3N2M0, Stage Ⅲ). Brain metastasis was detected owing to development of left hemiparesis. Craniotomy and tumorectomy were performed, left hemiparesis was improved. He died 10 months after diagnosis of brain metastasis due to progression of other metastatic lesions. Case 2: A 61-year-old female was diagnosed esophageal carcinoma and underwent esophagectomy(pT3N1M0, Stage Ⅲ). She developed right hemiparesis 5 months after esophagectomy, admitted to our hospital. Brain and lung metastases were detected, craniotomy and tumorectomy and were performed, right hemiparesis was improved. Although systemic chemotherapy was administered, she died 10 months after diagnosis of brain metastasis due to progression of lung metastasis. Conclusion: Aggressive surgical treatments for brain metastasis were one good treatment option to maintain QOL and ADL.

[A Case of Myocardial Metastasis of Esophageal Squamous Cell Carcinoma].

Myocardial metastasis for esophageal squamous cell carcinoma(ESCC)is relatively rare and it is diagnosed as a part of widespread metastasis in the terminal stage. We experienced a case of myocardial metastasis of ESCC treated effectively with chemoradiotherapy. A 56-year-old man was diagnosed ESCC(clinical T3N2M0, Stage III). He received neoadjuvant chemotherapy of 5-fluorouracil plus cisplatin followed by subtotal esophagectomy with dissection of the 3 regional lymph nodes. The pathological diagnosis was moderate differentiated squamous cell carcinoma, CT-pT3(T3), pN1, sM0, fStage III. Four months after surgery, he had no clinical symptom, however myocardial metastasis located in the apex was detected on the follow up positron emission tomography(PET). Chemoradiotherapy was performed for the myocardial metastasis. Myocardial metastasis treated effectively with chemoradiotherapy almost disappeared on the PET and computed tomography taken 3 months after chemoradiotherapy. He died, however, of multiple liver and bone metastases 15 months after the initial surgery.

[A Case of Advanced Gastric Cancer with Peritoneal Dissemination after Gastrectomy Effectively Treated with Combination Chemotherapy of Ramucirumab and Paclitaxel].

The REGARD and RAINBOW trials revealed the effectiveness of ramucirumab(RAM)for advanced gastric cancer patients who had been previously treated with chemotherapy. In the latest Japanese gastric cancer treatment guidelines, PAM plus paclitaxel(PTX)was positioned as a second-line chemotherapy for advanced gastric cancer. We report a case of advanced gastric cancer with peritoneal dissemination after gastrectomy effectively treated with RAM plus PTX. A 66-year-old woman underwent total gastrectomy with D2 lymph node dissection, splenectomy, and distal pancreatectomy. The pathological diagnosis was poorly differentiated adenocarcinoma, pT4b(pancreas), N3b, P1, CY1, Stage Ⅳ. She was treated with postoperative chemotherapy of S-1 plus cisplatin. However, 5 months after surgery, computed tomography(CT)showed ascites and recurrence of peritoneal dissemination. Cytological examination showed adenocarcinoma cells in the ascites. She was treated with combination chemotherapy of RAM and PTX as second line chemotherapy. After 1 course of this therapy, CT revealed complete disappearance of ascites and significant reduction in the size of the peritoneal dissemination. The patient survived without progression for 8 months after the recurrence was detected.

[Outcomes of Total Mesorectal Excision and Lateral Lymph Node Dissection following Neoadjuvant Chemotherapy for Lower Rectal Cancer with Lateral Lymph Node Metastasis].

INTRODUCTION: Progressive lower rectal cancer with metastasis to the lateral lymph nodes has poor prognosis, requiring systemic chemotherapy. In addition, because laparoscopic lateral lymph node dissection(LLND)in positive cases of metastasis to the lateral lymph nodes is difficult, it has not been commonly used. Here, we report the treatment results of neoadjuvant chemotherapy(NAC)and subsequent laparoscopic total mesorectal excision(TME)plus LLND in cases of lower rectal cancer with metastasis to the lateral lymph nodes. SUBJECTS AND METHODS: The subjects were 4 patients with metastasis to the lateral lymph nodes who underwent LLND after NAC. The surgical outcomes were investigated retrospectively. RESULTS: The mean surgical time was 398 minutes, and the mean bleeding amount was 150 g. In total, 33.5 lymph nodes were dissected, including 15.3 lateral lymph nodes. There was no switch to laparotomy, and no postoperative complications of Grade Ⅲ or higher according to the Clavien-Dindo classification were observed. CONCLUSION: Laparoscopic TME plus LLND after NAC is considered safe and useful as radical surgery for positive cases of metastasis to the lymph nodes.

[A Case of Laparoscopic Resection for Locally Advanced Primary Rectal Cancer after Neoadjuvant Chemotherapy].

We treateda 70-year-oldfemale patient with locally advancedrectal cancer accompaniedby metastases to other organs. Three courses of S-1 plus oxaliplatin(SOX)therapy were administered as neoadjuvant chemotherapy(NAC), andthe cancer was subsequently treatedwith laparoscopic rectal resection. She hadvisiteda physician with a chief complaint of melena. A type 2 tumor located in the rectum Rb was found during the lower gastrointestinal endoscopy, which was diagnosed as an adenocarcinoma by biopsy. Vaginal invasion andlymph node metastasis were observedon CT andMRI. After 3 courses of SOX therapy(NAC), her condition was categorized as SD. Laparoscopic rectal amputation(D3)combinedwith resection of the ovary, uterus, and vagina was performed. On histopathological examination, the tumor was an adenocarcinoma, muc> tub2, ypT4b(AI, vaginal wall), int, INF b, ly1, v2, EX(-), PN1a, grade 1, pPM0, pDM0, pRM0 and pStage Ⅲa. The histological analysis demonstrated that the therapeutic effect of chemotherapy was grade 1a. Laparoscopic surgery, which is a relatively safe procedure, may be useful after NAC for an R0 resection.

[The Impact of Neutrophil-Lymphocyte Ratio on the Prognosis in Patients Who Underwent Esophagectomy for Esophageal Cancer].

BACKGROUND: Thene utrophil-lymphocyteratio (NLR)reflects a patient's systemic inflammatory response. Several studies have revealed that the NLR is associated with a poor prognosis in several types of malignant tumors such as colorectal and lung cancer. The aim of this study was to evaluate the impact of preoperative NLR on the prognosis of patients with esophageal cancer. METHODS: The NLR was calculated for 93 consecutive patients with clinical Stage II or III esophageal cancer, who underwent curative esophagectomy following neoadjuvant chemotherapy between 2011 and 2013. The impact of preoperativeNLR on overall survival(OS)after esophagectomy was evaluated. The NLR cut off value was set to 2. RESULTS: The 3-year OS of patients with NLR≥2 was significantly shorter than patients with NLR<2(40.5% vs 67.9%, p=0.005). In a multivariateCox model, NLR≥2(HR: 2.342, 95%CI: 1.095-5.007, p=0.028), pathological depth of tumor(HR: 3.207, 95%CI: 1.114- 9.233, p=0.031), and an ageove r 60(HR: 2.342, 95%CI: 1.117-6.501, p=0.027)were identified as independent prognostic factors for OS after esophagectomy. CONCLUSIONS: The preoperative NLR was significantly associated with a poor prognosis in esophageal cancer patients who underwent curative esophagectomy following neoadjuvant chemotherapy.

[Laparoscopic Lateral Lymph Node Dissection for Rectal Cancer with Lateral Lymph Node Metastasis - A Case Report].

BACKGROUND: Lateral lymph node dissection(LLND)for locally advanced lower rectal cancer is the standard treatment procedure in Japan. We performed LLND with an extraperitoneal approach. Recently, we introduced laparoscopic surgery for locally advanced rectal cancer and laparoscopic LLND. We performed laparoscopic LLND in a patient havinglower rectal cancer with lateral lymph node metastasis that was detected via preoperative imaging. CASE PRESENTATION: The patient was a woman in her 50s who experienced melena and visited a physician. Colonoscopy revealed a tumor in the lower rectum and computed tomography showed lateral lymph node swelling and liver metastasis. The patient was referred to our institution and she was diagnosed with lower rectal cancer having lateral lymph node and synchronous liver metastases. We performed laparoscopic abdominoperineal resection and laparoscopic LLND. The operatingtime was 260 min, and the blood loss was 60g. CONCLUSION: The magnification of laparoscopy enables precision in the surgical operation of the narrow pelvis during lymph node dissection, allowingautonomic nerve preservation. Therefore, laparoscopic LLND is a helpful procedure in the treatment of locally advanced rectal cancer with a lateral lymph node metastasis.

[A Case of Pathological Complete Response after Neoadjuvant Chemotherapy(S-1 plus Oxaliplatin)and Laparoscopic Low Anterior Resection for Rectal Cancer].

We report a case of pathological complete response after neoadjuvant chemotherapy(NAC)(S-1 plus oxaliplatin)for rectal cancer. The patient was a 50-year-old man who had type 3 circumferential rectal cancer. An abdominal CT scan revealed locally advanced rectal cancer(cT3N2H0P0M0, cStage III b)with severe stenosis and oral-side intestinal dilatation. The patient was treated with NAC after loop-ileostomy. After 3 courses of chemotherapy, a CT scan revealed significant tumor reduction. Laparoscopic low anterior resection and bilateral lymph node dissection were performed 5 weeks after the last course of chemotherapy. The pathological diagnosis was a pathological complete response(no residual cancer cells). This case suggests that laparoscopic low anterior resection after NAC with S-1 plus oxaliplatin for locally advanced rectal cancer is a potentially effective procedure.

[A Case of Solitary Brain Metastasis from Stage 0 Esophageal Carcinoma after Neoadjuvant Chemotherapy Followed by Surgery].

Esophageal carcinoma rarely metastasizes to the brain. We experienced a case of solitary brain metastasis from Stage 0 esophageal carcinoma after surgery. A 54-year-old man was diagnosed with esophageal carcinoma (clinical T3N2M0, cStage Ⅲ). He received neoadjuvant chemotherapy consisting of 5-fluorouracil plus cisplatin followed by subtotal esophagectomy with dissection of 3 regional lymph nodes. The pathological diagnosis was poorly differentiated squamous cell carcinoma, CTpT1a- EP (T2), pN0, sM0, fStage 0. The pathological response of neoadjuvant chemotherapy was Grade 2. Eight months after surgery, abnormality of the right frontal lobe was identified with positron emission tomography(PET). Brain magnetic resonance imaging (MRI) uncovered a solitary 25 mm lobular tumor at the right frontal lobe, although no evidence of local recurrence or other metastatic sites was found. Gamma knife therapy was performed for the brain metastasis.He has survived for 35 months after esophagectomy without other metastases.

Strangulated bowel obstruction caused by an ileo-ileal knot: a rare case report.

BACKGROUND: Intestinal knot formation is a condition wherein two segments of the intestine are knotted together; however, reports of small-intestinal ileo-ileal knot formation are rare. CASE PRESENTATION: The patient was a 62-year-old Asian male with a history of endoscopic colorectal adenoma resection and a spontaneous pneumothorax. The patient had no history of a laparotomy. He consulted his local doctor with the chief complaint of abdominal pain and was admitted to our hospital with suspicion of an acute abdomen. The abdomen had muscular guarding with tenderness and rebound tenderness. Contrast-enhanced computed tomography (CT) showed torsion of the mesentery of the small intestine with poor contrast filling. The patient was referred to our department with strangulated bowel obstruction and underwent an emergency laparotomy. Intraoperative findings revealed that two segments of the ileum were wrapped around each other to form a knot, and the strangulated small bowel was necrotic. After the release of the knot, partial resection of the small intestine was performed from 220 cm distal to the ligament of Treitz to 80 cm proximal to the cecum. The patient had a good postoperative course and was discharged on the 11th postoperative day. CONCLUSION: Ileo-ileal knots should be considered as part of the differential diagnosis when treating strangulated bowel obstruction.

Diabetes, an independent poor prognostic factor of non-B non-C hepatocellular carcinoma, correlates with dihydropyrimidinase-like 3 promoter methylation.

A concurrent increase in the prevalence of hepatocellular carcinoma (HCC) with that of type 2 diabetes (T2D) and obesity has been reported in the absence of hepatitis B virus surface antigen-negative/hepatitis C virus antibody-negative HCC (NBNC-HCC). However, the prognostic relevance of this association remains unclear. Promoter methylation (PM) of the dihydropyrimidinase-like 3 gene (DPYSL3) has been implicated in virus-related HCC. However, it remains unclear whether T2D influences PM in NBNC-HCC. We determined the influence of T2D on clinicopathological profile and PM of DPYSL3 and CDK2NA in patients with NBNC-HCC who were divided into two groups: non-diabetes (non-DM; n = 46) and diabetes (DM; n = 47). DM was associated with a higher Union for International Cancer Control grade, marginal vascular invasion and tumour cell proliferation irrespective of the duration of T2D as well as higher rates of PM of DPYSL3 than non-DM; however, PM of CDK2NA was similar between both groups. PM of DPYSL3 reduced its expression which inversely correlated with reduced patient survival. In conclusion, T2D is associated with poor prognosis of NBNC-HCC in which a high frequency of PM of DPYSL3 may play a pivotal role in its pathogenesis.

Corrigendum: Normal High HbA1c a Risk Factor for Abnormal Pain Threshold in the Japanese Population.

[This corrects the article DOI: 10.3389/fendo.2019.00651.].

Management of acute ischemic stroke after pulmonary resection: incidence and efficacy of endovascular thrombus aspiration.

OBJECTIVE: We analyzed acute ischemic stroke by thromboembolism in the early period after lung cancer surgery. METHODS: A retrospective review of the clinical records of patients who underwent lung resection for primary lung cancer was performed. Patients who underwent lobectomy, bilobectomy, and pneumonectomy were included. The clinical characteristics of the patients, the incidence of atrial fibrillation (Af) after surgery, and the incidence of acute ischemic stroke were analyzed. The clinical courses of patients having acute ischemic stroke were also reviewed. RESULTS: In 4 (0.6%) of 696 patients, acute ischemic stroke occurred in the early period during hospitalization after lung cancer surgery. Acute ischemic stroke occurred within 4 days in three cases and after 4 days in one case. The resection site of the lung was the left side in all cases, and there were three cases of left upper lobectomy and one case of left lower lobectomy. As for the two recent patients, thrombus removal was performed by a neurosurgeon, and both cases achieved successful recanalization. The time between symptom detection and recanalization was 205 and 170 min, respectively. One patient was cured without any residual effect of disease, and the other patient's hemiplegia resolved and aphasia improved. CONCLUSION: Since cerebral infarction impairs the patient's quality of life, thrombus removal should be considered if possible.

Normal High HbA1c a Risk Factor for Abnormal Pain Threshold in the Japanese Population.

Purpose: Small fiber dysfunction is common in subjects with diabetic polyneuropathy (DPN). It is unsettled, however, whether marginal glucose intolerance is implicated in the onset and progression of small fiber dysfunction. Herein, we explored the relationship between glycated hemoglobin levels (HbA1c) and pain sensation in the Japanese population. Methods: A population-based study of 894 individuals (352 men, 542 women; average age 53.8 ± 0.5 years) and 55 subjects with impaired fasting glucose (IFG) in the 2017 Iwaki project were enrolled in this study. Individuals with diabetes were excluded. Relationships between pain threshold for intraepidermal electrical stimulation (P-IES) and parameters associated with metabolic syndrome were examined. Results: P-IES was elevated with increasing of age in women but not in men. Average P-IES (mA) was increased in IFG subjects (n = 55, 0.20 ± 0.03) compared with normoglycemic/non-IFG individuals (n = 894, 0.15 ± 0.11) (p < 0.01). It was comparable between IFG and a group of normal high HbA1c (5.9-6.4%). Univariate linear regression analyses showed no influence of sex, triglyceride, or cholesterol on the value of P-IES. In contrast, there were significant correlations between P-IES and serum HbA1c level (ß = 0.120, p < 0.001) Adjustments for the multiple clinical measurements confirmed positive correlation of P-IES with HbA1c (ß = 0.077, p = 0.046). Conclusion: Individuals with normal high HbA1c exhibited an elevated P-IES in a healthy Japanese population which may be useful for the screening of subclinical DPN.

Effect of sarcopenia on the outcomes after pancreaticoduodenectomy for distal cholangiocarcinoma.

BACKGROUND: The relationship between sarcopenia and patient outcomes after pancreaticoduodenectomy (PD) for distal cholangiocarcinoma (DCC) remains unclear. We assessed the impact of sarcopenia on the outcomes after PD for DCC. METHODS: We retrospectively analysed 65 patients who underwent PD for DCC. The quality of skeletal muscle indicated by the psoas muscle mass index (PMI) were measured on pre-operative computed tomography images. The impact of pre-operative sarcopenia on short- and long-term outcomes was evaluated. RESULTS: Regarding short-term surgical outcomes, there were no marked differences between the high and low PMI groups. Regarding long-term oncological outcomes, the rates of recurrence (23.5% versus 58.3%, P = 0.011) was significantly lower in the high PMI group than in the low PMI group. Furthermore, the recurrence-free survival and disease-specific survival were longer in the high PMI group (P = 0.023 and P = 0.043, respectively). On multivariate analyses, low PMI was an independent predictor of recurrence (hazard ratio (HR) 11.06; P = 0.022) and disease-specific death (HR 11.88; P = 0.043). CONCLUSIONS: Our findings suggested an association between pre-operative sarcopenia and poor long-term oncological outcomes after PD for DCC.

Worsened outcome in patients with pancreatic ductal carcinoma on long-term diabetes: association with E-cadherin1 (CDH1) promoter methylation.

Prevalence of pancreatic ductal carcinoma (PDC) is nearly twice in patients with diabetes mellitus, but the reason for this close association remains obscure. Recently promoter methylation of E-cadherin1 (CDH1) and CDKN2A genes, encoding E-cadherin and P16 respectively, are invoked in development of PDC. It is still unclear whether diabetes affects such epigenetic changes and malignant behavior in PDC. In this study, we studied whether diabetes influences the clinico-pathological profile and methylation status of CDH1 and CDKN2A genes in patients with PDC. PDC subjects were divided into 3 groups; 59 cases without diabetes (non-DM), 17 cases with short-term diabetes (short-DM)(diabetes duration 3 yrs>) and 33 cases with long-term diabetes (long-DM)(≧3 yrs). Compared to non-DM or short-DM, long-DM was associated with a higher histological grade of malignancy and a higher tumor stage. Promoter methylation of both CDH1 and CDKN2A was encountered more frequently in PDC patients with long-DM than non-DM or short DM. Cases with CDH1 promoter methylation showed reduced E-cadherin expression and worsened survival. We consider that the presence of long-DM has a negative impact on the prognosis of PDC patients which may be relevant to a high frequency of promoter methylation of CDH1.