Clinical characteristics and long-term prognosis of type 1 gastric neuroendocrine tumors in a large Japanese national cohort.

OBJECTIVES: Optimal management of type 1 gastric neuroendocrine tumors (T1-GNETs) remains unknown, with few reports on their long-term prognosis. This study investigated the clinical characteristics and long-term prognosis of T1-GNETs. METHODS: We reviewed the medical records of patients diagnosed with T1-GNET during 1991-2019 at 40 institutions in Japan. RESULTS: Among 172 patients, endoscopic resection (ER), endoscopic surveillance, and surgery were performed in 84, 61, and 27, respectively, including 27, 77, and 2 patients with pT1a-M, pT1b-SM, and pT2 tumors, respectively. The median tumor diameter was 5 (range 0.8-55) mm. Four (2.9%) patients had lymph node metastasis (LNM); none had liver metastasis. LNM rates were significantly higher in tumors with lymphovascular invasion (LVI) (15.8%; 3/19) than in those without (1.1%; 1/92) (P = 0.016). For tumors <10 mm, LVI and LNM rates were 18.4% (14/76) and 2.2% (2/90), respectively, which were not significantly different from those of tumors 10-20 mm (LVI 13.3%; 2/15, P = 0.211; and LNM 0%; 0/17, P = 1.0). However, these rates were significantly lower than those of tumors >20 mm (LVI 60%; 3/5, P = 0.021; and LNM 40%; 2/5, P = 0.039). No tumor recurrence or cause-specific death occurred during the median follow-up of 10.1 (1-25) years. The 10-year overall survival rate was 97%. CONCLUSIONS: Type 1 gastric neuroendocrine tumors showed indolent nature and favorable long-term prognoses. LVI could be useful in indicating the need for additional treatments. ER for risk prediction of LNM should be considered for tumors <10 mm and may be feasible for tumors 10-20 mm. TRIAL REGISTRATION: The study protocol was registered in the University Hospital Medical Information Network (UMIN) under the identifier UMIN000029927.

[A Case of Granulocyte-Colony Stimulating Factor Producing Esophageal Carcinoma].

The patient was a 42-year-old man who presented with dysphagia.Upper gastrointestinal endoscopy revealed a protruding lesion in the lower thoracic esophagus.Pathological analysis of the lesion showed squamous cell carcinoma.Laboratory data showed leukocytosis(21,200/mL)despite no evidence of infection, and the serum levels of granulocyte colony-stimu- lating factor(G-CSF)were elevated to 283 pg/mL.We diagnosed him with esophageal squamous cell carcinoma(Lt, type 1, cT4N4M0, cStage IV a).After administering 2 courses of docetaxel plus cisplatin plus S-1(DCS)as neoadjuvant chemotherapy, the patient underwent surgery.The pathological diagnosis was pType 2, T2, N4, M0, pStage IV a. G-CSF immunostaining was positive in tumor cells.After the surgery, the number of leukocytes and serum G-CSF levels decreased to within normal limits.Adjuvant chemotherapy was administered.

Treatment response of ethyl pyruvate in a mouse model of chronic obstructive pulmonary disease studied by hyperpolarized 129 Xe MRI.

PURPOSE: The purpose of this work was to investigate disease progression and treatment response in a murine model of chronic obstructive pulmonary disease (COPD) using a preclinical hyperpolarized 129 Xe (HPXe) magnetic resonance imaging (MRI) strategy. METHODS: COPD phenotypes were induced in 32 mice by 10 weeks of exposure to cigarette smoke (CS) and lipopolysaccharide (LPS). Efficacy of ethyl pyruvate (EP), an anti-inflammatory drug, was investigated by administering EP to 16 of the 32 mice after 6 weeks of CS and LPS exposure. HPXe MRI was performed to monitor changes in pulmonary function during disease progression and pharmacological therapy. RESULTS: HPXe metrics of fractional ventilation and gas-exchange function were significantly reduced after 6 weeks of CS and LPS exposure compared to sham-instilled mice administered with saline (P < 0.05). After this observation, EP administration was started in 16 of the 32 mice and continued for 4 weeks. EP was found to improve HPXe MRI metrics to a similar level as in sham-instilled mice (P < 0.01). Histological analysis showed significant alveolar tissue destruction in the COPD group, but relatively normal alveolar structure in the EP and sham-instilled groups. CONCLUSION: This study demonstrates the potential efficacy of EP for COPD therapy, as assessed by a noninvasive, translatable 129 Xe MRI procedure. Magn Reson Med 78:721-729, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

[Two Cases of Gastric Endocrine Cell Carcinoma].

The first patient was a man in his eighties who visited our department because of anemia. Gastrofiberscopy revealed a bleeding submucosal tumor, approximately 50mm in diameter, in the cardia ofthe stomach. Considering that he underwent coronary-artery bypass surgery and received 3 oral antithrombotic medicines, his bleeding tendency was so high that we decided to choose partial gastrectomy. A postoperative histopathological examination revealed that the tumor was a small cell endocrine carcinoma. The second patient was a woman in her seventies. She had consulted her personal physician because of gastric ulcers; periodic gastrofiberscopy revealed a type 3 gastric cancer, approximately 40mm in diameter, on the posterior wall ofthe middle section ofher stomach. It was histologically diagnosed as a poorly differentiated neuroendocrine carcinoma. On a preoperative blood examination, the levels ofhormones such as glucagon, serotonin, and gastrin were within their respective normal limits. Total gastrectomy was performed, and she received oral S-1 for adjuvant chemotherapy since her discharge from the hospital.

Transitional mesh repair for large incisional hernia in the elderly.

INTRODUCTION: Large incisional hernias are difficult to repair, especially in elderly patients with thin abdominal walls. Although most such incisional hernias are simply observed, they do not spontaneously resolve. Previously reported procedures are inadequate for repair of all incisional hernias. We herein propose an innovative technique for repair of ventral incisional hernias. PRESENTATION OF CASE: A 88-year-old woman had a large incisional hernia with bilateral inguinal hernias. Incisional hernioplasty was successfully performed for extraperitoneal reinforcement by combining underlay and onlay methods using one prosthesis with transitional sutures. Bilateral inguinal hernioplasty was performed simultaneously. Twelve months postoperatively, the patient is well, without hernia recurrence. DISCUSSION: Elderly patients often have thin, attenuated abdominal walls, and large incisional hernia reinforcement may require a prosthesis. In such cases, a retrorectal prosthesis position is recommended. However, the prosthesis cannot be placed on the cranial side in the presence of a destroyed or adhered abdominal wall is present. In this case, one prosthesis was placed using an underlay method on the caudal side and using an onlay method on the cranial side. The abdominal layers were shifted and each transition point was covered by the other layers to secure the overlapping margins between the abdominal wall and prosthesis. CONCLUSION: This transitional mesh repair was successfully performed for a large incisional hernia in an elderly patient. The procedure is a useful strategy for incisional hernia repair in patients with thin, destroyed abdominal walls. However, further studies are required for a more thorough evaluation of this technique.

Management and clinical outcomes of type I gastric carcinoid patients: retrospective, multicenter study in Japan.

BACKGROUND AND AIM: Type I gastric carcinoids (TIGC) are associated with chronic atrophic gastritis (CAG) with hypergastrinemia and hyperplasia of enterochromaffin-like cells. Several treatment options are currently available for these tumors including total gastrectomy, partial resection, antrectomy, endoscopic resection and endoscopic surveillance. The present study evaluated different treatment approaches and clinical outcomes of patients with TIGC in Japan. METHODS: Between 1991 and 2011, 82 patients with TIGC were identified at multicenter institutions in Japan. Patient demographics, tumor size, depth of invasion, vessel involvement, treatment approach, Helicobacter pylori infection, serum gastrin level, recurrence-free survival (RFS) and disease-specific survival (DSS) were analyzed. RESULTS: Median age of all patients at the time of diagnosis was 56 years (range, 24-79 years). There were 44 males and 38 females. Patients underwent endoscopic surveillance (n=25), endoscopic resection (n=41) or surgical resection (n=16). Intramucosal invasion was found in 19 patients, submucosal invasion in 44 patients and muscularis propria invasion in one patient. Tumor diameter was ≤ 10 mm in 71 patients, 11-20mm in five patients and ≥ 21 mm in five patients. None of the patients showed rapidly growing tumors, local recurrence or metastasis. The median (range) follow-up period was 7(0-20) years. RFS was 97.6% and DSS was 100% in all the patients. CONCLUSION: The prognosis of TIGC patients treated by different modalities in Japan is favorable regardless of the generational change of management for TIGC.

[Effectiveness of postoperative adjuvant chemotherapy using S-1 plus CDDP for type 4 gastric cancer].

BACKGROUND: Our aim was to evaluate postoperative adjuvant chemotherapy using S-1 plus cisplatin(S-1/CDDP)for type 4 gastric cancer. METHODS: We investigated 18 patients who had undergone curative operations for type 4 gastric cancer. They were classified into two groups of patients, one using S-1/CDDP(group A: 9)and one using S-1 alone(group B: 9), after surgery between 2000 and 2010. Median survival time(MST)and survival rates were reported retrospectively. Patients as- signed to group A were treated with the following regimen: S-1, 80-120mg/day(body surface area 1. 25m2>: 80mg/day, 1. 25-1. 5m2: 100mg/day, 1. 5m2<: 120mg), was administered for 21 consecutive days followed by a 14-day rest period, and CDDP, 60mg/m2, was administered on day 8 for 5 courses. After this course, S-1 80mg/m2 was given for 18 months. S- 1(80-120mg/day, body surface area 1. 25m2>: 80mg/day, 1. 25-1. 5m2: 100mg/day, 1. 5m2<: 120mg)was administered for 28 days followed by 14-day rest as one course. RESULTS: MST differed significantly between group A and group B (MST; group A: 1, 603 vs group B: 955 days). The overall survival rate at 5 years was 64. 8% in group A and 13% in group B, and the overall survival rate in group A was statistically better than that in group B(p=0. 02). CONCLUSION: Postoperative adjuvant chemotherapy using S-1/CDDP for resected type 4 gastric cancer contributes to prolonged life, compared with using S-1 in overall survival.

Laparoendoscopic single site partial resection of the stomach for gastrointestinal stromal tumor.

Laparoendoscopic single site surgery offers excellent cosmetic results and may be associated with decreased postoperative pain, reduced need for analgesia, and thus accelerated recovery. Preliminary experience with single-incision laparoscopic partial resection of the stomach for gastrointestinal stromal tumor (GIST) is reported. A single curved intraumbilical 25-mm incision was made with pulling out the umbilicus, and a 12-mm and two 5-mm ports were inserted. The submucosal gastric tumor located in the anterior wall of the stomach was resected with 2 endoscopic staplers under the retraction of 2-mm mini-loop retractor. The procedure was completed successfully without any perioperative complications, and there was no need to extend the skin incision. The operative time was 64 minutes. The final pathologic diagnosis was benign GIST. Postoperative follow-up did not reveal any umbilical wound complication. Laparoendoscopic single site partial resection of the stomach for GIST is feasible and a promising alternative method for scarless abdominal surgery.

Single-incision laparoscopic cholecystectomy: single institution experience and literature review.

Single-incision laparoscopic surgery is a rapidly evolving field as a bridge between traditional laparoscopic surgery and natural orifice transluminal endoscopic surgery. We report one of the initial clinical experiences in Japan with this new technique. Four cases of gallbladder diseases were selected for this new technique. A single curved intra-umbilical 25-mm incision was made by pulling out the umbilicus. A 12-mm trocar was placed through an open approach, and the abdominal cavity was explored with a 10-mm semi-flexible laparoscope. Two 5-mm ports were inserted laterally from the laparoscope port. A 2-mm mini-loop retractor was inserted to retract the fundus of the gallbladder. Dissection was performed using an electric cautery hook and an Endograsper roticulator. There were two women and two men with a mean age of 50.5 years (range: 40-61 years). All procedures were completed successfully without any perioperative complications. In all cases, there was no need to extend the skin incision. Average operative time was 88.8 min. Postoperative follow-up did not reveal any umbilical wound complication. Single-incision laparoscopic cholecystectomy is feasible and a promising alternative method as scarless abdominal surgery for the treatment of some patients with gallbladder disease.

[Effects of preoperative systemic chemotherapy with respect to expressions of hormone receptors and HER2 / neu].

SUBJECTS: Between August 2003 and January 2008, 35 patients with primary breast cancer received preoperative systemic chemotherapy(PSC). METHODS: The subjects were divided into 4 groups based on the expressions of ER, PgR, and HER2: luminal A and B, HER2, and basal-like groups. FEC75 followed by docetaxel was administered preoperatively. However, a regimen with trastuzumab was employed after 2006. RESULTS: The subjects consisted of 1 male and 34 females, with a mean age of 56.0 years. In 65.7% of these, axillar lymph node metastasis was detected before surgery: 13 patients in the luminal A, 4 in the luminal B, 13 in the HER2, and 5 in the basal-like groups. A clinical complete response(cCR)was achieved in 25.7% of the patients, and a partial response in 62.9%; the response rate was 88.6%. Pathologically, the grade was evaluated as 3 in 14.3% of the patients and 2 in 48.6%. In the basal-like and HER2 groups, the cCR and pCR rates were higher than those in the luminal groups. Combination therapy with trastuzumab was not effective in the HER2 or luminal B group. DISCUSSION: This simple classification method may be useful for predicting the effects of PSC.

Decreased death from gastric cancer by endoscopic screening: association with a population-based cancer registry.

OBJECTIVE: To determine death rates from gastric cancer when using endoscopic screening. MATERIAL AND METHODS: In this historical cohort study comprising 11,763 participants aged from 40 to 75 years without gastric disorders between 1990 and 1992, 2192 were examined by gastric endoscopy while 9571 were not examined by endoscopy or X-ray. The relative risk of gastric cancer death was compared between the two groups. RESULTS: When screened with endoscopy, 41 patients were diagnosed with gastric cancer and the ratio of early cancer was 78%. On matching the population-based cancer registry (the Fukui Cancer Registry), 63 patients in the examined group were diagnosed with gastric cancer within 10 years after the initial screening including the above 41 patients. In the non-examined group, 147 patients were diagnosed with gastric cancer in the same period. In the examined and non-examined groups, 5 and 63 patients, respectively, died from gastric cancer. The relative risk for gastric cancer death in the examined group was 0.3465 (95% CI: 0.1396-0.8605) when compared with the non-examined group. For male patients, the relative risk was 0.2174 (95% CI: 0.0676-0.6992). CONCLUSIONS: The death rate from gastric cancer decreased when endoscopic screening was used. Endoscopy is recommended as a population-based screening method for gastric cancer in regions or countries where mortality from this disease is high.

Difference in accuracy between gastroscopy and colonoscopy for detection of cancer.

BACKGROUND/AIMS: There are few reports regarding the accuracy of endoscopy in detecting cancer. We investigated the difference in the false-negative rates for cancer detection between gastroscopy and colonoscopy using the records of a population-based cancer registry, which is the most accurate in Japan. METHODOLOGY: Between 1990 and 1995, 51,411 gastroscopic and 7756 colonoscopic examinations were carried out in our hospital. These subjects were matched with the cancer registry and the patients whose gastric or colorectal cancers were missed by examinations were identified. RESULTS: The false-negative rate for the detection with gastroscopy was 25.8 percent at three years but that with colonoscopy was 11.1 percent. This difference was statically significant p = 0.01. CONCLUSIONS: We concluded that for routine examinations, surveillance after negative endoscopy should be discussed based on the difference in false-negative rates between gastroscopy and colonoscopy.

[Clinical examination of safety and effectiveness of primary chemotherapy with CEF followed by docetaxel in preoperative breast cancer].

SUBJECTS: The subjects were patients with resectable breast cancer who visited our department between August 2003 and November 2004, did not have any other risk factors defined in the St. Gallen Consensus Conference,and were receptor-negative or had axillary lymph node metastasis. METHODS: The histological type, ER, PgR, HER2, and histological grade were evaluated by needle biopsy. Four courses of CEF (5-FU: 500 mg/m(2)+EPI: 75 mg/m(2)+CPA: 500 mg/m(2)) were performed at 3-week intervals, followed by 4 courses of Docetaxel (70 mg/m(2)). RESULTS: Treatment was performed in 14 patients including a male. Their age ranged from 37 to 69 years (mean, 55.3 years). Stage IIA was observed in 5 patients, IIB in 4, IIIA in 1, and IIIB in 4. In patients with Grade 3 or more, leukocytopenia was observed in 7 patients and diarrhea in 1 as adverse events. CR was obtained in 6 patients, PR in 5, and NC in 3 (response rate, 78.5%). Pathological examination showed pCR in 1 patient and pPR in 10 (response rate, 78.5%). Of the 10 patients with pPR, 2 showed a state near pCR. DISCUSSION: Our results showed the safety and effectiveness of preoperative chemotherapy with CEF followed by Docetaxel.

Epstein-Barr virus-associated gastric carcinoma in the remnant stomach: de novo and metachronous gastric remnant carcinoma.

BACKGROUND: The remnant stomach corresponds to the gastric cardia, but is exposed to a completely different environment. The present study was performed to investigate the role of Epstein-Barr virus (EBV) infection in patients with gastric remnant carcinoma (GRC). METHODS: Clinicopathological features, gastritis, and infection by EBV were investigated in patients with two types of GRC: GRC occurring at an interval of 10 years or longer between operations (de novo GRC group) and GRC occurring within 10 years after the initial operation for gastric carcinoma (metachronous GRC group). RESULTS: EBV involvement in the de novo GRC group (23%) was not significantly different from that in the cardia of non-remnant carcinomas (controls; 18%). EBV involvement showed greater correlations in male patients (18/63; 28%), and in those with gastritis cystica polyposa (GCP; 13/41; 31%), and those with an interval of 20 years or longer (15/50; 30%) than with the other parameters. Multivariate analysis showed a significant correlation between GCP and EBV infection. Histologically, hyperplasia or mild atrophy, and mild lymphocytic infiltration were observed in 56% and 67% of non-neoplastic mucosa of EBV-associated GRC, respectively. In the metachronous GRC group, EBV-encoded mRNA in situ hybridization (EBER-ISH) of 27 pairs of primary gastric carcinomas (GCs) and metachronous GRCs indicated that only six EBV (+) metachronous GRCs were derived from EBV (+) GC. CONCLUSIONS: Epstein-Barr virus infection, together with long-standing inflammation, which causes GCP, may facilitate the development of de novo GRC. Close follow-up of patients treated with distal gastrectomy for EBV-associated GC is necessary to detect metachronous GRC.

Long-term follow up of patients with multiple gastric carcinoids associated with type A gastritis.

Little is known about the natural course of multiple gastric carcinoids associated with type A gastritis. Between 1993 and 2003, we enrolled eight patients, diagnosed as having multiple gastric carcinoids associated with type A gastritis, in a follow-up program without surgical resection. In these patients, endoscopy showed multiple small polyps on the gastric body, with nonantral atrophic gastritis. Histologically, biopsy specimens obtained from the polyps revealed carcinoid tumors. The serum gastrin level was found to be very high in all patients, and testing for anti-parietal cell antibody was positive in seven. The mean follow-up was 5.8 years (range, 1.5-10.8 years). The levels of serum gastrin increased in all patients, but, endoscopically, the carcinoid tumors did not change in size. Neither hepatic nor lymphatic metastasis was detected on abdominal computed tomography (CT). These patients were free of the development or metastasis of carcinoids, in spite of their continuous hypergastrinemia. It was concluded that multiple gastric carcinoids associated with type A gastritis may be indolent.

Regression of rectal mucosa-associated lymphoid tissue lymphoma but persistence of Helicobacter pylori infection of gastric mucosa after administration of levofloxacin: report of a case.

PURPOSE: Several articles have reported regression of rectal lymphoma of mucosa-associated lymphoid tissue after anti- Helicobacter pylori therapy. It remains unclear, however, whether lymphoma of rectal mucosa-associated lymphoid tissue is related to Helicobacter pylori infection. METHODS: A 60-year-old woman visited our hospital with a complaint of hematochezia. On colonoscopy a pale, ulcerated protrusion approximately 3.5 cm in diameter was found in the rectum. Pathologic diagnosis of a biopsy specimen was low-grade mucosa-associated lymphoid tissue lymphoma. The patient received a ten-day course of levofloxacin, and the cycle was repeated three times over seven months. RESULTS: Although persistence of Helicobacter pylori infection was confirmed, the tumor regressed completely. CONCLUSION: Our findings in this case suggest that rectal lymphoma of mucosa-associated lymphoid tissue may be related to unknown microorganisms other than Helicobacter pylori. Levofloxacin may be effective for treatment of rectal lymphoma of mucosa-associated lymphoid tissue regardless of Helicobacter pylori infection.