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Multiple genetic factors related to autism spectrum disorder (ASD) have been identified, but the biological mechanisms remain obscure. Timothy syndrome (TS), associated with syndromic ASD, is caused by a gain‐of‐function mutation, G406R, in the pore‐forming subunit of L‐type Ca2+ channels, Cav1.2. In this study, a mouse model of TS, TS2‐neo, was used to enhance behavioral phenotyping and to identify developmental anomalies in inhibitory neurons. Using the IntelliCage, which enables sequential behavioral tasks without human handling and mouse isolation stress, high social competitive dominance was observed in TS2‐neo mice. Furthermore, histological analysis demonstrated inhibitory neuronal abnormalities in the neocortex, including an excess of smaller‐sized inhibitory presynaptic terminals in the somatosensory cortex of young adolescent mice and higher numbers of migrating inhibitory neurons from the medial ganglionic eminence during embryonic development. In contrast, no obvious changes in excitatory synaptic terminals were found. These novel neural abnormalities in inhibitory neurons of TS2‐neo mice may result in a disturbed excitatory/inhibitory (E/I) balance, a key feature underlying ASD., Timothy syndrome (TS) associated with autism spectrum disorder (ASD) is caused by G406R mutation in L‐type Ca2+ channels. A TS mouse model, TS2‐neo, showed excess migrating inhibitory neurons, higher number of smaller‐sized inhibitory presynaptic terminals, and high social competitive dominance in the IntelliCage. These findings provide new insights into the Ca2+‐dependent developmental mechanisms of inhibitory neurons and the pathophysiology of TS.

Omentectomy is considered an essential part of curative gastrectomy for locally advanced gastric cancer (GC), albeit without solid evidence. We conducted a randomized phase II trial (the TOP-G trial) comparing omentectomy and omentum preservation for gastric cancer. This report describes the short-term findings regarding the trial’s secondary endpoints. The trial protocol was submitted to the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/ : UMIN000005421). The key eligibility criteria were histologically confirmed cT2–4a and N0–2 gastric adenocarcinoma. Short-term surgical outcomes, including morbidity and mortality, were compared between the omentectomy group (group A, control arm) and the omentum-preserving surgery group (group B, test arm). All procedures were performed via an open approach. Based on a non-inferiority margin of 7%, statistical power of 0.7, and type I error of 0.2, the sample size was set to 250 patients. A total of 251 patients were eligible and randomized (group A: 125 patients, group B: 126 patients) between April 2011 and October 2018. After excluding patients who had peritoneal metastasis or laparotomy history, safety outcomes were analyzed for 247 patients. Group A had a significantly longer median operation time (225 min vs. 204 min, p = 0.022) and tended to have greater median blood loss (260 mL vs. 210 mL p = 0.073). The incidences of morbidity were similar and

BACKGROUND AND AIM Many patients are not satisfied with chronic constipation (CC) treatments. The aim of this study was to identify factors linked to CC treatment satisfaction or dissatisfaction. METHODS Our study population included patients who received CC treatment at a clinic or hospital. CC was diagnosed by a physician based on the patient's complaint. Treatment satisfaction was evaluated using the 28th question of the Patient Assessment of Constipation Quality of Life questionnaire. RESULTS We conducted this study at 28 facilities. We included 167 patients (mean age 66.7 ± 15.2 years, male:female ratio is 1:3.07). Sixty-eight (40.7%) of patients were satisfied with their constipation treatment. Treatment dissatisfaction of CC was significantly associated with frequency of bowel movement

Background/aim We investigated the impact of the age-adjusted Charlson comorbidity index (ACCI) on esophageal cancer survival and recurrence after curative treatment. Patients and methods This study included 122 patients who underwent curative surgery followed by adjuvant chemotherapy for esophageal cancer between 2005 and 2017. The risk factors for the overall survival (OS) and recurrence-free survival (RFS) were identified. Results An ACCI of 5 was regarded as the optimal critical point of classification considering the survival rates. The OS rates at 3 and 5 years after surgery were 64.2% and 54.4% in the low-ACCI group, respectively, and 42.3% and 29.2% in high-ACCI group, respectively (p=0.035). The RFS rates at 3 and 5 years after surgery were 50.2% and 43.6% in the low-ACCI group, respectively, and 28.5% and 21.3% in high-ACCI group, respectively (p=0.021). A multivariate analysis demonstrated that ACCI was a significant independent risk factor for both the OS and RFS. Conclusion ACCI is a risk factor for survival in patients who undergo curative treatment for esophageal cancer. An effective plan for the perioperative care and surgical strategy should be developed according to ACCI.

Background and Aim Few studies have shown the associations between colonic diverticula and endoscopic findings such as location, inflammation, number of diverticula, sigmoid colon rigidity, and bowel habits. Methods Japanese subjects who underwent total colonoscopies at six centers in Japan from November 2015 to October 2016 were analyzed. Bowel habits were evaluated using the Gastrointestinal Symptom Rating Scale. Location and number of diverticula, inflammation, and sigmoid colon rigidity were evaluated from endoscopy results. Results A total of 762 subjects (486 men and 276 women [ratio, 1.76:1]) whose mean age was 65.5 ± 11.4 years were evaluated. In multivariate analysis, presence of constipation was associated with a significantly lower likelihood of left-sided colonic diverticula (odds ratio = 0.40, 95% confidence interval 0.20–0.82, P = 0.012), whereas right-sided and bilateral-sided colonic diverticula, multiple colonic diverticula, inflammation findings, and sigmoid colon rigidity were not related to bowel habits. Conclusions Among endoscopic findings related to colonic diverticula and bowel habits, only left-sided colonic diverticula were inversely associated with constipation, whereas inflammation findings, multiple diverticula, and sigmoid colon rigidity were not related to bowel habits. However, the association of inflammation findings with colonic diverticula and bowel habits should be further studied. Investigation of changes in left-sided colonic diverticula may lead to new treatments for constipation.

We report a long-surviving case of malignant peritoneal mesothelioma requiring 4 operations in 5 years. A 63-year-old man was diagnosed with gastrointestinal stromal tumor(GIST)that was excised for the first time in June 2011. The pathological diagnosis was malignant peritoneal mesothelioma. Thereafter, we excised recurrences of the tumor in the hepatic hilum in December 2011. Similar operations were performed in March 2012 and August 2015 because of tumors in the small bowel mesentery and the segment 8 of the liver. The pathological diagnosis was malignant peritoneal mesothelioma. It is an extremely rare variant of malignant peritoneal mesothelioma. There is no record of multiple excision of malignant peritoneal mesothelioma for recurrences. In this case, the cause of long survival was considered to be the excision of recurrent tumors.

This is a case of a 76-year-old man who had no significant past medical or family history. In the current medical history, in November 2017, upper gastrointestinal endoscopy showed a semicircular protruding lesion in the posterior wall of the gastric antrum, and gastric cancer was diagnosed following biopsy. Endoscopic submucosal dissection(ESD)was performed in the same year for the treatment of gastric cancer(cT1aN0M0). Pathological findings after ESD treatment showed invasion into the submucosa requiring non-curative resection. For this reason, laparoscopic pylorus side gastrectomy(D1 dissection)and Billroth Ⅰ reconstruction were performed as additional procedures in March 2018. The patient was discharged on the 10th postoperative day and was followed-up on an outpatient basis. On the postoperative day 14, he was re-admitted with complaints of upper abdominal pain and exacerbation of inflammation. Medical treatment, such as antibiotic administration was followed, however, a high degree of inflammatory response, renal dysfunction, and occult blood in urine were observed. Because of suspicion of vasculitis-related nephritis, the case was diagnosed as anti-GBM antibody type rapid progressive nephritis. We came across a case of rapidly progressive glomerulonephritis after laparoscopic pylorus side gastrectomy performed for early gastric cancer, and hence, We will review the related literature.

Undifferentiated cancer of the small intestine has a poor prognosis and has rarely been reported.We report a case of undifferentiated intestinal carcinoma.A 55-year-old man presented with epigastralgia in December 2018. Blood test results showed a high degree of anemia.Contrast -enhanced abdominal CT showed a small intestinal tumor with a diffuse thickened wall along with multiple liver metastases.Capsule endoscopy revealed a bleeding tumor.It was diagnosed as carcinoma by transhepatic-ultrasound-guided core needle biopsy.Given the preoperative diagnosis of intestinal carcinoma, we resected the tumor along with a part of the small intestine and the enlarged lymph nodes.The pathological diagnosis was undifferentiated intestinal carcinoma.The patient was discharged on the 6th postoperative day after surgery.He was scheduled to receive postoperative chemotherapy.There was no evidence of undifferentiated intestinal carcinoma.Herein, we review case reports from the literature.

This case involved a 42-year-old woman who had no remarkable findings in terms of case history and family history. Upper gastrointestinal series performed during a medical examination revealed ulcerative lesions in the anterior wall of the stomach body. Upper gastrointestinal endoscopy was performed, and a submucosal tumor with a maximum diameter of 50mm accompanied by an ulcerative lesion was found in the anterior wall of the lower part of the stomach. She was diagnosed with a schwannoma based on endoscopic ultrasonography-guided fine needle aspiration, and we received consultation for surgical purpose. Surgery was performed with laparoscopic partial resection of the stomach and lymph nodes in the lesser curvature of the stomach. She was discharged on the 7th day after the surgery. The postoperative pathologic findings showed no nuclear fissure or atypia with a diagnosis of a schwannoma and no lymph node metastasis. Gastric schwannoma is a rare disease that arises from Schwann cells of the Auerbach's plexus of the gastric wall muscularis and comprises 0.1-0.2% of all stomach tumors. Preoperative diagnosis is often extremely difficult, and there are reports of malignancy. Treatments and surgical methods should be carefully considered. Herein, we encountered a case of a resected giant gastric schwannoma by laparoscopic surgery, which is reported with a literature review.

This is a case of a 70-year-old man. Two courses of docetaxel/cisplatin/S-1 combination therapy were administered after clinical trial registration with diagnosis of Stage Ⅳ gastric cancer(ypT3N3aM1). In June 2014, gastrectomy and splenectomy were performed. Postoperative S-1 adjuvant chemotherapy was administered; however, in September 2014, aorticl ymph node metastasis was diagnosed as recurrent. After recurrence, irinotecan/cisplatin therapy was administered. In February 2015, recurrent lymph node metastasis increased, and chemotherapy was changed to paclitaxel. In May 2015, numbness (Grade 2)of the fingers was observed, and treatment was changed to oxaliplatin/S-1. In February 2016, storage of ascites became remarkable; therefore, chemotherapy was discontinued as per policy. After that, we continued outpatient visit and observed increased recurrent lymph node metastasis on image evaluation; however, as the patient's general condition was good, chemotherapy was restarted. Ramucirumab/paclitaxel therapy started in February 2017. During the course of treatment, neutropenia(Grade 2)was observed as an adverse event, but therapy continuation was possible without loss of ramucirumab only with loss of paclitaxel. Thereafter, the recurrence of lymph node metastasis was reduced, and the ascites accumulation decreased. Until now, 1 year after the start of ramucirumab/paclitaxel therapy, the patient still visits the outpa- tient clinic.

285 Background: A complete resection of the omentum has been believed as a standard procedure for advanced gastric cancer. However, there was no evidence for survival significance of omentectomy. Therefore, we conduct the Phase II trial (TOP-G trial) comparing gastrectomy with omentectomy and omentum preserving gastrectomy. Here, we present the short-term outcomes which was a secondary endpoint of TOP-G trial. Methods: Enrollment criteria included histologically confirmed cT2-4a and N0-2 gastric adenocarcinoma. The extent of nodal dissection was performed based on the Gastric Cancer Treatment Guidelines in Japan. All procedure was performed through laparotomy. Laparoscopic approach was not accepted. Surgical outcomes morbidity, and mortality were compared between gastrectomy with omentectomy group (group A) and omentum preserving gastrectomy group (group B). Postoperative complication was evaluated with Clavien-Dindo classification. Results: A total of 251 patients were randomly assigned to group A (n = 125) or group B (n = 126) between April 2011 and October 2018. After excluding patients who received bypass or no surgery, 246 patients were analyzed as actual treatment group. There was no difference between two groups in patient characteristics and pathological findings. There was no difference in operation time (median 244 vs 204 min, p = 0.156) and in blood loss (median 260 vs. 210 ml, p = 0.371). Median number of totally retrieved lymph nodes was similar (median 36 vs. 37, p = 0.758). There was no difference in the incidence of any postoperative complication (28.9% vs. 25.8%, p = 0.584). There was no mortality in both groups. Conclusions: Omentum preserving gastrectomy for advanced gastric cancer was similar short-term outcomes with gastrectomy with omentectomy. Clinical trial information: UMIN000005421.

A 59-year-old woman was diagnosed with advanced gastric cancer with para-aortic and Virchow's lymph node metastases (L, Less, type 2, tub1, cT3N2H0P0M1[LYM: #16, Virchow's]). Four courses of S-1(80mg/m / 2, days 1-21)and CDDP(60mg/ m2, day 8)were administered. After the chemotherapy, CT showed that the primary tumor and para-aortic and Virchow's lymph nodes had reduced in size. The clinical stage was ycT3N1H0P0M0, stage III A. The patient underwent distalgastrectomy, D2 dissection, and sampling of the para-aortic lymph nodes(#16b1lat, #16a2int). The pathological diagnosis was L, less, type 1, por1/2, pT2N2H0P0M0CY0, pStage III B. The patient was treated with S-1(80mg/m2, days 1-28)as adjuvant chemotherapy. After 3 courses had been administered(6 months after the resection), swelling of a para-aortic lymph node (#16b1int)was detected using CT. Based on the diagnosis of recurrence in the lymph node, weekly paclitaxel(80mg/m2, days 1, 8, and 15)was administered. After receiving 9 courses of weekly paclitaxel, the swelling of the lymph node disappeared, and the response evaluation was complete response. She discontinued the chemotherapy 5 years and 9 months after the surgery. To date, she has survived more than 6 years after surgery without recurrence. We report a long-surviving patient with advanced gastric cancer with para-aortic lymph node metastasis who received combined modality therapy.

Neuronal migration is a crucial event in neuronal development for the construction of brain architecture and neuronal networks. Newborn neurons proliferate in the germinal zone and start migration toward their final destination. Migrating neurons adopt different routes, cell shapes and migratory modes depending on extracellular factors and outer physical substrates. Intracellular Ca2+ is an essential second messenger that regulates diverse cellular functions by activating Ca2+-dependent signalling molecules that underlie Ca2+-responsive cellular functions. Neuronal migration during brain architecture construction is no exception. Spontaneous Ca2+ transients are observed in several types of migrating neurons, and a series of Ca2+-dependent signalling molecules governing neuronal migration has been identified. In this review, we first summarize the molecular mechanisms that trigger intracellular Ca2+ elevation in migrating neurons. In the latter half of this review, we provide an overview of the literature on Ca2+-dependent signalling molecules underlying neuronal migration.

Several retrospective studies have shown that bone disorders occur after gastric cancer surgery. This study was designed to prospectively evaluate the changes in bone metabolism after gastrectomy for gastric cancer. We prospectively enrolled 39 men with early gastric cancer who underwent gastrectomy. We excluded women to avoid the effects of menopause. We employed dual energy X-ray absorptiometry (DEXA) to measure bone mineral density (BMD) of the lumbar spine. DEXA was performed before and 1 and 2 years after surgery. The serum levels of alkaline phosphatase (ALP), 1,25-dihydroxy vitamin D [1,25(OH)2VD], 25-hydroxy vitamin D [25(OH)VD], and estradiol were measured before surgery and every 3 months until 2 years after surgery. DEXA revealed that BMD significantly decreased by 0.036 ± 0.033 g/cm2 12 months after gastrectomy (P

Few studies have shown the associations between colonic diverticula and endoscopic findings such as location, inflammation, number of diverticula, sigmoid colon rigidity, and bowel habits.Japanese subjects who underwent total colonoscopies at six centers in Japan from November 2015 to October 2016 were analyzed. Bowel habits were evaluated using the Gastrointestinal Symptom Rating Scale. Location and number of diverticula, inflammation, and sigmoid colon rigidity were evaluated from endoscopy results.A total of 762 subjects (486 men and 276 women [ratio, 1.76:1]) whose mean age was 65.5 ± 11.4 years were evaluated. In multivariate analysis, presence of constipation was associated with a significantly lower likelihood of left-sided colonic diverticula (odds ratio = 0.40, 95% confidence interval 0.20-0.82, P = 0.012), whereas right-sided and bilateral-sided colonic diverticula, multiple colonic diverticula, inflammation findings, and sigmoid colon rigidity were not related to bowel habits.Among endoscopic findings related to colonic diverticula and bowel habits, only left-sided colonic diverticula were inversely associated with constipation, whereas inflammation findings, multiple diverticula, and sigmoid colon rigidity were not related to bowel habits. However, the association of inflammation findings with colonic diverticula and bowel habits should be further studied. Investigation of changes in left-sided colonic diverticula may lead to new treatments for constipation.

The aim of this study was to evaluate the safety and feasibility of gastrectomy in elderly patients aged over 80 years.A total of 393 patients who underwent gastrectomy for gastric cancer were assigned to 2 groups: those aged over 80 years(n=48; elderly group)and those less than 80 years(n=345).Clinicopathological features, operative factors, post-operative complications(Clavien-Dindo Grade II or higher), and mortality were retrospectively analyzed.Rates of distal gastrectomy(73% vs 59%, p=0.043)and D1 or D1+dissection(73% vs 58%, p=0.046)were significantly higher in the elderly group.There were no significant differences in post-operative complication rates(23% vs 20.3%, p=0.255)or mortality rates(2.1% vs 0.6%).Our results indicate that gastrectomy in elderly patients aged over 80 years may be safe and feasible.

The aim of this study was to evaluate the safety of laparoscopic-assisted colorectomy(LAC)for elderly patients more than 70 years old.The outcomes of 131 patients more than 70 years old who underwent LAC between April 2013 and March 2014 were retrospectively analyzed.Morbidity and mortality were evaluated using the Clavien-Dindo classification.Postoperative complications exceeding Grade II in the Clavien-Dindo classification were found in 20 patients(15.3%).No mortalities were observed in this study.LAC can be performed safely for elderly patients older than 70 years.

10 Background: Several reports have showed that bone disorders occur after gastric cancer surgery, however there are few studies that compared pre- and postoperative bone mineral density of the same patient. The purpose of this study was to assess changes in bone metabolism after gastric cancer surgery prospectively. Methods: We prospectively enrolled 39 men undergoing gastrectomy for early gastric cancer. We excluded women to avoid the effect of menopause. Patients with severe kidney disease requiring dialysis treatment, patients with severe liver disease and patients with treatment with bisphosphonates or any other bone-active drugs were also excluded. Dual energy X-ray absorptiometry (DEXA) was performed before and 1 and 2 years after surgery to evaluate bone mineral density (BMD). The serum levels of 1,25-dihydroxy vitamin D (1,25(OH)2VD), 25-hydroxy vitamin D (25(OH)VD), estradiol, and alkaline phosphatase (ALP) were measured before surgery and every three months until two years after surgery. Results: DEXA revealed that BMD was significantly decreased by 0.036±0.033 g/cm2 at 12 months after gastrectomy (P < 0.001). The serum ALP was significantly increased by 38.88±6.42 IU/l at 24 months after surgery (P = 0.013), and there was a marginally significant correlation between the changes in BMD and the changes in the serum ALP at 24 months after surgery; the correlation coefficient was -0.30 (P = 0.090). The serum 25(OH)VD was significantly decreased by 4.88±6.42 ng/ml at 24 months after surgery (P < 0.001), however there was no significant correlation between the changes in BMD and the changes in the serum 25(OH)VD. The serum 1,25(OH)2VD and estradiol were not significantly changed before and after surgery. The factor significantly correlated to the reductions of BMD at 12 months after surgery included preoperative lower body mass index (BMI); the correlation coefficients was 0.37 (P = 0.025). Conclusions: This study showed a significant reduction in the BMD of gastric cancer patients at 12 months after gastrectomy and suggested that low preoperative BMI could be a high risk factor for the bone disorder after gastric cancer surgery.

We report a case of gastric carcinoma with metastasis to the liver responding to surgery and chemotherapy.The patient was a 74-year-old man with gastric cancer, clinically diagnosed as P0H0M0T3N0.We initially planned to perform an open distal gastrectomy.However, intraoperative findings revealed metastatic tumors in the liver.Therefore, the patient underwent a D1 distal gastrectomy.After surgery, the patient received the following chemotherapy regimens: 1 course of S-1 and 8 courses of a S-1 and cisplatin (CDDP) combination.After 8 courses of S-1 plus CDDP treatment, liver metastases could not be detected by computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET). The patient was assessed to have a clinical complete response.Fifty months after surgery, the patient is alive without recurrence.

Endotoxin (ETX) primes polymorphonuclear cells (PMNs) for the subsequent release of reactive oxygen species (ROS) in response to various stimulants such as phorbol myristate acetate (PMA). Although PMNs contribute to oxidative stress after stimulation by standard stimulants and after priming by many humoral factors, it is unknown whether the PMNs from patients at different postoperative times exhibit the same response to the same standard stimulant. We examined the response of PMA—induced production of ROS from PMNs at various intervals after major abdominal surgery in response to ETX priming. This study was a prospective clinical and laboratory study conducted over a 7-day period that involved 25 patients who were referred for elective major abdominal surgery (8 for gastric cancer, 9 for colonic cancer, 8 for rectal cancer). Blood was sampled on the day before operation and on postoperative days (PODs) 1, 3, and 7. For each sample we measured luminol-dependent chemiluminescence (CL), the time to peak counts (Tmax) of PMNs stimulated by PMA, and the serum ETX level. We studied the correlation between CL and ETX in samples from PODs 1 and 3. We also studied the CL of PMNs on PODs 1 and 3 preincubated (primed) with various concentrations of ETX (0, 20, 40, 60, and 100 pg/ml). We found that CL decreased on POD 1 compared with the preoperative level (p

The aim of this study was to evaluate the safety and feasibility of gastrectomy after neoadjuvant chemotherapy in patients with gastric cancer.Forty-five patients received neoadjuvant chemotherapy and curative gastrectomy between December 2002 and May 2011. Surgical complications were evaluated according to the Clavien- Dindo classification.The median age of the patients was 63 years. Twenty-three patients received a PTX and CDDP regimen, 20 received an S-1 and CDDP regimen, 1 received an S-1 regimen, and 1 received an CPT-11 and CDDP regimen as neoadjuvant chemotherapy. Distal gastrectomy was performed in 6 patients, and total gastrectomy was performed in 39 patients. The median operation time was 268 minutes, and the median blood loss was 249.5 mL. Complications more severe than grade 2 were observed in 10 patients: anatomic bleeding( grade 3a) was observed in 2 patients; abdominal abscess( grade 2), in 1 patient; and pancreatic fistula( grade 2), in 7 patients. No surgical mortality was observed.The results of our study suggest that gastrectomy after neoadjuvant chemotherapy for the treatment of patients with gastric cancer is safe and feasible.

Eicosapentaenoic acid-enriched oral nutritional supplements (Prosure®; Abbott Japan, Tokyo, Japan) may attenuate surgical stress and catabolism after gastric cancer surgery. The present study aimed to evaluate the effects of Prosure® on body weight loss( BWL) and compliance with S-1 adjuvant chemotherapy after gastrectomy.Patients who underwent curative total gastrectomy for gastric cancer were selected to undergo adjuvant S-1 chemotherapy at Kanagawa Cancer Center between December 2010 and October 2011. The patients received a normal postgastrectomy diet and two 240 mL packs of Prosure® for 21 postoperative days. BWL was defined as %BWL and calculated as %BWL=(preoperative body weight-1-month postoperative body weight)×100/preoperative body weight. Time to S-1 treatment failure was calculated.Five patients were enrolled in this study. The median age was 62.0 years. One patient was male, and 4 were female. The 1-month postoperative BWL was 92.1%. Compared to our previous report, a 20% risk reduction was observed in this study (Prosure® group vs control group, 92.1% vs 89.7%). Moreover, all the patients continued with the S-1 adjuvant chemotherapy for longer than 6 months.Prosure® may inhibit BWL at 1 month after gastrectomy. Moreover, Prosure® improved the patients' compliance with the adjuvant chemotherapy after gastrectomy.

The aim of this study was to clarify the human epidermal growth factor receptor 2( HER2) positivity, clinicopathological characteristics, and survival of patients with recurrent HER2-positive gastric cancer who received S-1 adjuvant chemotherapy.Thirty-eight patients with recurrent gastric cancer who underwent curative D2 surgery and received S-1 adjuvant chemotherapy between June 2002 and December 2011 were examined. HER2 positivity was determined as defined in the ToGA study.The positivity score was assessed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) as follows: IHC 0 in 27 patients, IHC 1+in 4, IHC 2+/FISH-in 3, IHC 2+/FISH+in 1, and IHC 3+in 3. The HER2 positivity rate was 10.5% (4/38). HER2-positive recurrent gastric cancer was characterized by a differentiated histological feature and frequent blood vessel invasion. However, the recurrence and survival rates were not significantly different between the HER2-negative and HER2-positive tumors.The HER2 positivity rate after S-1 adjuvant chemotherapy did not differ significantly between patients with recurrent gastric cancer and those with primary Stage II/III gastric cancer, suggesting that S-1 adjuvant chemotherapy was equally effective, regardless of HER2 status.

高齢者急性上腸間膜動脈 (SMA) 閉塞症, 小腸壊死に対する広範囲小腸切除後に, 1期的吻合を行ったので, その有用性と安全性を検討した. 83, 78, 75歳の女性の急性SMA閉塞症3例に広範囲小腸切除を行った. 小腸壊死と血性腹水を認めたが, 腸管穿孔はなかった. 数cmの小腸温存には固執せず, 確実に安全と思われる部位で切離し, 器械吻合で1期的に再建した (側端, 側端, 端側吻合). 残存小腸は, Treitz靭帯から30cm, 幽門輪から50cm, Treitz靭帯から30cm, 経口摂取は, 各16, 17, 10病日から開始した. 経口摂取後の排便回数は, 各3～4, 0～1, 15回前後/日と端側吻合で頻回の傾向にあった. 維持輸液も各2,000ml, 1,000, 2,000～1,000ml/日前後であった. 全例, 縫合不全や残存腸管の虚血の進展の徴候はなかった. 高齢であることから消化吸収能をある程度犠牲にして, 空腸瘻とせず一期的に吻合を行ったことで, 近位空腸瘻のデメリットを回避した. 術後造影検査での造影剤の移動速度から, 側端吻合が消化, 吸収に有用と思われた.

We experienced an emergency operation for a case of acute appendicitis with human immunodeficiency virus (HIV) infection. This paper reports on our strategy for dealing with the patient and the perioperative changes in inflammatory reaction. A 28-year-old man, who was pointed out hemophilia B at the age two and HIV infection at the age 18, had a right lower abdominal pain on February 12, and high grade fever on February 16, 1996. He was diagnosed as acute appendicitis at another hospital and was referred to our center because of HIV infection. On admission, white blood cell count was 3000/mm3 (2600/mm3 in October, 1995) and the level of CRP was 4.9mg/dl. At laparotomy, the vermiform appendix was swollen and covered with omentum, but adhesion was not prominent. Ascitis and the contents of vermiform appendix was old bloody fluid, and no pus was detected. Pathological study showed that the inflammation was phregmonous or gangrenous and nonspecific. High grade fever continued for 3 days after the operation. White blood cell count was 7700/mm3 at just after the operation and decreased to 1500/mm3 at the 5th postoperative day, and such change was thought to be due to natural course in HIV infection. The level of CRP increased after the operation to 7.6mg/dl on the 2nd post-operative day and decreased to 0.6mg/dl onthe 5th postoperative day. There was no delay of wound healing.

We examined gross type classification after chemotherapy in response to histopathological effects in patients who received neoadjuvant chemotherapy. Out of 33 cases subjected to neoadjuvant chemotherapy with cisplatin and 5-fluorouracil from September 1991 to August 1993, 31 cases with depressed lesions were enrolled in the present study. The cross sections of residual tumors from resected preparations were morphologically classified into the following 4 types: I. Those which maintain the original form almost completely. II. Those of which rand walls decrease in height, but with depressed surface. III. Those of which rand walls are lost completely, without depressed surface. IV. Those which are divided into small cancer foci. The above types were well correlated with histopathological responses. Considering that type III lesions are subdivided into (A) elevated lesions, (B) flat lesions, and (C) submucosal tumor lesions, and that the mucous membrane raised with the rand wall covers the tumor surface as the rand wall height decreases, gross types of our classification were well correlated with histopathological effects.

The patient was a 31-year-old man with advanced gastric cancer, clinically diagnosed as ML, Less, Type 3, sig, cT3, cN0, cH0, cP0, cM0, cCY0, cStage IIA. He underwent D2 distal gastrectomy. On microscopic examination, tumor cells were detected in the distal margin of the resected stomach. After surgery, he received 1 course of S-1 followed by chemoradiation therapy(1.8 Gy×25, a total of 45 Gy) with 90 mg/m2 of paclitaxel and 40 mg/m2 of CDDP on days 1, 15, and 29 over 5 weeks. Subsequently, he received 5 cycles of S-1 chemotherapy. To date, no recurrence has been observed 5 years after surgery. This sequential therapy is an option to consider for enabling local and systemic control after gastric cancer surgery.

Postoperative anastomotic hemorrhage is a relatively rare complication. However, when it does occur, immediate treatment is needed.In all, 1,700 patients underwent curative gastrectomy between 2000 and 2010. Anastomotic hemorrhage was observed in 9 patients after surgery. The clinical course of these 9 patients was analyzed.The median age of the patients was 62 years, and all patients were men. Two patients underwent distal gastrectomy, 1 underwent laparoscopic distal gastrectomy, and 6 underwent total gastrectomy. Bleeding occurred as follows: 5 were at gastro- or esophagojejunostomic site, 2 were at gastroduodenostomic site, and 2 were at jejunojejunostomic site. Five patients received conservative treatment and 2 underwent re-operation. Two additional patients achieved complete hemostasis with endoscopic treatment. The patients who received endoscopic treatment were discharged earlier than those who received other treatments.Endoscopic intervention was useful for the diagnosis and treatment of postoperative anastomotic hemorrhage.

We report a case of gastric small cell carcinoma with metastatic liver tumors responding to surgery and chemotherapy. The patient was a 67-year-old man with advanced gastric cancer, clinically diagnosed as P0H1M0CY0T3N1. He was registered in a phase III trial, and was scheduled to undergo gastrectomy and S-1 plus CDDP chemotherapy after surgery. He underwent D1 total gastrectomy and Roux-en-Y reconstruction. Small cell carcinoma of the stomach was diagnosed from the histopathological findings. After surgery, he received the following chemotherapy: 13 courses of CPT-11 plus CDDP chemotherapy, 2 courses of S-1, 5 courses of paclitaxel, and 6 courses of CPT-11. The patient is alive 22 months after his operation. We conclude that the combination of surgery and chemotherapy was effective for small cell carcinoma of the stomach, which was considered to have a poor prognosis.

Body weight loss is a common outcome in patients with gastric cancer who have undergone gastrectomy. However, the rate of body weight loss after surgery is unknown.In this retrospective study, we selected patients who underwent radical gastrectomy for gastric cancer and were diagnosed with Stage II or III disease. Further, we compared the body weight loss after surgery between patients in the surgery alone group and the S-1 adjuvant chemotherapy group.We evaluated 163 patients, of which 81 underwent only surgery, and 82 underwent surgery followed up with S-1 adjuvant chemotherapy. The body weight loss rate at 1, 3, and 6 months in the surgery alone group were 93.1%, 92.9%, and 94.9%, while those in the S-1 adjuvant group were 92.9%, 90.4%,and 91.9%, which was a significant difference.Body weight loss after gastrectomy was higher in the S-1 adjuvant group than in the surgery alone group. Further, nutritional support is required for these patients to maintain body weight after surgery.

A 55-year-old man was seen at the hospital because of nausea and vomiting, and admitted for close examination. On admission Hb was 9.2g/dl, indicating slight anemia. Upper gastrointestinal series and barium enema revealed no abnormality. Intestinal fluoroscopy visualized a whole-circumference stenosis 15cm anal side from the Treitz ligament. Superior mesenteric arteriography showed a moderate degree of hypervascularization locating at the same area as the tumor existed, as well as vascular obstruction and extension. Endoscopy of the small intestine revealed an irregular whole-circumferential elevated lesion at the same site. Biopsy indicated a growth of atypical gland, moderate degree of atypical cell. From these findings a preoperative diagnosis of malignant tumor of the small intestine was made. Partial excision of the small intestine with lymph nodes dissection was carried out. Histopathologically it was well differentiated adenocarcinoma. This paper presents a case of malignant tumor of the small intestine which was able to be diagnosed preoperatively.

As a project of the Kanagawa Colorectal Cancer Study Group, we performed this study to analyze the efficacy and the safety of modified FOLFIRI (irinotecan: 150 mg/m2) therapy for Japanese patients with metastatic colorectal cancer.We treated PS 0-1 Japanese patients with measurable or assessable colorectal cancer who either had not received preliminary treatment, or were postoperative with metastasis and had undergone radiation therapy or adjuvant chemotherapy before more than four weeks, and further had provided written acceptance of our proposed procedures. Twenty patients received modified FOLFIRI therapy as a 2-hour infusion of CPT-11 150 mg/m/2 and l-LV 200 mg/m2 followed by a bolus 5-FU 400 mg/m/2 and 46-hour infusion 5-FU 2, 400 mg/m2. Tumor response was assessed by RECIST and toxicity by NCI-CTC.Thirty males and seven females underwent an average 10 courses of treatment. This therapy achieved a 50% response rate, 80%disease-control rate, and 316+/-40 days PHS. Regarding hematological toxicity, 11 patients (55%) experienced leukemia, which developed to grade 3/4 in 5 (25%) of them. Twelve patients (65%) experienced neutropenia, which developed to grade 3/4 in 10 (50%) of them. Digestive toxicity was observed in 16 patients (80%), which developed to grade 3/4 in only one patient (5%) with gastric ulcer. Six patients (30%) experienced alopecia, which was grade 1/2 only.This clinical study was safely carried out. The efficacy was as good as in previous reports using a regular dose of CPT-11.

A 67-year-old woman was admitted to the center because of choking sensation in the throat at eating which occurred since June, 1990. X-ray examination of the esophagus revealed a funnel type stenosis but no irregular mucous membrane was observed. Esophagoscopy revealed a whole-circumference stenosis 37 cm distant from the incisor line. Biopsy disclosed no possible malignancy. On August 13 the lower part of the esophagus and cardiac part were resected. The tumor was located in the region Ei, about 3 cm in diameter, whole-circumferentially growed like a submucosal tumor, and had a IIc-like excavation in the oral-side end. Histopathologically the carcinoma was solid, and mainly comprized of basaloid cells. Partially, there were cancer cell nests showing the squamous cell differentiation which were stained acidophillically, and some parts revealing pseudoduct-like structure. From these results, a diagnosis of basaloid carcinoma was made. As the pathological classification of carcinomas of the esophagus was revised in 1990, the definition for this case may be somewhat different from the conventional one. Setting it aside, some discussion is presented by reviewing domestic cases of basaloid carcinoma seen in a part one decade.

消化管吻合部狭窄の治療法として, 内視鏡的切開およびブジーによる拡大術の適応と限界について検討した.吻合部狭窄35例 (瘢痕性26例, 癌性9例) を対象とした.瘢痕性狭窄の長さによる狭窄解除率をみると, 2cm未満14/15 (93.3%), 2cm以上3cm未満8/9 (88.9%), 3cm以上0/2 (0%) であった.一方, 癌性狭窄は0/9 (0%) と効果不良であった.効果不良例13例 (瘢痕性4例, 癌性9例) の内, 癌性3例を除く10例に他の治療を加えた.3例 (瘢痕性1例, 癌性2例) に手術, 7例 (瘢痕性3例, 癌性4例) に食道ブジー挿管術を施行した.手術では, 狭窄が解除出来たのは1例のみで他は試験開腹および合併症死におわった.食道ブジー挿管術は7例全例狭窄を解除でき退院可能であった.皮膚管瘢痕性狭窄1例のみ皮膚瘻孔を形成し手術を要した.食道ブジー挿管術は難治性吻合部狭窄の非観血的治療法として有用であった.

The aim of this study was to evaluate the efficacy and toxicity of 5-fluorouracil (5-FU) and l-leucovorin (l-LV) given at the same dose intensity and administered monthly (given weekly for 3 weeks followed by a week of rest; arm A) or every 2 months (given weekly for 6 weeks followed by 2 weeks rest; arm B) to patients with advanced colorectal carcinoma. The dose of 5-FU was 500 mg/body or 750 mg/body, with an average dose of 432.8 mg/m2. A total of 7 institutions participated in this multi-center study and were randomly divided into 2 groups of arms A and B. Thirty-three patients were entered into arm A and 21 into B. The overall response rate was significantly (p = 0.007) greater in arm B (23.5%) than in arm A (0%). The most frequently observed toxicity was diarrhea, which was observed in 6.5% of arm A and in 33.3% of arm B, marking a significant difference (p = 0.034). These data suggest that a monthly 5-FU/l-LV regimen might be less toxic than a 2-months regimen and less effective at the dose given as above. Further study is needed to evaluate the efficacy of a monthly regimen.

We have made various attempts to prevent postoperative respiratory tract infection in patients with cancer of the esophagus. In the first series, subjects were 48 patients undergoing esophagectomy for 2 years from June 1988. They were divided into 4 (penicillin-, 1st generation cephem-, 2nd generation cephem- or 3rd generation cephem-treated) groups. Discharge collected through an intratracheal tube was cultured every day. Second and third generation cephems made the airway aseptic in 67% and 86% of the total cases, respectively. Despite this excellent result, an aseptic state was suggested to easily lead to MRSA infection. In the second series, subbects were 22 patients undergoing esophagectomy for one year from February 1991. They received penicillins or 1st generation cephems alone. Intratracheal discharge was likewise cultured. The normal flora of the respiratory tract was preserved. This served to prevent MRSA infection and eventually deaths in the hospital. These studies indicate that preserving the normal flora of the respiratory tract is useful to prevent MRSA infection and improves the operative results of esophageal cancer.

As endoscopic procedures become various and complicated, it becomes necessary to develop alternative techniques for tissue suture and ligation. We have developed a new suture technique intracorporeal knotting.An 8-cm suture material having a knot on the other side of a needle, was used in laparoscopic surgery. Furthermore, a 5-mm2 Vicryl mesh was pierced as a buttress. The Lapra-ty was used to secure the tissue. Under laparotomy, the forestomach of a male Donryu rat at 6 weeks of age was incised and sutured with 3-0 Vicryl. 3-0 Vicryl was secured with the knot substitute (group A) or three-throw knot (group B) under Nembutal anesthesia. The animals were sacrificed 7 days after operation. Specimens were taken from the forestomach. Those were fixed with 10% formalin and stained with hematoxylin eosin and Elastica Wangieson methods. The histological findings were compared between group A and group B. A successful laparoscopic closure using Lapra-ty is reported in a patient with a perforation of the sigmoid colon.Microscopically, in this method, neither erosion, ulcer nor microabscess is evidenced. This method may make an intracorporeal knot easy. Also we treated a patient who had a perforation of the sigmoid colon using Lapra-ty. The patient recovered without any trouble.This method could make ligation technique much easier and the operating time shorter.

Carcinosarcoma, which comprises less than one percent of all gall bladder neoplasms, is characterized by the presence of variable proportions of carcinomatous and sarcomatous elements. We report a case of gall bladder carcinosarcoma arising in 69-year-old female. The patient was admitted to our hospital because of epigastric pain. CT revealed gall bladder tumor and liver invasion, portal vein invasion and peritoneal dissemination of the tumor. At the time of diagnosis, the tumor was considered inoperable. Following diagnosis, the patient received chemotherapy (1 course of gemcitabine). It was effective, and the tumor became operable. Curative surgical resection was performed. Histologically, viable tumor component remained mainly in the gall bladder. The tumor component consisted of sarcomatous and carcinomatous elements, and the latter was composed of squamous cell carcinoma and adenocarcinoma. In addition, remarkable necrosis and fibrosis was seen inside the tumor, especially in the part of liver invasion. We thought that the necrotic and fibrotic change indicated antitumor activity of the chemotherapy. On the basis of these findings, the tumor was diagnosed as carcinosarcoma of gall bladder. In summary, we reported the rare case of carcinosarcoma arose in gall bladder, which showed good response to the chemotherapy.

There are two basic techniques for esophageal prosthesis intubation: Pulsion and traction. The pulsion technique is superior to the traction technique in that there are fewer associated complications. Also, there is less invasion to the patient. Even so, with pulsion, general anesthesia is sometimes necessary, in cases of highly advanced stricture, to pass a prosthesis with or without the support of esophagoscopy or an introducer. With some cases of highly advanced stricture, it is necessary to use a general anesthesia, to be able to pass the prosthesis through.