Efficacy of Endoscopic Management for Early Remnant Gastric Cancer: Is Completion Gastrectomy Truly Necessary in Cases with Marginally Noncurative Histopathologic Features?

BACKGROUND: For patients with early primary gastric cancer, endoscopic management has become a standard of care. However, its efficacy for early remnant gastric cancer (ERGC) remains controversial and an invasive surgical procedure remains the primary choice of treatment. METHODS: A multi-institutional database of ERGC cases was retrospectively reviewed. Efficacy of endoscopic resection was analyzed by reviewing the clinicopathologic features of patients who underwent endoscopic resection and comparing the long-term outcomes with those of surgical resection. RESULTS: Of the 121 patients who were histopathologically diagnosed with ERGC after distal gastrectomy, 80 underwent endoscopic resection and 41 underwent completion gastrectomy (Group S). According to the histopathological criteria, 55 of the 80 endoscopic resection cases were classified as "curative resection" (Group E1) and the remaining 25 were classified as "noncurative resection" (Group E2). Tumor recurrence was observed only in three patients (12%) in Group E2, and no tumor recurrence was confirmed in Group S and Group E1. Multivariate analyses confirmed that completion gastrectomy [hazard ratio (HR), 6.2; 95% confidence interval (CI), 1.5-26.3] was associated with poor survival compared with endoscopic resection, and lymphovascular infiltration (HR 9.5; 95% CI 2.5-36.7) was correlated with tumor recurrence. Histopathological positive resection margin, tumor size, or deeper tumor invasion were not correlated with tumor recurrence after endoscopic resection. CONCLUSIONS: Endoscopic management might be an effective treatment option for ERGC with potential long-term survival advantage over the completion gastrectomy even in cases with histopathological features, suggesting noncurative resection.

[A Case of GIST with Extensive Peritoneal Dissemination Controlled over Long-Term by Low-Dose, Intermittent Administration of Imatinib after Weight Loss Surgery].

A 67-year-old man presented with abdominal pain and fever. Many abdominal tumors were detected by enhanced computed tomography(CT). The largest tumor, measuring 20 cm, had perforated the ileum and formed an abscess. Emergency surgery was performed to remove multiple tumors in the peritoneal cavity as much as possible. Immunostaining showed c-kit and CD34 positivity, and the tumors were diagnosed as gastrointestinal stromal tumor(GIST). During postoperative imatinib therapy for the residual tumor, low-dose intermittent administration was required due to side effects, but the disease was controlled for over 91months. For advanced GIST with peritoneal dissemination, 200mg/day imatinib or intermittent administration after volume reduction surgery might be effective depending on the patient's general condition.

Re-evaluation of the role of thoracoscopic esophagectomy as a Japanese-style radical surgery.

PURPOSE: To investigate the value of thoracoscopic surgery in radical esophagectomy with three-field lymphadenectomy. MATERIALS AND METHOD: The subjects were 329 consecutive patients who, without preoperative chemoradiotherapy, underwent R0 radical esophagectomy with three-field lymphadenectomy for thoracic squamous cell esophageal cancers during 1998-2013. Open thoracotomy was applied in 212 (O), and thoracoscopic surgery in 117 (V). Survivals according to TNM Stages and Efficacy index (EI) were analyzed. RESULTS: Hospital death rates of O/V were 1.9/0%. The survivals of V according to TNM Stages had significantly better prognosis in TNM6th cStage III and showed not worse prognosis in general. In the analysis using Cox proportional hazards model, "V or O" was a significant prognostic factor indicating better prognosis of V. More bilateral paratracheal lymph nodes along the recurrent laryngeal nerves tended to be classified as mediastinal instead of cervical in V. Efficacy index of mediastinal paratracheal nodes was higher in V than in O, while cervical lymphadenectomy maintained high EI. DISCUSSION AND CONCLUSION: Though our series have limitations of retrospective study and substantial bias, the feasibility and safety of thoracoscopic esophagectomy with three-field lymphadenectomy was shown. Higher paratracheal lymph nodes along the recurrent laryngeal nerves could be dissected from the mediastinal side in V group. Thoracoscopic esophagectomy, which is regarded as minimally invasive surgery in other countries, is being accepted in Japan mainly in the expectation of more thorough and meticulous lymphadenectomy. At the same time, the dissection range is continuously re-evaluated for safer surgery maintaining radicality.

Proximal gastrectomy with exclusion of no. 3b lesser curvature lymph node dissection could be indicated for patients with advanced upper-third gastric cancer.

BACKGROUND: Proximal gastrectomy has been introduced for early gastric cancer located in the upper third of the stomach, but expansion of its indication to advanced tumors has not been generally accepted in terms of lesser curvature lymph node dissection. METHODS: We reviewed the medical records of 385 patients with tumors in the upper third of the stomach, and the incidence of metastasis and the therapeutic index related to the proximal (no. 3a) and distal (no. 3b) lymph nodes of the lesser curvature were analyzed and compared with those of tumors in the middle third (n = 1093) and lower third (n = 922) of the stomach. RESULTS: The no. 3a rate of metastasis from advanced tumors in the upper third of the stomach was significantly higher than that from tumors in the middle third or lower third of the stomach. The no. 3b metastasis rate did not show any significant differences between the three locations, but the therapeutic index of no. 3b lymph nodes in the upper third of the stomach (1.7) was far lower than that in the middle third (7.1) or lower third (7.0). Further, the rate of metastasis from tumors with the distal border ending in the upper third of the stomach (2.2 %) was significantly (P < 0.0001) lower than that from tumors located in the upper third of the stomach but extending to the middle third (19.6 %), as well as from tumors located in middle third (17.1 %) or lower third (19.6 %), with the therapeutic index being only 1.1. The four no.-3b-positive tumors all measured more than 40 mm, and included one T3 tumor and three T4 tumors. CONCLUSION: Proximal gastrectomy with exclusion of no. 3b lymphadenectomy could be indicated for at least T2 tumors measuring less than 40 mm localized in the upper third of the stomach.

Lymphadenectomy along the infrapyloric artery may be dispensable when performing pylorus-preserving gastrectomy for early middle-third gastric cancer.

This study investigated the incidence of gastric cancer metastasis to the lymph nodes along the infrapyloric artery (IPA), namely no. 6i, by reviewing our medical records of 348 patients who underwent complete no. 6 dissection. Metastasis to these nodes was observed in 11 (3.2 %) patients. In these patients, one huge tumor was located in the middle third and ten including two early tumors were located in the lower third; the metastasis rate in early lower-third tumors was 2.1 % and reached 19.5 % in advanced tumors. In contrast, no early middle-third gastric cancers had no. 6i metastasis. The median diameter of 6i-positive tumors was 62 (range 18-115) mm, and the distance from the distal tumor border to the pyloric ring was no more than 44 mm. Lymphadenectomy along the IPA is important for treating gastric cancer invading the antrum, but may be dispensable when performing pylorus-preserving gastrectomy for early middle-third cancer.

Process of Pancreas Head as a Risk Factor for Postoperative Pancreatic Fistula in Laparoscopic Gastric Cancer Surgery.

BACKGROUND: Postoperative pancreatic fistula (POPF)-often caused by pancreatic injury during dissection of the peripancreatic lymph nodes-is a serious complication after gastric cancer surgery. We defined protruding pancreatic tissue on the anterior side of the pancreas head as "process of the pancreas head" (PPH) and investigated whether PPH is a predictable risk factor for POPF after laparoscopic gastrectomy. METHODS: We reviewed 255 patients who underwent laparoscopic total or distal gastrectomy for gastric cancer. The perioperative outcomes of 142 patients operated in the study's early phase were investigated to evaluate the risk factors for POPF. To evaluate whether preoperative identification of PPH by computed tomography (CT) and intraoperative prediction of pancreas head outline could reduce the risk of POPF, the outcomes of 113 patients operated in the late phase were assessed. RESULTS: Of the 142 early-phase patients, PPH was identified intraoperatively in 38 patients (26.8 %). A total of 13 patients (9.1 %) developed POPF > grade 2. PPH was identified as a risk factor for POPF (P < 0.01). In early-phase patients with PPH, the POPF rate was 21.0 %; in the late phase, it decreased to 4.3 %. Further, the POPF rate in early-phase patients with BMI > 25 and PPH was 42.6 %, decreasing to 0 % in the late-phase patients. CONCLUSIONS: The presence of PPH is a risk factor for POPF after laparoscopic gastrectomy for gastric cancer. Identifying PPH using preoperative CT images and predicting the shape of the pancreas head during infrapyloric lymph node dissection are valuable in preventing POPF following laparoscopic gastric cancer surgery.

IgG4-related epididymo-orchitis associated with bladder cancer: possible involvement of BAFF/BAFF-R interaction in IgG4-related urogenital disease.

We describe herein a patient who presented with immunoglobulin G4-related disease (IgG4-RD) involving the testis and prostate as well as the submandibular glands. Massive infiltration of IgG4-expressing plasma cells was observed in testis and prostate tissues. Serum concentrations of B cell activating factor belonging to the tumor necrosis factor family (BAFF) were elevated in parallel with serum IgG4 concentrations, and infiltration of BAFF-receptor (BAFF-R)-expressing B cells and BAFF-expressing lymphoid cells was observed around the ectopic lymphoid foci in the affected urogenital tissues. To date, testicular involvement in a patient diagnosed with IgG4-RD had not been reported, making this the first reported case of IgG4-related epididymo-orchitis. These findings suggest that the immune mechanism underlying ectopic lymphoneogenesis in IgG4-RD may involve enhanced BAFF/BAFF-R interactions among lymphoid cells.

Identification and characterization of an insulin receptor substrate 4-interacting protein in rat brain: implications for longevity.

The hypothalamus is organized as a collection of distinct, autonomously active nuclei that regulate discrete functions, such as feeding activity and metabolism. We used suppression subtractive hybridization (SSH) to identify genes that are enriched in the hypothalamus of the rat brain. We screened a subtractive library of 160 clones, and 4 genes that were predominantly expressed in the hypothalamus, compared to other brain regions. The mRNA for a member of the WD-repeat family of proteins, WDR6, was abundantly expressed in the hypothalamus, and we found that WDR6 interacted with insulin receptor substrate 4 (IRS-4) in the rat brain. Interestingly, WDR6 gene expression in the hypothalamic arcuate nucleus was decreased by caloric restriction, and in growth hormone (GH)-antisense transgenic rats, both of which are associated with an increased life span. Insulin-like growth factor (IGF)-I and insulin treatment increased WDR6 gene expression in mouse hypothalamus-derived GT1-7 cells. Our results might suggest that WDR6 participates in insulin/IGF-I signaling and the regulation of feeding behavior and longevity in the brain.

Identification of fasting-induced genes in the rat hypothalamus: relationship with neuroprotection.

During food shortage, organisms activate defense mechanisms to maximize their chance of survival. At least in part, these responses are triggered by changes in hormonal status and neural status during starvation. The hypothalamus is organized as a collection of distinct autonomously active nuclei and is considered to play crucial roles in these survival responses. To isolate factors involved in these pathways, we carried out suppression subtractive hybridization analyses using complementary DNAs (cDNA) from the hypothalami of fasted and fed rats. We identified four genes, namely ubiquitin-conjugating enzyme E2D 3 (UBE2D3), cAMP-dependent protein kinase C beta subunit (PKCbeta), excitatory amino acid carrier 1 (EAAC1), and ferritin heavy polypeptide 1 (Fth1), that were upregulated after a 48-h fast compared to the fed status. According to previous reports, these genes have been implicated in protection against neuronal cell death under various neurodegenerative stresses, such as hypoxia-ischemia and oxidative stress. Thus, the increased expressions of the genes identified in the present study may have protective effects against neural damage that could otherwise result in cell death.