[Usefulness of an Epidural Catheter with a Subcutaneous Port for Locally Advanced Rectal Cancer Pain Which Was Difficult to Manage with Opioids-A Case Report].

A 56-year-old woman was diagnosed with advanced rectal cancer, with tumor invasion to the sacrum and levator muscle of the anus and multiple lymph node metastasis. After construction of an artificial anus, chemotherapy was started. However, tumor invasion and the cancer pain progressed. Finally, she was hospitalized for pain control; an anesthesiologist planned to insert an epidural catheter. The epidural catheter was placed at the L5-S1 interspace, and continuous administration of 0.2% ropivacaine was started. Cancer pain in the buttocks improved quickly. Therefore, an epidural catheter with a subcutaneous port was placed to prevent catheter-related infection after a long period. The postoperative course was uneventful, and she was discharged from the hospital on the 10th day postoperatively. She could receive home medical care and pain control treatment in an outpatient clinic. Finally, she died due to progression of the rectal cancer, 3 months after placement of the epidural catheter with the subcutaneous port. Some patients with advanced rectal cancer develop cancer pain even though they are sufficiently treated with opioids or palliative radiation therapy. Here, we describe the case of a patient with locally advanced rectal cancer, treated with an epidural catheter with a subcutaneous port for cancer pain that was difficult to manage with opioids alone.

Changes in the Gustave Roussy Immune Score as a Powerful Prognostic Marker of the Therapeutic Sensitivity of Nivolumab in Advanced Gastric Cancer: A Multicenter, Retrospective Study.

BACKGROUND: Identification of positive biomarkers for the effects of nivolumab on patients with advanced gastric cancer (AGC) is significant. The Gustave Roussy Immune Score (GRIm-s) is associated with therapeutic resistance of immune checkpoint inhibitors (ICIs) in other cancers. This multicenter, retrospective study was designed to analyze the association of GRIm-s with therapeutic sensitivity of nivolumab in patients with AGC. METHODS: We reviewed 58 patients with AGC treated with nivolumab from October 2017 to November 2018 at five participating institutions. We performed blood tests before the start of nivolumab and after administration of two courses. We evaluated the correlation between the best overall response and GRIm-s. Additionally, we focused on the changes in GRIm-s before the start of nivolumab and after administration of two courses. RESULTS: Of the 58 patients, 21 (36.2%) were classified into the disease control (DC) group and 37 (63.8%) into the progressive disease (PD) group. GRIm-s before nivolumab treatment did not correlate with the best therapeutic response (p = 0.086). However, GRIm-s after two courses of nivolumab showed that significantly more PD cases were in the high-risk group (p < 0.0001). After two courses of nivolumab, overall survival was significantly worse in the high-risk group (p < 0.0001). For progression-free survival, the high-risk group had a significantly worse prognosis both before (p = 0.04) and after two courses of nivolumab treatment (p < 0.0001). CONCLUSIONS: GRIm-s after two courses of nivolumab and its changes compared to pretreatment values proved beneficial in predicting nivolumab sensitivity.

Clinical features as potential prognostic factors in patients treated with nivolumab for highly pretreated metastatic gastric cancer: a multicenter retrospective study.

BACKGROUND: Although nivolumab (anti-programmed cell death-1 antibody) is a promising approach for advanced gastric cancer (AGC), the response rate remains limited. The aim of this multicenter retrospective study was to determine if clinical features could serve as prognostic factors of the efficacy of nivolumab in patients with AGC. METHODS: Fifty-eight patients with AGC who were treated with nivolumab as a third or later line from October 2017 to December 2018 at any of five clinical sites were enrolled in the study. The correlation between the best overall response and clinical features was investigated. Overall survival and progression-free survival after initiation of nivolumab were calculated and clinical features that could be predictors of the prognosis were sought. RESULTS: The disease control rate (DCR) for nivolumab was 36.2% and was significantly correlated with performance status (p = 0.021), metastasis to one organ (p = 0.006), and grade 2 or higher immune-related adverse events (p = 0.027). There was also a significant association between response to nivolumab and ability to receive subsequent chemotherapy (p = 0.022). In the analysis of overall survival, the following variables were identified as being significantly associated with a poor outcome: Eastern Cooperative Oncology Group performance status ≥1, prior treatment with trastuzumab, no immune-related adverse events, lack of a response to nivolumab, and inability to receive subsequent chemotherapy. CONCLUSION: The findings of this study suggest that nivolumab may be ineffective for AGC in patients with poor performance status and those with a history of treatment with trastuzumab.

Role of PD-L1 Expression during the Progression of Submucosal Gastric Cancer.

INTRODUCTION: Programmed death-ligand 1 (PD-L1) expression is a prognostic marker for gastric cancer that correlates with tumor diameter and depth of penetration. But the role of PD-L1 and mechanism(s) employed in the initial phase of invasion in early gastric cancer is yet to be understood. OBJECTIVE: This study aims to elucidate the role of PD-L1 during the progression of gastric cancer, specifically invading the submucosa beyond the lamina muscularis mucosa. METHODS: Using 107 patients with pathological submucosal gastric cancer, we determined the expression of PD-L1 based on the staining of the cell membrane or cytoplasm of tumor cells in the central and invasive front of the tumor. Samples were categorized into 3 groups based on the intensity of PD-L1 expression. CD8+ lymphocytes expressing PD-1 and CD163+ macrophages were used to determine the number of cell nuclei at the invasive front, similar to PD-L1. CMTM6 levels were determined and used to stratify samples into 3 groups. RESULTS: PD-L1 expression was higher in the invasive front (26.2%) than in the central portion of the tumors (7.4%; p < 0.001). Moreover, lymphatic and vascular invasion were more frequently observed in samples with high levels of PD-L1 (lymphatic invasion: 60.7 vs. 35.4%, p = 0.0026, and vascular invasion: 39.3 vs. 16.5%, p = 0.0018). There was no correlation between PD-L1 expression and the levels of PD-1, CD8, CD163, and CMTM6. CONCLUSIONS: PD-L1-expressing cancer cells at the invasive front of gastric cancer influence the initial stages of tumor invasion and lymphovascular permeation in early-stage gastric cancers. Immune checkpoint signaling may be the driving force in the invasive front during the invasion of the submucosa beyond the lamina muscularis mucosa.

Chest Pain after Endoscopic Submucosal Dissection for Esophageal Cancer: The Simple and Clinically Useful Surrogate Marker for Transmural Thermal Injury by Electrocoagulation.

BACKGROUND: Endoscopic submucosal dissection (ESD) of early esophageal cancer (EC) is becoming more widespread. Post-ESD coagulation syndrome (CS) has been proposed as temporary inflammatory signs that occur during the post-ESD period caused by transmural thermal injury by electrocoagulation. This retrospective study aimed to evaluate the association between chest pain and abnormal levels of inflammatory markers during the post-esophageal ESD period. We also investigate the clinical importance of chest pain to define the post-esophageal ESD CS. METHODS: We examined 42 patients with thoracic EC who underwent ESD. RESULTS: The incidence of chest pain after esophageal ESD is 35.7% and associated with elevation of WBC count on postoperative day 1 (WBC day 1) (p = 0.022). Multivariate logistic regression analysis using the procedure-related factors revealed that WBC day 1 was an independent predictive factor for chest pain (p = 0.034). The elevation of WBC count is associated with the resected esophageal circumference (p for trend = 0.018), specimen size (p = 0.031), and procedural time (p = 0.004). The incidence of post-esophageal ESD CS was estimated ranging from 11.9 to 54.8% using previously reported criteria. CONCLUSIONS: The incidence of chest pain after ESD was only associated with postoperative elevation of WBC day 1. In considering the elevation of WBC count associated with procedure-related factors, chest pain possibly reflected transmural thermal injury by electrocoagulation during ESD. Post-esophageal ESD chest pain is a simple and clinically useful surrogate marker for transmural thermal injury and is a vital sign of post-esophageal ESD CS.

Clinical outcomes of gastric tube reconstruction following laparoscopic proximal gastrectomy for early gastric cancer in the upper third of the stomach: experience with 100 consecutive cases.

BACKGROUND: Gastric tube reconstruction is a form of esophagogastrostomy performed after laparoscopic proximal gastrectomy (LPG). It is a simple and safe technique, but it may cause reflux esophagitis (RE) and impair postsurgical QOL. For several years, we have developed the gastric tube reconstruction and performed it on more than 100 patients. This study aimed to determine whether gastric tube reconstruction can be a feasible choice after LPG in regard to surgical safety and postoperative nutritional status. METHODS: The subjects consisted of 171 patients who underwent LPG (n = 102) or laparoscopic total gastrectomy (LTG) (n = 69). We compared the two groups in terms of surgical outcomes, incidence rate of RE, and nutritional status including postoperative weight loss and hemoglobin levels. RESULTS: There were no significant differences with regard to the surgical duration and blood loss between the two groups. The incidence of RE was not significantly higher with LPG than with LTG (16.7% vs. 10.1%, respectively; P = 0.07). Later than 2 years and 6 months after surgery, the body weight percentage of preoperative body weight in the LPG group was significantly higher than that in the LTG group. Hemoglobin and ferritin levels in the LPG group were significantly higher than those in the LTG group, later than one after surgery. The overall survival rates were similar between the two groups (5-year survival rates: 97.1% vs. 94.2% in the LPG and LTG groups, respectively; P = 0.69). CONCLUSIONS: Gastric tube reconstruction after LPG is simple and had better outcomes than LTG in terms of postoperative nutritional status.

Migrating contractions of the afferent and Roux limbs show peristaltic movement independently of each other in conscious dogs after Roux-en-Y reconstruction after distal gastrectomy.

PURPOSE: The Roux-en-Y (RY) procedure is used frequently for surgical reconstruction after gastrectomy. However, a minority of patients suffer a serious motility disorder of the Roux and afferent limb postoperatively. We conducted this study to clarify the association between the motility and peristaltic direction of two limbs in conscious dogs. METHODS: We performed distal gastrectomy on five dogs and implanted seven force transducers on the serosal surfaces of the remnant gastric body and afferent and Roux limbs. We then analyzed the electric signals from these force transducers. RESULTS: Migrating contractions were observed in the two limbs, but not in the gastric remnant body. Migrating contractions in the forward direction propagated independently from the most proximal side in each limb. There was no propagation of contraction across the jejunojejunostomy between the two limbs. CONCLUSIONS: Each proximal part of the Roux and afferent limbs has an independent motility pacemaker in conscious dogs after gastrectomy with RY reconstruction.

High RAD18 Expression is Associated with Disease Progression and Poor Prognosis in Patients with Gastric Cancer.

BACKGROUND: RAD18 plays an important role in DNA damage repair by inducing monoubiquitinated PCNA (mUB-PCNA) in both cancer and normal tissues. Previous studies have not determined the significance of RAD18 expression in clinical gastric cancer (GC) samples. Thus, this study aimed to clarify the expression and functional significance of RAD18 in GC. METHODS: Overall, 96 resected GC samples were subjected to an immunohistochemical analysis of RAD18. GC cell lines were also subjected to functional RNA interference analyses of RAD18. RESULTS: RAD18 expression was predominantly nuclear and was observed at higher levels in GC tissues than in normal tissues. In GC tissues, strong RAD18 expression was associated with progression of lymph node metastasis (p = 0.0001), lymphatic invasion (p = 0.0255), venous invasion (p < 0.0001), recurrence (p = 0.028), and disease stage (p = 0.0253). Moreover, GC patients with high tumor RAD18 expression had shorter overall survival (p = 0.0061) and recurrence-free survival durations (p = 0.035) than those with low tumor RAD18 expression. RAD18 knockdown inhibited GC proliferation and invasiveness and increased chemosensitivity by suppressing mUB-PCNA. CONCLUSIONS: RAD18 expression may be a useful marker of progression and poor prognosis of GC. Moreover, therapeutic strategies that target RAD18 might be a novel chemosensitizer to eradicate the refractory GC.

High Stromal TGFBI in Lung Cancer and Intratumoral CD8-Positive T Cells were Associated with Poor Prognosis and Therapeutic Resistance to Immune Checkpoint Inhibitors.

BACKGROUND: We investigated whether the expression of transforming growth factor-beta-induced protein (TGFBI) and intratumoral immune cells including CD8- and Forkhead box protein P3 (Foxp3)-positive T cells in clinical lung cancer patients could predict the therapeutic response to nivolumab. METHODS: Thirty-three patients who were treated with nivolumab were enrolled in this study. Immunohistochemical analyses of TGFBI, PD-L1, CD8, Foxp3, and vimentin expression were conducted. Serum concentrations of TGFBI and transforming growth factor-beta1 (TGF-ß1) were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Cancer TGFBI was not associated with prognosis and therapeutic response to nivolumab, but cancer stromal TGFBI and intratumoral CD8-positive T cells were associated with them. Therefore, we evaluated cancer stromal TGFBI and intratumoral CD8-positive T cells. The high-TGFBI-expression group had poorer clinical responses than did the low-TGFBI-expression group (p < 0.0001). The number of times nivolumab was administered in the high-CD8-expression group was significantly higher than that in the low-CD8-expression group (p = 0.0046). The high-CD8-expression group had better clinical responses than did the low-CD8-expression group (p = 0.0013). Interestingly, all patients in the high-TGFBI/low-CD8-expression group had progressive disease (PD). In contrast, all patients in the low-TGFBI/high-CD8-expression group had PR + SD (partial response + stable disease) by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). CONCLUSIONS: The dual evaluation of stromal TGFBI and intratumoral CD8-positive T cells could be a useful predictive marker for nivolumab.

Pathophysiology of Vomiting and Esophageal Perforation in Boerhaave's Syndrome.

BACKGROUND AND AIMS: Boerhaave's syndrome, involving esophagus rupture, is considered a pathological response to vomiting that may occur just before perforation. However, the mechanism of vomiting and occurrence of this disease have not been clearly demonstrated. METHODS: We identified patients with esophageal perforation between 1995 and 2017 and reviewed endoscopic findings at retching during upper gastrointestinal endoscopy. Finally, we proposed a theory for the underlying pathological mechanism. RESULTS: We retrospectively investigated 10 patients with esophageal perforation between 1995 and 2017. All patients presented after vomiting associated with large volumes of food and alcohol intake. Nine were treated by primary closure of the perforation and drainage of the thoracic cavity, and one was conservatively treated. In all cases, the perforations were longitudinal tears (1-4 cm) and located in the left of the esophagus, just above the gastric cardia. CONCLUSIONS: We hypothesize that vomiting occurred by retrograde propagation of gastrointestinal motor contraction from the jejunum to the gastric antrum, followed by prolapse of the gastric fornix mucosal into the esophagus. Subsequent esophageal perforation probably resulted from excessive prolapse due to strong contraction and destruction of the muscularis mucosa of the left side of abdominal esophagus, with longitudinal stretching of the whole left esophageal wall due to traction. We also propose that Boerhaave's syndrome is defined as "post-emetic esophageal perforation" to ensure broader recognition and more expedient diagnosis and treatment. Remaining conditions without any definite causes may be labeled "idiopathic" or "spontaneous" rupture of the esophagus.

Four stay-sutures method: a simplified hand-sewn purse-string suture in laparoscopic circular-stapled esophagojejunostomy.

Laparoscopic esophagojejunostomy is a challenging procedure because of its technical difficulty. We herein report a new method involving circular-stapled anastomosis using a hand-sewn suture with four stay-sutures and evaluate its outcomes. Esophagojejunostomy using this method was performed in 36 consecutive patients with clinical stage I gastric cancer at the authors' institutions. The key feature of our procedure was the placement of four full-thickness stay-sutures to anchor the esophageal stump prior to the hand-sewn purse-string suture. The median operation time and mean anvil fixation time were 315.5 and 21.9 min, respectively. The mortality rate was 0%, although anastomotic leakage following esophagojejunostomy was observed in 1 patient (2.8%), and anastomotic stenosis was observed in another patient (2.8%). Intracorporeal esophagojejunostomy using the four stay-sutures method appears to be safe and feasible. We believe that this method enables hand-sewn purse-string suturing to be performed more easily.

High expression of forkhead box protein C2 is associated with aggressive phenotypes and poor prognosis in clinical hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the major causes of tumor death; thus, the identification of markers related to its diagnosis and prognosis is critical. Previous studies have revealed that epithelial-to-mesenchymal transition (EMT) is involved in tumor invasion and metastasis, and the forkhead box protein C2 (FOXC2) has been shown to promote tumor cell proliferation, invasion, and EMT. In the present study, we examined the clinicopathological significance of FOXC2 and EMT-related markers in clinical HCC specimens and identified factors related to the diagnosis and prognosis of HCC. METHODS: The expression of FOXC2 and EMT-related markers was evaluated by immunohistochemistry in 84 cases of hepatocellular carcinoma. RESULTS: A high expression of FOXC2 was observed in 26 of 84 cases, and expression was significantly correlated with background liver cirrhosis, poor tumor differentiation, high serum AFP, and elevated cell proliferation markers. In addition, this high expression was related to the induction of the Cadherin switch and vimentin expression and was an independent predictor for poor prognosis. CONCLUSION: The high expression of FOXC2 in HCC is correlated with tumor malignancy and poor prognosis, suggesting that FOXC2 may be an important prognostic factor for HCC.

High stromal transforming growth factor ß-induced expression is a novel marker of progression and poor prognosis in gastric cancer.

BACKGROUND AND OBJECTIVES: Transforming growth factor ß-induced (TGFBI) protein is a secreted extracellular matrix protein with conflicting roles in cancer, acting as a tumour suppressor and a promoter, which appears to be tissue specific. The role of TGFBI in gastric cancer (GC) remains unclear, which we aimed to investigate using the clinical samples as well as an in vitro coculture model of GC. METHODS: The clinical significance of TGFBI was assessed in 208 GC samples using immunohistochemistry. Molecular function of TGFBI in the GC cells was examined by small interfering RNA-mediated TGFBI downregulation in the gastric fibroblasts cocultured with the GC cells. RESULTS: TGFBI expression was localised mainly in the cancer stroma and not in the noncancerous gastric tissue or the GC cells. High TGFBI expression was significantly associated with poor prognosis and cancer progression. Downregulation of TGFBI in the cocultured gastric fibroblasts inhibited the invasion and migration abilities of the GC cells. CONCLUSIONS: High stromal TGFBI expression might be a useful predictive marker for poor prognosis in GC patients. Furthermore, TGFBI in the cancer stromal cells is a promising target for GC treatment.

Long-Term Imatinib Treatment for Patients with Unresectable or Recurrent Gastrointestinal Stromal Tumors.

BACKGROUND: Only limited data are available concerning the long-term outcomes of imatinib treatment among Japanese or Asian patients with advanced or recurrent gastrointestinal stromal tumors (GIST). Our multicenter study, which was conducted in northern Kanto, Japan, aimed to assess the efficacy of imatinib mesylate against advanced or recurrent GIST. SUMMARY: The clinicopathological data of 234 GIST patients who were treated at one of the 11 participating hospitals from 2001 to 2011 were retrospectively reviewed (GREAT study). Imatinib was administered as a first-line therapy in cases involving unresectable disease or postoperative recurrence (41 cases). The patients treated with imatinib (n = 41) exhibited 1-, 3-, and 5-year overall survival (OS) rates of 92.3, 74.9, and 53.8% respectively. In univariate and multivariate analyses, imatinib continuation with dose reduction and achieving a complete or partial response were found to be associated with increased OS. The results of 2 large-scale, long-term trials demonstrate that the risk of tumor progression decreases with increased treatment duration. Furthermore, the interruption of imatinib treatment in responsive and controlled patients results in a high risk of disease progression. Key Messages: Long-term imatinib treatment is recommended for patients with nonprogressive disease. If patients experience significant toxicities, temporary dose reduction and treatment continuation might be useful.

High STMN1 level is associated with chemo-resistance and poor prognosis in gastric cancer patients.

BACKGROUND: Stathmin1 (STMN1) is a cytosolic phosphoprotein that regulates cellular microtubule dynamics and is known to have oncogenic activity. Despite several reports, its roles in gastric cancer (GC) remain unclear owing to a lack of analyses of highly metastatic cases. This study aimed to investigate STMN1 as a prognostic and predictive indicator of response to paclitaxel therapy in patients with GC, including inoperable cases. METHODS: Immunohistochemical analysis of STMN1 was performed on both operable (n=95) and inoperable GC (n=61) samples. The roles of STMN1 in cancer cell proliferation and sensitivity to a microtubule-targeting drug, paclitaxel, were confirmed by knockdown experiments using GC cell lines. RESULTS: Multivariate and Kaplan-Meier analyses demonstrated that high STMN1 was predictive of poor prognosis in both the groups. In the operable cohort, STMN1 expression correlated with cancer curability, recurrence, and resistance to adjuvant therapy. A correlation with paclitaxel resistance was observed in inoperable cases. Knockdown of STMN1 in GC cell lines inhibited proliferation and sensitised the cells to paclitaxel by enhancing apoptosis. CONCLUSIONS: STMN1 is a possible biomarker for paclitaxel sensitivity and poor prognosis in GC and could be a novel therapeutic target in metastatic GC.

Restoration of gastrointestinal motility ameliorates nutritional deficiencies and body weight loss of patients who undergo laparoscopy-assisted proximal gastrectomy.

BACKGROUND: Esophagogastrostomy after proximal gastrectomy (PG) is a simple and safe reconstruction, but it leads to a high incidence of reflux esophagitis and impairs postoperative quality of life. We have already reported gastric tube (GT) reconstruction after PG and performed it on more than 100 patients. No studies have reported long-term outcomes after PG-GT. The aim of this study was to investigate long-term outcomes, including nutrition indices, such as body weight, serum albumin, total protein, hemoglobin, and ferritin after PG, and observe recovery of upper gastrointestinal tract motility. METHODS: We analyzed body weight loss and laboratory findings at our outpatient clinic at 1, 6, 12, 24, 36, 48, and 60 months postoperatively. Manometric recording was carried out at 1, 2, 3, 4, and 5 years after surgery. RESULTS: The percentage change in body weight in the PG-GT group was significantly larger than that in the PG-JI and TG-RY groups at 2.5, 3, 4, and 5 years after surgery. The levels of hemoglobin and ferritin in the PG-GT and PG-JI groups were significantly higher than those in the TG-RY group at all time points except 6 months after surgery. In the fasted state, the phase III originated at the gastric tube was propagated to the duodenum 3 years after surgery. In the fed state, phasic contractions of the duodenum were in harmony with gastric tube contractions 3 years after surgery. CONCLUSIONS: PG-GT is the least invasive procedure, and restoration of gastrointestinal motilities in the gastric tube and duodenum may ameliorate body weight loss and nutritional status, including anemia, in patients after PG.

[Investigation of the Pathophysiology and Diagnostic Methods Through a Case of Acute HIV Infection in which the Western Blot Method Remained Negative Over the Long Term and the 4th Generation Screening Assay Became Negative for a Certain Period of Time after Initiating Antiretroviral Therapy].

Confirmatory tests using Western blot (WB) and HIV-1 nucleic acid testing (HIV-1 RNA) following a positive screening test are required for the diagnosis of HIV-1 infection according to the current Japanese guidelines for HIV-1/2 diagnosis. We report herein on a rare case in a patient who remained negative for WB over 10 months in spite of being positive by fourth-generation immunoassays (4thGIA) and who subsequently seroreverted by 4thGIA for three months after initiating antiretroviral therapy. Case: A man in his early twenties previously visited a hospital because of fever in October 2012. Laboratory data revealed leukocytopenia, thrombocytopenia and increased serum ferritin, suggesting hemophagocytic syndrome (HPS). During that visit, he tested positive for a 4thGIA, but negative for HIV-1 WB and his result of HIV-1 RNA result was detected invalid because of the presence of some inhibitory material in his RNA preparation. Thereafter, he was diagnosed as having cytomegalovirus-associated HPS treatment was for which initiated. In January 2013, he developed Pneumocystis jirovecii pneumonia, and his HIV-1 RNA viral load was 7.7 × 105 copies/mL in February 2013. Acute HIV infection was suspected, because the HIV-1 WB remained negative. He was started on antiretroviral therapy in April 2013. His 4thGIA was converted to negative in May 2013 and was reconverted to positive in August 2013. HIV-1 WB, however, continued to be indeterminant until February 2014, in which it turned positive for the first time according to the CDC criteria. Methods and Results: The genetic analyses of HIV-1 were done on the gag, env, nef and pol region of the HIV-1 gene from the patient. There was no clear element to delay antibody production on the virus side. Preserved specimens of the patient were measured with eight kinds of HIV screening assay. It was thought that the fourth generation assay was positive only by the presence of the antigen until March 2013 because the antibody had not been detected. Discussion: We encountered a case of acute HIV infection in which the WB result was negative for 10 months after the first positive response of the 4thGIA. The 4thGIA is essential for the early diagnosis and early treatment of HIV infection; therefore, the 4thGIA should be strictly recommended to avoid the use of older generations of immunoassay in the diagnostic guidelines. The role of the WB test should be examined closely from various aspects for use as a confirmatory test under recent laboratory situations in which highly sensitive and specific methods, e.g. the 4th GIA, have become available. In addition, unnecessary confusion due to the diversities of antibody formation should be avoided. The antibody detection tests for HIV are still necessary and indispensable for the confirmation of the disease or the diagnosis of the acute infection stage. Therefore development of a newer antibody measuring method which could achieve an easier operation and should have a higher sensitivity and specificity for HIV confirmation is strongly expected.

Nuclear PRMT1 expression is associated with poor prognosis and chemosensitivity in gastric cancer patients.

BACKGROUND: Metastatic and refractory gastric cancer (GC) are associated with a poor prognosis; therefore, the identification of prognostic factors and chemosensitivity markers is extremely important. Protein arginine methyltransferase 1 (PRMT1) may play a role in chemosensitivity/apoptosis induction via activation of the tumor suppressor forkhead box O1 (FOXO1). The purpose of this study was to clarify the expression of and relationship between PRMT1 and FOXO1 to evaluate the applicability of PRMT1 as a prognostic marker and a therapeutic tool in GC. METHODS: We investigated the clinical and functional significance of PRMT1 and FOXO1 in 195 clinical GC samples using immunohistochemistry. We performed suppression analysis of PRMT1 using small interfering RNA to determine the biological roles of PRMT1 in chemosensitivity. RESULTS: PRMT1 and FOXO1 in GC samples were predominantly expressed in the nucleus. Patients with lower PRMT1 expression (n = 131) had suppressed nuclear accumulation of FOXO1, higher recurrence after adjuvant chemotherapy, and poorer prognosis than those with higher PRMT1 expression (n = 64). PRMT1 downregulation in GC cells by RNA interference inhibited cisplatin and 5-fluorouracil sensitivity. The expression of phosphorylated FOXO1 and phosphorylated BCL-2 antagonist of cell death was upregulated in PRMT1 small interfering RNA groups. CONCLUSION: Our data suggest that the evaluation of PRMT1 expression in GC is a useful predictor of poor prognosis and recurrence after adjuvant chemotherapy. Moreover, these data suggest that PRMT1 is a promising therapeutic tool for overcoming refractory GC.

Outcomes of patients with early gastric cancer who underwent double endoscopic intraluminal surgery.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) has been used to treat patients with nonulcerated early gastric cancers of 2  cm or less, because the incidence of lymph node metastasis is negligible. However, the standard ESD procedure is long, complex, and associated with high complication rates. To overcome these limitations, we devised a double endoscopic intraluminal operation (DEILO) and assessed its efficacy and safety for superficial gastric neoplasms in a preliminary prospective study. METHODS: The DEILO procedure was performed on 101 patients with gastric cancers. Two endoscopes were simultaneously inserted into the stomach. One endoscope was used to lift the lesion, and the other was used to excise the lesion. RESULTS: The DEILO technique was performed successfully, and en bloc resection was achieved for 98 (97.0%) of 101 patients. Histologically curative resection was achieved for 85 lesions (84.2%). The mean operating time was 70 min (range 20-178 min). Perforation occurred in four patients (4.0%), all of whom were successfully treated nonsurgically. Three patients developed postoperative hemorrhage, which was controlled endoscopically. CONCLUSION: The DEILO procedure appears to shorten the operating time for ESD, with efficacy and complication rates comparable with the standard procedure.