A phase II study of neoadjuvant chemotherapy with docetaxel, cisplatin, and S-1, followed by gastrectomy with D2 lymph node dissection for high-risk advanced gastric cancer: results of the KDOG1001 trial.

BACKGROUND: The prognosis of patients with gastric cancer with bulky node metastasis, linitis plastica (type 4), or large ulcero-invasive-type tumors (type 3) remains poor. We conducted a phase II study to evaluate the safety and efficacy of neoadjuvant chemotherapy with docetaxel, cisplatin, and S-1 (DCS) for establishing a new treatment modality that improves prognosis. METHODS: Patients received up to four 28-day cycles of DCS therapy (docetaxel at 40 mg/m2, cisplatin at 60 mg/m2 on day 1, and S-1 at 40 mg/m2 twice daily for 2 weeks) followed by gastrectomy with D2 nodal dissection. S-1 chemotherapy was administered for 1 year after surgical resection. The primary endpoint was the percentage of complete resections of the primary tumor with clear margins (R0 resection). The planned sample size was 40; this was calculated based on an expected R0 rate of 85% and a threshold R0 rate of 65%, with a one-sided alpha of 5% and a power of 90%. RESULTS: Between 2010 and 2017, 40 patients were enrolled. The R0 resection rate was 90%. The most common grade 3 or 4 adverse events during DCS therapy were leukocytopenia (27.5%), neutropenia (55.0%), and hyponatremia (22.5%). The most common grade 3 or 4 surgical morbidity was pancreatic fistula (12.5%); mortality was 0%. The pathological response rate was 57.5% with a grade 3 histological response rate of 8%. CONCLUSIONS: Neoadjuvant chemotherapy with DCS was feasible and showed a sufficient R0 resection rate. A future study with a sufficient follow-up period should confirm survival outcomes.

Effectiveness and safety of endoscopic aspiration mucosectomy and endoscopic submucosal dissection in patients with superficial esophageal squamous-cell carcinoma.

BACKGROUND: Endoscopic submucosal dissection (ESD) has been performed in a high proportion of patients with superficial esophageal squamous-cell carcinoma. Endoscopic aspiration mucosectomy (EAM) is a more straightforward technique that is easier to perform. We retrospectively evaluated the safety and efficacy of EAM and ESD to clarify the advantages and disadvantages of each procedure. METHODS: A total of 374 patients (423 lesions) who underwent endoscopic resection were retrospectively studied. The following variables were evaluated (1) procedure time and adverse events as safety, and (2) en bloc complete resection rate, local recurrence rate, lymph node recurrence rate, overall survival rate, and cause-specific survival rate as efficacy. RESULTS: EAM was performed in 134 patients (149 lesions), and ESD was performed in 240 patients (274 lesions). The procedure times of EAM and ESD were 31.0 ± 22.4 and 85.7 ± 46.5 min (p < 0.001), respectively. The perforation rates were 0 and 6.2% (p = 0.002), respectively. The en bloc complete resection rates were 48.3 and 91.6% (p < 0.001), respectively. The local recurrence rates were 5.5 and 0% (p < 0.001), respectively. For lesions measuring less than 15 mm in diameter, EAM had a relatively good en bloc complete resection rate (EAM, 76.1% vs. ESD, 100%) and a significantly short procedure time (EAM, 25.2 ± 15.2 min vs. ESD, 62.7 ± 35.2 min; p < 0.001). CONCLUSIONS: ESD has a higher en bloc complete resection rate and a better local control rate than EAM. For lesions measuring less than 15 mm in diameter, EAM may be a treatment option.

Comparison of double-flap and OrVil techniques of laparoscopy-assisted proximal gastrectomy in preventing gastroesophageal reflux: a retrospective cohort study.

BACKGROUND: Laparoscopy-assisted proximal gastrectomy (LAPG) with esophagogastrostomy using the double-flap technique has been reported to rarely cause gastroesophageal reflux. However, quantitative evaluation of the reflux has hardly been performed. The aim of this study was to clarify the superiority of the double-flap technique of LAPG with esophagogastrostomy compared with the OrVil technique in terms of preventing gastroesophageal reflux. METHODS: A total of 40 and 51 patients who underwent LAPG with esophagogastrostomy using the double-flap and OrVil techniques, respectively, for upper one-third gastric cancer were included in this study. Of these, 22 and 13 patients in the double-flap and OrVil groups, respectively, consented to undergo a 24-h impedance-pH monitoring test at 3 months postoperatively. Postoperative complications, including gastroesophageal reflux and anastomotic stricture, were assessed retrospectively. RESULTS: No significant differences were observed in the patients' background between both groups, except for a higher D1+ dissection rate observed in double-flap group than in the OrVil group (93% vs 25%, P < 0.001). Operative time was significantly longer in the double-flap group than in the OrVil group (353 min vs 280 min, P < 0.001). All reflux % time was significantly lower in the double-flap group than in the OrVil group (1.29% vs 2.62%, P = 0.043). On the other hand, the proportion of anastomotic stricture requiring endoscopic balloon dilatation was lower in the double-flap group than in the OrVil group but without statistical significance (18% vs 27%; P = 0.32). CONCLUSIONS: Despite its longer operative time and still relatively high anastomotic stricture rate, the double-flap technique would be better than the OrVil technique in terms of preventing gastroesophageal reflux in patients who underwent LAPG with esophagogastrostomy.

Robust vascular invasion concurrent with intense EGFR immunostaining can predict recurrence in patients with stage IB node-negative gastric cancer.

PURPOSE: The prognosis of most patients with stage IB node-negative gastric cancer is good without postoperative chemotherapy; however, about 10% suffer recurrence and inevitably die. We conducted this study to establish the optimal indications for postoperative adjuvant chemotherapy in patients at risk of recurrence. METHODS: The subjects of this retrospective study were 124 patients with stage IB node-negative gastric cancer, who underwent gastrectomy at the Kitasato University East Hospital, between 2001 and 2010. We reviewed EGFR immunohistochemistry (IHC) as well as clinicopathological factors. RESULTS: Of the 124 patients, 47 (38%) showed intense EGFR IHC (2+ or 3+), with significantly less frequency than in stage II/III advanced gastric cancer (p < 0.001). According to univariate analysis, intense EGFR IHC was significantly associated with relapse-free survival (RFS) (p = 0.023) and associated with overall survival (OS) (p = 0.045) as well as vascular invasion (p = 0.031). On the multivariate Cox proportional hazards model, intense EGFR IHC(p = 0.016) was an independent prognostic predictor for RFS, and both vascular invasion (p = 0.033) and intense EGFR IHC (p = 0.031) were independent prognostic predictors for OS. The combination of both factors increased the risk of recurrence (p = 0.001). CONCLUSIONS: In stage IB node-negative gastric cancer, vascular invasion and intense EGFR IHC increase the likelihood of recurrence. We recommend adjuvant chemotherapy for such patients because of the high risk of metachronous recurrence.

Prognostic Advantage of Docetaxel/Cisplatin/ 5-Fluorouracil Neoadjuvant Chemotherapy in Clinical Stage II/III Esophageal Squamous Cell Carcinoma due to Excellent Control of Preoperative Disease and Postoperative Lymph Node Recurrence.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has become prevalent in esophageal squamous cell carcinoma (ESCC), but its long-term prognostic advantages remain unclear. The latest prognostic outcomes in clinical Stage (cStage) II/III ESCC with NAC were herein elucidated. PATIENTS AND METHODS: NAC prior to curative treatment was done in 115 cStage II/III ESCC patients with either cisplatin (CDDP)/5-fluorouracil (5-FU; CF) (n = 41) or docetaxel/CDDP/5-FU (DCF) NAC (n = 74) between 2007 and 2013. RESULTS: (1) Esophagectomy was finally performed in 35 of the 41 CF NAC cases and in 48 of the 74 DCF NAC cases. The preservation rate of the esophagus was higher in the DCF NAC than in the CF NAC (p = 0.018). (2) The overall survival was better in DCF NAC than in CF NAC (p = 0.071), and progression-free survivals were 58.3% with DCF and 30.5% with CF (p = 0.0060). DCF NAC was associated with fewer cases of progression than CF NAC (p = 0.0040), largely due to excellent control of the preoperative disease (p = 0.018) and postoperative lymph node recurrence (p = 0.014). CONCLUSION: DCF NAC in cStage II/III ESCC could have a great potential to achieve a better prognosis due to suppression of specific progression events with a higher preservation rate of the esophagus.

DNA diagnosis of peritoneal fluid cytology test by CDO1 promoter DNA hypermethylation in gastric cancer.

BACKGROUND: Minimal residual disease of the peritoneum is challenging for early cancer detection in gastric cancer (GC). Utility of PCR amplification of cancer-derived DNA has been considered feasible due to its molecular stability, however such markers have never been available in GC clinics. We recently discovered cancer-specific methylation of CDO1 gene in GC, and investigated the clinical potential to detect the minimal residual disease. METHODS: One hundred and two GC patients were investigated for peritoneal fluid cytology test (CY), and detection level of the promoter DNA methylation of CDO1 gene was assessed by quantitative methylation specific PCR (Q-MSP) in the sediments (DNA CY). RESULTS: (1) CY1 was pathologically confirmed in 8 cases, while DNA CY1 was detected in 18 cases. All 8 CY1 were DNA CY1. (2) DNA CY1 was recognized in 14.3, 25.0, 20.0, and 42.9%, in macroscopic Type II, small type III, large type III, and type IV, respectively, while it was not recognized in Type 0/I/V. (3) DNA CY1 was prognostic relevance in gastric cancer (p = 0.0004), and its significance was robust among Type III/IV gastric cancer (p = 0.006 for overall survival and p = 0.0006 for peritoneal recurrence free survival). (4) The peritoneal recurrence was hardly seen in GC patients with potent perioperative chemotherapy among those with DNA CY1. CONCLUSIONS: DNA CY1 detected by Q-MSP for CDO1 gene promoter DNA methylation has a great potential to detect minimal residual disease of the peritoneum in GC clinics as a novel DNA marker.

Promoter DNA methylation of CDO1 gene and its clinical significance in esophageal squamous cell carcinoma.

We have demonstrated that CDO1 methylation is frequently found in various cancers, including esophageal squamous cell carcinoma (ESCC), but its clinical relevance has remained elusive. CDO1 methylation was investigated in 169 ESCC patients who underwent esophagectomy between 1996 and 2007. CDO1 methylation was assessed by Q-MSP (quantitative methylation specific PCR), and its clinical significance, including its relationship to prognosis, was analyzed. (i) The median TaqMeth value of CDO1 methylation was 9.4, ranging from 0 to 279.5. CDO1 methylation was significantly different between cStage I and cStage II/III (P = 0.02). (ii) On the log-rank plot, the optimal cut-off value was determined to be 8.9; ESCC patients with high CDO1 methylation showed a significantly worse prognosis than those with low CDO1 methylation (P = 0.02). (iii) A multivariate Cox proportional hazards model identified only CDO1 hypermethylation as an independent prognostic factor (HR 2.00, CI 1.09-3.78, P = 0.03). (iv) CDO1 hypermethylation stratified ESCC patients' prognosis in cStage II/III for both neoadjuvant chemo(radio)therapy (NAC)-positive and NAC-negative cases. Moreover, the CDO1 methylation level was significantly lower in cases with Grade 2/3 than in those with Grade 0/1 (P = 0.02) among cStage II/III ESCC patients with NAC. Promoter DNA hypermethylation of CDO1 could be an independent prognostic factor in ESCC; it may also reflect NAC eradication of tumor cells in the primary tumors.

Conversion surgery after combination chemotherapy of docetaxel, cisplatin and S-1 (DCS) for far-advanced gastric cancer.

PURPOSE: A triplet regimen of docetaxel, cisplatin, and S-1(DCS) is highly effective against metastatic gastric cancer. We performed this study to clarify the safety and efficacy of surgical resection in patients with initially unresectable gastric cancer, after down-staging or disease control was achieved by DCS chemotherapy. METHODS: The subjects of this retrospective study were 31 consecutive patients with initially unresectable gastric cancer, who underwent surgical resection between October, 2006 and December, 2012, after down-staging or disease control was achieved by DCS chemotherapy. We evaluated the clinicopathological factors and clinical outcomes and assessed radiographic response based on the RECIST criteria, not by central review. RESULT: Before DCS chemotherapy, 18 patients had extra-regional lymph node metastasis, 5 had liver metastasis, 8 had macroscopic peritoneal metastasis, and 8 had pancreatic head invasion. Twenty-three (74.2%) of the 31 patients underwent R0 resection. Postoperative morbidity and mortality rates were 16.1 and 0%. During chemotherapy, grade 3/4 toxicities included neutropenia (54.8%), leukopenia (32.3%), and anemia (16.1%). Median progression-free survival and median overall survival (OS) were 42.1 and 56.1 months, respectively. These results were similar for all patients, except those with locally advanced disease alone. In the multivariate analysis for OS, ypN remained an independent negative prognostic factor (p = 0.018). CONCLUSION: Surgical resection after DCS chemotherapy for initially unresectable gastric cancer was safe and provided a reasonable R0 resection rate and good mid-term survival.

Potential benefits of laparoscopy-assisted proximal gastrectomy with esophagogastrostomy for cT1 upper-third gastric cancer.

BACKGROUND: Few reports have compared laparoscopy-assisted proximal gastrectomy (LAPG) with laparoscopy-assisted total gastrectomy (LATG) in patients with cT1N0 gastric cancer. This study assessed the safety and feasibility of LAPG with esophagogastrostomy in these patients and compared postgastrectomy disturbances and nutritional status following LAPG and LATG. METHODS: This study compared 40 patients who underwent LAPG with esophagogastrostomy and 59 who underwent LATG with esophagojejunostomy, both with OrVil™. Surgical outcomes, postoperative complications, nutritional status at 1 and 2 years, and relapse-free survival were compared in these two groups. RESULTS: Operation time was significantly shorter in the LAPG group than in the LATG group (280 min vs. 365 min, P < 0.001). Although the rate of surgical complications was similar in the two groups, the rate of anastomotic stricture was significantly higher in the LAPG group than in the LATG group (28 vs. 8.4 %; P = 0.012). Rates of reflux esophagitis graded A or higher in the Los Angeles classification were 10 and 5.1 %, respectively. Hemoglobin levels 2 years after surgery, relative to baseline levels, were significantly higher in the LAPG group than in the LATG group (98.6 vs. 92.9 %, P = 0.020). Body weight, albumin and total protein concentrations, and total lymphocyte count 1 and 2 years after surgery were slightly, but not significantly, higher in the LAPG group. Relapse-free survival rates were similar, as were 5-year overall survival rates (86 vs. 79 %, P = 0.42). CONCLUSIONS: LAPG with esophagogastrostomy using OrVil™ was safe and feasible for patients with cT1N0 gastric cancer. LAPG may have nutritional advantages over LATG, but the rate of anastomotic stricture was significantly higher for LAPG than for LATG.

Long-term prognostic outcome of cT1 gastric cancer patients who underwent laparoscopic gastrectomy after 5-year follow-up.

PURPOSE: We have reported that short-term and middle-term clinical outcomes including prognosis after laparoscopy-assisted gastrectomy (LAG) are excellent in cT1 gastric cancer. METHODS: In this study, long-term prognosis was finally confirmed in detail in 491 cT1 gastric cancer patients who underwent LAG between 1998 and 2010, where clinical course was completely pursued for recurrent cases. RESULTS: Among the 491 cases, follow-up examination at 5 years (60 months) after operation was done in 423 (86.2 %). Recurrent cases were seen in nine cases (1.8 %) who inevitably died despite aggressive multimodality treatments. The initial recurrent sites were the peritoneum in three, the liver in two, the bone in one, the ovary in one, the liver/bone in one, and the Virchow lymph node/bone in one. As a result, the 5-year disease-specific survival (DSS) was 98.3 %. cT1 gastric cancer was finally diagnosed as pathological stages IA to III, and the 5-year DSS was 99.7 % in pathological stage IA, 96.9 % in pathological stage IB, and 81 % in pathological stage II/III. The initial recurrent sites were the liver/bone in stage IA (M/N0), the liver in stage IB (MP/N0), the liver in stage IIA (MP/N1), the liver and the ovary in two stages IIB (T1N3), 3 peritoneum and 1 Virchow lymph node/bone in four stage III cases. Importantly, there were no initial recurrences in the regional lymph node, and all recurrences were seen within 5 years after operation. CONCLUSIONS: Although long-term prognostic outcome was extremely good in cT1 gastric cancer patients who underwent LAG, cases with recurrence inevitably died due to disease progression.

Laparoscopic versus open distal gastrectomy for early gastric cancer in Japan: long-term clinical outcomes of a randomized clinical trial.

PURPOSE: We report the long-term clinical outcomes of a randomized clinical trial comparing laparoscopy-assisted distal gastrectomy (LADG) with open DG (ODG). METHODS: Between 2005 and 2008, 63 patients with clinical T1 (cT1) gastric cancer were randomly assigned to undergo either LADG or ODG. Long-term clinical outcomes included prospective questionnaire-based symptoms and survival. RESULTS: Based on the responses to the prospective questionnaires, patients who underwent LADG reported greater satisfaction and were more likely to favor the procedure than those who underwent ODG. The most notable difference in symptoms was related to wound pain and diarrhea. After ODG, wound pain reduced in intensity but persisted throughout the follow-up. Surprisingly, diarrhea was more frequent after LADG than after ODG, possibly due to overeating, because symptoms elicited by overeating, such as vomiting after a meal or heartburn, were also more frequent after LADG. In terms of long-term survival, there were no cases of recurrence in either group. CONCLUSIONS: LADG was associated with less wound pain during long-term follow-up after surgery, whereas symptoms related to overeating were common. Based on our findings and the patients' reported satisfaction, we recommend LADG for cT1 gastric cancer as an effective procedure with excellent long-term survival.

Prognostic impact of venous invasion in stage IB node-negative gastric cancer.

BACKGROUND: Little is known about risk factors for recurrence in stage IB gastric cancer without lymph node metastasis. The aims of this study were to determine prognostic factors associated with long-term survival and to clarify patterns of recurrence. METHODS: We retrospectively reviewed the medical records of 130 patients with primary gastric cancer who underwent gastrectomy at Kitasato University East Hospital from 2001 through 2010 and analyzed clinicopathological characteristics associated with survival and patterns of recurrence. RESULTS: Of the 130 patients, 12 (9.2%) had recurrence, among whom 10 (83%) patients died. Four patients (3.1%) died of other diseases. The 5-year overall survival rate was 89%. Of the 12 patients with recurrence, 7 (58%) had liver metastasis, 3 (25%) had distant lymph-node metastasis, 2 (17%) had peritoneal dissemination, and 1 (8.3%) had locoregional recurrence. Patients with tumors more than 5 cm in diameter tended to have recurrence within 1 year. Patients who had recurrence more than 2 years after surgery tended to survive for longer than 5 years after recurrence. Moderate or marked venous invasion (v2 or v3) and age >65 years were significantly associated with relapse-free and overall survival on univariate analysis. On multivariate analysis, the only independent prognostic factor for relapse-free and overall survival was venous invasion. CONCLUSIONS: Moderate or marked venous invasion (v2 or v3) is an independent predictor of relapse-free and overall survival in stage IB node-negative gastric cancer. Postoperative adjuvant chemotherapy, currently not given to this subgroup of patients, may improve the outcomes of patients with stage IB node-negative gastric cancer, particularly when accompanied by venous invasion.

A preliminary study on pre-operative tumor volumetry measured by three-dimensional computer tomography in gastric cancer.

BACKGROUND/AIMS: The aim of the present study was to evaluate the clinical significance of tumor volumetry measured by three-dimensional (3-D) multidetector row computed tomography (MD-CT). METHODOLOGY: A total of 50 patients with gastric cancer who had undergone pre-operative tumor volumetry using 3D-MD-CT followed by subsequent laparotomy (11 women, 39 men; mean age 63.9 years) were examined. Tumor volume and conventional clinicopathological factors were studied and then analyzed with respect to survival. RESULTS: Tumor volume was distributed widely and ranged from 0.16 cm3 to 363.5 cm3 with a mean of 43.6 cm3 (<10 cm3, 21 tumors; ≥10 cm3, 29 tu- mors). Significant differences in survival were found for volume (<10.0 cm3 vs. ≥10.0 cm3; p=0.0414), and depth of invasion (T1-2 vs. T3-4; p=0.0475), but not for diameter (<50 mm vs. ≥50 mm; p=0.2142), location (proximal third vs. middle or distal third; p=0.3254), macroscopic type (localized vs. invasive; p=0.3619), or microscopic type (differentiated vs. undifferentiated; p=0.1230). CONCLUSIONS: The present findings suggest that tumor volume measured by pre-operative 3D-MD-CT offers an alternative indicator for determining the prognosis in gastric cancer.

Preoperative tumor size is a critical prognostic factor for patients with Borrmann type III gastric cancer.

PURPOSE: This study was designed to clarify whether preoperative tumor size is an independent prognostic factor (IPF) for patients with Borrmann type III gastric cancer. METHODS: The study group comprised 350 patients with Borrmann type III gastric cancer. We performed a log-rank plot analysis to establish the threshold value of preoperative tumor size for the prediction of overall survival (OS). Factors with P < 0.10 on univariate prognostic analyses for OS were put into a Cox's proportional hazards model to identify the IPFs. RESULTS: Peritoneal lavage cytology (CY) was the strongest IPF for patients with Borrmann type III gastric cancer (P < 0.0001). We were able to measure the tumor size preoperatively in 135 patients with negative CY results (CY0). The cutoff tumor size for the prediction of OS was 5.3 cm. A Cox's proportional hazards model showed that pathological lymph-node metastasis (P = 0.007) and preoperative tumor size (P = 0.018) were significant IPFs in the CY0 patients. Patients with a preoperative tumor size of <5.3 cm had satisfactory outcomes, with a 5-year OS rate of >80 %. CONCLUSIONS: Preoperative tumor size is an IPF for patients with Borrmann type III gastric cancer and CY0. Thus, preoperative tumor size may be a useful factor for deciding on whether neoadjuvant chemotherapy is indicated.

Immunohistochemical analysis of RTKs expression identified HER3 as a prognostic indicator of gastric cancer.

Standard treatment in Japan for the 13th Japanese Gastric Cancer Association stage II/III advanced gastric cancer is postoperative adjuvant S-1 administration after curative surgery. High expression of receptor type tyrosine kinases (RTKs) has repeatedly represented poor prognosis for cancers. However it has not been demonstrated whether RTKs have prognostic relevance for stage II/III gastric cancer with standard treatment. Tumor tissues were obtained from 167 stage II/III advanced gastric cancer patients who underwent curative surgery and received postoperative S-1 chemotherapy from 2000 to 2010. Expression of the RTKs including EGFR, HER2, HER3, IGF-1R, and EphA2 was analyzed using immunohistochemistry (IHC). Analysis using a multivariate proportional hazard model identified the most significant RTKs that represented independent prognostic relevance. When tumor HER3 expression was classified into IHC 1+/2+ (n = 98) and IHC 0 (n = 69), the cumulative 5-year Relapse Free Survival (5y-RFS) was 56.5 and 82.9%, respectively (P = 0.0034). Significant prognostic relevance was similarly confirmed for IGF-1R (P = 0.014), and EGFR (P = 0.030), but not for EphA2 or HER2 expression. Intriguingly, HER3 expression was closely correlated with IGF-1R (P < 0.0001, R = 0.41), and EphA2 (P < 0.0001, R = 0.34) expression. Multivariate proportional hazard model analysis identified HER3 (IHC 1+/2+) (HR; 1.53, 95% CI, 1.11-2.16, P = 0.0078) as the sole RTK that was a poor prognostic factor independent of stage. Of the 53 patients who recurred, 40 patients (75.5%) were HER3-positive. Thus, of the RTKs studied, HER3 was the only RTK identified as an independent prognostic indicator of stage II/III advanced gastric cancer with standard treatment.

Multimodality Treatment and Prognosis in Esophageal Squamous Cell Carcinoma Requiring Esophagectomy.

BACKGROUND/AIMS: MuItimodality treatment improves esophageal squamous cell carcinoma (ESCC) prognosis, however the most optimal treatment still remains controversial. METHODOLOGY: In 213 ESCC patients who had operation at Kitasato University Hospital between 1996 and 2007, prognosis was evaluated in terms of cStage and adjuvant therapy. RESULTS: Survival outcome of with the 62 cStage I ESCC were excellent (2 recurrences) with infrequent postoperative treatment (Adj). Of 129 ESCC patients with cStage II/III, 45 patients including suspicious cT4 (cT3.5) were given neoadjuvant therapy (Neo), and pStage 0/I patients showed excellent prognosis. Of 84 cStage II/III patients not given Neo, 67 (79.8%) underwent R0 esophagectomy, among whom 20 cases had pN0 (pStage II/IIa) with 3 recurrences (15%) despite infrequent Adj. On the other hand, among the 45 cStage II/III patients with Neo, 8 pStage IIa patients exhibited poor prognosis with 5 recurrences (62.5%) as well as pStage III/IV. In pStage IIb ESCC, cStage IIa showed poorer prognosis than cStage I/IIb (P = 0.0072). Among the 21 cStage IV ESCC patients, 5 long-term survivors were experienced by multimodality treatments. CONCLUSIONS: Both cStage and Neo greatly affect ESCC prognosis irrespective of identical pStage, which must be allowed for in order to determine therapeutic strategy against ESCC.

Comparison of the Heller-Toupet procedure with the Heller-Dor procedure in patients who underwent laparoscopic surgery for achalasia.

PURPOSE: We compared the outcomes of Toupet fundoplication with those of Dor fundoplication in patients with achalasia who underwent laparoscopic Heller myotomy. METHODS: Seventy-two patients with achalasia and dysphagia underwent laparoscopic Heller myotomy with fundoplication performed by a single surgeon. Heller-Toupet fundoplication (HT) was performed in 30 patients, and Heller-Dor fundoplication (HD) was done in 42. The symptoms and esophageal function were retrospectively assessed in both groups. RESULTS: The dysphagia scores significantly decreased after both the HT and HD procedures, and did not differ significantly between them. The incidence of reflux symptoms was significantly higher after HT (26.7%) than after HD (7.1%). The lower esophageal sphincter (LES) resting pressure significantly decreased after both HT and HD. Upon endoscopic examination, the incidence of reflux esophagitis was significantly higher after HT (38.5%) than after HD (8.8%). During esophageal pH monitoring, the fraction time at pH <4 was similar in the patients who underwent HT and HD. CONCLUSIONS: Laparoscopic Heller myotomy provided significant improvements in the dysphagia symptoms of achalasia patients, regardless of the type of fundoplication. The incidences of reflux symptoms and reflux esophagitis were higher after HT than after HD. However, the results of pH monitoring did not differ between the procedures.

Laparoscopic antireflux surgery improves esophageal body motility in patients with severe reflux esophagitis.

PURPOSE: This study was designed to clarify whether laparoscopic antireflux surgery (LARS) improves the esophageal body motility (EBM) in patients with reflux esophagitis. METHODS: Thirty-five patients with gastroesophageal reflux disease (GERD) scheduled to undergo LARS were divided into a mild esophagitis group (ME; n = 18, Grade O:A:B = 7:10:1) and a severe esophagitis group (SE; n = 17, Grade C:D = 13:4), according to the Los Angeles classification of reflux esophagitis. The types of fundoplication (Nissen/Toupet) were 6/12 in the ME group and 4/13 in the SE group. Esophageal pH monitoring and manometry were performed before and 1 year after surgery. RESULTS: The fraction time of a pH below 4 significantly decreased after surgery in both groups. The LES pressures did not change significantly after surgery in the ME group, but significantly increased in the SE group. The peristaltic amplitudes 18 and 13 cm above the LES did not change significantly after surgery in either group. The peristaltic amplitudes 8 and 3 cm above the LES did not change significantly after surgery in the ME group, but significantly increased after surgery in the SE group. CONCLUSIONS: The preoperative EBM was not improved by LARS in patients with GERD and mild mucosal breaks in the esophagus, but the preoperative middle to distal EBM was improved by LARS in patients with GERD and severe mucosal breaks.

The impact of meropenem shortage and post-prescription review and feedback on broad-spectrum antimicrobial use: An interrupted time-series analysis.

Background: Meropenem (MEPM) holds significance in treating severe infections and drug-resistant bacteria. There are concerns that antimicrobial shortages may lead to the use of alternative antimicrobials that are less effective and safer. We have responded to the MEPM shortage with post-prescription monitoring and feedback (PPRF) with no restrictions on MEPM initiation. We aimed to assess the impact of the MEPM shortage and the PPRF on broad-spectrum antimicrobial use and mortality. Methods: This retrospective study was conducted in a single hospital in Japan. The period from October 2021 to August 2022 was defined as the period before the MEPM shortage, and the period from September 2022 to March 2023 was defined as the period during the MEPM shortage. To support the appropriate use of antimicrobials during MEPM shortages, the antimicrobial stewardship team (AST) developed a list of alternatives to MEPM. An interrupted time series analysis was used to assess changes in use and mortality among patients receiving broad-spectrum antimicrobials over the study period. Discussion: The shortage of MEPM and PPRF temporarily increased the use of alternative cefepime; however, the subsequent change in days of therapy and days of coverage of broad-spectrum antimicrobials suggests a decrease in the use of these antimicrobials. Despite these shifts, the mortality rates remained stable, suggesting that the response to the shortage did not adversely affect treatment outcomes. Conclusion: In the context of antimicrobial shortages, AST support plays an important role in enabling physicians to make optimal use of antimicrobials.

Analysis of the Factors That Affect the Detection Duration of SARS-CoV-2 in Loop Mediated Isothermal Amplification among COVID-19 Inpatients.

In COVID-19 patients who are immunocompromised or have severe COVID-19, the duration of infectious viral shedding may be longer, and a longer isolation duration is recommended. At the National Sagamihara Hospital, a decline in the viral load to end the isolation of hospitalized patients with COVID-19 was confirmed using loop-mediated isothermal amplification (LAMP). However, a subset of patients displayed LAMP positivity for more than 20 days after symptom onset. Therefore, we conducted a retrospective observational study to investigate the factors that affect the persistence of LAMP positivity. This study included a total of 102 participants. The severity of COVID-19 was mild (25.5%), moderate (67.6%), or severe (6.9%). The median number (interquartile range) of days until negative LAMP results from symptom onset were 16 (14-19) days. Multivariate logistic regression analysis showed that patients ≥55 years and/or those with the delta variant were correlated with persistent LAMP positivity for more than 20 days after symptom onset. This study identified age, the delta variant, and oxygen requirement as factors that contribute to persistently positive LAMP results. Therefore, it is posited that in these patients, the implementation of LAMP for deisolation would result in a prolonged isolation duration.