Prognostic Role of Preoperative Chemotherapy in Liver-Limited Metastasis from Gastric Cancer.

BACKGROUND: We investigated the prognostic role of preoperative chemotherapy in patients who underwent hepatectomy for liver-limited metastasis (LLM) from gastric cancer (GC). METHODS: A retrospective analysis was conducted for 52 consecutive patients who underwent macroscopically complete (R0 or R1) resection for synchronous or metachronous LLM from GC. RESULTS: Of the 52 patients, 18 (35%) received preoperative chemotherapy (PC group), while 34 (65%) underwent upfront surgery (US group). The PC group had a significantly longer overall survival than the US group (cumulative 5-year OS rate: 47.6% vs. 24.8%, p = 0.041). Multivariate analysis of OS revealed that preoperative chemotherapy was an independent favorable prognostic factor (hazard ratio: 0.445, p = 0.036). Patients showing a partial response to preoperative chemotherapy on RECIST had an improved OS compared with those exhibiting stable or progressive disease after preoperative chemotherapy and with US (p = 0.025), even among those with solitary LLM (p = 0.062) and multiple LLM (p = 0.026). At recurrence after hepatectomy for LLM, the PC group had a significantly higher incidence of solitary tumors than the US group (p = 0.043) and had a higher chance to undergo surgical resection for recurrent sites (p = 0.006). CONCLUSIONS: Preoperative chemotherapy can be recommended for patients with LLM from GC. The evaluation of the efficacy of preoperative chemotherapy offers additional information to determine the surgical indication for LLM.

Clinical application of targeted tumour sequencing tests for detecting ERBB2 amplification and optimizing anti-HER2 therapy in gastric cancer.

BACKGROUND: Evaluation of human epidermal growth factor receptor 2 (HER2) overexpression caused by erb-b2 receptor tyrosine kinase 2 (ERBB2) amplification (AMP) by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) is essential for treating unresectable metastatic gastric cancer (GC). A targeted tumour sequencing test enables comprehensive assessment of alterations in cancer-related genes, including ERBB2. This study aimed to evaluate the concordance between the targeted tumour sequencing test and IHC/FISH for detecting HER2-positive GC and to clarify the significance of ERBB2 AMP and concomitant genetic alterations in HER2 downstream pathways (DPs) in anti-HER2 therapy for unresectable metastatic GC patients. METHODS: ERBB2 copy number alteration (CNA) was examined via a targeted tumour sequencing test in 152 formalin-fixed paraffin-embedded (FFPE) GC tissues. ERBB2 CNA was compared to HER2 status evaluated by IHC/FISH in FFPE block sections, which were identical to those subjected to the targeted tumour sequencing test. Treatment outcomes of anti-HER2 therapy in 11 patients with unresectable metastatic GC was evaluated. RESULTS: ERBB2 AMP (≥ 2.5-fold change) was detected by the targeted tumour sequencing test in 15 patients (9.9%), and HER2 positivity (IHC 3 + or IHC 2+/FISH positive) was detected in 21 patients (13.8%). The overall percent agreement, positive percent agreement, negative percent agreement and Cohen's kappa between ERBB2 CNA and HER2 status were 94.7%, 66.7%, 99.2% and 0.75, respectively. Progression-free survival for trastuzumab therapy in patients with ERBB2 AMP was significantly longer than that in patients with no ERBB2 AMP detected by the targeted tumour sequencing test (median 14 months vs. 4 months, P = 0.007). Treatment response to trastuzumab therapy was reduced in patients with ERBB2 AMP and concomitant CNAs of genes in HER2 DPs. One patient with ERBB2 AMP and concomitant CNAs of genes in HER2 DPs achieved a durable response to trastuzumab deruxtecan as fourth-line therapy. CONCLUSIONS: A targeted tumour sequencing test is a reliable modality for identifying HER2-positive GC. ERBB2 AMP and concomitant genetic alterations detected through the targeted tumour sequencing test are potential indicators of treatment response to trastuzumab therapy. The targeted tumour sequencing test has emerged as a plausible candidate for companion diagnostics to determine indications for anti-HER2 therapy in the era of precision medicine for GC.

Macroscopic type is implicated in the prognostic impact of initial chemotherapy on peritoneal lavage cytology-positive gastric cancer with no other noncurative factors.

BACKGROUND: Initial chemotherapy (Initial-C) followed by surgery is a promising treatment strategy for peritoneal lavage cytology-positive gastric cancer (CY1 GC) with no other noncurative factors. The aim of this study was to investigate the survival advantage of Initial-C compared to initial surgery (Initial-S) for this disease according to the macroscopic type, which was associated with prognosis and the efficacy of chemotherapy in GC. METHODS: One hundred eighty-nine patients who were diagnosed with CY1 GC with no other noncurative factors at four institutions from January 2007 to December 2018 were enrolled. The patients were divided into a macroscopic type 4 group (N = 48) and a non-type 4 group (N = 141). The influence of initial treatment on overall survival (OS) in each group was evaluated. RESULTS: In the type 4 group, the 5-year OS rates of Initial-C (N = 35) and Initial-S (N = 13) were 11.6% and 0%, respectively (P = 0.801). The multivariate analysis could not show the survival advantage of Initial-C. In the non-type 4 group, the 5-year OS rates of Initial-C (N = 41) and Initial-S (N = 100) were 48.4% and 29.0%, respectively (P = 0.020). The multivariate analysis revealed that Initial-C was independently associated with prolonged OS (hazard ratio, 0.591; 95% confidence interval, 0.375-0.933: P = 0.023). CONCLUSIONS: Initial-C improves the prognosis of non-type 4 CY1 GC with no other noncurative factors. On the other hand, further development of effective chemotherapeutic regimens and innovative treatment strategies are required for type 4 CY1 GC.

Predictive significance of surgery-induced lymphopenia on the survival after curative resection for locally advanced gastric cancer: a retrospective cohort analysis.

BACKGROUND: Following the establishment of the anti-cancer effect of immune checkpoint inhibitors, lymphopenia has attracted attention as a parameter of preexisting cancer-related immune tolerance. Although the pretreatment absolute lymphocyte count (ALC) has been reported as a prognostic factor in gastric cancer patients, the impact of perioperative changes in the ALC remains unknown. The aim of the present study was to explore the relationship between surgery-induced lymphopenia and outcome. METHODS: Database entries for 584 patients who underwent curative resections for pathological Stage IB-III gastric cancer were reviewed. We retrospectively compared clinicopathological factors including pretreatment ALC (pre-ALC) and ALC at first visit after discharge (post-ALC) with the survival. The low ALC was defined as < 1000/µL. RESULTS: The ALC decreased significantly at 1 and 3 days after surgery and then recovered to the baseline value. A low pre-ALC (p < 0.001) and a low post-ALC (p < 0.001) were both correlated with a poor relapse-free survival (RFS). A multivariate analysis of RFS identified a low post-ALC (hazard ratio 1.875, 95% CI 1.156-3.402, p = 0.01), age, gender, BMI, T disease, N disease, severe vessel invasion, type of gastrectomy and postoperative morbidity as independent factors. The low post-ALC group had a poor RFS among patients with Stage II (p = 0.04) and Stage III (p = 0.04) disease, but not among patients with Stage IB disease (p = 0.13). Consistently, the overall survival (OS) rate was significantly lower among patients with a low post-ALC for all stage (p < 0.001), stage II (p = 0.02) and stage III (p = 0.01) disease, not for stage IB (p = 0.09). A low post-ALC was identified as an independent factor for predicting OS by multivariate analysis (hazard ratio: 2.275, 95% CI 1.373-3.769, p = 0.01). CONCLUSIONS: A decrease in post-ALC was correlated with both of RFS and OS after curative resection in patients with locally advanced gastric cancer. HIGHLIGHTS: Postoperative lymphopenia was a poor prognostic factor for gastric cancer.

A comparison of the effects of anti-reflux procedures during esophagogastrostomy after proximal gastrectomy on the postoperative quality of life.

PURPOSE: To investigate the postoperative quality of life (QOL) in patients with proximal gastric cancer (PGC) or esophago-gastric junction cancer, a nationwide multi-institutional study (PGSAS NEXT trial) was conducted. METHODS: Patients who had undergone radical resection more than 6 months previously were enrolled from 70 Japanese institutions between July 2018 and June 2020. The Postgastrectomy Syndrome Assessment Scale (PGSAS)-45 questionnaire was distributed to eligible patients, and responses were collected by mail. The main outcome measures of the PGSAS-45 were then calculated and compared. RESULTS: Questionnaires were retrieved from 1950 participants, and data from 300 patients who had undergone a proximal gastrectomy (PG) with esophagogastrostomy for PGC were analyzed. The mean esophageal reflux subscale value was 1.9 among the 276 patients who underwent an anti-reflux procedure, which was significantly better than the mean value (2.6) for the 21 patients who did not undergo an anti-reflux procedure (p = 0.002). The esophageal reflux subscale values were also compared among 3 major anti-reflux procedures: the double-flap technique (N = 153), the pseudo-fornix and/or His angle formation (N = 67), and fundoplication (N = 44); no statistically significant differences were observed. CONCLUSION: An anti-reflux procedure during esophagogastrostomy after PG for PGC is necessary to improve postoperative esophageal reflux symptoms, regardless of the type of procedure. TRIAL REGISTRATION: The PGSAS NEXT study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; registration number: 000032221).

Intracorporeal hand-sewn anastomosis following pylorus-preserving gastrectomy: surgical technique and short-term surgical outcome.

BACKGROUND: Although several procedures for mechanical anastomosis have recently been reported, intracorporeal manually hand-sewn anastomosis for totally laparoscopic pylorus-preserving gastrectomy (TLPPG) is considered technically difficult. Here, we report a new technique for laparoscopic reconstruction using hand-sewn sutures. METHODS: Together with a proper lymphadenectomy, the stomach was detached and resected using separate two-layer incisions, similar to the original laparotomy method. An approximately 5-cm antral cuff was left in place. The essential concept of this new method was to align the anastomotic site by rotating each clamped gastric stump. This allowed us to perform a secure, hand-sewn, two-layer anastomosis successfully. The short-term surgical outcome after TLPPG was retrospectively compared with that for patients who underwent a conventional laparoscopy-assisted procedure (LAPPG). RESULTS: Of the 20 consecutive patients who underwent pylorus-preserving gastrectomy in our department between 2014 and 2021, the first 8 patients and the subsequent 12 patients underwent LAPPG and TLPPG, respectively. The operation time was significantly longer in the TLPPG group (median, 302 vs. 269 min). The morbidity was comparable (8.3% in TLPPG vs. 12.5% in LAPPG). Postoperative delayed gastric emptying was only observed in one patient in the LAPPG group. TLPPG reduced the cost of the operation by reducing the number of linear stapler cartridges required. CONCLUSION: A purely hand-sewn gastrogastrostomy is safe, feasible, and cost-effective, and it omits the need for a mini-laparotomy in the upper abdomen.

Simple modifications of conventional esophagogastrostomy after proximal gastrectomy adequately reduces the postoperative reflux esophagitis: a retrospective analysis of posterolateral fundoplication.

PURPOSE: While proximal gastrectomy is being performed increasingly frequently for the treatment of gastric cancer, a standard reconstruction method to obtain optimal postoperative quality of life (QOL) still remains to be established. We modified the original esophagogastrostomy technique by introducing an additional posterolateral fundoplication (PLF) technique to minimize the risk of reflux esophagitis in patients undergoing proximal gastrectomy. The aim of this study was to clarify the clinical benefit of PLF. METHODS: A retrospective analysis of the database was conducted to evaluate the effects of PLF. The data were compared between 44 patients in whom PLF was performed (PLF group) and 17 patients in whom conventional esophagogastrostomy without PLF was performed (C group). A number of incidence of postoperative reflux esophagitis and symptoms were assessed by findings of endoscopic examination and the PGSAS-45 questionnaire, respectively. RESULTS: The incidence of grade B or worse esophagitis after surgery was significantly lower in the PLF group than in the C group (0% vs. 58.8%, P < 0.01). The score for the esophageal reflux subscale, as the main outcome measure of PGSAS-45, was significantly better in the PLF group (PLF: 1.5 vs C: 2.4, P < 0.01). Cohen's d value was 1.75, which suggested a rather large effect size. Postoperative benign anastomotic stricture was encountered in 10 cases (22.7%) of the PLF group and 4 cases (23.5%) of the C group, all of whom were successfully treated by brief endoscopic mechanical dilatation. CONCLUSION: PLF is an expedient procedure for reconstruction after proximal gastrectomy.

Conversion surgery for stage IV gastric cancer: a multicenter retrospective study.

BACKGROUND: Recent improvements in systemic chemotherapy have provided an opportunity for patients with stage IV gastric cancer (GC) to undergo conversion surgery (CS). The aim of this study was to evaluate the long-term outcomes of patients who underwent CS and to elucidate the prognostic factors for CS in stage IV GC. METHODS: A total of 79 patients who underwent CS with the aim of R0 resection for stage IV GC at six institutions from January 2008 to July 2019 were enrolled. We retrospectively reviewed the clinicopathological data and prognosis. RESULTS: Of the 79 patients, 23 (31.1%) had initially resectable disease (IR) before chemotherapy, defined as positive for cancer on peritoneal cytology (CY1), resectable hepatic metastasis, or para-aortic lymph node No. 16a2/b1 metastasis. Of the 56 remaining patients with primary unresectable disease, 39 had peritoneal dissemination. R0 resection was accomplished in 63 patients (79.7%). The 3-year OS rates for patients with IR and unresectable disease were 78.3% and 44.5%, respectively. Multivariate analysis showed that IR (P = 0.014) and R0 (P = 0.014) were statistically significant independent prognostic factors for favorable OS. Among patients with peritoneal dissemination alone, OS was significantly better for patients with R0 resection than for patients with R1/2 resection, with the 3-year OS rates of 65.5% and 23.1%, respectively (P = 0.011). CONCLUSIONS: CS is a treatment option for selected patients with stage IV GC. Patients with IR and patients who achieve R0 resection may obtain a survival benefit from CS.

The incidences of metachronous multiple gastric cancer after various types of gastrectomy: analysis of data from a nationwide Japanese survey.

BACKGROUND: The incidence of metachronous multiple gastric cancer (MMGC) after gastrectomy remains unclear. This study evaluated the incidences of MMGC according to specific gastrectomy types, including pylorus-preserving gastrectomy (PPG), proximal gastrectomy (PG), and function-preserving gastrectomy (FPG), which was categorized as segmental gastrectomy and local resection. METHODS: We conducted a questionnaire survey of the Japanese Society for Gastro-Surgical Pathophysiology members, who were asked to report their institutional numbers of radical gastrectomy cases for cancer between 2003 and 2012. The cases were categorized according to whether the remnant stomach's status was followed for > 5 years, confirmation of MMGC, time to diagnosis, and treatment for MMGC. We calculated the "precise incidence" of MMGC by dividing the number of MMGC cases by the number of cases in which the status of remnant stomach was followed up for > 5 years. RESULTS: The responses identified 33,731 cases of gastrectomy. The precise incidences of MMGC were 2.35% after distal gastrectomy (DG), 3.01% after PPG, 6.28% after PG (p < 0.001), and 8.21% after FPG (p < 0.001). A substantial proportion of MMGCs (36.4%) was found at 5 years after the initial surgery. The rates of MMGC treatment using endoscopic submucosal dissection were 31% after DG, 28.6% after PPG, 50.8% after PG (p < 0.001), and 67.9% after FPG (p < 0.001). CONCLUSIONS: The incidence of MMGC was 2.4% after DG, and higher incidences were observed for larger stomach remnants. However, the proportion of cases in which MMGC could be treated using endoscopic submucosal dissection was significantly higher after PG and FPG than after DG.

Impact of preoperative chemotherapy as initial treatment for advanced gastric cancer with peritoneal metastasis limited to positive peritoneal lavage cytology (CY1) or localized peritoneal metastasis (P1a): a multi-institutional retrospective study.

BACKGROUND: Gastric cancer (GC) patients with peritoneal metastasis are defined as stage IV in the Japanese classification of GC. For patients with peritoneal metastasis limited to positive peritoneal lavage cytology (CY1) and/or localized peritoneal metastasis (P1a), gastrectomy followed by S1 monotherapy is one of the most widely accepted therapeutic strategy in Japan. This study investigated the efficacy of preoperative chemotherapy as initial treatment in GC patients with CY1 and/or P1a. METHODS: We retrospectively reviewed GC patients diagnosed with CY1 and/or P1a at 34 institutions in Japan between 2008 and 2012. Selection criteria were: adenocarcinoma, no distant metastasis except CY1 or P1a, and no prior treatment. The subjects were divided into an Initial-Chemotherapy group and an Initial-Surgery group, according to the initial treatment. RESULTS: A total of 824 patients were collected and 713 eligible patients were identified for this study. As the initial treatment, 150 patients received chemotherapy (Initial-Cx), and 563 patients underwent surgery (Initial-Sx). Initial-Cx regimens were cisplatin plus S1/docetaxel plus cisplatin plus S1/others (n = 90/37/23). Both overall survival (OS) and progression-free survival (PFS) were similar between the Initial-Cx and Initial-Sx groups (median OS 24.8 and 24.0 months, HR 1.07, 95% CI 0.87-1.3; median PFS 14.9 and 13.9 months, HR 1.04, 95% CI 0.85-1.27). The 5-year OS rates were 22.3% in the Initial-Cx group and 21.5% in the Initial-Sx group. CONCLUSIONS: Although, the preoperative chemotherapy did not show a survival benefit for GC patients with CY1 and/or P1a, initial-Cx showed favorable survival in patients who converted to P0 and CY0.

Efficacy and safety of ramucirumab plus paclitaxel therapy for advanced gastric cancer patients treated previously with docetaxel-containing chemotherapy.

BACKGROUND: Ramucirumab (RAM) plus paclitaxel (PTX) therapy has shown promising results as a standard second-line treatment for advanced gastric cancer patients. Recently, combined docetaxel (DOC) plus S-1 (DS) therapy could be regarded as the new standard adjuvant chemotherapy for patients with curatively resected stage III gastric cancer. However, the efficacy and safety of RAM plus PTX therapy in patients treated previously with DOC-containing therapy remains unclear. METHODS: This study assessed the clinical outcomes of RAM plus PTX therapy in advanced gastric cancer patients with or without a previous history of treatment with a DOC-containing regimen. RESULTS: In a series of 107 consecutive patients enrolled for this study, the median PFS and OS were 4.2 and 6.2 months, respectively. Fifty-five patients had a history of prior therapy with DOC and 52 did not. There was no significant difference between with and without DOC groups in the ORR (22.2% vs. 23.5%), PFS (4.2 vs. 5.3 months), or OS (7.2 vs. 6.4 months). In a comparison taking into account the interval from the DOC-containing therapy to the RAM plus PTX therapy, the number of treatment courses was significantly smaller and the PFS significantly shorter in the patient group with an interval of ≤ 6 months (median, 2 vs 4.5 courses, P = 0.033; 3.4 months vs. 5.1 months, P = 0.043). CONCLUSIONS: RAM plus PTX therapy in patients with advanced gastric cancer is effective even in patients who have previously received DOC-containing chemotherapy, especially if the interval is > 6 months.

Efficacy of Postoperative Chemotherapy After Resection that Leaves No Macroscopically Visible Disease of Gastric Cancer with Positive Peritoneal Lavage Cytology (CY1) or Localized Peritoneum Metastasis (P1a): A Multicenter Retrospective Study.

BACKGROUND: Gastric cancer (GC) patients with positive peritoneal lavage cytology (CY1) and/or localized peritoneum metastasis (P1a) are defined as stage IV in the 15th edition of the Japanese Classification of Gastric Cancer. In Japan, the most common treatment for patients with CY1 and/or P1a is gastrectomy followed by postoperative chemotherapy. PATIENTS AND METHODS: Subjects in this multi-institutional retrospective study were GC patients with CY1 and/or P1a who received surgical resection that leaves no macroscopically visible disease. Patients were selected from 34 institutions in Japan between 2007 and 2012. Selection criteria included adenocarcinoma, no distant metastasis except CY1 and P1a, and no prior treatment for GC before surgery. RESULTS: Among 824 patients registered, 506 were identified as eligible, with a background of P0CY1, P1aCY0, or P1aCY1 (72.5%, 16.0%, and 11.5% of subjects, respectively). Sixty-two patients had not received postoperative chemotherapy (no-Cx), whereas 444 patients had received postoperative chemotherapy: S-1 monotherapy (S-1; n = 267, 52.7%), cisplatin plus S-1 (CS; n = 114, 22.5%), and others (n = 63, 12.6%). Overall survival (OS) was 29.5, 24.7, 25.4 and 9.9 months in the S-1, CS, 'others', and no-Cx groups, respectively [CS vs. S-1: hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.89-1.50; p = 0.275]. In multivariate analysis, OS was similar between the S-1 and CS groups (CS vs. S-1: HR 1.19, 95% CI 0.92-1.55; p = 0.18). CONCLUSIONS: Postoperative chemotherapy after gastrectomy that leaves no macroscopically visible disease may have some survival benefits for GC patients with CY1 and/or P1a. In contrast, S-1 plus cisplatin seems to have no additional benefit over S-1 treatment alone.

Incidence of Multiple Metachronous Gastric Cancers After Pyloric-Preserving Gastrectomy.

AIM: Pylorus-preserving gastrectomy (PPG) is widely used for early gastric cancer located in the middle third of the stomach. The minimization of the extent of gastrectomy may increase the risk of metachronous multiple gastric cancer (MGC). We report the findings of a study that was conducted to evaluate the prevalence of MGC after PPG. METHODS: The clinical data of 533 patients who underwent PPG for gastric cancer between 1993 and 2018 were reviewed. The clinicopathological characteristics at the time of the primary treatment that were predictive of the development of MGC were explored. The median (range) observation period was 112.4 (8.1-290.7) months. RESULTS: Metachronous MGC was diagnosed in 33 of the 533 patients. The cumulative 5-year and 10-year event rates were 3.3% and 6.2%, respectively. The patient gender, presence/absence of synchronous MGC and the macroscopic type of the primary gastric cancer were significantly associated with the risk of development of metachronous MGC. Multivariate analysis identified the presence of synchronous MGC (hazard ratio [HR]: 4.828, 95% confidence interval [CI]; 1.611-12.30, p = 0.004) and Type 0-IIa primary gastric cancer (HR 2.810, 95% CI; 1.113-7.090, p = 0.029) as independent factors associated with the risk of development of MGC. All the patients could be treated by surgical or endoscopic resection for the metachronous MGC. Recurrence was observed in one patient. CONCLUSIONS: There was quite a few incidence of development of metachronous MGC after PPG. Nevertheless, PPG remains reasonable treatment option, if adequate postoperative surveillance can be ensured.

Oncological outcomes of function-preserving gastrectomy for early gastric cancer: a multicenter propensity score matched cohort analysis comparing pylorus-preserving gastrectomy versus conventional distal gastrectomy.

OBJECTIVE: This study aimed to clarify the oncological safety of pylorus-preserving gastrectomy (PPG) compared with conventional distal gastrectomy (DG). METHODS: From three institutions specializing in cancer, the medical records for a cohort of 2898 consecutive patients who had undergone DG (n = 2208) or PPG (n = 690) for clinical stage I gastric cancer between January 2006 and December 2012 were analyzed. A propensity score for each patient was estimated on the basis of 38 preoperative clinical and tumor-related factors. After propensity score matching had been done, 1004 patients (502 DG patients, 502 PPG patients) were included in the analysis. The overall survival, relapse-free survival, and occurrence of secondary gastric cancer were then compared. The median observation period was 48.6 months (range 1-109.8 months). RESULTS: The 5-year overall survival rate was 98.4 % for the PPG group and 96.6 % for the DG group (hazard ratio 0.48, 95 % confidence interval 0.21-1.09, P = 0.07). The 3-year relapse-free survival rate was 99.5 % for the PPG group and 98.0 % for the DG group (hazard ratio 0.39, 95 % confidence interval 0.12-1.33, P = 0.12). Postoperative secondary gastric cancer was encountered in eight patients (1.6 %) in the PPG group and four patients (0.8 %) in the DG group. No significant differences in either overall survival, relapse-free survival, or the occurrence of secondary gastric cancer were observed between the two groups. CONCLUSIONS: Given the adequate estimation of the clinical tumor stage, the oncological safety of PPG for clinical T1N0 gastric cancer in the middle portion of the stomach was comparable to that of DG.

[Long-Term Complete Response in Postoperative Multiple Lung and Mediastinal Lymph Node Metastases of Esophageal Cancer Using Systemic Chemotherapy with DCF Treatment - A Case Report].

A 59-year-old man was diagnosed with advanced thoracic esophageal cancer.He underwent neoadjuvant chemotherapy with cisplatin(CDDP), 5-fluorouracil(5-FU)(CF)followed by transthoracic esophagectomy with three-field lymphadenectomy. Histopathological examination revealed that the tumor was poorly differentiated squamous cell carcinoma invading the adventitia with 6 regional lymph node metastases.Four months after surgery, follow-up thoracic computed tomography (CT)showed multiple lung and mediastinal lymph node metastases.The patient's general condition was favorable, and he underwent systemic chemotherapy with docetaxel, CDDP, 5-FU(DCF).After 2 courses of DCF, chest CT revealed that the lung and mediastinal lymph node metastases had markedly decreased in size to the point of being unmeasurable.After receiving additional chemotherapy consisting of 2 courses of DCF and 8 courses of monthly docetaxel, the patient has been followed up without treatment.No tumor re-recurrence has occurred in the 6 years and 8 months since the first recurrence.In cases of recurrent or unresectable esophageal cancer, the rate of clinical response is reported to be higher for DCF than for CF. DCF is a tolerable regimen, even for postoperative patients, provided that monitoring is conducted for severe adverse events. In patients whose general conditions are favorable, DCF should be considered as a treatment option for recurrent esophageal cancer.

Long-term Outcomes of Laparoscopic Versus Open Surgery for Clinical Stage I Gastric Cancer: The LOC-1 Study.

BACKGROUND: Clinical trials comparing laparoscopic gastrectomy (LG) versus traditional open gastrectomy (OG) have been planned, their surgical outcomes reported but their oncologic outcomes are still pending. Consequently, we have conducted this large-scale historical cohort study to provide relevant information rapidly to guide our current practice. METHODS: Through a consensus meeting involving surgeons, biostatisticians, and epidemiologists, 30 variables of preoperative information possibly influencing surgeons' choice between LG versus OG and potentially associating with outcomes were identified to enable rigorous estimation of propensity scores. A total of 4235 consecutive patients who underwent gastrectomy for gastric adenocarcinoma were identified and their relevant data were gathered from the participating hospitals. After propensity score matching, 1848 patients (924 each for LG and OG) were selected for comparison of long-term outcomes. RESULTS: In the propensity-matched population, the 5-year overall survival was 96.3% [95% confidence interval (CI) 95.0-97.6] in the OG as compared with 97.1% (95% CI, 95.9-98.3) in LG. The number of all-cause death was 33/924 in the OG and 24/924 in the LG through the entire period, and the hazard ratio (LG/OG) for overall death was 0.75 (95% CI, 0.44-1.27; P = 0.290). The 3-year recurrence-free survival was 97.4% (95% CI, 96.4-98.5) in the OG and 97.7% (95% CI, 96.5-98.8) in the LG. The number of recurrence was 22/924 in the OG and 21/924 in the LG through the entire period, and the hazard ratio was 1.01 (95% CI, 0.55-1.84; P = 0.981). CONCLUSIONS: This observational study adjusted for all-known confounding factors seems to provide strong enough evidence to suggest that LG is oncologically comparable to OG for gastric cancer.

Gene copy number gain of EGFR is a poor prognostic biomarker in gastric cancer: evaluation of 855 patients with bright-field dual in situ hybridization (DISH) method.

BACKGROUND: EGFR overexpression is a prognostic biomarker and is expected to be a predictive biomarker for anti-EGFR therapies in gastric cancer. However, few studies have reported the clinical impact of EGFR gene copy number (GCN) and its correlation with EGFR overexpression. METHODS: We used dual in situ hybridization (DISH) to detect EGFR GCN and chromosome 7 centromere (CEN7) in a set of tissue microarrays representing 855 patients with gastric cancer. These data were compared with those of immunohistochemical (IHC) analysis of EGFR expression to evaluate prognostic value. RESULTS: EGFR GCN gain (≥ 2.5 EGFR signals per cell) was detected in 194 patients (22.7%) and indicated poor prognosis. Among 194 patients, EGFR amplification (EGFR/CEN7 ≥ 2.0) was observed in 29 patients (14.9%), which was almost identical to the IHC 3+ subgroup and worst prognostic subgroup. Patients with EGFR GCN gain but not amplification, including those exhibiting polysomy, also exhibited poorer prognosis than GCN non-gain patients and were distributed between IHC 0/1+ and 2+ subgroups. GCN gain was frequently observed in patients with more advanced disease, but served as an independent prognostic factor regardless of the pathological stage. CONCLUSIONS: EGFR GCN gain is a more accurate prognostic biomarker than EGFR overexpression in patients with gastric cancer.

Efficacy of neoadjuvant chemotherapy with docetaxel, cisplatin and S-1 for resectable locally advanced gastric cancer.

BACKGROUND: The prognosis for locally advanced gastric cancer (AGC) remains unsatisfactory, even with S-1 adjuvant chemotherapy. We investigated the efficacy of neoadjuvant chemotherapy consisting of docetaxel, cisplatin and S-1 (DCS). METHODS: We retrospectively reviewed 59 patients who underwent neoadjuvant DCS therapy for clinical stage III tumors or serosa-positive tumors between January 2009 and December 2013 at Niigata Cancer Center Hospital. The patients received S-1 (40 mg/m(2) bid) on days 1-14, and docetaxel (35 mg/m(2)) and cisplatin (35 mg/m(2)) on days 1 and 15 every 4 weeks. RESULTS: Forty-three patients (72.9 %) received two courses of DCS therapy, while 16 patients (27.1 %) received one course of treatment. The clinical response rate of the primary tumor was 74.6 %, and the disease control rate was 100 %. A pathological response, defined as one-third or more of the affected tumor, was observed in 71.2 % of patients. The common grade 3/4 adverse events from chemotherapy were leucopenia (16.9 %), neutropenia (44.1 %), febrile neutropenia (8.5 %), anemia (10.2 %), anorexia (8.5 %) and nausea (6.8 %). Postoperative complications occurred in 11 patients (18.6 %). There was no treatment-related mortality or reoperation. The 3- and 5-year overall survival rates were 88 and 68.6 %, respectively. Clinical responders had a significantly higher survival rate than non-responders. Multivariate analysis identified clinical response as the only independent prognostic factor. CONCLUSIONS: Neoadjuvant DCS therapy demonstrated a very high clinical and pathological response rate with acceptable toxicities. Therefore, this therapy may improve the prognosis of locally AGC.