Tumor Response Predicts Survival Time of Nivolumab Monotherapy for Advanced Gastric Cancer: A Subgroup Analysis of the DELIVER Trial (JACCRO GC-08).

BACKGROUND: This prospective observational study evaluated the real-world effectiveness of nivolumab monotherapy in previously treated advanced gastric cancer (GC). A preplanned 2-year final analysis was performed to confirm survival and tumor behavior with nivolumab monotherapy. PATIENTS AND METHODS: The primary endpoint was overall survival (OS). The data regarding tumor size were prospectively collected and evaluated using the RECIST criteria. Exploratory analyses were performed for survival according to the tumor response and depth of response (DpR) in patients with measurable lesions who were receiving nivolumab monotherapy as third- or later-line therapy. RESULTS: In 487 patients, the median OS and progression-free survival (PFS) were 5.8 (95% CI 5.3-6.9) months and 1.8 (95% CI 1.7-2.0) months, respectively. The response rate (RR) was 14.5% in 282 patients with measurable lesions. In 234 patients treated with third- or later-line, the DpR was found to be associated with PFS and OS in the Spearman analysis (r = 0.55 and 0.44, respectively) as well as using a discrete variable. When the DpR was divided into 5 groups (-20%≥DpR; -20%

Short-term outcomes of preoperative chemotherapy with docetaxel, oxaliplatin, and S-1 for gastric cancer with extensive lymph node metastasis (JCOG1704).

BACKGROUND: The prognosis for marginally resectable gastric cancer with extensive lymph node metastasis (ELM) remains unfavorable, even after R0 resection. To assess the safety and efficacy of preoperative docetaxel, oxaliplatin, and S-1 (DOS), we conducted a multicenter phase II trial. METHODS: Eligibility criteria included histologically proven HER2-negative gastric adenocarcinoma with bulky nodal (bulky N) involvement around major branched arteries or para-aortic node (PAN) metastases. Patients received three cycles of docetaxel (40 mg/m2, day 1), oxaliplatin (100 mg/m2, day 1), and S-1 (80-120 mg/body, days 1-14), followed by gastrectomy with D2 plus PAN dissection. Subsequently, patients underwent postoperative chemotherapy with S-1 for 1 year. The primary endpoint was major (grade ≥ 2a) pathological response rate (pRR) according to the Japanese Classification of Gastric Carcinoma criteria. RESULTS: Between October 2018 and March 2022, 47 patients (bulky N, 20; PAN, 17; both, 10) were enrolled in the trial. One patient was ineligible. Another declined any protocol treatments before initiation. Among the 45 eligible patients who initiated DOS chemotherapy, 44 (98%) completed 3 cycles and 42 (93%) underwent R0 resection. Major pRR and pathological complete response rates among the 46 eligible patients, including the patient who declined treatment, were 57% (26/46) and 24% (11/46), respectively. Common grade 3 or 4 toxicities were neutropenia (24%), anorexia (16%), febrile neutropenia (9%), and diarrhea (9%). No treatment-related deaths occurred. CONCLUSIONS: Preoperative chemotherapy with DOS yielded favorable pathological responses with an acceptable toxicity profile. This multimodal approach is highly promising for treating gastric cancer with ELM.

Early endpoints of a randomized phase II trial of preoperative chemotherapy with S-1/CDDP with or without trastuzumab followed by surgery for HER2-positive resectable gastric or esophagogastric junction adenocarcinoma with extensive lymph node metastasis: Japan Clinical Oncology Group study JCOG1301C (Trigger Study).

BACKGROUND: This randomized phase II study explored the superiority of trastuzumab plus S-1 plus cisplatin (SP) over SP alone as neoadjuvant chemotherapy (NAC) for HER2-positive resectable gastric cancer with extensive lymph node metastasis. METHODS: Eligible patients with HER2-positive gastric or esophagogastric junction cancer and extensive lymph node metastasis were randomized to receive three or four courses of preoperative chemotherapy with SP (arm A) or SP plus trastuzumab (arm B). Following gastrectomy, adjuvant chemotherapy with S-1 was administered for 1 year in both arms. The primary endpoint was overall survival, and the sample size was 130 patients in total. The trial is registered with the Japan Registry of Clinical Trials, jRCTs031180006. RESULTS: This report elucidates the early endpoints, including pathological findings and safety. The study was terminated early due to slow patient accruals. In total, 46 patients were allocated to arm A (n = 22) and arm B (n = 24). NAC was completed in 20 patients (91%) in arm A and 23 patients (96%) in arm B, with similar incidences of grade 3-4 hematological and non-hematological adverse events. Objective response rates were 50% in arm A and 84% in arm B (p = 0·065). %R0 resection rates were 91% and 92%, and pathological response rates (≥ grade 1b in Japanese classification) were 23% and 50% (p = 0·072) in resected patients, respectively. CONCLUSIONS: Trastuzumab can be safely added to platinum-containing doublet chemotherapy as NAC, and it has the potential to contribute to higher antitumor activity against locally advanced, HER2-positive gastric or esophagogastric junction cancer with extensive nodal metastasis.

Randomized controlled phase III trial to investigate superiority of robot-assisted gastrectomy over laparoscopic gastrectomy for clinical stage T1-4aN0-3 gastric cancer patients (JCOG1907, MONA LISA study): a study protocol.

BACKGROUND: Laparoscopic gastrectomy (LG) is considered a standard treatment for clinical stage I gastric cancer. Nevertheless, LG has some drawbacks, such as motion restriction and difficulties in spatial perception. Robot-assisted gastrectomy (RG) overcomes these drawbacks by using articulated forceps, tremor-filtering capability, and high-resolution three-dimensional imaging, and it is expected to enable more precise and safer procedures than LG for gastric cancer. However, robust evidence based on a large-scale randomized study is lacking. METHODS: We are performing a randomized controlled phase III study to investigate the superiority of RG over LG for clinical T1-2N0-2 gastric cancer in terms of safety. In total, 1,040 patients are planned to be enrolled from 46 Japanese institutions over 5 years. The primary endpoint is the incidence of postoperative intra-abdominal infectious complications, including anastomotic leakage, pancreatic fistula, and intra-abdominal abscess of Clavien-Dindo (CD) grade ≥ II. The secondary endpoints are the incidence of all CD grade ≥ II and ≥ IIIA postoperative complications, the incidence of CD grade ≥ IIIA postoperative intra-abdominal infectious complications, relapse-free survival, overall survival, the proportion of RG completion, the proportion of LG completion, the proportion of conversion to open surgery, the proportion of operation-related death, and short-term surgical outcomes. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in January 2020. Approval from the institutional review board was obtained before starting patient enrollment in each institution. Patient enrollment began in March 2020. We revised the protocol to expand the eligibility criteria to T1-4aN0-3 in July 2022 based on the results of randomized trials of LG demonstrating non-inferiority of LG to open surgery for survival outcomes in advanced gastric cancer. DISCUSSION: This is the first multicenter randomized controlled trial to confirm the superiority of RG over LG in terms of safety. This study will demonstrate whether RG is superior for gastric cancer. TRIAL REGISTRATION: The protocol of JCOG1907 was registered in the UMIN Clinical Trials Registry as UMIN000039825 ( http://www.umin.ac.jp/ctr/index.htm ). Date of Registration: March 16, 2020. Date of First Participant Enrollment: April 1, 2020.

Multicenter phase II study of capecitabine plus oxaliplatin in older patients with advanced gastric cancer: the Tokyo Cooperative Oncology Group (TCOG) GI-1601 study.

BACKGROUND: Capecitabine plus oxaliplatin (CapeOX) is a standard treatment option for advanced gastric cancer (AGC). We conducted a prospective multicenter phase II study to evaluate the efficacy and safety of CapeOX as a first-line therapy for AGC in older patients. METHODS: Chemotherapy-naive patients aged ≥ 70 years with AGC were eligible. Initial treatment comprised capecitabine (2000 mg/m2 on days 1-14) and oxaliplatin (130 mg/m2 on day 1) every 3 weeks. After the initial feasibility assessment, the dose was reduced considering toxicity (capecitabine, 1500 mg/m2 on days 1-14; and oxaliplatin, 100 mg/m2 on day 1 every 3 weeks). The primary endpoint was overall survival (OS). RESULTS: In total, 108 patients were enrolled, of whom 104 were evaluated. Thirty-nine patients received the original-dose treatment, whereas 65 received the reduced-dose treatment. The median OS, progression-free survival (PFS), and time to treatment failure (TTF) were 12.9 (95% CI 11.6-14.8), 5.7 (95% CI 5.0-7.0), and 4.3 (95% CI 3.9-5.7) months, respectively, for all patients; 13.4 (95% CI 9.5-16.0), 5.8 (95% CI 4.1-7.8), and 5.3 (95% CI 3.5-7.2) months in the original-dose group; and 12.8 (95% CI 11.3-15.3), 5.7 (95% CI 4.4-7.0), and 4.1 (95% CI 3.7-5.7) months in the reduced-dose group. The most common grade 3/4 toxicities were neutropenia (17.9%), anemia (12.8%), and thrombocytopenia (12.8%) in the original-dose group and neutropenia (13.8%) and anorexia (12.3%) in the reduced-dose group. CONCLUSIONS: These findings demonstrate CapeOX's efficacy and safety in older AGC patients.

[A Case of Advanced Esophageal Cancer with Esophago-Bronchial Fistula Closed by Pembrolizumab plus Chemotherapy Therapy].

We report a case of unresectable advanced esophageal cancer with an esophageal fistula that was treated with pembrolizumab plus CDDP plus 5-FU therapy and the fistula was closed. A 73-year-old male was diagnosed with cervical-upper thoracic esophageal cancer and esophago-bronchial fistula on CT and esophagogastroduodenoscopy. He underwent chemotherapy containing pembrolizumab. The fistula was closed after 4 cycles and oral intake became possible. Six months have passed since the first visit and chemotherapy is ongoing. The prognosis of esophago-bronchial fistula is extremely poor, and there is no established treatment, including fistula closure. Chemotherapy containing immune checkpoint inhibitors could considered to be expected not only for local control but also for long-term survival.

Survival analysis of a prospective multicenter observational study on surgical palliation among patients with malignant bowel obstruction caused by peritoneal dissemination of gastric cancer.

BACKGROUND: Our previous report showed that surgical palliation maintained quality of life (QOL), improved solid food intake, and had an acceptable surgical safety among patients with malignant bowel obstruction (MBO) caused by advanced gastric cancer. This study performed a survival analysis stratified by the patients' QOL to elucidate its impact on survival. METHODS: Patients who underwent resection or bypass of the small intestine/colon or ileostomy/colostomy for bowel obstruction caused by peritoneal dissemination of gastric cancer were included. Validated instruments (EuroQoL-5 Dimensions) were used to assess QOL at baseline and 2 weeks, 1 month, and 3 months following surgical palliation. Postoperative improvement in oral intake was also evaluated using the Gastric Outlet Obstruction Scoring System (GOOSS). Univariate and multivariate survival analyses were performed using baseline characteristics and changes in QOL and GOOSS scores 2 weeks after surgery to determine prognostic factors. RESULTS: We enrolled 60 patients with a median survival time of 6.64 (95% CI 4.76-10.28) months. Patients who received postoperative chemotherapy and had lower baseline C-reactive protein (CRP) levels, higher baseline albumin levels, better baseline EuroQoL-5 Dimensions (EQ-5D) scores, and improved oral intake after palliative surgery exhibited significantly better survival. Multivariate analysis identified postoperative chemotherapy, lower baseline CRP levels, and improved oral intake as independent prognostic factors. CONCLUSIONS: The current study revealed that baseline QOL and postoperative QOL changes did not affect survival. Moreover, improved oral intake, lower baseline CRP levels, and postoperative chemotherapy were significant prognostic factors in patients who underwent palliative surgery for advanced gastric cancer with MBO.

Evaluation of Neoadjuvant Chemoradiotherapy Followed by Surgery for Borderline Resectable Esophageal Squamous Cell Carcinoma.

BACKGROUND: It is occasionally difficult to diagnose cT3 or cT4b using imaging examinations for esophageal cancer. The optimal treatment strategy for borderline resectable esophageal squamous cell carcinoma (BR-ESCC) is unclear. METHODS: We included 131 patients with cT3 ESCC who received neoadjuvant chemoradiotherapy (NCRT) followed by surgery. The patients were classified as having definitive cT3 (D-cT3) or borderline resectable cT3 (BR-cT3), based on presence of undeniable adjacent organ invasion on pretreatment CT. Surgical outcomes and prognoses were compared among patients with D-cT3 and BR-cT3 tumors, and the risk factors for non-R0 resection were assessed. RESULTS: Ninety and 41 patients were classified as D-cT3 and BR-cT3, respectively. Although BR-cT3 had a significantly higher non-R0 resection rate than D-cT3 (D-cT3 3.7%; BR-cT3 14.6%), BR-cT3 was not correlated with shorter overall survival (OS) (D-cT3 5-year OS, 50.8%; BR-cT3 5-year OS 38.4%; p = 0.234). Conversely, non-R0 resection was significantly associated with poor OS (R0 resection 5-year OS 48.8%; non-R0 resection 5-year OS 22.2%; p = 0.031). Cox regression analysis of OS demonstrated that BR-cT3 was not a prognostic factor. In the analysis of risk factors for non-R0 resection, BR-cT3 (p = 0.027), suspected invasion of the trachea or bronchus (p = 0.046), and high SUVmax of the primary lesion after NCRT (p = 0.002) were risk factors. CONCLUSIONS: NCRT followed by surgery achieved a relatively high R0 resection rate and an almost equal overall survival rate for BR-cT3 compared with D-cT3 ESCC. Thus, NCRT followed by surgery is an effective treatment strategy for patients with BR-cT3 ESCC.

Gastrectomy with or without neoadjuvant S-1 plus cisplatin for type 4 or large type 3 gastric cancer (JCOG0501): an open-label, phase 3, randomized controlled trial.

BACKGROUND: Specific treatment strategies are sorely needed for scirrhous-type gastric cancer still, which has poor prognosis. Based on the promising results of our previous phase II study (JCOG0210), we initiated a phase III study to confirm the efficacy of neoadjuvant chemotherapy (NAC) in type 4 or large type 3 gastric cancer. METHODS: Patients aged 20-75 years without a macroscopic unresectable factor as confirmed via staging laparoscopy were randomly assigned to surgery followed by adjuvant chemotherapy with S-1 (Arm A) or NAC (S-1plus cisplatin) followed by D2 gastrectomy plus adjuvant chemotherapy with S-1 (Arm B). The primary endpoint was overall survival (OS). RESULTS: Between October 2005 and July 2013, 316 patients were enrolled, allocating 158 patients to each arm. In Arm B, in which NAC was completed in 88% of patients. Significant downstaging based on tumor depth, lymph node metastasis, and peritoneal cytology was observed using NAC. Excluding the initial 16 patients randomized before the first revision of the protocol, 149 and 151 patients in arms A and B, respectively, were included in the primary analysis. The 3-year OS rates were 62.4% [95% confidence interval (CI) 54.1-69.6] in Arm A and 60.9% (95% CI 52.7-68.2) in Arm B. The hazard ratio of Arm B against Arm A was 0.916 (95% CI 0.679-1.236). CONCLUSIONS: For type 4 or large type 3 gastric cancer, NAC with S-1 plus cisplatin failed to demonstrate a survival benefit. D2 surgery followed by adjuvant chemotherapy remains the standard treatment.

QOL assessment after palliative surgery for malignant bowel obstruction caused by peritoneal dissemination of gastric cancer: a prospective multicenter observational study.

BACKGROUND: Patients with peritoneal dissemination of gastric cancer have poor oral intake caused by malignant bowel obstruction (MBO). Palliative surgery has often been undertaken to improve quality of life (QOL), but few prospective studies on palliative surgery in this patient population have been published. PATIENTS AND METHODS: We prospectively investigated the significance of palliative surgery using patient-reported QOL measures. Patients underwent palliative surgery by small intestine/colon resection or small intestine/colon bypass or ileostomy/colostomy for MBO. The primary endpoint was change in QOL assessed at baseline, 14 days, 1 month, and 3 months following palliative surgery using the Euro QoL Five Dimensions (EQ-5D™) questionnaire and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire gastric cancer module (QLQ-STO22). Secondary endpoints were postoperative improvement in oral intake and surgical complications. RESULTS: Between April 2013 and March 2018, 63 patients were enrolled from 14 institutions. The mean EQ-5D™ utility index baseline score of 0.6 remained consistent. Gastric-specific symptoms mostly showed statistically significant improvement from baseline. Forty-two patients (67%) were able to eat solid food 2 weeks after palliative surgery and 36 patients (57%) tolerated it for 3 months. The rate of overall morbidity of ≥ grade III according to the Clavien-Dindo classification was 16% (10 patients) and the 30-day postoperative mortality rate was 3.2% (2 patients). CONCLUSIONS: In patients with MBO caused by peritoneal dissemination of gastric cancer, palliative surgery did not improve QOL while improving solid food intake, with an acceptable postoperative morbidity and mortality rate.

Association between skeletal muscle loss and the response to nivolumab immunotherapy in advanced gastric cancer patients.

BACKGROUND: Skeletal muscle loss is a hallmark of malignancies, including advanced gastric cancer (GC). Although programmed death (PD)-1 inhibitors, including nivolumab, have promising anti-cancer effects, there is limited information regarding markers that can predict these therapeutic effects, which include PD-ligand 1 (PD-L1) expression and the tumor mutation burden. Therefore, we evaluated whether the baseline psoas muscle mass index (PMI, a surrogate for skeletal muscle mass) could predict the response of GC to nivolumab treatment, based on progression-free survival (PFS), the objective response rate, and the disease control rate. METHODS: This retrospective study evaluated 31 Japanese patients who received nivolumab for advanced GC and underwent imaging analysis between November 2017 and November 2019. The computed tomography results were used to estimate the psoas major muscle mass. Sex-specific cut-off values were used for the PMI, with low PMI values defined as < 3.6 cm2/m2 for male patients and < 2.9 cm2/m2 for female patients. RESULTS: The median PFS interval was 2.3 months for the patients with stage IV GC. Nine patients (29%) had a low baseline PMI, and these patients had significantly shorter median PFS than the group with a non-low baseline PMI (0.5 months vs. 2.4 months, P = 0.004). CONCLUSIONS: As a surrogate marker for skeletal muscle loss, the PMI may be useful for predicting the response to nivolumab among patients with advanced GC.

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.

Clinical Significance of 18F-Fluorodeoxyglucose-Positron Emission Tomography-Positive Lymph Nodes to Outcomes of Trimodal Therapy for Esophageal Squamous Cell Carcinoma.

BACKGROUND: The clinical significance of lymph node (LN) status determined by preoperative 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) has not been investigated in patients with locally advanced esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (NCRT) followed by surgery (trimodal therapy). METHODS: This study reviewed 132 consecutive patients with ESCC who had been preoperatively evaluated using FDG-PET before and after NCRT to analyze associations among LN status according to PET findings, pathologic LN metastasis, and prognosis of ESCC after trimodal therapy. RESULTS: Lymph nodes that were PET-positive both before and after NCRT comprised significant predictive markers of pathologic LN metastasis in station-by-station analyses (sensitivity, specificity, and accuracy respectively 41.7%, 95.0%, and 92.7% before, and 12.0%, 99.4%, and 95.6% after NCRT; both p < 0.0001). The numbers of LNs evaluated using PET before and after NCRT were significantly associated with those of pathologic metastatic LNs. Uni- and multivariable analyses selected LN status determined by PET before NCRT as a significant independent predictor of both recurrence-free [LN-negative vs LN-positive: hazard ratio (HR) 1.90; 95% confidence interval (CI) 1.02-3.23; p = 0.045] and overall survival (HR 2.62; 95% CI 1.29-5.30; p = 0.01). CONCLUSIONS: The status of LN determined by preoperative FDG-PET is significantly associated with pathologic LN status and the prognosis of ESCC with trimodal therapy. Thus, FDG-PET is a useful diagnostic tool for preoperative prediction of pathologic LN metastasis and survival among patients with ESCC.

Gastrectomy for invasive micropapillary carcinoma is associated with poorer disease-free and disease-specific survival.

BACKGROUND: Invasive micropapillary carcinoma (IMPC) is a relatively rare subtype of gastric adenocarcinoma and has aggressive histopathologic characteristics, including lymphatic and vascular invasion. However, the associated long-term survival outcomes remain unclear. This study aimed to compare the clinicopathological characteristics and prognosis of gastric adenocarcinoma with and without IMPC using propensity score-matched (PSM) analysis. METHODS: Patients with gastric adenocarcinoma who underwent gastrectomy between 2006 and 2015 were included in the analysis. PSM analysis was performed to compensate for the background heterogeneity between the groups. The primary endpoint was disease-free survival (DFS) after gastrectomy, and the secondary endpoints were disease-specific survival (DSS) and recurrence pattern. RESULTS: Of 882 patients who underwent gastrectomy for gastric adenocarcinoma, with a follow-up duration greater than 36 months, 35 were diagnosed as having gastric adenocarcinoma with IMPC. After PSM, 70 patients, including 35 with IMPC and 35 without IMPC, were selected. Gastric adenocarcinoma with IMPC is characterized by lymphatic invasion (94% versus 69%, p = 0.012). Patients with IMPC had significantly poorer DFS than those without IMPC, with 3-year DFS rates of 62.2% and 93.4% (p = 0.003), respectively. Furthermore, a significant difference was also observed in DSS (p = 0.016); patients with IMPC more frequently developed liver metastasis (20%) than those without IMPC (3%, p = 0.006). CONCLUSIONS: Resected gastric carcinoma with IMPC was associated with poorer DFS and DSS; furthermore, an increased rate of lymphatic invasion and liver metastasis was noted than in cases without IMPC.

Treatment Outcomes and Prognostic Factors After Recurrence of Esophageal Squamous Cell carcinoma.

BACKGROUND: The evaluation of treatment outcomes and detection of prognostic factors after recurrence are very important for tailoring optimal therapies for individual patients with recurrent esophageal cancer. METHODS: We reviewed 133 patients in whom esophageal squamous cell carcinoma (ESCC) recurred after curative surgery, and assessed recurrence patterns, treatment outcomes and prognostic factors. RESULTS: Recurrence in 57 (42.9%), 54 (40.6%) and 22 (16.5%) patients was locoregional, distant and combined, respectively. The median amounts of elapsed time until recurrence and median survival after recurrence for all patients were 9.1 and 8.3 months, respectively. Univariate and multivariate analyses selected time to recurrence (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.97-0.999; p = 0.04), recurrence location (locoregional vs. distant: HR, 1.63; 95% CI, 1.03-2.61; p = 0.04), number of organs with recurrence (1 vs. 3: HR, 3.49; 95% CI, 1.23-9.87; p = 0.02) and treatment after recurrence (best supportive care, [BSC] vs. chemotherapy [CT] or radiation therapy [RT]: HR, 0.37; 95% CI, 0.15-0.94; p = 0.04; BSC vs. CT and RT: HR, 0.50; 95% CI, 0.26-0.94; p = 0.03; BSC vs. surgery: HR, 0.47; 95% CI, 0.25-0.88; p = 0.02) as independent factors for survival after recurrence. Seventeen (12.8%) patients who had localized lymph node recurrence and lung oligometastasis and received multidisciplinary therapy after recurrence survived for >3 years thereafter. CONCLUSION: Despite the poor survival of patients with ESCC and early or distant recurrence or recurrence in ≥3 recurrent organs, appropriate multimodal therapies should be tailored for individual patients with recurrent ESCC.

Evaluation of Prognostic Factors for Esophageal Squamous Cell Carcinoma Treated with Neoadjuvant Chemoradiotherapy Followed by Surgery.

BACKGROUND: Intensive trimodality therapy is needed for locally advanced esophageal squamous cell carcinoma (ESCC). However, some patients develop recurrence and die of cancer even after trimodality therapy. METHODS: We evaluated prognostic factors based on data from 125 patients with ESCC who underwent neoadjuvant chemoradiotherapy (NCRT) comprising concurrent chemotherapy and 40 Gy of radiation, followed by curative-intent esophagectomy. RESULTS: Thirty-four (27.2%) patients achieved a pathological complete response (pCR) after NCRT. The 5-year recurrence-free (RFS) and overall survival (OS) rates of all patients were 49.2 and 52.9%, respectively, and were significantly better for patients with pCR than without pCR (p = 0.01 and 0.02, respectively). Univariate and multivariate analyses selected performance status [PS 0 vs. 1: hazard ratio (HR) 2.05; 95% confidence interval (CI) 1.30-4.84; p = 0.01] and ypN (0 vs. 1: HR 2.33; 95% CI 1.12-4.84; p = 0.02; 0 vs. 2/3: HR 3.73; 95% CI 1.68-8.28; p = 0.001) as independent covariates for RFS. Furthermore, PS (0 vs. 1; HR 2.94; 95% CI 1.51-5.72; p = 0.002) and ypN (0 vs. 1; HR 2.26; 95% CI 1.09-4.69; p = 0.03; 0 vs. 2/3: HR 3.90; 95% CI 1.79-8.48; p = 0.001) were also independent covariates for OS. CONCLUSIONS: Performance status 1 and ypN+ were significantly associated with a poor prognosis after trimodality therapy for ESCC.

Short-term outcomes of laparoscopic surgery in octogenarians with colorectal cancer: a single-institution analysis.

PURPOSE: The number of elderly patients with colorectal cancer (CRC) treated with surgery has gradually increased. The aim of this study was to evaluate the short-term outcomes in patients ≥80 years of age who underwent laparoscopic or open surgery for CRC using a propensity score-matched analysis to make uniform the patient background characteristics affecting the postoperative morbidity and mortality. METHODS: We compared the short-term outcomes of open vs. laparoscopic surgery in patients with CRC ≥80 years of age between 2010 and 2015. Fifty-two patients undergoing laparoscopic colectomy for CRC were matched to 52 patients undergoing open colectomy with respect to gender, age, body mass index, performance status, prognostic nutritional index, Charlson Comorbidity Index score, tumor-node-metastasis stage, and tumor location. The operative time, blood loss, length of hospital stay, and postoperative complications were investigated. RESULTS: Blood loss was less during laparoscopic surgery than during open surgery (40 vs. 140 ml, p < 0.001). In the laparoscopic surgery group, the hospital stay was shorter (11 vs. 14 days, p < 0.001) and the morbidity rate lower (21.2 vs. 40.4%) than in the open surgery group. The mortality for both groups was similar (0 vs. 1.9% for laparoscopic surgery vs. open surgery). CONCLUSION: Laparoscopic surgery in octogenarians with CRC is a safe, low-invasive alternative to open surgery with less blood loss and a shorter hospital stay.

Role of Postoperative C-Reactive Protein Levels in Predicting Prognosis After Surgical Treatment of Esophageal Cancer.

BACKGROUND: Elevated preoperative serum C-reactive protein (CRP) levels are reportedly associated with a poor prognosis for patients with various types of malignant tumors. However, the impact of postoperative CRP levels on the prognosis of patients with esophageal cancer remains unknown. The present study aims to clarify the prognostic significance of postoperative CRP levels on the survival of patients with esophageal cancer. METHODS: We reviewed the records of consecutive 202 patients with thoracic esophageal squamous cell carcinoma who underwent transthoracic esophagectomy. We measured serum CRP levels on postoperative days (PODs) 1, 2, 3, 5 and 7 and evaluated the relationships between postoperative CRP levels and survival. RESULTS: The findings of Cox regression analyses suggested that elevated CRP levels on POD 3, 5 and 7 were associated with poor recurrence-free survival (RFS). We divided CRP levels on POD 7 into three tertiles and found that RFS could be clearly stratified, being the poorest (p < 0.001) in the highest tertile (high CRP). The trend was similar even in patients with or without infectious complications and with or without advanced pathological stage. Multivariate analysis showed that pathologically advanced stage (Hazard ratio [HR], 5.14; 95% confidence interval [CI] 2.67-9.87; p < 0.001) and high CRP (HR, 2.27; 95% CI 1.3-3.96; p = 0.004) were independent predictors of RFS. CONCLUSION: Postoperative CRP levels could predict the prognosis of patients with esophageal cancer. We propose that the clinical course of postoperative CRP level should be carefully monitored as a predictor of survival.

[Abdominoperineal Resection for Anal Metastasis of Rectal Cancer].

Anal metastasis of colorectal cancer is rare, and no standardized effective therapeutic strategy exists. We report a case of abdominoperineal resection for anal metastasis of rectal cancer. A 65-year-old man underwent laparoscopic low anterior resection for rectal cancer in August 2013. Histopathological examination revealed a moderately differentiated adenocarcinoma( tub2, pSS, ly3, v2, pN1, H0, P0, M0, Stage III a, Cur A). In February 2015, he complained of anal discomfort, and tumor markers were elevated. Enhanced CT revealed a 15-mm high-density solid tumor in the anal canal. The results of needle biopsy indicated a moderately differentiated adenocarcinoma. This tumor was suspected to be metastasis from rectal cancer, and we performed abdominoperineal resection. Histopathological examination revealed a moderately differentiated adenocarcinoma, which was the same histological type as the primary rectal cancer and was covered with normal anal epithelium. Collectively, the findings indicated anal metastasis from rectal cancer. The patient is alive without recurrence for 18 months after resection. Anal metastasis should be considered as a differential diagnosis in patients with anal discomfort who have a history of colon/rectal cancer. Abdominoperineal resection may be an effective treatment modality for this condition.

Clinical Significance of FDG-PET to Predict Pathologic Tumor Invasion and Lymph Node Metastasis of Superficial Esophageal Squamous Cell Carcinoma.

PURPOSE: To determine the preoperative ability of [18F]-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) to predict pathologic tumor invasion and lymph node status in cT1N0M0 esophageal squamous cell carcinoma (ESCC). METHODS: We retrospectively analyzed 40 consecutive patients diagnosed with cT1N0M0 ESCC between February 2006 and April 2011. All patients were treated by esophagectomy with two- or three-field lymphadenectomy without neoadjuvant therapy. We evaluated the relevance between clinical variables including maximum standardized uptake values (SUVmax) of the primary tumor on FDG-PET and pathologic tumor invasion and lymph node status using a logistic regression model. RESULTS: Tumors invaded the middle submucosal layer (SM2) and beyond in 21 (52.5 %) patients, and 6 (15 %) had lymph node metastases. The areas under receiver operating characteristic (ROC) curves for SUVmax of the primary tumor used to predict factors involved in tumor infiltration to SM2 or deeper and lymph node metastasis were 0.75 (p = 0.006) and 0.79 (p = 0.025), respectively. The optimal SUVmax cutoff was 2.7. The findings of univariate and multivariate analyses identified SUVmax as the only significant preoperative predictor associated with tumor infiltration into SM2 or beyond and lymph node metastasis. Furthermore, SUVmax ≥ 2.7 of the primary tumor on FDG-PET was associated with poor recurrence-free and disease-specific survival (p = 0.019 and p = 0.012, respectively). CONCLUSIONS: FDG-PET is helpful for diagnosing tumors that can infiltrate SM2 and beyond as well as occult lymph node metastasis of cT1N0M0 ESCC that are valuable indications in deciding therapeutic strategies for superficial ESCC.