[A Case of Synchronous-Metachronous Cancer of the Rectum, Stomach, Pharynx, Esophagus and Small Intestine].

A 71-year-old man presented with the chief complaint of fecal occult blood. Based on imaging studies, the patient was diagnosed advanced rectal cancer. He received laparoscopic low anterior resection. Three months after the rectal cancer operation, upper gastrointestinal endoscopy revealed gastric cancer. The patient had a diagnosis of synchronous cancer of the rectum and stomach, and received laparoscopic distal gastrectomy. Two years after the rectal cancer operation, liver metastasis(S4)was detected and resected. Three years after the rectal cancer operation, esophageal cancer and laryngeal cancer were detected synchronously and chemoradiotherapy was performed. Five years after the rectal cancer operation, small intestinal cancer with infiltration of descending colon and esophagus cancer were detected synchronously. Small intestinal resection and Hartmann procedure were performed for small intestinal cancer. ESD was performed for esophageal cancer. Six years after the rectal cancer operation, FDG-PET showed the peritracheal lymph node metastasis, lumbar spine metastasis and local recurrence in the pelvis. Currently, systemic chemotherapy is undergoing. We report a rare case of synchronous- metachronous cancer of the rectum, stomach, pharynx, esophagus and small intestine.

[A Case of Sigmoid Colon Cancer with Intussusception Prolapsing through the Anus].

A 76-year-old woman presented to the hospital with the colon prolapsing through the anus. The enhanced abdominal computed tomography(CT)showed intussusception of the sigmoid colon due to sigmoid colon cancer. It was difficult to reduce the intussusception, and we did not recognize the ileus and ischemic change of the colon. Therefore, we performed an elective surgery. Hartmann's procedure and lymph node dissection were performed 8 days after the hospitalization. The postoperative course was uneventful. We report a case of sigmoid colon cancer with intussusception prolapsing through the anus.

Does anastomotic leakage after rectal cancer resection worsen long-term oncologic outcome?

PURPOSE: The influence of anastomotic leakage on long-term survival in patients with rectal cancer is debatable. The aim of this study was to evaluate relationships between anastomotic leakage and long-term survival. METHODS: In this multicenter retrospective cohort study, 395 consecutive stage I to III rectal cancer patients underwent anterior resection between 2007 and 2012. Five-year overall survival, 5-year disease-free survival, and 5-year local recurrence-free survival were compared between patients with leakage (Leakage (+)) and patients without leakage (Leakage (-)). RESULTS: Of 395 patients, 50 (12.7%) had anastomotic leakage. Of these 50, 34 (68.0%) required urgent surgery and 16 (32.0%) could be managed by watchful waiting or with percutaneous drainage. The median follow-up period was 62.6 months. Five-year overall survival did not differ between the two groups (Leakage (+) 93.8% vs. Leakage (-) 89.0%, P = 0.121). Five-year disease-free survival also did not differ between the two groups (81.6% vs. 80.3%, P = 0.731), and neither did 5-year local recurrence-free survival (91.9% vs. 86.1%, P = 0.206). In a multivariable Cox regression model, BMI > 25, preoperative CA19-9 > 37, pathological T stage, pathological N stage, and circumferential resection margin (CRM) positive were independent predictors of disease-free survival. Moreover, pathological T stage, pathological N stage, and CRM positive were the only independent predictors of overall survival and local recurrence-free survival. Anastomotic leakage was not a risk factor for overall survival, disease-free survival, or local recurrence-free survival. CONCLUSION: Anastomotic leakage is not associated with a significant decrease in long-term survival in rectal cancer patients.

Risk Factors and Outcome of Portal Vein Thrombosis After Laparoscopic and Open Hepatectomy for Primary Liver Cancer: A Single-Center Experience.

BACKGROUND: Post-hepatectomy portal vein thrombosis (PH-PVT) is a severe complication. The risk factors of PH-PVT after laparoscopic and open hepatectomy have not been clarified yet. We aimed to retrospectively investigate the risk factors and outcome of PH-PVT in patients with primary liver cancer. METHODS: We enrolled 622 consecutive patients who underwent hepatectomy in our hospital between January 2006 and August 2016. RESULTS: Of 21 patients (3.4%) with PH-PVT, 7 had grade I; 13, grade II; and 1, grade III. The patients with PH-PVT were significantly older than those without PH-PVT. Of the 413 patients who underwent open hepatectomy, those who underwent a major right hepatectomy (4.1%) had a slightly higher incidence of PH-PVT. Of the 209 patients who underwent laparoscopic hepatectomy, those who underwent a left lateral sectionectomy (21.2%) and major right hepatectomy (16.7%) had high incidence rates of PH-PVT. The treatment was only observation in five patients, medication with an antithrombotic drug in 15 patients, and reoperation in one patient. PH-PVT diminished in 17 patients. Cavernous transformation and/or stenosis of the portal vein developed in three patients. The patient with grade III PH-PVT after open right hemihepatectomy underwent reoperation but died of hepatic failure. CONCLUSION: This study demonstrated that patient age, left lateral sectionectomy were risk factors of PH-PVT. Laparoscopic left lateral sectionectomy and major right hepatectomy might bring about relatively higher risk of PH-PVT. Major right hepatectomy tends to lead to severe PH-PVT. Careful handling of the PV during hepatectomy and early treatment of PH-PVT are necessary.

Our experience with laparoscopic partial gastrectomy by the 'lift-and-cut method' for gastric gastrointestinal stromal tumor with maximal preservation of the remnant stomach.

BACKGROUND: Wedge resection is the most commonly used method in laparoscopic partial gastrectomy for gastric gastrointestinal stromal tumor (GIST). However, this method can involve inadvertent resection of additional gastric tissue and cause gastric deformation. To minimize the volume of resected gastric tissue, we have developed a laparoscopic partial gastrectomy with seromyotomy which we call the 'lift-and-cut method' for gastric GIST. Here, we report a case series of this surgery. METHOD: First, the seromuscular layer around the tumor is cut. Because the mucosa and submucosa are extensible, the tumor is lifted toward the abdominal cavity. After sufficient lifting, the gastric tissue under the tumor is cut at the submucosal layer with a linear stapler (thus 'lift-and-cut method'). Finally, the defect in the seromuscular layer is closed with a hand-sewn suture. RESULTS: From April 2011 to December 2015, 28 patients underwent laparoscopic partial gastrectomy by this method at Osaka Red Cross Hospital. Average operation time was 126 min (range 65-302 min) and average blood loss was 10 ml (range 0-200 ml). No intraoperative complications including tumor rupture or postoperative complications regarded as Clavien-Dindo Grade II or higher occurred. All patients took sufficient solid diet at discharge. Median postoperative hospital stay was 7 days (range 5-21 days). On median follow-up of 26.6 months (range 6-54 months), no recurrence was reported. CONCLUSION: Laparoscopic partial gastrectomy by the lift-and-cut method is safe and simple, and widely applicable for gastric GIST.

The PD-1/PD-L1 axis may be aberrantly activated in occupational cholangiocarcinoma.

An outbreak of cholangiocarcinoma in a printing company was reported in Japan, and these cases were regarded as an occupational disease (occupational cholangiocarcinoma). This study examined the expression status of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) in occupational cholangiocarcinoma. Immunostaining of PD-1, PD-L1, CD3, CD8, and CD163 was performed using tissue sections of occupational cholangiocarcinoma (n = 10), and the results were compared with those of control cases consisting of intrahepatic (n = 23) and extrahepatic (n = 45) cholangiocarcinoma. Carcinoma cells expressed PD-L1 in all cases of occupational cholangiocarcinoma, whereas the detection of PD-L1 expression in cholangiocarcinoma cells was limited to a low number of cases (less than 10%) in the control subjects. In cases of occupational cholangiocarcinoma, occasional PD-L1 expression was also noted in precancerous/preinvasive lesions such as biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct. Additionally, tumor-associated macrophages and tumor-infiltrating T cells expressed PD-L1 and PD-1, respectively. The number of PD-L1-positive mononuclear cells, PD-1-positive lymphocytes, and CD8-positive lymphocytes infiltrating within the tumor was significantly higher in occupational cholangiocarcinoma compared with that in control cases. These results indicate that immune escape via the PD-1/PD-L1 axis may be occurring in occupational cholangiocarcinoma.

Prognostic value of biomarkers in metastatic colorectal cancer patients.

BACKGROUNDS: The prognostic value of biomarkers in metastatic colorectal cancer (mCRC) patients with liver metastases remains unclear. We assessed the difference of expression of biomarkers between primary tumors and liver metastases treated with chemotherapy in mCRC patients, as well as the prognostic value of these markers. METHODS: Forty-three mCRC patients with liver-limited disease from January 2007-November 2011 were analyzed. They all received resection of primary tumors followed by oxaliplatin-based chemotherapy. After chemotherapy, they all received hepatic resection. Forty-three paired primary and metastatic tumor specimens were collected to measure the messenger RNA expression of six biomarkers by the Danenberg tumor profile method (thymidylate synthase, dihydropyrimidine dehydrogenase [DPD], excision repair cross-complementing gene1, thymidine phosphorylase [TP], folylpolyglutamate synthase, and regenerating islet-derived family, member 4). RESULTS: Thirty-six patients' messenger RNA was used for analysis. All markers showed similar expression between primary and metastatic sites. The low-expression group of Danenberg tumor profile and TP in the primary tumor showed significantly higher overall survival than the high-expression group (P < 0.001 and P = 0.033), but for DPD and TP in liver metastases, there were no significant differences of overall survival between the two groups. The ratios of marker expression in liver metastatic site to that in primary site of DPD and TP were significantly higher in chemo-responders than in non-chemo-responders (P = 0.034 and P = 0.022). CONCLUSIONS: Biomarkers' expressions in liver metastases were similar to those in the primary tumor. DPD and TP in the primary lesion may be a prognostic factor in chemotherapy-naïve mCRC patients with liver-limited disease, but those in liver tumor were not. Further validated analysis to our results would be warranted.

Effect of nucleoside analog use in patients with hepatitis B virus-related hepatocellular carcinoma.

AIM: To examine the effect of nucleoside analog (NA) therapy on clinical outcome in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) who underwent curative therapy. METHODS: A total of 131 patients with HBV-related HCC who underwent curative therapy were analyzed. They were divided into an NA group who received NA therapy (n = 99, group A) and a control group (n = 32, group B). Group A was further classified into two groups of patients who either received NA therapy before HCC therapy (n = 34, group Aa) or who received NA therapy with initial HCC therapy (n = 65, group Ab). Overall survival (OS) and recurrence-free survival (RFS) were compared in the three groups. RESULTS: The 1- and 3-year cumulative OS rates were both in group Aa, 100% and 88.0% in group Ab, and 100% and 75.7% in group B (overall significance, P = 0.002), respectively. The corresponding RFS rates were 93.1% and 36.0% in group Aa, 78.3% and 45.7% in group Ab, and 78.0% and 38.0% in group B (overall significance, P = 0.734), respectively. Multivariate analysis revealed that being part of group Aa (P < 0.001) or group Ab (P < 0.001) and having albumin levels of 4.0 g/dL or more (P = 0.040) were significantly associated with OS, while HCC stage (P = 0.001) and hepatitis B e-antigen positivity (P < 0.001) were independent predictors linked to RFS. CONCLUSION: NA therapy in patients with HBV-related HCC may improve survival after curative therapy.

[Transnasal and transanal tube decompression versus self-expanding metallic stent as a bridge to surgery for obstructive colorectal cancer].

PURPOSE: The aim of this study was to compare the efficacy between the use of transnasal and transanal tube decompression and self-expanding metallic stents (SEMS) as a bridge to surgery for obstructive colorectal cancer. MATERIALS: Of a total of 42 patients with obstructive colorectal cancer, 29 were managed with transnasal or transanal tubes and 13 were managed by SEMS. RESULTS: The management duration to surgery in the stent group was longer than that in the tube group (18 vs 11 days; p<.05). More patients in the stent group could be discharged and take food or liquid normally. There was no difference in overall complications including anastomotic leakage, surgical side effects, or primary anastomosis. Perforation occurred in 2 patients in the tube group, while stent migration occurred in 1 patient in the stent group. There was no difference in complications between 2 groups. CONCLUSIONS: SEMS as a bridge to surgery for obstructive colorectal cancer could improve patients' quality of life during the preoperative period. Evaluations of the complications during decompression are needed for both methods.

[Therapeutic strategy for perforated colorectal cancer].

A total of 37 patients were surgically treated for a colorectal perforation between May 2006 and December 2013. The patients were divided into 2 groups: those with perforation due to colorectal cancer(colorectal cancer group, n=12) and those with perforation due to benign colorectal disease(non-colorectal cancer group, n=25). We examined the influence that onset near the perforation had on colorectal cancer clinical outcome. There was no significant difference in patient backgrounds between the two groups. In the colorectal cancer group, curative resections were performed in eight of the cases (67%), while there were 7 cases (58%) of regional lymph node dissection and all patients received a stoma without bowel anastomosis. In the colorectal cancer group, 1 patient (8%) died of a pulmonary embolism after surgery, whereas 2 patients (8.3%) in the non-colorectal cancer group died of sepsis after surgery. Nine of those patients (75%) received adjuvant chemotherapy. Four patients survived without recurrence. Prompt judgment of the disease severity and selection of optical surgical procedures including tumor resection and regional lymph node dissection is important for colorectal cancer perforation, and an adjuvant setting for the purpose of the long-term survival is necessary.

Cholangiocarcinoma among offset colour proof-printing workers exposed to 1,2-dichloropropane and/or dichloromethane.

OBJECTIVES: The present study was conducted to investigate the relationship between occupational chemical exposure and incidence of cholangiocarcinoma among workers in the offset colour proof-printing section of a small printing company in Osaka, Japan. METHODS: We identified 51 men who had worked in the proof-printing room, and 11 men who had worked in the front room for at least 1 year between 1991 and 2006. We interviewed them about the chemicals they used, and estimated their levels of exposure to chemicals. We also investigated the medical records of 11 cholangiocarcinoma patients, and calculated the standardised mortality ratio (SMR) from 1991 to 2011. RESULTS: Workers used 1,2-dichloropropane (1,2-DCP) from approximately 1985 to 2006, and dichloromethane (DCM) from approximately 1985 to 1997/1998. Exposure concentrations were estimated to be 100-670 ppm for 1,2-DCP and 80-540 ppm for DCM among the proof-printing workers. All 11 patients were pathologically diagnosed with cholangiocarcinoma. Ages at diagnosis were 25-45 years, and ages at death were 27-46 years among the six deceased individuals. The primary cancer site was the intrahepatic bile duct for five patients, and the extrahepatic bile ducts for six. All patients were exposed to 1,2-DCP for 7-17 years and diagnosed with cholangiocarcinoma 7-20 years after their first exposure. Ten patients were also exposed to DCM for 1-13 years. The SMR for cholangiocarcinoma was 2900 (expected deaths: 0.00204, 95% CI 1100 to 6400) for all workers combined. CONCLUSIONS: These findings suggest that 1,2-DCP and/or DCM may cause cholangiocarcinoma in humans.

Feasibility and potential benefit of preoperative chemotherapy for colorectal liver metastasis (CLM): a single-centered retrospective study.

PURPOSES: The benefit of neo-adjuvant chemotherapy for liver-limited metastatic colorectal cancer is still controversial. This study defined the resectability regardless of the size and number of liver metastases, and attempted curative hepatic resection in all cases. METHODS: Sixty-four patients that tolerated chemotherapy were diagnosed with CLM (colorectal liver metastases) without extrahepatic metastase from January 2007 to November 2010, and received an oxaliplatin-based regimen. This study assessed the resectability after chemotherapy, and the patients were divided in two groups; the resected and unresected group. Sixteen patients underwent hepatic resection without chemotherapy. RESULTS: Thirty-five patients underwent surgical resection (resected group) and twenty-nine patients were considered unresectable (unresected group). All 35 patients in the resected group safely received oxaliplatin-based chemotherapy safely without serious adverse effects. No serious postoperative complications were observed. The median overall survival (MST) was significantly higher in the resected than in the unresected group (56.93 [95% CI 38.13-75.73] and 25.07 months [95% CI 17.87-32.26], respectively; P < 0.001). The median disease-free survival was 20.2 [95% CI 8.82-31.65] months in the resected group. CONCLUSION: Preoperative chemotherapy for CLM is well tolerated and does not increase postoperative complications. Curative surgery with preoperative chemotherapy has the potential to improve the overall survival in patients with CLM.

[Long-term survival of a patient with extrahepatic cholangiocarcinoma treated with adjuvant radiotherapy for positive ductal margins after surgical resection].

A 57-year-old man with abdominal discomfort visited our hospital. Abdominal computed tomography (CT) revealed no tumorous lesions. Endoscopic retrograde cholangiography (ERC) revealed a tumorous lesion in the middle bile duct. Peroral cholangioscopy-assisted biopsy was performed, and the lesion was diagnosed as a papillary adenocarcinoma. Extra bile duct resection and regional lymph node dissection were performed; however, residual carcinoma in situ was detected at the ductal margins by intraoperative frozen section analysis. Therefore, external radiation therapy at a dose 50.4 Gy/28 Fr was administered after the operation. No complication due to radiotherapy occurred. The patient remains alive and recurrence -free for more than 7 years after the operation. We report the long-term disease-free survival of a patient with extrahepatic cholangiocarcinoma who was treated with external radiation therapy for positive ductal margins after surgical resection.

Comparison of percutaneous radiofrequency thermal ablation and surgical resection for small hepatocellular carcinoma.

BACKGROUND: The purpose of this investigation was to compare the outcome of percutaneous radiofrequency thermal ablation therapy (PRFA) with surgical resection (SR) in the treatment of single and small hepatocellular carcinoma (HCC). METHODS: We conducted a retrospective cohort study on 231 treatment naive patients with a single HCC ≤ 3 cm who had received either curative PRFA (162 patients) or curative SR (69 patients). All patients were regularly followed up after treatment at our department with blood and radiologic tests. RESULTS: The 1-, 3- and 5-year overall survival rates after PRFA and SR were 95.4%, 79.6% and 63.1%, respectively in the PRFA group and 100%, 81.4% and 74.6%, respectively in the SR group. The corresponding recurrence free survival rates at 1, 3 and 5 years after PRFA and SR were 82.0%, 38.3% and 18.0%, respectively in the PRFA group and 86.0%, 47.2% and 26.0%, respectively in the SR group. In terms of overall survival and recurrence free survival, there were no significant differences between these two groups. In comparison of PRFA group patients with liver cirrhosis (LC) (n = 127) and SR group patients with LC (n = 50) and in comparison of PRFA group patients without LC (n = 35) and SR group patients without LC (n = 19), there were also no significant differences between two groups in terms of overall survival and recurrence free survival. In the multivariate analysis of the risk factors contributing to overall survival, serum albumin level was the sole significant factor. In the multivariate analysis of the risk factors contributing to recurrence free survival, presence of LC was the sole significant factor. The rate of serious adverse events in the SR group was significantly higher than that in the PRFA group (P = 0.023). Hospitalization length in the SR group was significantly longer than in the PRFA group (P = 0.013). CONCLUSIONS: PRFA is as effective as SR in the treatment of single and small HCC, and is less invasive than SR. Therefore, PRFA could be a first choice for the treatment of single and small HCC.

Vaccine Based on Dendritic Cells Electroporated with an Exogenous Ovalbumin Protein and Pulsed with Invariant Natural Killer T Cell Ligands Effectively Induces Antigen-Specific Antitumor Immunity.

(1) Background: Cancer vaccines are administered to induce cytotoxic CD8+ T cells (CTLs) specific for tumor antigens. Invariant natural killer T (iNKT) cells, the specific T cells activated by α-galactosylceramide (α-GalCer), play important roles in this process as they are involved in both innate and adaptive immunity. We developed a new cancer vaccine strategy in which dendritic cells (DCs) were loaded with an exogenous ovalbumin (OVA) protein by electroporation (EP) and pulsed with α-GalCer. (2) Methods: We generated bone marrow-derived DCs from C57BL/6 mice, loaded full-length ovalbumin proteins to the DCs by EP, and pulsed them with α-GalCer (OVA-EP-galDCs). The OVA-EP-galDCs were intravenously administered to C57BL/6 mice as a vaccine. We then investigated subsequent immune responses, such as the induction of iNKT cells, NK cells, intrinsic DCs, and OVA-specific CD8+ T cells, including tissue-resident memory T (TRM) cells. (3) Results: The OVA-EP-galDC vaccine efficiently rejected subcutaneous tumors in a manner primarily dependent on CD8+ T cells. In addition to the OVA-specific CD8+ T cells both in early and late phases, we observed the induction of antigen-specific TRM cells in the skin. (4) Conclusions: The OVA-EP-galDC vaccine efficiently induced antigen-specific antitumor immunity, which was sustained over time, as shown by the TRM cells.

Laparoscopic vs open surgery for colorectal cancer patients with high American Society of Anesthesiologists classes.

INTRODUCTION: Laparoscopic surgery has become popular for colorectal cancer treatment in recent years. However, its success rate even among high-risk patients remains debatable. The present study aims to compare the short- and long-term outcomes between laparoscopic and open surgeries in the American Society of Anesthesiologists (ASA) classes 3 and 4 patients with colorectal cancer. METHODS: This was a single-center, retrospective, cohort study performed at a university hospital, with 78 patients suffering from colorectal cancer who underwent surgery in ASA classes 3 and 4 as respondents. Patient and tumor characteristics, operative outcomes, and prognoses were factors compared between the open and laparoscopic groups. RESULTS: Compared with the open group, laparoscopic group had longer operation time (median 287.5 vs 204.5 minutes, P = .001), less operative blood loss (median 40 vs 240 mL, P = .020), and fewer postoperative complications (24% vs 55%, P = .011). In addition, operative approach (open vs laparoscopic) served as an independent factor for the occurrence of postoperative complications [HR = 3.963 (1.344-12.269), P = .013]. In terms of overall survival and recurrence-free survival (P = .171 and .087, respectively), no significant difference was found between the two groups. CONCLUSION: Laparoscopic surgery is thus associated with more favorable short-time outcomes and could be adopted as treatment even for colorectal cancer ASA class 3 and 4 patients.

Evaluation of the venous drainage pattern of the splenic flexure by preoperative three-dimensional computed tomography.

INTRODUCTION: Anatomical evaluation of the splenic flexure vein is essential for complete mesocolic excision with central vascular ligation when treating patients with splenic flexure cancer. Although there have been several studies relating to the arterial branches of the splenic flexure, very limited data are available regarding the variation in venous anatomy in this region. METHODS: Sixty-six patients with colorectal cancer who underwent preoperative 3-D CT between April 2016 and April 2017 were included in this retrospective study. The pattern of the venous drainage of the splenic flexure and its association with the inferior border of the pancreas were evaluated. RESULTS: The inferior mesenteric vein flowed into the splenic vein in 32 patients (48.5%), into the superior mesenteric vein in 27 patients (40.9%), and into the confluence of splenic vein and superior mesenteric vein in 7 patients (10.6%). The splenic flexure vein joined the inferior mesenteric vein in 62 patients (93.9%), the splenic vein in 2 patients (3.0%), and the middle colic vein in 2 patients (3.0%). The splenic flexure vein flowed into the inferior mesenteric vein below the level of the inferior border of the pancreas in 58 patients (90.6%) and above it in 4 patients (6.3%). CONCLUSION: Preoperative evaluation of the venous pattern of the splenic flexure on 3-D CT is useful before complete mesocolic excision with central vascular ligation to avoid intraoperative bleeding during splenic flexure cancer surgery.

Neoadjuvant Chemotherapy Increases PD-L1 Expression and CD8+ Tumor-infiltrating Lymphocytes in Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIM: The aim of this study was to investigate PD-L1 expression and its association with prognosis in esophageal squamous cell carcinoma (ESCC) before and after neoadjuvant chemotherapy (5-fluorouracil and cisplatin, NAC-FP). PATIENTS AND METHODS: Using a database of 69 ESCC patients, we analyzed PD-L1 expression on tumor cells (TCs) and immune cells (ICs), as well as the density of CD8+ tumor-infiltrating lymphocytes (TILs) in pretreatment biopsy specimens-versus-surgical specimens after resection. We determined the prognostic significance of these factors. RESULTS: The fraction of ESCC containing ICs expressing PD-L1 and having a high CD8+ TIL density was significantly increased after neoadjuvant treatment. However, PD-L1 expression on TCs or ICs, and CD8+ TIL density, was not significantly associated with patient survival in ESCC patients. CONCLUSION: NAC-FP induced PD-L1 expression on ICs and CD8+ TILs in ESCC patients. This finding suggests that PD-1/PD-L1 blockade could be combined with NAC-FP to treat ESCC patients.