Prognostic Nutrition Index as a Biomarker for Treatment Sensitivity to Chemotherapy and Nivolumab as the First-Line Treatment in Patients with Unresectable Advanced or Recurrent Gastric Cancer: A Multicenter Study.

INTRODUCTION: This multicenter study aimed to determine whether the pretreatment prognostic nutrition index (PNI) or a change in the index after two treatment courses could be a biomarker for predicting treatment sensitivity in patients with unresectable advanced or recurrent gastric cancer (GC) treated using chemotherapy and nivolumab as the first-line treatment. METHODS: This multicenter retrospective study with 104 patients was conducted at 12 institutions. PNI was calculated before treatment and after two courses of treatment in each case. We also focused on changes in PNI from the pretreatment value. RESULTS: After two courses of chemotherapy plus nivolumab treatment, the high PNI group had significantly better rates of overall survival (OS) (p = 0.0016) and time to treatment failure (p = 0.0060). Low PNI was an independent prognostic factor predicting both therapeutic sensitivity to chemotherapy plus nivolumab treatment and poorer OS. Furthermore, correlation with low pretreatment PNI transitioning to high after two courses of treatment was not noted in any patient in the progressive disease group (p = 0.0075). CONCLUSIONS: PNI is a score composed of a patient's albumin level and lymphocyte count that can be easily assessed in daily clinical practice. Evaluating it is easy for each treatment; thus, when there is a focus on its transition, PNI could be a very powerful biomarker for predicting treatment sensitivity.

A case of completely resected cecum cancer with synchronous metastases to the small intestine found in acute appendicitis.

PURPOSE: Risk of malignant tumors increase with age;hence, careful examination of older patients should be consdiered when identifying the causes of acute appendicitis. Here, we report a case of a patient with cecum cancer with synchronous metastases to the small intestine that was found during acute appendicitis. CASE REPORT: A 74-year-old man presented with right lower abdominal pain. Physical examination revealed deep tenderness at McBurney's point. Enhanced computed tomography scan showed an abscess around the enlarged appendix and a thickened cecum wall. Colonoscopy revealed a type 2 tumor in the ileocecal region, and pathological examination of the biopsied specimen revealed adenocarcinoma. Microscopic findings revealed two type 2 tumors in the small intestine, pathologically diagnosed as cecum cancer metastases. The final diagnosis was acute appendicitis caused by cecum cancer with synchronous metastases to the small intestine, pStage ⅣB pT4bN1aM1b. The patient received adjuvant chemotherapy and has currently been disease-free for 24 months. CONCLUSIONS: In prolonged appendicitis among older adults, the possibility of malignancy should be considered during preoperative examination and prior to selecting a treatment plan. Delays in the diagnosis of colorectal cancer and metastases may lead to missed opportunities for complete resection and poor prognosis. J. Med. Invest. 71 : 293-297, August, 2024.

Impact of Tumoral ß2-Adrenergic Receptor Expression on Chemotherapeutic Response and Prognosis in Patients with Advanced Colorectal Cancer.

BACKGROUND: The ß2-adrenergic receptor (ß2-AR) is a therapeutic target for circulatory agonists and exhibits oncogenic activity in several cancers. However, its role in advanced colorectal cancer (CRC) treated using chemotherapy remains unclear. We investigated the potential of ß2-AR as a novel chemosensitivity marker and therapeutic target in inoperable CRC. METHODS: ß2-AR expression was evaluated immunohistochemically in 80 advanced or recurrent CRC cases for which untreated resected specimens were available before systemic chemotherapy implementation. We assessed the relationship among ß2-AR protein expression, clinicopathological factors, therapeutic response, and prognosis. Furthermore, we evaluated the significance of ß2-AR as an in vitro and in vivo therapeutic target using CRC cell lines and a CRC xenograft model treated with the ß-blocker, propranolol, and other anticancer agents. RESULTS: High tumoral ß2-AR expression was associated with shorter progression-free survival and chemotherapeutic resistance in patients treated with oxaliplatin-based regimens and bevacizumab-based regimens. We found no synergistic effect between propranolol and oxaliplatin. However, combined administration of propranolol and bevacizumab induced significant tumor shrinkage in the CRC xenograft model. CONCLUSIONS: ß2-AR is a possible biomarker for chemosensitivity and prognosis in advanced CRC. Repositioning existing ß-blockers could be beneficial for treating CRC resistant to existing treatment regimens.

Identification of Biomarkers for Assessing Treatment Efficacy of Chemotherapy plus Nivolumab as the First Line in Patients with Unresectable Advanced or Recurrent Gastric Cancer: A Multicenter Study.

INTRODUCTION: In this study, we aimed to identify biomarkers for predicting treatment outcomes and efficacy of chemotherapy plus nivolumab, as well as predict immune-related adverse events (irAEs) characteristics of immune checkpoint inhibitors. METHODS: This multicenter study included 104 patients who received chemotherapy plus nivolumab as the primary treatment for unresectable advanced recurrent gastric cancer. Blood test results were collected before the start and after two courses of treatment. The neutrophil-lymphocyte ratio, prognostic nutritional index, and lactate dehydrogenase/albumin ratio (LAR) were examined after treatment in each case to determine changes compared to values before the start of treatment. RESULTS: A total of 57 (54.8%) patients experienced a complete or partial response. The LAR of the stable disease/progressive disease group significantly increased (p = 0.018). An examination of the presence of grade ≥3 irAEs and changes in related factors showed that the LAR of all patients increased. CONCLUSION: The LAR was correlated with the best therapeutic response; therefore, it may be a potential biomarker of treatment outcomes and efficacy.

Conversion Surgery After Chemotherapy Plus Nivolumab as the First-Line Treatment for Unresectable Advanced or Recurrent Gastric Cancer and a Biomarker Study Using the Gustave Roussy Immune Score: A Multicenter Study.

BACKGROUND: There are few reports on conversion surgery (CS) after chemotherapy plus nivolumab as a first-line treatment in patients with unresectable advanced or recurrent gastric cancer (GC). This multicenter study was conducted to analyze real-world data on CS after chemotherapy plus nivolumab as a first-line treatment and to identify predictive biomarkers. METHODS: This multicenter study included 104 patients who received chemotherapy plus nivolumab as primary treatment for unresectable advanced recurrent GC from 12 institutes. We investigated and analyzed patient characteristics and blood test data in the presence or absence of CS, the relationship between the Gustave Roussy Immune Score (GRIm-s) and CS, and the characteristics of CS cases. RESULTS: CS was performed in 12 patients (11.5%). Eastern Cooperative Oncology Group Performance Status (ECOG-PS) was significantly better in patients who underwent CS (p < 0.0001). There were no CS cases with high-risk GRIm-s (0%), however there were 22 non-CS cases (23.9%). No high-risk GRIm-s cases were converted to CS. Minimally invasive surgery was performed in 50.0% of the cases, with R0 resection in all cases and only one case of urinary retention (Grade II) as a postoperative complication, indicating a good postoperative short-term outcome. There were two cases of postoperative recurrence (16.7%), both of which were grade 1b. CONCLUSIONS: The short-term postoperative results of CS after chemotherapy plus nivolumab as the first-line treatment for GC were acceptable in this study. There were no high-risk GRIm-s cases among those who underwent CS, suggesting that the GRIm-s may be a predictor of CS.

A Mature Tertiary Lymphoid Structure with a Ki-67-Positive Proliferating Germinal Center Is Associated with a Good Prognosis and High Intratumoral Immune Cell Infiltration in Advanced Colorectal Cancer.

Tertiary lymphoid structures (TLSs) are complex lymphocyte clusters that arise in non-lymphoid tissues due to inflammation or cancer. A mature TLS with proliferating germinal centers is associated with a favorable prognosis in various cancers. However, the effect of TLS maturity on advanced colorectal cancer (CRC) remains unexplored. We analyzed the significance of TLS maturity and tumor Ki-67 expression in surgically resected tumors from 78 patients with pathological T4 CRC. Mature TLS was defined as the organized infiltration of T and B cells with Ki-67-positive proliferating germinal centers. We analyzed the relationship between TLS maturity and intratumoral immune cell infiltration. Mature TLS with germinal center Ki-67 expression was associated with microsatellite instability and improved survival; however, high tumor Ki-67 expression was associated with poor survival in the same cohort. Multivariate analysis identified the absence of mature TLS as an independent predictor of poor post-recurrence overall survival. Intratumoral infiltration of T lymphocytes and macrophages was significantly elevated in tumors with mature TLS compared to those lacking it. High Ki-67 levels and absent mature TLS were identified as poor prognostic factors in advanced CRC. Mature TLS could serve as a promising marker for patients at high-risk of CRC.

Risk Factors of Poor Outcomes After Colorectal Cancer Surgery for Patients With Severe Comorbidities.

BACKGROUND/AIM: An increasing number of patients with complicated systemic comorbidity can undergo colorectal cancer (CRC) surgery. Such patients have a high risk of developing poor postoperative outcomes. This study aimed to identify preoperative factors, including nutritional and sarcopenia statuses, leading to poor postoperative outcomes in patients with severe systemic comorbidities. PATIENTS AND METHODS: This study included 114 patients who underwent radical CRC resections and had American Society of Anesthesiologists Physical Statuses ≥3. We retrospectively analyzed the relationships between clinical factors, postoperative complications (within 28 days postoperatively and Clavien-Dindo classification grade ≥2), length of hospital stay, discharge destination, and overall survival (OS). RESULTS: The median patient age was 74.5 years (range=41.0-93.0 years). Thirty-six patients had postoperative complications (31.6%), and the risk factors in the multivariate analyses were rectal cancer and preoperative nutritional disorders with Prognostic Nutritional Index ≤40. In patients with nutritional disorders, the postoperative hospital stay was longer, and a higher (but not statistically significant) percentage were not discharged home. Moreover, the independent factors for OS identified in the multivariate analyses were body mass index (BMI) and hemodialysis. CONCLUSION: In patients with CRC and severe systemic comorbidities, those with Prognostic Nutritional Index ≤40 have a high risk of developing postoperative complications, leading to a prolonged postoperative hospital stay and possibly preventing discharge home. Additionally, among these patients, OS was poor in those with low BMI or preoperative hemodialysis.

Poorly cohesive gastric cancer with increased epithelial­mesenchymal transition is associated with a poor prognosis.

The present study examined the surgical outcome and prognosis of patients with poorly cohesive carcinoma (PCC), and characterized the molecular pathological factors, epithelial-mesenchymal transition (EMT) and interstitial signals of the disease. A total of 281 patients who underwent gastric cancer (GC) surgery between April 2015 and August 2020 were included. Furthermore, tissue samples from another 197 patients with GC who underwent surgery between 1999 and 2003 were assessed using a tissue microarray. Preoperatively treated cases and endoscopic submucosal dissection cases were excluded, and multiple blocks containing the invasion region were collected for tissue microarray. For tissue microarray analysis, the clinicopathological factors of protein wnt3a (wnt3a), leucine-rich repeat-containing G-protein coupled receptor 5, transforming growth factor-ß-induced, phosphorylated serine/threonine-protein kinase mTOR and E-cadherin expression were collected as EMT markers. The results of the surgical case evaluation and tissue microarray indicated that PCC was more common in younger patients and women, as the ratio of women to men was higher in the PCC group compared with that in the non-PCC group. However, none of the results revealed that the prognosis was worse in all patients with PCC compared with the non-PCC group. Furthermore, in the tissue microarray study, PCC samples exhibited significantly decreased expression of the cell adhesion molecule E-cadherin, suggesting enhanced EMT, which activates wnt3a signaling. PCC with increased EMT was significantly associated with a poor prognosis.

The Gustave Roussy Immune score is a powerful biomarker for predicting therapeutic resistance to chemotherapy in gastric cancer patients.

PURPOSE: It is highly important to be able to predict the therapeutic efficacy of chemotherapy on patients with unresectable advanced or recurrent gastric cancer (GC). The Gustave Roussy Immune Score (GRIm-s) is a predictor of therapeutic sensitivity to chemotherapy and immune checkpoint inhibitors (ICIs) in other cancers. The present study aimed to analyze the association of the GRIm-s with the therapeutic sensitivity of first-line chemotherapy in GC patients. METHODS: We included 156 patients receiving primary chemotherapy treatment for unresectable or advanced recurrent GC between January 2012 and December 2021 at our institution. We evaluated the correlation between the GRIm-s and therapeutic sensitivities to chemotherapy. The GRIm-s was assessed before the start of first-line chemotherapy. RESULTS: Among the 156 patients, 138 (88.5%) and 18 (11.5%) were classified in the low- and high-risk groups, respectively. The GRIm-s high-risk group was significantly older (p = 0.013), had more advanced unresectable cancer (p = 0.0098), and was significantly less likely to progress to second-line chemotherapy (p = 0.014). The overall survival rate (OS) (p = 0.039) and the progression free survival rate (PFS) (p = 0.017) were significantly worse in the GRIm-s high-risk group. The high GRIm-s was an independent prognostic factor for poor survival in multivariate analysis (p = 0.0094). CONCLUSIONS: Focusing on the GRIm-s before first-line chemotherapy initiation for unresectable advanced or postoperative recurrent GC was useful in predicting the therapeutic resistance to chemotherapy, transition to second-line chemotherapy, and poor prognosis.

Importance of duodenal stump reinforcement to prevent stump leakage after gastrectomy: a large-scale multicenter retrospective study (KSCC DELICATE study).

BACKGROUND: The significance of reinforcement of the duodenal stump with seromuscular sutures and the effectiveness of reinforced staplers in preventing duodenal stump leakage remain unclear. We aimed to explore the importance of duodenal stump reinforcement and determine the optimal reinforcement method for preventing duodenal stump leakage. METHODS: This retrospective cohort study was conducted between January 1, 2012 and December 31, 2021, with data analyzed between December 1, 2022 and September 30, 2023. This multicenter study across 57 institutes in Japan included 16,475 patients with gastric cancer who underwent radical gastrectomies. Elective open or minimally invasive (laparoscopic or robotic) gastrectomy was performed in patients with gastric cancer. RESULTS: Duodenal stump leakage occurred in 153 (0.93%) of 16,475 patients. The proportions of males, patients aged ≥ 75 years, and ≥ pN1 were higher in patients with duodenal stump leakage than in those without duodenal stump leakage. The incidence of duodenal stump leakage was significantly lower in the group treated with reinforcement by seromuscular sutures or using reinforced stapler than in the group without reinforcement (0.72% vs. 1.19%, p = 0.002). Duodenal stump leakage incidence was also significantly lower in high-volume institutions than in low-volume institutions (0.70% vs. 1.65%, p = 0.047). The rate of duodenal stump leakage-related mortality was 7.8% (12/153). In the multivariate analysis, preoperative asthma and duodenal invasion were identified as independent preoperative risk factors for duodenal stump leakage-related mortality. CONCLUSIONS: The duodenal stump should be reinforced to prevent duodenal stump leakage after radical gastrectomy in patients with gastric cancer.

Risks and Outcomes of Early Dose Reduction in Adjuvant CAPOX Therapy for Colorectal Cancer.

BACKGROUND/AIM: Adjuvant capecitabine and oxaliplatin (CAPOX) therapy is standard strategy for colorectal cancer with risk of recurrence. Early dose reduction (EDR) of CAPOX therapy is commonly used in real-world practice. However, there is limited evidence regarding the effectiveness of CAPOX for patients who had EDR. Therefore, this study aimed to clarify the risks of EDR and its effect on long-term outcomes and body composition factors. PATIENTS AND METHODS: Patients who received CAPOX therapy after radical surgery for colorectal cancer between June 2013 and December 2021 were included. EDR was defined as dose reduction within four courses of CAPOX therapy. Body composition factors were measured for 1 year following surgery to determine the EDR effects. RESULTS: Eighty-four patients were included; 35 (42%) of them had EDR. The multivariate analysis revealed that underweight [odds ratio (OR)=4.95, 95% confidence interval (CI)=1.13-21.7, p=0.03] was a risk factor for EDR. Relapse-free survival (RFS) was significantly better in the non-EDR group (p=0.01). The 5-year RFS rates for the non-EDR and EDR groups were 88.7% and 65.4%, respectively. The multivariate analysis revealed that age >65 years [hazard ratio (HR)=3.97; 95% CI=1.16-13.62, p=0.03] and EDR (HR=7.62; 95% CI=1.71-33.91, p=0.005) were associated with poorer RFS. The 1-year body composition analysis revealed decreases in all factors in the EDR group. CONCLUSION: Preoperative underweight status was associated with EDR, which resulted in decreased RFS and body composition factors when compared with the non-EDR group. Therefore, avoiding EDR and early nutritional intervention after EDR may improve outcomes.

Preoperative factors associated with lateral lymph node metastasis in lower rectal cancer and the evaluation of the middle rectal artery.

PURPOSE: This study aimed to identify cases in which lateral lymph node (LLN) dissection (LLND) can be excluded by clarifying preoperative factors, including an evaluation of the middle rectal artery (MRA), associated with LLN metastasis. METHODS: Fifty-five consecutive patients who underwent preoperative positron emission tomography-computed tomography (PET/CT) and total mesorectal excision with LLND for rectal cancer were included. We retrospectively investigated the preoperative clinical factors associated with pathological LLN (pLLN) metastasis. We analyzed the regions of pLLN metastasis using MRA. RESULTS: pLLN metastasis occurred in 13 (23.6%) patients. According to a multivariate analysis, clinical LLN (cLLN) metastasis based on short-axis size and LLN status based on PET/CT were independent preoperative factors of pLLN metastasis. The negative predictive value (NPV) was high (97.1%) in patients evaluated as negative based on PET/CT and cLLN short-axis size. MRA was detected in 24 patients (43.6%) using contrast-enhanced CT, and there was a significant relationship between pLLN metastasis and the presence of MRA. pLLN metastasis in the internal iliac region but not in the obturator region was significantly correlated with the presence of MRA. CONCLUSION: Combined cLLN metastasis based on short-axis size and PET/CT showed a higher NPV, suggesting this to be a useful method for identifying cases in which LLND can be excluded.

Damage to the Descending Colon after Endoscopic Balloon Dilatation following a Minor Traffic Accident in a Patient with Crohn's Disease: A Case Report.

Introduction: Crohn's disease (CD) is complicated by intestinal strictures and fistula formation; however, intestinal perforation is relatively rare. Case Presentation: Following a traffic accident in the evening, a 39-year-old woman experienced abdominal pain that worsened the following morning and was taken to the emergency department. She had a 17-year history of CD and eight endoscopic balloon dilations for descending colonic strictures. She presented with a high fever of 40.0°C, along with tenderness and rebound pain throughout her abdomen, with the most substantial point being in the lower left abdomen. Computed tomography showed thickening of the descending colon wall, increased fat concentration around the wall, and a slight presence of air in the mesentery near the intestinal wall. We diagnosed the patient with generalized peritonitis due to traumatic penetration of the mesentery of the descending colon and performed emergency surgery. Intraoperative observation of the abdominal cavity with a laparoscope revealed purulent ascites but no apparent perforation or edematous mesentery, with white moss and redness in the descending colon. This prompted the decision to perform peritoneal lavage drainage and a transverse colonic double colostomy. The postoperative course was favorable, and the patient was discharged from the hospital on the postoperative day 14. Four months after discharge, colostomy closure was performed. Conclusion: Relatively minor trauma in patients with CD can result in colon injury. An injured bowel is usually accompanied by active lesions due to CD; however, caution is required, as endoscopic balloon dilatation without accompaniment may be a background factor.

Squamous cell carcinoma of the anus successfully treated with multidisciplinary therapy for metachronous metastatic and local recurrences after DCF chemotherapy: a case report.

BACKGROUND: Docetaxel, cisplatin, and 5-fluorouracil (DCF) chemotherapy is reportedly an effective treatment strategy for squamous cell carcinoma of the anus (SCCA). However, studies regarding its use in Japanese patients remain scarce. CASE PRESENTATION: Here, we present the case of an 82-year-old woman with SCCA, cStage IIIB. Chemoradiotherapy was initiated after colostomy of the anorectal mass; however, para-aortic lymph node recurrence was observed 3 months after treatment completion. Five courses of DCF chemotherapy were subsequently administered, resulting in a complete response (CR). Two years and 1 month later, the aortic lymph node was enlarged again, and the patient achieved CR again after radiotherapy. Nine months later, local recurrence was detected in the anal canal, and laparoscopic perineal rectal amputation was performed. The patient remains progression-free 5 years and 10 months after the initial treatment and 1 year and 7 months after the final treatment. CONCLUSIONS: Our findings suggest that complementary treatment after DCF chemotherapy may be efficacious in Japanese patients with SCCA and help achieve CR. Despite occasional local recurrences, this approach may help achieve long-term progression-free survival.

Efficacy of thoracic endovascular aortic repair for aorto-esophageal fistula due to esophageal cancer: a systematic review and meta-analysis.

Aorto-esophageal fistula (AEF) due to esophageal cancer (EC) is a life-threatening condition characterized by sudden hemorrhage, which often causes sudden death. To evaluate the efficacy and safety of thoracic endovascular aortic repair (TEVAR) for AEF due to EC, we performed a systematic review and meta-analysis. We searched the MEDLINE (PubMed) databases, the Cochrane Library databases, Ichushi-Web (the databases of the Japan Medical Abstract Society), and CiNii (Academic information search service of the National Institute of Information from Japan) from January 2000 to November 2023 for articles about TEVAR for an emergent aortic hemorrhage (salvage TEVAR [S-TEVAR]), and the prophylactic procedure (P-TEVAR). Six studies (140 cases) were eligible for meta-analysis. The 90-day mortality of S-TEVAR and P-TEVAR was 40% (95% CI 23-60, I2 = 36%) and 8% (95% CI 3-17, I2 = 0%), respectively. Post-S-TEVAR hemorrhagic and infectious complications were 17% (95% CI 3-57, I2 = 71%) and 20% (95% CI 5-57, I2 = 66%), respectively. Post-P-TEVAR hemorrhagic and infectious complications were 2% (95% CI 0-10, I2 = 0%) and 3% (95% CI 1-12, I2 = 0%), respectively. TEVAR for AEF due to EC may be a useful therapeutic option to manage or prevent hemorrhagic oncological emergencies.

Two-Team Transanal Total Mesorectal Excision and En Bloc Resection of the Lateral Pelvic Lymph Nodes, Main Iliac Vessels, and Pelvic Plexus for Locally Advanced Rectal Cancer With Lateral Lymph Node Metastasis.

BACKGROUND: Here, we describe the precise surgical technique for a novel procedure involving 2-team transanal total mesorectal excision with en bloc lateral pelvic lymph node (LPLN) dissection combined with resection of the involved main internal iliac vessels and pelvic plexus. METHODS: From September 2020 to May 2023, 4 patients underwent the procedure at our hospital. RESULTS: The operation time and blood loss were 272 to 412 minutes and 10 to 124 mL, respectively. No patients required conversion to open surgery or exhibited Clavien-Dindo grade III or worse postoperative complications, although 2 developed grade II urinary dysfunction. All surgical margins were negative. CONCLUSIONS: Our novel 2-team method can facilitate safe and satisfactory surgery, even for highly advanced rectal cancer. The transanal approach offers excellent visibility and operability, even during LPLN and adjacent structure dissection. Furthermore, initial dissection of the distal branches of the iliac vessels prevents excessive lymphatic tissue congestion, facilitating easier, and clearer dissection.

Retrograde drainage for duodenal stump leakage using ileal decompression tube guided by double-balloon endoscopy: a novel case report.

BACKGROUND: Duodenal stump leakage is a serious post-gastrectomy complication, and there have been no reports on endoscopic drainage. CASE PRESENTATION: We report a case of duodenal stump leakage after laparoscopic gastrectomy with Roux-en-Y reconstruction in a 68-year-old man. First-line conservative management was ineffective. Reoperation was performed because of severe abdominal pain and increased ascites. After reoperation, duodenal stump leakage recurred with bleeding from the anterior superior pancreaticoduodenal artery. Coil embolization and pigtail catheter insertion were performed. Furthermore, we retrogradely inserted an ileal tube for tube decompression near the duodenal stump using double-balloon endoscopy for effective drainage. After tube insertion, duodenal stump leakage decreased; on the 47th primary postoperative day, the patient was discharged. The primary postoperative course was uneventful after 1 year and 9 months of follow-up. CONCLUSIONS: This is the first successful case of duodenal stump leakage treated with retrograde decompression tube insertion near the duodenal stump using double-balloon endoscopy.

Effectiveness of Combination Chemotherapy With Docetaxel, Nedaplatin, and 5-Fluorouracil for Advanced and Recurrent Esophageal Cancer.

BACKGROUND/AIM: Chemotherapy and immunotherapy have been recently developed as potentially useful first-line treatments for unresectable, advanced, or recurrent esophageal cancer. We performed a retrospective study of the therapeutic effectiveness of triplet chemotherapy with docetaxel, nedaplatin, and 5-fluorouracil therapy for advanced, recurrent, and unresectable advanced esophageal cancer at our hospital and compared the regimen's results with those of current and possible future treatment options. PATIENTS AND METHODS: The study cohort comprised 101 patients who received docetaxel, nedaplatin, and 5-fluorouracil for advanced or recurrent esophageal cancer at Gunma University from May 2008 to December 2017. We retrospectively evaluated the results of this combination chemotherapy and postulated future treatment strategies. RESULTS: The overall response and disease control rates, the latter including stable disease, for docetaxel, nedaplatin, and 5-fluorouracil were 33.6% and 61.4%, respectively. The median overall survival and progression-free survival were 12.26 months and 5.1 months, respectively. In patients with recurrence, the median overall and progression-free survivals were 14.97 months (449 days) and 5.1 months (152 days), respectively. No study patients developed acute kidney injury and there were no treatment-related deaths. However, leukopenia and neutropenia were frequent hematologic toxicities. CONCLUSION: Treatment with docetaxel, nedaplatin, and 5-fluorouracil for advanced or recurrent esophageal cancer is particularly useful for recurrent cases and has the advantage of not causing severe renal dysfunction.

Prognostic value of a modified­immune scoring system in patients with pathological T4 colorectal cancer.

Tumor-infiltrating immune cells, such as lymphocytes and macrophages, have been associated with tumor aggressiveness, prognosis and treatment response in colorectal cancer (CRC). An immune scoring system, Immunoscore (IS), based on tumor-infiltrating T cells in stage I-III CRC, was used to predict prognosis. An alternative immune scoring signature of immune activation (SIA) reflects the balance between anti- and pro-tumoral immune components. The present study aimed to evaluate the prognostic value of modified IS (mIS) and modified SIA (mSIA) in locally advanced pathological T4 (pT4) CRC, including stage IV CRC. Immunohistochemical staining for immune cell markers, such as CD3 (pan-T cell marker), CD8 (anti-tumoral cytotoxic T cell marker) and CD163 (tumor-supportive macrophage marker), in specimens from patients with radically resected pT4 CRC at stages II-IV was performed. mIS levels in the T4 CRC cohort were not associated with prognosis. However, low mSIA levels were associated with low survival. Furthermore, low mSIA was an independent predictor of recurrence in patients with radically resected pT4 CRC. In patients with CRC who did not receive postoperative adjuvant chemotherapy, low mSIA was a major poor prognostic factor; however, this was not observed in patients receiving adjuvant chemotherapy. Evaluation of the tumor-infiltrating immune cell population could serve as a valuable marker of recurrence and poor prognosis in patients with locally advanced CRC. mSIA assessment after radical CRC resection may be promising for identifying high-risk patients with pT4 CRC who require aggressive adjuvant chemotherapy.