Adverse Events in Patients With Esophageal Cancer Treated With Nivolumab in Combination With Radiotherapy.

BACKGROUND/AIM: When nivolumab is administered as second-line therapy for esophageal cancer, radiotherapy may also be provided in cases either concurrently or sequentially. The aim of this study was to retrospectively examine whether the incidence of adverse events increases in such cases. PATIENTS AND METHODS: Twenty-two esophageal cancer patients [17 males and 5 females; mean age 71 years (range=58-87 years)] treated with nivolumab were included. Patients were divided into two treatment groups: nivolumab alone (N group) (12 patients) and nivolumab combined with radiotherapy (R group) (10 patients). All patients had squamous cell carcinoma. The primary outcomes measured were the severity and frequency of adverse events. RESULTS: Adverse events were seen in 6 of the 12 patients in the N group and 8 of the 10 in the R group. There were significantly more adverse events in the R group (p=0.035), but no difference in Grade 3 or higher adverse events (p=0.781), indicating that the adverse events were controllable. There was no significant difference in treatment effect between the N and R groups. CONCLUSION: In this report, 50% of adverse events in the N group were grade 3-4, 25% of which were grade 4, as seen in previous reports. In the present study, the side effects were not enhanced by treatment with immune checkpoint inhibitors plus radiotherapy. Immune checkpoint inhibitors plus radiation therapy would be a relatively safe treatment and may become an option for esophageal cancer treatment in the future.

Prognostic Nutritional Index as a Predictor of Prognosis in Postoperative Patients With Gastric Cancer.

BACKGROUND/AIM: The prognostic nutritional index (PNI) has been reported as an immunonutritional index that can easily evaluate nutritional status and immunocompetence from blood tests. The purpose of this study was to investigate the usefulness of PNI as a prognostic factor in postoperative gastric cancer patients. PATIENTS AND METHODS: In this retrospective cohort study, we evaluated 258 patients with pStage I-III gastric cancer who underwent radical resection at Yokohama City University Hospital, from 2015 to 2021. To examine the association with prognosis, we analyzed clinicopathological factors including PNI (<47/≥47), age (<75/≥75), sex (male/female), depth (pT1/≥pT2), lymph node metastasis (pN+/pN-), lymphatic invasion (ly+/ly-), vascular invasion (v+/v-), histological type (enteric/spread) and postoperative complications. RESULTS: In univariate analysis, PNI (p<0.001), depth of tumor invasion (p<0.001), lymph node involvement (p<0.001), age (p=0.002), lymphatic invasion (p<0.001), vascular invasion (p<0.001), and postoperative complications (p=0.003) were associated with overall survival. In multivariate analysis, PNI (HR=2.100, 95% confidence interval 1.225-3.601, p=0.007), tumor invasion, lymph node metastasis, and postoperative complications were shown as poor prognostic factors for overall survival. CONCLUSION: PNI is an independent prognostic factor for overall and recurrence-free survival in postoperative gastric cancer patients. PNI could be implemented in clinical practice to identify patients at higher risk for poor outcomes.

Prognostic Value of the Perioperative Systemic Inflammation Score for Patients With Curatively Resected Gastric Cancer.

BACKGROUND/AIM: The systemic inflammation score (SIS) is a promising tool for the evaluation of prognosis. The present study aimed to evaluate the clinical impact of the preoperative SIS status in gastric cancer (GC) patients who underwent curative resection. PATIENTS AND METHODS: This study retrospectively analyzed 258 patients with primary gastric cancer who received curative treatment at Yokohama City University. The SIS was evaluated before surgery as determined by the lymphocyte-to-monocyte ratio (cut-off value=4.44) and serum albumin level (cut-off value=4.0 g/dl). RESULTS: A high SIS was identified as an independent predictor of overall survival [hazard ratio (HR)=1.784, p<0.05] and multivariate analysis showed marginal significance for recurrence-free survival (HR=1.710, p<0.05). CONCLUSION: The preoperative SIS score was correlated with both the OS and RFS of GC patients, as well as the clinical course of adjuvant chemotherapy. Thus, the SIS score is a promising prognostic factor for GC.

[A Case of Rectal Cancer with Brain and Skin Metastasis with Long-Term Survival Managed by Multidisciplinary Therapy].

A 74-year-old man presented with a metastatic brain tumor in the right parietal lobe observed through an MRI scan. Lower gastrointestinal endoscopy revealed that the tumor was located in the rectum. He was diagnosed with Stage Ⅳb rectal cancer(cT4aN1bM1b[BRA, SKN]). After prior stereotactic radiotherapy for brain metastases, the patient underwent rectal amputation and D3 dissection as management for the primary tumor. His postoperative course was uneventful, and he was discharged from the hospital 33 days postoperatively. He displayed partial response with capecitabine plus L-OHP therapy, and chemotherapy was terminated due to the development of renal dysfunction. On follow-up, elevated tumor markers, enlarged left mediastinal lymph nodes, and FDG accumulation on PET-CT were observed. Despite initiating UFT/UZEL therapy, the patient was judged to have progressive disease. The patient was then administered 5-FU plus l-LV plus CPT-11. However, this was later discontinued due to the development of hyperammonemia. The patient was placed on follow-up observation due to the decrease in his tumor markers and the disappearance of his enlarged lymph nodes. He is still alive seven years after his initial diagnosis. We report a case of a patient with rectal cancer that metastasized to the brain and the skin. He was successfully managed with multidisciplinary therapy. A relevant literature discussion is also included.

Evaluating prognostic significance of preoperative C-reactive protein to albumin ratio in older patients with pathological stage II/III colorectal cancer.

Purpose: This study was performed to evaluate the prognostic value of preoperative C-reactive protein to albumin ratio (CAR) in older patients with colorectal cancer (CRC) undergoing curative resection. Methods: We retrospectively analyzed 244 older patients (aged 75 years or higher) with pathological stage II/III CRC who underwent curative surgery between 2008 and 2016. The optimal value of CAR was calculated and its correlation with the clinicopathological factors and prognosis was examined. Results: The optimal cutoff value of the CAR was 0.085. High preoperative CAR was significantly associated with high carcinoembryonic antigen levels (P=0.001), larger tumor size (P<0.001), and T pathological (pT) factor (P=0.001). On multivariate analysis, high CAR was independent prognostic factor for relapse-free survival (P=0.042) and overall survival (P=0.001). Conclusion: Preoperative elevated CAR could be considered as an adverse predictor of both relapse-free survival and overall survival in older patients with CRC undergoing curative surgery.

The Systemic Inflammation Score Is an Independent Prognostic Factor for Esophageal Cancer Patients who Receive Curative Treatment.

BACKGROUND/AIM: Perioperative systemic inflammation affects the long-term oncological outcomes in cases of malignancies. We evaluated the clinical impact of the preoperative systemic inflammation score (SIS) in resectable esophageal cancer patients who received curative treatment. PATIENTS AND METHODS: This study included 168 patients who underwent curative surgery followed by perioperative adjuvant chemotherapy for esophageal cancer between 2005 and 2018. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. RESULTS: Based on the 3- and 5-year OS rate, we set the cut-off value for SIS at 2 in the preset study. Among the 168 total patients, 119 were categorized as the Low-SIS group, and 49 were categorized as the High-SIS group. The respective 3- and 5-year OS rates were 61.9% and 52.4% in the Low-SIS group and 33.3% and 26.6% in the High-SIS group. There were significant differences in OS (p<0.001). The SIS was therefore selected for the final multivariate analysis model (hazard ratio=2.094, 95% confidence interval=1.355-3.234, p<0.001). On comparing the perioperative clinical course between the High- and Low-SIS groups, there were significant differences in the rate of postoperative anastomosis leakage of grade ≥2 between the groups (61.5% in the High-SIS group vs. 30.3% in the Low-SIS group; p=0.021). CONCLUSION: The systemic inflammation score had a clinical effect on the long-term oncological outcomes in esophageal cancer patients, suggesting that it might be a promising prognostic factor for esophageal cancer patients.

Impact of Infectious Complications on Survival and Recurrence of Patients With Stage II/III Colorectal Cancer: A Multicenter Retrospective Study.

BACKGROUND/AIM: Postoperative complications are associated with increased recurrence in colorectal cancer (CRC). We investigated the impact of infectious complications on the recurrence of CRC and overall survival after curative surgery in a single study group. PATIENTS AND METHODS: In total, 1,668 patients who underwent radical resection for CRC in Yokohama City University, Yokohama Minami Kyosai Hospital, and Kanagawa Cancer Center between 2011 and 2019 were reviewed. Patients were classified into those with infectious complications (IC group) and those without infectious complications (Non-IC group). The risk factors for recurrence-free survival (RFS) and overall survival (OS) were analyzed. RESULTS: Postoperative complications were found in 560 of the 1,668 patients (33.5%), and IC, which occurred in 312 patients (18.7%), included pneumonia, anastomotic leakage, and intraperitoneal abscess. The 5-year OS rates in the Non-IC and IC groups were 95.5% and 90.4%, respectively, while the 5-year RFS rates were 74.4% and 68.1%, respectively. The multivariate analysis demonstrated that postoperative IC were significant independent risk factors for OS and RFS. CONCLUSION: The presence of postoperative IC after CRC resection is associated with decreased long-term survival. The surgical procedure, surgical strategy, and perioperative care should be carefully planned in order to avoid causing IC.

Clinical Impact of Preoperative Albumin-Bilirubin Status in Esophageal Cancer Patients Who Receive Curative Treatment.

BACKGROUND/AIM: The albumin-bilirubin (ALBI) score, which evaluates the perioperative liver function, was developed, and had a clinical impact on both the short- and long-term oncological outcomes in some malignancies. We evaluated the clinical impact of preoperative albumin-bilirubin status in patients with resectable esophageal cancer who received curative treatment. PATIENTS AND METHODS: The study included 121 patients who underwent curative surgery followed by adjuvant chemotherapy for esophageal cancer between 2005 and 2018. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. RESULTS: Based on the 3- and 5-year OS rates, we set the cut-off value for the ALBI score at -2.7. Eighty patients were classified into the ALBI-low group (ALBI score <-2.7), 41 patients were categorized into the ALBI-high group (ALBI score >-2.7). The 3- and 5-year OS rates were 62.2% and 53.2%, respectively, in the ALBI-low group, and 42.2% and 35.2% in the ALBI-high group. There was a significant difference in OS (p=0.0113). The 3- and 5-year RFS rates were 43.1% and 40.3%, respectively, in the ALBI-low group and 37.7% and 26.1% in the ALBI-high group. There was a significant difference in RFS (p=0.048). When comparing the perioperative clinical course between the ALBI-high and ALBI-low groups, the incidence of postoperative anastomotic leakage was 46.3% (19/41) in the ALBI-high group, and 27.5% (22/80) in the ALBI-low group (p=0.038). CONCLUSION: The ALBI status had a clinical impact on both OS and RFS in esophageal cancer patients. Therefore, ALBI may have potential application as a prognostic factor for esophageal cancer patients.

Solitary Cardiac Metastasis from Colorectal Cancer: A Case Report.

A 73-year-old woman with silent cardiac metastasis underwent high anterior resection for rectal cancer 3 years ago. Follow-up computed tomography showed a tumor in the right atrium. Partial vascular resection of the superior vena cava and right atrium was performed. Early postoperative recurrence occurred, and chemotherapy was unsuccessful. The patient died 7 months after surgery.

Can D3 Lymph Node Dissection for Patients With Colon Cancer With a Poor C-Reactive Protein/Albumin Ratio Improve Survival Outcomes?

AIM: D3 lymph node dissection (LND) for stage II and III colon cancer has been shown to improve prognosis, however, it generally increases surgical stress. Studies have reported that the C-reactive protein/albumin ratio (CAR) may be a useful inflammatory-nutritional biomarker to predict postoperative complications and poor prognosis for with various types of cancer. Our purposes were to assess the short- and long-term outcomes of D3 LND in patients with a high preoperative CAR (≥ 0.04). PATIENTS AND METHODS: This was a retrospective cohort analysis reviewing a prospectively collected database of Yokohama City University and three affiliated hospitals. A total of 449 patients with stage II or III colon cancer with high CAR who underwent primary resection with D2 or D3 LND were identified between 2008 and 2020. The primary and secondary outcomes of interests were the 3-year recurrence-free survival and postoperative complication rates. RESULTS: After propensity matching, 230 patients were evaluated. There was no significant difference between the D3 and D2 groups in the rate of postoperative complications overall (14.8% versus 11.3%, p=0.558), however, the incidence of anastomotic leakage tended to be greater in the D3 group (9.6% versus 2.6%, p=0.050). The long-term findings showed that there was no significant difference between the two groups (3-year recurrence-free survival rate: 77.2% versus 77.2%, p=0.880). CONCLUSION: D3 LND did not improve survival outcomes for patients with colon cancer with a poor CAR in this study. D2 LND may be a treatment option for patients with stage II-III colon cancer with a high preoperative CAR.

The Impact of Severe Infectious Complications on Long-term Prognosis for Gastric Cancer.

BACKGROUND: The aim of this study was to evaluate the impact of postoperative infectious complications on long-term outcomes after curative resection of gastric cancer. PATIENTS AND METHODS: Patients who underwent curative gastrectomy with lymphadenectomy for gastric cancer at Yokohama City University and Kanagawa Cancer Center from January 2000 to August 2015 were retrospectively selected from medical records. Clinicopathological factors between patients with and without infectious complications were compared. Prognostic factors of long-term survival were analyzed by univariate and multivariate Cox proportional hazards analyses. RESULTS: A total of 2,254 patients were eligible for inclusion in the present study. Fifty-eight patients had postoperative infectious complications (IC group); 2,196 had no postoperative infectious complications (NC group). In the IC group, the median age (p=0.031), body mass index (p=0.004), American Society of Anesthesiologists physical status (p=0.006) and percentage of male patients (p<0.001) were higher in comparison to the NC group. The operation time was longer (p<0.001) and the incidence of intestinal-type histology was higher (p=0.017) in the IC group. The 5-year overall survival rates of the IC and NC groups were 59.8% and 83.2%, respectively (p<0.001). Univariate and multivariate analyses demonstrated that postoperative infectious complications were a significant risk factor for poorer overall survival (hazard ratio=2.38; 95% confidence interval=1.47-3.85, p<0.001). CONCLUSION: Perioperative management is necessary to reduce the incidence of postoperative infectious complications and improve the survival of patients after curative resection of gastric cancer.

[Resected Metachronous Pancreatic Metastasis from Rectal Cancer-A Case Report].

A 68-year-old woman had undergone laparoscopic high anterior resection for rectal cancer. Two years postoperatively, metachronal pulmonary metastases and cerebellar metastasis were surgically resected. Three and a half years after the primary surgery, computed tomography(CT)demonstrated a nodule at the pancreatic tail. Under suspected primary pancreatic cancer or metastasis from rectal cancer, we performed distal pancreatectomy. Histological examination of the pancreatic tumor suggested a metastasis from the rectal cancer since tumor cells were negative for CK7 and positive for CK20 and CDX2 immunohistochemically. Three months after the pancreatic resection, CT demonstrated hepatic and cerebellar metastases. After subsequent chemotherapy, liver metastasis disappeared. The cerebellar metastasis shrank with radiotherapy.

[A Case of Metastatic Small Intestinal Tumor Diagnosed with Intestinal Obstruction].

A 76-year-old man with a past history of liver transplantation because of liver cirrhosis visited a hospital in October 2018 because of vomiting and abdominal pain. Although the patient underwent conservative medical treatment, no improvement of the symptoms was observed, and he received consultation at our hospital. After thorough examination, and because of the policy of inpatient treatment after the diagnosis of adhesion ileus obstruction post liver transplantation surgery, intestinal decompression was performed using an ileus tube. However, there was no improvement in the symptoms even after inserting the ileus tube, and intestinal obstruction was diagnosed in November 2018. During the preoperative examination, a tumorous shadow was found in the right lung, although it became a policy of scrutiny after improvement of the bowel obstruction. During the laparotomy, a macroscopic tumor exposed on the serosal surface was observed on the anal side at 120 cm from the Treitz ligament, and this site was considered to be the blocking origin. Partial resection of the small intestine including the blockage site was performed. The pathological result revealed the diagnosis of adenosquamous carcinoma. Furthermore, immunostaining was CK7 positive, CK20 negative, TTF-1 negative, and Napsin negative, suggesting the possibility of a metastatic tumor derived from lung cancer. The postoperative course was uneventful, and the patient was discharged on postoperative day 9. On day 30 after surgery, the left pleural effusion increased and pleural effusion cytology revealed a diagnosis of primary lung adenocarcinoma Stage Ⅳ. Considering the patient's PS, it became a best supportive care(BSC)policy after consultation with the family, and it ended on postoperative day 70. Here, we report about a case diagnosed with metastatic small bowel cancer and intestinal obstruction and conduct a literature review.

[A Case Altered Consciousness Due to 5-Fluorouracil-Induced Hyperammonemia in a Patient with Recurrent Colorectal Cancer].

We report a case of altered consciousness related to hyperammonemia due to FOLFIRI plus bevacizumab therapy in a patient with recurrent colorectal cancer and renal dysfunction.A 76-year-old man received third-line chemotherapy for left mediastinal lymph node metastasis.He complained of diarrhea on the evening of the same day, and mental confusion on day 3 of the first FOLFIRI therapy.He had a JCS of Ⅲ(200).The laboratory results revealed a marked hyperammonemia.5 - fluorouracil(5-FU)-induced hyperammonemia was diagnosed and the patient was ventilated and managed with branchedchain amino acid solutions, lactulose, and hemodialysis in the ICU.After hemodialysis, the blood ammonia level reduced to the normal limits, and the symptoms of encephalopathy resolved on the following day.He was discharged home on the 19th day of hospitalization.5 -FU-containing therapy should be carefully administered in patients with renal dysfunction.Herein, we report a case of 5-FU-induced hyperammonemia with literature considerations.

[A Case of Resection for Bleeding from a Gallbladder Tumor].

A 77-year-old woman was taking anticoagulant medication for pulmonary hypertension. Black stools were noted in August 2018. Close abdominal ultrasonography revealed a broad-based tumor at the base of the gallbladder. Lower endoscopy showed no obvious digestive tract hemorrhage but hemorrhage from a gallbladder tumor was suspected. The resected procedure was suspected for gallbladder cancer(cT2N0M0, cStageⅡ), but dizziness 5 days before operation. The patient complained of severe anemia, and underwent laparoscopic cholecystectomy for hemorrhage control. In the macroscopic examination of the specimens, tumorous lesions and blood clots were found adhered to the bottom of the gallbladder. The histopathological diagnosis was papillary adenocarcinoma.

[A Case of a Resected Giant Gastric Schwannoma by Laparoscopic Surgery].

This case involved a 42-year-old woman who had no remarkable findings in terms of case history and family history. Upper gastrointestinal series performed during a medical examination revealed ulcerative lesions in the anterior wall of the stomach body. Upper gastrointestinal endoscopy was performed, and a submucosal tumor with a maximum diameter of 50mm accompanied by an ulcerative lesion was found in the anterior wall of the lower part of the stomach. She was diagnosed with a schwannoma based on endoscopic ultrasonography-guided fine needle aspiration, and we received consultation for surgical purpose. Surgery was performed with laparoscopic partial resection of the stomach and lymph nodes in the lesser curvature of the stomach. She was discharged on the 7th day after the surgery. The postoperative pathologic findings showed no nuclear fissure or atypia with a diagnosis of a schwannoma and no lymph node metastasis. Gastric schwannoma is a rare disease that arises from Schwann cells of the Auerbach's plexus of the gastric wall muscularis and comprises 0.1-0.2% of all stomach tumors. Preoperative diagnosis is often extremely difficult, and there are reports of malignancy. Treatments and surgical methods should be carefully considered. Herein, we encountered a case of a resected giant gastric schwannoma by laparoscopic surgery, which is reported with a literature review.

Influence of Postoperative Pneumonia on Esophageal Cancer Survival and Recurrence.

BACKGROUND/AIM: Postoperative pneumonia after esophageal cancer can lead to additional pain, prolonged hospital stay, and respiratory failure. These adverse events might lead to early recurrence and/or death. We investigated the influence of postoperative pneumonia on the esophageal cancer survival and recurrence after curative surgery. PATIENTS AND METHODS: This study included 122 patients who underwent curative surgery for esophageal cancer between 2008 and 2018. The patients were classified into: i) those with postoperative pneumonia (pneumonia group) and ii) those without postoperative pneumonia (non-pneumonia group). The risk factors for the overall survival (OS) and recurrence-free survival (RFS) were identified. The rate of postoperative pneumonia was measured by the revised Uniform Pneumonia Score. RESULTS: Postoperative complications were found in 34 of the 122 patients (27.9%). The OS rate at 5 years following surgery was 28.2% in the pneumonia group and 55.1% in the non-pneumonia group (p=0.006). The RFS rate at 5 years after surgery was 18.9% in the pneumonia group and 49.2% in the non-pneumonia group (p=0.061). A multivariate analysis showed that postoperative pneumonia was a significant independent risk factor for OS. CONCLUSION: The development of postoperative pneumonia was a risk factor for a decreased overall survival in patients who underwent curative surgery for esophageal cancer. The surgical procedure, perioperative care and surgical strategy should be carefully planned in order to avoid postoperative pneumonia.