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Abstract In later-line treatment of metastatic colorectal cancer (mCRC), there may be large differences in treatment efficacy depending on cancer cachexia. Recently, the cachexia index (CXI), which was calculated from the skeletal muscle mass index (SMI), serum albumin concentration, and neutrophil-to-lymphocyte ratio, was developed to evaluate cancer cachexia. We retrospectively examined the CXI of 80 patients who were treated with trifluridine/thymidine phosphorylase inhibitor (FTD/TPI) + bevacizumab (Bmab) therapy as a later-line treatment for mCRC, and assessed the impact of cancer cachexia on chemotherapeutic efficacy using CXI. Progression-free and overall survival rates were significantly worse in the low CXI group than in the high CXI group, although there were no marked differences in tumor factors, such as the number of metastatic organs or gene mutations, between the two groups. As the cross-sectional area of the iliopsoas muscle was significantly associated with that of the skeletal muscle, the accuracy of the CXI based on the psoas mass index (P-CXI), which is easier to calculate than the SMI, in predicting treatment outcomes was equivalent to that of the CXI based on the SMI (S-CXI). Cancer cachexia is an important factor related to treatment efficacy in later-line treatments, such as FTD/TPI + Bmab therapy.

Abstract Anastomotic-leakage incidence has been reported to be reduced on using polyglycolic acid (PGA) sheets as reinforcing materials; however, there is insufficient evidence regarding the reinforcement mechanism. Therefore, we investigated effects of PGA sheets on gastrointestinal anastomoses in rats. In the first approach, five rats underwent laparotomy; the PGA sheet was pasted onto the normal cecal wall. After five days, the cecum was removed and histologically evaluated. In the second approach, ten rats were randomly divided into two groups of five animals each. The rats underwent laparotomy; the cecal wall was sutured after a full-thickness incision. In the PGA group, a PGA sheet was used to cover the suture area. After 5 days, the cecum was removed, and the physical pressure resistance was evaluated. We confirmed the growth of a fibrous capsule measuring 855 (648–1048) µm outside the cecal serosa in the first approach. The median pressure resistance in the second approach was 57.0 (45.0–90.0) and 90.0 (82.5–94.5) mmHg in Control and PGA groups, respectively. The pressure resistance was significantly higher in the PGA group (p = 0.046). In summary, the PGA sheet may form a barrier of fibrosis on the intestinal wall and provide reinforcement to prevent anastomotic leakage.

Abstract Background Intra‐abdominal infectious complications (IAICs) following minimally invasive gastrectomy (MIG) for cancer sometimes worsen short‐ and long‐term outcomes. In this study, we focused on the minimum umbilicus–vertebra diameter (MUVD) in preoperative computed tomography (CT) images and robotic surgery to prevent severe IAIC occurrence. Patients and Methods A total of 400 patients with gastric cancer who underwent 204 laparoscopic gastrectomy (LG) and 196 robotic gastrectomy (RG) procedures were enrolled in this study. We retrospectively investigated the significance of the MUVD and robotic surgery for preventing severe IAICs following MIG using multivariate and propensity score matching analysis. Results The MUVD cutoff value was 84 mm by receiver operating characteristic (ROC) curve using severe IAICs as the end point. The MUVD and visceral fat area (VFA) had significantly higher area under the curve (AUC) than BMI (MUVD vs. BMI, p = 0.032; VFA vs. BMI, p

Abstract Background Robotic-assisted surgery is steadily becoming more prominent. The majority of reports regarding port site hernias (PSHs) have involved laparoscopic procedures. Currently, it is common to suture the fascia at port sites that are 10 mm or larger; however, the closure of 5-mm port sites is not considered mandatory. The da Vinci® surgical system (Intuitive Surgical Inc., Sunnyvale, CA, USA) utilizes a distinctive 8-mm port. We report a case of an early-onset PSH at an 8-mm port site after robotic-assisted ileocecal resection. Case presentation A 74-year-old male patient with a body mass index of 19.7 kg/m2 was diagnosed with cecal cancer and underwent robotic-assisted ileocecal resection. A 3-cm midline incision was made at the umbilicus for insufflation. Under laparoscopic visualization, three ports (12 mm, 8 mm, and 8 mm) were inserted in the lower abdomen. An 8-mm port was inserted in the left subcostal region, and a 5-mm port was inserted in the left lateral abdomen. The procedure was performed without significant intraoperative complications. The fascia was closed only at the umbilicus and 12-mm port site; the fascia at the 8-mm port sites was not closed. The patient was initially discharged without complications; however, on postoperative day 11, the patient was urgently hospitalized again because of PSH incarceration. After manual reduction, the fascia was sutured closed under local anesthesia. The hernial defect was small and barely allowed the insertion of a little finger. There was no evidence of compression or significant damage to the fascia. On postoperative day 27, the patient was discharged after experiencing good recovery. Conclusions Robotic-assisted colectomy could contribute to the risk of PSHs because of its surgical characteristics. Although routine closure of the fascia at 8-mm port sites is not mandatory, it may be beneficial in certain cases.

Introduction: Reexposure to anti-EGFR antibodies, such as a reintroduction or rechallenge with anti-EGFR antibodies, has attracted much attention in the field of metastatic colorectal cancer. A reintroduction of anti-EGFR antibodies often shows good therapeutic outcomes, as most patients eligible for such reintroduction discontinued treatment due to adverse events despite a good treatment response during front-line treatment. We herein report a case demonstrating an improvement in exertional dyspnea after the reintroduction of anti-EGFR antibody in a patient with metastatic rectal cancer who developed cancerous lymphangiopathy. Case Presentation: A 68-year-old man who had undergone curative surgery for stage IIIB rectal cancer was diagnosed with multiple lung metastases. During the late-line treatment, respiratory failure developed because of multiple lung metastases and cancerous lymphangiopathy. Two months after the initiation of irinotecan + cetuximab, which had been discontinued due to acneiform eruptions despite a good treatment response as a first-line treatment, his dyspnea and performance status dramatically improved. Conclusion: This case indicates that the reintroduction of anti-EGFR antibody to patients who have discontinued anti-EGFR antibody due to skin toxicity despite a good treatment response is a very useful treatment option for metastatic colorectal cancer.

Abstract Purposes Subtotal esophagectomy for esophageal cancer (EC) is associated with high morbidity rates. Tight glycemic control using an artificial pancreas (AP) is one of the promising strategies to reduce postoperative inflammation and morbidities. However, the effects of tight glycemic control using AP in patients with EC are yet to be fully elucidated. Method This study reviewed 96 patients with EC who underwent subtotal esophagectomy. The postoperative inflammation parameters and morbidity rates were compared between patients who used the AP (n = 27) or not (control group, n = 69). AP is a closed-loop system that comprises a continuous glucose monitor and an insulin pump. Results The numbers of white blood cells (WBC) and Neutrophils (Neut) were noted to be lower in the AP group than in the control group, but with no significant difference. The ratio in which the number of WBC, Neut, and CRP on each postoperative day (POD) was divided by those tested preoperatively was used to standardize the results. The ratio of WBC and Neut on 1POD was significantly lower in the AP group than in the control group. The rate of surgical site infection was lower in the AP group than in the control group. Conclusion AP significantly decreased WBC and Neut on 1POD; this suggests the beneficial effects of AP in alleviating postoperative inflammation.

Abstract Background Gastric cancer is primarily treated by surgery; however, little is known about the changes in the intraperitoneal immune environment and the prognostic impact of surgery. Surgical stress and cancer-associated inflammation cause immune cells to mobilize into the abdominal cavity via numerous cytokines. One such cytokine, CX3CR1, has various immune-related functions that remain to be fully explained. We characterized the intraperitoneal immune environment by investigating CX3CR1+ cells in intraperitoneal lavage fluid during gastric cancer surgery. Methods Lavage fluid samples were obtained from a total of 41 patients who underwent gastrectomy. The relative expression of various genes was analyzed using quantitative real-time PCR. The association of each gene expression with clinicopathological features and surgical outcomes was examined. The fraction of CX3CR1+ cells was analyzed by flow cytometry. Cytokine profiles in lavage fluid samples were investigated using a cytometric beads array. Results CX3CR1high patients exhibited higher levels of perioperative inflammation in blood tests and more recurrences than CX3CR1low patients. CX3CR1high patients tended to exhibit higher pathological T and N stage than CX3CR1low patients. CX3CR1 was primarily expressed on myeloid-derived suppressor cells and tumor-associated macrophages. In particular, polymorphonuclear myeloid-derived suppressor cells were associated with perioperative inflammation, pathological N, and recurrences. These immunosuppressive cells were associated with a trend toward unfavorable prognosis. Moreover, CX3CR1 expression was correlated with programmed death–1 expression. Conclusions Our results suggest that CX3CR1+ cells are associated with an acute inflammatory response, tumor-promotion, and recurrence. CX3CR1 expression could be taken advantage of as a beneficial therapeutic target for improving immunosuppressive state in the future. In addition, analysis of intra-abdominal CX3CR1+ cells could be useful for characterizing the immune environment after gastric cancer surgery.

Abstract Background The efficacy of robotic gastrectomy (RG) on postoperative complications in patients with gastric cancer (GC) is unclear in terms of the volume of intra‐abdominal fat tissue. Patients and Methods We enrolled 403 patients with GC who had minimally invasive surgery between January 2015 and July 2022. During this time, 197 RG and 206 laparoscopic gastrectomies (LG) were performed on the study participants. According to the computed tomography scan, patients were defined as having or not having visceral obesity based on the visceral fatty area (VFA). In each high and low VFA group, we compared short‐term outcomes between the RG group and LG group. Results After PS matching for patients with high VFA, the two groups were well matched, with 71 cases in both the RG and LG groups. The median surgical time in the RG group was significantly longer (420 vs. 365 min, p

Abstract Complete mesocolic excision (CME) with central vascular ligation (CVL) in laparoscopic surgery for right-sided colon cancer (RSCC) requires a precise understanding of the vascular anatomy. The efficacy of intraoperative ultrasound (IUS) in the identification of blood vessels for RSCC surgery was not evaluated. The aim of this study was to compare the intraoperative and short-term outcomes of CME with CVL with or without IUS by laparoscopic surgery for RSCC. We performed IUS on 26 patients of RSCC and compared with a total of 124 patients who underwent the surgery for RSCC at our institution. Propensity score matching (PSM) was performed to reduce the confounding effects to imbalances in the use of IUS. The IUS identified the main feeding artery and the accompanying vein in all 26 cases. After PSM, the amount of intraoperative blood loss in the IUS group was significantly lower than that in the conventional group (5 ml vs. 30 ml, p = 0.035) and no significant difference of the postoperative complications was observed. The IUS reduced the risk of bleeding in the surgery for RSCC. The IUS is a safe and feasible technique that help the surgeons for anatomical understandings under real-time condition in the laparoscopic surgery of RSCC.

Abstract The metabolic and signaling pathways regulating aggressive mesenchymal colorectal cancer (CRC) initiation and progression through the serrated route are largely unknown. Although relatively well characterized as BRAF mutant cancers, their poor response to current targeted therapy, difficult preneoplastic detection, and challenging endoscopic resection make the identification of their metabolic requirements a priority. Here, we demonstrate that the phosphorylation of SCAP by the atypical PKC (aPKC), PKCλ/ι promotes its degradation and inhibits the processing and activation of SREBP2, the master regulator of cholesterol biosynthesis. We show that the upregulation of SREBP2 and cholesterol by reduced aPKC levels is essential for controlling metaplasia and generating the most aggressive cell subpopulation in serrated tumors in mice and humans. Since these alterations are also detected prior to neoplastic transformation, together with the sensitivity of these tumors to cholesterol metabolism inhibitors, our data indicate that targeting cholesterol biosynthesis is a potential mechanism for serrated chemoprevention.

Abstract Background Immune checkpoint inhibitors (ICIs), including nivolumab, have been approved to treat esophageal cancer. However, these remedies are not fit for all patients with esophageal cancer; therefore, a predictive surrogate marker is needed to assess their effectiveness. CD103+CD8+ tumor-infiltrating lymphocytes, defined as tissue-resident memory T cells (TRM), are promising indicators of response to ICIs, but it remains to be elucidated. This study investigated the association between the efficacy of ICIs and TRM. Methods The relationships between TRM infiltrating esophageal cancer, clinicopathological features, and prognosis after nivolumab initiation were examined using immunostaining. Tissue samples were obtained from surgically resected specimens of 37 patients with esophageal cancer who received nivolumab as a secondary or subsequent therapy. In addition, TRM infiltration was compared with programmed death-ligand 1 (PD-L1) expression and blood count parameters as predictors of nivolumab effectiveness. Results TRM-rich patients had a significant survival benefit after nivolumab initiation (12-months overall survival 70.8% vs 37.2%, p = 0.0485; 12-months progression-free survival 31.2% vs 0%, p = 0.0153) and experienced immune-related adverse events more frequently than TRM-poor patients (6 vs 2 patients). TRM infiltration was weakly correlated with PD-L1 positivity (r = 0.374, p = 0.022), but TRM may indicate more sensitive response to ICIs than PD-L1 expression in this study. Some blood test parameters also weakly correlated with TRM but did not impact prognosis. Conclusions TRM-rich patients have a favorable prognosis after nivolumab initiation. Our results suggest that TRM are vital for antitumor immunity and are a promising predictor of ICIs effectiveness.

Abstract Mesenchymal activation, characterized by dense stromal infiltration of immune and mesenchymal cells, fuels the aggressiveness of colorectal cancers (CRC), driving progression and metastasis. Targetable molecules in the tumor microenvironment (TME) need to be identified to improve the outcome in CRC patients with this aggressive phenotype. This study reports a positive link between high thrombospondin-1 (THBS1) expression and mesenchymal characteristics, immunosuppression, and unfavorable CRC prognosis. Bone marrow-derived monocyte-like cells recruited by CXCL12 are the primary source of THBS1, which contributes to the development of metastasis by inducing cytotoxic T-cell exhaustion and impairing vascularization. Furthermore, in orthotopically generated CRC models in male mice, THBS1 loss in the TME renders tumors partially sensitive to immune checkpoint inhibitors and anti-cancer drugs. Our study establishes THBS1 as a potential biomarker for identifying mesenchymal CRC and as a critical suppressor of antitumor immunity that contributes to the progression of this malignancy with a poor prognosis.

Abstract Background Thoracic duct cysts are extremely rare mediastinal tumors. We report a case of a thoracic duct cyst extending from the caudal aspect of the left main bronchus to the left renal artery that was safely and completely resected via bilateral thoracoscopic surgery in the prone position. Case presentation A 77-year-old male was referred to our hospital for follow-up computed tomography (CT) of prostate cancer, which revealed a mediastinal tumor and fatty low-density along the posterior mediastinum of the para-aortic artery with a slightly high-density component. Magnetic resonance imaging revealed a T2-weighted image with high intensity. The preoperative radiological diagnosis was lipoma or well-differentiated liposarcoma. CT in the prone position suggested that the tumor could be resected from the thoracic cavity to the caudal side, and bilateral thoracoscopic surgery was performed in the prone position. Based on the surgical findings, the tumor was diagnosed as a thoracic duct cyst rather than a lipoma. Dissection around the thoracic duct cyst was performed using a vessel-sealing system to prevent leakage of the chyle, and reliable clipping was performed to resect the cisterna chyli. Histopathological examination revealed smooth muscle structures around the cyst, suggestive of a thoracic duct cyst. The diagnosis of a thoracic duct cyst was made based on a high triglyceride level of 1310 mg/dL on examination of the milky-white cyst fluid. The patient's postoperative course was uneventful, and he was discharged 4 days postoperatively. A CT scan performed 13 months after surgery showed no recurrence. Conclusions A rare thoracic duct cyst extending from the mediastinum to the cisterna chyli was safely and completely resected using bilateral thoracoscopic surgery, with the patient in the prone position.

Abstract Background The powered circular stapler, which was developed with the aim of providing reliable and reproducible anastomosis, provides complete anastomosis, resulting in a reduced risk of anastomotic leakage. The aim of this study was to compare the incidence of anastomotic leakage between a conventional manual circular stapler (MCS) and the ECHELON CIRCULAR™ Powered Stapler (ECPS) in patients with left-sided colorectal cancer who underwent anastomosis with the double stapling technique. Methods A total of 187 patients with left-sided colorectal cancer who underwent anastomosis with the double stapling technique with a conventional MCS or the ECPS during surgery at Osaka City University Hospital between January 2016 and July 2022 were enrolled in this study. Results The incidence of anastomotic leakage in the ECPS group was significantly lower than that in the MCS group (4.4% versus 14.3%, p = 0.048). Furthermore, even after propensity score matching, an association was found between the use of the ECPS and a reduced incidence of anastomotic leakage. Conclusion The ECPS has the potential to help reduce the rate of anastomotic leakage in left-sided colorectal surgery.

BackgroundSubtotal esophagectomy with lymph node dissection followed by neoadjuvant chemotherapy (NAC) is the standard treatment for stage II-III esophageal cancer. Esophagectomy is still associated with high morbidity rates, and reducing these rates remains challenging. Among several complications, postoperative pneumonia (PP) is sometimes fatal, which has been reportedly caused by sarcopenia. Thus, nutritional support and rehabilitation may be promising for preventing skeletal muscle mass loss and reduce the incidence of PP.MethodsThis single-center, randomized, open-label, pilot trial will randomize a total of 40 patients with esophageal cancer in a 1:1 ratio either to ISOCAL Clear + rehabilitation arm or only rehabilitation arm. Although all patients will be educated about rehabilitation by a specialized physician and will be asked to undergo the prespecified rehabilitation program, patients treated with ISOCAL Clear + rehabilitation arm will be supplemented by 400 mL of ISOCAL Clear (Nestlé Japan Ltd, Tokyo, Japan) per day during two courses of NAC with docetaxel, cisplatin, and fluorouracil. Body composition will be assessed using Inbody (Inbody Co., Ltd., Tokyo, Japan) just before starting NAC and surgery. The primary endpoint is the change of skeletal muscle index (SMI) during NAC. Secondary endpoints include (i) body weight, total skeletal muscle mass, appendicular skeletal muscle mass, and lean body mass index changes; (ii) the percentage of ISOCAL Clear continuation; (iii) appetite evaluation; (iv) the percentage of targeted calorie achievement; (v) adverse events of NAC; (vi) postoperative complication rates; and (vii) postoperative hospital stay.DiscussionThis prospective trial assesses the efficacy of nutritional support in addition to rehabilitation during NAC for patients with esophageal cancer. The results will be utilized in assessing whether the effects of nutritional support by ISOCAL Clear are promising or not and in planning future larger clinical trials.

BackgroundMaintaining good communication and engagement between people with dementia and their caregivers is a major challenge in dementia care. Cognitive stimulation is a psychosocial intervention that supports communication and engagement, and several digital applications for cognitive stimulation have been developed. Personalization is an important factor for obtaining sustainable benefits, but the time and effort required to personalize and optimize applications often makes them difficult for routine use by nonspecialist caregivers and families. Although artificial intelligence (AI) has great potential to support automation of the personalization process, its use is largely unexplored because of the lack of suitable data from which to develop and train machine learning models. ObjectiveThis pilot study aims to evaluate a digital application called Aikomi in Japanese care homes for its potential to (1) create and deliver personalized cognitive stimulation programs to promote communication and engagement between people with dementia and usual care staff and (2) capture meaningful personalized data suitable for the development of AI systems. MethodsA modular technology platform was developed and used to create personalized programs for 15 people with dementia living in 4 residential care facilities in Japan with the cooperation of a family member or care staff. A single intervention with the program was conducted with the person with dementia together with a care staff member, and for some participants, smell stimulation was provided using selected smell sticks in conjunction with the digital program. All sessions were recorded using a video camera, and the combined personalized data obtained by the platform were analyzed. ResultsMost people with dementia (10/15, 67%) showed high levels of engagement (>40 on Engagement of a Person with Dementia Scale), and there were no incidences of negative reactions toward the programs. Care staff reported that some participants showed extended concentration and spontaneous communication while using Aikomi, which was not their usual behavior. Smell stimulation promoted engagement for some participants even when they were unable to identify the smell. No changes in well-being were observed following the intervention according to the Mental Function Impairment Scale. The level of response to each type of content in the stimulation program varied greatly according to the person with dementia, and personalized data captured by the Aikomi platform enabled understanding of correlations between stimulation content and responses for each participant. ConclusionsThis study suggests that the Aikomi digital application is acceptable for use by persons with dementia and care staff and may have the potential to promote communication and engagement. The platform captures personalized data, which can provide suitable input for machine learning. Further investigation of Aikomi will be conducted to develop AI systems and create personalized digital cognitive stimulation applications that can be easily used by nonspecialist caregivers.

Abstract Background To prevent anastomotic leakage in patients with left-sided colorectal cancer who underwent double-stapling technique (DST) anastomosis, we investigated a new method: DST anastomosis with a polyglycolic acid (PGA) sheet. This procedure has been shown to have the potential to decrease the rate of anastomotic leakage. However, due to the small number of cases enrolled in our previous study, it was not possible to compare the outcomes of the new and conventional procedures. The aim of this study was to evaluate the effect of the PGA sheet on preventing anastomotic leakage in patients with left-sided colorectal cancer who underwent DST anastomosis by retrospectively comparing the anastomotic leakage rate between the PGA sheet and conventional groups. Methods A total of 356 patients with left-sided colorectal cancer who underwent DST anastomosis during surgery at Osaka City University Hospital between January 2016 and April 2022 were enrolled in this study. Propensity score matching was performed to reduce the confounding effects secondary to imbalances in the use of PGA sheets. Results The PGA sheet was used in 43 cases (PGA sheet group) and it was not used in 313 cases (conventional group). After propensity score matching, the incidence of anastomotic leakage in the PGA sheet group was significantly lower than that in the conventional group. Conclusion DST anastomosis with PGA sheet, which is easy to perform, contributes to the reduction of anastomotic leakage rate by increasing the strength of the anastomotic site.

Abstract Background Systemic inflammation is recognized as a hallmark of cancer that contributes to tumor development and progression in various malignancies. The Naples prognostic score (NPS) was established as a prognostic indicator for colorectal cancer (CRC). This study aims to examine the predictive value of the NPS for survival in CRC patients undergoing curative resection by a propensity score matching (PSM) analysis. Methods A total of 533 CRC patients were enrolled in this study. Overall survival (OS) and disease-free survival (DFS) were compared between high-NPS and low-NPS groups. A time-dependent receiver operator characteristic (ROC) curve analysis was conducted to calculate the area under curve (AUC) of the NPS for OS. A multivariable Cox-proportional hazards regression analysis and PSM analysis were used to identify independent prognostic factors for OS and DFS. We compared the predictive value of the NPS to that of the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), Onodera prognostic nutritional index (PNI), and controlling nutritional status score (CONUT) for OS. Results High-NPS was significantly associated with worse OS and DFS. After PSM, 123 patients were included in each group. A multivariate analysis revealed that Age ≥ 68, ASA-PS ≥ 3, high NPS and undifferentiated tumor type were independently associated with OS, while high NPS, advanced T and N stage were independently associated with DFS after PSM. The NPS had the greatest AUC for OS in comparison to the NLR, LMR, PNI and CONUT. Conclusions We successfully validated the prognostic utility of the NPS for CRC patients after curative resection.

Abstract Purpose A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. Methods After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. Results Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042). Also, the disease-free survival periods were prolonged following treatment of hyperlipidemia (p = 0.047, hazard ratio: 0.399) and statin administration (p = 0.028, hazard ratio: 0.328). Conclusion In cT1 breast cancer, the results suggest that oral statin therapy may contribute to favorable outcomes.

Abstract Background Lipid metabolism has been recently reported to affect the prognosis and tumor immune activity in cancer patients. However, the effect of lipid metabolism on chemosensitivity in patients with breast cancer treated with neoadjuvant chemotherapy (NAC) remains unclear. Methods We examined 327 patients with breast cancer who were treated with NAC followed by curative surgery. The correlations between the serum levels of total cholesterol (TC) and triglyceride (TG) and the clinicopathological features, including the efficacy of NAC, neutrophil-to-lymphocyte ratio (NLR), and absolute lymphocyte count (ALC), were evaluated retrospectively. Results Serum TG levels were increased after NAC in all the subtypes, and the rate of change was the highest, especially in triple-negative breast cancer (TNBC) (21.0% → 48.1%). In addition, only TNBC patients with an objective response (OR) had significantly higher TG levels after NAC than those without (P = 0.049). Patients with a high ALC before NAC had significantly higher TG levels after NAC than patients with all breast cancer (P = 0.001), HER2-enriched breast cancer (P = 0.021), and TNBC (P = 0.008). Patients with a low NLR before NAC had significantly higher TG levels after NAC only among patients with TNBC (P = 0.025). In patients with human epidermal growth factor receptor 2-enriched breast cancer, the group with normal TC levels before NAC had significantly better OS than those with high TC levels (P = 0.013, log-rank test), and in patients with TNBC, the group with high TC levels after NAC had significantly better OS than those with normal TC levels (P = 0.014, log-rank test). Conclusions Good systemic immune activity and chemosensitivity may be associated with lipid metabolism regulated by NAC in TNBC patients.

Abstract Background Postoperative complications of colorectal cancer mainly include infections (surgical site infection, remote infection, etc.), post-operative ileus (POI), and anastomosis leakage. POI reportedly prolongs the hospital stay and increases medical costs. Therefore, predicting POI is very important. There have been some reports on the relationships between sarcopenia and postoperative complications in colorectal cancer patients, but none have been limited to POI. We therefore conducted a retrospective clinical study with a logistic regression analysis to confirm the risk factors for ileus after colorectal cancer surgery. Methods We retrospectively analyzed 213 patients who underwent elective oncological colorectal surgery for colorectal cancer from November 2017 to July 2021. The skeletal muscle mass (SMM, kg) was estimated using a whole-body bioelectrical impedance analysis (BIA), and the skeletal muscle index (SMI) was calculated as the SMM/height2. We divided all patients into 2 groups based on a low SMI (male

Abstract Background Mediastinal foreign bodies might cause mediastinal organ injury or mediastinal abscess. The prompt removal surgery of mediastinal foreign bodies is needed to prevent those complications. We report a case in which a mediastinal foreign body was removed by video-mediastinoscopy. Case presentation The patient, a 74-year-old man with a chief complaint of hoarseness, was referred to our department for surgical management of a wooden foreign body that had traumatically migrated into the superior mediastinum. During the surgery, the video-mediastinoscopy was introduced under the pneumomediastinal pressure. We could dissect the scar tissue and remove the azalea tree branch safely and carefully, without damaging the other mediastinal organs. He was discharged on postoperative day 5, with no complications. Conclusions Video-mediastinoscopic approach under pneumomediastinal pressure is minimally invasive and could provide wide surgical view. Therefore, we consider it useful and effective for removal of foreign bodies in the mediastinum.

Abstract Background The surgical Apgar score (SAS) predicts postoperative complications (POCs) following gastrointestinal surgery. Recently, the SAS was reported to be a predictor of not only POCs but also prognosis. However, the impact of the SAS on oncological outcomes in patients with colorectal cancer (CRC) has not been fully examined. The present study therefore explored the oncological significance of the SAS in patients with CRC, using a propensity score matching (PSM) method. Methods We retrospectively analyzed 639 patients who underwent radical surgery for CRC. The SAS was calculated based on three intraoperative parameters: estimated blood loss, lowest mean arterial pressure, and lowest heart rate. All patients were classified into 2 groups based on the SAS (≤6 and >6). The association of the SAS with the recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS) was analyzed. Results After PSM, each group included 156 patients. Univariate analyses revealed that a lower SAS (≤6) was significantly associated with a worse OS and CSS. A multivariate analysis revealed that the age ≥75 years old, ASA-Physical Status ≥3, SAS ≤6, histologically undifferentiated tumor type, and an advanced pStage were independent factors for the OS, and open surgery, a SAS ≤6, histologically undifferentiated tumor type and advanced pStage were independent factors for the CSS. Conclusions A lower SAS (≤6) was an independent prognostic factor for not only the OS but also the CSS in patients with CRC, suggesting that the SAS might be a useful biomarker predicting oncological outcomes in patients with CRC.

Background/Aim: Despite the remarkable developments in chemotherapy for gastric cancer (GC), rapid tumor growth is sometimes experienced during chemotherapy. This study investigated the association of tumor growth rate (TGR) during second-line chemotherapy with the prognosis of patients with GC. Patients and Methods: We retrospectively reviewed 29 patients with GC treated with nab-paclitaxel plus ramucirumab as second-line chemotherapy between 2017 and 2019 at Osaka Metropolitan University. Of them, 13 cases with target lesions were classified into two groups according to TGR using a cutoff value of 0.25. Clinicopathological factors and survival outcomes were compared between the high TGR (n=5) and low TGR (n=8) groups. Results: The median duration of first-line chemotherapy was significantly longer in the high TGR group than in the low TGR group [median 298 days vs. 72.5 days, p=0.030]. Progressive disease (PD) was observed in 60% of patients with high TGR, whereas stable disease (SD) was observed in 75% patients with low TGR. The median survival time (MST) after starting chemotherapy was 488 days in the low TGR group but was not reached in the high TGR group (log rank p=0.215). The MST after PD was 145 days in the low TGR group but was not estimated in the high TGR group (log rank p=0.345). Conclusion: Based on the absence of significant differences in survival outcomes between the high and low TGR groups, sequential late-line chemotherapy might be considered important, even for patients with high TGR. [ABSTRACT FROM AUTHOR]

Abstract Background The efficacy of adjuvant chemotherapy for high-risk stage II colon cancer (CC) has not been well established. We compared the effects of surgery with and without oral uracil and tegafur plus leucovorin (UFT/LV) in patients with high-risk stage II CC, adjusting for potential risk factors. Methods We enrolled patients with histologically confirmed stage II colon adenocarcinoma with at least one of the following conditions: T4 disease, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, or

This study aimed to investigate the effect of cognitive reserve (CR) on the rate of cognitive decline and cerebral glucose metabolism in amnestic mild cognitive impairment (MCI) using the Study on Diagnosis of Early Alzheimer’s Disease-Japan (SEAD-J) dataset. The patients in SEAD-J underwent cognitive tests and fluorodeoxyglucose-positron emission tomography (FDG-PET). MCI to be studied was classified as amnestic MCI due to Alzheimer’s disease (AD) with neurodegeneration. A total of 57 patients were visually interpreted as having an AD pattern (P1 pattern, Silverman’s classification). The 57 individuals showing the P1 pattern were divided into a high-education group (years of school education ≥13, N = 18) and a low-education group (years of school education ≤12, N = 39). Voxel-based statistical parametric mapping revealed more severe hypometabolism in the high-education group than in the low-education group. Glucose metabolism in the hippocampus and temporoparietal area was inversely associated with the years of school education in the high- and low-education groups (N = 57). General linear mixed model analyses demonstrated that cognitive decline was more rapid in the high-education group during 3-year follow-up. These results suggest that the cerebral glucose metabolism is lower and cognitive function declines faster in patients with high CR of amnestic MCI due to AD defined by FDG-PET.

Background The AT(N) classification was proposed for categorising individuals according to biomarkers. However, AT(N) profiles may vary depending on the markers chosen and the target population.Methods We stratified 177 individuals who participated in the Japanese Alzheimer’s Disease Neuroimaging Initiative by AT(N) classification according to cerebrospinal fluid (CSF) biomarkers. We compared the frequency of AT(N) profiles between the classification using total tau and neurofilament light chain (NfL) as N markers (AT(N)tau and AT(N)NfL). Baseline characteristics, and longitudinal biological and clinical changes were examined between AT(N) profiles.Results We found that 9% of cognitively unimpaired subjects, 49% of subjects with mild cognitive impairment, and 61% of patients with Alzheimer’s disease (AD) dementia had the biological AD profile (ie, A+T+) in the cohort. The frequency of AT(N) profiles substantially differed between the AT(N)tau and AT(N)NfL classifications. When we used t-tau as the N marker (AT(N)tau), those who had T− were more frequently assigned to (N)−, whereas those who had T+were more frequently assigned to (N)+ than when we used NfL as the N marker (AT(N)NfL). During a follow-up, the AD continuum group progressed clinically and biologically compared with the normal biomarker group in both the AT(N)tau and AT(N)NfL classifications. More frequent conversion to dementia was observed in the non-AD pathological change group in the AT(N)tau classification, but not in the AT(N)NfL classification.Conclusions AT(N)tau and AT(N)NfL in CSF may capture different aspects of neurodegeneration and provide a different prognostic value. The AT(N) classification aids in understanding the AD continuum biology in various populations.

Abstract Background Port site metastasis (PSM) after curative gastrectomy for gastric cancer and muscular metastasis from gastric cancer are rare manifestations. Similarly, subcutaneous metastasis from gastric cancer is rare, and muscular and subcutaneous metastases are associated with poor prognosis. We report a case of long-term survival in a patient who underwent curative resection of gastric cancer and repeated recurrence of port site, muscular and subcutaneous metastases from gastric cancer, treated by resection. Case presentation A 75-year-old man was diagnosed with gastric cancer and referred to our department. Upper endoscopy demonstrated a 5-cm circumferential ulcerated lesion at the cardia. Biopsy findings showed a poorly differentiated tubular adenocarcinoma. He underwent laparoscopic total gastrectomy with lymph node dissection, and pathologic examination revealed a moderately differentiated tubular adenocarcinoma stage T4aN1M0 and IIIA according to the UICC (Union for International Cancer Control) classification. He refused adjuvant chemotherapy and was only carefully observed. Twenty-three months after the primary gastrectomy, computed tomography (CT) revealed an irregular mass near the port site wounds. Then the patient underwent mass resection, and the pathological diagnosis was consistent with metastatic adenocarcinoma, located in the subcutaneous tissue at the port site wounds. Thirteen months after the second surgery, CT revealed an enhanced mass in the abdominal wall. Positron emission tomography (PET) CT showed an elevated uptake in the rectus abdominis muscle and a standardized uptake value (SUV) of 3.1. The patient underwent another mass resection, and the pathological diagnosis was consistent with metastatic adenocarcinoma in the rectus abdominis muscle. Thirty-five months after the third surgery, CT revealed a mass in the left gluteal subcutaneous region. Furthermore, PET-CT revealed a 35-mm mass with an elevated SUV of 9.6. Another mass resection procedure was performed, and the pathological diagnosis was consistent with metastatic adenocarcinoma in the subcutaneous tissue. Since tumor cells were present at the resection margin, additional radiation therapy was performed. The patient has survived 78 months after primary gastrectomy. Conclusion The prognosis of muscular and subcutaneous metastases from gastric cancer is poor. However, if the metastatic tumor is solitary, surgical excision could be a feasible treatment option and might prolong survival.

Background/Aim: The present study examined the impact of circular stapler size on anastomotic complications, including leakage and stricture in patients undergoing double-stapling technique (DST) anastomosis for left-sided colon or rectal cancer. Patients and Methods: A total of 403 patients were enrolled in this study, with circular stapler sizes of 25, 28, and 29 mm. Results: A small circular stapler (25 mm) was used in 170 cases (42.2%), and a medium-sized circular stapler (28/29 mm) was used in 233 cases (57.8%). After propensity score matching, there was no marked difference in the incidence of anastomotic leakage/stricture between the groups (13.9% vs. 10.9%, 3.0% vs. 1.0%, respectively). Conclusion: The size of the circular stapler was not associated with the incidence of anastomotic leakage or stricture in this cohort. [ABSTRACT FROM AUTHOR]

Abstract Although the incidence of hematological toxicity due to Trifluridine/tipiracil (FTD/TPI) treatment is high, the incidence of severe adverse events has been reported to be relatively low. However, it should be noted that patients with renal impairment are prone to severe hematological adverse events.

Abstract Background Anastomotic leakage is a serious, sometimes critical complication of upper gastrointestinal (GI) surgery. The cavity and target drainage tubes are difficult to reach; therefore, a nasogastric tube (NGT) and fasting are required for an extended period. We successfully treated and managed two patients with anastomotic leakage using percutaneous transesophageal gastro-tubing (PTEG). Case presentation In case 1, a 79-year-old man with gastric cancer underwent total gastrectomy; 1 week later, he underwent emergent open laparotomy due to panperitonitis attributed to anastomotic leakage-related jejunojejunostomy. We resected the portion between esophagojejunostomy and jejunojejunostomy and reconstructed it using the Roux-en-Y technique. On postoperative day (POD) 9, anastomotic leakage was diagnosed at the esophagojejunostomy site and jejunotomy staple line. After using a circular stapler for jejunojejunostomy, a stapled jejunal closure was added. We inserted an NGT and performed aspiration for bowel decompression. As he did not improve within 2 weeks, we decided to perform PTEG to free him of the NGT. We kept performing intermittent aspiration; leakage stopped shortly after, due to effective inner drainage. The PTEG catheter was removed after oral intake was restarted. In case 2, an 81-year-old man with esophagogastric junction cancer underwent resection of the distal esophagus and proximal stomach. After shaping the remnant stomach, esophagogastrostomy was performed under the right thoracotomy. On POD 11, anastomotic leakage was identified, along with a mediastinal abscess. We inserted an NGT into the abscess cavity through the anastomotic leakage site. On POD 25, we performed PTEG and inserted a drainage tube, instead of an NGT. Although the abscess cavity disappeared, anastomotic leakage persisted as a fistula. We exchanged the PTEG with a double elementary diet (W-ED) tube with jejunal extension, with the side hole located near the anastomosis. The anastomotic fistula disappeared after treatment. Dysphagia persisted due to disuse atrophy of swallowing musculature; PTEG was useful for enteral feeding, even after the leakage occurred. Conclusion Patients are sometimes forced to endure pain for a long time for transnasal inner drainage. Using PTEG, patients will be free of sinus pain and discomfort; PTEG should be helpful for patients withstanding NGT.

Abstract Background Nonocclusive mesenteric ischemia (NOMI) has been reported to be a life-threating disease. Gastric conduit necrosis is known as a critical postoperative complication after esophagectomy for esophageal cancer. We encountered a rare case of NOMI of a wide area of the intestine accompanied by gastric conduit necrosis after esophagectomy, which was successfully treated with an emergency operation. Case presentation A 67-year-old man presented with dysphagia. He was diagnosed with middle thoracic advanced esophageal cancer. After neoadjuvant chemotherapy, he underwent subtotal esophagectomy with lymphadenectomy and gastric conduit reconstruction. On postoperative day (POD) 2, he had diarrhea, high fever, and low blood pressure, which were treated with catecholamines. Laboratory data revealed acidosis and severe sepsis with multi-organ failure, including the kidneys. Although enhanced computed tomography did not exhibit definite findings of bowel ischemia, upper gastrointestinal endoscopy revealed necrotic mucosal changes in the whole gastric conduit. Therefore, we made a diagnosis of septic shock caused by gastric conduit necrosis and performed an emergency operation. When we explored the abdominal cavity, we found not only gastric conduit necrosis but also intermittent necrotic changes in the intestinal wall from the jejunum to the rectum. Therefore, NOMI was diagnosed. We performed an excision of the gastric conduit and 2 m of the small intestine, as well as total colectomy. After the second operation, prostaglandin E1 was administered intravenously as the treatment for NOMI, and sepsis was improved. On POD 122, he was self-discharged. He died of recurrence of lung metastasis from the esophageal cancer 9 months after the first operation. Conclusion When a patient has a critical status, including severe sepsis or severe acidosis, after esophagectomy, we should consider the possibility of NOMI in addition to gastric conduit necrosis and aim to diagnose and treat it immediately with an urgent operation.

Abstract Background We report a rare case of giant esophageal lipoma treated with thoracoscopic enucleation successfully. Case presentation A 69-year-old woman was referred to our department with dysphagia. Computed tomography examination revealed a large hypoattenuating submucosal mass with dense fat in the middle and lower esophagus. Upper gastrointestinal endoscopy revealed a submucosal mass with normal mucosa on the middle and lower esophageal wall. On a diagnosis of esophageal lipoma, we performed a video-assisted thoracoscopic operation and the 14.0 × 6.5 × 3.0 cm in size submucosal tumor was completely enucleated. We could successfully avoid a subtotal esophagectomy with high invasiveness. The patient was discharged on the 36th day after operation, and no symptoms had been noted. Conclusions Video-assisted thoracoscopic enucleation with minimal invasiveness may be an appropriate treatment option even for such a huge benign esophageal submucosal tumor.

IntroductionIt has recently been reported that the placement of a transanal drainage tube after rectal cancer surgery reduces the rate of anastomotic leakage. However, transanal drainage tube cannot completely prevent anastomotic leakage and the management of transanal drainage tube needs to devise. We investigated the information obtained during transanal drainage tube placement and evaluated the relationship between these factors and anastomotic leakage.Patients and methodsFifty-one patients who underwent anterior resection of rectal cancer was retrospectively reviewed. transanal drainage tube was placed for more than 5 days after surgery. The daily fecal volume from transanal drainage tube was measured on postoperative day 1-5, and the defecation during transanal drainage tube placement was investigated.ResultsAnastomotic leakage during transanal drainage tube placement occurred in 4 patients. The anastomotic leakage rate during transanal drainage tube placement in patients whose maximum daily fecal volume or total fecal volume from the transanal drainage tube during postoperative days 1-5 was large was significantly higher than that in patients whose fecal volume was small. The anastomotic leakage rate of the patients with intentional defecation during transanal drainage tube placement was significantly higher than that of the patients without intentional defecation during transanal drainage tube placement. The maximum daily fecal volume and the total fecal volume from the transanal drainage tube during postoperative days 1-5 in patients who experienced intentional defecation during transanal drainage tube placement was significantly higher than that of patients without intentional defecation during transanal drainage tube placement.ConclusionA large fecal volume from transanal drainage tube after anterior rectal resection or intentional defecation in patients with transanal drainage tube placement were suggested to be risk factors for anastomotic leakage.

Ramucirumab is an antiangiogenic agent targeting vascular endothelial growth factor receptor (VEGF)-2 that has been approved for second-line treatment of patients with metastatic colorectal cancer. VEGF-targeted therapy has various distinctive adverse effects owing to its antitumour effects. However, little is known with regard to its skin toxicity, such as its ability to cause skin ulcers. We report a case of large skin ulceration around a colostomy and delayed healing caused by ramucirumab. A 58-year-old patient diagnosed with rectal cancer with liver and lung metastases. He was administered folinic acid, fluorouracil (5-FU), and oxaliplatin (FOLFOX) and bevacizumab as first-line treatment. A laparoscopic colostomy was performed for suspected worsening of the bowel obstruction. He was then administered folinic acid, 5 fluorouracil, and irinotecan (FOLFIRI) and ramucirumab as second-line treatment after surgery. However, dehiscence and a small skin ulceration caused by ramucirumab developed around the colostomy which increased in size and became necrotic; therefore, he was administered only FOLFIRI, without ramucirumab. The ulcer decreased in size slightly with surgical debridement and showering. He resumed FOLFIRI and ramucirumab.

Abstract Background Growing evidence indicates that inflammation contributes to cancer progression, and several inflammatory markers have been reported to be associated with the clinical outcomes in patients with various types of cancer. Recently, the advanced lung cancer inflammation index (ALI) has been developed as a prognostic marker in patients with lung cancer. The difference between the ALI and the inflammatory markers reported in the previous studies is that the ALI contains not only indices related to inflammation but also the body mass index (BMI), which was reported to correlate with the sarcopenic status. The aim of this study was to evaluate the prognostic significance of the ALI in patients with unresectable metastatic colorectal cancer. Methods We retrospectively reviewed a database of 159 patients who underwent combination chemotherapy for unresectable metastatic colorectal cancer between 2008 and 2016. The BMI was calculated by dividing the weight by height squared. The neutrophil-to-lymphocyte ratio (NLR) was calculated from a blood sample by dividing the absolute neutrophil count by the absolute lymphocyte count. The ALI was defined as follows: ALI=BMI × serum albumin concentration/NLR. Results The overall survival rate was significantly worse in the low-ALI group than in the high-ALI group (p

BackgroundTumor-infiltrating lymphocytes (TILs) have been reported to reflect the anti-tumor immune status. However, recent investigations have demonstrated that intratumoral fibrosis is important as a factor affecting the infiltration of TILs. This study investigated the organ specificities of TIL infiltration and intratumoral fibrosis in primary colorectal cancer and distant metastases, as well as the relationship between the distribution of TILs and intratumoral fibrosis.MethodsPatients who underwent resection of primary tumors or distant metastases for colorectal cancer with distant metastases were enrolled. We evaluated the TIL infiltration by immunohistochemical staining with CD3&CD8 and intratumoral fibrosis by immunohistochemical staining with α-SMA positive cancer-associated fibroblasts and Masson's trichrome staining against collagen fibers. The "ImageJ" was used to evaluate fibrosis, and the density of TILs in the dense and sparse areas of fibrosis was calculated. The Immunoscore (IS) was obtained based on the density of CD3+/CD8+TILs in the tumor center and invasive margin of the primary tumor.ResultsThe degree of CD3+/CD8+TIL infiltration in peritoneal metastases was significantly lower than that in liver and lung metastases. The area ratio of α-SMA positive cancer-associated fibroblasts and collagen fibers in peritoneal metastases was significantly higher than that of liver and lung metastases. Furthermore, the density of TILs in the high-fibrosis area was significantly lower than that in the low-fibrosis area. In the high-IS group of primary tumors, the degree of TIL infiltration in distant metastases was significantly higher than that in the low-IS group.ConclusionThe infiltration of T lymphocytes into tumors is prevented in peritoneal metastases of colorectal cancer due to the high intratumoral fibrosis, which may lead to treatment resistance and a poor prognosis.

BackgroundsThis study was undertaken to investigate the impact of coexisting chronic kidney disease (CKD) on short- and long-term outcomes of laparoscopic gastrectomy in patients with gastric cancer (GC).MethodsWe reviewed the data of 798 patients treated for GC by laparoscopic gastrectomy. All procedures took place between January 2010 and December 2017. Patients were divided into three groups according to their estimated glomerular filtration rate (eGFR): severe CKD group, 44 patients with eGFR < 45 mL/min/1.73 m2; moderate CKD group, 117 patients with 45 ≤ eGFR < 60; control group, 637 patients with eGFR ≥ 60.ResultsBased on multivariate analysis, severe CKD (eGFR < 45) emerged as an independent predictor of anastomotic leak (Hazard ratio 4.63, 95% confidence interval [CI] 1.62-11.54). The 5-year overall survival (OS) rates by group were 46.3% (severe CKD), 76.6% (moderate CKD), and 81.5% (control). Multivariate analysis likewise identified severe CKD (eGFR < 45) as an independent correlate of poor 5-year OS. The 5-year cancer-specific survival (CSS) rates did not differ significantly by group.ConclusionsAn eGFR value less than 45 mL/min/1.73 m2 is a useful factor for predicting both anastomotic leak and 5-year OS in GC patients undergoing laparoscopic gastrectomy. Clinical care to improve eGFR should be reinforced before and after gastrectomy for GC patients with severe CKD.

BackgroundAlthough low skeletal muscle mass has an adverse impact on the treatment outcomes of cancer patients, whether the relationship between preoperative skeletal muscle mass and gastrectomy outcomes in gastric cancer (GC) differs between men and women is unclear. The study aimed to clarify this relationship based on gender.MethodsBetween January 2007 and December 2015, 1054 patients who underwent gastrectomy for GC at Osaka City General Hospital were enrolled in this study. We evaluated sarcopenia by the skeletal muscle index (SMI), which was measured by computed tomography (CT) using areas of muscle in the third lumbar vertebral body (L3). Male and female patients were each divided into two groups (low skeletal muscle and high skeletal muscle).ResultsThe SMI emerged as an independent predictor of 5-year overall survival (OS) in male GC patients (Hazard ratio 2.51; 95% confidence interval (CI) 1.73-3.63, p < 0.001) based on multivariate analysis. However, this index was not an independent predictive determinant of 5-year cancer-specific survival (CSS). The SMI was not an independent predictor of either OS or CSS in female GC patients. The incidence of leakage and major complication (Clavien Dindo grade ≧ 3) did not differ significantly across groups.ConclusionsPreoperative skeletal muscle mass is a valuable prognostic predictor of OS in male GC patients.

We report the successful management of stage III colon cancer in an elderly patient who received an adjuvant chemotherapy regimen of capecitabine plus oxaliplatin (CAPOX) with the Japanese kampo medicine ninjin'yoeito (NYT). A 75-year-old woman with a medical history of hypertension presented at another institution with fecal occult blood, and a colonoscopy that showed a type II tumor in the sigmoid colon. She was referred to our hospital for tumor resection, where colonoscopy confirmed the location of the type II tumor in the sigmoid colon. Histopathology of the biopsy specimen indicated a moderately differentiated tubular adenocarcinoma. Enhanced computed tomography of the thorax and abdomen indicated thickening of the sigmoid colon wall. Regional lymph node metastasis was suspected, but distant metastasis was not indicated. A blood examination revealed an elevated carcinoembryonic antigen (CEA) concentration (32.7 ng/ml). Following a diagnosis of cancer of the sigmoid colon, clinical stage IIIb [cT4a, N1b, M0], a laparoscopic sigmoid colectomy was performed without complications. The postoperative histopathological examination revealed a moderately differentiated to mucinous adenocarcinoma. Three of 16 retrieved lymph nodes contained malignant cells. The final tumor classification was Stage IIIb [pT4a, pN1b, M0]. The patient recovered uneventfully, and was discharged 10 days after surgery with a recommendation for adjuvant chemotherapy with CAPOX starting 4 weeks after surgery. The patient also received 7.5 g of NYT daily throughout the adjuvant chemotherapy course. She did not report any loss of appetite, general fatigue, peripheral neuropathy, neutropenia, or febrile neutropenia. During a 1-year postoperative follow-up, she has not experienced any recurrence. We conclude that NYT might be useful for reducing the adverse effects of anticancer therapy, particularly in elderly patients.

With advances in new cytotoxic drugs and molecular-targeted drugs, the prognosis of patients with metastatic colorectal cancer (mCRC) has improved. However, physicians often hesitate to administer intensive standard regimens to elderly patients with mCRC. Recently, first-line regimens that are effective in and well-tolerated by patients who are not eligible for intensive chemotherapy have been established. However, the therapeutic strategies to adopt after the failure of first-line treatment for patients who are not eligible for intensive chemotherapy remain unclear. We herein report two cases of long-term control of mCRC via FTD/TPI+bevacizumab (Bmab) as second- or third-line treatment in elderly patients without severe adverse events. In case 1, first-line treatment with Tegafur-Uracil, which is a prodrug of 5-FU, caused disease progression in a short period after the initiation of chemotherapy. In case 2, intensive first-line treatment caused severe adverse events, and treatment was discontinued. However, in both cases, disease control was obtained for a long time without severe adverse events by subsequent treatment with FTD/TPI+Bmab. The success in these present cases indicates that FTD/TPI+Bmab as a second- or third-line treatment is a therapeutic option for elderly patients with mCRC who are not eligible for intensive chemotherapy, even after failure of treatment with 5-FU.

As a result of recent major advances in chemotherapy for metastatic colorectal cancer, the prognosis for patients with metastatic colorectal cancer has improved. However, elderly patients often cannot receive intensive therapy. There are still many problems to solve regarding treatment for elderly patients with metastatic colorectal cancer. We herein report a case of complete response of pulmonary metastases from rectal cancer to tegafur-uracil (UFT)/leucovorin (LV) + bevacizumab (Bmab) in an elderly patient. An 80-year-old woman who had undergone curative surgery for rectal cancer 5 years ago was diagnosed with pulmonary metastases. Taking into account her advanced age and low renal function (creatinine clearance: 41.2 mL/min), UFT/LV + Bmab therapy was selected. The patient received UFT (300 mg/m2/day) and LV (75 mg/day) on days 1–5, 8–12, and 15–19 and Bmab (7.5 mg/kg) on day 1. The treatment cycle was repeated every 21 days. Following 17 courses of treatment without adverse events, a complete response was observed. Furthermore, there was no recurrence within 6 months after the final course of therapy. This case indicates that UFT/LV + Bmab is suitable for the treatment of elderly patients with metastatic colorectal cancer.

Abstract Background The anticancer immune response has been reported to correlate with cancer progression. Tumor-infiltrating lymphocytes (TILs), which are one of the indicators of host immunity, affect the tumor growth, metastasis and chemoresistance. Both TILs in the primary tumor and those in the metastatic tumor have been reported to be a useful predictor of the survival and therapeutic outcome. However, the correlation between the density of TILs in the primary and metastatic tumor is unclear. The aim of this study was to elucidate the correlation between the density of TILs in the primary and metastatic tumor. Methods A total of 24 patients with stage IV colorectal cancer who underwent concurrent resection of the primary tumor and liver metastasis were enrolled in order to assess the correlation between the density of TILs in the primary tumor and that in the metastatic tumor. Hematoxylin and eosin (HE)-stained tumor sections were used for the evaluation of TILs. The density of TILs was assessed by the measurement of the area occupied by mononuclear inflammatory cells over the total stromal area at the invasive margin. In addition, to evaluate TIL subsets and the activation/suppression status of the lymphocytes, immunohistochemistry for CD4, CD8, Forkhead boxprotein P3 (FOXP3), programmed cell death 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), inducible T-cell co-stimulator (ICOS), Glucocorticoid induced tumor necrosis factor receptor related protein (GITR), Human Leukocyte Antigen - antigen D Related (HLA-DR) and Granzyme B was performed, and the number of immunoreactive lymphocytes was counted. Results According to the evaluation using the HE-stained sections, the density of tumor-infiltrating mononuclear inflammatory cells in the primary tumor was significantly associated with that in the metastatic tumor. In addition, according to the immunohistochemistry evaluation, the density of CD4+, CD8+ and FOXP3+ TILs in the primary tumor and that in the metastatic tumor were significantly correlated with that in the metastatic tumor. Furthermore, the activation/suppression marker values of the lymphocytes (i.e., such as PD-1, ICOS, Granzyme B and the PD-1/CD8 ratio) in the primary tumor were correlated with values in the metastatic tumor. Conclusions The local immune status of the primary tumor was revealed to be similar to that of the metastatic tumor. This suggests that the evaluation of the local immunity of the primary tumor may be a substitute for the evaluation of the local immunity of the metastatic lesion. Therefore, information on the primary tumor may be useful when considering treatment strategies for metastatic lesions.