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Background Immune checkpoint inhibitors targeting the programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway have demonstrated antitumor effects in patients with various malignancies, including esophageal cancer. Thus, a better understanding of local immunity in esophageal cancer is crucial for improving treatment and clinical outcomes. Methods We evaluated PD-1 expression on tumor-infiltrating lymphocytes (TILs), as well as PD-L1 expression on cancer cells, by immunohistochemistry and immunofluorescence using a nonbiased database of 433 curatively resected esophageal cancers. With the idea of application as liquid biopsy, PD-1 expression status on peripheral lymphocytes was evaluated by flow cytometry. Results The cutoff value of PD-1 expression was the median PD-1 count. Compared with cases of low PD-1 expression (n = 219), cases with high levels of PD-1 expression (n = 213) showed significantly worse overall survival (log-rank P = .0017). The prognostic effect of PD-1 differed according to the preoperative treatment status (P for interaction = .040); PD-1 expression was associated with high overall mortality among patients without preoperative therapy, while no such association was present among those with preoperative treatment. A stratification based on PD-1 and PD-L1 status was also significantly associated with overall survival (log-rank P = .0005). PD-1 expression on TILs was significantly associated with that on peripheral lymphocytes (P Conclusions PD-1 expression on TILs was associated with an unfavorable clinical outcome in esophageal cancer, supporting its role as a prognostic biomarker. The combination of PD-1 and PD-L1 expression enabled further classification of patients according to clinical outcome.

Gastrectomy may induce significant postoperative disabilities and worsen the quality of life in elderly patients. Without a functioning esophagogastric junction (EGJ), swallowing is impaired because of the anatomical and physiological changes after surgery, which increases the risk of postoperative pneumonia. The aim of this study was to identify the impact of the type of surgical procedure on death from pneumonia in elderly patients with gastric cancer (GC) over the long term. We analyzed the data of 343 patients with GC who underwent curative gastrectomy in our hospital. We divided the patients into elderly and non-elderly groups. Among them, 109 patients aged ≥ 75 years who underwent curative resection were analyzed, their clinicopathological factors and clinical outcomes were compared, and the impact of the type of surgical procedure on death from pneumonia over the long term was evaluated. The institutional scientific review board of Kumamoto University Hospital was approved for data collection and analysis (No. 1037). There were significantly higher levels of American Society of Anesthesiologists (ASA) and poor nutrition in the elderly group; however, gender, BMI and factors related to pneumonia did not differ significantly between groups. The median duration of follow-up time 1588 days. On the multivariate analysis, age and surgical procedure were selected as independent predictive factors for pneumonia-related survival. Preservation of the EGJ as much as possible while maintaining curability is useful for reducing postoperative death from pneumonia over the long term in elderly patients with gastric cancer.

This study aimed to examine whether preoperative serum transferrin, a rapid-turnover protein, correlates with short- and long-term outcomes after esophagectomy. Preoperative transferrin levels, calculated by summing serum iron and unsaturated iron-binding capacity, were evaluated in 224 patients who underwent esophagectomy for stage I–III esophageal cancer without preoperative treatment. Transferrin levels are directly proportional to total iron-binding capacity (TIBC), and we defined TIBC

A 41-year-old woman was admitted to our hospital for epigastralgia. She had been admitted to another hospital for fundic gland polyposis (FGP) without any symptoms, and no malignancy had been noted in her previous endoscopy. However, a biopsy performed at our hospital revealed adenocarcinoma, and computed tomography (CT) revealed multiple liver and peritoneal metastases. We clinically suspected gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) and indicated genetic testing. The point mutation in exon 1B of APC was revealed. She was diagnosed with GAPPS with multiple liver metastases and underwent systemic chemotherapy. She has two older brothers who also have FGP. The same genomic mutation was observed in both brothers and their mother, and they were also diagnosed with GAPPS. The brothers underwent prophylactic laparoscopic total gastrectomy with D1 lymph-node dissection.

High preoperative hemoglobin A1c (HbA1c) levels have been suggested to increase complications after esophagectomy. Minimally invasive esophagectomy (MIE) is less invasive than open esophagectomy (OE) and may reduce postoperative complications. However, it has not been established whether MIE contributes to low morbidity in patients with high preoperative HbA1c levels. Thus, the current study aimed to elucidate the effect of preoperative HbA1c levels on the incidence of complications each after OE and MIE. A total of 280 patients who underwent OE and 304 patients who underwent MIE for esophageal cancer between April 2005 and April 2020 were retrospectively analyzed. The OE and MIE groups were further divided into two groups according to their preoperative HbA1c levels (

An appropriate strategy is needed to determine the therapeutic effect of chemotherapy on primary lesions in esophageal cancer. This multicenter cohort study aimed to examine the usefulness of a novel criterion obtained by multiplying the lengths of the major and minor esophageal axes from helical computed tomography as a tool to evaluate the therapeutic effect of neoadjuvant chemotherapy and to predict prognosis after surgery in locally advanced esophageal cancer. A first investigation evaluated the reproducibility of the new criterion between two independent examiners. In a second investigation, we examined the association of the novel criterion with pathological tumor regression grade and long-term outcomes. Pretreatment primary lesions less than 20 mm on computed tomography were excluded. In an initial cohort of 81 patients, the intraclass correlation coefficient for the novel criterion was higher than that for the tumor major axis both before and after neoadjuvant chemotherapy. In the second cohort of 255 patients, the novel criterion significantly correlated with tumor regression grade (p = 0.0003), overall survival (p < 0.0001), and disease-free survival (p < 0.0001). It was also an independent predictor for overall survival (p = 0.0023), along with age, tumor regression grade, and pathological stage. The measurement derived by multiplying the esophageal major and minor axes on computed tomography is easy to obtain and has better objectivity and reproducibility for tumors of any shape. This novel criterion may be clinically useful because it can estimate therapeutic effect, tumor regression grade, and prognosis after neoadjuvant chemotherapy followed by surgery for esophageal cancer.

Background Solitary fibrous tumor (SFT) is a relatively rare mesenchymal tumor that mainly affects adults. Its prognosis is good after curative resection, but distant recurrences after 10 years or longer have been reported. Recurrent SFT usually arises as a local lesion; distant metastasis is rarely reported. Here, we report lung metastases that recurred a decade after excising a retroperitoneal primary SFT. Case presentation A 44-year-old woman had an SFT resected from her right retroperitoneum at our hospital. Ten years later, at age 54, she underwent a lung resection after CT showed three suspected metastases in her left lung. All three were histologically diagnosed as lung metastases from the retroperitoneal SFT. However, whereas the primary SFT had 1–2 mitotic cells/10 high power fields (HPF), the metastatic lesion increased malignancy, at 50/10 HPF. Conclusion Patients who have had resected SFTs should be carefully followed up, as malignancy may change in distant metastasis, as in this case.

Stage IV Gastric/Esophagogastric junction cancer (G/EGJ) has an unfavorable prognosis and poor curability. In this study, we report the case of long-term survival after multidisciplinary treatments for advanced esophagogastric junction cancer. A 53-year-old male patient was diagnosed with HER2 positive advanced esophagogastric junction cancer and mediastinal and paraaortic lymph node metastasis. After systemic chemotherapy for 1 year, minimally invasive esophagectomy was conducted as conversion surgery. However, peritoneal and liver metastasis was observed on 3 months after curative surgery. 2 years after operation, solitary brain metastasis was detected and stereotactic radiosurgery (SRS) using a gamma knife was underwent. After 1 year, despite the continuous administration of Nivolumab, the paraaortic lymph node increased in size again and radiation therapy was conducted. Currently, he is alive and undergoing chemotherapy.

Background Fusobacterium nucleatum (F. nucleatum) is a gut microbe implicated in gastrointestinal tumorigenesis. Predicting the chemotherapeutic response is critical to developing personalised therapeutic strategies for oesophageal cancer patients. The present study investigated the relationship between F. nucleatum and chemotherapeutic resistance in oesophageal squamous cell carcinoma (ESCC). Methods We examined the relationship between F. nucleatum and chemotherapy response in 120 ESCC resected specimens and 30 pre-treatment biopsy specimens. In vitro studies using ESCC cell lines and co-culture assays further uncovered the mechanism underlying chemotherapeutic resistance. Results ESCC patients with F. nucleatum infection displayed lesser chemotherapeutic response. The infiltration and subsistence of F. nucleatum in the ESCC cells were observed by transmission electron microscopy and laser scanning confocal microscopy. We also observed that F. nucleatum modulates the endogenous LC3 and ATG7 expression, as well as autophagosome formation to induce chemoresistance against 5-FU, CDDP, and Docetaxel. ATG7 knockdown resulted in reversal of F. nucleatum-induced chemoresistance. In addition, immunohistochemical studies confirmed the correlation between F. nucleatum infection and ATG7 expression in 284 ESCC specimens. Conclusions F. nucleatum confers chemoresistance to ESCC cells by modulating autophagy. These findings suggest that targeting F. nucleatum, during chemotherapy, could result in variable therapeutic outcomes for ESCC patients.

Family 1: a 39-year-old woman and her sister were admitted to our hospital for fundic gland polyps (FGPs). Their mother died of gastric cancer with FGPs. We performed repeated biopsies at close intervals, suspecting gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). After a 1-year follow-up, the sisters were diagnosed with gastric cancer with FGP. We performed laparoscopic total gastrectomies with D1+lymph node dissection. Promoter 1B (exon 1B) of the APC gene (chr5: 112,043,224 T>C) contained a point mutation. The sisters were subsequently diagnosed with GAPPS as per the mutational analysis. Family 2 (unrelated to Family 1): a-24-year-old woman was referred for epigastralgia. EGD revealed FGPs localized in the proximal stomach. Pathological biopsy results showed severe dysplasia and adenocarcinoma in situ. Her father was simultaneously diagnosed with FGPs with GC localized in the proximal stomach. We performed laparoscopic total gastrectomies with D1+lymph node dissection. They had the same gene mutation as the family 1. Here, we report two Asian families with GAPPS successfully treated via laparoscopic total gastrectomy.

Neuroendocrine tumors (NETs) are rare neoplasms, with an estimated annual incidence of 6.9/100 000. They arise from cells of the diffuse endocrine system, which are mainly dispersed throughout the gastrointestinal (GI), pancreatic, and respiratory tracts. The incidence of GI‐NETs has recently begun to show a steady increase. According to the Surveillance, Epidemiology, and End Results database, 53% of patients with NETs present with localized disease, 20% with locoregional disease, and 27% with distant metastases at the time of diagnosis. Surgery is the mainstay for the treatment of locoregional GI‐NETs. Endoscopic resection is an option for well‐differentiated early GI‐NETs, which are thought to very rarely metastasize to lymph nodes. A lesion that is technically difficult to resect via endoscopy is an indication for local resection (partial resection without lymph node dissection). GI‐NETs with possible lymph node metastasis is an indication for enterectomy with lymph node dissection. For NETs with metastatic lesions, cytoreduction surgery can control hormonal hypersecretion and alleviate symptoms; therefore, cytoreduction surgery is recommended. The indications for surgery vary and are based on the organ where the NET arose; therefore, an understanding of the patient's clinical state and individualized treatment that is based on the characteristics of the patient's GI‐NET is needed. This review summarizes surgical treatments of GI‐NETs in each organ., The indications for surgery vary and are based on the organ where the neuroendocrine tumors (NET) arose; therefore, an understanding of the patient's clinical state and individualized treatment that is based on the characteristics of the patient's gastrointestinal NET are needed.

Background The predictive significance of programmed death ligand 1 (PD-L1) for programmed death 1 (PD-1) inhibitors remains unclear in gastric cancer (GC) due to the dynamic alteration by treatments. We aimed to elucidate the effects of trastuzumab (Tmab) on PD-L1 expression in GC. Methods PD-L1 expression was evaluated by multicolour flow cytometry analysis after co-culturing GG cell lines and immune cells with Tmab. IFN-γ in the co-culture experiments was quantified. Immunohistochemistry (IHC) for PD-L1 expression using clinical samples was also performed to confirm PD-L1 alteration by Tmab. Results PD-L1 expression was significantly upregulated by Tmab in HER2-amplified GC cell lines co-cultured with peripheral blood mononuclear cells (PBMCs). PD-L1 upregulation by Tmab was also observed in the GC cells co-cultured with NK cells in time-dependent manner, but not with monocytes. IFN-γ concentration in conditioned media from co-cultured PBMCs and NK cells with Tmab was significantly higher and anti-IFN-γ significantly suppress the Tmab-induced PD-L1 upregulation. IHC also suggested PD-L1 upregulation after Tmab treatment. Conclusions Tmab can upregulate PD-L1 expression on GC cells through interaction with NK cells. These results suggest clinical implications in the assessment of the predictive significance of PD-L1 expression for PD-1 inhibitors.

Extracellular vesicles (EV) from cancer-associated fibroblasts (CAF) are composed of diverse payloads. Although CAFs impact the aggressive characteristics of gastric cancer cells, the contribution of CAF-EV to gastric cancer progression has not been elucidated. Here, we investigated the molecular mechanism of the changes in gastric cancer characteristics induced by CAF-EV. CAF abundance in gastric cancer tissues was associated with poor prognosis of patients with gastric cancer receiving chemotherapy. Moreover, CAF-EV induced tubular network formation and drug resistance of gastric cancer cells in the extracellular matrix (ECM). Comprehensive proteomic analysis of CAF-EV identified that Annexin A6 plays a pivotal role in network formation and drug resistance of gastric cancer cells in the ECM via activation of β1 integrin-focal adhesion kinase (FAK)-YAP. A peritoneal metastasis mouse model revealed that CAF-EV induced drug resistance in peritoneal tumors, and inhibition of FAK or YAP efficiently attenuated gastric cancer drug resistance in vitro and in vivo. These findings demonstrate that drug resistance is conferred by Annexin A6 in CAF-EV and provide a potential avenue for overcoming gastric cancer drug resistance through the inhibition of FAK-YAP signaling in combination with conventional chemotherapeutics. Significance: This study elucidates a novel molecular mechanism through which Annexin A6 in CAF-EV activates FAK-YAP by stabilizing β1 integrin at the cell surface of gastric cancer cells and subsequently induces drug resistance.

High MCV is suggested to be relevant to the incidence and prognosis of several malignancies. However, few studies investigating the correlation between MCV and survival outcome of esophageal cancer have been conducted. Methods This study included 570 patients with esophageal cancer who underwent radical esophagectomy between April 2005 and December 2017. Patients were divided into two groups according to the standard value of pretreatment MCV: normal (83–99 fL) and high (>99 fL) groups. Clinical backgrounds, short-term outcomes, and prognostic outcomes post-esophagectomy were retrospectively compared between the groups. Results Of all patients, 410 (71.9%) had normal MCV, and 160 (28.1%) had high MCV. High MCV was significantly associated with lower body mass index, higher frequency of habitual alcohol and tobacco use, and higher incidence of multiple primary malignancies other than esophageal cancer. High MCV also correlated with higher incidence of postoperative morbidity of the Clavien–Dindo classification ≥II and pulmonary morbidity. Overall survival was significantly worse in patients with high MCV. Multivariate analysis suggested that high MCV was an independent risk factor for worse survival outcome (hazard ratio, 1.54; 95% confidence interval, 1.098–2.151; p = 0.012). Conclusion Patients with high MCV have various disadvantages in clinical background that can adversely affect both short-term and long-term outcomes after esophagectomy. MCV can become a predictive marker to estimate survival outcome after esophagectomy for esophageal cancer.

The application of laparoscopic subtotal gastrectomy (LsTG) in the management of early gastric cancer located in the upper third of the stomach creates an extremely small remnant stomach (SRS). However, it is unclear whether retaining such an SRS improves patients’ postoperative outcomes in a similar manner to a conventional remnant stomach (CRS). Four hundred and nine of 878 patients undergoing laparoscopic distal gastrectomy (LDG) between 2006 and 2012 underwent Roux-en-Y reconstruction. Among them, we selected 73 patients who underwent LsTG with an SRS (SRS group), and 83 patients with the tumor in the lower third of the stomach who underwent LDG with a CRS (CRS group). The surgical outcomes at 1 and 6 months, 1, 2, and 3 years after gastrectomy were retrospectively analyzed and compared between the two groups. One year after gastrectomy, the postoperative:preoperative bodyweight ratio of the SRS group was 2% lower than that of the CRS group. Both groups had comparable total protein and albumin levels, and incidence of reflux esophagitis; however, hemoglobin was lower in the SRS group. This difference in hemoglobin level between the SRS and CRS groups became larger over time, although the total protein and albumin levels of the two groups remained similar. An SRS slightly decreases bodyweight and hemoglobin level compared with a CRS. Several objective outcomes of the SRS group are almost equal to those of the CRS group, which suggests LsTG is worth performing even though its remnant stomach is very small.

Background The incidence of synchronous gastrointestinal neuroendocrine tumors (GI-NETs) and colorectal cancer is very low. Case presentation We present a 72-year-old man diagnosed with a rectal neuroendocrine tumor (NET) with multiple organ metastases and simultaneous sigmoid colon cancer. Although the NET was his prognostic factor, he underwent a laparoscopic sigmoidectomy at first because it was expected that the colon cancer would cause obstruction or bleeding during NET treatment. Subsequently, he started taking everolimus. Conclusions We should consider surgical resection of the synchronous cancer before systemic therapy for a GI-NET regardless of the difference in prognosis between synchronous tumors, if the cancer may impair the continuation of systemic therapy.

Abnormal function of human body enzymes and epigenetic alterations such as DNA methylation have been shown to lead to human carcinogenesis. Lysyl oxidase (LOX) enzyme has attracted attention due to its involvement in tumor progression in various cancers. The purpose of this study was to clarify the clinical importance of LOX expression and its epigenetic regulation in the pathogenesis of esophageal squamous cell carcinoma (ESCC). Using a database of 284 ESCCs, we examined LOX expression and its prognostic characteristics. The functional role of LOX was assessed by in vitro growth, migration, and invasion assays. The relationship between LOX expression, global DNA hypomethylation (ie, LINE‐1 methylation), and LOX promoter methylation was evaluated by using mRNA expression arrays and pyrosequencing technology. High LOX expression cases had a significantly shorter overall survival and cancer‐specific survival (log‐rank, P, This is the first study to provide the evidence for the relationship between lysyl oxidase (LOX) expression, poor prognosis, and aggressive phenotype in esophageal cancer. In addition, we revealed that LOX expression was regulated epigenetically by genome‐wide hypomethylation using in vitro assay and integrated gene analysis in tissues and cell lines.

Background Persistent descending mesocolon (PDM) is caused by the absence of fusion of the descending colon to the retroperitoneum. We herein report two colorectal cancer cases with PDM that were treated with laparoscopic surgery. Case presentation Case 1: a 50-year-old man with sigmoid colon cancer and synchronous liver metastasis. After neoadjuvant chemotherapy, he underwent laparoscopic sigmoidectomy with lymph node dissection cutting the root of the inferior mesenteric artery (IMA) and synchronous liver resection. He experienced postoperative stenosis of the reconstructed colon possibly due to an impaired arterial blood flow in the reconstructed colon. Case 2: a 77-year-old man with rectal cancer. Laparoscopic low anterior resection preserving the left colic artery (LCA) was performed. Intraoperative infrared ray (IR) imaging using indocyanine green (ICG) showed good blood flow of the reconstructed colon. He had no postoperative complications. In cases of PDM, the mesentery of the descending and sigmoid colon containing the LCA is often shortened, and the marginal artery of the reconstructed colon is located close to the root of the LCA. Lymph node dissection accompanied by cutting the LCA carries a risk of marginal artery injury. Therefore, we recommend lymph node dissection preserving the LCA in colorectal cancer patients with PDM in order to maintain the blood flow of the reconstructed colon. If the IMA and LCA absolutely need to be cut for complete lymph node dissection, the marginal artery should be clearly identified and preserved. In addition, intraoperative IR imaging is extremely useful for evaluating colonic perfusion and reducing the risk of anastomotic complications. Conclusion In colorectal cancer surgery in patients with PDM, surgeons should be aware of these tips for maintaining the blood flow of the reconstructed colon and thereby avoid postoperative complications caused by an impaired blood flow.

The tumor proportion score (TPS) and combined positive score (CPS) have been developed to assess programmed death ligand 1 (PD-L1) expression in gastric cancer (GC). This study aimed to elucidate the role of TPS and CPS as prognostic biomarkers. A total of 191 patients with GC who received curative gastrectomy were retrospectively enrolled. Double immunohistochemistry of PD-L1 and ionized calcium binding adaptor molecule 1 was performed to clearly distinguish PD-L1 expression between tumor cells and macrophages. Survival analysis for PD-L1 expression by TPS and CPS was performed. PD-L1 positivity was detected in 39 patients (20.4%) by TPS and in 137 patients (71.7%) by CPS. Patients with PD-L1 positivity by CPS experienced significantly shorter overall survival (OS) (P

Immune checkpoint inhibitors, such as antibody against programmed cell death protein (PD-1), have demonstrated antitumour effects in patients with malignancies, including oesophageal cancer. A lymphocytic reaction observed by pathological examination is a manifestation of the host immune response to tumour cells. It was hypothesized that a stronger lymphocytic reaction to tumours might be associated with favourable prognosis in oesophageal cancer.Using a database of resected oesophageal cancers, four morphological components of lymphocytic reactions (peritumoral, intranest, lymphoid and stromal) to tumours were evaluated in relation to clinical outcome, PD-1 expression by immunohistochemistry and total lymphocyte count in blood.Resected oesophageal cancer specimens from 436 patients were included in the study. Among the four morphological components, only peritumoral reaction was associated with patient prognosis (multivariable P for trend0·001); patients with a higher peritumoral reaction had significantly longer overall survival than those with a lower reaction (multivariable hazard ratio 0·48, 95 per cent c.i. 0·34 to 0·67). The prognostic effect of peritumoral reaction was not significantly modified by other clinical variables (all P for interaction0·050). Peritumoral reaction was associated with total lymphocyte count in the blood (P 0·001), supporting the relationship between local immune response and systemic immune competence. In addition, higher morphological peritumoral reaction was associated with high PD-1 expression on lymphocytes in tumours (P = 0·034).These findings should help to improve risk-adapted therapeutic strategies and help stratify patients in the future clinical setting of immunotherapy for oesophageal cancer.Los inhibidores de los puntos de control inmunitario (checkpoints) (p.ej. los anticuerpos anti-PD-1) han demostrado efectos antitumorales en pacientes con tumores malignos, incluido el cáncer de esófago. La reacción linfocítica detectada en estudios anatomopatológicos es una manifestación de la respuesta inmune del huésped a las células tumorales. Se estableció la hipótesis de que una mayor reacción linfocítica a los tumores podría asociarse con un mejor pronóstico en el cáncer de esófago. MÉTODOS: Usando una base de datos de 436 cánceres de esófago resecados, se evaluaron cuatro componentes morfológicos (peritumoral, intra-epitelial, linfoide y estromal) de las reacciones linfocíticas a tumores en relación con los resultados clínicos, la expresión inmunohistoquímica de PD-1 y el recuento total de linfocitos en sangre.De los cuatro componentes, solamente la reacción peritumoral se asoció con el pronóstico del paciente (P multivariable para tendencia 0,001): los pacientes con mayor reacción peritumoral presentaron una supervivencia global significativamente más prolongada que aquellos pacientes con menor reacción peritumoral (cociente de riesgos instantáneos multivariable, hazard ratio, HR: 0,48; i.c. del 95%: 0,34 -0,67; P0,001). El efecto pronóstico de la reacción peritumoral no se modificó significativamente por otras variables clínicas (todas las P para la interacción 0,05). La reacción peritumoral se asoció con el recuento total de linfocitos en la sangre (P 0,001), lo que respalda la relación entre la respuesta inmune local y la competencia inmune sistémica. Además, una elevada reacción morfológica peritumoral se asoció con una alta expresión de PD-1 en linfocitos tumorales (P = 0,034). CONCLUSIÓN: Estos hallazgos deberían ayudar a mejorar las estrategias terapéuticas adaptadas al riesgo y contribuir a estratificar a los pacientes en el entorno clínico futuro de la inmunoterapia para los pacientes con cáncer de esófago.

Background The incidence of metastatic spread of gastrointestinal malignancies to the thyroid gland is relatively low and most of these malignancies originate from the colorectum. Thyroid metastasis originating from the esophagus is poorly documented. Case presentation A 79-year-old man presented with hoarseness of voice and swallowing difficulty. Eighteen months earlier, he had undergone preoperative chemotherapy (S-1 and oxaliplatin [SOX] therapy) and subtotal esophagectomy with regional lymph nodes dissection and retrosternal narrow gastric tube reconstruction for advanced Barrett’s esophageal adenocarcinoma. In the ultrasonographic examination, there was a hypoechoic, indistinct border and heterogeneous nodule in the left lobe of the thyroid gland. Pathological examination of an ultrasound-guided fine-needle aspiration showed adenocarcinoma, supporting a diagnosis of esophageal adenocarcinoma metastases in the thyroid. Conclusion This is a first case of a patient with thyroid metastasis from Barrett’s esophageal adenocarcinoma after subtotal esophagectomy.

Indoleamine 2, 3‐dioxygenase 1 (IDO1) is a primary enzyme that generates immunosuppressive metabolites. It plays a major role in tumor immunology and is a potential immune‐based therapeutic target. We have reported that IDO1 protein expression was associated with an unfavorable clinical outcome in esophageal cancer. Recently, it has been reported that IDO1 expression is regulated by methylation of the IDO1 promoter. Thus, the aim of this study was to examine the relationship between IDO1 expression, IDO1 promoter methylation, and clinicopathological features in esophageal cancer. We first confirmed changes in IDO1 expression levels in vitro by treating cells with 5‐azacytidine. We then evaluated the relationship between IDO1 expression levels, IDO1 promoter methylation (bisulfite pyrosequencing), and clinicopathological features using 40 frozen samples and 242 formalin‐fixed, paraffin‐embedded samples resected from esophageal cancer patients. We treated cell lines with 5‐azacytidine, and the resulting hypomethylation induced significantly higher IDO1 expression (P

The effect of resection of the thoracic duct (TD) along with surrounding lymph nodes (LN) on short- and long-term outcomes of esophagectomy in esophageal cancer patients is not well defined. A total of 537 consecutive patients suffering from esophageal cancer who underwent three-incision esophagectomy between April 2005 and August 2018 were eligible for short-term outcome analysis. Among them, 487 patients who underwent surgery before August 2017 were eligible for analysis of long-term outcomes. Moreover, 164 patients who underwent esophagectomy after August 2012 and had no recurrence at 1-year postoperative follow-up were prospectively investigated for postoperative nutritional status. A total of 145 patients (27.0%) underwent TD resection with surrounding LN. Since the clinical stage was significantly more advanced in the removal group, preoperative treatment was more frequently performed in them. The operative time was significantly longer in the removal group. Intraoperative bleeding was higher in the removal group. Morbidity of Clavien–Dindo classification (CDc) ≥ II and pulmonary morbidities were frequently observed in the removal group. Multivariate analysis suggested that TD resection was an independent risk factor for pulmonary morbidities. Moreover, it may be associated with the incidence of CDc ≥ II morbidity. Greater numbers of LN were dissected in the thorax of patients in the removal group. However, overall survival was equivalent irrespective of the TD procedure in each stage. Nutritional status at 1-year follow-up was equivalent between the groups. On the basis of the present results, routine removal of the TD during esophagectomy is not recommended.

Thymic carcinoma, a rare mediastinal neoplasm, is characterized by extensive local invasion and distant metastasis. To our knowledge, this is the first case report demonstrating the efficacy of laparoscopic dissection for pelvic lymph node metastases from thymic carcinoma. A 64-year-old man was found to have a mediastinal mass by CT and underwent radical resection. Six months after resection of his thymic carcinoma, follow-up CT revealed a gluteal tumor and enlarged pelvic lymph nodes. The gluteal tumor was resected percutaneously. Two months after this procedure, PET showed that the three pelvic lymph nodes had abnormal uptake of 18 F-fluorodeoxyglucose and had enlarged further. The patient accordingly underwent laparoscopic dissection of these lymph nodes. Pathological examination of all resected specimens showed metastatic thymic carcinoma. We recommend laparoscopic dissection of pelvic lymph node metastases because it provides a clear intraoperative view and is minimally invasive.

Although para-aortic lymph node (PALN) metastasis from gastric cancer is a non-curative lesion, gastrectomy with complete PALN dissection (PAND) following neoadjuvant chemotherapy (NAC) is a tentative standard treatment in Japan, based on the results of a small-scale phase II clinical trial. However, whether complete PAND (C-PAND) is always necessary for such diseases is open to debate. Patients who received NAC followed by R0 gastrectomy for gastric cancer with clinical PALN metastasis at the Cancer Institute Hospital in Tokyo from 2005 to 2017 were reviewed in the present study. We assessed surgical findings and long-term outcomes. In total, 44 patients receiving gastrectomy with C-PAND (n = 22) or limited PAND (L-PAND; n = 22) were included. Operation time was significantly longer in the C-PAND than in the L-PAND groups (363 min vs. 271 min, P = 0.037). There was no difference between the two groups in the ypStage classification and pattern of recurrence. The 5-year overall survival (OS) and relapse-free survival (RFS) curves were higher in the L-PAND group than the C-PAND group, without reaching a significant difference. The 5-year OS (42.9% vs. 75.7%, p = 0.017) and RFS (14.3% vs. 48.6%, p = 0.002) were significantly worse in the group of three or more, than in the group of less than three pathological PALN metastasis, whereas increasing numbers of harvested PALN were not associated with improved survival. Curative gastrectomy with L-PAND following NAC for gastric cancer involving PALN may be an alternative treatment to C-PAND.

Clinical significance of red blood cell distribution (RDW) as a predictive marker for the incidence of postoperative morbidity after esophagectomy for esophageal cancer has not been established. This study included 634 consecutive patients who underwent three-incisional esophagectomy with lymphadenectomy for esophageal cancer between April 2005 and November 2020. Correlation between pretreatment RDW and patient background, cancer background, and short-term outcome after esophagectomy were retrospectively investigated. Eighty patients (12.6%) had a high pretreatment RDW (> 14.2), which correlated with malnutrition estimated by body mass index, hemoglobin, total lymphocyte count, albumin, and total cholesterol. High pretreatment RDW was an independent risk factor for postoperative severe morbidity of grade IIIb or higher based on the Clavien–Dindo classification (hazard ratio [HR] 3.90, 95% confidence interval [CI] 1.707–8.887; p = 0.0012) and reoperation (HR 4.39, 95% CI 1.552–12.390; p = 0.0053) after open esophagectomy (OE). However, RDW was not associated with postoperative morbidity incidence after minimally invasive esophagectomy (MIE). Pretreatment RDW may be a surrogate marker for nutritional status and could be a predictive marker for postoperative severe morbidity, reoperation, and possibly pneumonia after OE. On the contrary, the lower invasiveness of MIE may have reduced the effect of pretreatment malnutrition on morbidity incidence, which could explain the insignificant relationship between RDW and poor short-term outcomes in MIE.

Background Solid pseudopapillary neoplasm of the pancreas is a rare tumor in young women, metastasizing in only 5–15% of cases, and most commonly to the liver. Although treatment guidelines have not been established, surgical resection is usually performed. We report a rare case of repeat hepatectomy for liver metastases after distal pancreatectomy with solid pseudopapillary neoplasm. Case presentation The patient was a 71-year-old woman who underwent distal pancreatectomy for solid pseudopapillary neoplasm, and liver metastasis occurred 4 years after the first surgery. Partial liver resection was performed for four liver metastases, and histopathological examination revealed a diagnosis of liver metastasis from solid pseudopapillary neoplasm. However, 18 months later, liver metastases were detected again; three tumors were identified, and partial resection was performed, which has provided 18 months’ recurrence-free survival. Conclusions Long-term prognosis can be expected following R0 resection for resectable liver metastasis from solid pseudopapillary neoplasm.

Summary: In the tumor microenvironment, senescent non-malignant cells, including cancer-associated fibroblasts (CAFs), exhibit a secretory profile under stress conditions; this senescence-associated secretory phenotype (SASP) leads to cancer progression and chemoresistance. However, the role of senescent CAFs in metastatic lesions and the molecular mechanism of inflammation-related SASP induction are not well understood. We show that pro-inflammatory cytokine-driven EZH2 downregulation maintains the SASP by demethylating H3K27me3 marks in CAFs and enhances peritoneal tumor formation of gastric cancer (GC) through JAK/STAT3 signaling in a mouse model. A JAK/STAT3 inhibitor blocks the increase in GC cell viability induced by senescent CAFs and peritoneal tumor formation. Single-cell mass cytometry revealed that fibroblasts exist in the ascites of GC patients with peritoneal dissemination, and the fibroblast population shows p16 expression and SASP factors at high levels. These findings provide insights into the inflammation-related SASP maintenance by histone modification and the role of senescent CAFs in GC peritoneal dissemination.

Background Clinical significance of red blood cell distribution (RDW) as a predictive marker for the incidence of postoperative morbidity after esophagectomy for esophageal cancer has not been established. Methods This study included 634 consecutive patients who underwent three-incisional esophagectomy with lymphadenectomy for esophageal cancer between April 2005 and November 2020. Correlation between pretreatment RDW and patient background, cancer background, and short-term outcome after esophagectomy were retrospectively investigated. Results Eighty patients (12.6%) had a high pretreatment RDW (> 14.2), which correlated with malnutrition estimated by body mass index, hemoglobin, total lymphocyte count, albumin, and total cholesterol. High pretreatment RDW was an independent risk factor for postoperative severe morbidity of grade IIIb or higher based on the Clavien–Dindo classification (hazard ratio [HR] 3.90, 95% confidence interval [CI] 1.707–8.887; p = 0.0012) and reoperation (HR 4.39, 95% CI 1.552–12.390; p = 0.0053) after open esophagectomy (OE). However, RDW was not associated with postoperative morbidity incidence after minimally invasive esophagectomy (MIE). Conclusions Pretreatment RDW may be a surrogate marker for nutritional status and could be a predictive marker for postoperative severe morbidity, reoperation, and possibly pneumonia after OE. On the contrary, the lower invasiveness of MIE may have reduced the effect of pretreatment malnutrition on morbidity incidence, which could explain the insignificant relationship between RDW and poor short-term outcomes in MIE. Supplementary Information The online version contains supplementary material available at 10.1245/s10434-021-10719-2.

OBJECTIVE To elucidate the latest epidemiology and risk factors for multiple primary cancers (MPCs), and the association between neoadjuvant chemotherapy (NAC) and postoperative metachronous cancer (PMC) in patients with esophageal squamous cell carcinoma (ESCC) who underwent esophagectomy. SUMMARY OF BACKGROUND DATA Background data to derive appropriate screening strategies are insufficient. METHODS This study consisted of three retrospective investigations. A total of 766 consecutive patients with ESCC who underwent esophagectomy between April 2005 and December 2019 were eligible for epidemiological analysis. Of these, 688 patients without missing data were analyzed for the risk of MPCs. In total, 364 patients who underwent NAC (115) and no preoperative treatments (249) were investigated for the association between NAC and PMC. RESULTS Of 766 patients, 288 (38%) patients experienced 357 MPCs in their life. PMCs identified after the completion of 5-year postoperative follow-up were significantly more advanced (P = 0.019). Male sex [hazard ratio (HR) = 3.04, P = 0.038], older age (HR = 2.39, P < 0.001), and diabetes mellitus (HR = 1.76, P = 0.034) were risk factors for preoperative metachronous cancers. Heavy smoking (HR = 1.70, P = 0.014) and drinking (HR = 1.61, P = 0.029) were risk factors for synchronous cancers. NAC significantly reduced PMC incidence (P = 0.043). NAC showed a trend to contribute to improved survival via reduced deaths from PMCs, although this did not reach significance (P = 0.082). CONCLUSIONS ESCC is associated with a high risk of MPCs. Continuing follow-up for PMCs after the completion of 5-year postoperative follow-up is important. NAC may reduce PMCs, representing a novel mechanism for improving survival in patients with locally advanced ESCC.

Introduction The present study assessed the utility of a dry box time trial during laparoscopic surgical training to improve laparoscopic surgical skills and surgical outcomes. Methods In a monthly time trial, surgeon trainees twice completed a set task that involved grasping a suture, aligning a needle with a needle holder, passing the suture, making three knots, and cutting the two tails of the suture. The mean suturing time was then analyzed. To assess the utility of this time trial, we analyzed the short-term outcomes of patients with stage I to III colon cancer who had undergone laparoscopic colectomy before and after the introduction of the time trial. Results The monthly time trial was introduced in October 2018, and 52 surgeon trainees participated in the trials examined in this study. Within 6 months of the program's introduction, the mean suturing time had significantly declined to less than 70% of the time trial, while the standard deviations had declined to less than 30%. In comparisons of the short-term outcomes of laparoscopic colon cancer surgery before (n = 49) and after (n = 46) the introduction of the time trial, the operative time tended to decline (P = .074) after the introduction of the time trial, and blood loss was significantly reduced (P = .018). The rate of postoperative complications was similar before and after the introduction. Conclusion Regular time trials of laparoscopic surgical suture training using a dry box can be useful for improving laparoscopic surgical skills and surgical outcomes. Moreover, time trials can keep trainees motivated.

Background IgG4-related disease (IgG4-RD) is an immune-mediated disorder in which abundant IgG4-positive plasma cells infiltrate affected organs. There have been reported four cases of probable IgG4-RD presenting as a submucosal tumor of the stomach. We herein report the first case of definite IgG4-RD presenting as a submucosal tumor of the stomach resected with laparoscopic endoscopic cooperative surgery (LECS). Case presentation A 70-year-old woman with a 6-year history of autoimmune pancreatitis was referred to our department because a 15-mm submucosal tumor in the greater curvature of the lower part of the stomach had been identified via upper gastrointestinal endoscopy. Endoscopic ultrasonography showed a 10-mm low-echoic lesion derived from the submucosal layer of the stomach. A fine-needle aspiration biopsy was attempted, but the tumor was too hard for sampling. F-fluorodeoxyglucose (FDG) positron emission tomography showed an FDG uptake, suggesting a possibility of malignant disease. As the diagnosis could not be confirmed, LECS for both the diagnosis and curative treatment was performed. A histopathological examination showed a tumor with IgG4-positive lymphoplasmacytic infiltration and fibrosis. The ratio of IgG4+/IgG+ lymphoplasmacytic cells was > 80%. A laboratory examination showed elevation of the serum IgG4 levels preoperatively. Thus, the final diagnosis was IgG4-RD of the stomach. No recurrence was observed within 1 year after surgery. Conclusions We encountered a case of definite IgG4-RD presenting as a gastric SMT in which a correct diagnosis was achieved by a minimally invasive LECS technique. IgG4-RD may present as a gastric lesion and should be taken into consideration as a differential diagnosis.

Liver fibrosis influences liver regeneration and surgical outcomes, and several noninvasive models based on laboratory data have been developed to predict liver fibrosis. This study was performed to determine whether the Fibrosis-4 (FIB-4) index, a noninvasive fibrosis marker, can predict the prognosis in patients with colorectal liver metastases (CRLM) undergoing hepatectomy. This retrospective study involved 193 consecutive patients with CRLM who underwent hepatectomy. The FIB-4 index was calculated by laboratory data and age before hepatectomy and before preoperative chemotherapy. The FIB-4 cut-off was determined using survival classification and regression tree analysis. Patients were divided into two groups (high and low FIB-4 index), and post-hepatectomy overall survival (OS) and recurrence-free survival (RFS) were investigated. In total, 193 patients were evaluated. Chemotherapy before hepatectomy was performed in 105 (54.4%) patients. A high FIB-4 index (> 2.736) was found in 39 (20.2%) patients. OS was significantly shorter in patients with a high FIB-4 index than those with a low FIB-4 index in the univariate (45.9 vs. 74.4 months, log-rank p = 0.007) and multivariate analysis (hazard ratio 2.28, 95% confidence interval 1.39–3.74; p = 0.001). Among patients who received chemotherapy before hepatectomy, those with a high FIB-4 index had significantly shorter RFS (6.9 vs. 45.3 months, log-rank p = 0.047) and OS (23.9 vs. 55.0 months, log-rank p = 0.003) than those with a low FIB-4 index. This association was also confirmed by multivariate analysis (hazard ratio 4.28, 95% confidence interval 1.46–12.6; p = 0.008). Both the preoperative and prechemotherapy FIB-4 index can predict long-term outcomes after hepatectomy in patients with CRLM.

Advanced esophageal cancer often results in esophageal stenosis or tracheoesophageal fistula. Esophageal bypass surgery and esophageal stent insertion are palliative treatments for esophageal cancer. With improvements in metallic stents and the stent insertion technique, esophageal stent insertion appears to be performed more frequently than bypass surgery, worldwide. The aim of this study was to evaluate the outcomes of bypass surgery and stent insertion in our hospital and reevaluate which patients would benefit from bypass surgery. A total of 70 esophageal cancer patients who could not tolerate oral feeding due to esophageal stenosis or tracheoesophageal fistula underwent palliative treatment [esophageal bypass surgery (N = 34) and esophageal stent insertion (N = 36)] at Kumamoto University. We retrospectively investigated the clinicopathological factors, postoperative outcomes, and complications. Both treatments could significantly improve the amount of food intake and the dietary form (P

Background To date, only a few cases of multiple GISTs with different clones in different organs have been published. However, a case of multiple GISTs with different clones occurring in a single organ has never been reported. Case presentation A 41-year-old patient underwent laparoscopic partial gastrectomy for gastric gastrointestinal stromal tumor (GIST) in 2012. The pathological findings showed high-risk characteristics for recurrence, so he received adjuvant therapy with imatinib for 3 years. In 2018, 3 years after completing the adjuvant therapy, tumor lesions at residual gastric cardia were incidentally identified by follow-up computed tomography (CT). The pathological findings of the tumor biopsy revealed gastric GIST. He underwent secondary laparoscopic partial gastrectomy and was diagnosed with high-risk GIST. Adjuvant therapy with imatinib was restarted immediately. The two gastric GISTs had the same exon 11 mutations in the c-kit gene, but they had different missense mutations. This molecular heterogeneity suggested that they were derived from different origins. Conclusion We reported a multiple heterochronic GIST in the stomach detected 6 years after resection. There may be a possibility that another heterochronic GIST will occur in the remnant stomach in the future, so close follow-up will be needed.

Background: Regorafenib and TAS-102 are standard salvage-line treatment options for patients with chemorefractory metastatic colorectal cancer (mCRC). We aimed to evaluate the prognostic significance of skeletal muscle mass in mCRC patients receiving these salvage-line therapies. Methods: We conducted a retrospective analysis of 52 patients with mCRC who received regorafenib or TAS-102 as salvage-line treatment. Skeletal muscle cross-sectional area was measured by pretreatment CT to obtain the skeletal muscle index (SMI, cm2/m2). We divided patients into 2 groups (low-SM/high-SMI) based on the median value of SMI. Result: The median SMI was 51.8 cm2/m2 in males and 39.2 cm2/m2 in females. In Kaplan-Meier analysis, patients in the low-SMI group showed significantly shorter overall survival (3.7 vs. 7.3 months, log-rank p = 0.002) and progression-free survival (1.9 vs. 2.8 months, log-rank test p = 0.009) than those in the high-SMI group. Subsequent multivariate analysis revealed that the SMI was an independent prognostic factor (hazard ratio = 2.381, 95% CI 1.189–4.944, p = 0.014). Patients in the low-SMI group had significantly more grade 3 or 4 adverse events than those in the high-SMI group (46 vs.12%, p = 0.013). Conclusion: Low skeletal muscle mass is a negative factor for survival outcomes in mCRC patients treated with salvage-line chemotherapy.

Radiofrequency ablation (RFA) can be a minimally invasive therapeutic option in patients with lung metastasis from colorectal caner. We aimed to elucidate the safety and survival benefit of computed tomography (CT)-guided percutaneous RFA for lung metastasis from colorectal cancer. A total 188 lesions were ablated in 43 patients from 2005 to 2017. The clinicopathological and survival data of patients were collected retrospectively. The short- and long-term outcomes and prognostic factors were analyzed. Eight patients (18.6%) had viable extrapulmonary metastasis at RFA treatment. The median number of treated lung tumors was 2, and the median maximum diameter was 12 mm. Complications, such as pneumothorax, pleural effusion and subcutaneous emphysema, occurred in 24 (55.8%) patients. Although chest tube drainage for pneumothorax was needed in 6 patients (14.0%), there were no mortalities. Repeated RFA for lung recurrence after primary RFA was performed in 14 patients (32.6%). In a median follow-up of 24.3 months, the median progression-free and overall survival (OS) were 6.8 months and 52.7 months, respectively. The presence of extrapulmonary metastasis and a maximum tumors size of > 15 mm were independently associated with a worse disease-free survival and OS. The OS of patients who underwent repeated RFA was significantly better than that of patients who underwent RFA only once. CT-guided percutaneous RFA for lung metastasis from colorectal cancer is a safe and effective procedure in patients not eligible for surgery, particularly for lesions smaller than 1.5 cm without extrapulmonary metastasis.

One-year adjuvant S-1 monotherapy following D2 gastrectomy has been the Japanese treatment standard for pathological stage II or III gastric cancer since the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC) was concluded in 2007. Trial patients were selected according to the 13th edition of the Japanese classification (JC-13). The JC-13 and the TNM classification underwent major revisions in 2010 (JC-14/TNM-7). However, neither the recent therapeutic results for patients with stage II/III disease defined by the current system nor comparisons with the ACTS-GC-results have been reported.The 390 study patients had pathological stage II/III gastric cancer defined by the JC-14/TNM-7 and treated with S-1 following D2 gastrectomy between 2008 and 2012. The completion rate of 1-year S-1, first relapse site, and stage-specific survival according to the JC-14/TNM-7, JC-13, and TNM-6 were examined and the results compared with those of the ACTS-GC.The completion rate for 1-year S-1 (69.5%) was slightly higher than in the ACTS-GC. The recurrence pattern was almost identical. The 5-year overall survival rates of pathological IIA, IIB, IIIA, IIIB, and IIIC in the JC-14/TNM-7 were 96.0, 85.5, 81.8, 72.0, and 51.1%, respectively. Their 5-year overall and relapse-free survival rates by the JC-13 and TNM-6 systems were favorable as compared to those of ACTS-GC patients for all substages.Survival outcome shown in this study of patients treated with 1-year adjuvant S-1 after D2 gastrectomy at a high-volume cancer hospital will provide a reference for future adjuvant trials targeting JC-14/TNM-7 stage II/III disease.

Programmed death ligand 1 (PD-L1) expression as a predictive biomarker for programmed cell death 1 (PD-1) inhibitor efficacy in gastric cancer (GC) remains controversial. We hypothesised that the conflicting results may be due to the inaccurate assessment of PD-L1 expression using biopsy samples. A total of 191 patients with GC who received radical resection were enrolled. PD-L1 expressions in biopsy and paired resected samples by immunohistochemistry staining were compared according to the number of biopsies. The numbers of PD-L1-positive patients determined by biopsy and resected samples were 89 (46.6%) and 135 (70.1%), respectively. The accordance rate was 64.4% (κ = 0.31). Single biopsy showed a lower accordance rate compared with multiple biopsies. Our study revealed that single biopsy cannot fully reflect PD-L1 expression in the whole tumour in GC. Multiple biopsies are recommended for accurate diagnosis of PD-L1 expression in GC.

The occurrence of postoperative complications may have a significant negative impact on the prognosis of patients with gastrointestinal cancers. The inflammatory response releases systemic cytokines, which may induce residual cancer cell growth. Recently, neoadjuvant chemotherapy (NAC) was found to improve the prognosis of advanced gastric cancer (GC). We hypothesize that when postoperative complications occur after gastrectomy, NAC treatment of micrometastases can prevent residual cancer cell growth. This study included 101 patients who underwent curative resection after NAC for GC from 2005 to 2015. Clinical data, including intraoperative parameters, were collected retrospectively. Overall survival (OS) and relapse-free survival (RFS) were compared between the patients with complications and those without complications. Of the 101 patients, 35 (34.7%) had grade 2 or higher complications. Among those with complications, the 3- and 5-year OS rates were 63.5 and 58.2% and the 3- and 5-year RFS rates 41.7 and 41.7%, respectively. Among those without complications, the 3- and 5-year OS rates were 65.9 and 56.3% and the 3- and 5-year RFS rates 51.1 and 43.9%, respectively. There was no significant difference in prognosis between the patients with complications and those without complications. Our study is the first to demonstrate the potential of NAC to abolish the poor prognosis induced by postoperative complications after curative resection for GC.

Laparoscopic and endoscopic cooperative surgery (LECS) enables local full-thickness resection using a combination of endoscopic submucosal dissection (ESD) and laparoscopic surgery.1-3 Indications of LECS for colorectal tumors were as follows: 1) intramucosal cancer and adenoma accompanied by wide and severe fibrosis; 2) intramucosal cancer and adenoma involving the diverticulum or appendix; and 3) submucosal tumors.1 Needlescopic surgery is a minimally invasive technique using thin forceps (≤3 mm) while maintaining the surgical quality compared with conventional laparoscopic surgery.4-6 We developed a needlescopic and endoscopic cooperative surgery (NECS) technique combining LECS and needlescopic surgery as a new minimally invasive technique. We herein present a video http://links.lww.com/DCR/B436 of NECS being performed for a benign adenoma at the ascending colon. The tumor was endoscopically unresectable because it was involved with a diverticulum next to the tumor. In brief, the procedure was conducted as follows: 1) A Laparoscopic procedure was performed with a total of 4 ports, including two 3-mm ports. The ascending colon was mobilized from the retroperitoneum, preserving the right ureter and gonadal vessels. After mobilization of the ascending colon, we placed laparoscopic anchoring sutures to lift the colonic wall around the tumor. 2) Endoscopically, a circumferential mucosal incision and seromuscular layer cutting around the tumor and diverticulum were conducted using the ESD technique. 3) Laparoscopically again, the remaining part of the colonic wall was cut, and the tumor was removed. The colonic wall was then closed with a laparoscopic linear stapler while lifting the sutures that had been temporarily placed at a site near the incision line. 4) Endoscopy confirmed the closing line and good passage through the ascending colon. In this NECS technique, postoperative wounds are small and barely noticed. NECS is a viable alternative surgical approach for endoscopically unresectable colonic tumors.

Identification of a key person for supporting patients with activities of daily living after esophagectomy can contribute to patients’ nutrition, rehabilitation, mental status, and determination of treatments for cancer. It may also affect the patients’ prognostic outcomes. This retrospective study included 504 patients who underwent three-incisional esophagectomy for esophageal cancer between June 2005 and June 2018 at the Kumamoto University Hospital. The association between the type of key person identified and overall survival (OS) was investigated. The impact of the key person on postoperative nutrition and survival after recurrence was also examined. Clinical backgrounds in patients with and without wife as their key person were equivalent. OS among male patients who identified their wife as their key person was significantly better than that in those without their wife as key person (P = 0.0035). Cox regression analysis showed that absence of a wife was an independent risk factor for worse survival outcomes (hazard ratio, 0.62; 95% confidence interval, 0.393–0.987; P = 0.044) along with age, clinical stage, severe postoperative morbidity, and pathological curability. Presence of a wife did not affect postoperative nutritional status. Incidence of death due to other causes and OS after recurrence were better in male patients with a wife than in those without; however, this difference was not significant. Among males with esophageal cancer, their wives may be a significant contributor to extension of survival after surgery, via various support mechanisms.

The aim of this study was to elucidate the risk factors for and prognostic value of lateral pelvic lymph node (LPLN) metastasis in advanced rectal cancer patients, including those with stage IV disease. The treatment outcomes of 78 patients with advanced rectal cancer, the lower margin of which was located at or below the peritoneal reflection, who underwent curative-intent surgery with bilateral LPLN dissection from 2005 to 2018 were retrospectively analyzed. In total, 78 rectal cancer patients, including 13 patients with stage IV tumors, 9 patients (11.5%) had LPLN metastasis. A multivariate analysis to identify preoperative clinical factors associated with LPLN metastasis showed that tumor location (below the peritoneal reflection: Rb), LPLN metastasis on preoperative imaging and distant metastasis were independent predictors of LPLN metastasis. In addition, metastasis at the regional lymph nodes in the mesorectum was significantly associated with LPLN metastasis. Both the disease-free survival (DFS) and cancer-specific survival (CSS) of patients with LPLN metastasis were significantly worse in comparison to patients without LPLN metastasis, and the CSS of stage IV patients with LPLN metastasis was significantly worse in comparison to stage IV patients without LPLN metastasis. Tumor location (Rb), LPLN metastasis on preoperative imaging and distant metastasis were risk factors for LPLN metastasis. The prognosis of rectal cancer patients with LPLN metastasis is poor. There may not be the indication of LPLN dissection in stage IV lower rectal cancer except cases having complaints due to LPLN metastasis.

Respiratory morbidity is common after esophagectomy and can be a major cause of surgery-related mortality. Thus, it is important to identify novel predictors that can preoperatively estimate the incidence of postoperative respiratory morbidity. Asymptomatic sputum in the respiratory tract is sometimes observed on preoperative computed tomography (CT). This study aimed to determine the clinical importance of sputum in the respiratory tract as a predictor of postoperative morbidity after esophagectomy for esophageal cancer. The study included 609 consecutive patients who underwent three-incisional esophagectomy for esophageal cancer between April 2005 and November 2018. Among the patients, 76 (12.5%) had sputum in the respiratory tract on preoperative CT. This finding was significantly associated with older age, more extreme smoking habit, worse performance status, lower forced expiratory volume 1%, and more frequent pulmonary comorbidities. Additionally, the incidence of postoperative pneumonia was higher in these patients than in those without sputum (16 vs 8%, p = 0.028). Sputum in the main bronchus was associated with higher frequencies of morbidity of Clavien–Dindo classification (CDc) ≥ II (p = 0.019), severe morbidity of CDc ≥ IIIb (p = 0.058), pneumonia (p = 0.10), and pulmonary morbidity (p = 0.19) compared with the finding of sputum in the trachea alone. On multivariate analysis, sputum in the respiratory tract was an independent risk factor (hazard ratio, 2.07; 95% confidence interval, 1.019–4.207; p = 0.044) for postoperative pneumonia. Sputum in the respiratory tract is a novel predictor of postesophagectomy pneumonia. Patients with sputum in the more distal respiratory tract might have high risk of postoperative morbidities.

Few reliable prognostic markers have been established despite elucidation of the molecular mechanisms of gastrointestinal stromal tumor (GIST) development. We evaluated F-box and WD repeat domain-containing 7 (FBXW7), a cell-cycle-regulating and tumor suppressor, in GISTs. We aimed to determine the clinical relevance of FBXW7 in GISTs and characterize the molecular mechanism of FBXW7 in a GIST cell line. We measured FBXW7 expression in 182 GIST cases, correlated the expression levels with clinicopathological features, and characterized the molecular mechanism underlying suppressed FBXW7 expression in GIST cells in vitro. Of the 182 GISTs, 98 (53.8%) and 84 (46.2%) were categorized in the high and low FBXW7 expression groups, respectively. Compared with the high FBXW7 expression group, the low expression group showed a significantly poorer prognosis in terms of recurrence-free (P = 0.01) and overall (P = 0.03) survival. FBXW7 expression was a significant independent factor affecting the 10-year recurrence-free survival rate (P = 0.04). In vitro, FBXW7-specific siRNAs enhanced c-myc and Notch 1 protein expression and upregulated cell proliferation, invasion, and migration. FBXW7 is a potential predictive marker of recurrence after curative resection of GISTs. FBXW7 expression may help identify patients benefitting from adjuvant therapy more precisely compared with a conventional risk stratification model.

Double tract reconstruction (DT) after proximal gastrectomy (PG) is considered beneficial for postoperative nutrition status by preserving the physiological passage of food. We conducted this study to assess postoperative nutrition status based on food passage after this operation. The subjects of this retrospective study were 63 patients who underwent PG with DT. The patients were divided into two groups according to whether they had postoperative malnutrition (PM) 1 year postoperatively (PM group) or not (non-PM group). PM was defined by both weight loss > 10% and a low body mass index of

To elucidate the clinical value of mean corpuscular volume (MCV) for prognostic prediction in patients with esophageal cancer who underwent radical esophagectomy.High MCV is suggested to be relevant to the incidence and prognosis of several malignancies. However, few studies investigating the correlation between MCV and survival outcome of esophageal cancer have been conducted.This study included 570 patients with esophageal cancer who underwent radical esophagectomy between April, 2005 and December, 2017. Patients were divided into 2 groups according to the standard value of pretreatment MCV: normal (83-99 fL) and high (99 fL) groups. Clinical backgrounds, short-term outcomes, and prognostic outcomes postesophagectomy were retrospectively compared between the groups.Of all patients, 410 (71.9%) had normal MCV, and 160 (28.1%) had high MCV. High MCV was significantly associated with lower body mass index, higher frequency of habitual alcohol and tobacco use, and higher incidence of multiple primary malignancies other than esophageal cancer. High MCV also correlated with higher incidence of postoperative morbidity of the Clavien-Dindo classification ≥II and pulmonary morbidity. Overall survival was significantly worse in patients with high MCV. Multivariate analysis suggested that high MCV was an independent risk factor for worse survival outcome (hazard ratio 1.54, 95% confidence interval 1.098-2.151, P = 0.012).Patients with high MCV have various disadvantages in clinical background that can adversely affect both short-term and long-term outcomes after esophagectomy. MCV can become a predictive marker to estimate survival outcome after esophagectomy for esophageal cancer.