Significance of Comprehensive Analysis of Preoperative Sarcopenia Based on Muscle Mass, Muscle Strength, and Physical Function for the Prognosis of Patients with Esophageal Cancer.

BACKGROUND: The assessment of muscle mass loss, muscle strength, and physical function has been recommended in diagnosing sarcopenia. However, only muscle mass has been assessed in previous studies. Therefore, this study investigated the effect of comprehensively diagnosed preoperative sarcopenia on the prognosis of patients with esophageal cancer. METHODS: The study analyzed 115 patients with esophageal cancer (age ≥ 65 years) who underwent curative esophagectomy. Preoperative sarcopenia was analyzed using the skeletal mass index (SMI), handgrip strength, and gait speed based on the Asian Working Group for Sarcopenia 2019 criteria. Clinicopathologic factors, incidence of postoperative complications, and overall survival (OS) were compared between the sarcopenia and non-sarcopenia groups. The significance of the three individual parameters also was evaluated. RESULTS: The evaluation identified 47 (40.9%) patients with low SMI, 31 (27.0%) patients with low handgrip strength, and 6 (5.2%) patients with slow gait speed. Sarcopenia was diagnosed in 23 patients (20%) and associated with older age and advanced pT stage. The incidence of postoperative complications did not differ significantly between the two groups. Among the three parameters, only slow gait speed was associated with Clavien-Dindo grade 2 or greater complications. The sarcopenia group showed significantly worse OS than the non-sarcopenia group. Those with low handgrip strength tended to have worse OS, and those with slow gait speed had significantly worse OS than their counterparts. CONCLUSIONS: Preoperative sarcopenia diagnosed using skeletal muscle mass, muscle strength, and physical function may have an impact on the survival of patients with esophageal cancer.

Postoperative venous thromboembolism after surgery for locally recurrent rectal cancer.

BACKGROUND: Local recurrence is common after curative resections of rectal cancer. Surgical resection is considered a primary curative treatment option for patients with locally recurrent rectal cancer (LRRC). LRRC often requires a combined resection of other organs, especially in the case of posterior recurrence, which requires a combined resection of the sacrum, making the surgery highly invasive. Venous thromboembolism (VTE) is one of the lethal complications in the postoperative period, particularly in the field of pelvic surgery. We found no reports regarding the risks of postoperative VTE in surgery for LRRC, a typical highly invasive procedure in the field of colorectal surgery. This study aims to evaluate the risk of postoperative VTE in surgery for LRRC patients. METHODS: From April 2010 to March 2022, a total of 166 patients underwent surgery for LRRC in the pelvic region at our institutions. Clinicopathological background and VTE incidence were compared retrospectively. RESULTS: Among the 166 patients included in the study, 55 patients (33.1%) needed sacral resection. Pharmacological prophylaxis for prevention of VTE was performed in 121 patients (73.3%), and the incidence of VTE was 9.09% (5/55 patients) among those who underwent surgery for LRRC with sacral resection, while it was 1.8% (2/111 patients) in those without sacral resection. In univariate analysis, the combination with sacral resection was identified as a risk factor for VTE in surgery for LRRC (p = 0.047). CONCLUSIONS: This study demonstrates that surgery for LRRC combined with sacral resection could be a significant risk factor for VTE.

Prognostic impact of lateral sentinel lymph node biopsy using indocyanine green on oncological outcomes for clinical stage II/III lower rectal cancer without suspected lateral lymph node metastasis.

PURPOSE: Sentinel lymph node biopsy (SLNB) can detect occult nodal metastasis. We have previously reported the safety and feasibility of indocyanine green (ICG)-guided SLNB for clinical stage II/III lower rectal cancer (RC). However, little is known about the influence of lateral pelvic SLNB using ICG on oncological outcomes. The present study aimed to evaluate the prognostic impact of lateral pelvic SLNB on oncological outcomes compared with prophylactic lateral lymph node dissection (LLND). METHODS: Participants comprised consecutive patients with clinical stage II/III lower RC who underwent lateral pelvic SLNB or prophylactic LLND (Non-SLNB) between January 2010 and December 2020. The primary outcome measure was the 5-year cumulative incidence of local recurrence (LR). Secondary endpoints included cancer-specific survival (CSS), overall survival (OS), recurrence-free survival (RFS), local recurrence-free survival (LRFS), and distant recurrence-free survival (DRFS). RESULTS: Among the 150 eligible patients included, 79 patients underwent lateral pelvic SLNB. Of those 79 patients, 4 patients who were SLNB-positive underwent LLND. LLND was omitted for the 75 patients who were SLNB-negative. Median follow-up was 61.0 months (range, 1.3-143.2 months). The overall recurrence rate was 30.7% (46 patients), with LR in 12.0% (18 patients). LR comprised lateral lymph node recurrence in 2.6% and central pelvic recurrence in 9.4%. No significant differences were seen between groups in terms of the frequency of LR or in CSS, OS, RFS, LRFS, or DRFS. CONCLUSION: Oncological outcomes were not different between the SLNB and Non-SLNB groups. ICG-guided SLNB appears promising as a method for determining indications for LLND.

The clinical significance of the lymph node ratio as a recurrence indicator in ampullary cancer after curative pancreaticoduodenectomy.

BACKGROUND: The clinical significance of the lymph node ratio (LNR), the number of metastatic lymph nodes per dissected lymph node, has not been sufficiently clarified in ampullary cancer. METHODS: Among patients diagnosed histopathologically with ampullary cancer between 1980 and 2018, the study included 106 who underwent pathological radical resection by pancreaticoduodenectomy. The relationships between the LNR and metastatic lymph node sites and prognosis were examined. RESULTS: Multivariate analysis revealed that sex and lymph node metastasis were independent prognostic factors. In the 46 patients (43%) with metastatic lymph nodes, the LNR in the recurrence group was significantly higher than that in the non-recurrence group (0.15 ± 0.11 vs. 0.089 ± 0.071, p = 0.025). The receiver operating characteristic curve demonstrated that the LNR cut-off value, 0.07 (area under the curve = 0.70, sensitivity 81%, specificity 56%), was a significant indicator for recurrence (22% vs. 61%, p = 0.016) and prognosis (5-year survival: 48% vs. 83%, p = 0.028). Among the metastatic lymph node sites in the 46 positive cases, lymph node metastases developed from the peripancreatic head region (80%, 37/46) to the superior mesenteric artery (33%, 15/46) and para-aortic (11%, 5/46) regions. CONCLUSION: Lymph node metastasis is an independent prognostic factor, and the LNR is a significant indicator for recurrence and prognosis in patients with ampullary cancer.

Cancer-specific tissue-resident memory T-cells express ZNF683 in colorectal cancer.

BACKGROUND: Tissue-resident memory T (Trm) cells are associated with cytotoxicity not only in viral infection and autoimmune disease pathologies but also in many cancers. Tumour-infiltrating CD103+ Trm cells predominantly comprise CD8 T cells that express cytotoxic activation and immune checkpoint molecules called exhausted markers. This study aimed to investigate the role of Trm in colorectal cancer (CRC) and characterise the cancer-specific Trm. METHODS: Immunochemical staining with anti-CD8 and anti-CD103 antibodies for resected CRC tissues was used to identify the tumour-infiltrating Trm cells. The Kaplan-Meier estimator was used to evaluate the prognostic significance. Cells immune to CRC were targeted for single-cell RNA-seq analysis to characterise cancer-specific Trm cells in CRC. RESULTS: The number of CD103+/CD8+ tumour-infiltrating lymphocytes (TILs) was a favourable prognostic and predictive factor of the overall survival and recurrence-free survival in patients with CRC. Single-cell RNA-seq analysis of 17,257 CRC-infiltrating immune cells revealed a more increased zinc finger protein 683 (ZNF683) expression in cancer Trm cells than in noncancer Trm cells and in high-infiltrating Trm cells than low-infiltrating Trm in cancer, with an upregulated T-cell receptor (TCR)- and interferon-γ (IFN-γ) signalling-related gene expression in ZNF683+ Trm cells. CONCLUSIONS: The number of CD103+/CD8+ TILs is a prognostic predictive factor in CRC. In addition, we identified the ZNF683 expression as one of the candidate markers of cancer-specific Trm cells. IFN-γ and TCR signalling and ZNF683 expression are involved in Trm cell activation in tumours and are promising targets for cancer immunity regulation.

Clinical Impact of Early Tumour Shrinkage in Metastatic or Unresectable Oesophageal Cancer Treated with Pembrolizumab plus Chemotherapy.

INTRODUCTION: Metastatic or unresectable locally advanced oesophageal cancer remains a disease with high mortality. More recently, pembrolizumab plus chemotherapy has been indicated as the first-line treatment for those patients, but the predictive factors for treatment efficacy remain controversial. This study investigated the clinical utility of early tumour shrinkage (ETS) and depth of response (DpR) in metastatic or unresectable oesophageal cancer treated with pembrolizumab plus CF therapy. METHODS: ETS and DpR, defined as the percent decreases at the second evaluation and the percentage of the maximal tumour shrinkage during treatment, were measured in 53 eligible patients. The ETS and DpR cut-off values were 20% and 30%, respectively, based on survival outcomes. RESULTS: Twenty-seven patients (51%) were treatment-naïve, while 26 (49%) had received any treatment before initiating pembrolizumab plus CF therapy. The median progression-free survival (PFS) and overall survival (OS) for ETS ≥20% and <20% were 12.7 and 5.5 months and 14.4 and 8.2 months, and 12.7 and 4.9 months and 14.4 and 8.0 months for DpR ≥30% and <30%, respectively. ETS <20% showed early tumour growth, whereas ETS ≥20% had a good response rate with sufficient longer response duration. In addition, an ETS cut-off of 20% predicted the best overall response and was not associated with prior treatment. In multivariable analysis, ETS ≥20% and DpR ≥30% were independent factors of longer PFS. CONCLUSION: Our findings suggest that an ETS is a promising on-treatment marker for early prediction of further sensitivity to pembrolizumab plus CF therapy.

Clinical Significance of Preoperative and Postoperative Serum CEA and Carbohydrate Antigen 19-9 Levels in Patients Undergoing Curative Resection of Locally Recurrent Rectal Cancer.

BACKGROUND: Local recurrence is common after curative resection for rectal cancer. Although one expects radical resection of locally recurrent rectal cancer to be curative, the postoperative re-recurrence rate is relatively high. Therefore, identifying risk factors for recurrence may improve the prognosis of locally recurrent rectal cancer with early therapeutic intervention. OBJECTIVE: This study aimed to evaluate the relationship between perioperative serum CEA/carbohydrate antigen 19-9 levels and prognosis in locally recurrent rectal cancer to validate their usefulness for postoperative surveillance in locally recurrent rectal cancer. DESIGN: This was a single-center retrospective cohort study. SETTING: The study is based on data obtained from procedures at the Osaka University Hospital. PATIENTS: Ninety patients underwent radical resection for locally recurrent rectal cancer between January 2000 and January 2015. MAIN OUTCOME MEASURES: We evaluated the correlation between perioperative serum CEA/carbohydrate antigen 19-9 levels and prognosis after complete resection of locally recurrent rectal cancer and the serum CEA and carbohydrate antigen 19-9 levels at the diagnosis of postoperative re-recurrence. RESULTS: The median preoperative serum CEA level was 4 ng/mL and carbohydrate antigen 19-9 level was 12 U/mL. Of the 90 patients, 43.3% had serum CEA ≥5 ng/mL, and 15.6% had serum carbohydrate antigen 19-9 ≥37 U/mL. Preoperatively, this serum carbohydrate antigen 19-9 level strongly correlated with poorer prognoses regarding cancer-specific survival. Postoperatively, serum CEA ≥5 ng/mL significantly correlated with a worse prognosis. At the time of diagnosis of re-recurrence after resection of locally recurrent rectal cancer, 53.2% of patients had serum CEA ≥5 ng/mL, and 23.4% of patients had serum carbohydrate antigen 19-9 ≥37 U/mL. LIMITATIONS: The study was limited by its single-center retrospective design, an insufficient sample size, and a relatively long study period. CONCLUSIONS: High serum levels of carbohydrate antigen 19-9 preoperatively and CEA postoperatively are associated with poor prognosis after locally recurrent rectal cancer. Furthermore, we found a high rate of serum CEA elevation in the diagnosis of postoperative re-recurrence. See Video Abstract at http://links.lww.com/DCR/C106 . IMPORTANCIA CLNICA DE LOS NIVELES SRICOS PREOPERATORIOS Y POSOPERATORIOS DE CEA Y CA EN PACIENTES SOMETIDOS A RESECCIN CURATIVA DE CNCER DE RECTO LOCALMENTE RECURRENTE: ANTECEDENTES:La recurrencia local es común después de la resección curativa del cáncer de recto. Aunque se espera que la resección radical del cáncer rectal localmente recurrente sea curativa, la tasa de recurrencia posoperatoria es relativamente alta. Por lo tanto, la identificación de los factores de riesgo de recurrencia puede mejorar el pronóstico del cáncer de recto localmente recurrente con una intervención terapéutica temprana.OBJETIVO:Evaluamos la relación entre los niveles séricos perioperatorios de CEA/CA19-9 y el pronóstico en el cáncer de recto localmente recurrente para validar su utilidad para la vigilancia posoperatoria en el cáncer de recto localmente recurrente.DISEÑO:Este fue un estudio de cohorte retrospectivo de un solo centro.AJUSTE:El estudio se basa en datos obtenidos de procedimientos en el Hospital Universitario de Osaka.PACIENTES:Noventa pacientes fueron sometidos a resección radical por cáncer de recto localmente recurrente entre Enero de 2000 y Enero de 2015.PRINCIPALES MEDIDAS DE RESULTADOS:Evaluamos la correlación entre los niveles séricos perioperatorios de CEA/CA19-9 y el pronóstico después de la resección completa del cáncer de recto localmente recurrente y los niveles séricos de CEA y CA19-9 en el diagnóstico de recurrencia posoperatoria.RESULTADOS:La mediana de los niveles séricos preoperatorios de CEA y CA19-9 fueron de 4 ng/mL y 12 U/mL, respectivamente. De los 90 pacientes, el 43,3 % tenía CEA sérico ≥5 ng/mL y el 15,6 % tenía CA19-9 sérico ≥37 U/mL. Antes de la operación, este nivel sérico de CA19-9 se correlacionó fuertemente con peores pronósticos con respecto a la supervivencia específica del cáncer. Después de la operación, el CEA sérico ≥5 ng/mL se correlacionó significativamente con un peor pronóstico. En el momento del diagnóstico de recurrencia después de la resección del cáncer de recto localmente recurrente, el 53,2 % de los pacientes tenían CEA sérico ≥5 ng/mL y el 23,4 % de los pacientes tenían CA19-9 sérico ≥37 U/mL.LIMITACIONES:El estudio estuvo limitado por su diseño retrospectivo de un solo centro, un tamaño de muestra insuficiente y un período de estudio relativamente largo.CONCLUSIONES:Los niveles séricos altos de CA19-9 antes de la operación y de CEA después de la operación están asociados con un mal pronóstico después del cáncer de recto localmente recurrente. Además, encontramos una alta tasa de elevación del CEA sérico en el diagnóstico de recurrencia posoperatoria. Consulte el Video Resumen en http://links.lww.com/DCR/C106 . (Traducción-Dr. Yesenia Rojas-Khalil ).

Postoperative pain management after concomitant sacrectomy for locally recurrent rectal cancer.

PURPOSE: To assess pain management in patients post-sacrectomy, focusing on opioid use, and to identify the factors associated with postoperative pain. METHODS: Patients who underwent resection of locally recurrent rectal cancer (LRRC) with concomitant sacrectomy at one of two hospitals between 2007 and 2020 were reviewed retrospectively. We examined the use of opioids preoperatively and postoperatively. Patients were classified into high and low sacrectomy groups based on the sacral bone resection level passing through the S3 vertebra. RESULTS: Sixty-four patients were enrolled. Opioid use was significantly higher in the high sacrectomy group than in the low sacrectomy group at all times assessed: on postoperative days 7, 14, 30, 90, 180, and 365. Opioid use 3 months after locally recurrent rectal cancer surgery was significantly higher in patients with local re-recurrence of the tumor than in those without re-recurrence (p < 0.05), and the median morphine-equivalent opioid use 3 months postoperatively was significantly higher in the high sacrectomy group (30 vs. 0 mg/day; p < 0.05). CONCLUSIONS: Opioid use after concomitant sacrectomy for LRRC was higher in the high sacrectomy group. Prolonged postoperative pain or increasing pain was associated with local recurrence.

Impact of the preoperative prognostic nutritional index as a predictor for postoperative complications after resection of locally recurrent rectal cancer.

BACKGROUND: Local recurrence is common after curative resections for rectal cancer. Surgical intervention is among the best treatment choices. However, achieving a negative resection margin often requires extensive pelvic organ resections; thus, the postoperative complication rate is quite high. Recent studies have reported that the inflammatory index could predict postoperative complications. This study aimed to validate the correlation between clinical factors, including inflammatory markers, and severe complications after surgery for local recurrent rectal cancer. METHODS: This retrospective study included 99 patients that underwent radical resections for local recurrences of rectal cancer. Postoperative complications were graded according to the Clavien-Dindo classification. Grades ≥3 were defined as severe complications. Risk factors for severe complications were identified with univariate and multivariate logistic regression models and assessed with receiver-operating characteristic curves. RESULTS: Severe postoperative complications occurred in 38 patients (38.4%). Analyses of correlations between inflammatory markers and severe postoperative complications revealed that the strongest correlation was found between the prognostic nutrition index and severe postoperative complications. The receiver-operating characteristic analysis showed that the optimal prognostic nutrition index cut-off value was 42.2 (sensitivity: 0.790, specificity: 0.508). In univariate and multivariate analyses, a prognostic nutrition index ≤44.2 (Odds ratio: 3.007, 95%CI:1.171-8.255, p = 0.02) and a blood loss ≥2850 mL (Odds ratio: 2.545, 95%CI: 1.044-6.367, p = 0.04) were associated with a significantly higher incidence of severe postoperative complications. CONCLUSIONS: We found that a low preoperative prognostic nutrition index and excessive intraoperative blood loss were risk factors for severe complications after surgery for local recurrent rectal cancer.

Tolerability and safety of adjuvant chemoradiotherapy with S-1 after limited surgery for T1 or T2 lower rectal cancer.

BACKGROUND: Chemo-radiotherapy (CRT) after local excision for pT1 with high-risk features or pT2 rectal cancer is recommended as an optional treatment to achieve both curability and maintenance of quality of life. The aim of this study was to evaluate the short-term safety of combining limited surgery with adjuvant CRT for T1 or T2 lower rectal cancer. METHODS: This was a multicenter, single-arm, prospective phase II trial. Patients diagnosed with lower rectal or anal canal cancer (clinical T1 or T2 with a maximum diameter of 30 mm and N0 and M0) underwent local excision or endoscopic resection. Patients received CRT with S-1 (tegafur/gimeracil/oteracil) after confirmation of well- or moderately differentiated adenocarcinoma, and negative margins, and/or depth of submucosal invasion ≥ 1000 µm or muscularis propria, and/or positive lymphovascular invasion, and/or tumor budding grade of 2/3. The primary endpoint was relapse-free survival. Secondary endpoints included overall and local relapse-free survival, safety, anal sphincter preservation rate, and anal function. RESULTS: Pathological diagnosis was T1 in 36 patients and T2 in 16 patients. Serious complications after surgery were not reported. The CRT completion rate per protocol was 86.5% (45/52). Thirty-two patients developed 54 events of CRT-related adverse events, including only one patient with a grade 3 event (stomatitis). The most common CRT-related adverse event was diarrhea (n = 14). No patients showed deterioration of anal function at 3 years postoperatively. CONCLUSION: CRT with S-1 after limited surgery for T1 or T2 lower rectal cancer resulted in a low incidence of toxicities and maintenance of anal function.

Epithelial Cell Transformation and Senescence as Indicators of Genome Aging: Current Advances and Unanswered Questions.

The recent advances in deciphering the human genome allow us to understand and evaluate the mechanisms of human genome age-associated transformations, which are largely unclear. Genome sequencing techniques assure comprehensive mapping of human genetics; however, understanding of gene functional interactions, specifically of time/age-dependent modifications, remain challenging. The age of the genome is defined by the sum of individual (inherited) and acquired genomic traits, based on internal and external factors that impact ontogenesis from the moment of egg fertilization and embryonic development. The biological part of genomic age opens a new perspective for intervention. The discovery of single cell-based mechanisms for genetic change indicates the possibility of influencing aging and associated disease burden, as well as metabolism. Cell populations with transformed genetic background were shown to serve as the origin of common diseases during extended life expectancy (superaging). Consequently, age-related cell transformation leads to cancer and cell degeneration (senescence). This article aims to describe current advances in the genomic mechanisms of senescence and its role in the spatiotemporal spread of epithelial clones and cell evolution.

[Simultaneous Laparoscopic Sigmoid Colectomy and Malignant Lymphoma Biopsy-A Case Report].

The patient, a woman in her 70s, was diagnosed with occlusive ileus caused by sigmoid colon cancer.She underwent transanal stent placement to release the occlusion.Subsequent detailed testing revealed a 70×60mm mass on the dorsal side of the pancreas and PET-CT indicated an SUVmax 18.2 FDG uptake. EUS-FNA was performed twice.However, the mass was unable to be definitively diagnosed.The patient was then referred to our hospital.She underwent laparoscopic sigmoid colectomy and laparoscopic biopsy of the mass for sigmoid colon cancer.The patient progressed well postoperatively and was discharged home on postoperative day 9.The postoperative diagnosis was colon cancer(S, Type 2, 58×50 mm, tub2, pT4a [SE], pN1, Stage Ⅲa)and the biopsied mass was found to be a nodal marginal zone B-cell lymphoma according to histopathological testing.After undergoing chemotherapy at our hematology department, she has experienced no recurrence.

[A Case of GIST of the Stomach with Long-Term Survival after Multidisciplinary Treatment, Including Four Surgical Resections of Liver Metastases].

The most frequent relapse site of gastrointestinal stromal tumors(GIST)is the liver. We encountered a patient with longterm survival treated with multidisciplinary treatment, including4 hepatectomies for liver metastases. The patient was a woman aged 69 years at the time of the first medical treatment. She underwent total gastrectomy and S6 segmental hepatec- tomy for a stomach GIST with a hepatic metastasis. The tumor diameter was 24 cm and the mitotic figure was 65/50 HPF. According to the guidelines, it was diagnosed as a high risk GIST based on strong positive immunostaining for CD34 and c-kit. The tumor had metastasized to the liver and greater omentum. She took imatinib in the year following surgery. Because the GIST had spread to the lung1 8 months after the operation, she took imatinib again. Two years after the operation the pulmonary metastasis showed a clinical complete response(cCR)and the CR lasted for 4 years. Six years after the surgery she had a hepatic recurrence in S5, and she underwent an S5/4 partial hepatic resection. Seven years after the first operation, a liver S7 metastasis developed and she underwent S7 partial hepatectomy. Ten years after the first surgery, the GIST relapsed in liver S6 with right adrenal gland permeation. She underwent partial S6/7 liver resection and a right adrenal gland resection. She resumed takingimatinib after this surgical resection. Now, 11 years after the first operation, she is alive with an S1 hepatic recurrence taking sunitinib. Therefore, multidisciplinary treatment with surgical resection prolongs the survival of patients with resectable liver metastases of GIST.

A striking elevation of CA19-9 after preoperative therapy negates prognostic benefit from radical surgery in resectable and borderline resectable pancreatic cancer.

BACKGROUND: Identifying patients who can be spared nonbeneficial surgery is crucial, as pancreatic cancer surgery is highly invasive, with substantial negative effects on quality of life. The study objective was to investigate a useful indicator of patients who do not gain prognostic benefit from radical surgery after neoadjuvant therapy for resectable and borderline resectable pancreatic cancer. METHOD: We compared factors among 609 patients with resectable or borderline resectable pancreatic cancer receiving neoadjuvant therapy during 2005-2019. Patients were divided into a poor-prognosis group (no surgery or postresection recurrence within a year) and a good-prognosis group (no recurrence or recurrence >1 year after resection). RESULTS: Patients who experience a recurrence within a year of resection (poor-prognosis group) did no better than patients who received neoadjuvant therapy and progressed but never made it to surgery. The value of carbohydrate antigen 19-9 after neoadjuvant therapy was the most significant indicator to predict the poor prognosis group and the elevation of carbohydrate antigen 19-9 (>200 U/mL) identified only poor prognosis group with high specificity of 96.6%. The overall survival of patients with more than 200 of carbohydrate antigen 19-9 after neoadjuvant therapy was significantly very poor and their 2-year survival rate was only 41.4%. CONCLUSION: A striking elevation of carbohydrate antigen 19-9 after neoadjuvant therapy for resectable or borderline resectable pancreatic cancer is a good indicator of poor prognosis. Patients with carbohydrate antigen 19-9 >200 U/mL after neoadjuvant therapy should not undergo radical surgery.

Survival Impact of Inflammation-based Prognostic Scores in Metastatic or Unresectable Esophageal Cancer Treated With Pembrolizumab Plus Chemotherapy.

Pembrolizumab plus chemotherapy has been indicated as the first-line treatment for metastatic or unresectable locally advanced esophageal cancer. However, pretreatment biomarkers for predicting clinical outcomes remain unclear. We investigated the predictive value of inflammation-based prognostic scores in patients treated with pembrolizumab and chemotherapy. The Prognostic Nutritional Index (PNI), C-reactive protein/albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were calculated before initial treatment in 65 eligible patients with metastatic or unresectable locally advanced esophageal cancer receiving pembrolizumab plus CF therapy, and the relationship between these biomarkers and clinical outcomes was analyzed. The objective response rate (ORR) and progression disease (PD) were observed in 51% and 21% of all patients. Patients with PNI<39 have significantly worse treatment responses than those with PNI≥39 (ORR; 28% vs. 60%, PD; 44% vs. 13%, P =0.020). Progression-free survival (PFS) is significantly associated with the PNI and CAR ( P <0.001 and P =0.004, respectively). Overall survival (OS) is associated with PNI, CAR, and PLR ( P <0.001, P =0.008, and P =0.018, respectively). The PNI cutoff value of 39 is identified as an independent factor for PFS (odds ratio=0.27, 95% CI: 0.18-0.81, P =0.012) and OS (odds ratio=0.22, 95% CI: 0.08-0.59, P =0.003). Patients with PNI<39 have significantly worse 6-month PFS and 1-year OS than those with PNI≥39 (27.8% vs. 66.7%, 27.2% vs. 81.1%, respectively). In conclusion, inflammation-based prognostic scores are associated with survival in patients treated with pembrolizumab plus CF therapy. Pretreatment PNI is a promising candidate for predicting treatment response and survival.

Prognostic impact of dysphagia scores in patients with advanced resectable esophageal cancer who underwent radical esophagectomy after preoperative treatment.

BACKGROUND: Dysphagia caused by tumor strictures is a major symptom in patients with advanced esophageal cancer. However, the prognostic effect of dysphagia in resectable cases is insufficiently investigated. This study aimed to investigate the prognostic value of dysphagia scores in resectable advanced esophageal cancer who underwent radical esophagectomy after preoperative treatment. METHODS: This retrospective study enrolled 302 consecutive patients with advanced resectable esophageal cancer who received preoperative treatment. The preoperative dysphagia score was used to assess the relationship between tumor stricture and clinical outcomes. RESULTS: Almost half of the patients had dysphagia scores of 2 to 4 (n = 152 [50.3%]). Lower body mass index, circumferential tumors, and noncurative resection were significantly more common as dysphagia scores worsened. Patients with dysphagia had significantly more advanced ypT stage and worse histopathologic response than those without dysphagia. The 5-year disease-free survival and overall survival (OS) rates for dysphagia scores of 0 to 1, 2 to 3, and 4 were 52.9%, 35.3%, and 26.7% and 60.7%, 40.4%, and 26.7%, respectively. Multivariate analysis identified dysphagia score as an independent factor of OS, similar to surgical curability and ypN stage. The postoperative recurrence rate was significantly higher among patients with dysphagia scores of 2 to 3 (56%) and 4 (67%) than among those with dysphagia scores of 0 to 1 (36%) (P < .001 and P = .037, respectively). Furthermore, distant recurrence in dysphagia scores of 2 to 3 and 4 was higher than in dysphagia scores of 0 to 1 (26%, 46%, and 42%, respectively). CONCLUSION: The dysphagia score before initial treatment is associated with postoperative survival in patients with resectable advanced esophageal cancer.

Venous Thromboembolism Following Lateral Lymph Node Dissection for Rectal Cancer.

BACKGROUND/AIM: Postoperative venous thromboembolism (VTE) is a well-recognized complication that leads to morbidity and mortality. Lateral lymph node dissection (LLND) for rectal cancer is thought to potentially increase the risk of VTE due to its technical complexity. However, the relationship between LLND and VTE remains inadequately understood. The aim of this study was to elucidate the impact of LLND on the incidence of postoperative VTE. PATIENTS AND METHODS: This is a retrospective analysis of patients who underwent rectal cancer resection between 2010 and 2018 to identify the risk factors associated with postoperative VTE. Patients were divided into two groups: those who underwent surgery with LLND (LLND+ group) and those who underwent surgery without LLND (LLND- group). RESULTS: A total of 543 patients were enrolled in this study, and 113 patients underwent surgery for rectal cancer with LLND. VTE developed in 8 patients (1.47%), with the incidence rates being 4.42% in the LLND+ group and 0.69% in the LLND- group, respectively (p=0.012). Three of 8 patients had developed severe postoperative complications, and the other two patients needed intraoperative repair of the iliac vein during LLND procedure. Multivariate analysis identified the incidence of postoperative complications and LLND as the independent risk factors of VTE. CONCLUSION: Patients undergoing rectal cancer surgery with LLND should be closely monitored for signs of VTE.

Short-term Outcomes of Adjuvant Nivolumab After Neoadjuvant Chemotherapy in Patients With Resected Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIM: CheckMate 577 evaluated adjuvant nivolumab therapy after neoadjuvant chemoradiotherapy and surgery for esophageal cancers. However, the efficacy of this treatment in patients who received neoadjuvant chemotherapy remains unknown. This study investigated the short-term outcomes of adjuvant nivolumab therapy in patients with advanced esophageal squamous cell carcinoma post-neoadjuvant chemotherapy. PATIENTS AND METHODS: Out of 956 patients with thoracic esophageal cancer who underwent radical esophagectomy, 227 who exhibited ypN1-3 after neoadjuvant chemotherapy and surgery were included in this study. RESULTS: Among 227 patients, 30 received adjuvant nivolumab and 197 received non-nivolumab adjuvant therapy. The nivolumab group displayed a higher number of lymph node metastases compared to the control group. Patients with ypN1-2 tended to have longer recurrence-free survival (RFS) in the nivolumab group than in the non-nivolumab group (p=0.095). In the propensity score-matched cohort, no differences in patient characteristics were observed. Adjuvant nivolumab therapy significantly prolonged RFS in patients who received neoadjuvant chemotherapy (p=0.013). Patients with ypN1-2 in the nivolumab group had significantly longer RFS than their counterparts in the non-nivolumab group (p=0.001), but not in ypN3 (p=0.784). The 1-year postoperative recurrence rates were 59% for the non-nivolumab group and 24% for the nivolumab group (p=0.007). Nivolumab-related adverse events in patients receiving neoadjuvant chemotherapy were mostly consistent across all grades, while the frequency of increased aspartate aminotransferase (AST) levels was relatively higher compared to CheckMate577. CONCLUSION: Adjuvant nivolumab was more likely to prolong 1-year RFS in patients receiving neoadjuvant chemotherapy, especially in those with ypN1-2, and had acceptable adverse events.

Tumor-infiltrating T cells as a risk factor for lymph node metastasis in patients with submucosal colorectal cancer.

Approximately 10% of patients with colorectal cancer with submucosal invasion have lymph node metastasis. Pathological risk factors for lymph node metastasis have varying sensitivities and specificities. To predict the risk of lymph node metastasis, the identification of new risk factors is vital. Tumor-infiltrating T cells have been reported to improve the prognosis of many solid tumors. Therefore, the purpose of this study was to examine the relationship between lymph node metastasis and tumor-infiltrating T cells in patients with colorectal cancer with submucosal invasion. We examined CD8+ tumor-infiltrating T cells level as a risk factor for lymph node metastasis in patients with colorectal cancer with submucosal invasion. Using immunohistochemical staining, we identified CD8 + T cells in surgically resected specimens from 98 patients with SM-CRC. We showed that low CD8+ tumor-infiltrating T cells levels are positively correlated with lymph node metastasis. Furthermore, by combining the number of CD8+ tumor-infiltrating T cell and the number of CD103+ tumor-infiltrating T cells, the results showed a high positive predictive value for lymph node metastasis in cases with low numbers of both types of tumor-infiltrating T cells and a high negative predictive value in cases with high numbers of both types of tumor-infiltrating T cells.

High Level Sacral Bone Resection for Locally Recurrent Rectal Cancer.

BACKGROUND/AIM: Locally recurrent rectal cancer (LRRC) involving the upper sacrum is generally considered a contraindication for curative surgery. In the surgical management of LRRC, sacrectomy is frequently performed to secure clear resection margins. Nonetheless, the indications for high sacrectomy remain controversial due to potential postoperative complications, questions about radicality, and the increased complexity of the operation. Furthermore, comprehensive studies addressing this issue are notably absent. This study aimed to assess the feasibility, safety, and surgical prognosis in high sacrectomy for LRRC. PATIENTS AND METHODS: All patients with LRRC who required concomitant sacrectomy, but did not include the inferior margin of the second sacral vertebra, between 2003 and 2014, were reviewed retrospectively. RESULTS: Eight patients with a median age of 59 years were included in this study. The proximal resection line for sacral bone resection was the central part of the S1 vertebra in one patient, lower edge of the S1 vertebra in six patients, and central part of the S2 vertebra in one patient. Negative margin resection was achieved in five out of the eight patients. The median operative time was 922 min, and the median operative blood loss volume was 6,370 ml. Major complications included pelvic abscess (n=5), ileus (n=1), and pulmonary vein embolism (n=1), none of which proved fatal during the postoperative period. Both the 5-year local re-recurrence-free survival rate and the 5-year distant metastasis-free survival rate were 50% (4/8). CONCLUSION: High sacrectomy is safe and feasible to achieve negative margins in patients with LRRC.