Modified neoadjuvant rectal score as a novel prognostic model for rectal cancer patients who underwent chemoradiotherapy.

BACKGROUND: The neoadjuvant rectal score (NAR score) has recently been proposed as a better prognostic model than the conventional TNM classification for rectal cancer patients that have undergone neoadjuvant chemoradiotherapy. We recently developed an apoptosis-detection technique for assessing the viability of residual tumors in resected specimens after chemoradiotherapy. This study aimed to establish an improved prognostic classification by combining the NAR score and the assessment of the apoptosis of residual cancer cells. METHODS: We retrospectively enrolled 319 rectal cancer patients who underwent chemoradiotherapy followed by radical surgery. The recurrence-free survival and overall survival of the four models were compared: TNM stage, NAR score, modified TNM stage by re-staging according to cancer cell viability, and modified NAR score also by re-staging. RESULTS: Downstaging of the ypT stage was observed in 15.5% of cases, whereas only 4.5% showed downstaging of ypN stage. C-index was highest for the modified NAR score (0.715), followed by the modified TNM, TNM, and NAR score. Similarly, Akaike's information criterion was smallest in the modified NAR score (926.2), followed by modified TNM, TNM, and NAR score, suggesting that the modified NAR score was the best among these four models. The overall survival results were similar: C-index was the highest (0.767) and Akaike's information criterion was the smallest (383.9) for the modified NAR score among the four models tested. CONCLUSION: We established a novel prognostic model, for rectal cancer patients that have undergone neoadjuvant chemoradiotherapy, using a combination of apoptosis-detecting immunohistochemistry and neoadjuvant rectal scores.

Apoptosis-related Prognostic Factors in Advanced Colorectal Cancer Determined Using Tissue Microarrays.

BACKGROUND/AIM: Cancer cells evade apoptosis in colorectal cancer (CRC); however, overlap between apoptosis and poor prognosis marker proteins in the invasive front of tumors has not been reported. Here, we aimed to clarify the relationship between apoptosis, apoptosis-related protein expression, and prognosis in the central and invasive front regions of CRC using tissue microarrays. PATIENTS AND METHODS: Data of 207 patients with pathological stage 3 CRC, who underwent radical surgery between October 2010 and November 2014, were retrospectively reviewed. We assessed apoptosis using M30 CytoDEATH, CD163, and p53 immunostaining in tumor sections in the center and invasive front using tissue microarrays and correlated the results with the survival outcomes. RESULTS: M30 CytoDEATH staining was negative; 134 cases (64.7%) were apoptosis-negative in the center and 103 (49.8%) were apoptosis-negative at the invasive front. CD163 positivity was observed in 16 cases (7.8%) in the center and in 36 cases (17.6%) at the invasive front; p53 positivity was observed in 33 (15.9%) and 64 (30.9%) cases in the center and invasive front, respectively. CD163 and p53 expression was not associated with survival outcomes; however, the apoptosis-negative group at the invasive front had significantly poorer survival outcomes (overall survival: p=0.044, relapse-free survival: p=0.001). We identified cases with a poor prognosis by combining apoptosis and CD163 expression. CONCLUSION: A lower apoptosis percentage at the invasive front is associated with a poorer prognosis. CRC cases with a poor prognosis can be identified by evaluating apoptosis and CD163 expression in the invasive front.

Development of a Diagnostic Artificial Intelligence Tool for Lateral Lymph Node Metastasis in Advanced Rectal Cancer.

BACKGROUND: Metastatic lateral lymph node dissection can improve survival in patients with rectal adenocarcinoma, with or without chemoradiotherapy. However, the optimal imaging diagnostic criteria for lateral lymph node metastases remain undetermined. OBJECTIVE: To develop a lateral lymph node metastasis diagnostic artificial intelligence tool using deep learning, for patients with rectal adenocarcinoma who underwent radical surgery and lateral lymph node dissection. DESIGN: Retrospective study. SETTINGS: Multicenter study. PATIENTS: A total of 209 patients with rectal adenocarcinoma, who underwent radical surgery and lateral lymph node dissection at 15 participating hospitals, were enrolled in the study and allocated to training (n = 139), test (n = 17), or validation (n = 53) cohorts. MAIN OUTCOME MEASURES: In the neoadjuvant treatment group, images taken before pretreatment were classified as baseline images and those taken after pretreatment as presurgery images. In the upfront surgery group, presurgery images were classified as both baseline and presurgery images. We constructed 2 types of artificial intelligence, using baseline and presurgery images, by inputting the patches from these images into ResNet-18, and we assessed their diagnostic accuracy. RESULTS: Overall, 124 patients underwent surgery alone, 52 received neoadjuvant chemotherapy, and 33 received chemoradiotherapy. The number of resected lateral lymph nodes in the training, test, and validation cohorts was 2418, 279, and 850, respectively. The metastatic rates were 2.8%, 0.7%, and 3.7%, respectively. In the validation cohort, the precision-recall area under the curve was 0.870 and 0.963 for the baseline and presurgery images, respectively. Although both baseline and presurgery images provided good accuracy for diagnosing lateral lymph node metastases, the accuracy of presurgery images was better than that of baseline images. LIMITATIONS: The number of cases is small. CONCLUSIONS: An artificial intelligence tool is a promising tool for diagnosing lateral lymph node metastasis with high accuracy. DESARROLLO DE UNA HERRAMIENTA DE INTELIGENCIA ARTIFICIAL PARA EL DIAGNSTICO DE METSTASIS EN GANGLIOS LINFTICOS LATERALES EN CNCER DE RECTO AVANZADO: ANTECEDENTES:Disección de nódulos linfáticos laterales metastásicos puede mejorar la supervivencia en pacientes con adenocarcinoma del recto, con o sin quimiorradioterapia. Sin embargo, aún no se han determinado los criterios óptimos de diagnóstico por imágenes de los nódulos linfáticos laterales metastásicos.OBJETIVO:Nuestro objetivo fue desarrollar una herramienta de inteligencia artificial para el diagnóstico de metástasis en nódulos linfáticos laterales mediante el aprendizaje profundo, para pacientes con adenocarcinoma del recto que se sometieron a cirugía radical y disección de nódulos linfáticos laterales.DISEÑO:Estudio retrospectivo.AJUSTES:Estudio multicéntrico.PACIENTES:Un total de 209 pacientes con adenocarcinoma del recto, que se sometieron a cirugía radical y disección de nódulos linfáticos laterales en 15 hospitales participantes, se inscribieron en el estudio y se asignaron a cohortes de entrenamiento (n = 139), prueba (n = 17) o validación (n = 53).PRINCIPALES MEDIDAS DE RESULTADO:En el grupo de tratamiento neoadyuvante, las imágenes tomadas antes del tratamiento se clasificaron como imágenes de referencia y las posteriores al tratamiento, como imágenes previas a la cirugía. En el grupo de cirugía inicial, las imágenes previas a la cirugía se clasificaron como imágenes de referencia y previas a la cirugía. Construimos dos tipos de inteligencia artificial, utilizando imágenes de referencia y previas a la cirugía, ingresando los parches de estas imágenes en ResNet-18. Evaluamos la precisión diagnóstica de los dos tipos de inteligencia artificial.RESULTADOS:En general, 124 pacientes se sometieron a cirugía solamente, 52 recibieron quimioterapia neoadyuvante y 33 recibieron quimiorradioterapia. El número de nódulos linfáticos laterales removidos en los cohortes de entrenamiento, prueba y validación fue de 2,418; 279 y 850, respectivamente. Las tasas metastásicas fueron 2.8%, 0.7%, y 3.7%, respectivamente. En el cohorte de validación, el área de recuperación de precisión bajo la curva fue de 0.870 y 0.963 para las imágenes de referencia y antes de la cirugía, respectivamente. Aunque tanto las imágenes previas a la cirugía como las iniciales proporcionaron una buena precisión para diagnosticar metástasis en los nódulos linfáticos laterales, la precisión de las imágenes previas a la cirugía fue mejor que la de las imágenes iniciales.LIMITACIONES:El número de casos es pequeño.CONCLUSIÓN:La inteligencia artificial es una herramienta prometedora para diagnosticar metástasis en los nódulos linfáticos laterales con alta precisión. (Traducción-Dr. Aurian Garcia Gonzalez ).

CD133(+)HIF-1α(-) Expression After Chemoradiotherapy Predicts Poor Prognosis in Rectal Cancer.

BACKGROUND/AIM: CD133 and hypoxia-inducible factor 1α (HIF-1α) have been reported to be affected by chemoradiotherapy (CRT), but the combinatorial assessment of these markers for prognosis after CRT has not been fully investigated. Therefore, we aimed to predict recurrence and prognosis in patients with rectal cancer by assessing changes in the expression of both CD133 and HIF-1α after CRT. MATERIALS AND METHODS: CD133 and HIF-1α expression was evaluated by immunohistochemistry in surgical specimens from 243 patients with advanced low rectal cancer who received CRT followed by curative resection. RESULTS: The positivity rate of CD133 expression showed increase with increased HIF-1α expression. The combination of these two markers showed that the CD133(+)HIF-1α(-) group exhibited a markedly shorter relapse-free survival (p=0.007), higher liver recurrence (p=0.004), and higher local recurrence (p=0.006). CONCLUSION: CD133(+)HIF-1α(-) expression after CRT is a promising marker to predict recurrence in rectal cancer.

Impact of the viability assessment of lateral lymph node metastasis in rectal cancer after neoadjuvant chemoradiotherapy.

PURPOSE: Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME) without lateral lymph node (LLN) dissection is widely performed for lower advanced rectal cancer. However, it is unclear whether residual cancer cells in the LLNs undergo apoptosis, disappear, or regrow if unresected. METHODS: Overall, 293 consecutive patients with T3/4 rectal cancer who underwent CRT followed by radical surgery between September 2003 and December 2018 were retrospectively reviewed. We assessed apoptosis of the residual primary tumor, mesorectum lymph nodes (MLN), and LLN using M30 cytoDEATH immunostaining and evaluated the degree of apoptosis. The difference in the prognosis of the lateral lymph node metastasis positive (LLNM +) and lateral lymph node metastasis negative (LLNM-) groups was assessed. RESULTS: There were 31 patients (10.6%) who were diagnosed with a complete response by hematoxylin and eosin (HE) staining. The residual cancer cells showed complete apoptosis in the primary lesion in 28 patients, in the metastatic MLN in only two patients, and in the metastatic LLN in one patient. The LLNM + group had a significantly poorer distant recurrence, recurrence-free survival, and overall survival than the LLNM- group. CONCLUSION: The majority of the residual cancer tissue in LNs observed by HE staining was found to be non-apoptotic. If LLN metastasis is suspected on pretreatment imaging, performing LLN dissection together with TME should be considered.

Development of a novel apoptosis-based tumor regression grade to assess the efficacy of preoperative chemoradiotherapy for rectal cancer: a retrospective single-center study.

BACKGROUND: Preoperative chemoradiotherapy is used preferably for locally advanced rectal cancer, followed by a watch-and-wait strategy for cases showing clinical complete response. However, there is a discordance between pathological and clinical complete response rates. We aimed to propose a tumor regression grade (TRG) that truly reflects the therapeutic effects of preoperative chemoradiotherapy in locally advanced rectal cancer. METHODS: Overall, 293 consecutive patients with T3/T4a/T4b rectal cancer who underwent chemoradiotherapy followed by radical surgery between Sep 2003 and Dec 2018 were retrospectively reviewed. We assessed apoptosis using M30 cytoDEATH immunostaining and correlated that with conventional TRG (convTRG) evaluated using hematoxylin-eosin staining, and created a new TRG by evaluating apoptosis and convTRG. The modified TRG1-4 (modifTRG) classification was as follows: modifTRG1 comprised poor TRG, modifTRG2 moderate TRG, modifTRG3 good TRG, modifTRG4 complete apoptosis and convTRG3 (pathological complete response). We assessed the overall survival, relapse-free survival, and local recurrence rate. RESULTS: Pathological complete response rate was 10.6% when evaluated using conventional staining. Using M30 staining, apoptosis was observed in the residual disease in convTRG 1a 0%, convTRG 1b 0.3%, convTRG 2 9.2%. Combining the two, modifTRG4 was observed in 20.1%. The survival rates were similar between modifTRG4 and convTRG3, suggesting that modifTRG4 was equivalent to pathological complete response. However, in multivariate analysis, modifTRG but not convTRG was an independent risk factor for local and distant recurrences. CONCLUSION: The proposed modifTRG truly reflected the therapeutic effects of chemoradiotherapy and may be superior to the convTRG to stratify rectal cancer patients treated with chemoradiotherapy.

Therapeutic effects and limitations of chemoradiotherapy in advanced lower rectal cancer focusing on T4b.

PURPOSE: This study aimed to elucidate the benefits and limitations of preoperative chemoradiotherapy (CRT) in rectal cancer treatment, specifically in T4b rectal cancer. METHODS: This retrospective cohort study reviewed 1014 consecutive patients with clinical T3/4a/T4b adenocarcinomas of the lower rectum, who underwent total mesorectal excision at the Department of Surgical Oncology of the University of Tokyo Hospital and 22 referral institutions affiliated with the Japanese Study Group for Postoperative Follow-up of Colorectal Cancer. Patients were divided into two cohorts: cohort 1 comprised 298 consecutive patients who underwent CRT followed by radical surgery and cohort 2 comprised 716 consecutive patients who underwent curative surgery without preoperative therapy. We assessed the prognostic differences between the two cohorts, focusing particularly on T stages. RESULTS: In T3/4a patients, cohort 1 showed a significantly lower local recurrence rate than cohort 2 (4.8% vs. 9.4%, p=0.024), but not in T4b patients (23.5% vs. 16.0%, p=0.383). In contrast, no significant differences in survival were observed between T3/4a and T4b patients. T4b classification was found to be an independent predictive factor of local recurrence in cohort 1, but not in cohort 2. CONCLUSION: In T4b rectal cancer, preoperative CRT demonstrated a limited benefit for local control and survival. In cases of suspected T4b rectal tumors, additional therapies such as induction chemotherapy to conventional CRT may contribute to better outcomes.

Pneumatosis Cystoides Intestinalis in Patients with Systemic Sclerosis: A Case Report and Review of 39 Japanese Cases.

Pneumatosis cystoides intestinalis (PCI) is a rare gastrointestinal complication of systemic sclerosis (SSc) characterized by intramural accumulation of gas within thin-walled cysts. We report the case of an 82-year-old female patient with pneumoperitoneum due to PCI associated with SSc and review the features of the 39 Japanese cases. The median patient age was 57 years (range 24-83 years) and the male/female ratio was 1 : 12. In the recent decade, 14 out of 15 cases (93.3%) evaluated with CT scans were diagnosed with PCI. The results suggest that CT scan may be a useful diagnostic tool for detecting PCI. PCI in patients with SSc is usually benign and requires only conservative therapy. However, two patients (5.1%) with signs of peritoneal irritation required surgery. When peritoneal irritation secondary to additional pathology is observed, surgical treatment may be warranted; a precise diagnosis for this condition is therefore essential.

Underweight status predicts a poor prognosis in elderly patients with colorectal cancer.

The aim of the present study was to evaluate the effect of underweight status on the survival of elderly patients undergoing surgery for colorectal cancer (CRC). A total of 113 patients aged ≥75 years who underwent curative surgery for CRC were included. In addition to standard perioperative variables, body mass index (BMI) was assessed. The patients were categorized as underweight (BMI<18.5 kg/m2) or non-underweight (BMI≥18.5 kg/m2). The 3-year overall survival (OS) and cancer-specific survival (CSS) were analyzed. Of the 113 patients, 24 (21%) were underweight. The two groups were well-balanced regarding all factors evaluated. In the multivariate analysis, underweight status was an independent indicator of lower 3-year OS [hazard ratio (HR)=2.65; 95% confidence interval (CI): 1.08-6.50; P=0.033] and CSS (HR=3.51, 95% CI: 1.16-10.60; P=0.025) rates. Compared with the non-underweight group, the underweight group had significantly worse 3-year OS (66.7 vs. 86.5%, respectively; P=0.017) and CSS (74.1 vs. 90.9%, respectively; P=0.025) rates. Therefore, underweight status was a significant risk factor for poor survival in elderly CRC patients. The development of effective nutritional interventions may improve the prognosis of such patients.