Chemotherapy and COVID-19 Vaccination in Patients With Gastrointestinal Cancer.

BACKGROUND/AIM: Multiple doses of vaccines against the coronavirus disease (COVID-19) provide patients with cancer the opportunity to continue cancer treatment. This study investigated the safety and efficacy of COVID-19 vaccination in patients with cancer and the optimal timing of vaccination during chemotherapy. PATIENTS AND METHODS: A total of 131 patients with gastrointestinal (GI) cancer who received two doses of the COVID-19 vaccine were included in this study. This study combined two cohorts: an evaluation cohort of 79 patients receiving chemotherapy and a control cohort of 52 patients under follow-up after radical surgery. None of the patients had any history of COVID-19. Treatment- and vaccine-related adverse events (AEs) were recorded through outpatient interviews and self-reports. RESULTS: In the evaluation cohort, 62 patients (78.4%) experienced vaccine-related AEs after the first dose, and 62 patients (78.4%) experienced vaccine-related AEs with an increased rate of fever and fatigue after the second dose. In the control cohort, vaccine-related AEs occurred in 28 (53.8%) patients after the first dose and in 37 (71.2%) patients after the second dose, with increased fever and fatigue after the second dose. Of the 79 patients, 49 received chemotherapy before vaccination. Twelve patients (24.5%) changed their treatment schedule: four for safety reasons, four for myelosuppression, and four for convenience. Three patients discontinued the treatment because of disease progression. CONCLUSION: Systemic chemotherapy in patients with GI cancer does not have a markedly negative effect on COVID-19 vaccination, resulting in manageable vaccine-related AEs, and minimizing the need for treatment schedule changes.

Discovery of non-genomic drivers of YAP signaling modulating the cell plasticity in CRC tumor lines.

In normal intestines, a fetal/regenerative/revival cell state can be induced upon inflammation. This plasticity in cell fate is also one of the current topics in human colorectal cancer (CRC). To dissect the underlying mechanisms, we generated human CRC organoids with naturally selected genetic mutation profiles and exposed them to two different conditions by modulating the extracellular matrix (ECM). Among tested mutation profiles, a fetal/regenerative/revival state was induced following YAP activation via a collagen type I-enriched microenvironment. Mechanistically, YAP transcription was promoted by activating AP-1 and TEAD-dependent transcription and suppressing intestinal lineage-determining transcription via mechanotransduction. The phenotypic conversion was also involved in chemoresistance, which could be potentially resolved by targeting the underlying YAP regulatory elements, a potential target of CRC treatment.

Poor prognosis of young male patients with stage III colorectal cancer: A multicenter retrospective study.

BACKGROUND AND OBJECTIVES: The number of young patients with colorectal cancer (CRC) is increasing. However, sex-dependent differences in the prognosis of young CRC remain unknown. METHODS: We investigated patients aged <70 years with stage III CRC treated between January 2000 and December 2010 in 24 Japanese referral hospitals. Patients were divided into subgroups by age of 50 years (early-onset and late-onset groups) and sex, and clinical characteristics and survival outcomes were compared. Risk factors associated with poor survival outcomes were also analyzed. RESULTS: Among 4758 consecutive patients, 771 (16%) were <50 years. Regardless of sex, there were more patients with rectal cancer and treated with adjuvant chemotherapy in the early-onset group. Among males, tumors in the early-onset group were poorly differentiated (p < 0.001), and patients were diagnosed at an advanced N stage (p = 0.010). Among females, there were more patients with left-sided cancer in the early-onset group (p < 0.001). Relapse-free survival (RFS) and overall survival (OS) were worse in the early-onset group than in the late-onset group (5-year RFS rates: 58% and 63%, p = 0.024; 5-year OS rates: 76% and 81%, p = 0.041, respectively), while there were no age-dependent differences in the survival outcomes of female CRC patients. A multivariate analysis identified age <50 years as one of the independent risk factors associated with poor RFS in male stage III CRC patients (p = 0.032) CONCLUSIONS: Young male patients with stage III CRC showed poorer survival outcomes than their older counterparts. Therefore, age- and sex-related differences in the incidence of CRC recurrence need to be considered.

Robotic-assisted colectomy for right-sided colon cancer: Short-term surgical outcomes of a multi-institutional prospective cohort study in Japan.

Background: In Japan, there are no substantial reports on robotic-assisted colectomy because few institutions performed the procedure, as it was not covered by national insurance until March 2022. Aim: This study aimed to evaluate the safety and feasibility of robotic-assisted colectomy for patients with curatively resectable colon cancer in Japan. Methods: This multi-institutional, prospective, single-arm, observational study enrolled patients diagnosed with curatively resectable clinical stage I-IIIC colon adenocarcinoma with D2 or D3 lymph node dissection and treated with robotic-assisted colectomy. The primary endpoint was the conversion rate to laparotomy. The non-inferiority of outcomes for robotic-assisted colectomy versus laparoscopic colectomy, which was determined from historical data, was verified. Results: One hundred patients were registered between July 2019 and March 2022 and underwent robotic-assisted colectomy performed by seven expert surgeons at six institutions. Thirteen patients were excluded because their surgeons had insufficient experience performing robotic-assisted colectomy; therefore, 87 patients were eligible for the primary endpoint analysis. There was no conversion in these 87 patients, and robotic-assisted colectomy was non-inferior to laparoscopic colectomy in terms of conversion rate (90% confidence interval 0-3.38, p = 0.0006). No intraoperative adverse events occurred, and no mortality was observed in a total of 100 patients. The rate of patients with Clavien-Dindo complications grade III or higher was 4%. Conclusion: This study showed the non-inferiority of the conversion rates between robotic-assisted colectomy and laparoscopic colectomy. Favorable perioperative outcomes also suggest the safety and feasibility of robotic-assisted colectomy.

Prognostic Significance of Enlarged Lymph Nodes in Stage II Colorectal Cancer.

BACKGROUND: Many studies have reported a correlation between lymph node metastasis and prognosis in patients with colorectal cancer. However, the clinical significance of enlarged lymph nodes for prognosis has scarcely been explored. OBJECTIVE: This study aimed to assess the clinical significance of enlarged lymph nodes in stage II colorectal cancer. DESIGN: This is a multicenter retrospective observational study with a median follow-up period of 66.8 months. SETTINGS: Patients' medical records were retrospectively collected from the Japanese Study Group for Postoperative Follow-up of Colorectal Cancer database. PATIENTS: This study included 2212 patients with stage II colorectal cancer who underwent surgical resection between January 2009 and December 2012. Patients were classified into the enlarged lymph node and nonenlarged lymph node groups and their data were compared. MAIN OUTCOME MEASURES: Clinicopathological characteristics and prognoses of the 2 groups were compared. The main outcomes measured were recurrence-free survival and overall survival. RESULTS: The enlarged lymph node group showed significantly better overall survival and recurrence-free survival in pT4b cases but not in pT3 or pT4a cases. In pT4b cases, an enlarged lymph node (HR, 0.53; 95% CI, 0.29-0.98) was an independent prognostic factor for longer recurrence-free survival, whereas a rectal lesion (HR, 3.46; 95% CI, 1.90-6.29) was an independent prognostic factor for shorter recurrence-free survival. An enlarged lymph node was associated with a lower distant recurrence rate (HR, 0.49; 95% CI, 0.26-0.92) and a tendency to correlate with better overall survival (HR, 0.50; 95% CI, 0.22-1.14). LIMITATIONS: The retrospective design may have increased the risk of selection bias. Inadequate information regarding enlarged lymph nodes is another study limitation. CONCLUSIONS: This study showed that enlarged lymph nodes are associated with a favorable prognosis in patients with pT4b stage II colorectal cancer. See Video Abstract at http://links.lww.com/DCR/C246 . IMPORTANCIA PRONSTICA DE LOS GANGLIOS LINFTICOS AGRANDADOS EN EL CNCER COLORRECTAL EN ESTADIO II: ANTECEDENTES:Muchos estudios han informado una correlación entre la metástasis en los ganglios linfáticos y el pronóstico en pacientes con cáncer colorrectal. Sin embargo, apenas se ha explorado la importancia clínica de los ganglios linfáticos agrandados para el pronóstico.OBJETIVO:El objetivo fue evaluar la importancia clínica de los ganglios linfáticos agrandados en el cáncer colorrectal en estadio II.DISEÑO:Este es un estudio observacional retrospectivo multicéntrico con una mediana de seguimiento de 66,8 meses.CONFIGURACIÓN:Los registros médicos de los pacientes se recopilaron retrospectivamente de la base de datos del Grupo de estudio japonés para el seguimiento posoperatorio del cáncer colorrectal.PACIENTES:Incluimos 2212 pacientes con cáncer colorrectal en estadio II que se sometieron a resección quirúrgica entre enero de 2009 y diciembre de 2012. Los pacientes se clasificaron en grupos de ganglios linfáticos agrandados y no agrandados y se compararon sus datos.PRINCIPALES MEDIDAS DE RESULTADO:Se compararon las características clinicopatológicas y los pronósticos de los dos grupos. Los principales resultados medidos fueron la supervivencia sin recurrencia y la supervivencia general.RESULTADOS:El grupo de ganglios linfáticos agrandados mostró una supervivencia general significativamente mejor y una supervivencia libre de recurrencia en los casos pT4b, pero no en los casos pT3 ni pT4a. En los casos de pT4b, el agrandamiento de los ganglios linfáticos (CRI, 0,53; IC 95 %, 0,29-0,98) fue un factor pronóstico independiente para una supervivencia sin recidiva más prolongada, mientras que la lesión rectal (CRI, 3,46; IC 95%, 1,90-6,29) fue un factor pronóstico independiente para RFS más cortos. Los ganglios linfáticos agrandados se relacionaron con una tasa más baja de recurrencia a distancia (CRI, 0,49; IC 95%, 0,26-0,92) y una tendencia a correlacionarse con una mejor supervivencia general (CRI, 0,50; IC 95%, 0,22-1,14).LIMITACIONES:El diseño retrospectivo puede haber aumentado el riesgo de sesgo de selección. La información inadecuada sobre el agrandamiento de los ganglios linfáticos es otra limitación del estudio.CONCLUSIONES:Este estudio mostró que los ganglios linfáticos agrandados están asociados con un pronóstico favorable en pacientes con cáncer colorrectal pT4b en estadio II. Consulte Video Resumen en http://links.lww.com/DCR/C246 . ( Traducción - Dr. Mauricio Santamaria ).

Prognosis of Inferior Mesenteric and Para-aortic Lymph Node Metastases in Rectal Cancer: A Multicenter Study.

BACKGROUND/AIM: In colorectal cancer cases, treatment strategies differ between those with regional and extra-regional lymph node metastases. The inferior mesenteric lymph nodes are categorized as regional lymph nodes, while the para-aortic lymph nodes are classified as extra-regional lymph nodes. Although inferior mesenteric and para-aortic lymph node metastases are both associated with a dismal prognosis, few prognostic comparisons have been conducted. The present study aimed to clarify the prognosis of inferior mesenteric and para-aortic lymph node metastases in rectal cancer. PATIENTS AND METHODS: We retrospectively evaluated 71 patients with pathologically diagnosed rectosigmoid or rectal cancer with inferior mesenteric lymph node metastasis and 27 with pathologically diagnosed rectosigmoid or rectal cancer with para-aortic lymph node metastasis who underwent curative surgery. They were identified from the Japanese Study Group for Postoperative Follow-Up of Colorectal Cancer database. Overall survival, recurrence-free survival, and recurrence patterns were compared between the two groups. RESULTS: The five-year recurrence-free survival rates of patients with inferior mesenteric and para-aortic lymph node metastases were 31.2 and 28.1%, respectively (p=0.37), and the five-year overall survival rates were 43.1 and 39.6%, respectively (p=0.60). Furthermore, the survival curves of the two groups almost overlapped for both recurrence-free survival and overall survival rates. Recurrence patterns did not significantly differ between the two groups. CONCLUSION: In rectal cancer, the prognosis of inferior mesenteric lymph node metastasis is similar to that of para-aortic lymph node metastasis. Inferior mesenteric lymph node metastasis has a poor prognostic impact on rectal cancer.

Advantages of preoperative counseling with video for robotic rectal cancer surgery compared with conventional counseling: A randomized controlled trial.

PURPOSE: Surgeons should provide patients with appropriate explanations before surgery and obtain informed consent. However, this process requires time and effort and can be a great burden. The purpose of this study was to compare preoperative counseling with video (VC) and conventional counseling (CC) for rectal cancer patients. METHODS: Rectal cancer patients indicated for surgery were included between April 2021 and March 2022, and eligible patients were randomly assigned to the CC and VC groups. The primary outcomes were the comprehension, satisfaction, and anxiety levels, and the secondary outcome was the preoperative counseling time. This exploratory study protocol was registered with the UMIN Clinical Trials Registry (UMIN000038133). RESULTS: We included 13 patients in the CC group and 17 in the VC group. All eligible patients were scheduled for robotic rectal cancer surgery. There were no significant differences between the two groups, including patients' general condition, preoperative diagnosis, and planned procedures. Although the comprehension, satisfaction, and anxiety test scores were not significantly different between the groups, the preoperative counseling time was significantly shorter in the VC group than in the CC group (20 vs. 35 minutes, P = .002). A 4-year college degree significantly increased the counseling time, whereas VC significantly decreased it. CONCLUSION: Using videos in preoperative counseling for rectal cancer patients is useful. This novel method could reduce the burden on surgeons during preoperative counseling in the era of robotic surgery and work style reforms.

Collagen type I-mediated mechanotransduction controls epithelial cell fate conversion during intestinal inflammation.

BACKGROUND: The emerging concepts of fetal-like reprogramming following tissue injury have been well recognized as an important cue for resolving regenerative mechanisms of intestinal epithelium during inflammation. We previously revealed that the remodeling of mesenchyme with collagen fibril induces YAP/TAZ-dependent fate conversion of intestinal/colonic epithelial cells covering the wound bed towards fetal-like progenitors. To fully elucidate the mechanisms underlying the link between extracellular matrix (ECM) remodeling of mesenchyme and fetal-like reprogramming of epithelial cells, it is critical to understand how collagen type I influence the phenotype of epithelial cells. In this study, we utilize collagen sphere, which is the epithelial organoids cultured in purified collagen type I, to understand the mechanisms of the inflammatory associated reprogramming. Resolving the entire landscape of regulatory networks of the collagen sphere is useful to dissect the reprogrammed signature of the intestinal epithelium. METHODS: We performed microarray, RNA-seq, and ATAC-seq analyses of the murine collagen sphere in comparison with Matrigel organoid and fetal enterosphere (FEnS). We subsequently cultured human colon epithelium in collagen type I and performed RNA-seq analysis. The enriched genes were validated by gene expression comparison between published gene sets and immunofluorescence in pathological specimens of ulcerative colitis (UC). RESULTS: The murine collagen sphere was confirmed to have inflammatory and regenerative signatures from RNA-seq analysis. ATAC-seq analysis confirmed that the YAP/TAZ-TEAD axis plays a central role in the induction of the distinctive signature. Among them, TAZ has implied its relevant role in the process of reprogramming and the ATAC-based motif analysis demonstrated not only Tead proteins, but also Fra1 and Runx2, which are highly enriched in the collagen sphere. Additionally, the human collagen sphere also showed a highly significant enrichment of both inflammatory and fetal-like signatures. Immunofluorescence staining confirmed that the representative genes in the human collagen sphere were highly expressed in the inflammatory region of ulcerative colitis. CONCLUSIONS: Collagen type I showed a significant influence in the acquisition of the reprogrammed inflammatory signature in both mice and humans. Dissection of the cell fate conversion and its mechanisms shown in this study can enhance our understanding of how the epithelial signature of inflammation is influenced by the ECM niche.

Prognostic Value of Preoperative Carcinoembryonic Antigen and Carbohydrate Antigen 19-9 Levels for Adjuvant Chemotherapy in Stage II Colorectal Cancer: A Nationwide Multicenter Retrospective Study.

Objectives: Adjuvant chemotherapy for stage II colorectal cancer patients with high-risk factors for recurrence can be useful; however, its advantage in prognosis remains to be controversial. Thus, in this study, we aimed to assess whether a combination of preoperative serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels can predict the prognosis and advantage of adjuvant chemotherapy. Methods: Using a Japanese nationwide database, in total, 3,688 patients with curative resected stage II colorectal cancer were registered retrospectively between 2008 and 2012 in 24 referral institutions. Patients were classified into three groups as follows: Group A (both non-high levels of CEA and CA19-9), Group B (either high levels of CEA or CA19-9), and Group C (both high levels of CEA and CA19-9). Results: Multivariable Cox regression analysis, adjusting the depth of tumor invasion, number of dissected lymph nodes, tumor differentiation, lymphatic and venous invasion, and other covariates, showed that the 5-year disease-free survival and overall survival were shorter in Group C than in Groups A and B. Furthermore, in Group C, the 5-year disease-free survival rate was improved in the surgery-plus-AC group compared to the surgery-alone group. Conclusions: As with existing high-risk factors for recurrence, the combination assessment of preoperative serum CEA and CA19-9 can predict the prognosis for colorectal cancer. Adjuvant chemotherapy may provide a prolonged disease-free survival advantage in stage II colorectal cancer patients with high levels of both tumor markers.

Long-term outcomes of D2 vs. D3 lymph node dissection for cT2N0M0 colorectal cancer: a multi­institutional retrospective analysis.

BACKGROUND: According to Japanese guidelines, D2 or D3 lymph node dissection (LND) is indicated for cT2N0M0 colorectal cancer (CRC). In this study, we retrospectively compared the long-term outcomes between D2 and D3 LND among patients with cT2N0M0 CRC. METHODS: Our sample included 515 patients from the Japanese Study Group for Postoperative Follow-Up of Colorectal Cancer database, who underwent surgical resection for cT2N0M0 CRC between January 2009 and December 2012, 195 (37.9%) of whom underwent D2 LND and 320 (62.1%) D3 LND. The D2 and D3 groups were retrospectively compared in terms of long-term outcomes including overall survival (OS) and relapse-free survival (RFS). The prognostic factors for these outcomes were also evaluated. RESULTS: The D2 group had significantly older patients and higher proportion of men than the D3 group. The rates of OS (5-year OS; 94.8% in the D3 group vs. 93.4% in the D2 group, p = 0.38) and RFS (5-year RFS; 89.3% in the D3 group vs. 89.1% in the D2 group, p = 0.91) were comparable for both groups. On multivariate analysis, age ≥ 80 years was significantly associated with poor OS. The extent of LND was not associated with either OS or RFS. Long-term outcomes were similar between the two groups, independent of tumor location. CONCLUSION: The long-term outcomes did not differ between the D2 and D3 groups and the extent of LND was not associated with prognosis for cT2N0M0 CRC. Therefore, D2 LND may be sufficient for cT2N0N0 CRC treatment.

Laparoscopic Colectomy: A Risk Factor for Postoperative Peritoneal Metastasis.

BACKGROUND: The oncologic outcomes are generally considered equivalent for both laparoscopic and open surgery. However, our previous single-center study found a greater risk of postoperative peritoneal metastasis (PM) after laparoscopic colectomy (LC) than after open colectomy (OC) in patients with pathological T4a (pT4a) colon cancer. This multicenter study aimed to clarify if the risk of PM was increased after LC. METHODS: This study used the multicenter database of the Japanese Study Group for Postoperative Follow-up of Colorectal Cancer, which included patients with colorectal cancer treated between 1997 and 2012 in 24 referral hospitals across Japan. The analysis included 17,323 patients with pathological stage I-III colon cancer, including 2380 patients with pT4a disease. The risk of PM was compared between the LC and OC groups. RESULTS: The cumulative incidence of PM was significantly higher after LC in patients with pT4a colon cancer (13.0% vs. 7.7%; P = .001). Multivariable analyses showed LC was a significant risk factor for PM (hazard ratio [HR]: 1.36, 95% confidence interval [CI]: 1.04-1.78, P = .023), which was confirmed by propensity score analyses (HR: 1.36, 95% CI: 1.04-1.78, P = .024). CONCLUSION: This study demonstrated a significant increase in the risk of PM after LC than after OC.

Robotic-assisted Surgery: Expanding Indication to Colon Cancer in Japan.

In recent years, robotic-assisted surgery has demonstrated remarkable progress as a minimally invasive procedure for colorectal cancer. While there have been fewer studies investigating robotic-assisted surgery for the treatment of colon cancer than rectal cancer, evidence regarding robotic-assisted colectomy has been accumulating due to increasing use of the procedure. Robotic-assisted colectomy generally requires a long operative time and involves high costs. However, as evidence is increasingly supportive of its higher accuracy and less invasive nature compared to laparoscopic colectomy, the procedure is anticipated to improve the ratio of conversion to laparotomy and accelerate postoperative recovery. Robotic-assisted surgery has also been suggested for a specific level of effectiveness in manipulative procedures, such as intracorporeal anastomosis, and is increasingly indicated as a less problematic procedure compared to conventional laparoscopy and open surgery in terms of long-term oncological outcomes. Although robotic-assisted colectomy has been widely adopted abroad, only a limited number of institutions have been using this procedure in Japan. Further accumulation of experience and studies investigating surgical outcomes using this approach are required in Japan.

Clinical impact of primary tumor sidedness and sex on unresectable post-recurrence survival in resected pathological stage II-III colorectal cancers: a nationwide multicenter retrospective study.

BACKGROUND: Several studies have demonstrated that right-sided tumors have poorer prognosis than left-sided tumors in patients with unresectable colorectal cancer (CRC). The predictive ability of the tumor sidedness in CRC treated with chemotherapy in each sex is unclear. METHODS: Subjects were 964 unresectable recurrent patients treated with chemotherapy with stage II-III CRC after curative resection between 2004 and 2012. Post-recurrence cancer-specific survival (CSS) for each sex was examined. RESULTS: Patients were 603 males (222 right-side tumors (cecum to transverse colon) and 381 left-sided tumors (descending colon to rectum)), and 361 females (167 right-side tumors and 194 left-sided tumors). Right-sided tumors developed peritoneal recurrences in males and females. Left-sided tumors were associated with locoregional recurrences in males and with lung recurrences in females. Right-sided tumors were associated with shorter post-recurrence CSS in both sexes. In males, multivariate analyses showed that right-sided tumors were associated with shorter post-recurrence CSS (HR: 1.53, P < 0.0001) together with the presence of regional lymph node metastasis histopathological type of other than differentiated adenocarcinoma, the recurrence of liver only, the recurrence of peritoneal dissemination only, and relapse-free interval less than one-year. In females, multivariate analyses showed that right-sided tumors were associated with shorter post-recurrence CSS (HR: 1.50, P = 0.0019) together with advanced depth of invasion, the presence of regional lymph node metastasis, and recurrence of liver only. CONCLUSIONS: Primary tumor sidedness in both sexes in unresectable recurrent CRC patients treated with chemotherapy may have prognostic implications for post-recurrence CSS.

Identification of high-risk stage I colon and rectal cancer patients: a retrospective analysis of a large Japanese cohort.

PURPOSE: Data regarding risk factors for recurrence in stage I colorectal cancer patients are limited. The aim of this study was to clarify the existence of a high-recurrence-risk population among stage I colorectal cancer patients. METHODS: This analysis included 7,539 stage I colorectal cancer patients treated between 1997 and 2012 at 24 leading hospitals in Japan. Risk factors for time to recurrence were evaluated using a Cox proportional hazards model, and a high-risk group for recurrence was identified. Prognostic outcomes of high-risk stage I colorectal cancer patients were compared with those of low-risk stage I and stage II patients. RESULTS: Multivariable analyses identified left-sided location (hazard ratio [HR]: 1.65, 95% confidence interval [CI]: 1.09-2.58), T2 tumors (HR: 1.80, 95% CI: 1.21-2.66), and lymphatic invasion (HR: 1.55, 95% CI: 1.05-2.28) as risk factors for recurrence in stage I colon cancer, and patients with these three risk factors were classified as high risk. For stage I rectal cancer, patients with poor differentiation (HR: 2.86, 95% CI: 1.21-5.69), T2 tumors (HR: 1.53, 95% CI: 1.07-2.23), and venous invasion (HR: 1.51, 95% CI: 1.08-2.13) were identified as high risk. The Kaplan-Meier analysis of cumulative recurrence rate and recurrence-free survival revealed that the high-risk stage I colorectal cancer patients have poorer clinical outcomes than the low-risk patients. CONCLUSION: Although stage I colorectal cancer patients generally have a favorable prognosis after curative surgery, poorer prognosis was observed in high-risk stage I colorectal cancer patients than in low-risk patients.

The Eastern Cooperative Oncology Group Performance Status as a prognostic factor of stage I-III colorectal cancer surgery for elderly patients: a multi-institutional retrospective analysis.

PURPOSES: The relationship between the general condition and long-term prognosis in elderly patients with colorectal cancer (CRC) undergoing curative surgery remains unclear. This study investigated the risk factors for poor long-term outcomes in elderly patients with CRC. METHODS: Data of pStage I to III patients with CRC ≥ 80 years old who underwent curative surgery were collected from a multi-institutional database of the Japanese study group for postoperative follow-up of CRC. We retrospectively investigated the poor prognostic factors for the overall survival (OS) and relapse-free survival (RFS). RESULTS: A total of 473 patients with a median age of 83 years were investigated (315, 121, 34, and 3 with an Eastern Cooperative Oncology Group Performance Status [ECOG-PS] 0, 1, 2, and 3, respectively). Multivariate Cox regression analysis showed that ECOG-PS ≥ 2 and positive lymph node metastasis were independently associated with a poor OS (both p < 0.01). Positive lymph node metastasis (p < 0.01) and tumor depth (T3 or T4) (p = 0.02) were independently associated with a poor RFS. In Stages I and II, but not Stage III patients, the OS was significantly worse in those with ECOG-PS ≥ 2 than in those with ECOG-PS ≤ 1. CONCLUSION: Preoperative ECOG-PS was a significant prognostic factor for elderly patients with CRC after curative surgery.

Infrared Thermography and Ultrasonography of the Hands in Rheumatoid Arthritis Patients.

Ultrasonography (US) and power Doppler US (PDUS) are used worldwide for diagnosing rheumatoid arthritis (RA). Superb microvascular imaging (SMI) is a good tool for evaluating inflammatory activity. Thermal imaging is a noncontact, noninvasive procedure using skin temperature measurement. We report a case wherein the thermal and ultrasound images of the hand are compared and evaluated for inflammatory activity in patients with RA. Case: US imaging of the left hand of a 75-year-old woman with RA revealed a hypoechoic lesion of the left wrist joint. PDUS and SMI evaluated blood flow according to the blood flow at Grade 2. The temperature of the hypoechoic lesion with high blood flow was higher than that of the same location on the opposite side. This study shows that combining thermal and blood flow images may be useful for detecting inflammatory activity levels in RA patients.

PHLDA1 expression in ulcerative colitis: A potential role in the management of dysplasia.

Pleckstrin homology-like domain, family A, member 1 (PHLDA1) is a protein involved in cell proliferation, adhesion and migration in colon cancer. In normal large intestinal mucosa, this protein is expressed only in the crypts. By contrast, its expression in adenomas and cancers of the large intestine is spread throughout the glandular ducts, and it has been reported that PHLDA1 may be involved in the process of carcinogenesis. PHLDA1 may also be involved in the pathogenesis of ulcerative colitis (UC). The expression levels of PHLDA1 in tissues from patients with UC were analyzed using immunohistochemistry, and its relationship with the development of UC-associated colorectal cancer (UC-CRC) was examined. Overall, tissue samples from 143 lesions (90 colitis lesions, 39 dysplastic lesions and 14 UC-CRC lesions) were prepared from excised specimens of 49 patients with UC who underwent surgery in Tokyo Medical and Dental University Hospital between January 2004 and December 2017. Subsequently, immunostaining for PHLDA1 was performed. PHLDA1 expression was evaluated in UC-CRC and dysplastic tissues within the entire lesion area on the slide and in colitis over the area of the accompanying duct. The cytoplasmic staining intensity was classified into four levels, and the expression score (0-2 points) was calculated. The median PHLDA1 expression score was 0.295 for colitis, 0.607 for dysplasia and 0.865 for UC-CRC. The dysplasia expression score was significantly higher than the colitis score (P<0.001), while the UC-CRC expression score was significantly higher than the dysplasia score (P=0.003). The expression levels of PHLDA1 in UC cases were higher in colitis, followed by dysplasia and UC-CRC, which suggested that this protein may be involved in the carcinogenesis of UC-CRC. In addition, PHLDA1 immunostaining may help in the diagnosis of dysplasia, which is a type of precancerous lesion.

Prognostic Impact and Clinicopathological Features of Multiple Colorectal Cancers and Extracolorectal Malignancies: A Nationwide Retrospective Study.

INTRODUCTION: Multiple primary malignancies (MPMs) are likely to develop in patients with colorectal cancer (CRC); however, their prognoses are unclear. This study aims to investigate the prognostic impacts and clinicopathological features of multiple CRCs and extracolorectal malignancies (EMs) with CRC. METHODS: We retrospectively evaluated a total of 22,628 patients with stage I-III CRC who underwent curative resection at 24 referral institutes in Japan between January 2004 and December 2012. MPMs were classified as synchronous CRCs (SCRCs), metachronous CRCs, synchronous EMs (SEMs), and metachronous EMs. RESULTS: The presence of SCRCs (odds ratio 1.54, p < 0.001) was independently associated with SEMs in the multivariate analyses. SEMs were the strongest poor prognostic factor for OS (hazard ratio [HR] 2.21, p < 0.001) and RFS (HR 1.69, p < 0.001) compared with age, sex, and primary T and N factors. The incidence of stomach cancer was the highest in EMs, followed by lung, breast, and prostate cancers. Multiple CRCs were evenly distributed throughout the right-side colon to the rectum. DISCUSSION/CONCLUSION: SEMs were a strong poor prognostic factor for patients with stage I-III CRC. Patients with CRC, particularly those with SCRCs, should be surveyed for SEMs, especially for stomach and lung cancers.

Stage II colon cancer staging using the number of retrieved lymph nodes may be superior to current TNM staging for prognosis stratification: the Japanese study group for postoperative follow-up of colorectal cancer.

PURPOSE: The purpose of the study was to compare staging of stage II colon cancer using the number of retrieved lymph nodes (RN) to current TNM staging for stratification of prognosis. METHODS: The subjects were 6307 patients with stage II colon cancer who underwent curative resection at 24 Japanese institutions. The cutoff for the number of RN was established using Akaike information criterion (AIC) values for relapse-free survival (RFS) and overall survival (OS). Comparison of survival using TNM and T + RN (TRN) staging was performed using a Cox proportional hazards regression model. RESULTS: AIC was lowest for 14 retrieved lymph nodes for RFS and OS. This number was used as the cutoff. In multivariate analysis, age (≥ 69), male gender, V1, CEA (> 5), pT (T4a, T4b), and RN-L were independent factors associated with RFS and OS. Six combinations of pT and RN categories were used to establish three subgroups: TRN stages IIA, IIB, and IIC. The 5-year RFS was 83.9%, 72.3%, and 71.8% in TNM stages IIA, IIB, and IIC; and 86.0%, 76.9%, and 60.3% in TRN stages IIA, IIB, and IIC. The 5-year OS was 90.0%, 81.3%, and 82.6% for the TNM stages; and 91.6%, 85.0%, and 71.9% for the TRN stages. The AIC for RFS was lower for TRN (22,318.2) than for TNM (22,390.6), and that for OS was also lower for TRN (16,285.3) than for TNM (16,355.1). CONCLUSION: Stage II colon cancer staging using the number of retrieved lymph nodes may be superior to current TNM staging for prognosis stratification.