Physical frailty recovery is slower than mental frailty recovery after non-cardiac surgery in older adult patients.

PURPOSE: Frailty is characterized by fragility and decline in physical, mental, and social activities; it is commonly observed in older adults. No studies have reported frailty status changes between the preoperative and postoperative periods, including mental and cognitive factors. Therefore, this study investigated frailty factors, including mental and cognitive functions, that change after non-cardiac surgery in older adults. METHODS: Patients aged ≥ 75 years who underwent non-cardiac surgery were surveyed using five tools (Eastern Cooperative Oncology Group-Performance Status (PS); handgrip strengths; Japan-Cardiovascular Health Study index (J-CHS index); Mini-Mental State Examination (MMSE); and Geriatric Depression Scale) for comprehensive evaluation of perioperative functions. The results before surgery, at discharge, and during follow-up at the outpatient clinic were compared. RESULTS: Fifty-three patients with a median age of 80 (IQR, 77-84) years were evaluated. MMSE scores did not change during the perioperative period. The PS and J-CHS index worsened significantly at discharge and did not improve at the outpatient clinic follow-up. The dominant handgrip strength decreased after surgery (p < 0.001) but improved during follow-up. Additionally, nondominant handgrip strength decreased after surgery (p < 0.001) but did not recover as much as the dominant handgrip strength during follow-up (p = 0.015). CONCLUSION: Changes in physical frailty and mental and cognitive functions were not identical perioperatively in older adult patients undergoing non-cardiac surgery. Physical frailty did not improve 1 month after surgery, mental function recovered early, and cognitive function did not decline. This study may be important for frailty prevention in older adult patients.

Microsatellite instability in the high-grade dysplasia component of duodenal adenoma is associated with progression to adenocarcinoma.

PURPOSE: We examined the microsatellite instability of duodenal tumors to evaluate their molecular features associated with the adenoma-carcinoma sequence. METHODS: Fifty-two non-ampullary duodenal epithelial tumors collected by endoscopic mucosal resection or surgical resection were studied. When a tumor had two or more dysplasia grades, the highest grade was considered. Representative areas were macro-dissected and subjected to a microsatellite instability analysis and immunohistochemical staining. RESULTS: The 52 tumors were classified as either adenoma with low-grade dysplasia (n = 18), adenoma with high-grade dysplasia (n = 20), or adenocarcinomas (n = 14). Among these, 3 adenocarcinoma cases showed microsatellite instability and the remaining 49 tumors showed microsatellite stability. Of the 14 adenocarcinoma cases, 3 contained both high-grade dysplasia and adenocarcinoma components, and 11 contained only the adenocarcinoma component. Interestingly, all three adenocarcinoma + high-grade dysplasia cases were microsatellite instability-high in both the adenocarcinoma and high-grade dysplasia components. Immunohistochemical staining of mismatch repair proteins showed mismatch repair deficiency in three microsatellite instability-high adenocarcinoma + high-grade dysplasia cases. CONCLUSIONS: Only adenocarcinoma cases with high-grade dysplasia components were microsatellite instability-high (in both the adenocarcinoma and high-grade dysplasia components). This suggests that microsatellite instability in the high-grade dysplasia component of duodenal adenoma is associated with progression to adenocarcinoma.

Intraoperative radiotherapy for resectable advanced lower rectal cancer-final results of a randomized controlled trial (UMIN000021353).

AIM: Pelvic autonomic nerve preservation (PANP) is useful to preserve voiding and sexual function after rectal cancer surgery. The aim of this study was to investigate the benefit of intraoperative radiotherapy (IORT) to have complete PANP without affecting oncological outcomes. METHODS: Patients undergoing potentially curative resection of the rectum were included. They were randomized to intraoperative radiotherapy of the completely preserved bilateral pelvic nerve plexuses (IORT group) or the control group without IORT, but with limited nerve preservation. The primary endpoint was pelvic sidewall recurrence. Moreover, patients' clinicopathologic parameters, postoperative complications, voiding function, and other oncologic outcomes were compared. RESULTS: From 79 patients, three were excluded from analysis, resulting in 38 patients in each group. Patients' demographic and pathological parameters were well balanced between the two groups. The trial was terminated prematurely in July 2017, because distant metastasis-free survivals were found to be significantly worse in the IORT group compared to the control group (odds ratio 2.554; 95% CI, 1.041 ~ 6.269; p = 0.041). Neither overall survival nor pelvic sidewall recurrence did differ between the two groups (overall survival: odds ratio 1.264; 95% CI, 0.523~3.051; p = 0.603/pelvic sidewall recurrence; odds ratio 1.350; 95% CI, 0.302~6.034; p = 0.694). Postoperative complications did not differ between the groups; however, the urinary function was significantly better in the IORT group in the short and long term. CONCLUSION: With the aid of IORT, complete PANP can be done without increase of pelvic sidewall recurrence; however, IORT may increase the incidence of distant metastases. Therefore, IORT cannot be recommended as a standard therapy to compensate less radical resection for advanced lower rectal cancer.

Intraoperative Colonoscopy in Laparoscopic Rectal Cancer Surgery Reduces Anastomotic Leakage.

Objectives: Anastomotic leakage (AL) is the most severe complication of colorectal surgery and is a frequent cause of postoperative mortality. This study aimed to identify the risk factors for AL, including the type of air leak test (ALT) performed, in patients undergoing laparoscopic colorectal cancer surgery. Methods: This study involved a retrospective review of 201 patients who underwent elective laparoscopic procedures using circular stapled anastomosis for colorectal cancer between January 2015 and December 2020 at Kyorin University Hospital, Tokyo, Japan. In all cases, the distance from the anal verge to the anastomotic site was within 15 cm. Results: Overall, AL was observed in 16 patients (8.0%). Univariate analysis revealed that the risk factors for AL included diabetes (P = 0.068), tumor location (P = 0.049), level of anastomosis (P = 0.002), number of linear stapler firings (P = 0.007), and intraoperative colonoscopy (IOCS; P = 0.069). Multivariate analysis revealed that the level of anastomosis (P = 0.029) and IOCS (P = 0.039) were significant and independent risk factors for AL. One of the 107 patients undergoing ALT without IOCS and 3 of the 94 patients undergoing ALT with IOCS were proven to be positive for air leak. However, these four patients underwent additional suturing intraoperatively and developed no AL following surgery. Conclusions: This study identified the level of anastomosis and ALT with IOCS as predictors for AL. The results of our study indicate that ALT with IOCS may be more effective than ALT without IOCS in the diagnosis and prevention of AL.

Site-specific risk factors for local recurrence after rectal cancer surgery.

BACKGROUND: Quite few studies examined risk factors for local recurrence after rectal cancer surgery with respect to local recurrence sites. METHODS: Local recurrence sites were categorized into axial, anterior, posterior, and lateral (pelvic sidewall), and axial, anterior, and posterior type were combined as the "other" type of local recurrence. Among 76 patients enrolled into our prospective randomized controlled trial to determine the indication for pelvic autonomic nerve preservation (PANP) in patients with advanced lower rectal cancer (UMIN000021353), multivariate analyses were conducted to elucidate risk factors for either lateral or the "other" type of local recurrence. RESULTS: Univariate analyses showed that tumor distance from the anal verge was significantly (p = 0.017), and type of operation (sphincter preserving operation (SPO) vs. abdominoperineal resection (APR)) was marginally (p = 0.065) associated with pelvic sidewall recurrence. Multivariate analysis using these two parameters showed that tumor distance from the anal verge was significantly and independently correlated with pelvic sidewall recurrence (p = 0.017). As for the "other" type of local recurrence, univariate analyses showed that depth of tumor invasion (p = 0.011), radial margin status (p < 0.001), and adjuvant chemotherapy (p = 0.037) were significantly associated, and multivariate analysis using these three parameters revealed that depth of tumor invasion (p = 0.004) and radial margin status (p < 0.001) were significantly and independently correlated with the "other" type of local recurrence. CONCLUSION: Risk factors for local recurrence after rectal cancer surgery were totally different with respect to the intra-pelvic recurrent sites. Site-specific probability of local recurrence can be inferred using these risk factors. TRIAL REGISTRATION NUMBER: UMIN000021353.

Changing Patterns of Distant Metastasis in Patients With Lower Rectal Cancer Undergoing Intraoperative Radiotherapy.

BACKGROUND/AIM: Local radiotherapy for primary tumors may increase the incidence of distant metastasis. However, the patterns of target organs have not been clarified yet. PATIENTS AND METHODS: In our randomized controlled trial examining the oncological efficacy of intraoperative radiotherapy (IORT) for advanced lower rectal cancer, the details of the metastatic organs were evaluated. RESULTS: In the IORT group (38 patients), 2 patients had metastasis in the liver and lung simultaneously, 9 in the liver, and 4 in the lung. In the control group (38 patients), 3 had metastasis in the lung, and 2 in the liver. The IORT group tended to have liver metastases more frequently (p=0.058). Among patients with liver metastases, distant metastasis-free intervals were significantly shorter in the IORT group, however, no significant difference was observed among patients with lung metastases. CONCLUSION: After curative rectal cancer surgery with IORT, liver metastasis may be increased and accelerated.

STK11 p.F354L Germline Mutation in a Case of Multiple Gastrointestinal Tumors.

Serine/threonine kinase 11 (STK11) is known as a critical tumor-suppressor gene that is frequently mutated in a broad spectrum of human cancers. Among these, the p.F354L mutation of STK11 has been identified in sporadic colon or lung cancer cases. Here, we report the case of a 75-year-old male patient who underwent surgical treatment for multiple tumors of the gastrointestinal system. Genetic mutations were screened in all resected samples, including duodenal high-grade adenoma, gastric high-grade adenoma, rectal adenocarcinoma, and liver metastasis of rectal adenocarcinoma, by next-generation sequencing for mutational hotspots involving 50 oncogenes and tumor suppressor genes. The characteristic hamartomatous polyp of Peutz-Jeghers syndrome was not detected in any tumor specimen. However, all samples as well as the normal rectal mucosa harbored the genetic mutation p.F354L in STK11. In addition, somatic mutations coexisted in the tumor samples, including KRAS p.A146T, TP53 p.G238X, and APC p.T1556fs in the duodenal adenoma; TP53 p.G238Y and APC p.T1556fs in the gastric adenoma; and TP53 p.R282W in the rectal adenocarcinoma and metastatic liver cancer. No somatic mutation was detected in the normal rectal mucosa as a control sample. To our knowledge, this is the first report of an STK11 germline mutation in a patient with multiple tumors of the gastrointestinal tract.