The prognostic and predictive significance of perineural invasion in stage I to III colon cancer: a propensity score matching-based analysis.

BACKGROUND: Colorectal cancer (CRC) presents with varying prognoses, and identifying factors for predicting metastasis and outcomes is crucial. Perineural invasion (PNI) is a debated prognostic factor for CRC, particularly in stage I-III patients, but its role in guiding adjuvant chemotherapy for node-positive colon cancer remains uncertain. METHODS: We conducted a single-center study using data from the Colorectal Section Tumor Registry Database at Chang Gung Memorial Hospital, Taiwan. This prospective study involved 3,327 CRC patients, 1,536 of whom were eligible after application of the exclusion criteria, to investigate the prognostic value of PNI in stage I-III patients and its predictive value for node-positive/negative cancer patients receiving adjuvant chemotherapy. Propensity score matching (PSM) was used to minimize selection bias, and follow-up was performed with standardized procedures. RESULTS: PNI-positive (PNI+) tumors were associated with higher preoperative CEA levels and more frequent adjuvant chemotherapy. After PSM, PNI + tumors were associated with marginally significantly lower 5-year disease-free survival (DFS) and significantly lower overall survival (OS) rates in stages III CRC. However, no significant differences were observed in stages I and II. Subgroup analysis showed that among PNI + tumors, only poorly differentiated tumors had higher odds of recurrence. PNI did not predict outcomes in node-negative colon cancer. Adjuvant chemotherapy benefited PNI + patients with node-positive but not those with node-negative disease. CONCLUSIONS: Our study indicates that PNI is an independent poor prognostic factor in stage III colon cancer but does not predict outcomes in node-negative disease. Given the potential adverse effects of adjuvant chemotherapy, our findings discourage its use in node-negative colon cancer when PNI is present.

Metformin increases pathological responses to rectal cancers with neoadjuvant chemoradiotherapy: a systematic review and meta-analysis.

BACKGROUND: To summarize the chemo-radio effect of metformin in rectal cancers with neoadjuvant chemoradiotherapy on pathological response, tumor regression grade (TRG), and T/N downstaging. METHODS: PubMed, MEDLINE, Embase, and Cochrane Database of collected reviews were searched up to June 30, 2022. This study conducted systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) sheet. Odds ratios (ORs) and confidence intervals (CIs) which calculated by random-effects models were displayed in forest plots. Newcastle-Ottawa scale was used to assess the risk of bias of the observational cohort studies. RESULTS: This systematic review and meta-analysis comprised eight cohorts out of seven studies, with 2294 patients in total. We performed two-way comparison for metformin in diabetic patients vs (1) non-metformin drugs in diabetic patients and (2) nondiabetic patients. In diabetes patient studies, the metformin group had a significantly increased pathological response on TRG (OR: 3.28, CI: 2.01-5.35, I2 = 0%, p < 0.001) and T downstaging (OR: 2.14, CI: 1.24-3.67, I2 = 14%, p = 0.006) in comparison with a non-metformin group. When compared with nondiabetic patients, the pathological response on TRG (OR: 2.67, CI: 1.65-4.32, I2 = 43%, p < 0.001) and T downstaging (OR: 1.96, CI: 1.04-3.71, I2 = 66%, p = 0.04) were also higher in metformin group. The limitation was that no randomized controlled trials were available based on current literature review. Small sample sizes for diabetic metformin or non-metformin users in rectal cancer patients reduced the power of the study. CONCLUSIONS: For patients with rectal cancer and treated with neoadjuvant chemoradiotherapy, metformin administration in diabetic patients increased the pathological response on tumor-regression grade and T downstaging. Further well-designed, high-quality randomized controlled trials are required to reveal the actual effect of metformin.

Upfront primary tumor resection versus upfront systemic therapy for metastatic colorectal cancer: a systematic review and meta-analysis.

PURPOSE: The standard initial treatment for metastatic colorectal cancer (mCRC) remains debated. This study investigated whether upfront primary tumor resection (PTR) or upfront systemic therapy (ST) provides better survival outcomes for patients with mCRC. METHODS: The PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched for studies published at any time from January 1, 2004, to December 31, 2022. Randomized controlled trials (RCTs) and prospective or retrospective cohort studies (RCSs) utilizing propensity score matching (PSM) or inverse probability treatment weighting (IPTW) were included. We evaluated overall survival (OS) and short-term (60-day) mortality in these studies. RESULTS: After reviewing 3,626 articles, we identified 10 studies including a total of 48,696 patients. OS differed significantly between the upfront PTR and upfront ST arms (hazard ratio [HR] 0.62; 95% CI: 0.57-0.68; p < 0.001). However, a subgroup analysis identified no significant difference in OS in RCTs (HR 0.97; 95% CI: 0.7-1.34; p = 0.83), whereas significant difference in OS occurred between the treatment arms in RCSs with PSM or IPTW (HR 0.59; 95% CI: 0.54-0.64; p < 0.001). Short-term mortality was analyzed in three RCTs, and 60-day mortality differed significantly between the treatment arms (risk ratio [RR] 3.52; 95% CI: 1.23-10.10; p = 0.02). CONCLUSIONS: In RCTs, upfront PTR for mCRC did not improve OS and enhanced the risk of 60-day mortality. However, upfront PTR seemed to increase OS in RCSs with PSM or IPTW. Therefore, whether upfront PTR should be used for mCRC remains unclear. Further large RCTs are required.

Usefulness of close surveillance for rectal cancer patients after neoadjuvant chemoradiotherapy.

It is controversial whether patients who achieve clinical complete remission (cCR) of rectal cancer should be treated with the "watch and wait" (W&W) or radical resection (RR) strategy. Our study aimed to compare the survival outcomes and ostomy rate of the W&W and RR strategies. Between January 2008 and December 2015, we investigated 26 patients who achieved pathologic complete remission after undergoing RR and 36 patients who adopted the W&W strategy because of cCR. The tumor regrowth, salvage surgery, recurrence, disease-free, and overall survival (OS) rates were assessed. In our study, recurrences occurred in nine and two patients from the W&W and RR groups, respectively. Each patient in the RR group had a temporary or permanent ostomy, but only three (8.3%) had an ostomy in the W&W group. The 5-year recurrence rate was 25.0% in the W&W group and 7.7% in the RR group. Six patients (16.7%) had tumor regrowth in the W&W group, and all were resectable when regrowth. The 5-year OS rates between the two groups were nonsignificant. There is no specific risk factor for recurrence and OS. Under close surveillance, the W&W group achieved similar OS to the RR group and benefited from a lower ostomy rate.

Association of Preoperative Physical Activity with Short- and Long-Term Outcomes in Patients Undergoing Palliative Resection for Metastatic Colorectal Cancer: An Inverse Probability of Treatment Weighting Analysis.

A lack of physical activity is a generally accepted risk factor for colorectal cancer. However, research on the effect of preoperative physical activity on postoperative and long-term outcomes is limited, especially in patients with stage IV colorectal cancer who underwent palliative surgery. Patients who underwent bowel resection for stage IV primary colorectal cancer between January 1995 and December 2016 were retrospectively enrolled. A total of 2185 patients were divided into two groups according to preoperative leisure-time weekly physical activity as assessed by metabolic equivalent of task (MET) values: MET < 12 (n = 1845) and MET ≥ 12 (n = 340). Inverse probability of treatment weighting (IPTW) was used to reduce imbalance and selection biases between the two groups. After the IPTW process, the MET < 12 group showed a higher postoperative morbidity rate (18.7% vs. 10.6%; p < 0.001) and mortality rate (2.4% vs. 0.6%; p < 0.001) than the MET ≥ 12 group. No significant difference was found in overall survival. Weekly preoperative leisure-time physical activity with MET ≥ 12 was associated with reduced short-term postoperative morbidity and mortality in patients undergoing palliative resection for metastatic colorectal cancer. However, no difference was detected in long-term survival.

The risk factors of local recurrence and distant metastasis on pT1/T2N0 mid-low rectal cancer after total mesorectal excision.

BACKGROUND: Radical resection is associated with good prognosis among patients with cT1/T2Nx rectal cancer. However, still some of the patients experienced cancer recurrence following radical resection. This study tried to identify the postoperative risk factors of local recurrence and distant metastasis separately. METHODS: This retrospective, single-center study comprised of 279 consecutive patients from Linkou branch of Chang Gung Memorial Hospital in 2005-2016 with rectal adenocarcinoma, pT1/T2N0M0 at distance from anal verge ≤ 8cm, who received curative radical resection. RESULTS: The study included 279 patients with pT1/pT2N0 mid-low rectal cancer with median follow-up of 73.5 months. Nineteen (6.8%) patients had disease recurrence in total. Nine (3.2%) of them had local recurrence, and fourteen (5.0%) of them had distant metastasis. Distal resection margin < 0.9 (cm) (hazard ratio = 4.9, p = 0.050) was the risk factor of local recurrence. Preoperative carcinoembryonic antigen (CEA) ≥ 5 ng/mL (hazard ratio = 9.3, p = 0.0003), lymph node yield (LNY) < 14 (hazard ratio = 5.0, p = 0.006), and distal resection margin < 1.4cm (hazard ratio = 4.0, p = 0.035) were the risk factors of distant metastasis. CONCLUSION: For patients with pT1/pT2N0 mid-low rectal cancer, current multidisciplinary treatment brings acceptable survival outcome. Insufficient distal resection margin attracted the awareness of risk factors for local recurrence and distant metastasis as a foundation for future research.

Survival analysis of local excision vs total mesorectal excision for middle and low rectal cancer in pT1/pT2 stage and intermediate pathological risk.

BACKGROUND: Local excision (LE) is a feasible treatment approach for rectal cancers in stage pT1 and presents low pathological risk, whereas total mesorectal excision (TME) is a reasonable treatment for more advanced cancers. On the basis of the pathology findings, surgeons may suggest TME for patients receiving LE. This study compared the survival outcomes between LE with/without chemoradiation and TME in mid and low rectal cancer patients in stage pT1/pT2, with highly selective intermediate pathological risk. METHODS: This retrospective study included 134 patients who received TME and 39 patients who underwent LE for the treatment of intermediate risk (pT1 with poor differentiation, lymphovascular invasion, perineural invasion, relatively large tumor, or small-sized pT2 tumor) rectal cancer between 1998 and 2016. RESULTS: Overall survival (OS), disease-free survival (DFS), and cumulative recurrence rate (CRR) were similar between the LE (3-year DFS 92%) and TME (3-year DFS 91%) groups. Following subgrouping into an LE with adjuvant therapy group and a TME without adjuvant therapy group, the compared survival outcomes (OS, DFS, and CRR) were found not to be statistically different. The temporary and permanent ostomy rates were higher in the TME group than in the LE group (p < 0.001). Rates of early and late morbidity following surgery were higher in the TME group (p = 0.005), and LE had similar survival compared with TME. CONCLUSION: For patients who had mid and low rectal cancer in stage pT1/pT2 and intermediate pathological risk, LE with chemoradiation presents an alternative treatment option for selected patients.

Risk Factor Analysis for the Outcomes of Indirect Traumatic Optic Neuropathy with No Light Perception at Initial Visual Acuity Testing.

BACKGROUND: The optimal management of indirect traumatic optic neuropathy (TON) is controversial. We aimed to compare the differences in visual improvement by treatment option in patients presenting with TON and no light perception (NLP). We also wanted to identify any patient-related factors that might favor the use of steroid pulse therapy or optic nerve decompression (OND). METHODS: We retrospectively identified 46 consecutive patients with indirect TON treated at Chang Gung Memorial Hospital between 2007 and 2015. The outcome was the improvement in visual acuity by improvement rate and degree of improvement. RESULTS: Females had a better improvement rate than did males. Compared with delayed treatment, patients receiving steroid pulse therapy within 14 hours or receiving OND within 26 hours had a better improvement rate/degree. In patients with an initial intraocular pressure (IOP) of 17-23 mm Hg, the improvement rate/degree was significantly better than for patients with an IOP outside this range. For patients treated by OND, an initially normal IOP (11-21 mm Hg) suggested a significantly better prognosis in the improvement rate/degree. CONCLUSIONS: For patients with indirect TON, initial NLP implies a poor prognosis, but steroid pulse therapy or OND are both feasible treatment options. These results emphasize the importance of timely treatment for patients with indirect TON and NLP. Females and patients with an initial IOP of 17-23 mm Hg were more likely to recover. The results of our study indicate that normal initial IOP (11-21 mm Hg) is good prognostic factor for patients with indirect TON treated with OND.

Risk Factors Analysis for the Outcome of Indirect Traumatic Optic Neuropathy With Steroid Pulse Therapy.

BACKGROUND: Although recent evidence suggests a controversy effect of steroids in the management of indirect traumatic optic neuropathy (TON), steroid pulse therapy remains one of the reasonable treatments for patients with indirect TON. It is thought that microcirculatory spasms, edema, and nerve cell necrosis can be prevented or reduced by large doses of steroids. The aim of this study is to analyze the predisposing factors for the recovery of patients with indirect TON who were treated with steroid pulse therapy. MATERIALS AND METHODS: In tracing the 2008 to 2014 data from the Trauma Center of Chang Gung Memorial Hospital, 20 consecutive cases of indirect TON were identified retrospectively. Twenty cases showed no light perception (NLP) under initial ophthalmologic examination. They all received steroid pulse therapy with methylprednisolone in IV form after examination by ophthalmologists, and they did not receive optic nerve decompression. The general data, fracture pattern from images, hospital courses, trauma-related data from ER record, and the initial and final visual data from ophthalmologic records are reviewed. The odds ratio (OR) and 95% confidence intervals (CI) are calculated. Fisher exact test is used for 2 variables to test differences between proportions. Nonparametric statistics are applied to compare the mean values of the data. RESULTS: The results show that for female patients (OR, 3.400; 95% CI, 1.628-7.101; P = 0.049), the administration of methylprednisolone in less than 24 hours from the injury (OR, 3.429; 0.297-39.637), lateral force fracture pattern (OR, 3.500; 0.313-39.153), age of 40 years or younger (OR, 2.333; 0.197-27.567), and pure facial trauma (OR, 3.667; 0.273-49.288) are the predisposing factors for improvement of visual acuity. Patients with orbital blowout fractures (OR, 9.800; 95% CI, 0.899-106.845; P = 0.070), initial free extraocular movement (EOM) (OR, 6.667; 0.809-54.597; P = 0.145), initial intraoptic pressure (IOP) greater than 25 mmHg (OR, 8.000; 0.598-106.936), and higher triage grade (OR, 3.000; 0.447-20.153) are at risk of showing no improvement. CONCLUSIONS: From this study, we might suggest to apply steroid pulse therapy on those patients without contraindication, with an incurring injury less than 24 hours previously. Factors such as sex, age, lateral force fracture pattern, and pure facial trauma revealed a better outcome for improvement of visual acuity. Orbital blowout fractures, initial free EOM, initial IOP greater than 25 mmHg, and higher triage grade suggested poor improvement of visual acuity.