Efficacy and Safety of a Parenteral Nutrition Program for Patients with RAS Wild-Type Metastatic Colorectal Cancer Administered First-Line Cetuximab Plus Chemotherapy: A Propensity Score Matching Study.

Malnutrition is a common problem in patients with metastatic colorectal cancer (mCRC) receiving targeted therapy plus chemotherapy, resulting in severe toxicity and decreased survival rates. This retrospective study employing propensity score matching (PSM) examined the efficacy and safety of a supplemental home parenteral nutrition (HPN) program for patients with RAS wild-type mCRC receiving cetuximab plus chemotherapy. This retrospective nationwide registry study included data from 14 medical centers/hospitals across Taiwan, and the data period ranged from November 2016 to December 2020. Patients with RAS wild-type mCRC receiving cetuximab plus chemotherapy as their first-line therapy were included and divided into HPN and non-HPN program groups. HPN was initiated based on patient-specific factors, such as baseline nutritional status, treatment-related toxicities, and comorbidities. Clinical outcomes were evaluated using response to therapy, duration of response (DoR), progression-free survival (PFS), and overall survival (OS). This study recruited 758 patients, of whom 110 and 648 were included in the HPN and non-HPN program groups, respectively. After 1:3 PSM, the data of 109 and 327 patients from the HPN and non-HPN program groups were analyzed, respectively. The HPN program group had a higher metastasectomy rate (33.9% vs. 20.2%, p = 0.005), and longer duration of treatment and DoR than the non-HPN program group (13.6 vs. 10.3 and 13.6 vs. 9.9 months, p = 0.001 and < 0.001, respectively). The HPN program group tended to have a longer median PFS (18.2 vs. 13.9 months, p = 0.102). Moreover, we noted a significant improvement in the median OS in the same group (53.4 vs. 34.6 months, p = 0.002). Supplemental HPN programs may be recommended for select patients with mCRC receiving targeted therapy plus chemotherapy to improve oncological outcomes.

Survival benefit of metastasectomy in first-line cetuximab therapy in patients with RAS wild-type metastatic colorectal cancer: a nationwide registry.

This multicenter study aimed to explore the survival benefit of metastasectomy by first-line cetuximab-based chemotherapy in real-world patients with RAS wild-type metastatic colorectal cancer (mCRC). The primary endpoints were overall survival (OS) and progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), and metastasectomy rate. The exploratory endpoint was the optimal treatment cycle for better OS and PFS. Receiver operating characteristic curve with the area under curve (AUC) was used to identify the optimal cut-off cycle for survival outcomes. A total of 758 mCRC patients were enrolled in this study, with a median OS of 35.1 months, median PFS of 14.6 months, and metastasectomy rate of 21.4%. Left-sided mCRC had a significantly higher DCR (88.9% vs. 73.1%, P<0.001) and better OS (36.4 vs. 19.6 months, P<0.001). There were no significant differences in PFS and metastasectomy rate between left-sided and right-sided mCRC. However, mCRC patients who underwent metastasectomy over the course of treatment had better OS (54.9 vs. 28.6 months, P<0.001) and PFS (21.0 vs. 13.1 months, P<0.001) than those who did not. Notably, right-sided mCRC who benefited from first-line cetuximab-based chemotherapy to underwent metastasectomy also had favorable outcomes, on a par with left-sided mCRC. The optimal treatment cycle was 14 cycles (AUC: 0.779, P<0.001). Patients who received ≥14 cycles had higher metastasectomy rates (27.5% vs. 13.5%, P<0.001), favorable OS (42.6 vs. 23.4 months, P<0.001) and PFS (18.1 vs. 8.6 months, P<0.001), and, importantly, had comparable adverse events compared with patients who received <14 cycles of treatment. Patients who underwent metastasectomy after or during first-line cetuximab therapy have an improved OS in both left-sided and right-sided mCRC. Furthermore, patients receive ≥14 cycles of treatment whenever possible to achieve a higher likelihood of metastasectomy was associated with favorable survival outcomes.

Colo-pancreaticoduodenectomy for locally advanced colon carcinoma-feasibility in patients presenting with acute abdomen.

BACKGROUND: En bloc right hemicolectomy plus pancreaticoduodenectomy (PD) is administered for locally advanced colon carcinoma that invades the duodenum and/or pancreatic head. This procedure may also be called colo-pancreaticoduodenectomy (cPD). Patients with such carcinomas may present with acute abdomen. Emergency PD often leads to high postoperative morbidity and mortality. Here, we aimed to evaluate the feasibility and outcomes of emergency cPD for patients with advanced colon carcinoma manifesting as acute abdomen. METHODS: We retrospectively reviewed 4898 patients with colorectal cancer who underwent curative colectomy during the period from 1994 to 2018. Among them, 30 had locally advanced right colon cancer and had received cPD. Among them, surgery was performed in 11 patients in emergency conditions (bowel obstruction: 6, perforation: 3, tumor bleeding: 2). Selection criteria for emergency cPD were the following: (1) age ≤ 60 years, (2) body mass index < 35 kg/m2, (3) no poorly controlled comorbidities, and (4) perforation time ≤ 6 h. Three patients did not meet the above criteria and received non-emergency cPD after a life-saving diverting ileostomy, followed by cPD performed 3 months later. We analyzed these patients in terms of their clinicopathological characteristics, the early and long-term postoperative outcomes, and compared findings between emergency cPD group (e-group, n = 11) and non-emergency cPD group (non-e-group, n = 19). After cPD, staged pancreaticojejunostomy was performed in all e-group patients, and on 15 of 19 patients in the non-e-group. RESULTS: The non-e-group was older and had a higher incidence of associated comorbidities, while other clinicopathological characteristics were similar between the two groups. None of the patients in the two groups succumbed from cPD. The postoperative complication rate was 63.6% in the e-group and 42.1% in the non-e-group (p = 0.449). The 5-year overall survival rate were 15.9% in the e-group and 52.6% in the non-e-group (p = 0.192). CONCLUSIONS: Emergency cPD is feasible in highly selected patients if performed by experienced surgeons. The early and long-term positive outcomes of emergency cPD are similar to those after non-emergency cPD in patients with acute abdominal conditions.

Determination of the UGT1A1 polymorphism as guidance for irinotecan dose escalation in metastatic colorectal cancer treated with first-line bevacizumab and FOLFIRI (PURE FIST).

AIM: Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) polymorphism plays a crucial role in the increased susceptibility of patients to irinotecan and its toxicity. This study is a multicenter, randomised clinical trial comparing the clinical outcomes and adverse events (AEs) in metastatic colorectal cancer (mCRC) patients treated with bevacizumab plus FOLFIRI with or without UGT1A1 genotyping and irinotecan dose escalation as the first-line therapy. METHODS: The control group received conventional biweekly FOLFIRI plus bevacizumab without UGT1A1 genotyping, whereas the study group received the same regimen with irinotecan dose escalation based on UGT1A1 genotyping. The primary end-point was progression-free survival (PFS), and secondary end-points were overall response rate (ORR), disease control rate (DCR), overall survival (OS), AEs and metastasectomy rate. RESULTS: Over a median follow-up of 26.0 months (IQR, 17.0-35.0 months), study group (n = 107) was superior to the control group (n = 106) in PFS, OS, ORR, DCR, and metastasectomy rate (all P < 0.05). Furthermore, there were no significant differences in AEs ≥ grade III between the two groups, even with the 1.36-fold increase in the relative dose intensity of irinotecan in the study group. Dose escalation of irinotecan, an independent factor of ORR (P < 0.001) and DCR (P = 0.006), improved PFS in mCRC patients with wild-type and mutant KRAS (P = 0.007 and P = 0.019, respectively). CONCLUSION: The current study revealed that mCRC patients, regardless of KRAS gene status, with UGT1A1 genotyping can tolerate escalated doses of irinotecan and potentially achieve a more favourable clinical outcome without significantly increased toxicities. CLINICAL TRIAL REGISTRATION: NCT02256800.

Neoadjuvant therapy of bevacizumab in combination with oxaliplatin and capecitabine (XELOX) for patients with metastatic colorectal cancer with unresectable liver metastases: a phase II, open-label, single-arm, noncomparative trial.

AIM: This phase II, open-label study evaluated the efficacy and safety of neoadjuvant therapy with bevacizumab plus XELOX (capecitabine and oxaliplatin) for untreated metastatic colorectal cancer with unresectable liver metastases and assessed conversion of unresectable to resectable metastases after neoadjuvant treatment. METHODS: Patients received bevacizumab 5 mg/kg and oxaliplatin 85 mg/m2 on day 1, and capecitabine 1000 mg/m2 twice daily on days 1-5 followed by 2 days of rest in a 14-day cycle for 12 cycles; bevacizumab was excluded in cycles 6 and 7. Patients were later divided into resected and unresected groups, depending upon whether they underwent curative resection after chemotherapy. Efficacy and safety were evaluated. RESULTS: Of 45 patients enrolled, 17.8% completed the study. The resection rate of liver metastases after neoadjuvant therapy was 42.2%. The median time to disease progression was 10.1 and 8.7 months in the resected and unresected groups, respectively (P = 0.1341). Response rate was significantly higher in the resected (47.4%) versus the unresected group (34.6%; P = 0.0010), and seven patients achieved complete response (resected group). Overall, 94.3% of adverse events were of mild or moderate severity, and grade ≥3 adverse events occurred in 4.3% and 7.3% of patients in the resected and unresected groups, respectively. The most common adverse events in both groups were palmar-plantar erythrodysesthesia syndrome, decreased appetite, thrombocytopenia, peripheral neuropathy, fatigue, diarrhea, vomiting, proteinuria and nausea. CONCLUSION: Neoadjuvant therapy with bevacizumab plus XELOX was well tolerated and effective in previously untreated metastatic colorectal cancer patients with initially unresectable liver metastases.

Surgically curable non-iron deficiency microcytic anemia: Castleman's disease.

BACKGROUND: Castleman's disease (CD) is a rare, benign lymphoproliferative disorder that can involve single lymph node stations or can be systemic. Unicentric CD in patients with microcytic anemia is rarely described in the English literature. CASE REPORT: We describe the case of a 19-year-old Chinese woman with hyaline vascular type of unicentric CD presenting as severe non-iron deficiency microcytic anemia. We report the clinical course from the initial presentation to diagnosis and surgical cure, and discuss the most up-to-date information on CD. CONCLUSIONS: CD should be included in the differential diagnosis of microcytic anemia. Imaging tools and pathological studies should be considered in order to make a more accurate diagnosis and to avoid the use of ineffective treatments.

Clinical experience in 89 consecutive cases of chronic radiation enterocolitis.

BACKGROUND: Pelvic irradiation has been a popular therapy modality for cervical cancer for many years, and its usage in rectal cancer and prostate cancer cases is on the rise. However, it is associated with significant side effects. In this study, we compared the different characteristics of surgical and nonsurgical patients who were treated for radiation enterocolitis, the treatment results, posttreatment quality of life (QOL), nutrition status, and predisposing factors for surgery. METHODS: From 1985 to 2009, the records of a total of 89 patients with chronic radiation enterocolitis in our hospital were retrospectively reviewed for demographic data, operative data and long-term treatment results. Posttreatment QOL and nutrition status were also recorded. Univariate and multivariate analyses were performed to identify the independent predicting factors associated with surgical intervention. Characteristics of surgical and nonsurgical patients were compared. RESULTS: Radiotherapy before 1995, concomitant radiation uropathy and smoking were independent predictive factors for surgery. Surgical and nonsurgical cases had similar Kaplan-Meier curves. Although the recurrence rate of radiation enterocolitis was much higher for the surgical group (p = 0.031), both groups had similar QOL score (median: 8 vs.7; p = 0.709), serum albumin level (3.29 g/dL vs. 3.16 g/dL; p = 0.095), and body mass index (20.19 vs. 19.86; p = 0.603). CONCLUSIONS: We confirmed that as compared with recently developed innovative techniques, early primitive radiotherapy techniques were associated with more severe radiotherapy complications that required surgery. Smoking may enhance patients' vulnerability to severe radiation injury. Surgery for radiation-induced intestinal obstruction, intestinal fistula and perforation is warranted because QOL, serum albumin level and body mass index were similar between the surgical and nonsurgical groups.

Recurrence of radiation enterocolitis within 1 year is predictive of 5-year mortality in surgical cases of radiation enterocolitis: our 18-year experience in a single center.

BACKGROUND: Pelvic irradiation is commonly used in the treatment of pelvic malignancies. Chronic radiation enterocolitis is the most serious complication resulting from such treatment, and it frequently requires surgery. The prognosis for patients after surgery remains ill-defined. We conducted a retrospective study to identify risk factors associated with mortality for patients who received surgery for chronic radiation enterocolitis. METHODS: From 1985 to 2009, a total of 89 patients were diagnosed as having chronic radiation enterocolitis in Taichung Veterans General Hospital. The chart records of 35 surgical and 54 nonsurgical patients were reviewed. A total of 21 candidate risk factors were selected from (1) those related to rapid disease progression (recurrence within 1 year, reoperation within 1 year, short latency), (2) those mentioned in published series (diabetes mellitus, history of smoking, history of abdominopelvic surgery), and (3) other risk factors that might adversely affect outcomes (older age, higher radiation dosage, longer latency period). Factors with p < 0.1 in univariate analysis were subjected to multivariate analysis to identify those that were independent risk factors. RESULTS: Surgical patients were significantly older (65.09 vs. 61.61 years, p = 0.011), had a longer latency period (17.08 vs. 8.09 months, p = 0.037), and were associated with a higher percentage of radiation uropathy (54.28 vs. 12.96%, p < 0.0001) than nonsurgical patients. There was no difference in radiation dosage between surgical and nonsurgical cases (p = 0.152). Recurrence of radiation enterocolitis within 1 year following surgery (p = 0.022), older age (p = 0.002), and uncured cancer (p = 0.001) were identified as independent risk factors for poor overall survival after surgery. All patients (100%) who had recurrent radiation enterocolitis within 1 year of surgery died within 5 years of recurrence. CONCLUSIONS: The surgical cases were older, had a longer latency period, and had a higher percentage of radiation uropathy .Recurrence of radiation enterocolitis within 1 year after surgery, older age, and uncured cancer were independent risk factors associated with mortality for patients who received surgery for chronic radiation enterocolitis.

Neoadjuvant concurrent chemoradiotherapy in treating locally advanced rectal cancer.

BACKGROUND: Colorectal cancer is a common cancer and a major cause of morbidity and mortality worldwide. Middle to lower rectal cancer, a challenge for surgeons, is problematic. Neoadjuvant concurrent chemoradiotherapy (CCRT), introduced in the last decade, leads the local control of advanced rectal cancer to a high percentage of R0 resection (margin negative under microscopic examination) and a low recurrence rate. METHODS: From January 2005 to June 2007, 46 patients with locally advanced rectal cancer who received neoadjuvant CCRT were included. Factors including disease-free survival time, overall survival time, local recurrence, metastasis, and postoperative complications were evaluated retrospectively. Response was defined according to Mandard's classification, in which TRG1 is no residual tumor and TRG2-3 is 50-100% tumor shrinkage. RESULTS: In this series, 3 patients who did not receive post-CCRT curative resection were excluded. The remaining 43 patients (22 males, 21 females) had received curative surgery and were included. Thirty-four patients had tumor shrinkage, and the response rate was 79% (Mandard's classification: TRG1-TRG3). The median follow-up time was longer than 1.5 years. Patients who responded to CCRT had lower local recurrence rates (5.9% vs. 55.6%; p = 0.002) and a greater curative resection rate (97.1% vs. 66.7%; p = 0.024). The complication rates of both groups were similar. CONCLUSION: Neoadjuvant CCRT gives locally advanced rectal cancer patients a more favorable result, with acceptable toxicity.

Local recurrence after laparoscopic resection of T3 rectal cancer without preoperative chemoradiation and a risk group analysis: an Asian collaborative study.

Risk factors for local recurrence and indication for preoperative radiation therapy have not been well evaluated for patients undergoing laparoscopic rectal cancer operation. From 1998 to 2004, 497 T3 rectal cancer patients with tumor located within 12 cm from the anal verge who had undergone laparoscopic surgery without preoperative radiation therapy by eight experienced laparoscopic surgeons in four Asian countries were reviewed retrospectively for the incidence of local recurrence and related factors. The median follow-up was 29.0 months (range, 6.0 to 92.3), and 31 cases of local recurrence were observed during the follow-up period (6 anastomosis site, 6 perineum, 17 pelvic wall, and 2 unclassified). The estimated local recurrence rates at 24 and 60 months were 5.42 and 9.41%, respectively. Patient's gender, tumor location, lymph node metastasis, and tumor perforation were independent factors for local recurrence by multivariate analysis. The local recurrence rate was comparable to previous studies using conventional open surgery with preoperative chemoradiation, except for a subgroup of male patients with the tumor located within 7 cm from the anal verge. The indication for preoperative radiation therapy would be different from those who will undergo conventional open surgery, and further evaluation of the benefits of preoperative radiation therapy is required for those with low risk tumor.

Laparoscopic coloanal anastomosis for low rectal cancer.

OBJECTIVES: Low anterior resection with hand-sutured coloanal anastomosis for low rectal cancer is technically feasible, and it does not compromise oncologic results. We describe herein the effectiveness of the operation in treating low rectal cancer by a laparoscopic approach followed by intraanal canal dissection. METHODS: From February 1999 to October 1999, we used a laparoscopic procedure to divide the inferior mesenteric vessels and to dissect downward into the pelvic cavity as low as possible. A purse-string suture 1-cm distal to the lower margin of the tumor was secured and transection of the rectum was performed circumferentially via the anal canal near the dentate line. The specimen was removed by the pull-through method and coloanal anastomosis was completed with hand suture. A protective loop ileostomy was fashioned. RESULTS: We operated on 8 patients (4 males) with low tumor localization (average 4-cm above the dentate line). The age ranged from 45 to 83 years, with a median age of 64. The average operation time was 210 minutes (150 to 360 minutes), and the average blood loss was 250 cc (minimal to 750 cc). No operative mortalities occurred, but 2 patients had minor anastomotic slough complications. The average hospital stay was 13 days (7 to 26 days). The postoperative pathologic stage was T2N0M0 in 4 patients, T3N0M0 in 2 patients, T2N1M0 in 1 patient, and T3N2M0 in 1 patient. No local recurrence or distant metastasis occurred during the median 14 months (12 to 20 months) of follow-up. CONCLUSION: Laparoscopic coloanal anastomosis combined with intraanal canal dissection is safe and technically feasible. The oncologic results seem not to be compromised, but need further evaluation.

Laparoscopic-assisted operation for familial adenomatous polyposis patients-two case reports.

OBJECTIVE: We describe herein the results of 2 laparoscopic operations to treat patients with familial adenomatous polyposis (FAP). METHODS: Two female FAP patients, aged 32 and 29 years old, were treated with restorative proctocolectomy and total colectomy with ileorectal anastomosis (hand-assisted laparoscopic surgery), respectively. RESULTS: The operative time was 360 minutes for the restorative proctocolectomy and 150 minutes for the total colectomy with ileorectal anastomosis. The blood loss was 500 cc for the restorative proctocolectomy and minimal for the total colectomy patient. The return of bowel movements took 3 days for each patient, and no complication occurred. Patients were discharged on the 15th and 7th postoperative days. CONCLUSION: A laparoscopic approach for restorative proctocolectomy or total colectomy with ileorectal anastomosis is safe and technically feasible, and provides good cosmesis.