Blood Perfusion Assessment by Indocyanine Green Fluorescence Imaging for Minimally Invasive Rectal Cancer Surgery (EssentiAL trial): A Randomized Clinical Trial.

OBJECTIVE: The aim of the present randomized controlled trial was to evaluate the superiority of indocyanine green fluorescence imaging (ICG-FI) in reducing the rate of anastomotic leakage in minimally invasive rectal cancer surgery. BACKGROUND: The role of ICG-FI in anastomotic leakage in minimally invasive rectal cancer surgery is controversial according to the published literature. METHODS: This randomized, open-label, phase 3, trial was performed at 41 hospitals in Japan. Patients with clinically stage 0-III rectal carcinoma less than 12 cm from the anal verge, scheduled for minimally invasive sphincter-preserving surgery were preoperatively randomly assigned to receive a blood flow evaluation by ICG-FI (ICG+ group) or no blood flow evaluation by ICG-FI (ICG- group). The primary endpoint was the anastomotic leakage rate (grade A+B+C, expected reduction rate of 6%) analyzed in the modified intention-to-treat population. RESULTS: Between December 2018 and February 2021, a total of 850 patients were enrolled and randomized. After the exclusion of 11 patients, 839 were subject to the modified intention-to-treat population (422 in the ICG+ group and 417 in the ICG- group). The rate of anastomotic leakage (grade A+B+C) was significantly lower in the ICG+ group (7.6%) than in the ICG- group (11.8%) (relative risk, 0.645; 95% confidence interval 0.422-0.987; P =0.041). The rate of anastomotic leakage (grade B+C) was 4.7% in the ICG+ group and 8.2% in the ICG- group ( P =0.044), and the respective reoperation rates were 0.5% and 2.4% ( P =0.021). CONCLUSIONS: Although the actual reduction rate of anastomotic leakage in the ICG+ group was lower than the expected reduction rate and ICG-FI was not superior to white light, ICG-FI significantly reduced the anastomotic leakage rate by 4.2%.

Impact of early tumor shrinkage on quality of life in patients treated with first-line cetuximab plus chemotherapy for unresectable metastatic colorectal cancer: results of Phase II QUACK trial.

PURPOSE: Although early tumor shrinkage (ETS) is a predictor of improved overall survival (OS), the association between ETS and health-related quality of life (HRQOL) remains unclear for patients with metastatic colorectal cancer (mCRC) treated with first-line cetuximab plus chemotherapy. METHODS: The data were collected from a prospective trial that assessed HRQOL using the EORTC QLQ-C30. The impact of ETS on HRQOL was estimated using a linear mixed-effects model for repeated measures. RESULTS: ETS was achieved in 82 (64.1%) of 128 mCRC patients treated with first-line cetuximab plus chemotherapy, and these patients had a significantly longer OS than those without ETS (HR, 0.38; 95% CI, 0.20-0.72; P = .002). Asymptomatic patients with ETS had a favorable OS, while symptomatic patients without ETS had a worse OS (2-year OS rates, 77.8% vs. 42.5%). Symptomatic patients with ETS had similar outcomes as asymptomatic patients without ETS (2-year OS rates, 64.1% vs. 67.0%). For symptomatic patients, ETS was associated with improved HRQOL scores between baseline and 8 weeks: the mean changes for patients with and without ETS were 5.86 and -4.94 for global health status (GHS)/QOL, 26.73 and 3.79 for physical functioning, and 13.58 and -3.10 for social functioning, respectively. The improved HRQOL was comparable to that of asymptomatic patients without ETS. For asymptomatic patients, ETS showed a decreased deterioration in HRQOL. CONCLUSION: Our findings highlight the importance of ETS for HRQOL and prognostic estimates, and assessing ETS may provide clinically useful information for physicians and patients to make more informed decisions.

Disagreement between patient- and physician-reported outcomes on symptomatic adverse events as poor prognosis in patients treated with first-line cetuximab plus chemotherapy for unresectable metastatic colorectal cancer: Results of Phase II QUACK trial.

The status and prognostic value of the disagreement between physician and patient assessments of symptomatic adverse events (AEs) remain unclear for patients with metastatic colorectal cancer treated with first-line cetuximab plus chemotherapy. Paired data on patient-reported outcomes using the EORTC QLQ-C30 and physician-reported outcomes using the NCI-CTCAE for eight symptomatic AEs (fatigue, pain, insomnia, dyspnea, constipation, appetite loss, nausea/vomiting, and diarrhea) were collected from a prospective trial assessing the relationships between treatment efficacy, AEs, and quality of life. The overall agreement rates between patient and physician reporting at 4 weeks ranged from 40.2% to 76.5% for 129 patients. The level of agreement based on Cohen's κ statistics was slight to poor for dyspnea, pain, fatigue, and insomnia, while it was moderate to fair for the remaining AEs. No clinicopathological characteristics of disagreement were found. The underreporting by physicians ranged from 12.5% (nausea/vomiting) to 56.7% (fatigue). The 2-year overall survival (OS) rate was more favorable for patients with high agreement than for those with low agreement (71.2% vs. 46.5%, p = .016), and the agreement status was an independent factor of OS (HR, 2.31; 95% CI, 1.13-4.71; p = .022). For patients who were reported as asymptomatic by the physician, the presence of patient-reported symptoms resulted in a trend toward poor prognostic outcomes for appetite loss, dyspnea, diarrhea, and constipation. These findings provide the clinical importance of the monitoring of patient-reported symptoms that can be complementary to physician-reported data to ensure more accurate clinical outcomes.

Patient-reported symptom burden as a prognostic factor in treatment with first-line cetuximab plus chemotherapy for unresectable metastatic colorectal cancer: Results of Phase II QUACK trial.

BACKGROUND: It remains unclear whether patients' self-perceptions of symptoms at baseline clinically impact the prognostic relevance, treatment efficacy, or toxicity profiles in metastatic colorectal cancer (mCRC) patients treated with the first-line cetuximab and standard chemotherapy. METHODS: The data were collected from a prospective trial that assessed the relationships between quality of life (QOL), treatment efficacy, and adverse events (AEs). RESULTS: The analysis of 137 mCRC patients revealed a significant association between the presence of baseline tumor-related symptoms and a lower overall survival (OS) compared to the absence of symptoms (HR, 2.49; 95% CI, 1.37-4.62; P = .003). The asymptomatic responders had favorable outcomes compared to the symptomatic nonresponders (2-year OS rates: 83.6% and 35.9%, respectively), while the symptomatic responders had similar outcomes to the asymptomatic nonresponders. The median postprogression survival differed significantly: 10.2 months for the symptomatic patients and 15.9 months for the asymptomatic patients (HR, 2.29; 95% CI, 1.25-4.29, P = .008). The objective response rates and patient toxicity profiles were similar irrespective of the severity of baseline symptoms. CONCLUSION: Baseline symptoms were associated with worse OS but not with impaired treatment efficacy or more frequent AEs in mCRC patients treated with cetuximab in addition to chemotherapy.

Acute iliac arterial thrombosis during laparoscopic abdominoperineal resection.

BACKGROUND: Acute iliac arterial thrombosis during surgery is very rare complication. There were few reports on this complication relative to gastroenterological surgery, and the risk has not been recognized. CASE PRESENTATION: A 70-year-old man, diagnosed with a rectal cancer (adenocarcinoma of rectum) with known history heavy cigarette smoking with no known history of peripheral vascular disease underwent a laparoscopic abdominoperineal resection. He presented severe pain in the left leg in the recovery room. A computed tomography (CT) scan revealed the complete obstruction of the left common iliac artery. A successful revasculization was achieved through a thrombotectomy and percutaneous transluminal angioplasty with a stent immediately after the diagnosis. The pain in the left leg disappeared immediately after the revasculization. CONCLUSION: An acute arterial thrombosis is a potential complication of the laparoscopic colorectal surgery with the lithotomy position.

A prospective Phase II study to examine the relationship between quality of life and adverse events of first-line chemotherapy plus cetuximab in patients with KRAS wild-type unresectable metastatic colorectal cancer: QUACK trial.

A prospective trial has not been performed to investigate associations between quality of life (QOL), adverse events (AEs), and overall survival (OS) in the first-line treatment with cetuximab plus standard chemotherapy for advanced/metastatic colorectal cancer (mCRC). Associations between patient outcome and health-related QOL (HRQOL) together with skin toxicity-related QOL were prospectively evaluated using EORTC QLQ-C30 and DLQI questionnaires. One hundred and forty mCRC patients were analyzed in this study, and 87.8% received pre-emptive skin treatment. Skin toxicity had no clinical impact on HRQOL or skin-related QOL during the first 8 weeks and throughout the study period. An early skin reaction with a grade ≥2 at 8 weeks was significantly associated with a favorable OS compared with a grade of ≤1 (HR, 0.50; 95% CI, 0.24-0.95; P = .035) and was confirmed to be an independent predictor of OS (HR, 0.48; 95% CI, 0.21-0.97; P = .040). Patients symptomatic at baseline who responded to treatment had improved HRQOL compared to nonresponding patients. Severe mucositis/stomatitis had a statistically significant and clinically meaningful negative impact on HRQOL (mean changes from baseline throughout the study period in global health status were -12.64 for a grade of ≥2 vs -0.35 for a grade of 0 or 1 (P = .005)). In conclusion, severe early skin reactions predict favorable OS for patients treated with cetuximab plus chemotherapy without impairing QOL. In addition, mucositis/stomatitis was the most substantial AE compromising both QOL and treatment compliance.

Successful treatment of refractory chylothorax by pedicled omentoplasty.

A 52-year-old female with a history of past surgery for arteriovenous malformation of the thoracic spinal cord presented with left chylothorax. Lymphangiography identified diffuse lymphatic vessel (LV) growth with ectasia at the left supradiaphragmatic level. On the right side, the LVs were absent due to previous surgery. Given the ineffectiveness of conservative management, the patient required surgery. Thoracotomy showed extensive pleural fibrosis, lung atelectasis, and diffuse chyle defluxion on the parietal pleura. The diffuse chyle defluxion was not resolved by ligation. Therefore, we performed pedicled omentoplasty to fill the pleural space and to utilize its drainage and angiogenic capacity. Two years after the procedure, there was no sign of relapse. There are very few reports of refractory chylothorax successfully treated by pedicled omentoplasty. The procedure would be useful for the treatment of chylothorax when non-surgical or typical surgical management fails.

[A case report of bi-weekly docetaxel and S-1 combination chemotherapy for gastric cancer with carcinomatous lymphangitis of the lung].

A 38-year-old man with complaints of nausea, epigastralgia, cough, and decrease body weight was given a diagnosis of advanced gastric cancer (type 4) with carcinomatous lymphangitis of the lung (UM-circ cT3, N3, H0, P0, M1, stage IV, por2). He was treated with combination of docetaxel (DOC) 40 mg/m(2)/day (days 1, 15) and S-1 orally 80 mg/m(2)/day (days 1-7, 15-21), 1 week administered 1 week rest. After 2 courses of treatment, the patient achieved a partial response in the carcinomatous lymphangitis of the lung. Tumor markers decreased and symptoms improved. He experienced grade 2 peripheral neuropathy but with no grade 3 adverse events. Although the prognosis of gastric cancer with carcinomatous lymphangitis is poor. These results indicate that bi-weekly DOC and S-1 combination chemotherapy might be effective for gastric cancer with carcinomatous lymphangitis of the lung.

A case of neurofibroma of the appendix in von Recklinghausen disease.

A 67-year-old man with von Recklinghausen disease (VRD) was found to have an ill-defined large mass in the ileocecal area on abdominal computed tomography when he was examined for abdominal pain in the right lower quadrant. Because of high serum C-reactive protein level and leukocytosis appendiceal tumor complicated by appendicitis was diagnosed. Due to the possibility of malignancy, standard cancer surgery was carried out to remove the mass, i.e., ileocecal resection together with dissection of the regional lymph nodes. The cecum was displaced by a remarkably enlarged appendix with a firm and thickened wall. The distal portion of the appendix was cystically dilated, forming an abscess. The pathological diagnosis was neurofibromatosis with mucus hyperplasia and abscess formation in the appendix. Neurofibroma of the appendix is very rare, even in patients with VRD. Although it is benign, prompt resection is recommended because of a high risk of appendicitis and malignant transformation.

[A case report of bi-weekly docetaxel and S-1 combination chemotherapy for gastric cancer with multiple liver metastases and esophageal invasion].

A 61-year-old man with the chief complaint of pressure with swallowing was referred to our hospital with type 3 cardiac gastric cancer. Gastrofiberscope showed type 3 cardiac cancer with esophageal invasion. On the abdominal computed tomography, there was evidence of lymph node swelling in the lesser curvature and multiple liver metastases. Blood tumor markers were elevated: CEA 200 ng/mL, CA19-9 2,490 U/mL. He was diagnosed as unresectable advanced gastric cancer UE-circ, type-3, c-T3N2H1P0M1, Stage IV. A biopsy revealed adenocarcinoma (tub2-por1). We started bi-weekly docetaxel and S-1 combination chemotherapy(DOC 40 mg/m2 day 1, 14, S-180 mg/m2 day 1-7, 14-21). After completion of the first course of this combination therapy, his feeling of pressure was relieved and CT showed reduction of multiple liver lesions and lymph node metastases, indicating partial response. No regrowth was seen for 7 courses of the therapy. Regarding toxicity, grade 2 nausea and grade 1 nail pain were observed. After 7 courses, because of serum CEA elevation, bi-weekly CPT-11/CDDP therapy (CPT-11 60 mg/m2, CDDP 30 mg/m2) was administered followed by weekly PTX therapy (65 mg/m2 day 1, 7, 14; total of 4 weeks). To date, 17 months after administration of chemotherapy, he has been treated on an outpatient basis. Biweekly DOC/S-1 therapy can be novel antitumor therapy which can be conducted safely in an outpatient setting for advanced gastric cancer.