Impact of malnutrition on cancer recurrence, colorectal cancer-specific death, and non-colorectal cancer-related death in patients with colorectal cancer who underwent curative surgery.

AIM: This study aimed to examine how malnutrition, as reflected by the Geriatric Nutritional Risk Index (GNRI), is associated with colorectal cancer (CRC) recurrence and cause of death. METHODS: Consecutive stage I-III CRC patients (n = 601) were divided into two groups using GNRI 98 as the cutoff. The relationship of GNRI with overall survival (OS) and recurrence-free survival (RFS) was evaluated, followed by competing risk analysis to determine prognostic factors of non-CRC-related death, and hazard function analysis to examine changes in the risk of recurrence and death. RESULTS: Median body mass index was lower in the low GNRI group than in the high GNRI group (19.8 vs. 23.5; p < 0.001). After adjusting for known prognostic factors, a low GNRI was independently associated with reduced OS/RFS, and was a significant predictor of non-CRC-related death. The risk of recurrence was higher and peaked earlier in the low GNRI group than in the high GNRI group, although after 3 years, both groups had a similar risk. Meanwhile, the low GNRI group had a higher risk of non-CRC-related death over the course of 5 years. CONCLUSION: It is important to consider preoperative nutritional status along with the cancer stage when developing strategies to improve outcomes for CRC patients.

Level of Inferior Mesenteric Artery Ligation in Sigmoid Colon and Rectal Cancer Surgery: Analysis of Apical Lymph Node Metastasis and Recurrence.

INTRODUCTION: Whether high or low ligation of the inferior mesenteric artery (IMA) is optimal for treating sigmoid colon and rectal cancers is controversial. The present study aimed to compare outcomes of high and low ligation of the IMA and determine the adequate extent of IMA lymph node dissection. METHODS: Subjects were 455 consecutive stage I-III colorectal cancer patients who underwent curative surgery between 2011 and 2019. We assessed the association between the level of IMA ligation and overall survival and recurrence-free survival (RFS) by propensity score matching analysis. Clinicopathological features of IMA lymph node metastasis and recurrence patterns were analyzed. RESULTS: After propensity score matching, the low ligation group had a significantly worse prognosis than that of the high ligation group for RFS (p = 0.039). Positive IMA lymph nodes were associated with pathological T3 or T4 stage and N2 stage. IMA lymph node recurrences in the high ligation group occurred at the superior left side of the IMA root. In contrast, all recurrences in the low ligation group occurred at the left colic artery bifurcation. CONCLUSION: High ligation of IMA is oncologically safe. However, even with high ligation, care must be taken to ensure adequate lymph node dissection.

Impact of severe postoperative inflammatory response on recurrence after curative resection of colorectal cancer.

PURPOSE: The relationship between recurrence and systemic inflammation in the early postoperative period of colorectal cancer (CRC) is unclear, and no study has examined changes in recurrence risk resulting from postoperative inflammation. This study aimed to investigate the prognostic impact of severe postoperative inflammatory response after curative resection of CRC. METHODS: Subjects were 422 consecutive CRC patients who underwent curative surgery between 2012 and 2016, with a follow-up period of 5 years after surgery. The prognostic impacts of high and low postoperative C-reactive protein (CRP) levels were examined, and temporal changes in recurrence risk were examined using hazard function analysis. RESULTS: Patients were divided into high (n = 68) and low (n = 354) CRP groups using CRP 12.5 mg/dL as the cut-off based on receiver-operating characteristic (ROC) curve analysis. Multivariable analysis revealed that high CRP was a significant predictor of recurrence (hazard ratio: 2.21; p < 0.001). According to the hazard function of recurrence risk, the hazard rate of the low CRP group peaked at 8.4 months postoperatively (peak hazard rate: 0.0073/month) and decreased thereafter, while that of the high CRP group peaked at 5.6 months (0.0142/month) and was persistently higher than that of the low CRP group for the study duration. CONCLUSIONS: A severe inflammatory response in the early postoperative period of CRC increased the recurrence risk, and the recurrence hazard of patients with high CRP levels was earlier and persistently higher than that of patients with low CRP levels. CRC patients with high CRP levels may require more frequent follow-up.

Association of nutritional risk and systemic inflammation with survival in patients with colorectal cancer who underwent curative surgery.

BACKGROUND & AIMS: Malnutrition and inflammation adversely affect the prognosis of patients with cancer. The Geriatric Nutritional Risk Index (GNRI) and systemic inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), lymphocyte-to-C reactive protein ratio (LCR), and C-reactive protein-to-albumin ratio (CAR), predict survival in colorectal cancer (CRC) patients. The present study aimed to examine the association of these two factors with CRC survival. METHODS: Subjects were 433 consecutive CRC patients who underwent curative surgery between 2013 and 2018. Patients were stratified by nutritional status, and relationships between overall survival (OS) and systemic inflammation were evaluated. The prognostic impact of combinations of the GNRI and inflammatory markers was assessed. Multivariable analyses were also performed. RESULTS: All assessed biomarkers predicted OS in univariable analysis (GNRI:P < 0.001, NLR:P = 0.048, LMR:P = 0.001, LCR:P = 0.010, CAR: P = 0.039). Stratified analysis showed that each inflammatory marker had a prognostic impact on OS in the low GNRI group (NLR:P = 0.028, LMR:P = 0.003, LCR:P = 0.05, CAR:P = 0.009). In contrast, inflammatory markers had no prognostic impact on OS in the high GNRI group. The combination of malnutrition and systemic inflammation had a high prognostic value (all P < 0.016). The multivariable analysis revealed that a low GNRI (hazard ratio: 2.58-2.89) was independently associated with reduced survival, whereas none of the inflammatory markers independently predicted poor prognosis. CONCLUSIONS: The GNRI is a useful prognostic biomarker for CRC patients, whereas systemic inflammatory markers can only serve as prognostic factors when patient nutritional status is taken into account. The combination of malnutrition and systemic inflammation may enhance the accuracy of prognostic prediction.

[A Case of Neoadjuvant Chemotherapy with Modified FOLFOXIRI plus Bevacizumab for Transverse Colon Cancer with Invasion of the Gastric Antrum].

A 66-year-old male diagnosed with transverse colon cancer was admitted to our hospital. Computed tomography, colonoscopy, and esophagogastroduodenoscopy revealed locally advanced cancer with invasion of the gastric antrum. We staged the disease as cT4a, cN2, cM0, Stage ⅢB, with wild-type RAS expression. We performed an ileostomy prior to administering chemotherapy. The patient received 4 courses of modified FOLFOXIRI plus bevacizumab and 2 courses of FOLFIRI. The size of the tumor noticeably decreased after chemotherapy. The patient experienced grade 3 neutropenia, anorexia, and oral mucositis during chemotherapy. We performed a right hemicolectomy(D3), partial gastrectomy and ileum resection after administering neoadjuvant chemotherapy. The pathological stage of the disease was ypT2, ypN0, ypM0, ypStageⅠ, and the effect of the chemotherapy was Grade 1b. After the resection, he received mFOLFOX6 and CapeOX for 3 months as adjuvant chemotherapy. He remained cancer-free for 1 year and 3 months after the surgery. This result suggests that preoperative modified FOLFOXIRI plus bevacizumab chemotherapy is a useful regimen for the treatment of locally advanced colon cancer.

Laparoscopic excision of a retroperitoneal completely isolated enteric duplication cyst in an adult male: A case report and review of literature.

INTRODUCTION: Duplication cysts are very rare congenital malformations in adults. They are lined by gastrointestinal mucosa, connect to the digestive tract, and share smooth muscular layers and a common blood supply. In rare cases, duplication cysts are completely isolated from the digestive tract and have a proper blood supply. Completely isolated duplication cysts in the retroperitoneum are unusual so it is hard to diagnose them without a surgical resection. PRESENTATION OF CASE: A 19-year-old male presented at our emergency department with sharp abdominal pain. Contrast-enhanced computed tomography detected a 5-cm multilocular cystic mass located in the retroperitoneum, caudal to the pancreatic body. The cystic mass was safely resected with laparoscopic surgery without any complication. The final pathological diagnosis was an epithelium-lined duplication cyst in the retroperitoneal space. There was no evidence of malignancy in the duplication cyst. Intracystic bleeding was assumed to be the cause of the abdominal pain. DISCUSSION: The most common differential diagnoses of retroperitoneal cystic masses are pseudocysts related to pancreatitis, cysts from surrounding structures, and neoplasms. In this case, the cystic mass was diagnosed as completely isolated duplication cyst after surgical resection. It is very rarely observed in adults, but it should be listed on differential diagnoses because it has some possibility of malignancy. CONCLUSION: A completely isolated duplication cyst is very rare but noteworthy because there is some possibility of malignancy, ulcerative bleeding, and perforation. A surgical resection is recommended for diagnostic treatment. Laparoscopic surgery is favorable for intraoperative inspection and it is minimally invasive.

Updated recommendation on molecular-targeted therapy for metastatic renal cell cancer.

Molecular-targeted therapy was recommended for the systemic therapy of renal cell cancer (RCC) in the RCC guidelines, but these guidelines do not address the order of administration of the multiple presently available agents. There are several aspects that remain unknown regarding the optimal administration order and combination of molecular-targeted drugs. Until the optimal treatment sequence is determined by clinical trials, treatment individualization is required for each patient based on patient and disease characteristics. We herein investigate 12 cases of RCC patients who received axitinib. Axitinib was used as the first-line drug in 4 cases, second-line in 5 cases, third-line in 1 case and as a fourth-line drug in 2 cases. Partial response (PR) was observed in 4 cases (30%) and stable disease in 4 cases (30%) during axitinib treatment, with an overall response rate of 60%. The duration of PR ranged from 6 to 19 months. Based on our cases, axitinib exhibited reasonable therapeutic efficacy as first- as well as second-line treatment. However, more cases are required to draw firm conclusions.

Metastatic colorectal cancer responsive to regorafenib for 2 years: a case report.

BACKGROUND: Regorafenib is an oral multikinase inhibitor that has been demonstrated as clinically effective in patients with metastatic colorectal cancer in phase III studies. Although disease control was achieved in 40% of the pretreated patients with metastatic colorectal cancer in the pivotal studies, radiological response has rarely been reported. Severe adverse events associated with regorafenib are known to occur during the first and second courses of treatment. We present a case of a 62-year-old Japanese patient whose metastatic colorectal cancer has been responding to treatment with regorafenib for 2 years. CASE PRESENTATION: A 54-year-old Japanese man visited our institute exhibiting general malaise, and he was diagnosed with ascending colon cancer in April 2006. He underwent right hemicolectomy, and the final staging was T3N0M0, stage II. After 19 months, pulmonary metastasis and anastomotic recurrences were detected, and a series of operations were performed to resect both metastatic lesions. After that, liver metastasis, a duodenal metastasis with right renal invasion, right adrenal metastasis, and para-aortic lymph node metastases were observed during follow-up, and chemotherapy and resection were performed. The patient had metastatic para-aortic lymph nodes after the fifth tumor resection and underwent multiple lines of chemotherapy in April 2014. Regorafenib monotherapy was started at 80 mg/day. Then, regorafenib was increased to 120 mg/day in the second cycle. Regorafenib monotherapy led to 60% tumor shrinkage within the initial 2 months, and the tumor further decreased in size over 4 months until it became unrecognizable on imaging studies. The clinical effects of regorafenib monotherapy have shown a partial response according to Response Evaluation Criteria in Solid Tumors criteria. No severe adverse events were observed, except for mild fatigue and hand-foot syndrome. The patient has received 24 courses of regorafenib over 2 years without exhibiting tumor progression. CONCLUSIONS: To the best of our knowledge, this is the longest treatment with regorafenib without tumor progression ever reported. A reduced dosage of regorafenib at induction may ameliorate the cutaneous and hepatic toxicity associated with its use.

[Successful Administration of Regorafenib to a Metastatic Colon Cancer Patient with Impaired Performance Status by Reducing the Initial Dose].

A 59-year-old woman had recurrences in the spleen and lung 10 years after radical excision of cecal cancer. After 27 months of treatment with 5-fluorouracil/Leucovorin, oxaliplatin, irinotecan, bevacizumab, and anti-EGFR antibodies, multiple bone metastases and a left adrenal metastasis developed, and the patient's performance status (PS) deteriorated to grade 3. Regorafenib was administered at 80 mg/day. The pain and appetite improved within 2 courses, and her PS improved from grade 3 to 2. Regorafenib was increased to 120 mg/day for the 2nd course, and the patient was treated for 5 months without severe adverse effects. Regorafenib is considered to be a salvage-line treatment only for patients in relatively good condition, because full-dose regorafenib treatment often leads to severe adverse effects. Dose escalation of regorafenib from the low initial dose of 80 mg/day may be a safe and effective way of providing an opportunity of this chemotherapy to patients with impaired PS.

[Long-term progression-free survival after reduction surgery and postoperative low-dose imatinib administration for multiple liver metastases of duodenal gastrointestinal stromal tumor].

A fifty-six year-old woman visited our institute, suffering from lower abdominal pain. A tumor was palpable in the pelvic cavity, having the diameter of 9.7 cm, as measured by transvaginal ultrasonography (US). Computed tomography and magnetic resonance imaging (MRI) revealed a high contrast-enhancement and the central necrosis of the tumor. Surgical resection was performed, and the tumor was found to have originated in the duodenum. Immunohistochemistry confirmed positive KIT, and the mitotic index was 4 per 50 high power field, so that the final diagnosis was a gastrointestinal stromal tumor of intermediate risk. After two years of observation, multiple liver metastases were found. Hepatectomy was performed as a volume reduction surgery, leaving three small lesions in the remnant liver. Imatinib administration was initiated at 400 mg a day two weeks after the surgery, but was interrupted two weeks later because of severe anorexia and a body weight gain of 7 kg due to the increased ascites and edema. Imatinib was resumed at 200 mg/day after a one-month interval. She has been enjoying relapse-free survival for 8 years since the recurrence was diagnosed. Although neither reduction surgery nor dose reduction of imatinib below 300 mg/day is recommended, there may be a possibility that a smaller tumor might be controlled by a lower dose of imatinib.

[A case of pagetoid carcinoma of the breast in nearly complete response by primary systemic therapy].

A 62-year-old female presented with an erosion of the left nipple. At the preoperative examination, it was diagnosed as a Pagetoid carcinoma with an invasive carcinoma. After primary systemic therapy(weekly paclitaxel/trastuzumab), we performed an operation. The only remaining Paget cell was confirmed in the resected specimen, and no other malignant cells were confirmed. There is no report that the preoperative chemotherapy for the Pagetoid carcinoma with an invasive carcinoma. The patient has had no evidence of recurrence 1. 5 years after the operation.