Survival outcomes of patients with stage III colorectal cancer aged ≥ 80 years who underwent curative resection: the HiSCO-04 prospective cohort study.

BACKGROUND: The efficacy of adjuvant chemotherapy in elderly patients aged ≥ 80 years with stage III colorectal cancer remains unclear. In parallel with a multicenter prospective phase II trial evaluating the efficacy of uracil-tegafur and leucovorin as adjuvant chemotherapy (HiSCO-03), we conducted a prospective observational study of these patients to assess survival outcomes, including those ineligible for chemotherapy. METHODS: This multi-institutional prospective cohort study included 17 institutions in Hiroshima, Japan. Patients aged ≥ 80 years with stage III colorectal cancer who underwent curative resection were enrolled. The primary endpoint was 3-year disease-free survival, and the secondary endpoints were 3-year overall and relapse-free survival. Propensity score matching was used to assess the effects of adjuvant chemotherapy on survival outcomes. RESULTS: A total of 214 patients were analyzed between 2013 and 2018, including 99 males and 115 females with a median age of 84 years (range 80-101 years). Recurrence occurred in 58 patients and secondary cancers were observed in 17. The 3-year disease-free, overall, and relapse-free survival rates were 63.3%, 76.9%, and 62.9%, respectively. Adjuvant chemotherapy was administered to 65 patients with a completion rate of 52%. In a study of 80 patients that adjusted for background factors using propensity score matching, patients who completed the planned treatment showed improved disease-free survival (3-year disease-free survival: completed, 80.0%; not received, 65.5%; and discontinued, 56.3%; p = 0.029). CONCLUSIONS: Completion of adjuvant chemotherapy may improve the prognosis of patients with colorectal cancer aged ≥ 80 years, although the number of patients who would benefit from it is limited.

Association between social background and implementation of postoperative adjuvant chemotherapy for older patients undergoing curative resection of colorectal cancers, sub-analysis of the HiSCO-04 study.

PURPOSE: Adjuvant chemotherapy is recommended following colorectal cancer resection based on risk of recurrence. In older patients, treatment decisions should consider recurrence rates and tolerability, as well as functional prognosis, residual disease, and social factors. This study aims to investigate factors, including social background, influencing implementation of postoperative adjuvant chemotherapy in older patients undergoing curative resection for colorectal cancer. METHODS: This multi-institutional prospective cohort study included 15 institutions belonging to the Hiroshima Surgical study group for Clinical Oncology. We analyzed 159 older patients aged ≥ 80 years, who underwent curative resection for stage III colorectal cancer between December 2013 and June 2018, as sub-analysis of the HiSCO-04 study. RESULTS: In total, 62 (39.0%) patients underwent postoperative adjuvant chemotherapy. Four factors were significantly associated with its implementation: performance status < 2, Charlson Comorbidity Index < 2, prognostic nutritional index ≥ 40, and presence of a spouse or siblings as lifestyle supporters. No significant difference was found in the backgrounds between complete and incomplete postoperative adjuvant chemotherapy patients. CONCLUSION: Performance status, Charlson Comorbidity Index, nutritional status, and presence of a spouse or siblings as lifestyle supporters are possible factors influencing the implementation of postoperative adjuvant chemotherapy in older patients. To select appropriate treatment options, including postoperative adjuvant chemotherapy, it is essential to consider physical condition and comorbidities of older patients, thoroughly explain the situation to their families, and establish a support system to enhance understanding of the available treatment options.

Predictive factors associated with anastomotic leakage after resection of rectal cancer: a multicenter study with the Hiroshima Surgical study group of Clinical Oncology.

PURPOSE: Several factors have been reported as risk factors for anastomotic leakage after resection of rectal cancer. This study aimed to evaluate the risk factors for anastomotic leakage, including nutritional and immunological indices, following rectal cancer resection. METHODS: This study used a multicenter database of 803 patients from the Hiroshima Surgical study group of Clinical Oncology who underwent rectal resection with stapled anastomosis for rectal cancer between October 2016 and April 2020. RESULTS: In total, 64 patients (8.0%) developed postoperative anastomotic leakage. Five factors were significantly associated with the development of anastomotic leakage after rectal cancer resection with stapled anastomosis: male sex, diabetes mellitus, C-reactive protein/albumin ratio ≥ 0.07, prognostic nutritional index < 40, and low anastomosis under peritoneal reflection. The incidence of anastomotic leakage was correlated with the number of risk factors. The novel predictive formula based on odds ratios in the multivariate analysis was useful for identifying patients at high risk for anastomotic leakage. Diverting ileostomy reduced the ratio of anastomotic leakage ≥ grade III after rectal cancer resection. CONCLUSIONS: Male sex, diabetes mellitus, C-reactive protein/albumin ratio ≥ 0.07, prognostic nutritional index < 40, and low anastomosis under peritoneal reflection are possible risk factors for developing anastomotic leakage after rectal cancer resection with the stapled anastomosis. Patients at high risk of anastomotic leakage should be assessed for the potential benefits of diverting stoma.

A prospective feasibility study of uracil-tegafur and leucovorin as adjuvant chemotherapy for patients aged ≥ 80 years after curative resection of colorectal cancer, the HiSCO-03 study.

PURPOSE: There is no consensus on the safety and effectiveness of adjuvant chemotherapy for patients with stage III colorectal cancer (CRC) aged ≥ 80 years. We conducted a prospective multi-institutional phase II study of uracil-tegafur and leucovorin (UFT/LV) as adjuvant chemotherapy in this population. PATIENTS AND METHODS: Patients with stage III CRC aged ≥ 80 years who underwent curative resection were enrolled. Eligible patients received UFT/LV therapy (UFT, 300 mg/m2 per day as tegafur; LV, 75 mg/day on days 1-28, every 35 days for five courses). Primary endpoint was feasibility, and secondary endpoints were safety and relative dose intensity. RESULTS: Sixty-nine patients were enrolled between 2013 and 2021. Of the 69 patients, 65 were included in the analysis. There were 32 males and 33 females with a median age of 82 years (range 80-88 years). In the primary endpoint, administration completion rate was 67.3% (95% confidence interval 54.9-77.6%), and the lower limit of the 95% confidence interval was below the threshold of 60%. 21 patients discontinued treatment because of adverse events (AEs) and refused treatment. The median relative dose intensities were 84% (range 4-100%) for UFT, and 100% (range 4-100%) for LV. Incidence of grade three or higher AEs were neutropenia (1.5%), aspartate transaminase elevation (3%), alanine transaminase elevation (1.5%), oral mucositis (3%), anemia (1.5%), and diarrhea (4.6%). CONCLUSIONS: The indications for adjuvant UFT/LV therapy for elderly CRC aged ≥ 80 years were considered limited. It is necessary to clarify the background of patients in whom drug administration is discontinued and investigate their impact on long-term prognosis.

Primary Small Intestinal Sarcomatoid Carcinoma: Report of a Rare Case and Literature Review.

Sarcomatoid carcinoma (SC) is a rare malignant tumor with properties of both epithelial and mesenchymal carcinomas. SC has been reported in various organs, but the number of reports for each type is small. Small intestinal tumors make up about 3-6% of gastrointestinal malignancies. Discovering them in the early stage is rare and difficult, with anemia and/or abdominal pain as the major symptoms of small intestinal tumors. Primary small intestinal SC (SISC) is rare among small intestinal tumors, and currently very few cases have been reported in the literature. Previous studies have reported that neither chemotherapy nor radiotherapy improves the overall survival rate of patients with SISC, and the prognosis is extremely poor. Currently, surgical resection remains the only optimal therapeutic approach for SISC. Here, we present the case of a 90-year-old woman who had acute peritonitis due to perforation of a small intestinal tumor. She underwent emergency exploratory laparotomy and partial resection of the small intestine, including the tumor. The tumor was pathologically identified as a primary SISC with mesenteric lymph node metastasis. Subsequently, she had recurrence in the intra-abdominal area and lymph node metastasis anterior to the inferior vena cava and died 15 months after surgery without any additional treatment.

Hemobilia after laparoscopic cholecystectomy that was successfully treated conservatively: Case report.

INTRODUCTION: Hemobilia due to pseudoaneurysm rupture is a rare, life-threatening complication of laparoscopic cholecystectomy (LC) that can cause rapid hemodynamic instability. Therefore, symptoms of hemobilia must be assessed carefully. PRESENTATION OF CASE: An 88-year-old woman underwent LC in our hospital, and blood tests revealed elevation of hepatobiliary enzyme levels on postoperative day (POD) 12. Computed tomography (CT) showed a high absorption area in the common bile duct (CBD), and a diagnosis of hemobilia and a pseudoaneurysm without active bleeding into the abdominal cavity was made. There was no leakage of contrast medium outside the CBD during endoscopic retrograde cholangiography; thus, an endoscopic nasobiliary drainage (ENBD) tube was inserted on POD 12 and an endoscopic retrograde biliary drainage (ERBD) stent was placed in the CBD on POD 13. Thereafter, hepatobiliary enzyme levels gradually normalized and the ENBD tube and ERBD stent were removed on POD 27 and POD 54, respectively. The patient was discharged on POD 66. DISCUSSION: Hemostasis establishment using surgery or intervention radiology is often required for the treatment of hemobilia due to pseudoaneurysms; however, conservative treatment was effective in our case and we were able to pursue a minimally invasive approach. Erosion due to clip penetration or incomplete clipping of the cystic artery or its branches during surgery may have caused the cystic artery pseudoaneurysm. CONCLUSION: Hemobilia could be life threatening and cause acute hemodynamic instability; therefore, prompt diagnosis is required. Although the frequency of complication is low, the possibility of hemobilia after LC should be considered.

A Case of Peritoneal Dissemination and Splenic Metastasis after Gastric Cancer Surgery That Could Be Controlled with Multidisciplinary Treatment.

Splenic metastasis is known to occur at the terminal stage of cancer. While peritoneal dissemination is the most frequent recurrence of gastric cancer, metastasis to the spleen from gastric cancer is very rare. Splenectomy is currently the most effective probable treatment for solitary splenic metastasis of gastric cancer; it provides a good patient prognosis. However, careful consideration of surgical indications is required, as splenic metastasis is typically accompanied by multi-organ metastasis and dissemination. One of the main cancer treatment methods is the "wait-and-see" approach using chemotherapy. In general, patients with gastric cancer are treated with systemic chemotherapy for distant metastases including peritoneal dissemination. Radiotherapy is not commonly used to prolong life in patients with gastric cancer as gastric cancer is predominantly adenocarcinoma. However, a recent report indicated that chemo-radiotherapy was performed successfully for unresectable gastric cancer, including peritoneal dissemination. Here, we present the case of a 67-year-old patient who was observed to have peritoneal dissemination and splenic metastasis after gastric cancer surgery. Once the peritoneal dissemination was localized, surgical excision and chemo-radiotherapy were performed. We treated the splenic metastasis with the "wait-and-see" strategy with chemotherapy. A complete response on imaging in accordance with the Response Evaluation Criteria in Solid Tumors was achieved using multidisciplinary treatment. Our strategy of intensive multidisciplinary therapy could be a treatment option for cases with peritoneal dissemination or splenic metastasis of gastric cancer.

Drug-Induced Interstitial Pneumonia due to Application of FOLFOX as Adjuvant Chemotherapy after Rectal Cancer Surgery: A Case Report and Literature Review.

The regimen of oxaliplatin with 5-fluorouracil plus l-leucovorin (FOLFOX) has become one of the most commonly used first-line chemotherapy for patients with advanced colorectal cancer and it provides an increase in disease-free survival as well as an overall survival benefit. Although FOLFOX chemotherapy has helped to improve the clinical outcomes in these patients, the regimen is associated with some therapeutic issues or uncontrolled side effects. Gastrointestinal, neurosensory, and hematological toxicities have frequently been observed in patients treated with FOLFOX, and consequently, some palliative treatment has been established to combat such complications. However, pulmonary toxicities including drug-induced interstitial pneumonia (DI-IP) is rarely observed in these patients and a curative treatment is yet to be established. DI-IP due to chemotherapy is most commonly observed in patients treated with mitomycin, paclitaxel, docetaxel, or gemcitabine. Steroid therapy is mostly used to treat DI-IP, although the efficacy of such treatments is not supported with adequate evidence. FOLFOX-induced interstitial pneumonia (FIIP) is rarely observed, and several case reports of FIIP treated with steroids have been published previously that showed the mortality is extremely high. Here, we present a 74-year-old woman who received modified FOLFOX6 as adjuvant chemotherapy after rectal cancer surgery. The patient experienced FIIP, which improved after application of steroid pulse (high-dose methylprednisolone at 1,000 mg/day for 3 days) and tapering (starting with prednisolone at 40 mg/day) therapy. Our data suggest that such a steroid therapy could represent an effective treatment option for FIIP.

A Rare Case of Gastric Schwannoma: A Case Report and Literature Review.

In general, schwannoma is a benign and slow-glowing neoplasm that rarely occurs in the gastrointestinal tract as a submucosal tumor (SMT), with the most common site being the stomach. As gastric schwannoma (GS) is a rare tumor, there is limited data in the literature about its clinical features. The diagnosis of schwannoma can only be made by pathological examination with positive staining for S-100 protein. It is necessary to obtain an accurate diagnosis to introduce optimal treatment options preoperatively. However, a precise diagnosis of GS is difficult, even with modern imaging techniques. On the other hand, a complete resection with a negative surgical margin (R0) of GS is considered the best treatment, with an excellent prognosis. We present a case of a 66-year-old female patient who underwent laparoscopic-assisted wedge gastrectomy for gastric SMT, pathologically diagnosed as GS, with positive staining for S-100 protein and negative for c-kit and CD34. At 12-month follow-up after surgery, there was no recurrence or metastasis of GS. Our treatment is appropriate and effective in case of GS exceeding 50 mm.

Rare Cases of Low-Grade Appendiceal Mucinous Neoplasm: Two Case Reports and a Literature Review.

Appendiceal mucocele (AM) is rare disease found in <1% of all appendectomy specimens. AM is often misdiagnosed as appendicitis because the most frequent symptom is right lower quadrant abdominal pain. AM should be considered in the differential diagnosis of abdominal pain. Although there are pathological classifications, surgical resection is accepted as the treatment to prevent the development of peritoneal pseudomyxoma (PP); however, the optimal surgical technique that must be used is unclear. We present two cases suspected of being AM prior to surgery that were pathologically diagnosed as low-grade appendiceal mucinous neoplasms. Each case progressed without developing PP. The surgical procedures we chose are considered appropriate for each case.

Complete Response to Chemotherapy against the Recurrence of Neuroendocrine Carcinoma of the Breast in the Anterior Mediastinal Lymph Nodes of a Patient on Hemodialysis: A Case Report.

In general, the cancer-bearing rate of patients on dialysis is considered to be higher than that of healthy individuals. There is no established chemotherapy regimen for patients on hemodialysis (HD), but some reports have described chemotherapy administration in such patients according to HD conditions, residual renal function, and the drug metabolic pathway. We present a case involving a 76-year-old female patient on HD who underwent chemotherapy for mediastinal lymph node recurrence of neuroendocrine carcinoma of the breast (NECB) using 5-fluorouracil, epirubicin, and cyclophosphamide (FEC 100) and docetaxel (DTX). The patient showed a complete response to the treatment and survived longer than expected. This is the first report demonstrating a complete response to chemotherapy for the recurrence of primary NECB with the patient having survived for a long time after treatment.

A multi-institutional feasibility study of S-1/oxaliplatin plus bevacizumab in patients with advanced/metastatic colorectal cancer: the HiSCO-02 prospective phase II study.

PURPOSE: FOLFOX is a standard combination chemotherapy regimen for metastatic colorectal cancer (CRC). 5-Fluorouracil (5-FU) is infused continuously through a pump for 46 h; therefore, replacement of infused 5-FU with oral S-1 would be more convenient for patients. We investigated the efficacy and safety of S-1/oxaliplatin (SOX) plus bevacizumab regimen in a community setting. METHODS: We conducted a phase II clinical study in Hiroshima, Japan. We enrolled individuals aged 20-80 years who had metastatic CRC, an Eastern Cooperative Oncology Group performance status of 0 or 1, assessable lesions, and not received previous chemotherapy. Eligible patients were administered SOX plus bevacizumab (S-1 80 mg/m2/day, day 1-14 orally; and oxaliplatin 130 mg/m2 day 1 i.v., bevacizumab 7.5 mg/kg, day 1 i.v. q3w). The primary endpoint was response rate (RR), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Between May 2011 and January 2014, 55 patients (mean age 64 years) were enrolled at 12 institutions. Median follow up duration was 20.2 months (range 1.3-47.1 months). RR was 47.1 % [95 % confidence interval (CI) 33.7-60.6 %]. Median PFS and OS was 9.2 months (95 % CI 7.6-10.8) and 22.5 months (95 % CI 19.4-25.9), respectively. Major adverse events (grade 3/4) were neutropenia (9.3 %), thrombocytopenia (5.6 %), anorexia (18.5 %), and sensory neuropathy (16.7 %). CONCLUSION: These data suggested that SOX plus bevacizumab is effective and capable of being managed in metastatic CRC patients in our community clinical practice.

Frequent alterations in the Wnt signaling pathway in colorectal cancer with microsatellite instability.

It is generally accepted that both dysfunction of the Wnt signaling pathway, including mutations in the adenomatous polyposis coli (APC) and beta-catenin genes, and genetic instability play important roles in colorectal carcinogenesis. However, alteration of the components in the Wnt signaling pathway in colorectal cancer (CRC) with microsatellite instability (MSI) has not been elucidated. In order to assess the status of the Wnt signaling components in CRC with MSI, mutational analyses of the beta-catenin, APC, Axin 1, and T cell factor 4 (TCF4) genes were performed. Three of 33 samples had mutations in exon 3 of the beta-catenin gene and two in the APC gene. Eight mutations in seven samples were detected by single-strand conformation polymorphism and subsequent direct sequence analysis of the entire coding region of the Axin 1 gene. Furthermore, TCF4, which is one of the transcriptional factors in the Wnt signaling pathway and has a mononucleotide repeat sequence (a nine- adenine repeat, (A)9) in its C-terminal region, was mutated in 13 of the 33 samples. Thus, alteration in the Wnt signaling pathway is frequently observed in CRC with MSI, including hereditary nonpolyposis colorectal cancer, as well as in familial adenomatous polyposis and sporadic CRC without MSI.