Weekday Surgery Associated With Short-Term Outcomes in Patients With Colorectal Cancers.

INTRODUCTION: The "weekday effect" on elective surgery remains controversial. We aimed to examine the association between the day of surgery and short-term outcomes after elective surgery for stage I-III colorectal cancer (CRC). METHODS: We performed a multicenter retrospective analysis of 2574 patients who underwent primary colorectal resection for CRC between January 2017 and December 2019 at 15 institutions belonging to the Hiroshima Surgical Study Group of Clinical Oncology. Patients were divided into two groups according to the day of surgery: Friday and non-Friday (Monday to Thursday). After propensity score matching (PSM), we compared 30-day mortality and postoperative outcomes. RESULTS: Out of the total, 368 patients underwent surgery on Fridays, and the remaining 2206 underwent surgery on non-Fridays. The overall mortality rate was 0.04% (n = 1). In 1685 patients with colon cancer, the proportion of American Society of Anesthesiologists scores was significantly lower in the Friday group than in the non-Friday group before PSM. After PSM of patient, tumor, and operative characteristics, operative time was slightly more prolonged and blood loss was slightly greater in the Friday group; however, these differences were not clinically meaningful. In the 889 patients with rectal cancer, the proportion of patients with abnormal respiratory patterns was significantly lower in the Friday group than in the non-Friday group before PSM. After PSM, the Friday group had a higher incidence of morbidity (≥ Clavien-Dindo 3a), higher incidence of digestive complications, and prolonged postoperative hospital stay. CONCLUSIONS: The results may be useful in determining the day of the week for CRC surgery, which requires more advanced techniques and higher skills.

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.

Prediction of anastomotic leakage after left-sided colorectal cancer surgery: a pilot study utilizing quantitative near-infrared spectroscopy.

BACKGROUND: Anastomotic leakage (AL) occurs with some frequency in all types of colorectal cancer surgery and is associated with increased morbidity, mortality and recurrence rates. Complications might be prevented by monitoring intra-operative bowel perfusion at the anastomotic site. A pilot study concerning the objective and quantitative measurement of tissue perfusion by monitoring regional tissue saturation of oxygen (rSO2) was conducted, using the In Vivo Optical Spectroscopy (INVOS™) system (Medtronic, Minneapolis, MN, USA). METHODS: This study evaluated the ability of the INVOS™ system to predict AL after left-sided colorectal cancer surgery. rSO2 measurements of the oral side of the site of bowel anastomosis were taken before anastomosis in 73 patients. Clinical factors, including rSO2, were analyzed to identify risk factors for AL. RESULTS: Among 73 patients, 6 (8.2%) experienced AL. The rSO2 values of the oral anastomotic site were significantly lower in AL patients than in non-AL patients. In the multivariate analysis, the rSO2 value of the oral anastomotic site was an independent risk factor for AL. CONCLUSION: Monitoring the rSO2 at the anastomotic site enabled the prediction of AL. A prospective study to evaluate the efficacy of the INVOS™ system for monitoring intestinal rSO2 is in progress.

Tumor budding as a predictive marker for 5-fluorouracil response in adjuvant-treated stage III colorectal cancer.

BACKGROUND: Tumor budding (TB) has been described as an adverse prognostic marker for operable colorectal cancer (CRC); however, a limited number of studies have demonstrated the prognostic significance of TB in patients with drug therapy. This study was conducted to determine the predictive power of TB in stage III CRC patients who received adjuvant chemotherapy. METHODS: We retrospectively collected clinicopathological data including TB of 237 stage III colorectal cancer patients at Hiroshima University Hospital between July 1, 2006 and June 31, 2019. Differential disease-free survival (DFS) was investigated according to TB status. RESULTS: This study included 237 patients with a median age of 67 years, comprising patients who underwent surgery alone (n = 65), 5-fluorouracil (5-FU) monotherapy (n = 129), and oxaliplatin-based chemotherapy (n = 43). Overall, 81 patients developed disease recurrence, and 33 patients died of cancer-related causes. The TB status was categorized into two groups: 99 with low budding (< 5 buds) and 138 with high budding (≥ 5 buds). Overall, the low budding cases demonstrated significantly better DFS. In the 5-FU monotherapy group, low-risk patients (T1, T2, or T3 and N1) with low budding showed a remarkably higher 3-year DFS (91%) compared to high budding (55%). CONCLUSION: Our results indicate that TB could play a subsidiary role in selecting patients who could maintain a favorable prognosis with 5-FU monotherapy in stage III CRC.

Oncogenic mutation in RAS-RAF axis leads to increased expression of GREB1, resulting in tumor proliferation in colorectal cancer.

BRAFV600E mutation accounts for up to 90% of all BRAF mutations in human colorectal cancer (CRC), and constitutively activates the MEK-MAPK pathway. It is recognized that neutralizing mAbs for epidermal growth factor receptor alone are not effective for CRC with BRAFV600E mutation. Therefore, there is increasing interest in identification of the possible therapeutic targets in downstream of BRAF mutation in CRCs. To address this, we studied genome engineered mouse models for colonic neoplasia that has BrafV600E mutation on the basis of Apc inactivation, induced in 2 distinct Cre mouse models, CDX2P-G22Cre and CDX2P-CreERT2 mice. We carried out oligonucleotide microarray analysis for colonic neoplasia generated in these mouse models, and compared gene expression profiles among Kras/Braf WT, Kras-mutated, and Braf-mutated mouse colon tumors to seek new molecular targets corresponding to the KRAS-BRAF-MAPK axis. We found that the expression of the growth regulation by estrogen in breast cancer protein 1 (Greb1) was the most upregulated gene in Braf-mutated mouse tumors compared to Kras/Braf WT counterparts. The silencing of GREB1 significantly reduced the proliferation and tumorigenesis of CRC cell lines, whereas the overexpression of GREB1 promoted cell proliferation. Although GREB1 was first identified as a hormone-responsive gene mediating estrogen-stimulated cell proliferation in endometriosis, breast, and ovarian cancers, these results suggest that RAS-RAF-MAPK signaling upregulates GREB1 expression in CRC, resulting in cellular proliferation. Thus, GREB1 is a possible therapeutic target for CRCs with BrafV600E mutation.

The prognostic value of organ/space surgical site infection in stage I colorectal cancer recurrence.

PURPOSE: Evidence on risk factors for postoperative recurrence in patients with colorectal cancer (CRC) confined to pathological stage I is limited. Therefore, this study aimed to identify the risk factors for recurrence in patients with stage I CRC. METHODS: Data on clinicopathological factors and blood tests of patients diagnosed with pathological stage I CRC at Hiroshima University Hospital between April 1, 2010, and December 31, 2018, were retrospectively obtained. The statistical significance between the clinical factors and postoperative recurrence was also investigated. RESULTS: A total of 244 patients were included. The median observation period was 45 months. There were 17 patients (6.6%) with a postoperative recurrence (8 local and 9 distant recurrences). In the log-lank test, rectal cancer (p = 0.004), pT2 (p = 0.020) and organ/space surgical site infection (SSI) (p = 0.008) were significantly associated with postoperative recurrence. In a multivariate analysis, rectal cancer (hazard ratio [HR] 3.678, 95% confidence interval [CI] 1.184-11.425, p = 0.024) and organ/space SSI (HR 3.137, 95% CI 1.013-9.713, p = 0.047) were independently associated with a higher recurrence rate. Among 18 patients with organ/space SSI, 4 recurrences occurred, all of which were distant metastases. CONCLUSION: Organ/space SSI significantly affects the postoperative recurrence in patients with stage I CRC.

Preoperative incremental maximum squeeze pressure as a predictor of fecal incontinence after very low anterior resection for low rectal cancer.

PURPOSE: Very low anterior resection (VLAR) is performed widely, but some patients are left with fecal incontinence (FI), which compromises their quality of life (QOL) severely. This study sought to identify the predictive factors of postoperative FI after VLAR, which remain unclear. METHODS: We evaluated the anorectal manometry data of patients who underwent VLAR to identify the risk factors for postoperative FI among the various clinicopathological factors and manometric characteristics. FI and QOL were analyzed using the Wexner score and EORTC QLQ-C30, respectively. RESULTS: The subjects of this study were 40 patients who underwent VLAR for low rectal cancer between April, 2015 and May, 2018. There were 11 (27%) patients in the major-FI group and 29 (73%) in the minor-FI group. Multivariate analysis revealed that low preoperative incremental maximum squeeze pressure (iMSP) was an independent risk factor for postoperative major-FI. Postoperative QOL tended to be worse in the major-FI group. CONCLUSIONS: Preoperative low iMSP increases the risk of major-FI and impaired QOL after VLAR. This highlights the importance of performing preoperative anorectal manometry to evaluate the patient's anal function as well as to select the most appropriate operative procedure and early multifaceted treatment such as medication, rehabilitation, and biofeedback for postoperative FI.

Surgical techniques for advanced transverse colon cancer using the pincer approach of the transverse mesocolon.

BACKGROUND: Laparoscopic surgery for colorectal cancer, not only early cancer but also advanced cancer, has become standardized by some randomized controlled studies. However, cases involving advanced transverse colon cancer were excluded from these studies due to the technical difficulty of the surgery. Hence, laparoscopic surgery for advanced transverse colon cancer is still a theme that we need to overcome. To solve these issues, it is necessary to establish a standardized approach and surgical technique. SURGICAL TECHNIQUES: The advantage of our method, which approaches from both sides of the transverse mesocolon, is that it is easier to achieve hemostasis when active bleeding occurs because this approach provides space for ligating and sealing. This allows the surgeon to perform lymphadenectomy around the superior mesenteric artery and vein. CONCLUSIONS: We introduced the usefulness of the "Pincer approach of the transverse mesocolon" to standardize laparoscopic surgery for advanced transverse colon cancer.

Is laparoscopic colorectal surgery with continuation of antiplatelet therapy safe without increasing bleeding complications?

PURPOSE: The number of patients on antiplatelet therapy (APT) who need surgery is increasing; however, it is unclear whether APT should be continued for abdominal surgery, particularly laparoscopic colorectal surgery. We investigated the safety of continuing APT for patients undergoing laparoscopic colorectal surgery. METHODS: We collected retrospective data from 529 patients who underwent laparoscopic colorectal surgery at Hiroshima University between January, 2013 and December, 2018. We analyzed information related to APT. Thirty-six pairs were matched by the propensity score method between patients on APT (APT+) and those not on APT (APT-). We compared the surgical outcomes of both groups. RESULTS: Among 463 patients eligible for the study, 48 were on APT for cerebrovascular or cardiovascular disease, and 36 continued to take aspirin. In the case-matched comparison, the amount of intraoperative blood loss in the APT+ group was not significantly higher than that in the APT- group, and the incidences of bleeding complications, thromboembolic complications, and other complications were not significantly different between the groups. CONCLUSION: In a case-matched comparison, continuation of aspirin during laparoscopic colorectal surgery did not increase perioperative complications. In laparoscopic colorectal surgery, continuation of aspirin is an acceptable strategy for patients with thromboembolic risk caused by interruption of APT.

Risk factors for postoperative pneumonia in elderly patients with colorectal cancer: a sub-analysis of a large, multicenter, case-control study in Japan.

PURPOSE: Postoperative pneumonia affects the length of stay and mortality after surgery in elderly patients with colorectal cancer (CRC). We aimed to determine the risk factors of postoperative pneumonia in elderly patients with CRC, and to evaluate the impact of laparoscopic surgery on elderly patients with CRC. METHODS: We retrospectively investigated 1473 patients ≥ 80 years of age who underwent surgery for stage 0-III CRC between 2003 and 2007. Using a multivariate analysis, we determined the risk factors for pneumonia occurrence from each baseline characteristic. RESULTS: Among all included patients, 26 (1.8%) experienced postoperative pneumonia, and restrictive respiratory impairment, obstructive respiratory impairment, history of cerebrovascular events, and open surgery were determined as risk factors (odds ratio [95% confidence interval], 2.78 [1.22-6.20], 2.71 [1.22-6.30], 3.60 [1.37-8.55], and 3.57 [1.22-15.2], respectively). Furthermore, postoperative pneumonia was more frequently accompanied by increasing cumulative numbers of these risk factors (area under the receiver operating characteristic curve = 0.763). CONCLUSIONS: Laparoscopic surgery may be safely performed in elderly CRC patients, even those with respiratory impairment and a history of cerebrovascular events.

Increased Calcineurin A Expression Is Associated with a Lower Relapse-Free Survival Rate after Colorectal Cancer Surgery.

OBJECTIVE: Increased expression of calcineurin in colorectal cancer (CRC) has been reported. Although the oncogenic function has been suggested, the clinical relevance is still unclear. We herein studied calcineurin expression as a prognostic biomarker in patients receiving curative surgery for stages I-III CRC. METHODS: In 121 patients with stages I-III CRC treated at Hiroshima University between 1997 and 2003, calcineurin A expression was examined using immunohistochemistry (IHC) staining of surgical specimens. Specimens were considered positive for calcineurin A if any IHC-stained cells were observed within the carcinomatous area, and clinicopathological characteristics and survival outcomes were compared between IHC-positive and -negative groups. RESULTS: Calcineurin A was preferentially expressed in the cytoplasm of cancer cells, and a median of 8% of the cells (range: 0-80%; interquartile range: 0-22.5%) were stained within the carcinomatous areas. Of 121 cases, 81 were determined as IHC positive while 40 were determined to be negative. Positive expression of calcineurin A, as well UICC-TNM stage, was associated with low relapse-free survival (RFS) rates in multivariate analyses (hazard ratio = 2.92; 95% CI: 1.27-7.92; p = 0.010). CONCLUSION: Increased calcineurin A expression is associated with lower RFS rates and may have clinical value in predicting recurrence.

Clinical Significance of Pharmacological Prophylaxis based on the Original Risk Classification of Venous Thromboembolism after Lower Abdominal Surgery.

Pharmacological prophylaxis was not routinely administrated following gastroenterological surgery because of concerns about bleeding complications. We tried to establish the original risk classification to determine the indication for pharmacological prophylaxis for selected patients at high risk of venous thromboembolism (VTE). One hundred and fifty-six consecutive patients who underwent lower abdominal elective surgery were divided into three groups (highest, high, and low risk groups) based on the original risk classification. Pharmacological prophylaxis was indicated for patients in the highest and high risk groups. We investigated safety and efficacy of the pharmacological prophylaxis based on this classification. Sixteen patients were classified in the highest, 50 in the high, and 90 in the low risk groups. Pharmacological prophylaxis was used for 59 cases (37.8%). There was no symptomatic pulmonary embolism or major bleeding complications. There were no significant differences in the occurrence of postoperative complications, analgesia use, and median postoperative pain scores for the three groups. In the highest and high risk groups administrated pharmacological prophylaxis, fibrin degradation products (FDP) and D-dimer did not change between postoperative day 1 and day 7. These data suggested the clinical significance of the pharmacological prophylaxis based on the original risk classification.

Up-front systemic chemotherapy is a feasible option compared to primary tumor resection followed by chemotherapy for colorectal cancer with unresectable synchronous metastases.

BACKGROUND: In stage IV colorectal cancer (CRC) with unresectable metastases, whether or not resection of the primary tumor should be indicated remains controversial. We aim to determine the impact of primary tumor resection on the survival of stage IV CRC patients with unresectable metastases. METHODS: We retrospectively investigated 103 CRC patients with stage IV colorectal cancer with metastases, treated at Hiroshima University Hospital between 2007 and 2013. Of these, those who had resectable primary tumor but unresectable metastases and received any chemotherapy were included in the study. We analyzed the overall survival (OS) and short-term outcomes between the patients who received up-front systemic chemotherapy (USC group) and those who received primary tumor resection followed by chemotherapy (PTR group). RESULTS: Of the 57 included patients, 15 underwent USC and 42 PTR. The median survival times were 13.4 and 23.9 months in the USC and PTR groups, respectively (P = 0.093), but multivariate analysis for the overall survival showed no significant difference between the two groups (hazard ratio, 1.30; 95% confidence interval (CI), 0.60 to 2.73, P = 0.495). In the USC group, the disease control rate of primary tumor was observed in 12 patients (80.0%), but emergency laparotomy was required for 1 patient. Morbidity in the PTR group was observed in 18 cases (42.9%). CONCLUSIONS: The overall survival did not differ significantly between the USC and PTR groups. USC may help avoid unnecessary resection and consequently the high morbidity rate associated with primary tumor resection for stage IV CRC with unresectable metastases.

A case of pancreatic adenosquamous cell carcinoma with a pseudocyst following curative surgery.

BACKGROUND: Pancreatic adenosquamous cell carcinoma (PASC) is a relatively rare histological type of pancreatic malignancy, and preoperative diagnosis is difficult because of its rarity. PASC accounts for 1-4% of all pancreatic cancers, and even after curative surgery, its prognosis is poorer than that of ordinary pancreatic adenocarcinoma. Pathologically, it shows glandular and squamous differentiation of cells. Complete resection is the only method to achieve a good long-term prognosis, and an increasing doubling time of PASC is considered to indicate early recurrence after surgery. Here, we report a rare case of PASC with an infected pancreatic cyst that was difficult to treat, along with a review of the literature. CASE PRESENTATION: A woman in her 80s with a history of breast cancer presented with pericardial pain. Computed tomography revealed a 20-mm hypovascular tumor in the body of the pancreas and a 27-mm pseudocyst. Endoscopic retrograde cholangiopancreatography showed a severe main pancreatic duct stenosis in the body of the pancreas that made cannulation impossible, and contrast media extravasation was due to pancreatic duct disruption in the pancreatic tail. Endoscopic fine-needle aspiration revealed that the tumor was a PASC. Because the patient had an infected pancreatic cyst, central intravenous nutrition and antibiotics were administered, which stabilized her general condition. She was diagnosed with resectable PASC and underwent distal pancreatectomy with lymphadenectomy. The postoperative course was uneventful. Immunohistochemical analysis of the resected specimen confirmed T2N0M0 stage IB. Systemic adjuvant chemotherapy with S-1 is ongoing. CONCLUSION: Appropriate preoperative management and preoperative accurate staging (T2N0M0 stage IB) of PASC with curative surgery can ensure predictable outcomes.

Evaluation of the short-term complications of intracorporeal anastomosis in right-sided colectomy.

INTRODUCTION: The benefits of intracorporeal anastomosis in laparoscopic colorectal cancer surgery remain unclear. Therefore, we aimed to investigate the short-term postoperative outcomes of intracorporeal anastomosis. METHODS: We retrospectively analyzed 87 patients who underwent laparoscopic surgery for right-sided colon tumors using a colon database. RESULTS: Of the 87 patients, 23 underwent intracorporeal anastomosis and 64 underwent extracorporeal anastomosis. Intraoperative bleeding, wound length, exhaust gas, preoperative white blood cell count, and C-reactive protein (postoperative day 1) were higher in the extracorporeal anastomosis group than in the intracorporeal anastomosis group. The incidence of wound infection was higher in the intracorporeal anastomosis group than in the extracorporeal anastomosis group. In the irrigation water bacterial culture collected after anastomosis, the positive group had a higher white blood cell count on postoperative day 1 and higher C-reactive protein levels on postoperative day 3 than did the negative group. Patients who underwent chemical preparation had lower C-reactive protein levels on postoperative day 1 than did the group who did not undergo chemical preparation. CONCLUSION: Despite the advantages of intracorporeal anastomosis in terms of wound length and intraoperative bleeding, the risk of infection may increase during the introduction phase. Fever and inflammatory responses are significantly elevated in culture-positive cases.

Intracystic papillary neoplasm diagnosis following an extended cholecystectomy: a case report and literature review.

We report a case of intracystic papillary neoplasms (ICPN) that was difficult to differentiate from adenocarcinoma of the gallbladder. A 64-year-old man visited our hospital for an examination of gallbladder tumors. At the preoperative examination, the tumor was revealed a papillary type of tumor in the body of the gallbladder without the findings that without the findings that suggested the tumor invasion into the deep subserosal layer. The patient underwent an extended cholecystectomy. Papillary lesions were observed mainly in the body of the gallbladder, with flattened elevated lesions at the gallbladder fundus. Within each of these tumors, cells corresponding to intraepithelial adenocarcinoma were irregularly interspersed, leading to a diagnosis of ICPN. The patient is currently undergoing follow-up with no recurrence postoperatively. The prognosis of ICPN is generally good; however, preoperative diagnosis remains challenging. Therefore, a treatment plan for gallbladder cancer should be applied.

Clinical Phase I Study of TAS102/Irinotecan/Bevacizumab Combination Therapy in Japanese Patients With Unresectable Metastatic Colorectal Cancer (mCRC).

BACKGROUND: In this phase I study, we aimed to examine the safety of a triple combination (TAS-102/irinotecan/bevacizumab) therapy in patients with previously treated metastatic colorectal cancer (mCRC). METHODS: In the TAS-102 dose-escalation phase, we determined dose-limiting toxicity (DLT), estimated the maximum tolerated dose (MTD), and determined the recommended dose (RD); in the expansion phase, we evaluated safety. The RD was administered in advance for 10 patients. The TAS-102 dose was increased to 25-35 mg/m2 and administered orally twice on days 1-5 and 8-12. Irinotecan (100 mg/m2) and bevacizumab (5 mg/m2) were administered on days 1 and 15 of the treatment, respectively. RESULTS: Fifteen patients were enrolled in dose-escalation Levels 1-3, and ten in the expansion phase. A 30 mg/m2 TAS-102 dose at Level 2 was administered to three patients, with one presenting grade 4 neutropenia. A 35 mg/m2 TAS-102 dose at Level 3 was administered to five patients, with three patients presenting grade 4 neutropenia and grade 3 DLTs. We added three patients at Level 2 and set the MTD at 30 mg/m2, with no DLTs. The RD was fixed at 25 mg/m2, with no DLTs (N = 10) or treatment-related deaths. One patient showed complete response at Level 2, four presented partial response, and eleven individuals maintained stable disease for over four months. The median progression-free survival duration was 7.6 months, while the median overall survival period was 16.9 months. CONCLUSION: The TAS-102/irinotecan/bevacizumab combination therapy was safe, effective, and well-tolerated in patients previously treated with mCRC.

Surgical treatment of hepatic xanthogranuloma arising from a giant hepatic cyst causing gastrointestinal obstruction: a case report.

Hepatic cysts are benign liver lesions and are often asymptomatic. Large hepatic cysts may cause jaundice and portal hypertension; however, they rarely cause gastrointestinal obstruction. Symptomatic cysts require treatment, and when malignancy is suspected, cyst puncture for pathological examination of the fluid may pose a risk of dissemination. Herein, we describe a case of xanthogranuloma arising from a large hepatic cyst that was causing duodenal obstruction. Thus, cyst puncture was performed for emergency decompression. Cytological examination of the puncture fluid revealed no malignant findings. Hence, laparoscopic deroofing was performed to treat the hepatic cyst. As the cyst and duodenal wall were firmly adherent, the cyst wall was left behind without dissection from the duodenum. A two-stage approach of cyst puncture followed by surgery may be an option for patients requiring urgent treatment for potentially malignant hepatic cysts.

Small bowel cancer arising from a scar site more than 60 years after ileostomy closure: a case report.

Although small bowel cancer is rare, cases of carcinoma arising from the abdominal wall have not been reported. We report a case of a tumor arising from a stoma scar site, following ileostomy closure that was performed 60 years earlier. The tumor was resected for both therapeutic and diagnostic purposes and was found to be a primary cancer of the small intestine. The small intestinal mucosa survived long-term at the stoma scar site and developed carcinoma. No similar reports of small bowel cancer arising from the mucosa at the stoma scar site (on the abdominal wall) exist. After tumor resection, the patient received chemotherapy for lung metastases and has survived, thus far, for 2 years since the surgery.