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1.
Ann Surg Open ; 5(1): e402, 2024 Mar.
Article En | MEDLINE | ID: mdl-38883952

Objective: To determine whether Aquacel Ag Hydrofiber dressings containing ionic silver are superior to film dressings for preventing superficial surgical site infections (SSI) in patients undergoing elective gastrointestinal surgery. Background: Multiple clinical trials have assessed the effectiveness of silver-containing wound dressings; however, systematic reviews failed to find any advantages of these dressings and concluded that there was insufficient evidence to indicate that they prevented wound infections. This study aimed to evaluate the efficacy of Aquacel Ag Hydrofiber dressings for preventing superficial SSIs in patients undergoing gastrointestinal surgery. Methods: Patients undergoing elective gastrointestinal surgery were randomly assigned to receive either Aquacel Ag Hydrofiber (study group) or film dressings (control group). The primary end point was superficial SSI within 30 days after surgery (UMIN Clinical Trials Registry ID: 000043081). Results: A total of 865 patients (427 study group, 438 control group) were qualified for primary end-point analysis. The overall rate of superficial SSIs was significantly lower in the study group than in the control group (6.8% vs 11.4%, P = 0.019). There was no significant difference in superficial SSI rates between the groups in patients undergoing upper gastrointestinal surgery; however, the rate was significantly lower in the study group in patients undergoing lower gastrointestinal surgery (P = 0.042). Multivariate analysis identified Aquacel Ag Hydrofiber dressings as an independent factor for reducing superficial SSIs (odds ratio, 0.602; 95% confidence interval, 0.367-0.986; P = 0.044). Conclusions: Aquacel Ag Hydrofiber dressings can reduce superficial SSIs compared to film dressings in patients undergoing elective gastrointestinal surgery, especially lower gastrointestinal surgery.

2.
Cancers (Basel) ; 16(5)2024 Feb 20.
Article En | MEDLINE | ID: mdl-38473211

The sphingolipid metabolic pathway, an important signaling pathway, plays a crucial role in various physiological processes including cell proliferation, survival, apoptosis, and immune regulation. The liver has the unique ability to regenerate using bioactive lipid mediators involving multiple sphingolipids, including ceramide and sphingosine 1-phosphate (S1P). Dysregulation of the balance between sphingomyelin, ceramide, and S1P has been implicated in the regulation of liver regeneration and diseases, including liver fibrosis and hepatocellular carcinoma (HCC). Understanding and modulating this balance may have therapeutic implications for tumor proliferation, progression, and metastasis in HCC. For cancer therapy, several inhibitors and activators of sphingolipid signaling, including ABC294640, SKI-II, and FTY720, have been discussed. Here, we elucidate the critical roles of the sphingolipid pathway in the regulation of liver regeneration, fibrosis, and HCC. Regulation of sphingolipids and their corresponding enzymes may considerably influence new insights into therapies for various liver disorders and diseases.

3.
Gan To Kagaku Ryoho ; 51(2): 181-183, 2024 Feb.
Article Ja | MEDLINE | ID: mdl-38449406

A 38-year-old woman was admitted to our hospital due to severe anemia. CT showed a 13×12 cm tumor with moderately enhanced wall thickening in the right upper abdomen. The huge tumor located adjacent to the jejunum and compressed the right transverse colon. Hemorrhagic necrosis and air were observed within the tumor, suspecting tumor penetration into the jejunum. The patient was diagnosed with abdominal GIST with jejunal infiltration. Laparotomy revealed a 13× 11 cm solid mass with intra-tumoral hemorrhage and invasion into the jejunum, located in the transverse mesocolon. Tumor resection combined with partial jejunectomy and transverse colectomy were performed. Immunohistochemical findings of the resected specimen was positive for c-kit and DOG-1, and the MIB-1 positive rate was 10%. Three weeks after the operation, re-anastomosis was performed due to transverse colon anastomotic stricture. She was discharged 45 days after first operation. Currently, 9 months after the operation, patient has been prescribed imatinib and is alive without recurrence.


Colon, Transverse , Neoplasms , Female , Humans , Adult , Colon, Transverse/surgery , Jejunum/surgery , Mesentery , Hemorrhage
4.
Gan To Kagaku Ryoho ; 51(2): 193-195, 2024 Feb.
Article Ja | MEDLINE | ID: mdl-38449410

BACKGROUND: Watch and wait(W & W)for rectal cancer after chemoradiotherapy(CRT)is attracting attention. PURPOSE: To examine regimens and indications from the results of follow-up of cases undergoing W & W in our department. MATERIALS AND METHODS: CRT(SOX therapy 2-5 cycles, 45 Gy)was performed on patients with lower rectal cancer over a period of 2016 to 2020, and 7 patients with clinical complete response(cCR)were followed up. RESULTS: With a median follow-up of 33 months(10-74), 4 of 7 patients(57.1%)remained in cCR. Two patients had local relapse more than a year after the start of treatment, were able to undergo salvage surgery, and are alive after surgery. Patients with lateral lymph node metastasis before CRT had para-aortic lymph node metastasis at 8 months. CONCLUSIONS: Patients with maintained cCR were those with localized, node-negative disease. On the other hand, in patients with lymph node metastasis, including lateral metastasis, it was not possible to perform salvage surgery due to distant metastasis. Careful case selection and follow-up are necessary in the future.


Neoplasms, Second Primary , Rectal Neoplasms , Humans , Lymphatic Metastasis , Rectal Neoplasms/therapy , Chemoradiotherapy , Lymph Nodes
5.
J Gastroenterol ; 59(5): 376-388, 2024 05.
Article En | MEDLINE | ID: mdl-38411920

BACKGROUND: The clinicopathological features and prognosis of primary small bowel adenocarcinoma (PSBA), excluding duodenal cancer, remain undetermined due to its rarity in Japan. METHODS: We analyzed 354 patients with 358 PSBAs, between January 2008 and December 2017, at 44 institutions affiliated with the Japanese Society for Cancer of the Colon and Rectum. RESULTS: The median age was 67 years (218 males, 61.6%). The average tumor size was 49.9 (7-100) mm. PSBA sites consisted of jejunum (66.2%) and ileum (30.4%). A total of 219 patients (61.9%) underwent diagnostic small bowel endoscopy, including single-balloon endoscopy, double-balloon endoscopy, and capsule endoscopy before treatment. Nineteen patients (5.4%) had Lynch syndrome, and 272 patients (76.8%) had symptoms at the initial diagnosis. The rates for stages 0, I, II, III, and IV were 5.4%, 2.5%, 27.1%, 26.0%, and 35.6%, respectively. The 5-year overall survival rates at each stage were 92.3%, 60.0%, 75.9%, 61.4%, and 25.5%, respectively, and the 5-year disease-specific survival (DSS) rates were 100%, 75.0%, 84.1%, 59.3%, and 25.6%, respectively. Patients with the PSBA located in the jejunum, with symptoms at the initial diagnosis or advanced clinical stage had a worse prognosis. However, multivariate analysis using Cox-hazard model revealed that clinical stage was the only significant predictor of DSS for patients with PSBA. CONCLUSIONS: Of the patients with PSBA, 76.8% had symptoms at the initial diagnosis, which were often detected at an advanced stage. Detection during the early stages of PSBA is important to ensure a good prognosis.


Adenocarcinoma , Capsule Endoscopy , Duodenal Neoplasms , Ileal Neoplasms , Intestinal Neoplasms , Jejunal Neoplasms , Aged , Humans , Male , Adenocarcinoma/diagnosis , Adenocarcinoma/pathology , Duodenal Neoplasms/diagnosis , Duodenal Neoplasms/pathology , Ileal Neoplasms/diagnosis , Intestinal Neoplasms/diagnosis , Intestinal Neoplasms/therapy , Japan/epidemiology , Jejunal Neoplasms/diagnosis , Prognosis
6.
JCO Glob Oncol ; 10: e2300392, 2024 Feb.
Article En | MEDLINE | ID: mdl-38330276

PURPOSE: Limited information is available regarding the characteristics and outcomes of stage IV small bowel adenocarcinoma (SBA) in Japan. This study examined the clinical and pathological characteristics and outcomes according to the treatment strategies in patients with stage IV SBA. METHODS: This retrospective observational study used the data of patients with jejunal or ileal adenocarcinoma collected by the Small Bowel Malignant Tumor Project of the Japanese Society for Cancer of the Colon and Rectum. Descriptive statistics were expressed as the mean (standard deviation) or median (range). Survival analysis was performed using Kaplan-Meier curves and pairwise log-rank tests. RESULTS: Data from 128 patients were analyzed. The treatment strategies were chemotherapy alone (26 of 128, 20.3%), surgery alone (including palliative surgery; 21 of 128, 16.4%), surgery + chemotherapy (74 of 128, 57.8%), and best supportive care (7 of 128, 5.5%). The median (range) overall survival was 16 (0-125) months overall, and 11 (1-38) months, 8 (0-80) months, 18 (0-125) months, and 0 (0-1) months for the chemotherapy, surgery, surgery + chemotherapy, and best supportive care groups, respectively. Three main categories of chemotherapeutic regimen were used: a combination of fluoropyrimidine and oxaliplatin (F + Ox), fluoropyrimidine and irinotecan (F + Iri), and single-agent fluoropyrimidine. Among patients treated with chemotherapy, the median (range) OS was 16 (1-106) months overall, and 17 (1-87) months, 29 (7-39) months, and 16 (1-106) months in patients treated with fluoropyrimidine, F + Iri, and F + Ox, respectively. CONCLUSION: Patients treated with surgery, chemotherapy, or both had a better prognosis than those who received best supportive care. Among patients who received chemotherapy, survival did not differ according to the chemotherapeutic regimen.


Adenocarcinoma , Antineoplastic Combined Chemotherapy Protocols , Humans , Japan , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Intestine, Small/pathology , Irinotecan/therapeutic use , Adenocarcinoma/drug therapy , Oxaliplatin/therapeutic use
7.
Surg Case Rep ; 10(1): 25, 2024 Jan 22.
Article En | MEDLINE | ID: mdl-38252200

BACKGROUND: Ampullary adenomas are premalignant lesions. However, biliary obstruction causing jaundice is rare. Duodenal intussusception secondary to an ampullary adenoma rarely occurs because of the fixed position of the duodenum in the retroperitoneum. Herein, we have described a rare case of ampullary adenoma with jaundice caused by duodenal intussusception. CASE PRESENTATION: A 40-year-old woman presenting with vomiting and yellowish discoloration of the skin was admitted to another hospital. The patient had experienced recurrent epigastric pain and vomiting for the past 18 months. Blood test results showed elevated levels of bilirubin (3.9 mg/dL), and abdominal computed tomography (CT) showed a 60-mm hypovascular mass in the third part of the duodenum and a left lateral shift of the dilated common bile duct. The patient was referred to our hospital for further evaluation. She recovered from hyperbilirubinemia spontaneously (levels of bilirubin, 1.0 mg/dL), and the CT showed a tumor shift from the third part of the duodenum to the second part and improvement of the dilated common bile duct. Hypotonic duodenography revealed a tumor that moved easily from the second to the third portion of the patient's position. Upper gastrointestinal endoscopy revealed a large papillary tumor occupying the second part of the duodenum, which was diagnosed as an adenoma through biopsy. The possibility of malignancy could not be negated owing to the presence of jaundice and an elevated carbohydrate antigen 19-9 level (76.0 U/mL). Pancreaticoduodenectomy was performed. The resected specimen showed a 60 × 40 × 40-mm pedunculated ampullary mass with submucosal elongation. The pathological examination indicated that the ampullary tumor was a high-grade intestinal adenoma. The postoperative course was uneventful, and the patient was discharged 26 days postoperatively. CONCLUSIONS: This report describes a rare case of a patient with an ampullary adenoma presenting with jaundice resulting from duodenal intussusception. Owing to the possibility of a postoperative cancer diagnosis which may have caused the biliary obstruction and the difficulty in making an accurate preoperative diagnosis, it is imperative to choose the appropriate surgical procedure such as a pancreaticoduodenectomy.

8.
Ann Gastroenterol Surg ; 7(5): 765-771, 2023 Sep.
Article En | MEDLINE | ID: mdl-37663965

Aim: To establish a new Japanese classification of synchronous peritoneal metastases from colorectal cancer. Methods: This multi-institutional, prospective, observational study enrolled patients who underwent surgery for colorectal cancer with synchronous peritoneal metastases. Overall survival rates were compared according to the various models using objective indicators. Each model was evaluated by Akaike's information criterion (AIC). The region of peritoneal metastases was evaluated by the peritoneal cancer index (PCI). Results: Between October 2012 and December 2016, 150 patients were enrolled. The AIC of the present Japanese classification was 1020.7. P1 metastasis was defined as confined to two regions. The minimum AIC was obtained with the cutoff number of 10 or less for P2 metastasis and 11 or more for P3 metastasis. As for size, the best discrimination ability between P2 and P3 metastasis was obtained with a cutoff value of 3 cm. The AIC of the proposed classification was 1014.7. The classification was as follows: P0, no peritoneal metastases; P1, metastases localized to adjacent peritoneum (within two regions of PCI); P2, metastases to distant peritoneum, number ≤10 and size ≤3 cm; P3, metastases to distant peritoneum, number ≥11 or size >3 cm; P3a, metastases to distant peritoneum, number ≥11 and size ≤3 cm, or number ≤10 and size >3 cm; P3b, metastases to distant peritoneum, number ≥11 and size >3 cm. Conclusion: This objective classification could improve the ability to discriminate prognosis in patients with synchronous peritoneal metastases from colorectal cancer.

9.
Lancet Reg Health West Pac ; 33: 100680, 2023 Apr.
Article En | MEDLINE | ID: mdl-37181532

Background: There are no standardised criteria for the 'regional' pericolic node in colon cancer, which represents a major cause of the international uncertainty regarding the optimal bowel resection margin. This study aimed to determine 'regional' pericolic nodes based on prospective lymph node (LN) mapping. Methods: According to preplanned in vivo measurements of the bowel, the anatomical distributions of the feeding artery and LNs were determined in 2996 stages I-III colon cancer patients who underwent colectomy with resection margin >10 cm at 25 institutions in Japan. Findings: The mean number of retrieved pericolic nodes was 20.9 (standard deviation, 10.8) per patient. In all patients except seven (0.2%), the primary feeding artery was distributed within 10 cm of the primary tumour. The metastatic pericolic node most distant from the primary tumour was within 3 cm in 837 patients, 3-5 cm in 130 patients, 5-7 cm in 39 patients and 7-10 cm in 34 patients. Only four patients (0.1%) had pericolic lymphatic spread beyond 10 cm; all of whom had T3/4 tumours accompanying extensive mesenteric lymphatic spread. The location of metastatic pericolic node did not differ by the feeding artery's distribution. Postoperatively, none of the 2996 patients developed recurrence in the remaining pericolic nodes. Interpretation: The pericolic nodes designated as 'regional' were those located within 10 cm of the primary tumours, which should be fully considered when determining the bowel resection margin, even in the era of complete mesocolic excision. Funding: Japanese Society for Cancer of the Colon and Rectum.

10.
Gan To Kagaku Ryoho ; 50(1): 84-86, 2023 Jan.
Article Ja | MEDLINE | ID: mdl-36759994

An 81-year-old woman was admitted to our hospital due to frequent bleeding and hemorrhagic shock. Blood tests revealed anemia and contrast-enhanced abdominal CT revealed a pancreatic tail tumor with a diameter of 60 mm. The boundary between pancreatic tumor and the transverse colon, stomach and spleen was unclear, and invasion of the transverse colon as well as the stomach and spleen was suspected. Hemorrhage due to colon invasion of the pancreatic tail cancer and intra-tumoral hemorrhage were suspected. Due to persistent bleeding, the patient had emergency surgery to control bleeding. The pancreatic tail tumor invaded not only the colon but also stomach and spleen, distal pancreatectomy, partial gastrectomy and splenectomy was performed in combination with resection of the transverse colon, and transverse colon colostomy. We report a case of gastrointestinal bleeding caused by transverse colon invasion of pancreatic tail cancer, which resulted in emergency surgery.


Colon, Transverse , Pancreatic Neoplasms , Female , Humans , Aged, 80 and over , Colon, Transverse/surgery , Colon, Transverse/pathology , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/pathology , Stomach/pathology , Pancreatectomy/adverse effects , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/surgery , Pancreatic Neoplasms
11.
Gan To Kagaku Ryoho ; 50(1): 102-104, 2023 Jan.
Article Ja | MEDLINE | ID: mdl-36760000

An 83-year-old woman developed jaundice, and was diagnosed as perihilar cholangiocarcinoma. Abdominal contrast- enhanced CT revealed coexisting portosystemic shunt between portal vein and inferior vena cava, however, her blood ammonia level was normal. She underwent right hemihepatectomy and caudate lobectomy combined with extrahepatic bile duct resection and portal vein resection. Postoperatively, hyperammonemia refractory to conservative treatment was observed. The blood ammonia level increased to 180µg/dL and she was suffered from grade Ⅲ hepatic encephalopathy on the 20th postoperative day. CT showed an increase in the diameter of the portosystemic shunt, while there was only a slight increase in the remnant left lobe of the liver. These findings indicated that hepatic encephalopathy was caused by increased portosystemic shunt blood flow and decreased portal venous flow. Hepatic encephalopathy was rapidly improved by percutaneous transhepatic portosystemic shunt obliteration.


Bile Duct Neoplasms , Hepatic Encephalopathy , Klatskin Tumor , Portasystemic Shunt, Transjugular Intrahepatic , Humans , Female , Aged, 80 and over , Klatskin Tumor/complications , Hepatic Encephalopathy/etiology , Hepatic Encephalopathy/therapy , Ammonia , Portasystemic Shunt, Transjugular Intrahepatic/adverse effects , Bile Duct Neoplasms/complications , Bile Duct Neoplasms/surgery , Bile Duct Neoplasms/pathology
12.
Digestion ; 104(3): 233-242, 2023.
Article En | MEDLINE | ID: mdl-36646047

INTRODUCTION: Regorafenib is a multi-kinase inhibitor approved for patients with metastatic colorectal cancer (mCRC) who were previously treated with standard therapies. A few reports showed the impact of KRAS mutation on therapeutic efficacy of regorafenib. Only one study reported poor prognoses for patients treated with regorafenib who had large amounts of circulating cell-free DNA (cfDNA). In the present study, we evaluated the impact of KRAS mutations in tissue or plasma and amounts of cfDNA on prognoses of mCRC patients treated with regorafenib. METHOD: This is a biomarker investigation of the RECC study, which evaluated efficacy of regorafenib dose-escalation therapy. Plasma samples were obtained just before initiation of treatment with regorafenib. KRAS mutations were evaluated using tissue and plasma samples. cfDNA was extracted from plasma samples and quantified. RESULTS: Forty-five patients were enrolled in this biomarker study. Median progression-free survival (PFS) and overall survival (OS) of patients without KRAS mutations in tissues were 1.9 months (95% confidence interval [CI] 1.7-2.0) and 8.9 months (95% CI: 6.5-11.2), and those of patients with KRAS mutations were 1.4 months (95% CI: 1.3-1.5) and 6.8 months (95% CI: 5.0-8.5). Median PFS and OS of patients with plasma KRAS mutations were 1.9 months (95% CI: 1.8-1.9) and 7.0 months (95% CI: 5.3-8.7), respectively. Median PFS and OS of patients without plasma KRAS mutations were 1.7 months (95% CI: 1.1-2.3) and 8.9 months (95% CI: 6.7-11.2), respectively. Prior to administration of regorafenib, KRAS mutations were detected in 6 of 16 (37.5%) patients who had no tissue KRAS mutations. Median OS of patients with high cfDNA concentration (>median) was significantly poorer than that of patients with low cfDNA. CONCLUSION: KRAS mutations in the tissue or plasma have no impact on efficacy of regorafenib. KRAS emerging mutations were observed in quite a few patients. Large amounts of cfDNA may indicate poorer prognoses for patients receiving late-line regorafenib chemotherapy.


Colonic Neoplasms , Colorectal Neoplasms , Rectal Neoplasms , Humans , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Retrospective Studies , Proto-Oncogene Proteins p21(ras)/genetics , Prognosis
13.
Int J Clin Oncol ; 27(12): 1859-1866, 2022 Dec.
Article En | MEDLINE | ID: mdl-36201089

BACKGROUND: TAS-102 improves overall survival (OS) of patients with refractory colorectal cancer (CRC), resulting in median progression-free survival (PFS) of 2.0 months (RECOURSE trial). Subsequently, a combination of TAS-102 and bevacizumab was shown to extend median PFS by 3.7 months. However, approximately half of these patients experience grade 3/4 neutropenia. In this study, we evaluated whether biweekly TAS-102 and bevacizumab therapy has efficacy equal to that of conventional TAS-102 and bevacizumab therapy and whether it reduces adverse hematological effects. METHODS: This phase II, investigator-initiated, open-label, single-arm, multicenter study was conducted in Japan. Eligible patients had previously received first- and second-line chemotherapy for metastatic CRC. TAS-102 (35 mg/m2) was given twice daily on days 1-5 and days 15-19 in a 4-week cycle, and bevacizumab (5 mg/kg) was administered by intravenous infusion for 30 min every 2 weeks. The primary end point was progression-free survival (PFS), and secondary end points were time-to-treatment failure (TTF), response rate (RR), OS, and safety. RESULTS: 44 patients with metastatic colorectal cancer were enrolled in this study. Median PFS was 4.6 months (95% confidence interval [95% CI] 3.6-5.3) and median OS was 10.5 months (95% CI 9.6-11.4). A partial response was observed in 2 patients (4.5%, 95% CI 0.4-16.0%). The most common adverse event above grade 3 was neutropenia (7 patients, 15.9%, 95% CI 7.6-29.7%). CONCLUSIONS: Biweekly TAS-102 and bevacizumab therapy as third-line chemotherapy appears as effective as conventional TAS-102 and bevacizumab therapy, and this approach reduces adverse hematological effects.


Colorectal Neoplasms , Neutropenia , Humans , Bevacizumab , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Neoplasm Recurrence, Local/etiology , Colorectal Neoplasms/pathology , Neutropenia/chemically induced , Fluorouracil
14.
World J Clin Cases ; 10(24): 8709-8717, 2022 Aug 26.
Article En | MEDLINE | ID: mdl-36157792

BACKGROUND: Bronchogenic cysts are congenital cysts caused by abnormal sprouting from the ventral foregut during fetal life. They usually occur in the mediastinum or lung, but there are very rare cases of ectopic bronchogenic cysts that develop in the abdominal cavity. A unique intra-abdominal ectopic bronchogenic cyst with a mucinous neoplasm that was producing carcinoembryonic antigen (CEA), harboring a GNAS mutation, is reported. The present case may contribute to clarifying the mechanism of tumorigenesis and malignant transformation of ectopic bronchogenic cysts. CASE SUMMARY: In 2007, a man in his 50s was incidentally found to have an intra-abdominal cystic mass, 8 cm in diameter. Surgical resection was recommended, but he preferred to remain under observation. In 2020, his serum CEA level increased to 26.7 ng/mL, and abdominal computed tomography showed a 15 cm × 12 cm, multifocal, cystic mass located predominantly on the lesser curvature of the stomach. Since malignancy could not be ruled out, he finally underwent surgical resection. Histologically, the cystic wall was lined by ciliated columnar epithelium, accompanied by bronchial gland-like tissue, bronchial cartilage, and smooth muscle. Part of the cyst consisted of atypical columnar epithelium with an MIB-1 index of 5% and positive for CEA. Moreover, a GNAS mutation (p.R201C) was detected in the atypical epithelium, leading to a diagnosis of an ectopic bronchogenic cyst with a low-grade mucinous neoplasm. The patient is currently undergoing outpatient follow-up without recurrence. CONCLUSION: An extremely rare case of an abdominal bronchogenic cyst with a low-grade mucinous neoplasm harboring a GNAS mutation was reported.

15.
Int J Clin Oncol ; 27(8): 1300-1308, 2022 Aug.
Article En | MEDLINE | ID: mdl-35635652

BACKGROUND: Regorafenib significantly improves overall survival in previously treated metastatic colorectal cancer patients. However, various toxicities, such as hand-foot skin reaction (HFSR), fatigue, and liver dysfunction have limited the use of regorafenib. These toxicities appear soon after treatment initiation. The ReDOS study demonstrated the effectiveness of a weekly dose-escalation therapy of regorafenib starting with a lower daily dose; however, its usefulness in Asian subjects is unknown. We conducted a phase II study to evaluate the safety and survival benefit of regorafenib dose-escalation therapy for Japanese patients. METHODS: Patients with sufficient organ function, who had previously received more than two lines of chemotherapy were included. Regorafenib was started at 80 mg/day and escalated to 120 mg/day in Week 2 and 160 mg/day in Week 3, if no severe drug-related toxicities were observed. The primary endpoint was cancer progression-free survival (PFS). Tumor response and progression were assessed radiologically every 8 weeks. This study was registered in the University Hospital Medical Information Network (UMIN#UMIN000028933). RESULTS: 57 patients were enrolled and all started regorafenib at 80 mg/day. 32 patients (56.1%) were subsequently escalated to 120 mg/day and 19 (33.3%) to 160 mg/day. Only 8 patients (14.0%) discontinued treatment because of adverse events. Median PFS was 1.9 months. Median overall survival was 8.9 months, the response rate was 0%, and the disease control rate was 31.6%. The most frequent adverse event greater than grade 3 was hypertension (19.3%), followed by HFSR (14.0%). CONCLUSIONS: Regorafenib dose-escalation therapy is well tolerated with PFS-like regorafenib standard therapy.


Colonic Neoplasms , Colorectal Neoplasms , Rectal Neoplasms , Colonic Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Humans , Japan , Phenylurea Compounds/adverse effects , Pyridines/adverse effects , Rectal Neoplasms/drug therapy
16.
Cancer Med ; 11(14): 2735-2743, 2022 07.
Article En | MEDLINE | ID: mdl-35274487

Anal canal cancer (ACC) has been reported to be an uncommon cancer in Japan, as in the USA, Europe, and Australia. This retrospective multi-institutional study was conducted to clarify the characteristics of ACC in Japan. First, the histological ACC type cases treated between 1991 and 2015 were collected. A detailed analysis of the characteristics of anal canal squamous cell carcinoma (SCC) cases was then conducted. The results of the histological types revealed that of the 1781 ACC cases, 435 cases (24.4%) including seven cases of adenosquamous cell carcinomas were SCC and 1260 cases (70.7%) were adenocarcinoma. However, the most common histological type reported in the USA, Europe, and Australia is SCC. Most ACC cases are adenocarcinomas and there is a low incidence of SCC in Japan which is different from the above-mentioned countries. Moreover, we reclassified T4 into the following two groups based on tumor size: T4a (tumor diameter of 5 cm or less) and T4b (tumor diameter of more than 5 cm). The results of the TNM classification of SCC revealed that the hazard ratio (HR) to T1 of T2, T3, T4a, and T4b was 2.45, 2.28, 2.89, and 4.97, respectively. As T4b cases had a worse prognosis than T4a cases, we propose that T4 for anal canal SCC in Japan be subclassified into T4a and T4b.


Adenocarcinoma , Anus Neoplasms , Carcinoma, Squamous Cell , Adenocarcinoma/pathology , Anal Canal/pathology , Anus Neoplasms/epidemiology , Anus Neoplasms/pathology , Anus Neoplasms/therapy , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Humans , Japan/epidemiology , Retrospective Studies
17.
Gan To Kagaku Ryoho ; 49(2): 195-198, 2022 Feb.
Article Ja | MEDLINE | ID: mdl-35249059

We investigated the safety and efficacy of circadian chronotherapy via the hepatic artery(chrono-HAI)as a prehepatectomy chemotherapy for initially unresectable colorectal liver metastases. Five-day course of chrono-HAI using 5-FU, l-LV, and L-OHP plus systemic panitumumab with 9-day interval were administered to 24 patients with failure for previous chemotherapy. Response rate and Grade 3 adverse effect(AE) were 63% and 54%, respectively. Among 22 patients( excluding 2 CR patients), conversion surgery could be performed in 10(45%). Two-year overall survival of patients with surgery (58%)was longer in those without(20%, p=0.057). Although incidence of AE was a bit high, chrono-HAI plus systemic panitumumab is an effective prehepatectomy chemotherapy for patients with aggressive colorectal liver metastases.


Colorectal Neoplasms , Liver Neoplasms , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/surgery , Fluorouracil , Hepatic Artery/pathology , Hepatic Artery/surgery , Humans , Infusions, Intra-Arterial , Leucovorin , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Liver Neoplasms/surgery
18.
Minim Invasive Ther Allied Technol ; 31(6): 962-968, 2022 Aug.
Article En | MEDLINE | ID: mdl-35301932

INTRODUCTION: The present study was performed to compare postoperative pain following transinguinal preperitoneal repair (TIPP) and transabdominal preperitoneal repair (TAPP) performed by a single surgeon with adequate experience in each procedure. MATERIAL AND METHODS: Adult patients who underwent herniorrhaphy for elective unilateral primary inguinal hernia repair from April 2013 to October 2019 were identified. After propensity score matching, a numeric rating scale was used to compare postoperative pain scores at 1 day, 1 week, and 1 month between patients who underwent TAPP and TIPP. RESULTS: Among 784 patients who underwent herniorrhaphy during the study period, 354 were analyzed by propensity score matching (TAPP, n = 177; TIPP, n = 177). Postoperative pain during normal activity was significantly lower in the TAPP group than in the TIPP group on day 1 (2.75 ± 1.67 versus 3.59 ± 1.86, p < 0.01), at 1 week (0.98 ± 1.11 versus 1.75 ± 1.51, p < 0.01), and at 1 month (0.11 ± 0.48 versus 0.29 ± 0.78, p = 0.01). There was no difference in pain at rest on day 1 and at one week, although TAPP was associated with significantly less pain at rest at one month than was TIPP (0.01 ± 0.08 versus 0.1 ± 0.49, p = 0.02). CONCLUSION: TAPP is preferable to TIPP in patients undergoing elective unilateral primary inguinal hernia repair in terms of reducing short-term pain.


Hernia, Inguinal , Laparoscopy , Adult , Hernia, Inguinal/surgery , Herniorrhaphy/methods , Humans , Laparoscopy/methods , Pain, Postoperative/epidemiology , Surgical Mesh , Treatment Outcome
19.
J Anus Rectum Colon ; 6(1): 52-57, 2022.
Article En | MEDLINE | ID: mdl-35128137

BACKGROUND: Anti-epidermal growth factor receptor (EGFR) therapy has been identified to prolong the survival of metastatic colorectal cancer (mCRC) patients without RAS mutations. However, its efficacy is not always consistent for these patients. Genomic profiles of primary tumors and metastases are not always concordant; thus, chemotherapeutic agents can alter the tumor molecular profile. This molecular heterogeneity may explain resistance to anti-EGFR therapy. Liquid biopsy using circulating tumor DNA (ctDNA) is a novel, non-invasive diagnostic tool that can accommodate this molecular heterogeneity, providing a comprehensive, real-time view of the molecular landscape. In this study, we evaluated the predictive value of genomic mutations in ctDNA for primary and acquired resistance to anti-EGFR therapy. METHODS/DESIGN: This study is a prospective, multicenter, observational study of mCRC patients with wild-type tissue RAS treated with cytotoxic agents and anti-EGFR antibodies as first-line therapy. Genomic mutations, including RAS, BRAF, PIK3CA, and EGFR in ctDNA, are assessed via Droplet Digital PCR before starting chemotherapy and every 3 months thereafter until disease progression. The target sample size is estimated to be 100. The primary endpoint is the response rate in patients without RAS mutation in their blood sample before starting chemotherapy. DISCUSSION: This study will clarify the predictive value of baseline RAS mutation in ctDNA for responses to anti-EGFR therapy; the frequency of emerging RAS, BRAF, PIK3CA, and EGFR mutations in ctDNA; and the association with secondary resistance to anti-EGFR therapy in first-line therapy for wild-type tissue RAS mCRC patients.

20.
Front Med (Lausanne) ; 9: 1092879, 2022.
Article En | MEDLINE | ID: mdl-36687430

Background: Invasive Klebsiella-associated liver abscesses can progress rapidly and cause severe metastatic infections such as meningitis and hydrocephalus, which are associated with high morbidity and mortality. In patients with large multiloculated liver abscesses after failure of percutaneous drainage, rapid diagnosis of the abscess followed by hepatic resection is necessary for early recovery and to prevent severe secondary metastatic complications. Case presentation: An 84-year-old woman with a large liver abscess and in septic shock was transferred to our hospital. Abdominal CT showed multiloculated liver abscesses 15 cm in diameter in the right lobe of the liver. We first performed percutaneous liver abscess drainage. The patient was managed in the intensive care unit, as well as treated with intravenous administration of meropenem followed by cefozopran according to the antibiogram. Klebsiella pneumoniae with invasive infection was confirmed by a string test in an isolated colony of K. pneumoniae; the K1 serotype with the rmpA and magA genes was determined by polymerase chain reaction and Sanger sequencing. Additional percutaneous liver abscess drainage was performed due to initial inadequate drainage. Although the abscess had shrunk to a diameter of 8 cm after drainage in 4 weeks, the patient recovered from sepsis, but still had low-grade fever (occasionally 38°C) and continued to have symptoms of chronic inflammation with persistent hyper mucus discharge from the liver abscess. Surgical resection was chosen to prevent prolonged hospitalization and ensure early recovery. A right posterior sectionectomy of the liver, including liver abscess, was performed. The post-operative course was uneventful, with no complications, and she was discharged after 18 days. There were no signs of abscess recurrence 1 year after surgery. Conclusion: We present a case of successful hepatic resection after percutaneous drainage failure in a patient with invasive K. pneumoniae multiloculated liver abscess.

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