Impact of preoperative tumor rupture timing on gastrointestinal stromal tumor prognosis: a retrospective multicentric cohort study.

BACKGROUND: A gastrointestinal stromal tumor rupture entails a high risk of recurrence even after curative surgery. However, the definition of rupture is unclear, and the question of whether patients with a minor rupture should be treated with adjuvant imatinib remains controversial. METHODS: The present, retrospective, multicentric study enrolled 57 patients with gastrointestinal stromal tumor with a minor/major tumor rupture, of whom 46 were finally found to be eligible for analysis. Tumor ruptures were subclassified by their degree, timing and cause. Multivariate analysis was performed to identify the risk factors of all types of recurrence as well as of peritoneal recurrence only. RESULTS: The study cohort included minor (n = 24), intraoperative (n = 19) and iatrogenic (n = 20) ruptures besides the typical types (major, preoperative and spontaneous). All intraoperative ruptures were iatrogenic. In total, 27 patients (58.7%) had a recurrence in the peritoneum (n = 17) and/or the liver (n = 13) during a median follow-up period of 5.8 years, but no recurrence was observed in patients with tumor rupture as a single, high-risk factor. Multivariate analysis found the timing of tumor rupture to be an independent risk factor of poor recurrence-free survival (hazard ratio: 2.37; 95% confidence interval: 1.02-5.49; P = 0.045). CONCLUSIONS: Preoperative tumor rupture in patients with a ruptured gastrointestinal stromal tumor was associated with poor recurrence-free survival. Our results suggested that a distinction should be made between preoperative and intraoperative tumor ruptures when considering the indications for adjuvant imatinib therapy for gastrointestinal stromal tumor patients with tumor rupture as a single, high-risk factor of recurrence.

Sporadic intra-abdominal desmoid tumor with a very unusual onset: two case reports.

BACKGROUND: Intra-abdominal desmoid tumors are rare soft tissue tumors that arise mainly in the mesentery and pelvis. Their etiology may include genetic mutations, estrogen-associated changes after childbirth, and mechanical factors such as a history of abdominal surgery. However, there are cases of intra-abdominal desmoid tumors that develop in the absence of such causes. Since they are rare, diagnosis is often difficult based on clinical findings. We encountered two cases of patients with sporadic intra-abdominal desmoid tumors with a very unusual onset and contrasting features. CASE PRESENTATION: The first patient was a 51-year-old asian man who presented with sudden onset of abdominal pain. He was referred to our department because of a giant tumor detected on abdominal ultrasonography. Imaging revealed a 19-cm tumor with internal tumoral hemorrhage; however, no definitive diagnosis was made. Tumor resection was performed for diagnostic and therapeutic purposes. The second patient was a 41-year-old asian man, and right hydronephrosis was detected on abdominal ultrasonography during a periodic medical checkup. We diagnosed invasion of the primary mesenteric tumor into the right ureter using diagnostic imaging and performed ileocecal resection with partial right ureteral resection for a definitive diagnosis and therapeutic purposes. Although the tumors of both patients had developed from the ileal mesentery, the tumors were substantially different from each other based on their imaging findings, macroscopic morphology, and progression pattern. Meanwhile, they showed similar pathological characteristics. Both consisted of bundles of collagen fibrils of spindle-shaped fibroblasts with low cell atypia. Moreover, they were diagnosed as desmoid tumors using positive immunohistochemical staining for ß-catenin. CONCLUSIONS: Neither patient had susceptibility factors for desmoid tumors, and to our knowledge, there have been very few reports to date of intra-abdominal desmoid tumors that were diagnosed because of acute abdominal pain caused by tumoral hemorrhage or asymptomatic obstructive uropathy. Furthermore, it is clinically interesting that the two patients showed contrasting progression patterns and imaging findings. Intra-abdominal desmoid tumors are rare and may present with various symptoms and findings similar to those observed in our patients. Diagnosis therefore requires experience and knowledge that is not bound by preconceptions.

[A Case of Left Transverse Colon Cancer Safely Resected Using Three-Dimensional CT Angiography and Indocyanine Green Fluorography].

A 77-year-old man was admitted to our hospital because of a positive occult blood test result and diagnosed as having left transverse colon cancer(cT2N0M0)on detailed examination. The patient underwent a sigmoidectomy for colon cancer 24 years previously. Three-dimensional(3D)-CT angiography was performed before the present operation. The left branch of the middle colic artery, which was independently branched, and the marginal artery of the colon were found to be supplying blood from the left side of the transverse colon to the anastomosis of the sigmoid colon. In addition, the root of the left branch of the middle colic artery arose from the caudal side of the first jejunal vein. Therefore, a left hemicolectomy was performed. In accordance with the preoperative simulation, we safely resected the left branch of the middle colic artery at the root. Intraoperative blood flow evaluation using indocyanine green(ICG)fluorography clearly displayed the demarcation of the oral blood flow and the point of anastomosis. No notable complications occurred after the surgery. The results of the pathological analyses indicated a pT1bN0M0 tumor stage. Therefore, we conclude that 3D-CT angiography and ICG fluorography are useful for performing safer operations for left transverse colon cancers.

GSTP1 as a potential predictive factor for adverse events associated with platinum-based antitumor agent-induced peripheral neuropathy.

Glutathione S-transferase (GST) exhibits antidotal effects on numerous drugs, including platinum-based antineoplastic drugs. Furthermore, GST Pi 1 (GSTP1) polymorphism is associated with peripheral neuropathy. In the present study, it was determined whether GSTP1 can predict adverse events associated with platinum-based antitumor agent-induced peripheral neuropathy among Japanese patients. The subjects included 122 patients, among whom 105 patients had colorectal, 16 had gastric, and one patient had pancreatic cancer. It was indicated that wild type (AA) GSTP1 was expressed in 99 patients (81.1%), whereas heterozygous (AG) and homozygous (GG) GSTP1 polymorphisms were present in 22 (18.0%) and 1 (0.8%) patients, respectively. Among patients with colorectal cancer, the expression of homozygous GSTP1 was observed in 88 patients (83.8%), whereas that of heterozygous GSTP1 was observed in 17 patients (16.2%). Peripheral neuropathy of grade ≥3 occurred in 10 patients (9.5%) receiving mFOLFOX therapy (a biweekly cycle consisting of a 2-h infusion of 85 mg/m2 oxaliplatin and 200 mg/m2 leucovorin followed by a bolus administration of 400 mg/m2 5-fluorouracil and a continuous 48-h infusion of 2,400 mg/m2 5-fluorouracil) for colorectal cancer, which included 6 patients with the AA allele (6.8%) and 4 patients with the AG allele (23.5%). The number of peripheral neuropathy cases of grade ≥3 was increased among patients with the AG allele, compared with patients with the AA allele (P=0.032). In patients with gastric cancer, the AA and AG types of GSTP1 were expressed in 11 (68.8%) and 5 (31.2%) patients, respectively. Cisplatin, administered to patients with gastric cancer, did not induce peripheral neuropathy. The aforementioned indicated that GSTP1 genetic polymorphism is associated with peripheral neuropathy induced by oxaliplatin treatment for colorectal cancer, and therefore serves as a predictive marker. Furthermore, early dose reduction or drug withdrawal should be implemented depending on the severity of peripheral neuropathy as a potential method for reducing the number of patients discontinuing the drug, due to adverse events involving peripheral neuropathy.

[A Case of Early Rectal Cancer Recurring as Liver Metastasis Nine Months after ESD].

A 70-year-oldwoman underwent colonoscopy as a follow-up examination for colon polyps, during which early-stage rectosigmoid cancer was detected. Endoscopic submucosal dissection(ESD)was performed to remove this lesion. Additional radical anterior resection was recommended according to the histological findings but the patient chose to undergo observation. Nine months after the ESD, the patient decided to undergo additional surgical resection: a CT scan revealed liver metastasis in S6. Laparoscopic anterior resection andpartial resection of S6 of the liver was performed. Histological analysis showed no residual cancer in the rectosigmoid, no lymph node metastasis, and liver metastasis in S6. Carcinoma cells were exposed on the radial margin of the liver. After surgery, oral UFT/LV chemotherapy was administered for 6 months. The patient remains free of recurrence 4 years and6 months after the surgery.

Pre-existing interstitial lung disease as a risk factor for pneumonitis associated with ramucirumab and paclitaxel in patients with gastric cancer: The impact of usual interstitial pneumonia.

OBJECTIVE: Combination treatment with ramucirumab and paclitaxel shows significant efficacy in patients with advanced gastric cancer as a second-line standard therapy. However, limited information is available about the development of pneumonitis associated with this treatment in clinical practice. This study aimed to characterize this form of pneumonitis and identify the risk factors for its onset. METHODS: We retrospectively analyzed the medical records of 44 patients with gastric cancer who received combination treatment with ramucirumab and paclitaxel from 2016 to 2017. Then, the clinicopathological characteristics of patients who developed treatment-related pneumonitis were evaluated and further compared with those of patients who did not. RESULTS: Six patients (13.6%) developed pneumonitis within five treatment cycles, and in five cases, remission was observed after cessation of combination treatment alone. The onset of pneumonitis was independently associated with pre-existing interstitial lung disease (ILD) (p = 0.025; odds ratio = 206.4). Patients with pneumonitis showed reduced time to treatment failure (median 56 vs. 138 days; p = 0.008), as compared with those without pneumonitis. Most patients with pre-existing ILD with a usual interstitial pneumonia (UIP) pattern developed pneumonitis. CONCLUSIONS: In clinical practice, pneumonitis associated with the combination treatment of ramucirumab and paclitaxel was generally mild, but common. Patients with gastric cancer with pre-existing ILD, particularly those presenting with a UIP pattern, undergoing this combination treatment, should be carefully monitored for the development of treatment-related pneumonitis.

[Pathological Complete Response in 3 Patients with Esophageal Cancer Treated with Neoadjuvant Chemoradiation Therapy].

Neoadjuvant chemotherapy(NAC)for esophageal cancer is standard in Japan. However, the value of neoadjuvant chemoradiation therapy(NACRT)is unknown. Thirteen patients with cStage II and III squamous cell carcinoma of the esopha- gus were treated with NACRT(CDDP 70mg/m2/day on day 1, 5-FU 70 mg/m2/day on days 1-4, radiation 30 Gy/15 Fr). We report 3 pathological CR cases and 10 non-CR cases of esophageal cancer. Between the CR and non-CR group there was no difference in the incidence of postoperative complications. No serious adverse events were observed. There were no significant differences in OS and RFS. Five cases relapsed in the non-CR group. There were no relapsed cases in the CR group.

A case of a gastrointestinal stromal tumor with skeinoid fibers of the sigmoid colon.

An 80-year-old man was diagnosed with rectal cancer and underwent Hartmann's procedure. Although no tumors were identified during the preoperative examination, gross examination of the resected specimen incidentally revealed a submucosal tumor that was 9 mm in diameter at the oral side and located in the proximal stump of the specimen from the sigmoid colon. We suspected a concurrent gastrointestinal stromal tumor (GIST) and performed a histopathological examination. An L-shaped nodular lesion measuring 9 × 6 mm was histologically composed of a patternless proliferation of spindle cells intermingled with eosinophilic globules. Cellular atypia, prominent mitotic figures and necrotic foci were not observed in the nodule. The spindle cells were positive for CD34, CD117 and vimentin, but negative for CD56, smooth muscle actin and S-100 protein. MIB-1 positivity was estimated to be as low as approximately 1-2%. Electron microscopy showed a bundle of wool-like fibers with a periodicity of approximately 40 nm. We therefore considered the lesion to be a low-risk GIST with skeinoid fibers in the large intestine. Although numerous previous reports have reported skeinoid fibers in the stomach and small intestines, there have been only 9 cases (including the present case) of skeinoid fibers in the large intestine.

[Long survival and effective treatment of unresectable gastric cancer by TS-1 based chemotherapy with a sequential combination].

We report a case of peritoneal cancer dissemination and cytological appearance of cancer cells with Type 4 gastric cancer. Treatment with unichemotherapy and combination chemotherapy with TS-1 proved successful. The patient was a 58-year-old female,who complained of abdominal pain. She was diagnosed as unresectable Type 4 gastric cancer, T 3 NxH 0 P 1 CY 1 M 0, Stage IV (cytology: Class V). Thirteen days after surgery, chemotherapy with TS-1 (80 mg/body/day, 4 weeks) at 2-week intervals in 1 course was performed. However, due to side effects with marrow restraint of grade 1, we changed to the following chemotherapy regimen: TS-1 (80 mg/body/day, 2 weeks) at 4-week intervals as 1 course (23 courses in total). After 16 courses, a partial response (PR) was noted. As additional therapy to recover tumor marker (CA19-9) after 21 courses, combination chemotherapy with TS-1 (80 mg/body/day, 2 weeks) and CDDP (25 mg/body/day, day 1, 8, 15 drip infusion) was performed as one course. This chemotherapy was then performed in 3 courses and tumor markers did not deteriorate, so we changed docetaxel (DOC) (50 mg/body/day(day 1)) to CDDP, and tumor markers returned to the normal value. No recurrence and no side effects appeared (hematological or non-hematological) during this combination chemotherapy.

[A long-term survival case of metachronous liver metastasis from gastric cancer].

A 62-year-old man was admitted for gastric cancer. He was performed a distal gastrectomy with Billroth I reconstruction in August 1999. Then he had remnant gastric cancer and metachronous liver cancer in November 2002. He was performed a total gastrectomy and partial hepatic resection. The histological findings of remnant stomach and liver cancer showed a same pattern of the primary gastric cancer. Another metachronous liver cancer appeared in March 2006. He was treated with chemotherapy using S-1 (day 1-21) and CDDP 20 mg/m2 (day 1, 8 and 15) q5w. The size of liver metastasis was kept the same for 16 months.

[The efficacy of gastrojejunostomy for patients with unresectable gastric cancer].

We evaluated the efficacy of gastrojejunostomy for patients with unresectable gastric cancer. Thirteen patients had undergone gastrojejunostomy (GJ group) and 14 patients who couldn't receive gastrojejunostomy, but had only been observed into their abdomen in the operation (S group). Between two groups, there were no significant differences in the effective rate, median survival time and the number of dates the patient stayed home after the operation. Gastrojejunostomy was useful for patients with a strong case of stenosis in the stomach, and may improve the quality of life as one of the multimodal therapy.

[The efficacy of intra-peritoneal chemotherapy for the patients with cytology positive gastric cancer].

In this study, we assessed efficacy of repeated intra-peritoneal chemotherapy with CDDP for patients with cytology positive gastric cancer. The median survival time was 338 days, 1-year survival was 60% and 2-year survival was 45% of the patients. The POCY1 patients with repeated intra-peritoneal chemotherapy yielded a tendency to extend the survival rate than the patients without repeated intra-peritoneal chemotherapy (p = 0.06). But, no differences were found between the survival rate of P1CY1 patients with or without repeated intra-peritoneal chemotherapy. The patients using more than 3 anti-cancer drugs yielded a tendency to have a better prognosis than the patients using 2 or less anti-cancer drugs (p = 0.09). There was a possibility to which the multidiscipline treatment was effective for the POCY1 gastric cancer patients.

[A case of curatively resected gastric cancer through an effective response to chemotherapy].

The patient is a 66-year-old male who underwent gastrojejunostomy at another hospital with the diagnosis of type 3 unresectable gastric cancer. He was admitted to our hospital for adjuvant chemotherapy. A CT scan revealed both peritoneal dissemination and a large tumor directly invading the pancreas and liver. After 7 courses of combined chemotherapy with 5-FU, Leucovorin, cis-platinum and methotrexate, an effective response, tumor reduction and the disappearance of peritoneal dissemination, was verified by CT scan. Pancreatoduodenectomy with transverse colectomy was carried out and the pathological diagnosis was also curative (pT3, pN1, pP0, HO: stage III A). Although he unfortunately died from peritoneal recurrence after 9 months, he maintained good quality of life after re-operation. We think this case shows the possibility of NAC for patients with far advanced gastric cancer with peritoneal dissemination to improve their prognosis or QOL.

[The present and future of home care chemotherapy for patients with advanced and recurrent colorectal cancer].

PURPOSE: If the chemotherapy at home is as effective as the chemotherapy at an outpatient clinic, QOL of the patients will be improved. In this paper the future of chemotherapy at home was clarified from the outcome of the chemotherapy for advanced and recurrent colorectal cancer. METHOD: Hepatic arterial infusion chemotherapy (HAI) (5-FU 2,000 mg/w, continuous infusion for 7 days, n=123) for unresectable liver metastases and FL chemotherapy (5 FU 1,500 mg + l-LV 375 mg/w, continuous systemic chemotherapy for 7 days, n=32) for extra hepatic recurrence were carried out at home by a portable pump system every other week. RESULTS: The response rates were 61.2% in HAI and 18.8% in FL. MST were 14.7 months in HAI and 10.8 months in FL. It was important to establish a surveillance network system to continue the chemotherapy at home. CONCLUSIONS: It was suggested that the chemotherapy at home was effective and to maintain the patient's QOL as one of the options.

[A new systemic combination chemotherapy to be provided at home for patients with unresectable recurrent colorectal cancer].

We compared the effectiveness of 5-FU + l-LV with CDDP + 5-FU as a systemic chemotherapy for unresectable recurrence of colorectal cancer. The protocol we carried out in one group was as follows: (Group 1) 5-FU 2,000 mg mixed with l-LV 100-200 mg in the disposable balloon pump was administered continuously for 1 week. In the other group, (Group 2) we administered CDDP 5 mg/day every 5 days for a week and continuous 5-FU 500 mg/day for 3 weeks in the hospital, and in the outpatient clinic CDDP 5 mg/day every 2 days for a week with UFT-E 300-600 mg/day, orally, everyday. The response rate of Group 1 was 18.8% and that of Group 2 was 19.3%; the median survival time (MST) was 10.8 months for Group 1 and 8.4 months for Group 2. There were no significant differences between the 2 groups regarding these parameters. Hand foot syndrome (HFS) was observed in 43.8% of the patients, and stomatitis in 37.5% of all cases as adverse effect of systemic chemotherapy using 5-FU + l-LV. But the grade of the adverse effect was low and patients could continue with this systemic chemotherapy.

[A new systemic combination chemotherapy to be provided at home for patients with unresectable recurrent colorectal cancer].

We compared the effectiveness of 5-FU + l-LV with CDDP + 5-FU as a systemic chemotherapy for unresectable recurrence of colorectal cancer. The protocol we carried out in one group was as follows: (Group 1) 5-FU 2,000 mg mixed with l-LV 100-200 mg in the disposable balloon pump was administered continuously for 1 week. In the other group, (Group 2) we administered CDDP 5 mg/day every 5 days for a week and continuous 5-FU 500 mg/day for 3 weeks in the hospital, and in the outpatient clinic CDDP 5 mg/day every 2 days for a week with UFT-E 300-600 mg/day, orally, everyday. The response rate of Group 1 was 18.8% and that of Group 2 was 19.3%; the median survival time (MST) was 10.8 months for Group 1 and 8.4 months for Group 2. There were no significant differences between the 2 groups regarding these parameters. Hand foot syndrome (HFS) was observed in 43.8% of the patients, and stomatitis in 37.5% of all cases as adverse effect of systemic chemotherapy using 5-FU + l-LV. But the grade of the adverse effect was low and patients could continue with this systemic chemotherapy.