A case with liver resection of metastasis from rectal cancer after bevacizumab treatment

The advancement of systemic chemotherapy for colorectal carcinoma has improved a clinical response rate and expanded a possibility of resection, which we thought we could not have been operable at the initial visit. It also improved a prognosis of patients. We report here a case with liver resection of metastasis from rectal cancer followed by bevacizumab treatment.     

A case of rectal hemorrhage during chemotherapy with bevacizumab for local recurrence of rectal cancer

Chemotherapy with bevacizumab(BV)has been one of the standard treatments for patients with metastatic colorectal cancer. However, emergent treatments are sometimes required because of severe adverse events associated with it. We experienced a case of massive rectal hemorrhage during BV treatment, and interventional radiology(IVR)successfully controlled it. An 81-year-old male visited our hospital, suffering from local recurrence of rectal cancer. He underwent colostomy for fecal diversion, and chemoradiation therapy was performed. Systemic chemotherapy with XELOX+BV was performed for the residual tumor. On the 27th day after the first administration of BV, the patient was hospitalized because of anal bleeding and a state of shock. The colonoscopic examination showed a dimple caused by tumor shrinkage, which was closed by clipping. However, a state of shock was caused by intermittent hemorrhages again afterwards. The hemorrhagic point was identified as the oral side of the dimple by angiography, and coil embolization led to immediate hemostasis. The colonoscopic examination revealed nothing abnormal besides the dimple. It is therefore suspected that the cause of rectal hemorrhage might be induced by BV. During combination chemotherapy with BV, bleeding is one of the severe adverse events requiring an emergent treatment regardless of BV dose. IVR may be an effective treatment when bleeding can not be controlled by endoscopic hemostasis. Therefore, we should construct a system for emergency hemostasis including IVR.     

Sigmoid colon cancer with a tumor thrombosis in the splenic vein--a case report

A 63-year-old woman was admitted to the hospital for investigation of abdominal discomfort. Further examination revealed that she had sigmoid colon cancer. The serum CEA level was 20.1 ng/ml, and the CA19-9 level was 8.9 U/ml. Laparotomy findings showed H0, P0, and lymph-nodes swelling observed at LN253-LN16b2. Massive tumor thrombosis was present in IMV, the splenic vein, and the advanced region in the portal vein. Metastatic tumor was present in the pancreas body. An anterior resection of the colon combined with resection of lymph nodes, pancreas body and tail and spleen were performed. Resection of IMV and splenic vein including tumor thrombosis was performed prudently. Histological examination revealed that the pancreas tumor and tumor thrombosis were of the same origin (moderately differentiated from adenorarcinoma), and massive LN metastases existed. Post operative chemotherapy, an oral administration of UFT/UZEL, was performed. After 24 months of operation, there has been no sign of recurrence detected.     

A case of metastatic colon cancer treated with oxaliplatin combination chemotherapy

A 77-year-old male had been operated for ascending colon cancer with liver metastases. After hepatic artery injection therapy and CPT-11 plus 5'-DFUR combination therapy, oxaliplatin-based systemic chemotherapy was performed. Consequently, the tumor size was controlled for about 10 months. During the chemotherapy, we observed grade 3 neurological toxicity, but not grade 3-4 blood toxicity. Thus, the QOL of the patient was properly maintained. We conclude that the oxaliplatin-based chemotherapy may be useful for patients suffering 5-FU and CPT-11 resistant metastatic colorectal cancer in Japan.     

贝伐单抗结合化疗治疗晚期结肠癌的生存分析

目的:分析影响接受贝伐单抗结合化疗治疗晚期结肠癌患者生存情况的因素。方法:回顾性分析2008年5月至2012年5月期间接受贝伐单抗结合化疗治疗的60例晚期结肠癌患者的临床资料和随访记录,探讨治疗时间、心血管副反应、K-ras基因型、单器官转移部位及贝伐单抗维持治疗对生存期的影响。结果:接受治疗超过半年的患者中位无进展生存期(PFS)及总生存期(OS)长于治疗时间半年以内的患者,差异具有统计学意义(P=0.023;P=0.043)。出现心血管副反应的患者中位PFS及OS长于未出现心血管副反应的患者(P=0.014;P=0.032)。K-ras基因野生型和突变型患者的PFS及OS有统计学差异（P=0.024;P=0.039）。单器官转移至肝脏的患者与单器官转移到卵巢的患者,其PFS及OS无统计学差异（P=0.853;P=0.835）。行贝伐单抗维持治疗的患者,其OS长于未行维持治疗的患者(P=0.013)。结论:在贝伐单抗和化疗联合治疗的晚期结肠癌患者中,治疗时间和出现心血管副反应可能是患者的预后因素。行贝伐单抗维持治疗可使患者生存受益     

A case of multiple liver metastases from colon cancer successfully operated after intraarterial chemotherapy performed in home

A 60-year-old male patient had unresectable multiple liver metastases from a sigmoid colon cancer that had been resected, and thus hepatic arterial infusion therapy was planned. A heparin coated catheter was inserted from the left thoracoacromial artery to the proper hepatic artery. 5-fluorouracil (1,000 mg) was administered via the catheter 24 hours/week using an implantable vascular device and a small disposable pump in his home. After 59 weeks, the metastatic liver tumors had decreased remarkably in size, and all tumors could be resected completely through surgery. Three weeks after the operation, the same intraarterial chemotherapy was restarted to prevent the recurrence in the liver. However, the patient died of lymph node recurrences. The intraarterial chemotherapy is thought to be useful for neoadjuvant therapy in patients with inoperable liver metastasis from colon cancer.     

A case of multiple liver metastases from colon cancer successfully treated with pharmacokinetic modulating chemotherapy

The present patient was a 54-year-old woman with anemia. After examination to identify the cause of anemia, she was diagnosed with sigmoid colon cancer and multiple liver metastasis. Sigmoid colectomy and insertion of an intra-hepatic arterial catheter were carried out. Histopathological examination of the resection specimen revealed well-differentiated adenocarcinoma, with a depth of tumor invasion of ss and positive lymph node metastasis. Pharmacokinetic modulating chemotherapy (PMC) was performed after the operation. The PMC consisted of oral UFT 300 to 400 mg/day every day and continuous arterial infusion of 5-FU 750 to 1,000 mg/24 h once a week. On a CT scan of the abdomen performed 6 months after the operation, the liver metastasis had disappeared and the patient was in complete remission (CR). PMC was continued, but the hepatic artery became occluded 1 year and 11 months after the operation, and so PMC was replaced by systemic chemotherapy of 5-FU plus levofolinate at 2 years after the operation. This chemotherapy was discontinued after 3 courses. At present, 2 years and 10 months after the operation, the patient remains in CR and is followed as an outpatient.     

贝伐珠单抗联合化疗治疗结直肠癌肝转移的疗效观察

目的探讨贝伐珠单抗(BV)联合化疗治疗结直肠癌肝转移的临床疗效。方法选取2013年3月至2015年3月间济宁医学院附属医院湖西医院收治的86例结直肠癌肝转移患者,按入院时间随机分为观察组和对照组,每组43人。对照组患者采用奥沙利铂+亚叶酸钙+氟尿嘧啶(FOLFOX方案)化疗,观察组患者采用BV联合FOLFOX方案化疗。结果观察组疾病控制率高于对照组患者,差异有统计学意义(P<0.05)。两组患者严重不良反应发生率比较,差异无统计学意义(P>0.05)。观察组患者无进展生存时间高于对照组患者,差异有统计学意义(P<0.05)。观察组患者1年和2年生存率均高于对照组患者,差异有统计学意义(均P<0.05);两组患者3年生存率比较,差异无统计学意义(P>0.05)。治疗后,观察组患者上升时间(RT)和平均渡越时间(mTT)均显著升高,差异均有统计学意义(均P<0.05),而对照组的RT和mTT并无显著变化,差异无统计学意义(P>0.05),且观察组在不同检测时间点RT和MTT均高于对照组,差异均有统计学意义(均P<0.05)。结论 BV联合化疗治疗结直肠癌肝转移,可延长患者无进展生存时间,提高1年及2年生存率;超声造影定量参数RT和MTT可用来评估结直肠癌肝转移患者的早期疗效。     

Severe gastric and duodenal ulcer after chemotherapy of mFOLFOX6 and bevacizumab

A 74-year-old female had metastatic left inguinal lymph nodes 20 months after rectal amputation for cancer, and an attempt to adapt chemotherapy of mFOLFOX6/bevacizumab was made after resection of the nodes. She felt nausea 2 days and continued 1 week after starting chemotherapy. Then, an endoscopic examination revealed both active gastric and duodenal ulcers. Clipping and proton pump inhibitor medication was started. The ulcers healed to the healing stage at 18 days and to the scar stage at 28 days. Gastrointestinal complications often occur after chemotherapy, but severe ulcers are rarely reported. The chemotherapy included anti-VEGF antibody, but the ulcers have healed back to normal.     

A case with liver resection of metastasis from rectal cancer after FOLFOX4+bevacizumab treatment

We report a 59-year-old woman with rectal cancer who underwent low anterior resection in March 2007. After curative operation at Stage IIIb(pT3N2M0), multiple liver metastasis was diagnosed in May 2007. Chemotherapy with FOLFOX4+bevacizumab was performed from June to August in 2007, and liver resection(left lobectomy and partial resection)was performed in September 2007. Bevacizumab was newly available from June 2007 in Japan, and liver resection after bevacizumab administration was safely performed.     

A case of high CEA colon cancer responding to neoadjuvant chemotherapy with FOLFIRI

We report a case of high CEA advanced colon cancer, which we were able to down stage after treatment with FOLFIRI-1. The patient was a 56-year-old woman who had advanced sigmoid colon cancer with high CEA. It was suspected that the tumor had directly invaded the ovary by CT scan. For curative operation, hysterectomy was considered necessary. Neoadjuvant therapy was performed to avoid an extensive operation. After the fourth course, according to colonoscopy and CT findings, a significant tumor reduction was obtained. Sigmoid colorectomy with D3 nodal dissection was then performed. The histological diagnosis was pT1, pN0, PStage I. The histological effect was observed in lymph node metastasis. The patient was recurrence free at her 3-year follow-up examination.     

Efficacy of the combined use of bevacizumab and irinotecan as a postoperative adjuvant chemotherapy in colon carcinoma

We evaluated the efficacy of anti-human VEGF antibody (bevacizumab) with or without irinotecan (CPT-11) against lung metastases in which neovascularization was already induced, as a postoperative adjuvant therapy using orthotopically implanted colon cancer in rat. The high VEGF productive KM12SM human colon cancer cells were injected into the cecal wall. At 5 weeks after the injection, the cecum was removed including the tumor. Then, 5 mg/kg of bevacizumab and 40 mg/kg of CPT-11 were administered, alone or in combination, intravenously once a week for 3 weeks, from day 15 after the cecal removal. The results show that the incidences of macroscopic and/or microscopic lung metastases in the bevacizumab-alone group (B) and in the combination group (C) were significantly lower (B, p=0.001 and C, p=0.037) than that in the control group at day 35 after the cecal removal. The number of lung metastases in B was 0.8+/-0.8 (p=0.024) and in C 2.4+/-1.8 (p=0.060), each value lower than the 12.4+/-4.2 of the control group. The growth of a subcutaneously implanted tumor was significantly inhibited in the combination group compared to either the CPT-alone (p=0.003) or the bevacizumab-alone groups (p=0.027). Apoptosis was significantly (p<0.001) induced in the combination group. In conclusion, a beneficial effect of bevacizumab against postoperative lung metastases may be expected even after the establishment of neovascularization in metastatic foci in nude rat. The results from the present subcutaneously implanted tumor model suggested that a higher efficacy may be expected when bevacizumab is combined with the cytotoxic agent CPT-11, compared to bevacizumab alone, against tumors with a variety of VEGF production levels in clinical situations.     

A case report--TS-1/CDDP combined chemotherapy found effective for metastatic recurrence after operation for colon cancer

A 68-year-old male with a history of gastric resection for gastric cancer underwent resection of the sigmoid colon for a sigmoid colon cancer in February, 2000. The cancer was classified as stage III b. After operation, l-LV + 5-FU therapy was administered, but metastases to the abdominal wall, right inguinal lymph node and spleen developed in succession, and resection was repeated. In October 2001, 1 year and 8 months after sigmoidectomy, however, multiple metastasis to the intraperitoneal lymph node had developed. As surgery was not indicated, TS-1/CDDP combined chemotherapy was started. TS-1 80 mg/day was administered for 4 weeks, the drug was withdrawn for 2 weeks and CDDP 80 mg was injected by intravenous drip at the 8th day of TS-1 administration, which was used as one course. From the second course after inception of the administration, CA19-9 decreased, and after the third course the upper intraperitoneal metastatic lesion disappeared on CT. CR has been continued for 4 months up to the present. Our results suggest a possibility that this therapy is effective not only for gastric cancer but also for colon cancer. This therapy can be administered at home. It is considered to be a useful therapy from the viewpoint of QOL as well. The high DPD activity of the tumor may have been one reason this treatment was effective. This case also seems significant from the viewpoint of attaining individualization of the drug selection in chemotherapy.     

Locoregional recurrence patterns after mastectomy and doxorubicin-based chemotherapy: implications for postoperative irradiation.

PURPOSE: The objective of this study was to determine locoregional recurrence (LRR) patterns after mastectomy and doxorubicin-based chemotherapy to define subgroups of patients who might benefit from adjuvant irradiation. PATIENTS AND METHODS: A total of 1,031 patients were treated with mastectomy and doxorubicin-based chemotherapy without irradiation on five prospective trials. Median follow-up time was 116 months. Rates of isolated and total LRR (+/- distant metastasis) were calculated by Kaplan-Meier analysis. RESULTS: The 10-year actuarial rates of isolated LRR were 4%, 10%, 21%, and 22% for patients with zero, one to three, four to nine, or >/= 10 involved nodes, respectively (P <.0001). Chest wall (68%) and supraclavicular nodes (41%) were the most common sites of LRR. T stage (P <.001), tumor size (P <.001), and >/= 2-mm extranodal extension (P <.001) were also predictive of LRR. Separate analysis was performed for patients with T1 or T2 primary disease and one to three involved nodes (n = 404). Those with fewer than 10 nodes examined were at increased risk of LRR compared with those with >/= 10 nodes examined (24% v 11%; P =.02). Patients with tumor size greater than 4.0 cm or extranodal extension >/= 2 mm experienced rates of isolated LRR in excess of 20%. Each of these factors continued to significantly predict for LRR in multivariate analysis by Cox logistic regression. CONCLUSION: Patients with tumors >/= 4 cm or at least four involved nodes experience LRR rates in excess of 20% and should be offered adjuvant irradiation. Additionally, patients with one to three involved nodes and large tumors, extranodal extension >/= 2 mm, or inadequate axillary dissections experience high rates of LRR and may benefit from postmastectomy irradiation.     

Local-regional recurrence in breast cancer after mastectomy and adriamycin-based adjuvant chemotherapy: evaluation of the role of postoperative radiotherapy

In an attempt to determine whether patients treated for breast cancer with radical or modified radical mastectomy and adjuvant chemotherapy benefit from postoperative radiotherapy, 400 women with Stages II-III breast cancer who received adjuvant chemotherapy based on the combination of Adriamycin and Cytoxan were analyzed retrospectively. Prognostic features which predicted a high risk of isolated local-regional relapse were identified. Thirty-eight percent of these patients were also treated with postoperative radiation in addition to adjuvant chemotherapy and were compared to those patients treated only with adjuvant chemotherapy. With a median follow-up of 60 months, 15% of the patients reviewed developed local-regional disease as the first site of relapse without concommitant systemic relapse. When examined univariately, stage of disease, tumor size, nodal status, and estrogen receptor status were strong prognostic variables. Age, cell type, location of tumor within the breast, menstrual status, radiation dose, and type of treatment were not significantly related to isolated local-regional relapse. However, patients who received postoperative radiation were significantly more advanced in their disease condition. When the factors were examined multivariately, the type of treatment along with stage of disease were found to be statistically significant prognostic indicators. About half of the patients were tested for estrogen receptor status. Multivariate analysis performed on this subset of patients showed that estrogen receptor status, type of treatment, and axillary nodal status were significant predictors of the risk of isolated local-regional relapse. This study suggests that patients treated with mastectomy and Adriamycin and Cytoxan-based adjuvant chemotherapy may benefit from postoperative radiation in reducing the risk of isolated local-regional recurrence.     

A case of multiple pyomyositis after chemotherapy for lung cancer

We here describe a case of multiple pyomyositis in a 62-year-old man who had systemic chemotherapy for recurrent lung cancer. His initial symptoms consisted of fever and general fatigue, followed by progressive pain and swelling in his extremities, which mimicked deep venous thrombosis along with bacterial infection. He was admitted to the hospital for intravenous administration of antibiotics. MRI appeared very useful to find the intramuscular fluid collections with circumferential inflammatory changes, which confirmed diagnosis of the multiple pyomyositis. Surgical drainage as well as intravenous administration of antibiotics worked very well and improved clinical symptoms in a few weeks after the treatments. He could resume normal activities with minimum functional impairments in the extremities. Pyomyositis should be kept in mind as one of the adverse effects after chemotherapy for malignant tumors.     

A case of delayed colonic perforation after metallic stent placement for advanced descending colon cancer during bevacizumab-based chemotherapy

A 73-year-old man with advanced descending colon cancer and peritoneal metastases underwent a self-expandable metallic stent placement under fluoroscopic guidance on October 2007. The stent placement was successful without early complication. After 6 courses of FOLFOX4 followed by 7 courses of FOLFIRI, he received Bevacizumab-based chemotherapy from August 2008. In April 2009, he was admitted to our hospital with severe abdominal pain due to perforation of descending colon. Although emergent surgery was performed, he developed DIC and died on the 21 postoperative days. This case suggests that metallic stent placement for colorectal cancer cases might increase the risk of bowel perforation during Bevacizumab-based chemotherapy.     

A case of pathologically by complete response in advanced sigmoid colon cancer with multiple metastases of lung and Liver, left hydronephrosis after chemotherapy including bevacizumab/FOLFOX6

A 61-year-old complaining of anorexia and general fatigue was admitted to our hospital for further examination. She was diagnosed as advanced sigmoid colon cancer with multiple metastases of lung, liver, and left hydronephrosis. Since curative surgery was not deemed possible, we started chemotherapy with bevacizumab/FOLFOX6 (bi-weekly drip infusion). After the 6th course, colonoscopy revealed a significant tumor reduction and changes to the scar tissues. CT did not reveal a complete disappearance, but found some reductions in metastases of lung and liver. Sigmoidectomy and lymph node resection (D1) were performed. We did not disappeared any dissemination and the histological diagnosis revealed a complete disappearance of cancer cells in the main tumor. She was discharged 13 days after surgery, following chemotherapy which included bevacizumab and XELOX. The chemotherapy using bevacizumab/FOLFOX6 is a candidate for the standard treatment strategy for inoperable advanced colon cancer. Herein we report this rare case with a review of the literature.     

A surgical (pancreatoduodenectomy) case of lymph node metastatic recurrence of colon cancer after chemotherapy

A woman in her fifties underwent a right hemicolectomy (D3) for cancer of the ascending colon in October 2007, definitively and pathologically diagnosed as papillary adenocarcinoma invading to the subserosa, and no metastasis was detected to lymph node. But 13 months after the surgery, she was found to have a mass near the anastomosis by an abdominal CT scan. Colonoscopy showed an evaluating lesion with ulcer in the anal side of the anastomosis. We tried to resect the metastasis, but it was not resectable because of the invasion to the pancreas. The mFOLFOX regimen was effective. After the chemotherapy (6 courses), we decided to perform a radical resection. We conducted pancreatoduodenectomy in May 2009. She is still alive 12 months after surgery.