[Combined Modality Therapy for Giant Hepatocellular Carcinoma and Multiple Lung Metastases-A Case Study].

Here, we present the case of a 47-year-old woman with liver masses having distinct borders, which were located approximately 13 cm from the left hepatic lobe S4, as visualized on a CT scan. Hepatocellular carcinoma(HCC)was suspected from these contrast findings. Additionally, we found nodules in the right upper lobe of the lung and in the left apex. Although test results for hepatitis B and C viruses were negative, the α-fetoprotein(AFP)level was elevated. The tumor was diagnosed as a HCC with suspected multiple lung metastases. Thereafter, a resection was performed for the HCC. However, multiple recurrences were observed. Arterial embolization using transcatheterization was performed thrice 5 months after resection. Further, 6 months after resection, lenvatinib therapy was initiated as the pulmonary nodule increased in size. One year after the operation, a recurrent neoplastic lesion in the liver was detected on the contrast-enhanced MRI. Since the earlier treatment with transcatheter arterial embolization proved to be minimally effective, we opted for arterial injection chemotherapy with cisplatin plus 5-FU for approximately 3 months. The contrast-enhanced CT revealed that the lesion became a low absorption lesion in the liver outside the central area, and the AFP also decreased rapidly. Therefore, the therapy was considered effective. As a side effect of arterial injection chemotherapy, the patient developed a duodenal ulcer. However, after treating the ulcer, a pulmonary metastasectomy was performed and no obvious recurrence was noted. Typically, for treatment of extrahepatic metastases of HCC, drugs such as sorafenib or lenvatinib that have molecular targets are selected according to a treatment algorithm based on liver cancer practice guidelines. However, these drugs were not effective in this case, whereas arterial injection chemotherapy showed satisfactory therapeutic effect on the recurrences in the liver. Although there was a complication of duodenal ulcer, this case report highlights that combined modality therapy including arterial injection chemotherapy is successful in treating HCC.

[Study of the Treatment for Colorectal Cancer(CRC)in Elderly People Aged 80 Years or Older].

Aging in local cities is increasing in Japan, and Kitakyushu city is one of them. In particular, in the area in which our hospital is located, the old-age dependency ratio(ie, individuals who are 65 years old or older per hundred individuals who are 15-64 years old)is 35.2%, which is much higher than the old-age ratio of 26% in Japan, and the average age is 50.6 years. In Yahatahigashi-ku, elderly people who are older than 80 years of age account for 35.4%of the population. In consideration of this, we examined how far to do the treatment administered for CRC in elderly patients. We studied 17 patients who were older than 80 years of age and diagnosed with CRC in 2017. The performance status(PS)scores were PS 0, 1, 2, 3, and 4 in 4, 5, 1, 6, and 1 cases(s), respectively. The patients who were immobile, but still able to retain regular dietary intake, also underwent surgery. The degree of progression of the cancer was Stage Ⅰ, Ⅱ, ⅢA, ⅢB, and Ⅳ in 1, 11, 3, 0, and 2 cases, respectively, and chemotherapy was administered for the 2 patients with Stage Ⅳcancer. One patient died unexpectedly due to thoracic aortic rupture after the surgery. In our hospital, we positively perform surgeries for CRC to avoid decreases in ADL. On the other hand, we often encounter unexpected complications due to many comorbidities. We report the CRC treatment strategy for elderly people in our hospital with specific examples.

[A Case Report of Gastrointestinal Bleeding with Difficulty in Diagnosis].

The authors report a case involving a 55-year-old female patient who presented with melena and anemia 8 years ago. Esophagogastroduodenoscopy, colonoscopy, and CT did not reveal any sign of lesions except multiple uterine myoma. On reevaluation after the onset of melena, we did not find any lesions. However, the patient had a recurrent episode of melena with progressive anemia(Hb level 12.8 g/dL→9.8 g/dL). CT revealed a 29mm mass in the right side of the pelvis, which was retrospectively observed in the past CT scan, although its position had changed. We suspected gastrointestinal stromal tumor (GIST). Small intestine fluoroscopy revealed the tumor with effusion of barium inside the translucent areas of the ileum. For diagnostic treatment, laparoscopic partial jejunum resection was performed. Pathological diagnostic examination revealed that the tumor consisted of spindle cell disarray with moderate density, fewer heterocysts, and rare mitosis. The tumor cells were c-kit positive and CD34 negative in immunohistochemistry. All the results were consistent with GIST. Eight years had passed before diagnosis and surgical treatment were performed. This case report emphasizes the difficulty of diagnose of GIST because of its low malignancy and slow progression.

[Appendix Cancer with Long-Term Survival after Multimodality Therapy-A Case Report].

We report a case of long-term survival in a 65-year-old woman with recurrent appendix cancer. In March 2002, she was diagnosed with appendix cancer and underwent ileocecal resection. The pathological diagnosis was mucinous cystadenocarcinoma, pT2N0M0, Stage Ⅰ. In April 2006, ovariohysterectomy was performed for right ovarian metastases. In February 2011, tumor resection was performed for disseminated recurrence after 4 courses of systemic chemotherapy(bevacizumab plus mFOLFOX6). Although no recurrent lesions had been detected on imaging, stepwise elevation of serum CEA level was observed from June 2016. In November 2017, computed tomography scan revealed a slow-growing tumor on the liver. We performed partial resection of the right hemidiaphragm for the disseminated tumor, and the pathological diagnosis was mucinous adenocarcinoma. The patient has been on continuous postoperative follow-up without recurrence until June 2019. Appendix cancer is relatively rare and has a worse prognosis compared to colorectal cancer because of higher frequency of disseminated metastases. With the multimodality therapy, our patient showed long-term survival over 17 years despite a disseminated recurrence. In cases of mucinous cystadenocarcinoma of the appendix, persistent follow-up and aggressive treatment are recommended.

[Giant Retroperitoneal Liposarcoma Treated by Surgical Resection and Chemotherapy - A Case Report].

As the treatment for the liposarcoma, there is no effective chemotherapy and a surgical remedy is required. We present the case of a 64-year-old man who complained about difficulty in swallowing and discomfort of throat. Computed tomography revealed a large enhancing left sided retroperitoneal mass invading the retroperitoneal space and it was displaced to the right. Preoperative diagnosis was retroperitonealmal ignant tumor. Tumor excision were performed and around 4.0 kg tumor was removed though its size was too big and resected it separately. Tumors increased 5 months later and became the second enucleation. After the second operation, we used eribulin as postoperative adjuvant chemotherapy. However, we needed extraction 3 times by the surgery because it recurred as peritonealdissemination. We continue surgicaltreatment and chemotherapy together as there are a part increasing relatively slowly and a high grade part increasing rapidly.

[A Case Involving the Re-Application of TAE for the Rupture of Recurrent Dissemination Lesion after Initial TAE and Hepatectomy Was Performed for A Previous Rupture of HCC].

The patient was a 65-year-old man who had been previously diagnosed with chronic hepatitis B, but the patient had discontinued treatment while in his thirties. The patient was admitted to the emergency department after losing consciousness due to abdominal pain. Emergency contrast CT was performed in the shock state, and the diagnosis was hemorrhagic shock due to rupture of hepatocellular carcinoma(HCC). Emergency TAE was performed, and hemostasis was successful due to left hepatic arterial embolism. The tumor was confined to the liver lateral area and it was judged to be resectable curatively, upon state restoration. Ten days after TAE, lateral segmentectomy of the liver was performed. Pathological findings indicated moderately differentiated HCC, mostly necrotic and partially viable. He was discharged on 11POD. On 69POD, the patient reexperienced sudden abdominal pain after lunch. The abdominal pain continued while emergency contrast CT was performed at the time of visit in the shock state. Recurrence of multiple dissemination via high-absorption ascites was found around the largest tumor nest with lower left diaphragm diameter of 15cm, and it was judged that the HCC disseminated recurrence had ruptured. Emergency TAE was performed again, and hemostasis was successful by embolization of the left gastric artery and lower left diaphragm artery. Subsequently, tumor growth slowed after initiating oral administration of sorafenib, and the patient is alive 8 months after re-TAE.

[An Examination of Colon Cancer Treatment Policies for the Elderly].

Currently, the rate of aging is increasing rapidly and the number of elderly patients in hospitals is rising in Japan. Under such circumstances, we established an emergency care unit for the elderly at our hospital in July 2014 to provide acute healthcare of the community. Our unit has been active in providing treatment for acute diseases in elderly individuals in the community. We are also pursuing continuous medical care for elderly individuals in collaboration with the community comprehensive care unit at our hospital and other facilities in the community, such as care facilities for the elderly and specialist elderly nursing homes. From January to December 2015, we examined treatment policies for colon cancer at our hospital. The presence or absence of dementia and patient's age are factors considered before treatment at our hospital; however, in many cases colon cancer was treated using surgery if the patient's generalcondition permitted it. In colon cancer patients, this takes into consideration the decreased quality of life resulting from losing the ability to eat due to bleeding and intestinal obstruction. We hereby report specific cases of colon cancer treatment policies for elderly patients at our hospital, together with a discussion of the literature.

[Advanced Digestive Cancer in Super Elderly Patients More Than 85 Years Old - Two Cases That Required Major Invasive Surgery].

Case 1 involved an 87-year-old woman. She had increased serum amylase levels, and intraductal papillary mucinous adenocarcinoma( IPMC)in the accessory pancreatic duct was diagnosed following various medical examinations. Radical surgery is possible for such a lesion when there are no issues detected following evaluation. The patient and her family decided that she should undergo surgery; therefore, pancreatoduodenectomy was performed for Stage III IPMC. Various morbidities required medical treatment, but she was finally discharged from hospital 89 days after surgery. She has had no recurrence 2 years and 11 months after surgery. Case 2 involved a 90-year-old man. He had liver dysfunction, and progressive hepatocellular carcinoma( HCC)was diagnosed based on computed tomography(CT)findings. The tumor size reduced to around 10 cm with enforced 2 degrees TACE. The patient and his family chose for him to undergo radical surgery; therefore, right trisegmentectomy of the liver was performed for Stage III HCC. He was discharged from the hospital 22 days after surgery, and has had no recurrence for the past 1.6 years. More careful examination and a general assessment are necessary to make decisions on surgical indications in super elderly patients.

[A Case That in Most Part of the Metastatic Liver Tumor Fell into Spontaneous Necrosis after Surgery of Rectal Cancer].

We present a case of a 74-year-old woman treated with maintenance dialysis for chronic renal failure. She had undergone intravascular treatment of lower limb arteriosclerosis obliterans 3 times. Low anterior resection was performed for rectal cancer StageⅡ, but adjuvant chemotherapy was not administered after the operation. S5/S6 partial hepatectomy was performed after confirming a liver metastatic recurrence 7 months after the first operation. Tumor pathology examination of the resected specimen revealed necrosis in most parts of the specimen. Residual primary lesion similar to adenocarcinoma tissue was found only in a small part of the specimen. Artery wall embolism and recanalization image with cholesterol crystals indicated a Grison's lesion, which was considered to have likely developed into tumor necrosis from the embolization. Spontaneous regression of a malignant tumor is a rare condition found 1 case in 6-10 ten thousand cases. In hepatocellular carcinoma, secondary tumor infarction from tumor invasion and tumor thrombus may occur. The present case was a metastatic liver cancer, in which the cholesterol crystal embolism possibly reached the tumor necrosis. The suggested cause of the cholesterol crystal embolism in this case was intravascular treatment related.

[Relapse-Free Survival Following Multidisciplinary Therapy for Hepatocellular Carcinoma with Multiple Lung Metastases--A Case Report].

Chemotherapy is not effective for metastatic hepatocellular carcinoma(HCC); however, prolonged survival can be expected for patients with multiple metastases who are treated with surgical resection in addition to chemotherapy. We present a case of a 36-year-old woman with hepatitis B who developed HCC with multiple intrahepatic and lung metastases after undergoing resection of HCC in 2010 in Canada. The patient returned to Japan for additional treatment. She was treated with TACE therapy and systemic chemotherapy, but her lung metastases did not improve. The patient's PIVKA-Ⅱ levels remained moderately elevated after initiation of chemotherapy. Therefore, we performed surgical resection of the lung metastases in March 2014. Five months later, the patient received additional TACE therapy when an isolated metastasis was found in the residual liver. Since then, no recurrence of HCC has been found, and the patient's PIVKA-Ⅱ levels have remained in the normal range. This case demonstrates that surgical resection for multiple lung metastases is possible in select patients.

[No recurrent case of the combination of surgical management with chemotherapy].

A 61-year-old man consulted a nearby doctor with the chief complaint of lassitude in June 2010. Blood tests revealed a hemoglobin level of 3.7 g/dL. The observation of significant anemia resulted in a full medical workup. On computed tomography (CT) findings, a large mass (17 × 10 cm in diameter) was found in the abdominal region. The lumen was distended with accumulation of air and fluid. In addition, I continued with a bladder wall, but did not recognize the abnormality that was apparent to a bladder lumen. There was no evidence of ileus. A diagnosis of appendix cancer or sarcoma was made preoperatively. During surgery, the bladder was observed to have some permeation, but the bladder wall contained a lesion of small intestinal origin with only slight permeation. The neighboring small intestine was surrounded by the tumor, with 3 sites of penetration. Histopathologic diagnosis indicated a high-risk gastrointestinal stromal tumor (GIST) with mitotic figures (44/50 high power fields). In accordance with the recommended guidelines, imatinib was administered for 1 year. Two sites of recurrences were observed by CT after discontinuing imatinib. A second operation was performed without increase because of the absence other lesions. Separate lesions in the sigmoid colon and jejunum were removed surgically. The tumor in the sigmoid colon was a lesion with high denaturation for mesenchymal system tumor such as GISTs by pathologic diagnosis. The lesion in the small mesentery was a suture granuloma. In this case, the combination of surgical management with chemotherapy resulted in good quality of life with no recurrence despite the presence of a high-risk GIST.

[Multi-modarity treatment for colon liver metastases using biliary stent-report of a case].

We report the case of a 69-year-old male patient with diagnoses of sigmoid colon cancer, ascending colon cancer, and metastatic liver cancer. We performed sigmoidectomy, right hemicolectomy, and central venous port placement. Because the liver metastasis was multifocal, chemotherapy was first initiated and then hepatic resection was performed. However, during chemotherapy, ileus, with a peritoneal dissemination to the small intestine, developed. Small intestine resection and radiation therapy to the pelvic region of the transition were further performed. Thereafter, obstructive jaundice due to obstruction of the bile duct in the hilar area developed, and therefore, we inserted a biliary stent. However, 2 years 9 months after the first medical examination, this patient died of colon cancer. The guidelines above, still chemotherapy developed, treatment policy of recurrent colorectal cancer, have recommended surgical resection with respect to what resectable as local therapy. This case shows that combination therapy with chemotherapy, surgical therapy, radiation therapy, and local therapy such as biliary stenting, is useful.

[Case of early antral gastric cancer diagnosed during follow up of pyloric stenosis by the gastro-duodenal ulcer].

A 65-year-old man was admitted to our hospital with nausea, vomiting and appetite loss. First upper endoscopic examination and X-ray examination showed a peptic ulcer and a pyloric stenosis. Fiberscope could not go through the pyloric ring. Computed tomography examination and biopsy showed no evidence of malignancy. Though we considered surgical resection of the stenosis at first, he could eat a staple food with therapy of proton pump inhibitor. So we followed up with upper endoscopic examinations. Second, third and forth upper endoscopic examinations showed no evidence of malignancy. Fifth upper endoscopic examination showed an ulcer scar on the pyloric ring and a 0-IIc carcinoma in the antral greater curvature. Distal gastrectomy with D2 lymph node dissection and B-II reconstruction. Pathologically, a mucosal carcinoma with no lymph node metastasis and U1-III peptic ulcer were diagnosed.

[Multimodality therapy containing hepatic arterial infusion chemotherapy for liver metastasis of esophageal cancer-a case report].

A 60-year-old man who had had a subtotal esophagectomy for esophageal cancer was given the diagnosis of hepatic metastases ten months after his operation. Systemic chemotherapy was stopped after a short time because of adverse effects. He refused to continue any other systemic chemotherapy. He was going to receive hepatic arterial infusion chemotherapy(HAI)with the prospect of having less systemic effects. Combination regimen of 5-FU with low-dose CDDP was administered for five days every three weeks. Hepatic metastases decreased markedly without adverse effects. The tumor was well controlled for two years until occlusion of hepatic artery. Radiation therapy and liver resection were performed subsequently. The patient lived more than 4 years after the diagnosis of hepatic metastases. HAI can be a treatment of choice for esophageal cancer when metastasis is limited to the liver.

[A case of long-term survival following combined modality therapy for peritoneal disseminated recurrence of duodenal cancer].

A 65-year-old man was diagnosed with primary duodenal cancer and he underwent pancreaticoduodenectomy in June 2006. S-1 was administered as the postoperative adjuvant chemotherapy. A peritoneal disseminated recurrence was diagnosed together with a right reniportal node and right hydronephrosis in February 2007. A ureteral stent was inserted. DOC +S-1 combination therapy was administered from March 2007. Following progression of the recurrence, CDDP+S-1 combination therapy was administered from August 2007. Temporal diminution of the recurrence was achieved with radiotherapy from May to June 2009. Following re-progression of the recurrence, biweekly CPT-11 therapy was administered from February 2010. Weekly PTX therapy was administered from January 2011. The patient died due to progression of the recurrence in June 2011, 5 years after the operation. Our patient maintained a good quality of life and achieved long-term survival by combined modality therapy for peritoneal disseminated recurrence of duodenal cancer.

[A case of long-term survival due to combined modality therapy for liver metastasis of colon cancer].

The patient was a 68-year-old man. Because sigmoid colon cancer and metastatic liver cancer was diagnosed in August 2009, an indwelling central venous port and sigmoid colon resection were implemented. The metastatic liver cancer was a huge tumor occupying the right hepatic lobe and caudate lobe. In consideration of the risk associated with the resection and the possibility of early recurrence, the postoperative chemotherapy was selected. He underwent 9 courses of bevacizumab (Bev)+FOLFOX. The tumor was observed to reduce but continued to occupy the right lobe and caudate lobe. At this point, the surgical treatment was selected because the tumor has been shrunk and there is no appearance of new metastases. In order to preserve residual liver function, he underwent percutaneous transhepatic portal embolization and then resection of the right lobe of the liver in February 2010. Although the Bev+FOLFOX treatment was started again after surgery as adjuvant chemotherapy, the metastatic liver cancer recurred in the remnant liver in August 2010. Because it was about 6 months from the first recurrence of liver resection, we decided to continue chemotherapy immediately without resection. However, the chemotherapy was insufficient to shrink the tumor, which increased because it was present at 3 locations in the liver. Therefore, partial hepatectomy at the 3 locations with positron-emission tomography was performed in February 2011. Since then, chemotherapy has not been performed in patients, and there is no recurrence as of March 2012. In the guideline for the treatment of liver metastasis of colorectal cancer, even though chemotherapy is currently developed, the surgical procedure is recommended for patients who are responsive to local therapy. If the cancer recur immediately after resection, it is difficult to decide whether to re-resect. We report the case in which the tumor-free status can be observed as a result of a combination of systemic chemotherapy and local therapy.

A multicenter phase II clinical study of oxaliplatin, folinic acid, and 5-fluorouracil combination chemotherapy as first-line treatment for advanced colorectal cancer: a Japanese experience.

PURPOSE: This multicenter phase II study was designed to determine the efficacy and tolerability of oxaliplatin in combination with levofolinate and infusion 5-fluorouracil (FOLFOX4) as first-line therapy for Japanese patients with unresectable metastatic colorectal cancer. METHODS: Sixty consecutive patients with histologically confirmed advanced or metastatic colorectal cancer were enrolled in the study. Treatment was repeated every 2 weeks until disease progression or unacceptable toxicity occurred. RESULTS: Two patients were ineligible. Toxicity was evaluated in 60 patients, who had received a part or all of the protocol therapy. A partial response was observed in 20 patients. The overall response rate was 34.5% (95% CI, 22.5%-48.1%) and the tumor control rate (partial response + stable disease) was 82.8%. The median progression-free survival was 6.9 months (95% CI, 5.1-9.8 months), and the median overall survival was 31.5 months (95% CI, 18.1-40.1 months). There were no toxicity-related deaths. Grade 3 or 4 neutropenia occurred in 48.3% of patients and often caused a delay in the subsequent treatment course. Mild to moderate cumulative peripheral sensory neuropathy affected 71.7% of patients. CONCLUSION: The results showed good tolerability and efficacy for first-line FOLFOX4 in the treatment of patients with advanced colorectal cancer, indicating the promise of this regimen as first-line therapy for advanced colorectal cancer in the Japanese population.

A multicenter phase II clinical study of oxaliplatin, folinic acid, and 5-fluorouracil combination chemotherapy as second-line treatment for advanced colorectal cancer: a Japanese experience.

PURPOSE: This multicenter phase II study was designed to determine the efficacy and tolerability of oxaliplatin, levoforinate, and infusional 5-fluorouracil (FOLFOX4) as a second-line therapy for Japanese patients with unresectable advanced or metastatic colorectal cancer. METHODS: A total of 53 patients with progressive disease after first-line chemotherapy were enrolled in the study. The treatment was repeated every 2 weeks until disease progression or unacceptable toxicity occurred, or the patient chose to discontinue the treatment. RESULTS: Four patients were ineligible and one did not receive the protocol therapy. Therefore, the response rate, overall survival (OS), and progression-free survival (PFS) were evaluated in 48 patients; toxicity was evaluated in 52 patients, excluding the patient who had not received the protocol therapy. A partial response was observed in 10 patients. The overall response rate was 20.8% (95% confidence interval [CI], 10.5%-35.0%). The median PFS was 5.6 months (95% CI, 4.1-7.0 months) and the median OS was 19.6 months (95% CI, 11.4-24.3 months). The most frequently encountered grade 3/4 hematological symptom was neutropenia (43.1%). The toxicity profile was generally predictable and manageable. CONCLUSION: The results showed good tolerability and efficacy for second-line FOLFOX4 in patients with advanced colorectal cancer, thus indicating the promise of this regimen as an effective second-line therapy for advanced colorectal cancer in the Japanese population.

[A case successfully treated with abdominoperineal resection after preoperative chemoradiation therapy for anal cancer].

A 46-year-old female was diagnosed with anal squamous cell carcinoma. Chemoradiation therapy was administered for a first-line therapy. Two courses of enforced 5-FU/MMC combination therapy were administered along with radiotherapy (60 Gy). This chemoradiation therapy had complete response. However, three months after, anal cancer had a local recurrence. Since there was no distant metastasis, abdoninoperineal resection was performed. No complications were observed after the operation. We conclude that abdominoperineal resection may be effective in the treatment of anal cancer in cases which the local recurrence was observed after chemoradiation therapy.

[A case of long-term survival by combined modality therapy for liver and pulmonary metastasis of rectal cancer].

We report a case of rectal cancer diagnosed in 2001, which enforced a rectal low anterior resection. Then, metastatic liver cancer and metastatic lung cancer recurred and we enforced an operation for both. Furthermore, metastatic lung cancer recurred again and enforced chemotherapy with radiation and systemic chemotherapy for approximately seven years. The metastatic lung cancer was reduced now in 2011, so that the chemotherapy has not been used since then. In our case, we mainly performed a surgical and radiation therapy for a local recurrent site therapy in the first half because we did not have much choice for a systemic chemotherapy like we have now. In the later half, we mainly performed a systemic chemotherapy to control the local recurrent site. A treatment policy for colon cancer recommends a surgical treatment by the guidelines, or even though chemotherapy has been developed at present, if a local therapy is practical. There were many cases where metastases had occurred right after surgery so a local site therapy by excision was good at all unconditionally. However, as a result of our case in a local site therapy combined with whole body chemotherapy, we report here that a long- term survival was obtainable. We also include a brief literature review.