Current Roles of Ramucirumab in the Sequential Treatment of Unresectable Hepatocellular Carcinoma.

BACKGROUND/AIM: The treatment algorithm for systemic therapies for advanced hepatocellular carcinoma (HCC) has changed dramatically; however, the therapeutic landscape for sequential second-line or later-line treatments, including ramucirumab, remains controversial. This study aimed to investigate the role of ramucirumab for treating HCC. PATIENTS AND METHODS: We retrospectively analyzed data from 17 patients with advanced HCC who received ramucirumab, and 8 of them who received lenvatinib re-administration after ramucirumab treatment failure. RESULTS: The median overall survival of 17 patients treated with ramucirumab was 11.5 months. The median ratios of the 1-month post-treatment α-fetoprotein (AFP) levels and albumin-bilirubin (ALBI) scores to the pre-treatment AFP levels and ALBI scores following ramucirumab treatment were 0.880 and 0.965, respectively. The median ratios of the 1-month post-treatment AFP and ALBI levels to the pre-treatment levels were 1.587 and 0.970 for mALBI grade 1/2a, and 1.313 and 0.936 for mALBI grade 2b/3, respectively. Six of the eight patients who received lenvatinib rechallenge treatment exhibited a decrease in AFP levels one month post-lenvatinib treatment. Deterioration of liver function 3 months post-lenvatinib treatment was noted in five of the eight patients who received lenvatinib rechallenge treatment after ramucirumab. CONCLUSION: Ramucirumab may be equally useful in patients with unresectable HCC who have poor liver function or whose liver function is aggravated by other therapies. Rechallenge treatment with lenvatinib after ramucirumab may be a valid treatment option for HCC.

The Usefulness of Total Tumor Volume as a Prognostic Factor and in Selecting the Optimal Treatment Strategy of Chemotherapeutic Intervention in Patients with Colorectal Liver Metastases.

BACKGROUND: Few reports have discussed the association between total tumor volume (TTV) and prognosis in patients with colorectal liver metastases (CRLM). The present study aimed to evaluate the usefulness of TTV for predicting recurrence-free survival and overall survival (OS) in patients receiving initial hepatic resection or chemotherapy, and to investigate the value of TTV as an indicator for optimal treatment selection for patients with CRLM. PATIENTS AND METHODS: This retrospective cohort study included patients with CRLM who underwent hepatic resection (n = 93) or chemotherapy (n = 78) at the Kobe University Hospital. TTV was measured using 3D construction software and computed tomography images. RESULTS: A TTV of 100 cm3 has been previously reported as a significant cut-off value for predicting OS of CRLM patients receiving initial hepatic resection. For patients receiving hepatic resection, the OS for those with a TTV ≥ 100 cm3 was significantly reduced compared with those with a TTV < 100 cm3. For patients receiving initial chemotherapy, there were no significant differences between the groups divided according to TTV cut-offs. Regarding OS of patients with TTV ≥ 100 cm3, there was no significant difference between hepatic resection and chemotherapy (p = 0.160). CONCLUSIONS: TTV can be a predictive factor of OS for hepatic resection, unlike for initial chemotherapy treatment. The lack of significant difference in OS for CRLM patients with TTV ≥ 100 cm3, regardless of initial treatment, suggests that chemotherapeutic intervention preceding hepatic resection may be indicated for such patients.

Factors Predicting Over-Time Weight Increase After Liver Transplantation: A Retrospective Study.

BACKGROUND: Post-transplantation weight control is important for long-term outcomes; however, few reports have examined postoperative weight change. This study aimed to identify perioperative factors contributing to post-transplantation weight change. METHODS: Twenty-nine patients who underwent liver transplantation between 2015 and 2019 with an overall survival of >3 years were analyzed. RESULTS: The median age, model for end-stage liver disease score, and preoperative body mass index (BMI) of the recipients were 57, 25, and 23.7, respectively. Although all but one recipient lost weight, the percentage of recipients who gained weight increased to 55% (1 month), 72% (6 months), and 83% (12 months). Among perioperative factors, recipient age ≤50 years and BMI ≤25 were identified as risk factors for weight gain within 12 months (P < .05), and patients with age ≤50 years or BMI ≤25 recipients gained weight more rapidly (P < .05). The recovery time of serum albumin level ≥4.0 mg/dL was not statistically different between the 2 groups. The weight change during the first 3 years after discharge was represented by an approximately straight line, with 18 and 11 recipients showing a positive and negative slope, respectively. Body mass index ≤23 was identified as a risk factor for a positive slope of weight gain (P <.05). CONCLUSIONS: Although postoperative weight gain implies recovery after transplantation, recipients with a lower preoperative BMI should strictly manage body weight as they may be at higher risk of rapid weight increase.

Outcomes of the Sequential Treatment of Unresectable Hepatocellular Carcinoma Using Lenvatinib.

BACKGROUND/AIM: The chemotherapeutic landscape for hepatocellular carcinomas (HCCs) has changed dramatically with the availability of several treatment options. This study aimed to assess the long-term outcomes of lenvatinib treatment and analyze its feasibility in the sequential treatment of HCCs. PATIENTS AND METHODS: Eighty-five consecutive patients who received lenvatinib for unresectable HCCs were investigated retrospectively. Survival was assessed based on when the patients were first radiologically diagnosed with progressive disease. Among those with radiologically diagnosed stable or progressive disease at 3 months after lenvatinib administration, the cutoff α-fetoprotein (AFP) ratio (ratio of the AFP level after lenvatinib treatment to the pretreatment AFP level) that was predictive of survival was determined using receiver operating characteristic analysis. RESULTS: The median survival time (MST) was significantly worse among patients diagnosed with progressive disease at 1 month after treatment than among those diagnosed at 2-3 or 3-4 months after treatment [MSTs at 1, 2-3, and 3-4 months: 2.2, 10.2, and 17.3 months, respectively (p<0.001)]. An AFP ratio of 1.36 (computed using the AFP level at 3 months after lenvatinib treatment) was significantly predictive of survival in patients with stable or progressive disease (26.3 vs. 11.3 months, p=0.0024). CONCLUSION: The prognosis of patients on lenvatinib who develop early progressive disease is dismal. Thus, their treatment should be ceased or switched. The 3-month AFP ratio of 1.36 may be a potentially useful cutoff for considering a switch to other treatments in patients radiologically diagnosed with stable or progressive disease.

Laparoscopic gastrectomy with lymph node dissection for the treatment of remnant stomach gastrointestinal stromal tumors in incomplete-type Carney's triad: a case report.

BACKGROUND: We report a rare case of gastrointestinal stromal tumors (GISTs) in Carney's triad, successfully treated using laparoscopic gastrectomy with lymph node dissection after chemotherapy. CASE PRESENTATION: A 21-year-old woman presented to our hospital for treatment of recurrent GISTs. The patient had been admitted for treatment 11 years prior, with black stools being the chief presenting complaint at that time. On examination at that time, multiple submucosal tumors in the pyloric antrum and multiple pulmonary tumors had been observed. She underwent open partial gastrectomy, and the diagnosis of GISTs was confirmed. She was administered tyrosine kinase inhibitors to treat lung metastases from 2 months after surgery. Due to the increasing size of the lung tumors, a right upper lobectomy was performed 9 years after the index gastric surgery. Histopathological examination of the lung specimen, in combination with re-examination of the gastric specimens, was indicative of incomplete-type Carney's triad. Eleven years after the index gastric surgery, multiple GISTs were observed in her entire stomach. Tumor biopsy revealed a succinate dehydrogenase deficiency, confirming the diagnosis of recurrent GISTs. For treatment, the patient underwent laparoscopic completion gastrectomy, with D1 plus lymph node dissection. CONCLUSION: This is a first case report of completion gastrectomy performed laparoscopically for the treatment of GISTs associated with incomplete-type Carney's triad. The recurrent GISTs developed over a protracted period of 11 years from the index gastric surgery to tumor recurrence.

[A Case of Castleman's Disease with Lymphadenopathy during the Treatment of Gastric Cancer].

We report a patient who had Castleman's disease with lymphadenopathy during the treatment of gastric cancer. In May 2017, a 63-year-old man underwent gastrointestinal endoscopy, which revealed a tumor on the posterior wall of the lower part of the stomach. Based on a biopsy, he was diagnosed with suspected adenocarcinoma, Group 4. In June 2017, he visited our hospital, and endoscopic submucosal dissection(ESD)was performed. The pathological diagnosis of the resected specimens was L, Less, 20×10 mm, Type 0-Ⅱc, tub1, pT1a(M), UL(-), ly(-), v(-), pHM0, pVM0, pStage ⅠA. He was referred to our department for the treatment of abdominal lymphadenopathy. His lymphadenopathy was localized in the gastric lesser curvature as an enlarged lymph node 15mm in size, based on the findings of contrast-enhanced CT. On FDG- PET/CT, we found a slight accumulation of SUVmax 2.4 in the early phase in the same lymph node. We could not confirm a diagnosis, and we performed laparoscopic dissection of the lymph node for diagnosis and treatment. The size of the specimen was 14×14mm, surface was smooth, and lymph node was elastic and soft. We found lymphoid follicles with atrophic germinal center using HE staining. We also found increased hyperplastic blood vessels around the germinal center, and he was diagnosed with hypervascular Castleman's disease.

[Long-Term Survival of a Patient with Para-Aortic Lymph Node Recurrence Who Underwent Lymph Node Dissection and Received Chemotherapy Following Curative Gastrectomy].

A 66-year-old man underwent total gastrectomy for gastric cancer. S-1 was administered as adjuvant chemotherapy. Abdominal CT showed para-aortic lymph node recurrence 31 months after the surgery. There was no other recurrence according to PET-CT, and we performed para-aortic lymph nodes dissection 41 months after the surgery. Lymph node recurrence in the retrocrural space was observed 37 months after the 2nd surgery. We administered S-1 plus L-OHP chemotherapy. After 4 courses, CT revealed that he had achieved complete response, and he has remained disease-free for 79 months after lymph node dissection. Some patients with para-aortic lymph node recurrence after curative gastrectomy may benefit from treatment including chemotherapy and surgical dissection.

[Two Cases of Pancreatectomy for Pancreatic Metastasis from Renal Cell Carcinoma].

Metastasis of renal cell carcinoma to the pancreas is a relatively rare condition. We encountered 2 such cases. The first case was a 72-year-old man who underwent a left nephrectomy owing to left renal cancer in 2005. An abdominal dynamic CT scan 12 years after surgery revealed tumors in the pancreatic body and right kidney. A PET-CT scan revealed low intensity uptake of both tumors, and therefore, metastasis of the left renal cell carcinoma to the pancreas was suspected. We then performed partial resections of the pancreatic tail and right kidney. Pathologic findings confirmed that the pancreatic tumor and right renal tumor were metastases of the left renal cell carcinoma. The postoperative course was favorable, and the patient has been followed up in an outpatient setting for 10 months with no signs of recurrence. The second case was a 51- year-old woman with tumors in the left kidney and pancreatic head that were detected by abdominal contrast CT and MRI. We diagnosed the patient with left renal cell carcinoma with metastasis to the pancreas. We performed a radical nephrectomy of the left kidney and full pancreatectomy. Pathologic findings confirmed left renal cell carcinoma, pStage Ⅳ, with metastasis to the pancreas. The postoperative course was favorable without recurrence for 14 years. We report on two cases of metastasis of renal cell carcinoma to the pancreas in patients who underwent radical resections and had favorable postoperative courses, with some bibliographic consideration.

[A Case of Long-Term Survival after Repeated Multidisciplinary Treatment for Liver Metastasis of Ampullary Cancer].

The patient was a 79-year-old man. He underwent endoscopic papillectomy for ampullary cancer when he was 70 years old. At the ages of 71 and 73 years, liver metastasis in segment 6 was detected, and radiofrequency ablation(RFA)was performed and adjuvant chemotherapy(gemcitabine, S-1)was administered. At the age of 79 years, recurrence of liver metastasis appeared. Because there were no other metastatic lesions, we performed S6 subsegmentectomy. Five months after the surgery, no recurrence was observed. In general, the prognosis of patients with ampullary cancer with distant metastasis is very poor. This case suggested the efficacy of multidisciplinary treatment, including surgery, RFA, and chemotherapy, in a patient with ampullary cancer with distant metastasis.

[A Case of Resected Metachronous Pancreatic Metastasis from Rectal Carcinoma].

A 69-year-old man underwent a Miles operation with D3 lymph node dissection for rectal cancer. The pathological diagnosis was adenocarcinoma(Rb, A, ly2, v3, N2M0P0H0, Stage Ⅲb). Adjuvant chemotherapy was added for 6 months after the rectal resection. Metastasis in the left lung was detected 1 year and 10 months after rectal resection for which large segmental resection was performed. Without the onset of any new lesions, the patient underwent subsequent follow-up examinations. Abdominal CT performed for increased tumor marker levels observed at 6 years and 8 months after rectal resection revealed a mass suggestive of pancreatic ductal adenocarcinoma for which distal pancreatectomy was performed. The pathological diagnosis was metastasis to the pancreas from the rectal cancer as the tumor cells were immunohistochemically negative for cytokeratin 7 and positive for cytokeratin 20. There has been no indication of recurrence for 13 months after the pancreatic surgery. Resectable pancreatic metastasis from colorectal cancer is rarely reported. However, pancreatic resection may result in long-term survival in some cases. Patients that tolerate pancreatectomy and have no metastasis in the other organs should be considered good candidates for pancreatic resection. We present this case with a review of the literature.

[A Case of Multiple Tumor Neurosurgery for Brain Metastasis of Colorectal Cancer].

We report a patient with brain metastasis of rectal cancer who underwent metastatic tumor resection 3 times. In March 2012, a 76-years-old man, diagnosed with Stage III a rectal cancer, underwent Hartmann's operation. The lung metastasis was confirmed in July and November 2013, surgical resection for pulmonary metastasis was performed 2 times. In January 2016, he had difficulty of speaking, and isolated brain tumor was found. We performed surgical resection of brain metastasis in February 2016. In March and July 2016, the gamma knife radiosurgery was performed for other brain metastasis. In July 2016, he occurred nausea, headache and right identity hemi-blindness. Two new brain tumors were revealed. We performed surgical resection again. Three months after second brain surgery, he had dysarthria and a solitary brain tumor was confirmed. We performed third neurosurgical resection. All tumors of brain were found to be metastasis from rectal cancer in histological study. Currently, 16 months have passed since the first diagnosis of brain metastasis of this patient, and the quality of life was good relatively. The prognosis of the patients with brain metastasis is poor generally. However, this case suggested that multiple surgical resection of brain metastasis could improve prognosis and quality of life of patients. Accumulation of further cases is needed.

[A Case of Rectosigmoid Cancer with Intestinal Malrotation Treated with Laparoscopic Surgery].

A 67-year-old woman was diagnosed with rectal cancer using colonoscopy. Computed tomography revealed the so-called superior mesenteric vein rotation sign, and intestinal malrotation was suspected. We planned chemotherapy after the surgical resection of the primary cancer because she had multiple lung metastases. Laparoscopic high anterior resection with D3 dissection of lymph nodes was performed. Intraoperative findings showed a non-rotation type intestinal malrotation and severe intra-abdominal adhesion. However, careful releasing operation enabled the typical approach of laparoscopic surgery for rectal cancer. The postoperative course was generally good, and she was discharged on the 17th postoperative day. The pathological diagnosis was rectal cancer(T3, N0, M1a, pStage Ⅳ). In laparoscopic surgery for colorectal cancer with intestinal malrotation, determining the anatomy of blood vessels and the site of the tumor before surgery is important. Furthermore, awareness that some cases have severe intra-abdominal adhesions even without a history of laparotomy is necessary.

[Two Resected Cases of Non-Isolated Splenic Metastasis of Colon Cancer].

We report 2 resected cases of patients with non-isolated splenic metastasis of colon cancer. Case 1: A 67-year-old man who underwent partial transverse colectomy and partial hepatectomy for transverse colon cancer and liver metastasis. Approximately 18 months after the operation, splenectomy and partial hepatectomy were performed for metastasis to the spleen and liver. After partial hepatectomy for another recurrence, no signs of new recurrence have been observed for 42 months after splenectomy. Case 2: A 53-year-old woman who presented with bloating. CT and MRI scans revealed masses of the ileocecum, both ovaries, and spleen. We performed right hemicolectomy, total hysterectomy, bilateral salpingo-oophorectomy, pelvic lymphadenectomy, para-aortic lymphadenectomy, omentectomy, and splenectomy. Histological findings showed cecal cancer metastasizing to the bilateral ovaries and spleen. Metastatic splenic tumor is relatively rare(0.3-7.3%). Splenectomy was reported to be an effective treatment modality for isolated splenic metastasis, while that for non-isolated metastasis is uncertain. Surgical resection should be considered even in non-isolated splenic metastasis cases because of the evidence of long-term survival in case 1.