[A Case of Five Years Recurrence-Free Survival after Successful Multidisciplinary Treatment for Simultaneous Brain Metastasis and Heterochronic Small Intestinal Metastasis from Lung Cancer].

The patient was a 54-year-old male at the time of initial examination. He was aware of numbness and weakness in the left hemisphere of his body and came to see the hospital. He was diagnosed with brain metastasis of lung cancer and started treatment(cT2N0M1[Brain]). He underwent gamma knife for the head lesion and nivolumab for the lung lesion. The patient's lesions shrank with the success of the medical treatment, but recurred with small intestinal metastasis. He underwent a partial resection of the small intestine and was treated again with nivolumab, which resulted in a complete response. He is currently alive without recurrence. We have experienced a very rare case of recurrence-free survival after treatment for brain metastasis and small intestinal metastasis of lung cancer.

[Liver Resection after Chemotherapy for Simultaneous Liver Metastasis of Cecal Cancer-A Case Report].

A 78-year-old male patient was referred to another hospital for cecal cancer and metastatic liver tumor. After open ileocecal resection, he was referred to our hospital for treatment of liver lesions. CT scan showed a lesion with contrast effect of approximately 60 mm in S8, and the patient was judged to be resectable by right lobe resection. However, considering his age and the possibility of latent disease, it was decided to introduce preoperative chemotherapy. After 4 courses of XELOX, although the ICG worsened from 9% to 18% after chemotherapy, the tumor was reduced to approximately 30 mm. The patient underwent an open anterior segment resection of the liver. Colorectal cancer guidelines recommend that surgical resection is the first-line treatment for resectable liver metastases and that preoperative adjuvant chemotherapy should not be given to patients. In this report, we describe a case in which a liver metastasis was safely resected with chemotherapy.

[A Case of Histological Response of Grade 3 Achieved by Preoperative Chemotherapy with S-1/Oxaliplatin(SOX)].

Histological response of Grade 3 is relatively rare in gastric cancer patients but has recently been observed occasionally. We report the histological response of Grade 3 achieved by S-1/oxaliplatin(SOX)therapy. A 66-year-old man had suffered from epigastralgia when hungry. After 1 month, he visited the department of gastroenterology of our hospital. Upper gastrointestinal endoscopy revealed a type 3 tumor at the lesser curvature of middle gastric body, and poorly differentiated adenocarcinoma was detected by the biopsy examination. Abdominal/pelvic enhanced CT showed wall thickening of the lower gastric body, enlarged regional lymph nodes and para-aortic lymph nodes(No. 16b1). We diagnosed it with Stage Ⅳ. He received 4 courses of SOX therapy. After chemotherapy, upper gastrointestinal endoscopy revealed a residual tumor, although biopsy showed no cancer cells. Abdominal/pelvic enhanced CT showed significantly reduced lymph nodes despite the thickening of the gastric wall. PET-CT revealed indistinct para-aortic lymph nodes. Distal gastrectomy, D2 dissection without para-aortic lymph nodes dissection, and Billroth Ⅰ reconstruction were performed. Histological findings showed no cancer cells in the main lesion or lymph nodes, with only previous cancer cells suspected. The histological response was Grade 3. SOX therapy might be employed in the future as chemotherapy before conversion surgery for Stage Ⅳ gastric cancer.

Sentinel node mapping for post-endoscopic resection gastric cancer: multicenter retrospective cohort study in Japan.

BACKGROUND: Standard gastrectomy with systematic lymphadenectomy as an additional surgery after endoscopic resection (ER) causes a deterioration in long-term quality of life. If the sentinel lymph node (SN) basin concept can be applied in post-ER gastric cancer, minimal surgery can be applied without reducing the curability. This retrospective multicenter cohort study aimed to verify the validity of the SN basin concept in post-ER gastric cancer. PATIENTS AND METHODS: Individual data of 132 patients who underwent SN mapping after ER were collected from 8 university hospitals in Japan from 2001 to 2016. Tracers were injected endoscopically in the submucosal layer at four sites around the post-ER scar. We compared the SN basin distribution of post-ER gastric cancer with that of 275 patients with non-ER gastric cancer. RESULTS: Two cases of SN were unidentified, both involving a single tracer (SN detection rate: 98.5%). Nine cases (6.8%) of lymph node metastasis were found, of which eight had a metastatic lymph node within the SNs and one had a non-SN metastasis within the SN basin. The diagnostic sensitivity of SN mapping for lymph node metastasis was 88.9% in post-ER group and 95.7% in non-ER group (P = 0.490); the accuracy was 99.2% and 99.6% (P = 0.539), respectively. Regarding the SN basin, no significant intergroup differences were found regardless of the primary tumor location. CONCLUSIONS: Our findings clarified the feasibility of SN mapping based on the SN basin concept in patients with gastric cancer who previously underwent ER.

Postoperative outcomes of gastric carcinoma with lymphoid stroma.

BACKGROUND: Gastric carcinoma with lymphoid stroma (GCLS) is a rare subtype of gastric cancer. There have been several reports demonstrating the favorable prognosis of early GCLS without lymph node metastasis (LNM) compared with gastric adenocarcinomas. However, it remains unknown whether advanced GCLS (AGCLS) with LNM has a similar prognosis and clinicopathological features. This study aimed to assess the clinicopathological features of GCLS of all stages. METHODS: We retrospectively assessed 375 patients who were pathologically diagnosed with gastric cancer and underwent curative surgical resection at Tokyo Medical University, Japan, between September 2013 and October 2019. Of these patients, 357 (95.2%) patients were pathologically diagnosed with gastric adenocarcinomas, and 18 (4.8%) patients were diagnosed with GCLS. The GCLS patients (n = 18) were compared with the gastric adenocarcinoma patients (non-GCLS patients, control) (n = 357) in terms of their clinicopathological features and clinical outcome. RESULTS: The GCLS patients showed significantly predominant upper gastric locations (P = 0.003), lower number of LNM (P = 0.01), and better overall survival rate than the non-GCLS patients (P = 0.029). The predominant upper gastric locations (P = 0.0002), lower number of LNM (P = 0.003), and better overall survival rate (P = 0.04) were significantly correlated in the AGCLS with LNM patients compared with the advanced non-GCLS with LNM patients. For survival analyses, surgical procedure, tumor location, and numbers of positive LNM were adjusted by 1:1 propensity score matching. After adjustment, the overall survival rate was significantly higher in the AGCLS group than in the advanced non-GCLS group (P = 0.03). CONCLUSION: AGCLS has distinct clinicopathological features and clinical behavior that are similar to those of early GCLS. AGCLS with LNM patients showed a significantly lower number of LNM and a better survival rate than advanced non-GCLS with LNM patients. To our knowledge, this study is the first report to describe the clinicopathological features of AGCLS.

[Efficacy of Palliative Radiotherapy in Hemorrhage Control in Patients with Unresectable Gastric Cancer].

We report the case of an 80-year-old man with unresectable, advanced gastric cancer and pulmonary cancer because of multiple liver metastases. The serum hemoglobin level declined to 5.3 g/dL during fourth-line chemotherapy. Radiation therapy of 30 Gy was administered in 10 fractions. After radiation treatment was completed, the serum hemoglobin level increased to 8.5g/dL. No new adverse event was observed. Subsequently, the progression of anemia stopped, and oral intake became possible. Thus, palliative radiation therapy is useful for hemorrhage control in unresectable, advanced gastric cancer patients with a poor general condition and difficult surgical treatment.

[A Case of Local Remnant Esophageal Cancer after Chemotherapy Getting Complete Response by Radiotherapy].

This is a case of a 72-year-old woman who presented without anymajor complaint. An anemia was indicated during follow-up for diabetes at the internal medicine unit and an upper gastrointestinal endoscopy(GS)was performed. A type 2 tumor was detected in the middle thoracic esophagus and biopsyrevealed a squamous cell carcinoma. A tumor was detected in the middle thoracic esophagus bycervical thoracoabdominal computed tomography(CT)scan and no invasion of surrounding organs was noted. The lymph node 104R had enlarged significantlybut no distant metastasis was observed. The patient was diagnosed with advanced esophageal cancer, Mt, type 2, cT2N2M0, stage Ⅱ. For preoperative chemotherapy, CDDP plus 5-FU(FP)therapywas administered. Lung metastasis was found on CT examination and surgical resection was not indicated. Hence, 4 courses of docetaxel plus CDDP plus 5-FU(DCF)therapywere administered. Following treatment, lung and lymph node metastases disappeared on the image. However, the main tumor remained at the GS. Radiotherapy was administered as a local additional treatment. Thereafter, GS showed mucous membrane redness and white spots of the lesion. Biopsyfrom the same site showed no malignant findings. The patient has remained malignancy-free since 18 months.

[Administering Ramucirumab Safely after Inserting an Intestinal Stent, Due to Peritoneal Metastasis of Gastric Cancer-A Case Report].

The recent phase Ⅲ trials REGARD and RAINBOW have shown survival benefits and acceptable safetyprofiles of ramucirumab( RAM)alone and RAM plus paclitaxel. Based on this result, RAM is recommended as a secondarytreatment for advanced and recurrent gastric cancer bythe Japanese Gastric Cancer Association. Although the frequencyis not high, gastrointestinal perforation has been reported as a serious side effect. RAM is a human anti-vascular endothelial growth factor receptor 2(VEGFR-2)monoclonal antibodythat acts on vascular endothelial cells to inhibit angiogenesis. The detailed mechanism has not been elucidated, but it is thought that the ischemic state and delayed wound healing due to the inhibition of vascular endothelial growth factors could be the cause of perforation. Thus, the usage of angiogenesis inhibitors such as RAM while intestinal stents are placed, mayincrease the risk of gastrointestinal perforation. We report a case in which RAM was administrated with no adverse events after multiple gastrointestinal metal stents being inserted.

Endoscopic ultrasound-guided transmural drainage for subphrenic abscess: report of two cases and a literature review.

BACKGROUND: An intra-abdominal abscess can sometimes become serious and difficult to treat. The current standard treatment strategy for intra-abdominal abscess is percutaneous imaging-guided drainage. However, in cases of subphrenic abscess, it is important to avoid passing the drainage route through the thoracic cavity, as this can lead to respiratory complications. The spread of intervention techniques involving endoscopic ultrasonography (EUS) has made it possible to perform drainage via the transmural route. CASE PRESENTATION: We describe two cases of subphrenic abscess that occurred after intra-abdominal surgery. Both were treated successfully by EUS-guided transmural drainage (EUS-TD) without severe complications. Our experience of these cases and a review of the literature suggest that the drainage catheters should be placed both internally and externally together into the abscess cavity. In previous cases there were no adverse events except for one case of mediastinitis and pneumothorax resulting from transesophageal drainage. Therefore, we consider that the transesophageal route should be avoided if possible. CONCLUSIONS: Although further studies are necessary, our present two cases and a literature review suggest that EUS-TD is feasible and effective for subphrenic abscess, and not inferior to other treatments. We anticipate that this report will be of help to physicians when considering the drainage procedure for this condition. As there have been no comparative studies to date, a prospective study involving a large number of patients will be necessary to determine the therapeutic options for such cases.

Transhepatic arterial infusion chemotherapy using a combination of miriplatin and CDDP powder versus miriplatin alone in the treatment of hepatocellular carcinoma: a randomized controlled trial.

BACKGROUND: Based on promising results from a Phase I study of hepatic arterial infusion chemotherapy using a combination of miriplatin and cisplatin powder (DDP-H) for unresectable hepatocellular carcinoma (UMIN-CTR000003541), a multicenter, open-label, randomized phase II study was conducted to evaluate the efficacy and safety of the combination therapy versus miriplatin monotherapy. METHODS: Nineteen patients, five and fourteen Barcelona-Clinic Liver Cancer staging classification A and B cases, respectively, were randomly assigned to receive either miriplatin monotherapy (n = 9) or miriplatin/DDP-H combination therapy (n = 10). DDP-H and/or miriplatin were administered through the hepatic arteries supplying the lobes of the liver containing tumors, and progression free survival was analyzed as a primary end point in addition to other secondary endpoints. The corresponding therapy was repeated unless disease progression or severe adverse events were recorded. RESULTS: The monotherapy or combination therapy was performed for 15 or 36 sessions in total, respectively. Although there were no significant differences between the two groups for treatment intervals (p = 0.96) or the dose of miriplatin used in each session (p = 0.99), the progression free survival and overall disease control rate were significantly better in the combination therapy group (91 vs 423 days, p = 0.025; 40.0 vs 77.8%, p = 0.0025, respectively). Consistent with these observations, a trend of a significantly slower increase in des-γ-carboxyprothrombin was observed, and the number of treatment sessions was nearly significantly larger in the combination therapy group (p < 0.0001, p = 0.057, respectively). Conversely, the median survival time did not show a significant difference (706 days, monotherapy vs 733 days, combination therapy; p = 0.40). A significant decrease in cholinesterase was observed during the course of treatment only in patients receiving combination therapy (r = -0.86, p < 0.0001). A few cases in both arms showed hematological and/or non-hematological toxicities that were categorized as grade 1 (NCI-CTCAE). CONCLUSIONS: The higher disease control effects with the combination of miriplatin and DDP-H indicate that it is a promising alternative treatment for cases with multiple HCCs, especially for those that can tolerate the treatment without experiencing a reduction in hepatic reserve. TRIAL REGISTRATION: This study was registered on 1 January 2012 with the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/index.htm , UMIN000004691).

[A Case of T4 Esophageal Cancer with Refractory Chylothorax Developed Postoperatively].

A 65-year-old man was diagnosed as having middle thoracic esophageal cancer(c-T3N2M0, stage III ), and neoadjuvant chemoradiotherapy was performed.We performed surgical therapy.However, tumor and #113 lymph node invasion into the aortic arch was observed; therefore, it was judged that curative resection was difficult, and R2 surgery was performed instead. Postoperative diagnosis was Mt, CRT-type 5b, s-T4(aortic arch)N4(#113)M0, stage IV a.After surgery, pleural effusion was abundant and was diagnosed as chylothorax.Even though intestinal rest and octreotide administration were performed as a conservative treatment, chylothorax was not improved.Therefore, thoracoscopic thoracic duct ligation was performed on 8POD.After that, pleural effusion was still sustained, and pleural adhesions were performed.However, it did not prove to be effective.Furthermore, when Lipiodol lymphangiography was performed to identify the leakage site, the leakage of contrast medium was observed from the remaining lymph node.After lymphangiography twice(in total), pleural effusion disappeared, and the patient was discharged on the 75POD.In this case, we report an example in which lymph leakage disappeared due to lymphangiography for diagnostic purpose, while no improvement was observed in the lymphatic leakage from the remaining metastatic lymph node in T4 esophageal cancer with R2 surgery, nor with some treatments for chylothorax, including thoracic duct ligation.

[Effective Prevention of Hand-Foot Syndrome by the Consumption of Dried Bonito Broth].

To examine whether the consumption of dried bonito both is effective for the prevention of hand-foot syndrome(HFS), concentrated bonito broth was administered to 10 patients with HCC who were treated with sorafenib. Among the 10 patients, seven showed an increase in peripheral blood flow, as observed on Doppler ultrasonography. Only one patient showed Grade 1 HFS on day 14 after the initiation of sorafenib (10%); this incidence rate of HFS was significantly lower than that obtained in our previous studies and reported data. These results suggest that consumption of dried bonito broth contributes to the prevention of HFS by maintaining peripheral blood flow.

Long-term survival outcomes of advanced gastric cancer patients who achieved a pathological complete response with neoadjuvant chemotherapy: a systematic review of the literature.

BACKGROUND: A pathologic complete response (pCR) can sometimes be induced by intensive or long-term neoadjuvant chemotherapy (NAC). This prognostic research study based on a systematic review of the literature evaluated the impact of a pCR on the long-term survival of gastric cancer (GC) patients. METHODS: Articles were extracted from PubMed and the Japanese medical search engine "Ichu-shi," using the terms "GC," "NAC," and "pCR." Articles were selected based on the following criteria: (1) full-text case report, (2) R0 resection following NAC for locally advanced GC, and (3) pathological complete response in both the primary stomach and in the lymph nodes. A questionnaire regarding the patients' prognoses was sent to the corresponding authors of the articles selected in July 2013. RESULTS: Twenty-four articles met the criteria. Twenty authors responded to the questionnaire. Finally, 22 patients from 20 articles were entered into the present study. The median follow-up time (range) of the survivors was 76 (range 13-161) months. Tumors that were stage III/IV (86%: 19/22) and of an undifferentiated histology (61.9%: 13/21) were dominant. An S1-based regimen was frequently selected for the NAC. All patients underwent R0 resection and D2/D3 lymphadenectomy. The overall survival and recurrence-free survival rates at 3 and 5 years were 96% and 85% and 91% and 75%, respectively. CONCLUSIONS: Although a pCR was a relatively rare event, a high pCR rate would be helpful to select the regimen and courses of NAC, especially when the pathological response rates are similar.

Increase of fucosylated alpha-fetoprotein fraction at the onset of autoimmune hepatitis and acute liver failure.

AIM: Increased serum α-fetoprotein (AFP) has been associated with a good prognosis following acute liver failure (ALF), but the levels of the fucosylated fraction of AFP (Lens culinaris agglutinin-reactive fraction of AFP [AFP-L3]) following acute liver injury remain unknown. The aim of the present study was to investigate the clinical significance of AFP and AFP-L3 in patients with acute liver injury. METHODS: We investigated the serum levels of AFP and highly sensitive AFP-L3% in 27 patients with acute-onset autoimmune hepatitis (AIH), 28 patients with acute hepatitis (AH) and 22 patients with ALF at the onset using a highly sensitive immunoassay (micro-total analysis system). RESULTS: The serum AFP levels were increased in patients with AIH, AH and ALF, but the levels did not significantly differ among them. However, the mean AFP-L3% level was significantly higher in patients with AIH than in patients with AH (P = 0.0039). Moreover, significantly more patients with AIH demonstrated AFP-L3 positivity (≥10%) when compared with patients with AH (P = 0.014). Although the percentage of AFP-L3 positivity increased with AFP levels, at low serum AFP levels (<10 ng/mL), significantly more patients with AIH demonstrated AFP-L3 positivity than did patients with AH (P = 0.024) or ALF (P = 0.038). CONCLUSION: We demonstrated for the first time that highly sensitive AFP-L3% levels were increased at the onset of AIH. The mechanism underlying the increase in AFP-L3 remains to be elucidated, but this finding may reflect an alteration of the glycosylation such as hyperfucosylation, which can influence the modifications of self-antigens in hepatocytes.

Granulocytapheresis for the treatment of severe alcoholic hepatitis: a case series and literature review.

Severe alcoholic hepatitis has a high mortality rate due to limited therapeutic methods. Although corticosteroids have been used to control the inflammatory response, the outcomes vary and no standardized therapy has been established. Novel therapeutic approaches, such as anti-TNF-α, pentoxifilline, and others have been tested clinically on the basis of their cytokinemic pathophysiology with limited success. However, treatment of leukocytosis that causes cytokinemia and hepatic inflammation in patients via granulocytapheresis and leukocytapheresis showed promising results in a number of reports. Here, we report two cases of severe alcoholic hepatitis treated with granulocytapheresis. The liver function and inflammation recovered after the therapy. A review of 35 cases treated with granulocytapheresis and leukocytapheresis demonstrated their efficacy in treating alcoholic hepatitis by controlling leukocytosis as well as cytokines such as IL-8. Multidisciplinary treatment for severe alcoholic hepatitis should be considered case by case on the basis of the complexity and severity of the condition.

Targeting therapy for hepatocellular carcinoma by delivering microRNAs as exosomal cargo.

Exosomes, the smallest extracellular vesicles, have gained significant attention as key mediators in intercellular communication, influencing both physiological and pathological processes, particularly in cancer progression. A recent review article by Wang et al was published in a timely manner to stimulate future research and facilitate practical developments for targeted treatment of hepatocellular carcinoma using exosomes, with a focus on the origin from which exosomes derive. If information about the mechanisms for delivering exosomes to specific cells is incorporated, the concept of targeted therapy for hepatocellular carcinoma using exosomes could be more comprehensively understood.

Hypovascular hepatic nodules showing hypointense on the hepatobiliary-phase image of Gd-EOB-DTPA-enhanced MRI to develop a hypervascular hepatocellular carcinoma: a nationwide retrospective study on their natural course and risk factors.

OBJECTIVE: We aimed to investigate the natural outcome of nonhypervascular lesions detected in the hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI by performing a longitudinal study retrospectively enrolled in a nationwide manner. METHODS: Between February 2008 and March 2011, 224 patients with 504 nodules that were diagnosed as nonhypervascular by imaging were recruited from institutions that participated in the present study. We examined the natural outcome of nonhypervascular lesions and evaluated the risk factors. RESULTS: Of the 504 nodules, 173 (34.3%) showed hypervascular transformation. The overall cumulative incidence of hypervascular transformation was 14.9% at 12 months and 45.8% at 24 months. Multivariate analysis using the Cox regression model revealed previous treatment history for hepatocellular carcinoma (HCC; relative risk = 1.498; p = 0.036, 95% CI 1.03-2.19) and hyperintensity on T2-weighted images (relative risk = 1.724; p = 0.015, 95% CI 1.11-2.67) were identified as independent factors for hypervascular transformation. CONCLUSIONS: Patients who have a previous treatment history for HCC and with hypointense nodules showing hyperintensity on T2-weighted images need careful follow-up because of the high incidence of hypervascular transformation.