[Current Status of ICG Fluorescence Navigation in Laparoscopic Liver Resection].

The indocyanine green(ICG)fluorescence navigation that we have standardized for laparoscopic liver resection is useful for partial liver resection and anatomical liver resection for liver cancer, and extended cholecystectomy for gallbladder cancer. In partial liver resection we believe that it is possible to secure a resection margin by not exposing the fluorescence emission around the tumor. In anatomical liver resection, real-time navigation becomes possible by transecting the liver at the boundary between colored and non-colored area, which contributes to precise liver surgery. In extended cholecystectomy, it is difficult to inject ICG from the cystic artery which was performed in open liver resection. So, we encircled Calot's triangle using the Glissonean approach from the ventral side of the gallbladder plate and then taped the hilar Glissonean pedicles. After clamping this tape, ICG was injected into the vein. By using this method, laparoscopic surgery has become possible in the same way as open surgery. With further spread in the future, it is hoped that liver resection using ICG fluorescence navigation will not only be precise, but also safe and highly curative surgery.

Incidence, clinicopathological characteristics, and therapeutic strategy for gastric cancer patients with metastasis to the central nervous system.

AIM: This study aimed to analyze the clinicopathologic features and treatment outcomes of central nervous system (CNS) metastasis from gastric cancer. METHODS: A total of 419 patients diagnosed with unresectable advanced or recurrent gastric cancer at Kochi Medical School between January 2007 and December 2021 were evaluated. Data of patients were reviewed, and clinicopathological information and survival outcomes of those with CNS metastases were compared to patients without CNS metastases. RESULTS: In total, 12/419 (2.9%) patients (median age: 66.5 years [range, 41-82 years]) were diagnosed with CNS metastasis from gastric cancer. Eleven had diffuse-type gastric cancer which was significantly more common than in those without CNS metastasis (91% vs. 61%, p = .034). Human epidermal growth factor receptor 2 status was positive in one of the 12 patients. The median survival time was significantly lower for patients with CNS metastasis than for those without CNS metastasis (1.8 months vs. 11.4 months, p < .001). The median survival time for patients who underwent surgical resection, radiation, or chemotherapy for CNS metastasis was significantly higher than those who received only best supportive care (3.5 months vs. .6 months; p = .007). CONCLUSIONS: CNS metastasis was found in 2.9% (12/419) of patients with unresectable advanced or recurrent gastric cancer. Diffuse-type histology was a risk factor for CNS metastasis. Multidisciplinary treatment, including surgical resection, radiation treatment, or chemotherapy, for CNS metastasis from gastric cancer may benefit selected patients.

Laparoscopic total gastrectomy for concurrent gastric cancer and complete agenesis of the dorsal pancreas.

We present an unusual case of laparoscopic total gastrectomy with lymph node dissection in a 56-year-old woman with gastric cancer and agenesis of the dorsal pancreas (ADP). Esophagogastroduodenoscopy revealed erosive lesions with thickened gastric folds; biopsy specimens revealed a poorly differentiated adenocarcinoma. Abdominal contrast-enhanced computed tomography showed a thickened wall of the gastric body; the distal pancreas was not visualized. Under the clinical diagnosis of gastric cancer with ADP, the patient underwent laparoscopic total gastrectomy with standard lymphadenectomy. The absence of a pancreatic neck, body, and tail was confirmed; lymph nodes along the splenic artery were dissected. Pathological analysis demonstrated a poorly differentiated adenocarcinoma invading the serosa, with five lymph node metastases. The postoperative course was unremarkable; postoperative adjuvant chemotherapy was performed using S-1 plus oxaliplatin. No symptom recurrence was observed at the 6-month follow-up. Laparoscopic surgery, with careful preoperative anatomic evaluation, can be considered for concurrent gastric cancer and ADP.

[Long-Term Survival of an Adolescent and Young Adult Patient with Unresectable Advanced Gastric Cancer in Whom Multidisciplinary Treatment Was Effective].

We report the case of a long-term-surviving adolescent and young adult patient with unresectable advanced gastric cancer for whom multidisciplinary treatment was effective. A 29-year-old woman was referred to our hospital for further examination following a diagnosis of gastric cancer by a local physician. Esophagogastroduodenoscopy showed a deep ulcerated lesion in the lower third of the stomach, and analysis of biopsy specimens revealed an adenocarcinoma. Abdominal contrast- enhanced computed tomography showed gastric wall thickening in the lower third of the stomach. The patient underwent distal gastrectomy with lymph node dissection, including resection of localized peritoneal metastases, followed by Roux-en- Y reconstruction. The pathological diagnosis was serosa-invading poorly differentiated adenocarcinoma with 1 lymph node metastasis measuring 6.0×5.5 cm in the posterior wall of the lower third of the stomach and negative immunohistochemical staining for human epidermal growth factor receptor 2. The patient received postoperative chemotherapy with S-1 and oxaliplatin. She developed bilateral ovarian metastases measuring 13.0 cm and 7.8 cm after 17 months. The patient presented with severe lower abdominal pain and underwent an emergency bilateral ovarian metastasectomy, which revealed torsion of the right ovarian tumor, which had twisted twice on its pedicle, and a left ovarian mass. After the operation, 41 courses of ramucirumab with nab-paclitaxel were administered as a second-line treatment, and she received systemic drug treatment. Sixty months after the gastrectomy, the patient developed left hydronephrosis due to peritoneal metastases and was treated with nivolumab after ureteral stent replacement. No effective treatment was proposed in cancer multigene panel testing, and she died 66 months after the initial treatment because of disease progression. Comprehensive multidisciplinary treatment, including surgical and local therapy for peritoneal dissemination based on drug therapy for unresectable advanced gastric cancer, may result in long-term survival. Further research and accumulation of such cases would lead to the development of novel treatments.

Frequency and therapeutic strategy for patients with ovarian metastasis from gastric cancer.

PURPOSE: This study aimed to analyze the clinicopathological features and treatment outcomes of ovarian metastasis from gastric cancer. METHODS: This study included 155 female patients with unresectable advanced or recurrent gastric cancer at the Kochi Medical School between January 2007 and December 2021. A review of patients with ovarian metastasis was conducted, and their clinicopathological information and survival outcomes were compared with respect to ovarian metastasis. RESULTS: Fifteen patients were diagnosed with ovarian metastasis from gastric cancer with a median age of 54 years (range: 30-87 years) and an incidence of 9.7%. The median age of patients who developed ovarian metastasis was significantly lower those without ovarian metastasis (54 years vs. 71 years, P = 0.014). The median survival time (MST) for 15 patients with unresectable advanced gastric cancer who developed ovarian metastasis was 21.4 months (range: 0.2-41.4 months). The MST for 15 patients who underwent surgical resection and systemic drug treatment including chemotherapy to ovarian metastasis was significantly higher than those who received systemic drug treatment alone (28.1 months vs. 10.0 months; P = 0.021). CONCLUSION: Ovarian metastasis was found in 9.7% of female patients with unresectable advanced or recurrent gastric cancer and in younger patients than in those without ovarian metastasis. Multidisciplinary treatment, including surgical resection and systemic drug treatment for ovarian metastasis from gastric cancer, may benefit selected patients.

[Brain Metastasis Arising from Gastric Cancer during Long-Term Treatment Using Nivolumab].

Metastasis to the central nervous system from gastric cancer is exceedingly uncommon. We report a gastric cancer patient with cerebral metastasis during the period when durable response was obtained by systemic drug treatment using nivolumab. A 78-year-old male was referred to our hospital for further examination following diagnosis of gastric cancer by a local medical doctor. Esophagogastroduodenoscopy showed a slightly elevated lesion with central depressed area in the upper-third of the stomach, and analysis of biopsy specimens revealed an adenocarcinoma. The patient underwent laparoscopic total gastrectomy with lymph nodes dissection followed by Roux-en-Y reconstruction, resulting in submucosal invasive carcinoma and no lymph node metastasis. The patient developed solitary splenic metastasis measuring 4.2 cm after 28 months later, and the patient underwent a splenectomy, since there was no evidence of further metastatic lesions in any other organs. Subsequently, the patient was received S-1 plus oxaliplatin chemotherapy based on negative immunohistochemical staining of the resected specimens for human epidermal growth factor receptor 2. Four months after the splenectomy, the patient developed multiple liver metastases and was treated with ramucirumab plus paclitaxel. Because of disease progression, the patient was administered 3 mg/kg, iv, nivolumab every 2 weeks. After 4 courses of systemic treatment using nivolumab, abdominal computed tomography revealed marked shrinkage of the liver metastases. After 12 courses of nivolumab, the liver metastases had disappeared completely. The patient developed hypothyroidism, which could be controlled by thyroid hormone replacement treatment. The patient continues to receive nivolumab, and there is no evidence of disease recurrence in the 33 month period since starting nivolumab. However, he developed cerebral metastases after 69 months after surgery, complaining of articulation disorder. The patient underwent tumor resection by craniotomy followed by radiation therapy; however, he died 3 months after the operation. Although brain metastasis arising from gastric cancer is rare, future identification of risk factors and development of novel treatments are desired by further investigations and accumulation of these cases.

Pneumothorax during lenvatinib treatment for hepatocellular carcinoma with lung metastasis.

Lenvatinib is an inhibitor of tyrosine kinases, such as vascular endothelial growth factor receptor and fibroblast growth factor receptor, and was first approved for use in thyroid cancer in 2015 in Japan. Additional approval was given in March 2018 for its use as a first-line treatment for advanced or unresectable hepatocellular carcinoma. Herein, we report a case of pneumothorax during lenvatinib treatment for multiple lung metastases of hepatocellular carcinoma in a 71-year-old man. Although the development of pneumothorax during treatment with anticancer agents for lung metastases is well-known, this is the first report of pneumothorax induced by lenvatinib during treatment for lung metastases of hepatocellular carcinoma.

Lymph node retrieval after colorectal cancer surgery: a comparative study of the efficacy between the conventional manual method and a new fat dissolution method.

PURPOSE: This study compared the efficacy of two different methods for lymph node (LN) searching after colorectal cancer surgery: the fat dissolution and the conventional manual method. METHODS: For the fat dissolution method, we used a commercially available solution of collagenase and lipase (FD group). The primary endpoint was the number of identified LNs in the FD group compared to an historical control (control group) after adjusting by propensity score matching. RESULTS: Using 37 matched patients from each group, we identified 20.6 ± 7.2 LNs using the fat dissolution method compared to 13.5 ± 5.9 using the conventional method (t test, P < 0.01). Three patients in the FD group received an inappropriate LN examination in terms of number, while the number of the retrieved LNs was < 12 in 12 patients in the control group. The mean diameter of LNs without metastasis was 3.2 ± 1.9 mm in the FD group, and 40% of metastasis cases were found in LNs < 5 mm in diameter. A pathological examination confirmed that using the fat resolution method did not change the morphological or immunochemical staining findings. CONCLUSION: We demonstrated that fat dissolution had a positive impact on the number of retrieved LNs after colorectal cancer surgery without disturbing the microscopic observation.

Data on metabolic profiling of healthy human subjects' plasma before and after administration of the Japanese Kampo medicine maoto.

This data article contains the data on metabolic profiling of healthy human subjects' plasma before and after administration of the Japanese Kampo medicine maoto. Four healthy human subjects were recruited. Plasma samples were collected before and 0.25, 0.5, 1, 2, 4 and 8 h after maoto treatment. Endogenous and exogenous compounds in plasma were analyzed using MS. Endogenous compounds including saccharides, amino acids, organic acids and other hydrophilic metabolites were semi-quantitatively measured using GC-MS/MS. Lipid mediators such as arachidonic acid, docosahexaenoic acid and eicosapentaenoic acid were semi-quantitatively measured using LC-MS/MS. Maoto constituents in plasma were quantitatively measured using LC-MS/MS. The data files contain the area ratio values, which were normalized to the intensity of the internal standard, and plasma concentration of maoto compounds. The data article is related to the research article titled "Phenotyping analysis of the Japanese Kampo medicine maoto in healthy human subjects using wide-targeted plasma metabolomics" (Kitagawa et al., 2018).

Phenotyping analysis of the Japanese Kampo medicine maoto in healthy human subjects using wide-targeted plasma metabolomics.

Traditional herbal medicine (THM) consists of a vast number of compounds that exert pharmacological effects throughout the body. Comprehensive phenotyping analysis using omics is essential for understanding the nature of THM in detail. We previously reported that the Japanese Kampo medicine maoto ameliorated flu-like symptoms in a rat infection model and dynamically changed plasma metabolites as indicated by metabolome analysis. The aim of this study was to apply wide-targeted plasma metabolomics with quantitative analysis of maoto compounds in a human clinical trial to evaluate the effect of maoto on plasma metabolites. Four healthy human subjects were recruited. Plasma samples were collected before and 0.25, 0.5, 1, 2, 4 and 8 h after maoto treatment. Wide-targeted metabolomics and quantitative analysis of the main chemical constituents of maoto were then performed. Plasma metabolome analysis revealed that maoto administration decreased essential amino acids including branched-chain amino acids (BCAAs) and increased various kinds of ω-3 fatty acids including eicosapentaenoic acid and docosahexaenoic acid, consistent with previous studies in rats. Fifteen of the major compounds in maoto were identified in the systemic circulation. Finally, the correlation between endogenous metabolites and maoto compounds in plasma was analyzed and the results indicated that the decrease in plasma BCAAs might be caused by ephedrines present in maoto. The present study demonstrated that plasma metabolomic studies of endogenous and exogenous metabolites are useful for elucidating the mechanism of action of THM.

Serum carbohydrate antigen 125 is a significant prognostic marker in patients with unresectable advanced or recurrent gastric cancer.

PURPOSE: We evaluated the diagnostic and prognostic value of three tumor markers: carcino-embryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and carbohydrate antigen 125 (CA125), in the pretreatment serum of patients with unresectable advanced or recurrent gastric cancer. METHODS: The subjects of this retrospective analysis were 245 patients with unresectable advanced or recurrent gastric cancer diagnosed at Kochi Medical School between 2007 and 2015. We ascertained the sensitivity of CEA, CA19-9, and CA125 to identify a certain survival time and then evaluated the relative prognosis of the patients. RESULTS: The overall positive rates for each tumor marker in the study group were as follows: 57.6% (141/245) for CEA, 38.4% (94/245) for CA19-9, and 34.3% (84/245) for CA125; the sensitivity of these three biomarkers in combination was 73.1% (179/245). The median survival time of the CA125-positive patients was 4.5 months, which was significantly shorter than that of a normal range group (18.3 months, P < 0.001). Multivariate survival analysis identified that high CA125 was independently associated with a worse prognosis (HR 3.941; 95% CI 2.544-6.106; P < 0.001). CONCLUSIONS: Pretreatment serum CA125 is a useful prognostic biomarker in patients with unresectable advanced or recurrent gastric cancer. Evaluating a panel of serum tumor biomarkers is a useful diagnostic tool as elevated values might be associated with poor survival.

Gastric adenocarcinoma at the anastomotic site 50 years after gastrojejunostomy: A case report.

We herein report a rare case of superficially spreading early gastric cancer occurring 50 years after gastrojejunostomy. An 83-year-old woman was diagnosed with gastric cancer after complaining of epigastric discomfort. The patient had undergone gastrojejunostomy with Braun jejunojejunostomy for benign chronic peptic ulcer 50 years prior. Esophagogastroduodenoscopy revealed an irregular nodular lesion on the gastric side of the anastomosis of the gastrojejunostomy. No abnormal lesions were identified by abdominal contrast-enhanced computed tomography. The patient underwent distal gastrectomy with regional lymphadenectomy. The final diagnosis was signet ring cell carcinoma invading the gastric submucosal layer, without lymph node metastasis, located in the area surrounding the original gastrojejunostomy and measuring 9.5×4.5 cm. In addition, dilated cystic glands were found in the submucosal layer, indicating gastritis cystica profunda. Following surgery, the patient remained symptom-free without evidence of recurrence for 46 months. Although it is not clear whether the adenocarcinoma at the stomal site was associated with the superficial spreading-type tumor in the present case, the observations may provide clues as to the pathogenic process of this entity.

Metachronous solitary splenic metastasis arising from early gastric cancer: a case report and literature review.

BACKGROUND: The metastasis of malignant tumors to the spleen is rare, and only a small percentage of cases can be treated surgically, as splenic metastases generally occur in the context of multivisceral metastatic cancer at a terminal stage. We report a rare case of metachronous solitary splenic metastasis arising from early gastric cancer. CASE PRESENTATION: A 75-year-old man was initially referred to our hospital for examination of gastric cancer, diagnosed at a medical check-up. Esophagogastroduodenoscopy showed a slightly elevated lesion with a central irregular depression in the upper-third of the stomach. Biopsy specimens of the lesion showed a moderately-differentiated adenocarcinoma, and abdominal computed tomography showed no evidence of distant metastases. Endoscopic submucosal dissection was performed, with histological confirmation of a moderately-differentiated adenocarcinoma invading the submucosal layer. The patient subsequently underwent laparoscopic total gastrectomy with regional lymph node dissection, resulting in no residual carcinoma and no lymph node metastasis. Computed tomography, 28 months later, showed a well-defined mass measuring 4.2 cm in diameter in the spleen, and the patient underwent a splenectomy, since there was no evidence of further metastatic lesions in any other organs. Histological examination confirmed the diagnosis of a poorly-differentiated adenocarcinoma originating from the previous gastric cancer. The patient was alive 2 months after surgical resection of the splenic metastasis without any recurrence. CONCLUSION: To the best of our knowledge, this is only the second case of a solitary splenic metastasis from early gastric cancer to be reported in the English literature. The present case suggests surgical resection may be the preferred treatment of choice for patients with a solitary splenic metastasis from gastric cancer.

Juxtapapillary Duodenal Diverticulum Impacted with Enterolith.

A 64-year-old man underwent abdominal computed tomography (CT) as periodic follow-up following a distal gastrectomy with lymphadenectomy for gastric cancer and mucosal-associated lymphoid tissue (MALT) lymphoma conducted 31 months earlier. Contrast-enhanced CT demonstrated a well-circumscribed mass lesion with heterogeneous density measuring 2.2 cm in diameter located between the second segment of the duodenum and uncinate process of the pancreas. Esophagogastroduodenoscopy revealed no remarkable findings in the remnant stomach; however, the scope could not reach the duodenum due to altered anatomy by Roux-en-Y reconstruction after the distal gastrectomy. The patient underwent surgical resection of the mass lesion under the clinical diagnosis of MALT lymphoma relapse. An orange calculus was apparent in the thinly extended duodenal wall on stretching, and the hall was closed by meticulous primary suture after the duodenal resection. Macroscopically, the extracted calculus was solid and quite hard, measured 2.2 × 2.1 × 2.1 cm, and the cut surface revealed a layered structure in the outer areas with granulated contents in the center. Although duodenal diverticula are relatively common, an enterolith developing within a juxtapapillary duodenal diverticulum is rare, and to the best of our knowledge, this is the first such case due to altered anatomy after gastrectomy reported in the English literature.

Neurofibroma of the Gallbladder Not Associated with Neurofibromatosis.

An 82-year-old woman had visited her local clinic with a history of abdominal discomfort and dyspepsia related to meals over a period of several months. Esophagogastroduodenoscopy revealed a superficial spreading tumor that, on biopsy, was proven to be an adenocarcinoma, and colonoscopy revealed an ascending mass that was found to be an adenocarcinoma on biopsy, so the patient was referred to our hospital. Abdominal computed tomography revealed a mass in the ascending colon with regional lymph node swelling and a gallbladder stone measuring 1.5 cm in diameter. The patient underwent laparoscopy-assisted distal gastrectomy with cholecystectomy and right colectomy with regional lymph node dissection, resulting in a diagnosis of poorly differentiated adenocarcinoma invading the gastric submucosal layer and moderately differentiated tubular adenocarcinoma invading the colonic serosa with lymph node metastasis. Macroscopic examination of the gallbladder revealed a well-circumscribed, solid tumor measuring 0.3 x 0.3 cm with a firm consistency in the neck portion associated with lithiasis. Microscopic examination of the gallbladder tumor revealed infiltration of spindle-shaped neoplastic cells that were arranged in a fasciculated and woven pattern in abundant intersecting bundles. Immunohistochemical analyses were positive for S-100 protein and neurofilament. Although neurofibromas commonly occur in the superficial skin or subcutaneous region, isolated neurofibroma of the gallbladder is quite rare. To the best of our knowledge, this is only the 11th case of a neurofibroma of the gallbladder to be reported in English literature. In the present case, as in most previously reported cases, the tumor was found incidentally in the resected gallbladder following cholecystectomy for cholecystolithiasis.

Analysis of Factors Associated with Weight Loss After Esophagectomy for Esophageal Cancer.

AIM: To investigate the factors associated with weight loss (WL) after esophagectomy for esophageal cancer. PATIENTS AND METHODS: We retrospectively reviewed 136 patients who underwent esophagectomy for esophageal cancer. Preoperative characteristics, surgical methods, postoperative outcomes and weight changes at 6 months after surgery were analyzed. RESULTS: Seventy-eight patients had more than 10% WL compared to their weight at surgery. On univariate analysis, higher body mass index [(BMI): ≥20.8; p=0.012] and shorter length of hospitalization [(LOH); p=0.041] demonstrated an association with more than 10% WL. On multivariate analysis, higher BMI [odds ratio (OR)=2.821; 95% confidence interval (CI)=1.238-6.426; p=0.014] and shorter LOH (OR=2.953; 95% CI=1.009-8.646; p=0.048) were independently associated with more than 10% WL. CONCLUSION: Higher BMI and shorter LOH were unfavorable risk factors for WL after esophagectomy for esophageal cancer.