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.

Early gastric cancer with multiple submucosal heterotopic gastric gland: A case report.

A case of early gastric cancer involving multiple submucosal gastric glands that was treated by distal gastrectomy was described in the present case report. An 85-year-old man was referred to our hospital for the treatment of gastric cancer. Esophagogastroduodenoscopy revealed an irregular, nodular, elevated lesion on the posterior wall of the middle third of the stomach, and biopsy specimens indicated well-differentiated tubular adenocarcinoma. Submucosal tumor (SMT)-like lesions were detected in the area adjacent to the nodular lesion, in the anterior wall side of the middle third of the stomach. Abdominal contrast-enhanced computed tomography showed cystic lesions in the middle part of the stomach, and no mass lesions in the liver. The patient underwent distal gastrectomy with regional lymphadenectomy. Macroscopic examination of the resected specimen showed an SMT-like lesion measuring 2.8×2.6 cm in contact with a superficial, depressed lesion measuring 1.7×0.9 mm in the middle third of the stomach, and another SMT-like lesion measuring 1.5×1.4 cm in diameter, which was also in the middle third of the stomach. The pathological diagnosis was well-differentiated tubular adenocarcinoma invading the gastric submucosal layer without lymph node metastasis, but with nearby submucosal heterotopic gastric gland (SHGG) detected. Following surgery, the patient remained symptom-free without evidence of recurrence for 3 months. The finding of SHGG remains a rare entity, and further studies are warranted to clarify the association between these submucosal lesions and the development of cancer.

[Multidisciplinary Treatment for a Patient with Recurrent Gastric Cancer, Presenting 13 Years after the Radical Gastrectomy].

A 72-year-old woman was referred to our hospital for further examination of para-aortic lymph node swelling and elevated carbohydrate antigen 19-9 levels. Thirteen years ago, she had undergone distal gastrectomy for gastric cancer, and the final diagnosis was T4N1M0, Stage ⅢA. Abdominal contrast-enhanced computed tomography(CT)showed an enlarged para-aortic lymph node measuring 25 mm. Endoscopic ultrasound-guided fine-needle aspiration was performed, and biopsy specimens showed poorly differentiated adenocarcinoma. Under the clinical diagnosis of gastric cancer recurrence, the patient received chemotherapy with cisplatin plus S-1. After 5 cycles of systemic treatment, abdominal CT revealed a marked shrinkage of the para-aortic lymph node metastasis, with an 84% decrease. At 15 months after treatment, we switched to S-1 monotherapy because of general fatigue and the patient's preference. However, 22 months after the treatment, the patient was treated with ramucirumab due to the progression of para-aortic lymph node metastasis. After 33 months, the patient developed metastasis in the left ovary, measuring 11.0×8.5 cm. Because there was no evidence of further metastatic lesions in any other organs, she underwent left oophorectomy. After 37 months, the patient developed metastasis in the left cerebellum, measuring 3.2×2.5 cm, accompanied with headache and nausea. The patient underwent metastasectomy of the left cerebellum as palliative treatment. Simultaneous physical examination revealed a painful nodular elevated lesion in the subcutaneous tissue of the posterior neck region, measuring 18×15 cm. Pathological examination of the biopsy specimen showed infiltration of poorly differentiated adenocarcinoma cells into the subcutaneous mass. The patient received radiation therapy; however, she died due to septic shock with hydronephrosis 39 months after starting chemotherapy. Although late recurrence of gastric cancer is rare, identification of risk factors and the development of novel treatments should be achieved through further studies and accumulation of data from such cases.

Prognostic significance of serum alkaline phosphatase and lactate dehydrogenase levels in patients with unresectable advanced gastric cancer.

BACKGROUND: This study evaluated the prognostic value of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) together with host-related factors in patients with unresectable advanced gastric cancer. METHODS: The study enrolled 262 patients who received chemotherapy for unresectable advanced gastric cancer at Kochi Medical School from 2007 to 2015. Clinicopathological information and systemic inflammatory response data were analyzed for associations between baseline cancer-related prognostic variables and survival outcomes. RESULTS: The median survival time was significantly lower for patients with high ALP, high LDH, high total bilirubin, high aspartate aminotransferase, high alanine transaminase, high gamma-glutamyltransferase, high creatinine, a Glasgow prognostic score (GPS) of 1 or 2 score compared to GPS 0, higher compared to lower neutrophil to lymphocyte ratio (NLR) 3.9, lower compared to higher prognostic nutrition index 36.1, T3-4 compared to T1-2 tumor and diffuse-type compared to intestinal-type histology. Multivariate survival analysis identified high ALP 322 (HR 1.808; 95% CI 1.015-3.220; P = 0.044), T2-3 (HR 2.622; 95% CI 1.224-5.618; P = 0.013), and diffuse-type gastric cancer (HR 2.325; 95% CI 1.341-4.032; P = 0.003) as significant independent predictors of worse prognosis in the studied group of cancer patients. CONCLUSIONS: High level of ALP is an independent, worse prognosis factor for patients receiving chemotherapy for unresectable and recurrent gastric cancer.

Pathological Complete Response by S-1 Chemotherapy in Advanced Gastric Cancer.

A pathological complete response (pCR) to treatment for gastric cancer is a rare event, even when powerful treatment regimens are used. Herein, a case of 61-year-old male referred to our hospital with advanced gastric cancer who achieved a pCR following chemotherapy using S-1, and subsequently underwent total gastrectomy is reported. His initial esophagogastroduodenoscopy (EGD) revealed an irregular, nodular, ulcerated lesion in the upper third of the stomach that was analyzed by biopsy to be a moderately differentiated adenocarcinoma. Abdominal contrast-enhanced computed tomography (CT) showed gastric wall thickening and lymph node swelling in the perigastric area. The patient was clinically diagnosed with cT3N1M0, stage IIB advanced gastric cancer. The patient decided against curative surgery due to his work circumstances and was started on S-1 (80 mg/m2) chemotherapy administered orally twice a day for 4 weeks, followed by 2 weeks of no chemotherapy. After four such courses of systemic S-1 chemotherapy, EGD showed a small, reddened lesion with aggregated, whitish lines. The gastric wall thickening and lymphadenopathy in the perigastric area were also reduced remarkably. The patient subsequently agreed to surgery, undergoing total gastrectomy with D2 lymphadenectomy. Gross examination of the surgically resected specimen showed a slightly erythrogenic, flat lesion measuring 1.5×1.0 cm. Pathological examination of the resected specimen and harvested lymph nodes detected no malignant cells. The postoperative course was uneventful. The patient has continued to receive S-1 chemotherapy, with no evidence of recurrence at 4 months post-surgery. To the best of our knowledge, this is only the second case of a gastric cancer patient achieving a pCR by S-1 monotherapy reported in the English literature and indicates the potential adoption of curative resection after S-1 chemotherapy as a treatment strategy for advanced gastric cancer.

Successful treatment of liver metastases arising from early gastric cancer achieved clinical complete response by nivolumab.

BACKGROUND: Although a recent randomized clinical trial has demonstrated that the objective response rate to nivolumab for metastatic gastric cancer was 11.2%, there was no patients confirmed complete response. Herein, we report on a case of liver metastasis arising from early gastric cancer in which a complete clinical response was achieved to nivolumab as third-line therapy. CASE PRESENTATION: A 77-year-old man was referred to Kochi Medical School Hospital for the treatment of liver metastases from gastric cancer. The patient had undergone laparoscopic total gastrectomy with regional lymph node dissection 30 months prior for early gastric cancer, with a final diagnosis of T1N0M0, stage IA. The patient developed solitary splenic metastasis measuring 42 mm 28 months later and underwent splenectomy because there was no evidence of further metastatic lesions in any other organ. The patient was treated with S-1 plus oxaliplatin based on negative immunohistochemical staining of the resected specimens for human epidermal growth factor receptor 2 (HER2). 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, i.v., nivolumab every 2 weeks. After 4 cycles of systemic treatment using nivolumab, abdominal computed tomography revealed marked shrinkage of the liver metastases. After 12 cycles of nivolumab, the liver metastases had disappeared completely. The patient did not develop any adverse reactions, including immune-reactive adverse events, during treatment. The patient continues to receive nivolumab, and there is no evidence of disease recurrence in the 8-month period since starting nivolumab. CONCLUSIONS: To the best of our knowledge, this is the first case report in the English literature of a gastric cancer patient achieving a complete clinical response to nivolumab, and highlights the potential for successful treatment of metastatic gastric cancer using nivolumab.

A case of stage IA pancreatic ductal adenocarcinoma accompanied with focal pancreatitis demonstrated by contrast-enhanced ultrasonography.

A patient with slight dilatation of the main pancreatic duct was followed-up with ultrasonography every 6 months as a high-risk case of pancreatic cancer. Twelve years later, a faint hypoechoic area 13 mm in diameter was first detected on the body of the pancreas. Contrast-enhanced ultrasonography revealed a well-demarcated hypoenhanced area 8 mm in diameter and a hyperenhanced area with an unclear margin. The former was suspected to be a small pancreatic cancer lesion, and the latter to be focal pancreatitis accompanying cancer. However, contrast-enhanced dynamic CT did not suggest any tumor, diagnosis of adenocarcinoma was confirmed with pancreatic juice cytology through endoscopic retrograde pancreatography. Surgical resection was performed, and the lesion was pathologically diagnosed as invasive ductal carcinoma as follows: pTS1 (1.0 cm), infiltrative type (pT1), stage IA. When comparing the images from contrast-enhanced ultrasonography with the pathological findings, the hypoenhanced area corresponded to ductal adenocarcinoma, and the hyperenhanced area to focal pancreatitis. Contrast-enhanced ultrasonography was able to reveal detailed information on the focal lesion in the pancreas, and it was effective for the early diagnosis of pancreatic cancer.

Duodenal Hemorrhage from Pancreatic Cancer Infiltration Controlled through Combination Therapy with Gemcitabine and S-1.

2.6% of pancreatic cancer patients have the primary manifestation of gastrointestinal bleeding. It is not feasible to stop the duodenal hemorrhage caused by the pancreatic cancer infiltration. A 43-year-old woman who was diagnosed as having pancreatic cancer with multiple hepatic metastases and duodenal infiltration was administered gemcitabine and S-1 combination therapy. During the chemotherapy, initially, bleeding occurred due to duodenal infiltration. However, we continued the chemotherapy and duodenal infiltration was markedly reduced in size and did not rebleed. Aggressive chemotherapy contributed to maintenance of performance status as well as improvement of quality of life for the patient.