Successful Application of Tocilizumab in a Patient With Neoadjuvant Immunochemotherapy-Induced Cytokine Release Syndrome.

BACKGROUND: The expansion of preoperative immunochemotherapy has led to an increase in the number of patients with lung cancer receiving immune checkpoint inhibitors (ICIs). Therefore, oncologists should manage a variety of immune-related adverse events (irAEs). One of the rare, life-threatening, and recently proposed irAEs is cytokine release syndrome (CRS). Although the standard treatment of irAE is systemic administration of steroids, it has been suggested that tocilizumab may be an effective treatment option for CRS. CASE: This case describes a 69-year-old man with stage IIIA lung adenocarcinoma who received chemotherapy and nivolumab, which is an ICI, as neoadjuvant immunochemotherapy. After the first administration, the patient developed severe skin rash, fever, and arthralgia. We suspected irAEs and administered systemic steroids. However, fever and arthralgia did not improve, although the skin rash disappeared. These were also significant challenges for surgery. Noting the elevated levels of inflammatory cytokines, we consulted a rheumatologist. Finally, we decided to terminate neoadjuvant therapy after one cycle and administer tocilizumab. Tocilizumab dramatically improved the patient's symptoms and allowed him to undergo radical surgery. Pathological findings revealed that the patient achieved a major pathological response. CONCLUSION: This indicates the potential effectiveness of early tocilizumab administration for ICI-induced CRS, even in mild cases.

Successful application of lorlatinib in a 23-year-old patient with anaplastic lymphoma kinase (ALK)-positive lung cancer and multiple brain metastases.

BACKGROUND: Anaplastic lymphoma kinase (ALK)-positive lung cancer has a better long-term prognosis with ALK-inhibitor than other lung cancers. However, resistance to ALK-inhibitors and the control of metastases in the central nervous system (CNS) remain to be a challenge in the management of ALK-positive lung cancer. CASE: We present the case of a 23-year-old man who developed multiple brain metastases while receiving alectinib treatment for ALK-positive lung cancer. After 3 months of lorlatinib initiation, brain metastases disappeared, and complete response (CR) was maintained. CONCLUSION: While lorlatinib can be used as first line therapy, this drug may be considered as second line or later option for patients with multiple brain metastases if the patient has already been treated with other ALK-inhibitors since lorlatinib is thought to have good CNS penetration. This treatment option should be verified by further research.

[A Case of Mesh Infection Due to Transverse Colon Cancer].

A 69-year-old female underwent a mesh repair for an abdominal incisional hernia 4 years previously in our hospital. She visited local hospital for abdominal pain and fever. Abdominal CT showed a localizes abscess formation above the mesh, then she was taken to our hospital. We suspected mesh infection and performed emergent mesh removal. After the operation, we examined for her anemia. Her colonoscopy and CT findings pointed to transverse colon cancer. We performed right hemicolectomy, and final diagnosis was transverse colon cancer pT4aN0M0, pStage Ⅱb. She underwent adjuvant chemotherapy, and 9 months after surgery, no recurrence was found.

[Bilateral Multiple Liver Metastases after Pancreatoduodenectomy for a Duodenal Neuroendocrine Tumor-A Case Report].

The patient was a 79-year-old woman. In January 20XX, upper gastrointestinal endoscopy revealed a duodenal tumor with bleeding and ulceration. This tumor was diagnosed as a duodenal neuroendocrine tumor(NET)based on biopsy findings. In March 20XX, the patient underwent pancreatoduodenectomy with lymph node dissemination. Based on these pathological findings, the tumor was diagnosed as a duodenal NET(G2)with a lymph node metastasis(T2, N1, M0, Stage Ⅲ). Twenty months after the operation, abdominal CT revealed multiple liver metastases(S4, S7, and S8). After this recurrence, she underwent the subcutaneous somatostatin analogue injection therapy every 28 days, and transarterial chemoembolization( TACE)when these recurrent tumors showed remarkable regrowth, once a year, accounting for her age. She has maintained good disease control for 5 years.

[Laparoscopic Tumor Resection for Retroperitoneal Leiomyosarcoma-A Case Report].

A 59-year-old man visited our department because of cholecystectomy. Preoperative CT revealed a tumor shadow measuring 50 mm in front of the right iliopsoas muscle. MRI showed a low signal intensity on T1-weighted images and a slightly high signal intensity on the T2-weighted image. PET-CT showed accumulation of FDG(SUVmax 5.39)in the tumor but no other abnormal accumulations. We performed tumor resection for diagnostic purposes because malignancy could not be ruled out owing to the large size of the mass. Intraoperative findings showed a well-circumscribed margin of the tumor without invasion to other tissues. The retroperitoneum was incised circumferentially along the tumor under laparoscopic guidance, and the tumor was resected. Histopathological and immunostaining findings were consistent with leiomyosarcoma. In laparoscopic surgery, the surgical margin is observed in detail through the magnifying effect. Therefore, laparoscopic surgery can be a surgical option for tumors that may be completely excised based on preoperative findings.

[A Case of Mature Teratoma in the Hepatoduodenal Ligament].

A 60's woman was admitted to our hospital because of palpitations that occurred with exertion. Coronary angiography computed tomography(CT)of suspected angina detected a tumor in the pancreatic head region. Abdominal CT showed a poorly enhanced 40×32 mm solid tumor in the hepatoduodenal ligament that contained a fatty component and calcification. During surgery, the tumor was located in the hepatoduodenal ligament, adhered to the pancreatic head, common hepatic artery, gastroduodenal artery, portal vein and common bile duct. However, the tumor was resected by preserving them. The tumor contained stratified squamous epithelium, a sebaceous gland, nerve, a pancreatic gland, and an adrenal gland. The histological diagnosis was a mature cystic teratoma. The patient showed no recurrence in 2 years and 10 months post-surgery. Mature teratomas in the hepatoduodenal ligament are extremely rare. Some reports showed that combined resection was performed when the tumor was in contact with the common bile duct, portal vein, and arteries. However, in our case, the tumor was removed relatively safely without combined resection.

[A Long-Term Survival Case of Neuroendocrine Carcinoma of Gallbladder-Report of a Case].

The patient is 77-year-old man. He received open cholecystectomy and choledocholithotomy when he was 74 years old. Because postoperative diagnosis was small cell neuroendocrine carcinoma(NEC), the resection of gallbladder bed and hilus lymph nodes were performed. During the follow up period, the liver metastases and portal vein tumor thrombosis appeared. Therefore, chemotherapy was performed according to small cell lung cancer. In addition to chemotherapy, radiation therapy was performed for the purpose of local control. He is still alive about 3 years after the first operation. This case suggested the efficacy of multidisciplinary treatment including operation, chemotherapy, and radiation therapy in NEC of gallbladder patient with liver metastasis.

[Pathological Complete Response in a Case of Advanced Gastric Cancer with Para-Aortic Lymph Nodes Metastasis Treated by Preoperative Chemotherapy with S-1 and Oxaliplatin(SOX Therapy)].

The patient was a 73-year-old man, diagnosed as advanced gastric cancer with para-aortic lymph nodes(PAN)metastasis. He was treated by 3 courses of neoadjuvant chemotherapy(NAC)with S-1 and oxaliplatin(SOX therapy). CT showed significant reduction of both primary tumor and metastatic lymph nodes. We performed distal gastrectomy with D2 plus PAN dissection. The histopathological findings showed no residual viable tumor cell. The pathological effect of chemotherapy was judged Grade 3(pCR)in both primary tumor and dissected lymph nodes. He is alive without recurrence 21 months after surgery.

[A Case of Fibrolamellar Hepatocellular Carcinoma in a 25-Year-Old Vietnamese Male].

We report a rare case of hepatic fibrolamellar hepatocellular carcinoma(FLC). A 25-year-old Vietnamese male experienced loss of appetite and abdominal pain. He was referred for further examination of a 20 cm tumor in the left lobe of the liver detected in mass screening ultrasonography. He tested negative for HBs-antigen and HCV-antibody. The serum PIVKA- Ⅱ level was elevated. Liver function test findings were normal. The arterial phase of contrast enhanced abdominal CT revealed a 20×30 cm tumor that was well-enhanced, except for a central scar in the left lobe of liver. Enhanced MRI showed a high intensity tumor. T2-weighted MRI showed an iso-intensity tumor with a low-intensity central fibrous scar. Upon diagnosing the patient with FLC, we performed left hepatic trisegmentectomy. Pathological findings of the surgical specimen showed eosinophilic large neoplastic cells surrounded by fibrous stroma arranged in a lamellar fashion. This confirmed the diagnosis. FLC, which occurs in noncirrhotic livers of young patients, is a distinct clinicopathological variant of hepatocellular carcinoma. Hepatectomy for FLC should be accompanied with regional lymphadenectomy because of its association with lymph node metastasis. We also reviewed cases reported in Japan.

[Laparoscopic Surgery for Synchronous Retroperitoneal Tumor and Ovarian Mature Teratoma-A Case Report].

A 72-year-old woman was transferred to our hospital after being diagnosed with retroperitoneal and ovarian tumors. Abdominal computed tomography revealed a well-defined mass lesion measuring 35 mm on the dorsal side of the descending part of the duodenum that was surrounded by the head of the pancreas and inferior vena cava. In addition, a cystic mass measuring 90 mm was found in the pelvis. Hence, the patient was diagnosed synchronous retroperitoneal tumor and teratoma. Laparoscopic retroperitoneal tumor resection and right adnexectomy were performed. The pathological findings indicated that the retroperitoneal tumor was a diffuse large B-cell lymphoma and the pelvic tumor was a mature cystic teratoma of the ovary. On the basis of the computed tomography findings, we judged that the tumor had a poor tendency to infiltrate and could be peeled off and resected using laparoscopic surgery. In this rare case, the retroperitoneal tumor and mature teratocarcinoma were simultaneously resected laparoscopically.

[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.

[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.

[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 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 Cystic Biliary Hamartoma with a Difficult Preoperative Diagnosis].

Intrahepatic bile duct dilatation was detected in a 63-year-old man based on abdominal ultrasonography. The computed tomography and magnetic resonance imaging scans showed an intrahepatic cystic lesion in the hilar bile duct that led to intrahepatic bile duct dilatation. As a result, intraductal papillary neoplasm of the bile duct(IPNB)was suspected. Moreover, the intrahepatic bile duct dilatation was confirmed by endoscopic retrograde cholangiopancreatography(ERCP). Biliary and brushing cytology indicated that the cystic lesion was class Ⅱ and class Ⅲ, respectively. Radiological imaging test did not rule out the possibility of a malignant lesion. Hence, a radical left hepatectomy was performed. Histopathological examination of the resected specimen indicated that it was a non-malignant cystic biliary hamartoma. Cystic biliary hamartoma or the von Meyenburg complex is a relatively rare disease. Although this disease is categorized as benign, differential diagnosis between benign and malignant forms is difficult, and this is an important clinical issue.

[A Case of Superior Mesenteric Vein Thrombosis during Administration of Bevacizumab for Rectal Cancer].

A colonoscopy to investigate fecal incontinence revealed a type 3 tumor in the rectum of a 67-year-old man. Histological findings demonstrated rectal adenocarcinoma. CT revealed multiple metastases in the liver, and the patient was diagnosed as having rectal cancer(Rb, Ant, type 3, T3, N3, M1a[H2], cStage Ⅳa). No intestinal stenosis due to the tumor was found, and chemotherapy(FOLFIRI plus bevacizumab)was initiated. After 5 courses of the chemotherapy, a thrombus was found in the superior mesenteric vein on enhanced CT. The patient had no subjective symptoms, and anticoagulation therapy was started after admission. After confirming the shrinkage of the thrombus, laparoscopic abdominoperineal resection(prxD3)was performed to remove the primary tumor. The thrombus did not grow during the perioperative time and disappeared after 6 months. For the next 2 years, no new thrombus was detected. Mesenteric vein thrombosis is a notable complication of chemotherapy with bevacizumab.

[Laparoscopic Surgery for a Case of Double Digestive Cancers with X-Linked Agammaglobulinemia].

A 65-year-old man was diagnosed with agammaglobulinemia at the age of 53 years. To investigate the cause of the increased CRP value, CT was performed and revealed thickening of the walls of the ascending colon and rectum. Colonoscopy revealed tumors and stenoses in the ascending colon and rectum. Both tumors were found to be adenocarcinomas in histological examinations. The preoperative diagnosis of the ascending colon and rectal cancers was cT4aN0M0, cStageⅡb. Preoperatively, we administered 10.0 g of immunoglobulin intravenously. We performed laparoscopic right hemicolectomy and high anterior resection with D3 dissection of the lymph node. On postoperative day 1, we again administered 10.0 g of immunoglobulin intravenously. The patient recovered uneventfully and was discharged on postoperative day 13. Laparoscopic colectomy for patients with agammaglobulinemia can be performed safely by administering immunoglobulin during the perioperative period.

[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.

Brachial-to-ankle pulse wave velocity as an independent prognostic factor for ovulatory response to clomiphene citrate in women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) has a risk for cardiovascular disease. Increased arterial stiffness has been observed in women with PCOS. The purpose of the present study was to investigate whether the brachial-to-ankle pulse wave velocity (baPWV) is a prognostic factor for ovulatory response to clomiphene citrate (CC) in women with PCOS. METHODS: This study was a retrospective cohort study of 62 women with PCOS conducted from January 2009 to December 2012 at the university hospital, Yamagata, Japan. We analyzed 62 infertile PCOS patients who received CC. Ovulation was induced by 100 mg CC for 5 days. CC non-responder was defined as failure to ovulate for at least 2 consecutive CC-treatment cycles. The endocrine, metabolic, and cardiovascular parameters between CC responder (38 patients) and non-responder (24 patients) groups were analyzed. RESULTS: In univariate analysis, waist-to-hip ratio, level of free testosterone, percentages of patients with dyslipidemia, impaired glucose tolerance, and diabetes mellitus, blood glucose and insulin levels at 60 min and 120 min, the area under the curve of glucose and insulin after 75-g oral glucose intolerance test, and baPWV were significantly higher in CC non-responders compared with responders. In multivariate logistic regression analysis, both waist-to-hip ratio (odds ratio, 1.77; 95% confidence interval, 2.2-14.1; P=0.04) and baPWV (odds ratio, 1.71; 95% confidence interval, 1.1-2.8; P=0.03) were independent predictors of ovulation induction by CC in PCOS patients. The predictive values of waist-to-hip ratio and baPWV for the CC resistance in PCOS patients were determined by the receiver operating characteristic curves. The area under the curves for waist-to-hip ratio and baPWV were 0.76 and 0.77, respectively. Setting the threshold at 0.83 for waist-to-hip ratio offered the best compromise between specificity (0.65) and sensitivity (0.84), while the setting the threshold at 1,182 cm/s for baPWV offered the best compromise between specificity (0.80) and sensitivity (0.71). CONCLUSIONS: Both metabolic and cardiovascular parameters were predictive for CC resistance in PCOS patients. The measurement of baPWV may be a useful tool to predict ovulation in PCOS patients who receive CC.