Molecularly targeted drugs currently used in breast cancer target the epidermal growth factor receptors, and are less effective when used against breast cancer subtypes with low levels of these receptors. There is therefore an urgent need to identify a new target molecule for such breast cancer subtypes. Vasoactive intestinal peptide (VIP) receptor 2 (VIPR2) is a G-protein-coupled receptor that binds to Gαs, Gαi, and Gαq proteins to regulate their downstream signaling. VIPR2 is known to be highly expressed in the suprachiasmatic nucleus of the brain, but is also expressed in many peripheral organs. VIPR2 expression has also been reported in thyroid cancer, gastric cancer, lung cancer, pancreatic adenocarcinoma, sarcoma, and neuroendocrine tumors, and VIPR2 mRNA expression and VIPR2 gene copy number are particularly elevated in breast cancer. We therefore investigated the involvement of VIPR2 in the proliferation and migration of breast cancer cells. We showed that VIP-VIPR2 is a novel molecular mechanism that controls cell migration by activating phosphatidylinositol-3 kinaseγ (PI3Kγ), promoting the production of phosphatidylinositol 3,4,5-triphosphate, and then regulating the formation and extension of pseudopodia. VIP-VIPR2 also regulated cyclin D1 levels through the cAMP/PKA/extracellular signal-regulated kinase and PI3K/AKT/Akt-glycogen synthase kinase-3β signaling pathways, thereby controlling cell proliferation by regulating the G1/S transition in the cell cycle. Treatment with a selective VIPR2 antagonist peptide KS-133 suppressed VIP-induced cell proliferation and migration. These results suggest that VIPR2 is a novel target molecule associated with breast cancer and that KS-133 is a potential molecular targeted drug for breast cancer.

A49-year-old man noticed discomfort in the right scrotum and consulted a nearby medical institution. Magnetic resonance imaging revealed a 10 mm tumor in the right spermatic cord, showing low signal intensity on T1-weighted images and high signal intensity on T2-weighted and diffusion-weighted images. Since malignancy could not be ruled out, he was referred to our hospital. Physical examination revealed an elastic, mobile tumor in the right spermatic cord. Ultrasonography showed a solid tumor measuring 10 mm near the right testicle. Although differential diagnoses included lipoma and neurilemmoma, the possibility of malignancy prompted tumor resection. The tumor was a nodular lesion with a clear brown border. Histopathological examination confirmed the diagnosis of paraganglioma. Postoperative metaiodobenzylguanidine scintigraphy, computed tomographic imaging, and hormone testing did not reveal any significant findings, confirming the diagnosis of paraganglioma originating from the spermatic cord.

An 81-year-old woman to our hospital complaining of backpain and was diagnosed with a left renal tumor with lung and iliac metastasis. A renal tumor biopsy confirmed clear cell renal cell carcinoma. The patient began combination therapy with pembrolizumab and lenvatinib but experienced fatigue and edema after 1 month. Suspecting cardiac dysfunction induced by Lenvatinib, Lenvatinib was discontinued and treatment with pembrolizumab alone was continued. Three months after treatment initiation, the lung and iliac metastases had resolved, allowing for laparoscopic nephrectomy. Five months post-surgery, no new metastases were detected.

A 72-year-old woman was referred to our hospital complaining of abdominal pain. Contrast enhanced computed tomography revealed a 53 mm solid tumor with low contrast enhancement on the medial aspect of the right adrenal gland. On magnetic resonance imaging, the tumor showed low signal intensity on T1-weighted images, high signal intensity on T2-weighted images, and high signal intensity on diffusion-weighted images. The patient was diagnosed as having a right adrenal tumor and was referred to our hospital for surgery. Laparoscopic right adrenalectomy was performed. During surgery, we could easily peel the tumor from the adrenal gland, but it was strongly adhered at the inferior vena cava. Considering the possibility of a primary tumor of the inferior vena cava, we converted to open surgery and achieved complete tumor resection by combined partial resection of the inferior vena cava. The cut surface of the tumor was white and firm. Histopathological examination with hematoxylin-eosin staining revealed spindle cell proliferation forming bundle-like structures. Immunohistochemical staining was positive for DESMIN and α-SMA, suggesting leiomyosarcoma. Furthermore, the vascular smooth muscle structure of the resected inferior vena cava was completely replaced by leiomyosarcoma. Therefore, our diagnosis was venous leiomyosarcoma originating from the inferior vena cava. The patient has remained recurrence-free at 21 months after surgery.

A 60-year-old male patient with metastasis from sigmoid colon cancer in the pancreatic uncinate process who received chemotherapy was treated with edoxaban (EDO) because of deep vein thrombosis. The pancreatic metastasis appeared to shrink, but the patient had repeated acute pancreatitis. An upper gastrointestinal endoscopy was performed to determine the cause. Bleeding from the major papilla and the minor papilla was detected, and he was diagnosed with hemosuccus pancreaticus. Pancreatic duct stenting was conducted from the minor papilla. The pancreatitis was then improved and the EDO dosage was reduced. The pancreatic duct stent fell off during the course. Hemosuccus pancreaticus has not relapsed after 1 year from the dropout of the stent. EDO was considered responsible for hemosuccus pancreaticus.

A 69-year-old woman was diagnosed with extrahepatic portal vein occlusion and liver cirrhosis. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a ring-enhanced liver tumor. A liver tumor biopsy detected small bile duct proliferation without atypia and a map-like pattern on immunostaining for glutamine synthetase, resulting in a focal nodular hyperplasia diagnosis. CT after 4 years revealed the increased liver tumor. The patient was suspected of intrahepatic cholangiocarcinoma based on MRI findings. A liver tumor biopsy was re-conducted, and the patient was diagnosed with intrahepatic cholangiocarcinoma (small duct type), which was positive for BRAF V600E on immunostaining. We re-investigated the initial liver tumor biopsy tissue and diagnosed the BRAF V600E-positive bile duct adenoma, indicating a malignant transformation of the bile duct adenoma to an intrahepatic cholangiocarcinoma.

We report a case of Stage Ⅳ gastric cancer, in case systemic chemotherapy with nivolumab was effective and curative resection was possible. A man in his 50s visited our hospital with complaints of general fatigue and anemia. Esophagogastroduodenoscopy revealed a type 3 tumor extending from the gastric cardia to angler incisure in the stomach. Abdominal contrast-enhanced computed tomography showed pancreatic invasion from the primary tumor and multiple lymph node metastases. Additionally, a single subcutaneous nodule around the umbilicus was detected. Staging laparoscopy showed P0, CY0. Excisional biopsy of subcutaneous nodule confirmed adenocarcinoma, diagnosing it as skin metastasis. The patient was diagnosed as advanced gastric cancer cT4bN3P0CY0M1(skin), cStage Ⅳ. Five courses of SOX with nivolumab therapy were administered. After 4 months, examinations showed clinical response in the primary lesion and lymph nodes. No new distant metastases were observed, and curative surgery was considered possible. Laparoscopic total gastrectomy with D2 lymphadenectomy, combined resection of distal pancreatectomy and spleen, Roux-en-Y reconstruction, was performed. Pathological examination revealed no residual cancer, indicating a histopathological evaluation of Grade 3. No complications were observed postoperatively and the patient was discharged on the 19th postoperative day. No recurrence was observed 6 months post-surgery. The administration of chemotherapy combined with immune checkpoint inhibitors for oligometastatic Stage Ⅳ gastric cancer was effective and resulted in curative surgery.

We report a case of laparoscopic splenectomy after distal gastrectomy for gastric cancer. A 68-year-old woman underwent laparoscopic distal gastrectomy, D1+lymph node dissection and Billroth Ⅰ reconstruction for gastric cancer 5 years previously, with a final diagnosis of gastric cancer, M, Less-Ant, 0-Ⅱa, pT1b(SM), pN1(2/52), H0, P0, M0, pStage ⅠB(HER2 IHC 3+). Three years and 6 months after gastrectomy, CT scan showed a splenic tumor, and PET scan also showed FDG accumulation. Diagnosed as splenic metastasis post-gastric cancer surgery, she underwent chemotherapy with S-1, cisplatin, and trastuzumab. After 1 year and 6 months of chemotherapy, the splenic tumor showed mild shrinkage but persisted, leading to the decision for splenectomy due to difficulties in continuing chemotherapy. After laparoscopic splenectomy, intraoperative ICG fluorescence imaging confirmed blood flow in the remaining stomach, so the remnant stomach was preserved. No ischemic complications were observed postoperatively. The final pathology revealed an inflammatory pseudotumor of the spleen, and the patient is under observation. This case highlights successful management of a splenic tumor following distal gastrectomy with preservation of the remnant stomach using laparoscopic splenectomy and intraoperative ICG fluorescence imaging.

A 67-year-old man tested positive for fecal occult blood during a medical checkup. Colonoscopy revealed 2 circular narrowing sections and ulcers in the ascending colon. Subsequently, intestinal tuberculosis was suspected, and a biopsy revealed a well-differentiated adenocarcinoma. The patient underwent laparoscopic right colectomy. Pathological findings revealed adenocarcinoma, caseous granuloma, and acid-fast bacteria in the lesions. Therefore, we report a case of ascending colon cancer with intestinal tuberculosis.

An 86-year-old man underwent laparoscopic ileocecal resection with lymph node dissection(pT3N0M0, Stage Ⅱa, Ly1a, V1a). The patient did not receive any adjuvant chemotherapy. Two years later, the patient was diagnosed with a recurrence at the anastomotic site(RAS mutant, HER2 negative, MSI-low). After 4 courses of FOLFOX plus bevacizumab, the patient was admitted for ileus. Preoperative echocardiography revealed an ejection fraction(EF)of 35% and BNP level of 562.2 pg/ mL. Therefore, asymptomatic cardiomyopathy was suspected because of bevacizumab administration. Although the last bevacizumab dose was administered within 2 weeks, we performed a laparoscopic tumor resection with lymph node dissection. Histological examination revealed colon cancer recurrence without lymph node metastasis. The patient was discharged on 19 POD without heart failure and had no recurrence of UFT/UZEL for 11 months. Three months after surgery, EF increased to 61% and BNP level was 14 pg/mL. VEGF inhibitors are associated with a very high risk of cardiomyopathy according to the ESC guidelines(2022). These side effects in conversion therapy for cancer should be carefully considered, even though they are rare.

A 76-year-old female presented with multiple pancreatic cystic lesions, the largest measuring 10 mm in diameter, which were identified during an examination by another department at our hospital. Following referral to our department, she underwent observation because CT scans showed that the lesions tended to enlarge. Subsequent MRCP confirmed a diagnosis of a mixed-type IPMN, prompting surgical intervention. A distal pancreatectomy with D2 lymphadenectomy was performed. Pathological examination revealed IPMC(pT1cpN0M0, pStage ⅠA). Postoperatively, the patient received adjuvant S-1 therapy. In the second year after surgery, CT and MRI revealed hepatic recurrence in segments S8(12 mm)and S5 (5 mm). mFOLFIRINOX was initiated, and after 8 courses, a follow-up CT showed the complete disappearance of both lesions, achieving a complete response(CR). mFOLFIRINOX was continued for 21 courses, without recurrence, over the subsequent year. This case highlights the efficacy of mFOLFIRINOX in treating recurrent hepatic metastases of IPMC and warrants further investigation.

Resection of liver metastases from breast cancer is not widely accepted because the survival benefit of surgery has not been demonstrated. We report the cases of 2 patients who underwent resection of liver metastases from breast cancer. Case 1: This was a female patient in her 50s with synchronous metastasis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Resection was performed since the patient had exhausted all anti-HER2 therapies and had only a single liver metastasis. Immunohistochemical staining results of the resected specimens showed HER2 negativity. The patient had no recurrence 5 months postoperatively and received adjuvant chemotherapy with capecitabine. Case 2: This was a female patient in her 70s with metachronous metastasis of hormone receptor-positive disease. A single liver metastasis occurred 28 years after the primary tumor resection. During the 2-year hormone therapy, no new lesions appeared, and the tumor was stable; therefore, resection was performed. The resected specimen showed a complete pathological response. Furthermore, the patient has been recurrence-free for 1 year without any therapy.

The patient was a 90-year-old man with a PS score of 0 and no underlying disease. He visited our hospital with a fever and was diagnosed with cancer of the ascending colon with abscess formation due to retroperitoneal perforation. First, he underwent ileostomy with double orifices and abscess puncture drainage, followed by right semicolon resection plus ileostomy closure to resect the primary tumor. Three months after the surgery, metastases were found in the left cervical supraclavicular and periaortic lymph nodes. The primary tumor was a poorly differentiated adenocarcinoma, RAS wild, BRAF mutation(+), and MSI-high(+). Therefore, pembrolizumab therapy was initiated, which resulted in a complete response(CR) at the end of 6 courses. After 2 years of pembrolizumab treatment, the patient's CR status was maintained, with only Grade 1 hypothyroidism. We believe that pembrolizumab therapy for MSI-high, unresectable, advanced, recurrent colorectal cancer is useful in older patients with good PS, no major underlying disease, and a medical system that can respond to irAE.

The patient was a 55-year-old woman who had been diagnosed with neurofibromatosis type 1(NF1)since she was young. A 50 mm mass with skin changes was palpated on the outside of the left breast. As a result of a detailed examination of the whole body, invasive ductal carcinoma of Luminal B like was observed, and cT4N1M0, Stage ⅢB left breast cancer was diagnosed. After preoperative chemotherapy, total left mastectomy and axillary lymph node dissection were performed. NF1 is an autosomal overt inherited disease characterized by multiple neurofibromas and pigment spots. It is called von Recklinghausen disease, and it is said that there are many complications of malignant tumors such as breast cancer, mainly nervous system tumors. In breast cancer complicated by NF1, there is a high rate of diagnosis as advanced cancer due to delayed awareness of breast masses due to unique skin lesions and a tendency to refrain from visiting medical institutions or medical examinations due to latent shame about appearance. In this study, we report 1 case of advanced breast cancer complicated by NF1.

Preoperative understanding of the vascular morphology is important for preservation of the distal sigmoid colon and intraluminal processing of the mesentery in laparoscopic proximal sigmoid colon cancer surgery. We report a case of laparoscopic proximal sigmoid colon cancer surgery using sophisticated surgical-assisted CT colonography (CTC). The surgical-assisted CTC was created by combining a CTC created using SYNAPSE VINCENT and a vascular 3D-CT.

An 81-year-old woman had been constipated for a week and experienced nausea and decreased appetite 3 days earlier. She developed chills and general fatigue and was referred to our department. A plain abdominal computed tomography (CT)scan showed wall thickening of the descending colon, the oral side of the intestine was significantly dilated and filled with fecal masses, the anal side of the intestine was collapsed, and ascites and free air were present. Emergency surgery was performed. The area from the cecum to the descending colon was markedly dilated, and a tumor was identified in the descending colon. Fecal fluid leaked from 2 locations on the anterior wall of the cecum, and the walls from the cecum to the ascending colon were poorly colored and necrotic. The necrotic intestine was resected, and an ileostomy and transverse colon mucous fistula were constructed. Radical surgery was performed 26 days after the surgery. Invasion of the transverse colon by descending colon cancer was suspected; therefore, we performed resection from the transverse colon to the sigmoid colon, D3 dissection, and transverse colon-sigmoid colon anastomosis. After adjuvant chemotherapy, the ileostomy and mucous fistula were closed. Nearly 3 years have passed since the radical surgery, and the patient is currently under follow-up with no recurrence.

The case was 50-year-old woman, who was diagnosed with advanced rectosigmoid cancer with multiple liver metastases and solitary lung metastasis. She was started with chemotherapy. Two courses of mFOLFOX6+panitumumab and 8 courses of mFOLFOX6+bevacizumab were administered as a first-line. As a second-line, 1 course of FOLFIRI+ramucirumab was given. Six months later, CT showed that lung metastasis had disappeared and all liver metastases had become smaller, therefor surgery was selected. Laparoscopic partial hepatectomy was performed, and 2 months later, laparoscopic high anterior resection was added. She received 4 courses of capecitabine as adjuvant chemotherapy, but the lung metastasis had enlarged, and thoracoscopic partial lung resection was performed. Five months later, a nodule suspected metastasis was noted on the dissected surface of liver S5 on CT, and a right liver lobectomy was added. She was surviving for 2 years and 10 months after diagnosis of Stage Ⅳ rectal cancer, and had been progression-free for 10 months after last treatment.

A 63-year-old man with anemia was diagnosed as having cStage ⅣB gastric cancer with liver metastases. The patient was treated with SOX and nivolumab. After 3 courses of treatment, nivolumab administration was discontinued because of thyroiditis, and SOX was administered for 2 courses. Treatment resulted in RECIST: PR and surgery was planned. An indocyanine green(ICG)clearance test and 99mTc-GSA liver scintigraphy showed poor liver function, and liver biopsy revealed nivolumab-related hepatitis. After the recovery of liver function, the patient underwent total gastrectomy with splenectomy. However, he developed prolonged ascites postoperatively. Hepatitis/hepatotoxicity has been reported as an immune-related adverse event associated with nivolumab administration; however, its effect on surgery remains unknown.

Pancreaticopleural fistula is a rare complication of alcohol-induced chronic pancreatitis. Here, we report the successful treatment of a patient with recurrent gastric cancer who developed a pancreaticopleural fistula during chemotherapy. The patient underwent endoscopic pancreatic main duct stenting and was discharged after 26 days of hospitalization.

Tracheal adenoid cystic carcinoma(TACC)is relatively rare. Therapy for recurrent TACC has not yet been established. A woman in her late 80s was diagnosed with TACC just below the vocal folds. At the same time, a solitary lung metastasis in the right upper lobe was detected on admission. After tracheal tumor resection using rigid bronchoscopy, radiation therapy 40 Gy was administered. Subsequently, right upper lobectomy was performed. Two years after first admission(FA), radiation therapy 35 Gy for tracheal recurrence was performed. Two years and 6 months after FA, wedge resection was performed for metastases to the left lung. Three years after FA, multiple bilateral lung metastases were detected, and pembrolizumab was administered. Four years after FA, bloody sputum due to local tracheal recurrence was observed, and photodynamic therapy was initiated. Six years after FA, tracheostomy and tracheal cauterization under rigid bronchoscopy were performed for airway stenosis. At that time(7 years after FA), the patient was undergoing second-line chemotherapy. We report a case of recurrent TACC treated with multidisciplinary therapy.