The patient is a 50s-year-old man. He had a past history of familial adenomatous polyposis(FAP)and was diagnosed with hereditary multiple colorectal cancer(RS, Rb). Therefore, he underwent total colectomy with ileostomy. Six months after surgery, right lateral lymph node metastasis, liver metastasis, and bilateral lung metastasis were pointed out, so 5 courses of CAPOX+bevacizumab(Bmab)were subsequently administered. Since the patient was evaluated as a partial response(PR)on CT and PET-CT after chemotherapy, laparoscopic right lateral lymph node dissection, open partial hepatectomy, and robot-assisted partial lung resection were performed on each metastatic lesion at each 2 months intervals. He has no recurrence for 6 months since last surgery.

A66-year-old man was diagnosed with gastric cancer with cervical lymph node metastasis(cT4aN1pM1, Stage ⅣB). He received chemotherapy with 4 courses of SOX+nivolumab. The primary gastric tumor had shrunk significantly and the cervical lymph nodes could no longer be identified. The therapeutic effect was judged as partial response(PR). We decided to performed conversion surgery. Total gastrectomy and left cervical lymphadenectomy were performed. Histological examination revealed a Grade 2a response in the primary tumor, with no viable tumor cells found in the cervical lymph nodes (ypT4aN1M0, Stage ⅢA). Postoperative adjuvant chemotherapy with nivolumab was initiated. Approximately 16 months after surgery, no apparent recurrence has been observed.

A treatment policy for esophagogastric junction cancer is not well established in our country. In particular, there is an ongoing debate regarding treatment, including surgical procedures and chemotherapy, for locally advanced cases. Case 1: An 88-year-old male patient with a history of gastric cancer underwent upper gastrointestinal endoscopy, which revealed a type 2 advanced carcinoma on the lesser curvature of the residual stomach cardia. A biopsy confirmed the diagnosis of adenocarcinoma. Chest and abdominal CT showed enlarged lymph nodes, but no distant metastases. Based on the diagnosis of locally advanced adenocarcinoma of the esophagogastric junction(T3N+M0, cStage Ⅲ), laparoscopic total gastrectomy of the residual stomach was performed. During surgery, invasion into the diaphragmatic crus was suspected; therefore, combined resection was performed. Postoperative pathological examination revealed T3, Ly1b, V1b, N1, M0, and pStage Ⅱb. After surgery, the patient developed a mild pancreatic fistula, which improved with conservative treatment and he was discharged. Due to the patient's advanced age, adjuvant chemotherapy was not administered postoperatively, and there was no recurrence or metastasis 2 years after surgery. Case 2: A 68-year-old male patient presented with abdominal pain and a fever. Blood tests revealed elevated inflammatory marker levels. Abdominal CT revealed an abscess cavity in liver segments S6/7 and enlarged nearby lymph nodes, along with thickening of the wall extending from the lower esophagus to the gastric cardia. Gastrointestinal endoscopy revealed an ulcer with irregular surrounding elevation on the lesser curvature of the esophagogastric junction. A biopsy confirmed the diagnosis of adenocarcinoma. The liver abscess was drained, and cytology of the contents revealed no malignancy. Radical resection was performed using a transhiatal and right thoracic approach for a locally advanced adenocarcinoma of the esophagogastric junction(T4aN+M0, cStage Ⅲ). The postoperative pathological examination revealed T3, Ly1b, V1b, N2, M0, and pStage ⅢA. The patient's postoperative course was uneventful, and he was discharged. He is currently being administered adjuvant chemotherapy, and there has been no recurrence or metastasis 18 months after surgery.

An 81-year-old woman visited our hospital for severe anemia and was diagnosed with ascending colon cancer with a tumor thrombus in the superior mesenteric vein(SMV). After 8 courses of mFOLFOX6+bevacizumab therapy followed by 7 courses of fluorouracil and leucovorin+bevacizumab therapy, the primary lesion and tumor thrombus were found to be shrinkage. Then we performed robot-assisted right hemicolectomy and resection of SMV involving the tumor thrombus. The patient was discharged on postoperative day 19. Histological findings revealed residual tumor thrombus in the SMV. The patient is currently under observation at 4 months postoperatively without adjuvant chemotherapy.

An 85-year-old female underwent an upper gastrointestinal endoscopy revealed a type 4 tumor extending from the lesser curvature to the antecubital area, and stenosis of the pyloric lesion. Histology of the biopsy sample showed adenocarcinoma (tub2). CT revealed thickening of the stomach wall and numerous enlarged lymph nodes. Laparoscopic total gastrectomy, D2 dissection, Roux-en-Y reconstruction, and enterostomy were performed. After resection, the jejunum was removed from the abdominal cavity and transected 25 cm from the ligament of Treitz. An R anastomosis was created 10 cm from the anal side to the esophagojejunostomy anastomosis, and an enterocutaneous fistula tube was inserted from the blind end 10 cm from the R anastomosis. Laparoscopic esophagojejunostomy was performed using the overlap method. The enterocutaneous fistula was guided laparoscopically from the left costal region. Postoperatively, the patient was maintained on a diet with nutritional management via an enterostomy. No postoperative or enterostomy-related complications were observed. The postoperative course was uneventful and the patient was discharged from the hospital on the postoperative day 22. There was no deterioration in the nutritional status after discharge. Pathology results showed Stage Ⅳ, pT4aN3bM1. The patient did not receive chemotherapy per her request.

A 71-year-old man was diagnosed with advanced gastric cancer of the upper body of the stomach by esophagogastroduodenoscopy. CT scan showed enlarged left supraclavicular fossa and mediastinal lymph nodes. U, type 4, cT4aN2M1 (LYM), Stage ⅣB was diagnosed and chemotherapy(SOX)was administered. After chemotherapy, the distant lymph nodes shrank and PET-CT scan showed no distant lymph node involvement. ycT1bN0M0, Stage Ⅰ was diagnosed. Laparoscopic total gastrectomy D2 dissection was performed as conversion surgery. Pathological findings were ypT0N0(0/34)M0 and histological response Grade 3. As postoperative adjuvant chemotherapy, S-1 was administered for about 1 year. The left supraclavicular fossa and mediastinal lymph nodes remained reduced and patients were followed up while imaging studies were performed. Four years post-operatively, the patient was diagnosed with recurrence due to elevated tumor markers and rapid enlargement of supraclavicular fossa and mediastinal lymph nodes. We experienced a case in which the patient had a pathological complete response but recurred 4 years after surgery.

A 69-year-old man was referred to our hospital due to a rapid increase of HbA1c. Computed tomography(CT)showed a 40 mm hypo vascular tumor in the body of the pancreas, which was diagnosed as pancreatic squamous cell carcinoma by endoscopic ultrasound-fine needle aspiration. Also, esophagogastroduodenoscopy(EGD)revealed a type 2 tumor in the body of the stomach, which was diagnosed as well differentiated gastric cancer. Gemcitabine and S-1(GS)was performed for pancreatic cancer as neoadjuvant chemotherapy. Both pancreatic and gastric cancer were reduced in size once. However, after 9 courses, CT and EGD showed increase in size of gastric cancer. Trastuzumab plus capecitabine and oxaliplatin, followed trastuzumab plus S-1 and oxaliplatin(SOX), was employed for gastric cancer. While the gastric cancer was remarkedly reduced, the pancreatic cancer was increased in size. GS was administered again, but both pancreatic and gastric cancer were increased in size. Finally, trastuzumab plus SOX was employed for gastric cancer, and 60 Gy of radiotherapy followed nab-paclitaxel and gemcitabine(GA)was employed for pancreatic cancer. After that, distal pancreatectomy, total gastrectomy, splenectomy, and cholecystectomy were performed for pancreatic and gastric cancer. Histopathological findings revealed pancreatic squamous cell carcinoma, ypT3N0M0, and pathological response is Grade 2, also gastric cancer, ypT3 N0M0, and pathological response is Grade 2a. Adjuvant chemotherapy with S-1 was administered and is still ongoing.

A 49-year-old female patient was referred to our obstetrics and gynecology clinic in August 2017 with a chief complaint of vaginal defecation. Internal examination revealed a fistula on the posterior wall of the vagina, and rectal examination revealed an irregular mass on the anterior wall of the anal canal. Colonoscopy revealed an irregular mass spanning the lower rectum and anterior wall of the anal canal. Biopsy revealed squamous cell carcinoma. A diagnosis was made of vaginal invasion by an anal canal squamous cell carcinoma, T4N0M0, Stage ⅢB with no evidence of lymph node or distant metastasis. After laparoscopic colostomy of the sigmoid colon, chemoradiotherapy(CRT)with 5-FU/mitomycin C plus 59.4 Gy/33 Fr was performed. The patient had no local recurrence or distant metastasis 5 years after CRT, and the rectovaginal fistula closed spontaneously. Colostomy closure was not performed due to extensive rectal stenosis.

The development of new in vitro cell culture systems, the microphysiological systems(MPSs), is progressing rapidly around the world. MPS is a biomimetic cell culture system that recapitulate tissue biology(patho)physiologically using clinically derived specimens, organoids, or differentiated cells from stem cells on a culture device with circulation and detection devices. New disease model systems are being constructed using MPS and are used as proof-of-concept and drug evaluation systems, and are attracting attention as an approach to addressing unmet medical needs. In conventional anti-cancer drug research, in vitro culture systems are mainly used to evaluate the growth inhibitory potential of cancer cell line monocultures. On the other hand, MPS has made it possible to monitor cancer pathology, malignant traits, and pharmacological activity, such as reproduction of the cancer niche, interactions between cancer cells and various stroma in the tumor microenvironment, cancer cell movement, and immune cell accumulation in cancer tissue. MPS is also used to evaluate safety and adverse effects and pharmacokinetics, which are essential for anticancer drug development. Various MPSs have been developed and reported for these purposes also in Japan, MPS technology is being developed, including for use in the regulatory process for non-clinical studies. Through these efforts, it is expected to lead to innovation in drug discovery in the field of oncology.

A 62-year-old woman was diagnosed with bladder urothelial carcinoma in situ. Transurethral resection of bladder tumor (TURBT) was performed, followed by intravesical therapy with bacillus Calmette Guérin. Two months later, a papillary lesion was observed around the scar. The lesion was biopsied, and histological examination revealed papillary and tubular formation with inflammatory cell infiltration. Therefore, the lesion was diagnosed as nephrogenic adenoma. We opted for watchful waiting because the lesion had disappeared and nephrogenic adenoma is a benign tumor. At 6 months after the biopsy of the nephrogenic adenoma, the patient showed no signs of recurrence.

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.