Preoperative chemotherapy for gastric cancer with obstructive symptoms traditionally requires bypass surgery.

A 67-year-old male presented with severe epigastric pain in May 2023 and was diagnosed with Stage Ⅲ advanced gastric cancer(cStage Ⅲ)in June. Due to indistinct boundaries between lymph node #8a and the pancreas, non-resectional chemotherapy and enterostomy were performed during a diagnostic laparotomy. The diagnosis was updated to sStage Ⅳ with cy1. Beginning in July, the patient was administered SOX and nivolumab. Following 6 courses, CT scans in December revealed clearer boundaries, allowing for conversion surgery in January 2024. This surgery resulted in a pathological complete response(pCR), with no detectable malignant cells. Despite postoperative complications, the patient was discharged on day 34 and is currently receiving outpatient S-1 therapy. This case suggests that enterostomy may facilitate conversion surgery to achieve pCR, thereby providing a new treatment strategy for advanced gastric cancer.

A 61-year-old female presented with dyspnea. CT scan revealed an esophageal tumor with airway stenosis, and she was referred to our hospital. During endoscopy, oxygen desaturation necessitated emergency endotracheal intubation and mechanical ventilation. Following tracheostomy placement, a diagnosis of NEC cStage ⅣB was established. IP chemotherapy was initiated. The patient was successfully weaned from mechanical ventilation on hospital day 14. Follow-up CT demonstrated tumor shrinkage, and she was discharged home on day 52. After that, IP therapy was continued and the tracheotomy tube was removed on an outpatient visit. Although the patient underwent up to fourth-line treatment, she died of the underlying disease 1 year and 2 months after the starts of treatment.

A 67-year-old female was admitted to our hospital for the diagnosis of gastric cancer with pyloric stenosis. Upper gastrointestinal endoscopy and computed tomography(CT)revealed a type 3 tumor in the prepyloric region without evidence of distant metastasis. Laparoscopic-assisted distal gastrectomy with D2 lymph node dissection was performed, and the final diagnosis was T4(SE)N1M0, Stage ⅢA. Adjuvant therapy was not administered because the patient suffers from schizophrenia. Twelve months after the initial resection, a mass was palpated at the trocar site in the right hypochondriac region. A core needle biopsy was performed, revealing adenocarcinoma. Abdominal CT showed the mass to be localized above the fascia of the abdominal wall, with no evidence of distant metastasis or peritoneal dissemination. The mass was surgically resected, and the final pathology report confirmed port-site recurrence of gastric cancer. Nine months after the second resection, there were no signs of recurrence.

A 30s-year-old male complaining of abdominal distension and pain was referred to our hospital. The support by palliative care team was initiated soon after emergency admission. Colonoscopic examination revealed a circumferential ulcerated tumor of rectosigmoid and the tumor was diagnosed as an adenocarcinoma. Contrast-enhanced CT revealed multiple enlarged lymph nodes, diffuse peritoneal nodules and massive ascites, which led us to the diagnosis of advanced rectosigmoid cancer. Because bowel obstruction was not observed, early initiation of systemic therapy was planned. Although abdominal pain was alleviated with analgesics including opioids, discomfort from abdominal distension remained. So, we decided to perform cell-free and concentrated ascites reinfusion therapy(CART). To avoid the delay in the initiation of systemic chemotherapy due the adverse effects of CART, the first systemic chemotherapy was followed by CART. After single CART, the abdominal distention resolved without relapse, and seamless transition to outpatient treatment was made. Although the prognosis of colorectal cancer with diffuse peritoneal dissemination is poor, aggressive adoption of palliative therapy including CART may enable the introduction of systemic chemotherapy and the following alleviation of cancer-related symptoms.

A 56-year-old female received the low anterior resection for RS rectal cancer(T4aN1M0)in June 2010. In February 2011, abdominal CT showed paraaortic lymph node swelling, we resected it, because of lymphatic metastasis from rectal cancer suspected. The resected specimen showed the histological feature similar with ovarian cancer rather than rectal cancer. But uterus and adnexa were not unremarkable on gynecologic examination. She received FOLFOX therapy. In December 2012, abdominal CT revealed a growing mass lesion at posterior to the rectosigmoidal anastomosis. We suspected local recurrence of rectal cancer, chemoradiotherapy(S-1+39 Gy)was administrated, a recurrent lesion was reduced and was followed up. In September 2014, abdominal CT showed the local recurrent lesion enlarged, then we started FOLFIRI+cetuximab. However, tumor progressed with no effect of chemotherapy. In May 2015, we performed the low anterior resection with excision of the local recurrent lesion. Histopathological evaluation of the resected specimen revealed a serous adenocarcinoma, like an origin of ovarium on immunohistochemical examination, highly suspected primary peritoneal cancer. Systemic chemotherapy with 4 courses of carboplatin and docetaxel(DC)therapy was administrated as adjuvant chemotherapy. In December 2016, CA125 level increased, PET-CT showed FDG accumulation in the local recurrent lesion, so we started DC therapy again. The recurrent lesion was disappeared rapidly, followed by 9 courses. She is still alive without recurrence 7 years after DC therapy.

A 77-year-old woman was diagnosed with advanced transverse colon cancer(poorly differentiated adenocarcinoma)cT3N3H0P0, cStage Ⅲc and underwent extended left hemicolectomy in April 2020. The tumor tissue revealed RAS: wild type, BRAF: mutant type, dMMR(MLH1 deficiency)by immunochemical staining, and MSI-H by CDx. She received CAPOX as adjuvant chemotherapy after surgery. At the end of the 3 courses, she developed abdominal aortic lymph nodes recurrence( diameter 32×18 mm)and began to receive pembrolizumab therapy in August 2020. But the tumor re-grew 6 months after the start of this regimen. However the recurrent lesion was localized, radiation therapy(IMRT: 54 Gy/27 Fr) was added in combination with pembrolizumab. Two months later the tumor had shrunk significantly. As of June 2024, the patient has remained recurrence-free, suggesting that the abscopal effect may have been involved by immuno-radiotherapy in this case.

The patient was a 51-year-old woman. A left breast tumor was detected during a health checkup and the patient was referred to our hospital. Upon arrival, a mobile mass measuring 17 mm in diameter was palpable in the CD region of the left breast. The mammogram showed a sawtooth mass. Ultrasonography revealed a hypoechoic mass with abundant blood flow. Needle biopsy revealed invasive ductal carcinoma. Systemic examination revealed masses in both thyroid lobes, and a fine-needle aspiration cytology diagnosis showed it to be benign. A left circular mastectomy and sentinel lymph node biopsy were performed. Pathological examination revealed a resection margin negative, ER negative, PgR negative, HER2 negative invasive ductal carcinoma, with a tumor diameter of 20 mm and 17.2% Ki-67 positivity. Thirty months after surgery, the left thyroid tumor showed a tendency to grow, and fine-needle aspiration cytology was performed again, which revealed a papillary carcinoma. A left thyroid lobectomy and lymph node dissection were performed. Pathological examination revealed that the patient had papillary thyroid cancer, T1aN0M0=Stage Ⅰ(<55y). Currently, 3 years after surgery, there is no evidence of metastasis or recurrence of either cancer.

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.