We report a case of a patient with squamous cell carcinoma metastasis confined to a mediastinal lymph node, with no identifiable primary tumor. The patient remains cancer-free 2 years after diagnosis. Although various theories exist regarding the etiology of lymph node carcinoma of unknown primary origin, advances in elucidating its pathogenesis and integrating treatment strategies based on genetic profiling are expected to form the foundation of future clinical practice.

A 70s-year-old woman with a history of Lynch syndrome had ovarian, colon, and right renal pelvic cancers, all of which were detected early and surgically treated with no recurrence. Ten years have passed since the most recent surgical procedure. In September 2020, she developed hematuria and underwent an examination, which revealed left renal pelvic cancer with liver and lung metastases. Chemotherapy(GEM+CBDCA)was initiated in October 2020; however, imaging in April 2021 revealed disease progression. Treatment with an immune checkpoint inhibitor(ICI: pembrolizumab 240 mg/body)was initiated, but after 4 months, the disease progressed and the treatment was discontinued. The patient was then referred to our hospital. Immunological testing revealed a decrease in T cells; therefore, immune-cell therapy(αβT cell therapy)was initiated to improve this condition. After 4 sessions of αβT cell therapy at 2-week intervals, a CT scan in November 2021 revealed shrinkage of the liver metastases and renal pelvis tumor, and the patient was assessed as having a partial response. By February 2022, after a total of 7 sessions of αβT cell therapy, further tumor shrinkage was observed, and the tumor was almost completely resolved on imaging. Although further immunotherapy is rarely administered in patients for whom ICI is ineffective, our findings suggest the potential for significant immune-cell therapy efficacy even after ICI failure.

A 78-year-old male was under follow-up after gallbladder cancer surgery when CT imaging revealed thickening of the rectal wall, along with enlarged mesenteric and left-sided lymph nodes. Colonoscopy identified a semi-circumferential, tumor-like lesion in the lower rectum, and biopsy results confirmed a diagnosis of poorly differentiated adenocarcinoma. Pelvic MRI further revealed a separate tumor in the prostate, leading to a diagnosis of concurrent rectal and prostate cancer. The prostate cancer was managed with endocrine therapy following rectal resection. For the rectal cancer, neoadjuvant chemoradiotherapy(NACRT)was administered prior to surgical treatment. The resected specimen was evaluated for potential lymphatic metastasis of prostate cancer to the rectum. The patient is currently undergoing endocrine therapy and has remained recurrence-free for 2 years.

A 39-year-old man patient was admitted to a nearby clinic with bloody stool. Digital rectal examination revealed a mass lesion in the lower rectum. The patient was referred to our hospital and finally diagnosed with cT4a, N1b, M0, and c-Stage Ⅲb locally advanced rectal cancer. Neoadjuvant chemotherapy(NAC)with CAPOX and bevacizumab was administered to facilitate R0 resection, permitting anal preservation. When the chemotherapeutic regimen was evaluated to have achieved a complete clinical response, the patient underwent laparoscopic low anterior resection. He was shortly discharged without complications. No residual cancer was revealed upon histopathological examination, demonstrating a complete pathological response. Although NAC for rectal cancer has not been recommended by the Japanese guidelines, high response rates have recently been reported. Herein, we present the utility of NAC in the treatment of rectal cancer.

A 60-year-old female presented at our hospital with a mass in her left breast. Needle biopsy of the breast mass confirmed a diagnosis of invasive lobular carcinoma, and the patient underwent left mastectomy and axillary lymph node dissection. The patient received adjuvant chemotherapy and was started on continuous endocrine therapy. Three years post-surgery, she experienced recurrence of multiple bone metastases and received a combination of hormone therapy and selective cyclin-dependent kinases 4/6 inhibitors. Therapeutic efficacy was poor, allowing bone metastases to spread. Four months post-recurrence, blood tests revealed moderate thrombocytopenia. Despite the switch to chemotherapy, the patient's platelet count did not recover. CT revealed splenomegaly, which was not present three months earlier. Bone marrow biopsy revealed severe myelofibrosis with infiltration of small dysplastic cells into dense fibrotic tissue. The patient developed microangiopathic hemolytic anemia, but DIC was not observed during the course of the disease. Ten months after recurrence, a brain metastasis was detected, and the patient died the following month.

The prognosis for unresectable or recurrent biliary tract cancer is generally unfavorable. However, recent reports suggest that combination therapy with immune checkpoint inhibitors may improve outcomes. We report the case of a 79-year-old woman with intrahepatic cholangiocarcinoma who underwent radical resection. Three months post-surgery, she developed a recurrence in an intra-abdominal lymph node. Treatment with 4 courses of gemcitabine+cisplatin+durvalumab(GCD)resulted in a complete response, with no measurable lesions detected on imaging. The patient continued treatment and was subsequently transitioned to durvalumab monotherapy. Although treatment was discontinued due to drug-induced pneumonia, she has remained relapse-free since. To our knowledge, this is the first reported case of a complete response to GCD therapy in biliary tract cancer.

Intracystic papillary neoplasms(ICPN)are very rare. Pancreaticoduodenectomy was performed in patients with a history of cholecystectomy for ICPN. A 76-year-old woman with no complaints was referred to our hospital and was diagnosed with adenomyomatosis preoperatively. Laparoscopic cholecystectomy was performed, and the patient was diagnosed with ICPN based on pathological findings. A follow-up CT performed 6 months after the surgery showed dilated CBD and MPD. Cholangiography revealed a filling defect in the distal bile duct, with a positive cytology test. A pancreaticoduodenectomy was performed, and the patient was discharged on postoperative day 28. The pathological findings revealed the presence of ampullary cancer. Patients with ICPN may require sufficient follow-up and further detailed examinations, if necessary.

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.