CD98 heavy chain protein is overexpressed in non-small cell lung cancer and is a potential target for CAR T-cell therapy.

Chimeric antigen receptor (CAR) T cells are effective against hematological cancers, but are less effective against solid tumors such as non-small cell lung cancer (NSCLC). One of the reasons is that only a few cell surface targets specific for NSCLC cells have been identified. Here, we report that CD98 heavy chain (hc) protein is overexpressed on the surface of NSCLC cells and is a potential target for CAR T cells against NSCLC. Screening of over 10,000 mAb clones raised against NSCLC cell lines showed that mAb H2A011 bound to NSCLC cells but not normal lung epithelial cells. H2A011 recognized CD98hc. Although CAR T cells derived from H2A011 could not be established presumably due to the high level of H2A011 reactivity in activated T cells, those derived from the anti-CD98hc mAb R8H283, which had been shown to lack reactivity with CD98hc glycoforms expressed on normal hematopoietic cells and some normal tissues, were successfully developed. R8H283 specifically reacted with NSCLC cells in six of 15 patients. R8H283-derived CAR T cells exerted significant anti-tumor effects in a xenograft NSCLC model in vivo. These results suggest that R8H283 CAR T cells may become a new therapeutic tool for NSCLC, although careful testing for off-tumor reactivity should be performed in the future.

[A Case of Long-Term Survival with Tumor Resection and DOX plus DTIC Therapy for Desmoid Tumor after FAP Surgery].

The patient is a 22-year-old, female. She had a family history of familial adenomatous polyposis(FAP)and a prophylactic total colorectal resection was performed for FAP at age of 18. She presented with fever and abdominal distention and palpated a mass with tenderness in the right lower abdomen. Contrast-enhanced CT scan of the abdomen showed a heterogeneous contrast effect around the tumor margins. With the diagnosis of intra-abdominal desmoid tumor, a partial duodenal resection, small bowel mass resection, and right fallopian tube resection were performed along with the tumor, and an artificial anus was created with the jejunum. Contrast-enhanced CT scan of the abdomen 16 months after resection of desmoid tumor showed a 6.5 cm long desmoid tumor recurrence in the mesentery. She received 5 courses of doxorubicin (DOX)plus dacarbazine(DTIC)therapy followed by continued NSAIDs. Seven years after the operation, she has been able to maintain the shrinkage of the recurrent tumor and is still on medication. Long-term surveillance is necessary because of the possibility of the appearance of other associated lesions in the future.

[A Case of Right Hemicolectomy for Inflammatory Myofibroblastic Tumor Arising in the Right Transverse Colon].

The patient was a 21-year-old male. He presented with right lower abdominal pain and showed tenderness in the same area. An abdominal contrast-enhanced CT examination revealed a 45 mm tumor that continuously stained in the right transverse colon. The patient presented with tenderness and rebound tenderness. Due to a suspected submucosal tumor, laparotomy was performed and an elastic hard tumor of 5 cm in size was found on the serous membrane side of the right transverse colon. As malignancy could not be ruled out, a right hemicolectomy with lymph node dissection was performed. The pathological diagnosis was an inflammatory myofibroblastic tumor(IMT), characterized by the proliferation of spindle- shaped spindle-shaped fibroblast-like cells with inflammatory cell infiltration. As of 9 years post-surgery, there has been no recurrence. However, long-term surveillance is necessary.

[A Case of Surgery for Skin Metastasis of Papillary Thyroid Carcinoma in a Very Elderly Patient to Improve the Quality of Life].

The patient was a 100-year-old woman who underwent right lobe thyroidectomy for papillary thyroid cancer in another hospital around 1990. She developed local recurrence in 2010 and underwent anterior tracheal local recurrence resection in May 2017. Subsequently, metastases were confirmed in the lateral cervical lymph nodes, but the patient only received TSH suppression because of her advanced age. Multiple pulmonary metastases developed in November 2020 and supraclavicular lymph node metastases in July 2021, but the patient was under the care of a visiting physician on best supportive care. The patient was referred to our hospital in January 2022 due to the appearance of a cutaneous mass in the sternal incision area, which gradually increased in size. A well-mobile, well-defined, spherical mass was found in the sternotomy area. The maximum diameter was 19 mm. The cytological findings were consistent with cutaneous metastasis of papillary thyroid carcinoma. As the patient was elderly and had multiple pulmonary metastases, she was temporarily observed. However, by June 2022, the mass had increased from 19 mm to 33 mm with cutaneous discoloration. There was no tendency for multiple pulmonary metastases to grow during this period. The decision was made to operate in order to prevent a decline in quality of life due to self-destruction of the cutaneous metastasis. The tumor was removed under general anesthesia, including the cutaneous discoloration, and reconstructed with a rhomboid skin flap. Post-operatively, there was no local recurrence or significant increase in pulmonary metastases. It is suggested that resection of cutaneous metastasis of malignant tumors may be effective in preserving quality of life even in a 100-year-old elderly patient like the present case and should be considered as an indication.

Risk Factors for Predicting Lymph Node Metastasis in Submucosal Colorectal Cancer.

Objectives: The cornerstone of treating colorectal cancer (CRC) is generally a surgical resection with lymph node (LN) dissection. The tools for predicting lymph node metastasis (LNM) in submucosal (SM) CRC are useful to avoid unnecessary surgical resection. Methods: Retrospectively, we analyzed 526 consecutive patients with SM CRC who underwent surgical resection at the Osaka International Cancer Institute, Osaka University Hospital, and Minoh City Hospital, Japan, between 1984 and 2012. The Osaka International Cancer Institute group and the Osaka University Hospital group were randomly divided into a training set and a test set of 2:1. The prediction model was validated in Minoh City Hospital. Results: We partitioned patients using three risk factors involved in the presence or absence of LNM in SM CRC: lymphatic invasion (Ly), budding grade (BD) and the depth of submucosal invasion (DSI) (cut-off value 2789 µm) that were significantly different in the multivariate analysis. As a result, a predictive model of "LNM <5%" when "Ly negative and DSI <2789 µm" was evaluated. We similarly partitioned by DSI 3000 µm as easy-to-evaluate values in clinical use. We developed the additional model for predicting LNM is 1.05%, that is, LNM <5%, when there are "Ly negative and DSI <3000 µm." Conclusions: As a limitation, only patients who underwent surgical resection were included in this study. This predictive model could help clinicians and CRC patients decide on the additional surgery required after endoscopic resection.

[A Case of Malignant Rectal B Cell Lymphoma That Was Difficult to Differentiate from Rectal Neuroendocrine Tumor].

A 74-year-old woman with a chief complaint of hematochezia was admitted to our hospital. Colonoscopy revealed a 2 cm submucosal tumor with an erosion in the Rb of the rectum. Biopsy showed various inflammatory cell clusters, but no malignant findings. Thoracoabdominal CT and abdominal MRI showed no abnormal findings other than that of rectal wall thickening. Somatostatin receptor scintigraphy performed on suspected rectal NET showed no abnormal accumulation. A total of 3 biopsies were performed, but a definitive diagnosis was not confirmed, and transanal rectal mucosal resection was performed for diagnostic purposes. Immunohistochemistry showed CD20(+)and bcl-2(+), and the lesion was diagnosed as malignant rectal B cell lymphoma. For 1 year postoperatively, the patient showed no recurrence. For this case, biopsy often failed to confirm a definitive diagnosis on rectal submucosal tumors. If the tumor is >1 cm in diameter in a rectal NET, a rectal resection with lymph node dissection is required, and anal function may be impaired. Local tumor excision for diagnosis and treatment may be worthwhile in rectal submucosal tumors if pre-resection diagnosis with biopsy is difficult.

[A Case of Nivolumab Responding to Multiple Lymph Node Metastases during Multidisciplinary Treatment for Esophageal Cancer].

In nivolumab therapy for unresectable advanced esophageal cancer, there are a few cases that show a complete response, and long-term survival can be expected in such cases. Here, we report a case in which nivolumab had a complete response to multiple lymph node metastases during multidisciplinary treatment for esophageal cancer and survived for a relatively long period despite being elderly. Examination of complete response cases provides us with significant insights in considering the unexplained biomarkers of immune checkpoint inhibitors and treatment discontinuation during complete response.

A case of unusually persistent traumatic intrapulmonary hematoma.

Intrapulmonary hematomas are collections of blood within alveolar and interstitial spaces. They occur mainly following thoracic trauma. Typically, intrapulmonary hematomas without bleeding or infection spontaneously disappear after several weeks to 6 months. In the current case, the patient presented with an intrapulmonary nodule 17 months after a chest injury. The size of the nodule had not changed at 4 months after the first visit. Consequently, the patient was diagnosed with an intrapulmonary hematoma by surgical resection. To our knowledge, there are no previous studies that described the cause of the persistent intrapulmonary hematoma. This study reports the case of a patient who underwent surgical resection of a persistent traumatic intrapulmonary hematoma.

Usefulness of Disposable Skin Biopsy Punch for Cervical Occlusion after Cervical Conization.

Cervical occlusion is a rare but serious complication after conization of the uterine cervix. We report on a 69-year-old woman with cervical intraepithelial neoplasia (CIN) 2, who successfully underwent follow-up biopsy of an occluded cervical canal after conization using a disposable skin biopsy punch. The disposable skin biopsy punch was inserted into a slight dimple, which was considered a uterine os, in the direction of the cervical canal, and a sample of tissue was obtained from the occluded portion. This procedure was performed without anesthesia and was completed uneventfully. Histological examination of the excised tissue revealed CIN 3. In addition, the procedure resulted in recanalization of the occluded cervical canal. The occlusion was limited in the external portion of the cervical os and attributed to adhesion of scar tissue during the healing process. Our experience suggests that a disposable skin biopsy punch can be used for follow-up biopsy and recanalization in patients with cervical occlusion after conization as a less invasive approach.

Robot-assisted laparoscopic surgery after placing a self-expanding metallic stent for malignant rectal obstruction: a case report.

BACKGROUND: Approximately 20% of colorectal cancer patients show complete or incomplete bowel obstruction as an early symptom. Preoperative nonsurgical decompression such as placing a self-expanding metallic stent for malignant colorectal obstruction has been shown to be effective for reducing perioperative morbidity and mortality. However, there is a lack of published studies reporting robot-assisted laparoscopic surgery (RALS) after self-expanding metallic stent (SEMS) placement for malignant rectal obstruction (MRO). To our knowledge, this is the first report to do so. CASE PRESENTATION: An 80-year-old man with incomplete paralysis of the lower limbs as well as bladder-rectal disorder due to a spine fracture sustained in a fall accident 26 years ago presented with lower abdominal pain and vomiting. Abdominal multi-detector computed tomography revealed an obstructive rectal tumor with distended bowel on the oral side. Emergency colonoscopy was performed, and an SEMS placed. The patency of SEMS and decompression of the distended bowel was confirmed, and elective RALS was performed 29 days after SEMS placement. To our knowledge, this is the first report of RALS after decompression with SEMS placement for MRO. CONCLUSIONS: RALS after SEMS placement is a safe and feasible therapeutic strategy for MRO.

Increased number of mitochondria in capillaries distributed in stroke-like lesions of two patients with MELAS.

We investigated two autopsy cases of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) using immunohistochemical staining with an anti-mitochondrial antibody against translocase of the outer membrane 20 (TOMM20). In case 1, the patient was a 42-year-old man with a disease duration of 53 days, and in case 2, the patient was a 62-year-old woman with a disease duration of 27 months. In both the cases autopsy revealed moderate atrophy of the cerebrum and cerebellum and multifocal necrotizing lesions, irrespective of the vascular territory. Case 1 showed multiple areas with total necrosis in the cortex, accompanied by increases in number of protoplasmic astrocytes and acidophilic neurons as well as axonal swelling, suggestive of acute or subacute stage stroke-like lesions (SLLs). In case 2, most of the SLLs displayed laminar spongy change in a rarefied cortex, and were considered to be at the chronic stage. In both the cases, capillary proliferation was noted within the SLLs, particularly in the acute phase. Endothelial cells of proliferating capillaries were strongly positive for TOMM20. In the cortex outside the SLLs, microvessels displayed only a fine granular immunoreactivity, as is seen in the controls. Although smooth muscle cells and endothelial cells in pial arteries and arterioles were also strongly positive for TOMM20, the territories of the affected pial arteries and arterioles did not correlate with the distribution of the SLLs. Although MELAS is characterized by recurrent stroke-like episodes (SLEs), the pathogenetic relationship between SLEs and mitochondrial angiopathy remains unknown. An aberrant increase of mitochondria in the capillary endothelial cells of SLLs may disturb endothelial function, thus playing a role in the formation or development of SLLs.

Laparoscopic colectomy after self-expanding metallic stent placement through the ileocecal valve for right-sided malignant colonic obstruction: A case report.

A 78-year-old man with a history of open sigmoidectomy for sigmoid cancer presented with abdominal pain and vomiting. Abdominal multi-detector CT revealed an obstructive ileocecal tumor with distended small bowel on the oral side. We performed emergency drainage using a transnasal decompression tube, and 2 days later, we conducted a colonoscopic examination, which lead to a provisional diagnosis of obstruction with a malignant tumor invading the ileocecal valve. We then placed a self-expanding metallic stent (SEMS) through the ileocecal valve. We confirmed patency of the ileocecal valve and removed the transnasal decompression tube 2 days after SEMS placement. We then performed elective laparoscopic colectomy 8 days after SEMS placement. To the best of our knowledge, there has been only one previous report of laparoscopic colectomy after decompression with SEMS placement through the ileocecal valve for right-sided malignant colonic obstruction.

Unusual False-Positive Mesenteric Lymph Nodes Detected by PET/CT in a Metastatic Survey of Lung Cancer.

Positron emission tomography/computed tomography (PET/CT) is a credible diagnostic modality for detecting primary and metastatic malignancy. PET/CT sometimes shows false positives and negatives, which make clinical diagnosis difficult. A 42-year-old man who had undergone right upper lobectomy for lung cancer 1 year previously had PET/CT for a metastatic survey of the lung. The lung cancer was stage IB (pT2N0M0) bronchioloalveolar carcinoma. PET/CT showed massive (18)F-fluorodeoxyglucose (FDG) uptake in the mesenteric lymph nodes. Because the mesentery is an unusual site of metastasis, the patient was under watchful observation. Another PET/CT after 6 months still showed FDG uptake in the same location, with a slightly increased standard uptake value. A systemic survey was performed, but it did not reveal any malignancies or inflammatory diseases. Eventually, the patient underwent probing laparoscopic surgery. For complete resection of the lymph nodes, laparoscopic ileocecal resection was performed. Histologically, the resected lymph nodes showed reactive lymphadenitis. Glucose transporter 1 immunostainings of the lung cancer and the lymph node were positive and partially positive, respectively. Although PET/CT is a powerful diagnostic modality, clinical interpretation of unusual results is difficult.

[A Case of Angioimmunoblastic T-Cell Lymphoma Merged with Colorectal Cancer That We Were Able to Resect after a Chemotherapy Response].

The patient was 77-year-old man. He visited our hospital with the chief complaint of an abdominal mass in March 2015. We diagnosed the patient with transverse colon cancer and he was suspected of having malignant lymphoma. In March 2016, we attempted to perform right hemicolectomy for the transverse colon cancer, but it was difficult because swollen lymph nodes had formed a large mass with the surrounding tissue, including vessels of the mesentery. We could only complete the surgery after mesenteric lymph node biopsy. On the basis of the results of this biopsy, we diagnosed angioimmunoblastic Tcell lymphoma. At first, we administered THP-COP therapy for malignant lymphoma. However, after 3 courses of this therapy, the patient suddenly developed ileus due to the aforementioned colon cancer. According to enhanced CT performed at the onset of intestinal obstruction, chemotherapy dramatically reduced the size of the intraperitoneal lymph nodes. We therefore concluded that it was able to treat the colon cancer. We performed right hemicolectomy in June 2015. Angioimmunoblastic T-cell lymphoma comprises only 2-3% of all malignant lymphoma cases. We experienced a rare case of complications from angioimmunoblastic T-cell lymphoma and colorectal cancer.

[Successful Treatment of Local Recurrence of Advanced Gastric Cancer Using Curative Gastrectomy via Distal Pancreatectomy after Chemoradiotherapy].

The patient was a 65-year-old woman. She was diagnosed with advanced gastric cancer with liver invasion. After receiving systemic chemotherapy(S-1 plus PTX)for 3 months, she underwent total gastrectomy and partial hepatectomy in May 2008. Because she developed celiac artery circumference lymph node recurrence in November 2010 during postoperative adjuvant chemotherapy consisting of S-1 plus PTX, we changed her chemotherapy regimen to CPT-11 plus CDDP. We observed an increase in the size of the lymph nodes in August 2013 and the response was poor even after switching to DOC. However, the lymph nodes continued to increase in size and we administered radiotherapy of 60.4 Gy/33 Fr that resulted in shrinkage of the nodes. We observed an increase in lymph node size and pancreas invasion in September 2015, including an expansion of the mid pancreatic duct. We performed distal pancreatectomy without identifying the recurrence observed in November 2015 assuming it was an exacerbation. Six months after the surgery, the recurrence was not apparent. We report an example of long-term survival that was achieved for Stage IV gastric cancer. The patient underwent combined modality therapy for 8 years, and local recurrence was controlled via a primary operation.

[Two Cases of Small Intestinal Metastasis of Lung Cancer].

Case 1: A 66-year-old man who had undergone upper right lobe resection for large cell lung carcinoma 2 months earlier presented with abdominal pain and vomiting. Computed tomography showed intussusception of the small intestine. Partial resection of the small intestine was performed. The tumor was pathologically diagnosed as lung cancer metastasis to the small intestine. The patient died 30 days after surgery. Case 2: A 57-year-old man was admitted to hospital due to appetite loss. Computed tomography showed a large intestinal tumor and a small lung tumor, as well as multiple liver metastases and lymph node metastases. We diagnosed perforation of the small intestine tumor, and partial resection of small intestine was performed. Pathological examination and immunohistochemical staining revealed that the tumor was a metastatic adenocarcinoma, and the patient was diagnosed with small intestine metastasis of lung cancer. He died 75 days after surgery. Although small intestine metastasis of lung cancer is rare, the incidence is increasing. The prognosis of lung cancer metastasis of the small intestine is poor, and therefore, we must urgently decide the appropriate treatment.

[Renal Epithelioid Angiomyolipoma with Spontaneous Rupture: A Case Report].

A 66-year-old woman was referred to our hospital for a right renal mass found in the examination for sudden right flank pain. Abdominal computed tomography (CT) revealed a right renal tumor, 8.0 cm in diameter, with massive hemorrhage due to spontaneous tumor rupture. After transcatheter arterial embolization, right radical nephrectomy was successfully performed. The histopathological diagnosis of the renal tumor was epithelioid angiomyolipoma (eAML). Postoperative chest CT showed two lung tumors. Therefore, the lung tumors were resected and diagnosed as a primary lung adenocarcinoma and a sclerosing angioma. Although renal eAML is thought to have malignant potential, there has been no local reccurence nor distant metastases of renal eAML 11 months after the surgery.

[A Case in Which a Patient Was Operated for Intra-Abdominal Desmoid Tumors after Total Colectomy in FAP].

The patient was a 22-year-old woman with FAP, who had undergone laparoscopic total colectomy 3 years previously. She presented to our hospital with a high fever and abdominal pain. Large hard tumors were palpated in the right lower abdomen and pelvis. Blood examination showed an inflammatory response. CT scan revealed 17 cm diameter solid tumors. At surgery, 2 tumors arising from the mesentery of the small intestine were found, neither of which invaded any organs. We performed tumor extirpation with partial resection of the duodenum, ileum, right fallopian tube and rectum. A jejunal stoma was formed, leaving a length of remnant intestine of about 120 cm. The histopathological diagnosis was given as desmoid tumor with infection. The patient was discharged from the hospital on the 9th postoperative day. Desmoid tumor is the second most common cause of death in FAP patients. Although desmoids can also occur in the extremities, most FAP patients develop intra-abdominal tumors. Despite being histologically benign, they are locally infiltrative and can cause death through invasion and destruction of adjacent vital structures and organs. Here, we report a case of desmoid tumors with FAP with reference to the literature.

[Intraluminal Type Gastrointestinal Stromal Tumor Resected by Single-Incision Percutaneous Endoscopic Intragastric Surgery--A Case Report].

We report a patient with gastric gastrointestinal stromal tumor (GIST) who underwent single-incision percutaneous endoscopic intragastric surgery. The patient was a 70-year-old man. Esophagogastroduodenoscopy and abdominal computed tomography revealed the presence of an intraluminal type gastric submucosal tumor, 4 cm in diameter, in the posterior wall of the gastric body. Laparoscopic partial gastrectomy was performed via a single incision made in the epigastric region. The postoperative course was uneventful. The pathological diagnosis was a low-risk GIST. This method is easy and safe to perform; therefore, we consider it to be an important option for the treatment of intraluminal type gastric GIST.