[A Case of Specific Pneumonia Diagnosed as Peritumoral Infiltration during Nivolumab Treatment for Esophageal Cancer].

The patient is a 54-year-old man who was diagnosed with advanced unresectable esophageal cancer. He underwent three courses of FP therapy and was followed up for observation after chemoradiotherapy and PR. Metastasis appeared in the upper lobe of the left lung and new lung metastasis was found in the lower lobe of the right lung despite FP therapy 2 years and 1 month after the start of treatment. Nedaplatin and docetaxel were administered as a second-line chemotherapy; however, the lung metastasis worsened. Consequently, nivolumab was introduced as a third-line chemotherapy. The metastases in the lower lobe of the right lung disappeared with pneumonia after 6 courses of nivolumab, which was diagnosed as a peritumoral infiltration(PTI). PTI is difficult to distinguish from drug-induced lung injury and should be diagnosed carefully because it is an imaging finding that reflects the desired antitumor effect.

Robot-assisted completion gastrectomy preserving interposed jejunum in remnant gastric cancer following a proximal gastrectomy reconstructed by jejunal interposition: A case report.

Minimally invasive completion gastrectomy is technically demanding and comprises a variety of procedures depending on the previous operation. We present herein a case of robot-assisted completion gastrectomy preserving the interposed jejunum in remnant gastric cancer following a proximal gastrectomy reconstructed by jejunal interposition. A 76-year-old, male patient experienced newly developed stage cT1bN0M0 gastric cancer in the distal remnant stomach 5 years after his initial proximal gastrectomy. Endoscopic submucosal dissection was not feasible because of tumor depth and poor cancer cell differentiation. The robotic approach was chosen because of the early cancer stage, prior laparoscopic surgery, and the patient's advanced age. The interposed jejunum was successfully preserved, and a new overlap anastomosis was created between it and the retrocolic Roux-en-Y limb. Robot-assisted completion gastrectomy was safely performed even after a proximal gastrectomy with jejunal interposition.

Feasibility of intraoperative diagnosis of lung adenocarcinoma in situ to avoid excessive resection.

BACKGROUND: Limited lung resection is generally believed to be available for lung adenocarcinoma in situ (AIS). At our institute, intraoperative hematoxylin-eosin staining of frozen-section slides is routinely performed for evaluating tumor invasiveness after partial resection to avoid excessive lung resection. This study aimed to evaluate the feasibility and usefulness of intraoperative frozen-section diagnosis of AIS. METHODS: We retrospectively reviewed 143 patients with 151 AISs diagnosed by intraoperative frozen sections between 2012 and 2019 at our institute. All patients underwent limited resection because of the result of intraoperative frozen-section diagnosis. RESULTS: The total concordance rate between the diagnoses of AIS by intraoperative frozen sections and postoperative paraffin-embedded sections was 82.7% for 151 nodules. Although 21 minimally invasive adenocarcinomas (MIA) and 5 invasive adenocarcinomas were diagnosed as AIS intraoperatively, no patient had tumor recurrence after resection. Among 125 pathologically proven cases of AIS postoperatively, there were 67 (53.6%) radiologically invasive tumors including ground-glass nodules (GGNs) with part-solid component or pure-solid nodules. CONCLUSIONS: This intraoperative evaluation of frozen-section slides will help surgeons avoid excessive lung resection for AIS that was radiologically diagnosed as invasive adenocarcinoma. Intraoperative frozen-section diagnosis will provide to be clinically useful and lead to less invasive surgical treatment for lung nodules.

A resected case of ruptured peritoneal metastasis of hepatocellular carcinoma.

Peritoneal metastases of hepatocellular carcinoma (HCC) are occasionally observed, but rupture of such metastases is rare. We report a resected case with a single ruptured peritoneal HCC metastasis. A 57-year-old man with chronic hepatitis C underwent hepatic resection twice for hepatocellular carcinoma. Recurrence in S3 was found, and the tumor was treated by radiofrequency ablation therapy (RFA). One month after RFA, plane computed tomography (CT) showed a nodule with a diameter of 5 cm near the upper pole of the spleen, and the serum alpha-fetoprotein (AFP) level remained high. The patient was admitted to hospital, with a chief complaint of abdominal pain 4 days after the CT scan, and diagnosed with intra-abdominal hemorrhage caused by a ruptured peritoneal HCC metastatic nodule. We performed semi-urgent surgery, including splenectomy and peritoneal metastasis resection, and the patient was discharged on the 10th postoperative day. Histopathological examination of the nodule confirmed HCC metastasis. The patient is alive with no evidence of recurrence as of 1 year and 6 months after the operation, with AFP levels remaining within the normal range.

Lymphatic permeation and vascular invasion should not be integrated as lymphovascular invasion in lung adenocarcinoma.

OBJECTIVE: Lymphatic permeation (LY) and vascular invasion (VI) are well-known as postoperative prognostic factors in non-small cell lung cancer (NSCLC). Some reports use the term "lymphovascular invasion (LVI)" in reference to the integration of LY and VI. The purpose in this study is to elucidate whether NSCLC with LY or VI can be labeled as LVI-positive NSCLC or it should be treated as an LY- or VI-positive tumor, respectively. METHODS: We reviewed 601 completely resected lung adenocarcinomas and squamous cell carcinomas, and examined the respective prognostic and biological significance of LY and VI. RESULTS: Among 454 adenocarcinomas, multivariate survival analyses showed that LY and VI were unfavorable prognostic factors in stages II and III and stages I and II, respectively. Conversely, this relationship was not found among 147 squamous cell carcinomas. Patients with adenocarcinomas with LY and VI had a significantly worse prognosis than those with adenocarcinomas with LY or VI in stage II, but not in stage I. Among 149 recurrent adenocarcinomas, only VI had a strong effect on early recurrence and shorter post-recurrence survival. LY and VI were predictors for multiple organ recurrence of adenocarcinoma. The recurrence of adenocarcinoma with LY was high in the ipsilateral mediastinal lymph nodes, whereas VI was significantly correlated with distant metastasis to organs, such as the brain, liver, and adrenal gland. CONCLUSIONS: LY and VI have differing effects postoperative prognosis and recurrence-relevant events, suggesting that these pathological findings should not be integrated as LVI.

[Clinical Significance of Total Pancreatectomy for Multiple Pancreatic Metastases from Renal Cancer].

With the progress of replacement therapy for pancreatic endocrine and exocrine functions, the indications for a total pancreatectomy are expanding, and reports of multiple pancreatic metastases of renal cancer are on the rise. In the present, we investigated the utility of a total pancreatectomy for multiple pancreatic metastases of renal cancer. The subjects were 8 patients who underwent a total pancreatectomy for multiple pancreatic metastases of renal cancer between 2012 and 2021. The median, postoperative observation period was 31(3-92)months. Six of 8 patients survived without cancer, and one survived with chemotherapy(pazopanib plus axitinib)plus radiation therapy(maintaining stable disease). The one, remaining patient died of hypoglycemia. Of the 8 patients, 4 survived for 2 years or more, and 2 survived for more than 5 years. Postoperative, support for endocrine and exocrine functions is indispensable, but a total pancreatectomy for multiple pancreatic metastases of renal cancer promises to be a viable treatment option owing to its favorable long-term prognosis.

How long is cessation of preoperative smoking required to improve postoperative survival of patients with pathological stage I non-small cell lung cancer?

BACKGROUND: Smoking can cause non-small cell lung cancer (NSCLC). However, the effects of preoperative smoking on tumor progression are not well-known. In addition, the duration of smoking cessation that can provide NSCLC patients with smoking history similar postoperative prognosis as that of nonsmokers remains unknown. This study aimed to investigate the period of smoking cessation that may "compensate" for past smoking history regarding postoperative survival in cases of resected pathological stage I NSCLC by examining the relationship between clinicopathological factors and preoperative smoking. METHODS: We retrospectively examined clinicopathological factors including preoperative smoking status and postoperative survival in 453 patients with pathologically proven stage I NSCLC at our Institute. Smoking status was evaluated using the following four parameters: cigarettes per day, number of years of smoking, pack-years, and number of years since smoking cessation. RESULTS: Pathological factors that reflect tumor invasiveness including vascular invasion (VI) and pleural invasion (PL) were associated with the degree of preoperative smoking in adenocarcinomas, particularly invasive diameters of 2-3 cm. Such a relationship was not identified for non-adenocarcinomas. Heavy smoking status was significantly related to PL in lepidic or papillary predominant adenocarcinomas and to VI in acinar or solid predominant adenocarcinomas. Former smokers who quit smoking for ≥10 years had similar postoperative survival as non-smokers for adenocarcinoma ≤3 cm. CONCLUSIONS: Accumulative smoking habit correlated with VI and PL, particularly in 2-3 cm adenocarcinoma, whereas larger adenocarcinomas and non-adenocarcinomas of any size appear to grow and become invasive independent of preoperative smoking status. Longer smoking cessation ≥10 years can result in postoperative survival similar to that of non-smokers with adenocarcinomas ≤3 cm. Current smokers should quit smoking immediately to ensure longer survival even though they suffer from small-sized lung adenocarcinomas in the future.

Clinicopathological Factors Related to Recurrence Patterns of Resected Non-Small Cell Lung Cancer.

Even after complete resection, non-small cell lung cancer (NSCLC) shows preferential recurrence in the mediastinal lymph nodes, lungs, brain, bone, liver, and adrenal gland. However, the relationship between clinicopathological factors and recurrence patterns after resection has not been well-evaluated. Among 688 NSCLC cases with complete resection between 2004 and 2016, 233 cases recurred at our institute. On multivariate analyses, NSCLCs with lymph node metastasis and pulmonary metastasis at surgery commonly recurred in the mediastinal lymph nodes and lungs, respectively. Young age, adenocarcinoma, and vascular invasion were correlated with brain metastasis. Although no variable was associated with bone metastasis, vascular invasion was correlated with postoperative liver and adrenal gland metastasis. Pathologically proven stage II or III NSCLC, adenocarcinoma, and the presence of lymphatic permeation would result in multiple metastases. Vascular invasion, larger invasive size, and advanced stage were independent risk factors of early recurrence. Considering survival, vascular invasion, elderly age, and non-adenocarcinoma were unfavorable prognostic factors after recurrence. Some clinicopathological variables were correlated with organ-specific metastasis and post-recurrence survival. Particularly, vascular invasion was a biomarker of brain, liver, and adrenal gland metastases and a prognostic marker after recurrence among completely resected NSCLC. This information is useful for more frequent patient follow-up and identifying organ-specific distant metastasis.

Unexpected Mutations by CRISPR-Cas9 CTG Repeat Excision in Myotonic Dystrophy and Use of CRISPR Interference as an Alternative Approach.

Myotonic dystrophy type 1 is the most common type of adult-onset muscular dystrophy. This is an autosomal dominant disorder and caused by the expansion of the CTG repeat in the 3' untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. Messenger RNAs containing these expanded repeats form aggregates as nuclear RNA foci. Then, RNA binding proteins, including muscleblind-like 1, are sequestered to the RNA foci, leading to systemic abnormal RNA splicing. In this study, we used CRISPR-Cas9 genome editing to excise this CTG repeat. Dual cleavage at the 5' and 3' regions of the repeat using a conventional Cas9 nuclease and a double nicking with Cas9 nickase successfully excised the CTG repeat. Subsequently, the formation of the RNA foci was markedly reduced in patient-derived fibroblasts. However, contrary to expectations, a considerable amount of off-target digestions and on-target genomic rearrangements were observed using high-throughput genome-wide translocation sequencing. Finally, the suppression of DMPK transcripts using CRISPR interference significantly decreased the intensity of RNA foci. Our results indicate that close attention should be paid to the unintended mutations when double-strand breaks are generated by CRISPR-Cas9 for therapeutic purposes. Alternative approaches independent of double-strand breaks, including CRISPR interference, may be considered.