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Background; Emphysema is a common phenotype of chronic obstructive pulmonary disease (COPD). Although resection of emphysematous tissue can improve lung mechanics, it is invasive and fraught with adverse effects. Meanwhile, radiofrequency (RF) treatment is an extracorporeal method that leads to tissue destruction and remodeling, resulting in “volume reduction” and overall improvement in lung compliance of emphysematous lungs. Whether these changes lead to improved exercise tolerance is unknown. Here, we investigated the effectiveness of RF treatment to improve the exercise capacity of mice with emphysema.Methods;Fifty-two mice (7 weeks of age) were used in this experiment. A bilateral emphysema model was created by intratracheally instilling porcine pancreatic elastase (PPE) (1.5U/100g body weight). RF treatment (0.5W/ g body weight) was performed extracorporeally 14 days later and mice were sacrificed after another 21 days. The exercise capacity of mice was measured using a treadmill. Treadmill runs were performed just before PPE instillation (baseline), before RF treatment and before sacrifice. Following sacrifice, lung compliance and mean linear intercept (Lm) were measured and fibrosis was assessed using a modified Ashcroft score.Results; There were 3 experimental groups: controls (instilled with saline, n=12), emphysema (instilled with porcine pancreatic elastase, PPE, n=11) and emphysema + treatment (instilled with PPE and given RF, n=9). At endpoint, the maximum velocity of the emphysema + treatment group was significantly higher than that of the emphysema group, indicating improved exercise tolerance (86.29% of baseline vs 61.69% of baseline, p=0.011). Histological analysis revealed a significant reduction in emphysema as denoted by Lm between the two groups (median 29.60 µm vs 35.68 µm, p=0.033). The emphysema + treatment group also demonstrated a higher prevalence of lung fibrosis (≧Grade 3) compared with the emphysema group (11.7% vs 5.4%, p

Mai Tsutsui,1 Firoozeh Gerayeli,1 Don D Sin1,2 1Centre for Heart Lung Innovation, St. Paul’s Hospital, University of British Columbia, Vancouver, BC, Canada; 2Division of Respiratory Medicine, University of British Columbia, Vancouver, BC, CanadaCorrespondence: Don D SinCentre for Heart Lung Innovation, St. Paul’s Hospital, University of British Columbia, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, CanadaTel +1 604 806 8818Fax +1 604 806 9274Email don.sin@hli.ubc.caAbstract: Pulmonary rehabilitation (PR) is effective in reducing symptoms and improving health status, and exercise tolerance of patients with chronic obstructive pulmonary disease (COPD). The coronavirus disease 19 (COVID-19) pandemic has greatly impacted PR programs and their delivery to patients. Owing to fears of viral transmission and resultant outbreaks of COVID-19, institution-based PR programs have been forced to significantly reduce enrolment or in some cases completely shut down during the pandemic. As a majority of COPD patients are elderly and have multiple co-morbidities including cardiovascular disease and diabetes, they are notably susceptible to severe complications of COVID-19. As such, patients have been advised to stay at home and avoid social contact to the maximum extent possible. This has increased patients’ vulnerability to physical deconditioning, depression, and social isolation. To address this major gap in care, some traditional hospital or clinic-centered PR programs have converted some or all of their learning contents to home-based telerehabilitation during the pandemic. There are, however, some significant barriers to this approach that have impeded its implementation in the community. These include variable access and use of technology (by patients), a lack of standardization of methods and tools for evaluation of the program, and inadequate training and resources for health professionals in optimally delivering telerehabilitation to patients. There is a pressing need for high-quality studies on these modalities of PR to enable the successful implementation of PR at home and via teleconferencing technologies. Here, we highlight the importance of telerehabilitation of patients with COPD in the post-COVID world and discuss various strategies for clinical implementation.Keywords: pulmonary rehabilitation, COVID-19, telerehabilitation, COPD

Fluoropyrimidine has been commonly used not only in unresectable cases of metastatic colorectal cancer, but also in adjuvant therapy. Dihydropyrimidine dehydrogenase (DPD) is an enzyme encoded by the DPYD gene, which is responsible for the rate-limiting step in pyrimidine catabolism and breaks down more than 80% of standard doses of 5-fluorouracil (5-FU) and capecitabine, an oral prodrug of 5-FU. The lack of enzymatic activity increases the half-life of the drug, resulting in excess drug accumulation and toxicity which may lead to life-threatening side effects. There have been several published case reports about DPD deficiency in patients with colorectal cancer in Western countries. However, case reports of DPD deficiency in Japanese patients with colorectal cancer are rare because measuring DPD activity is not covered by public medical insurance in Japan, and it is not examined in our daily clinical practice currently. Therefore, we think that it is important to accumulate such case reports for further understanding. This report describes the case of a Japanese patient with colon cancer who experienced severe side effects while taking capecitabine, due to DPD deficiency. A 68-year-old man with ascending colon cancer underwent curative laparoscopic right hemicolectomy. Because final pathologic staging was Stage IIIa, standard adjuvant chemotherapy with capecitabine (3600 mg/body/day, days 1–14, every 3 weeks) was started on postoperative day 50. After 2 weeks, he started to experience Grade 3 diarrhea and was admitted to the hospital on postoperative day 66. On day 70, the patient had Grade 4 febrile neutropenia. Antibiotics and granulocyte-colony-stimulating factor were administered until his blood tests recovered to the normal degree. After 1 week of diarrhea, antidiarrheal agents were administered, and the patient gradually recovered. During the occurrence of diarrhea, specimen cultures were negative for infection. He was discharged on day 21 of the hospital stay. DPD deficiency was suspected, and 2 weeks later the DPD activity of the peripheral blood mononucleocytes was examined. The result was 10.3 U/mg protein which was remarkedly low (reference range 22.6–183.6 U/mg protein), and DPD deficiency was diagnosed. We always must consider the possibility of DPD deficiency in patients who experience severe side effects while taking capecitabine.

Fluoropyrimidine has been commonly used not only in unresectable cases of metastatic colorectal cancer, but also in adjuvant therapy. Dihydropyrimidine dehydrogenase (DPD) is an enzyme encoded by the DPYD gene, which is responsible for the rate-limiting step in pyrimidine catabolism and breaks down more than 80% of standard doses of 5-fluorouracil (5-FU) and capecitabine, an oral prodrug of 5-FU. The lack of enzymatic activity increases the half-life of the drug, resulting in excess drug accumulation and toxicity which may lead to life-threatening side effects. There have been several published case reports about DPD deficiency in patients with colorectal cancer in Western countries. However, case reports of DPD deficiency in Japanese patients with colorectal cancer are rare because measuring DPD activity is not covered by public medical insurance in Japan, and it is not examined in our daily clinical practice currently. Therefore, we think that it is important to accumulate such case reports for further understanding. This report describes the case of a Japanese patient with colon cancer who experienced severe side effects while taking capecitabine, due to DPD deficiency. A 68-year-old man with ascending colon cancer underwent curative laparoscopic right hemicolectomy. Because final pathologic staging was Stage IIIa, standard adjuvant chemotherapy with capecitabine (3600 mg/body/day, days 1–14, every 3 weeks) was started on postoperative day 50. After 2 weeks, he started to experience Grade 3 diarrhea and was admitted to the hospital on postoperative day 66. On day 70, the patient had Grade 4 febrile neutropenia. Antibiotics and granulocyte-colony-stimulating factor were administered until his blood tests recovered to the normal degree. After 1 week of diarrhea, antidiarrheal agents were administered, and the patient gradually recovered. During the occurrence of diarrhea, specimen cultures were negative for infection. He was discharged on day 21 of the hospital stay. DPD deficiency was suspected, and 2 weeks later the DPD activity of the peripheral blood mononucleocytes was examined. The result was 10.3 U/mg protein which was remarkedly low (reference range 22.6–183.6 U/mg protein), and DPD deficiency was diagnosed. We always must consider the possibility of DPD deficiency in patients who experience severe side effects while taking capecitabine.

Introduction The optimal surgical management strategy for isolated para-aortic lymph node (PALN) metastases from colorectal cancer (CRC) remains unclear. However, the complication rates for open approaches remain high. In this study, the outcomes of laparoscopic para-aortic lymphadenectomy in patients with clinically suspected PALN metastasis were evaluated. Methods Between April 2013 and April 2018, we performed laparoscopic primary resection and para-aortic lymphadenectomy in 11 patients with advanced colorectal cancer and clinically suspected PALN metastasis. This study was a single-center, retrospective, case series analysis, and the surgical outcomes were reviewed. Results There were no cases of perioperative mortality, and conversion to open surgery was necessary in only one patient (9%) because of invasion into a rib. One patient (9%) required a blood transfusion. Postoperative complications occurred in three patients, and the morbidity rate was 27% (3/11). Pathologically, PALN metastasis was confirmed in five patients (45%), all of whom received postoperative chemotherapy. The median survival time for all patients was 25 months, and one patient died of recurrence at 25 months after the initial surgery. Two other patients were alive with recurrence after 47 and 36 months, and two patients were alive without recurrence after 17 and 2 months. Conclusion Laparoscopic para-aortic lymphadenectomy for advanced colorectal cancer with clinically suspected PALN is technically feasible and may be beneficial in selected patients. It is necessary to investigate the feasibility of this procedure in a future case series, and information regarding true oncologic outcome will require long-term follow-up.

The patient was a 54-year-old female who presented with the chief complaint of melena. Lower gastrointestinal endoscopy detected a type 1 tumor extending from the anal canal to the rectum. CT did not detect any distant metastasis. Proximal D3 lymphadenectomy with laparoscopic abdominoperineal resection was performed for stage IA rectal cancer. In the histopathological examination, the tumor was identified as stage IIIa adenosquamous carcinoma. Although the patient underwent postoperative adjuvant chemotherapy with S-1, a recurrent left lateral lymph node tumor was detected on CT and PET 12 months later. The patient underwent the treatment with mFOLFOX + bevacizumab for 6 months. However, the tumor continued to progress, and therefore, extended lateral lymphadenectomy was performed 21 months after the first surgery. The patient did not undergo postoperative adjuvant therapy and is alive without recurrence 90 months after the first surgery and 70 months after the reoperation. Adenosquamous carcinoma of the rectum is a rare histological type of colorectal cancer for which there is no effective treatment besides surgical resection, and its prognosis is known to be worse than that of adenocarcinoma. Since there has been no report of long-term survival after extended lateral lymphadenectomy for recurrent lateral lymph node tumors following surgery for adenosquamous carcinoma of the rectum, herein, we report the case with a review of the literature.

It is a great honor to comment on the article entitled “Prognostic impact of hypochloremia in patients with stage I to III colorectal cancer after radical resection” by Qingguo Li and his colleagues in the Diseases of Colon and Rectum (1).

A 63-year-old man who underwent insertion of a lumboperitoneal shunt developed gait disturbance. He had undergone surgery for gastric cancer 7 years and for ileus 5 years previously. Head computed tomography (CT) revealed enlargement of the ventricles. Abdominal CT revealed a cyst in the abdominal region and the distal segment of the peritoneal shunt tube located within the cyst. Laparotomy revealed the cyst located between the small intestine, colon, and peritoneum. The anterior wall of the cyst was excised. The distal segment of the peritoneal shunt tube was replaced in the rectovesical pouch. Histological examination showed that the cyst wall consisted of inner fibrous tissue and outer fat tissue without epithelial lining, and invasion of lymphocytes. The diagnosis was pseudocyst. Only 29 cases of abdominal cerebrospinal fluid (CSF) pseudocysts have been reported in adults. Although the mechanism underlying the formation of abdominal pseudocyst remains to be clarified, several predisposing factors for cyst formation have been reported including changes in absorption of CSF due to inflammation or infection, peritoneal adhesions due to previous abdominal surgery, and increase in the protein content of the CSF. In our case, the medical history and histological features of the cyst wall indicated that formation of the abdominal pseudocyst was associated with previous surgery or inflammatory reaction.

A 29-year-old man with a type 4 tumor, in the lower third of the stomach, and carcinomatous ascites was diagnosed by aspiration cytology of the ascitic fluid. Curative resection was considered impossible, and S1 (120 mg/d) and cisplatin (90 mg/d) were given for 21 days in 1 course. The cancer lesion showed marked remission (partial response), and the ascites completely disappeared after the fourth course. Twenty-five days after completion of the S1 treatment, laparoscopy-assisted total gastrectomy was performed. Histopathological examination showed no remnant cancer cells in the resected specimen and no lymph node metastases. The tumor was replaced with fibrosis having a granulomatous change. The patient's postoperative course was uneventful. The patient was continued with S1 monotherapy after surgery, and no signs of recurrence or metastases have been seen on any examination 12 months after the surgery.

Background: Esophageal cancer has a poor prognosis due to early metastasis and direct invasion. Multimodal therapies including surgery, chemotherapy, and radiotherapy are necessary for advanced esophageal cancer. Although chemo or radiosensitivity is closely related to prognosis, it is currently impossible to predict the therapeutic effect of therapies. Patients with resistance to chemo or radiotherapy cannot derive benefit from the therapy but suffer side effects. Therefore, detecting resistant genes and mechanisms is essential for tailoring treatment to improve the prognosis. Drug and radiation resistance may be mediated by genetic changes in the tumor; therefore, the identification of gene mutations may lead to better therapeutic outcomes. We used a novel method involving transposons to screen and identify drug-resistant genes and radio-resistant genes. Methods: A modified piggyBac transposon was designed as an insertion mutagen, and a cytomegalovirus (CMV) promoter sequence was added to induce strong transcription. After establishing a transposon-tagged cell library, we treated cell lines derived from esophageal squamous cell carcinomas (ESCC) [Tohoku Esophagus (TE)] with cisplatin (CDDP) or radiation. We performed splinkerette PCR and TOPO cloning on the resistant colonies. Bacterial colonies were sequenced, and Next-Generation sequencing was used to identify the over-expressed/down-regulated sequences as candidate genes for CDDP resistance or radiation resistance, Results: We established 4 cell lines of transposon-tagged cells, TE 4, 5, 9, and 15. We treated the 2 relatively viable cell lines, TE4 and TE15, with CDDP or irradiation. We identified 37 candidate genes from 8 resistant colonies for CDDP. Eight genes were over-expressed whilst 29 were down-regulated. Eleven genes were detected as candidate radioresistant genes. Conclusions: The new gene screening technique was useful for detecting candidate of drug-resistant genes and radio-resistant genes in esophageal squamous cell carcinoma. We identified 37 candidate genes responsible for CDDP resistance in the two cell lines derived from ESCC cells. Eleven genes were detected as candidate radioresistant genes in the two cell lines derived from ESCC cells.The method is inexpensive, relatively simple, and capable of introducing activating and de-activating mutations in the genome, allowing for drug-resistant genes and radio-resistant genes to be identified. Citation Format: Hirofumi Kawakubo, Kazumasa Fukuda, Yu Kigasawa, Tomoko Takesue, Mai Tsutsui, Tsunehiro Takahashi, Rieko Nakamura, Norihito Wada, Hiroya Takeuchi, Yuko Kitagawa. The novel and comprehensive screening of genes resistant to an anticancer drug and radiation in esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2117.

121 Background: Although the prognosis of early gastric cancer is favorable, the treatment for advanced cases still have difficulty in achieving satisfactory results. Thus, more effective multimodality treatment should be established. Chemoradiotherapy has become a standard treatment for gastric cancer especially as an adjuvant therapy while radiotherapy has been expected as one of the modalities against highly advanced gastric cancer. Methods: Patients with advanced gastric cancer who were treated with chemotherapy of S-1 and cisplatin plus radiation were analyzed retrospectively. Concurrent radiation therapy (5 days/week) at 2 Gy/day was started with chemotherapy and repeated daily on days 1–5, 8–12, 15–19 and 22–26. Irradiation was planned using a computed tomography (CT) simulator for two rectangular portals with a pair of 45-degree wedge filters and was targeted at the primary tumor and surrounding lesions, including lymph nodes. Results: A total 109 patients were treated with chemoradiotherapy between 2002 and 2013 at our institute. The median age was 64 years. Histological type included 45 differentiated and undifferentiated 64 subtypes. The TNM stage before the treatment was diagnosed as IIIA: 11; IIIB: 10; IIIC: 14; IV: 74. Of the 98 evaluable patients, 69 patients had partial responses while no patients had a complete response, resulting in an overall response rate of 70%. Progressive disease (PD) occurred in 2 patients (4%). The most frequent adverse events more than grade 3 were hematologic toxicities, including leukocytopenia (47%), neutropenia (25%), and thrombocytopenia (24%). Non-hematologic toxicities such as general fatigue, renal-related events, and gastrointestinal toxicities were manageable with no treatment-related death. The median survival time was 537 days. Conclusions: While there were disadvantages of radiotherapy including the difficulty of confirming the area of irradiation due to peristaltic movement, risk of perforation and ulceration, recent technological advancement of radiation therapy has enabled pinpoint accuracy in treatment of primary gastric lesions and regional lymph nodes. There has been much anticipation that chemoradiotherapy will be a part of multidisciplinary treatment for advanced cancer.