BRAF Mutation Heterogeneity Detected Using Circulating Tumor DNA Sequencing in Synchronous Colon Cancer: A Case Report.

Background/Aim: Synchronous colorectal cancer, which occurs in approximately 4.8-8.4% of all colorectal cancers, has a genetic profile with a higher rate of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation and microsatellite instability-high than solitary colorectal cancer. However, little information is available on heterogeneity among tumor lesions because of difficulty in performing genetic tests in all lesions in clinical practice. Case Report: A 44-year-old man presented with multiple recurrent lung metastases 42 months after the endoscopic resection of early stage synchronous ascending and sigmoid colon cancers. The genetic testing of sigmoid colon cancer tissue samples, their state being more advanced than that of ascending colon cancer, revealed a v-Ki-ras 2 Kirsten rat sarcoma viral oncogene homolog mutation (G13C) and BRAF wild type. However, the tumor was refractory to initial chemotherapy and rapidly progressed to new liver metastases. Therefore, we suspected that there may be biological heterogeneity between the primary sigmoid colon lesion and liver metastases. Next, we performed next-generation sequencing on circulating tumor DNA from the patient's plasma (Foundation One Liquid CDx®), which revealed the V600E mutation of BRAF, suggesting that there was genetic heterogeneity among the synchronized primary lesions, one of which was responsible for the chemo-refractory rapid-growing liver metastases. Conclusion: Genetic profiling with liquid biopsy at the time of recurrence and metastasis may be useful in patients with multiple synchronous cancers because there is less heterogeneity between primary and metastatic sites.

The prevalence and risk factors associated with preoperative deep venous thrombosis in lung cancer surgery.

PURPOSE: Few studies have so far focused on the preoperative presence of venous thromboembolism (VTE) in lung cancer patients undergoing surgery. In this study, we investigated the prevalence and risk factors for preoperative deep venous thrombosis (DVT) in patients scheduled to undergo lung cancer surgery. METHODS: Between June 2013 and December 2018, 948 consecutive patients underwent lung cancer surgery in Kindai University Hospital. Four patients did not undergo screening for DVT; thus, 944 patients were enrolled in this study. Preoperatively, venous ultrasonography of the lower extremities was performed in patients deemed at risk for DVT, and the prevalence and risk factors for preoperative DVT were examined. RESULTS: Ninety-one patients (9.6%) were diagnosed with preoperative DVT, and postoperative symptomatic pulmonary thromboembolism occurred in one patient (0.11%). A multivariable logistic regression analysis demonstrated that female sex, age ≥ 72 years, history of VTE, a Wells score ≥ 2 points, chronic obstructive pulmonary disease (COPD), and lower hemoglobin levels were significantly associated with preoperative DVT. CONCLUSION: Female sex, age ≥ 72 years, history of VTE, Wells score ≥ 2 points, COPD, and lower hemoglobin levels were identified to be independent risk factors for preoperative DVT. Monitoring for these risk factors and management considering them should help improve the outcomes after lung cancer surgery.

The Long-term Efficacy of Endoscopic Submucosal Dissection in the Treatment of Symptomatic Mucosal Prolapse Syndrome.

Mucosal prolapse syndrome (MPS) is a benign inflammatory disease of the rectum that causes symptoms such as blood-stained stools and anemia. However, there is no treatment with a proven long-term efficacy for MPS. A 53-year-old man presented with blood-stained stools and anemia due to MPS and was treated conservatively for 1 year. However, his symptoms did not improve. We performed endoscopic submucosal dissection (ESD) for MPS. He has had no symptoms for six years after ESD, and the recurrence of MPS was not seen on endoscopy. This case shows that ESD can be effective for the long-term treatment of symptomatic MPS.

Prognostic value of plasma fibrinogen and D-dimer levels in patients with surgically resected non-small cell lung cancer.

PURPOSE: A high plasma level of either fibrinogen or D-dimer has been shown to correlate with a poor prognosis in patients with surgically resected non-small-cell lung cancer (NSCLC). The present study aimed to identify whether or not both markers combined had a superior prognostic value to either alone. METHODS: Of the 1344 patients who underwent surgical resection for NSCLC at our institution between January 2007 and December 2016, 1065 had preoperative plasma fibrinogen and D-dimer data available and were included in the analysis. RESULTS: The recurrence-free survival (RFS) and overall survival (OS) rates were similar for patients with high plasma levels of either or both fibrinogen (> 4.0 g/L) or D-dimer (> 1.0 µg/mL); therefore, these three groups were combined for a further analysis into a single group with high plasma levels of either or both proteins. The high-level group had significantly lower 5-year RFS (53% vs. 68%, p < 0.001) and 5-year OS (65% vs. 80%, p < 0.001) rates than patients with normal plasma levels of fibrinogen and D-dimer (control group). CONCLUSIONS: Our results suggest that preoperative tests for both plasma fibrinogen and D-dimer are necessary to identify patients with surgically resected NSCLC likely to have a poor RFS and OS.

Comparison of PD-L1 Expression Status between Pure-Solid Versus Part-Solid Lung Adenocarcinomas.

Although lung adenocarcinomas (LADs) with ground-glass opacity (GGO; part-solid tumors) have been shown to differ from those without GGO (pure-solid tumors) in clinicopathological features and prognoses, whether programmed death ligand-1 (PD-L1) protein expression differs between these two tumor types is unclear. This study included 124 patients with clinical T1a-c LAD who received pulmonary resections during 2007-2009. The E1L3N antibody was used to stain for PD-L1 in primary LAD specimens. The specimens were considered PD-L1+ if ≥1% of tumor cells showed membrane staining, and were classified as having a high PD-L1+ tumor proportion score (TPS) if ≥50% of the tumor cells did so. Among the 124 patients, 45 had part-solid tumors and 79 had pure-solid tumors. These two groups did not significantly differ in terms of clinical factors. However, the rates for PD-L1 positivity (4% vs. 25%, p < 0.01) and high PD-L1+ TPS (2% vs. 16%, p = 0.02) were significantly higher in the pure-solid tumors. The multivariate analyses (logistic regression model) showed that the odds ratios for PD-L1 positivity and high PD-L1+ TPS in pure-solid LADs were 5.9 (95% CI; 1.2-29.7) and 8.0 (95% CI; 1.0-63.8), respectively. In conclusion, LADs with GGO were correlated with a lower incidence of PD-L1 expression than pure-solid tumors.

Laparoscopic surgery for colovesical fistula associated with sigmoid colon diverticulitis: a review of 39 cases.

OBJECTIVES: Colonic diverticular disease is widespread in Western countries and its associated with aging. In Japan, diverticulitis and colovesical fistula are also occurring more frequently. Colonic resection for diverticula-related fistulas is frequently technically demanding because of associated acute or chronic inflammation. We evaluated the safety and efficacy of a standardized laparoscopic procedure. METHODS: Data from 39 consecutive patients who had undergone laparoscopic surgery for colovesical fistula between October 2006 and August 2017 were retrospectively reviewed. RESULTS: The patients' median age was 60 years and comprised 35 men and four women. Sigmoidectomy was performed in 33 patients, Hartmann's procedure in four, and anterior resection in two. The median operative time was 203 minutes and estimated blood loss 15 mL. There were no intraoperative complications or conversion to open surgery. No patients required bladder repair; three had minor postoperative complications, and none had recurrent diverticulitis or fistula at a mean follow-up of 5.1 years. CONCLUSIONS: The magnified vision and minimal invasiveness make a laparoscopic approach the ideal means of managing colovesical fistula. To our knowledge, this is the largest study of colovesical fistula managed by a standardized laparoscopic procedure.

Long-term complete response in a patient with postoperative recurrent ALK-rearranged lung adenocarcinoma treated with crizotinib: A case report.

Anaplastic lymphoma kinase (ALK) gene rearrangements are identified in approximately 5% of patients with non-small cell lung cancer (NSCLC). Despite initial dramatic responses to ALK inhibitors, the majority of patients relapse within 1 year, owing to the development of resistance. Herein we present a case of variant type 2 ALK-rearranged lung adenocarcinoma recurrence with multiple lung metastasis that maintained complete response over 5 years with crizotinib, which is the first approved ALK inhibitor. The efficacy of crizotinib may vary among ALK fusion variants and thus, variant type may represent an important factor in guiding the treatment strategy for ALK-rearranged lung adenocarcinoma.

Sensitivity and Resistance of MET Exon 14 Mutations in Lung Cancer to Eight MET Tyrosine Kinase Inhibitors In Vitro.

BACKGROUND: MNNG HOS transforming gene (MET) exon 14 mutations in lung cancer, including exon 14 skipping and point mutations, have been attracting the attention of thoracic oncologists as new therapeutic targets. Tumors with these mutations almost always acquire resistance, which also occurs in other oncogene-addicted lung cancers. However, the resistance mechanisms and treatment strategies are not fully understood. METHODS: We generated Ba/F3 cells expressing MET exon 14 mutations by retroviral gene transfer. The sensitivities of these cells to eight MET-tyrosine kinase inhibitors (TKIs) were determined using a colorimetric assay. In addition, using N-ethyl-N-nitrosourea mutagenesis, we generated resistant clones, searched for secondary MET mutations, and then examined the sensitivities of these resistant cells to different TKIs. RESULTS: Ba/F3 cells transfected with MET mutations grew in the absence of interleukin-3, indicating their oncogenic activity. These cells were sensitive to all MET-TKIs except tivantinib. We identified a variety of secondary mutations. D1228 and Y1230 were common sites for resistance mutations for type I TKIs, which bind the active form of MET, whereas L1195 and F1200 were common sites for type II TKIs, which bind the inactive form. In general, resistance mutations against type I were sensitive to type II, and vice versa. CONCLUSIONS: MET-TKIs inhibited the growth of cells with MET exon 14 mutations. We also identified mutation sites specific for TKI types as resistance mechanisms and complementary activities between type I and type II inhibitors against those mutations. These finding should provide relevant clinical implication for treating patients with lung cancer harboring MET exon 14 mutations.

Appendiceal mucinous neoplasm with myxoglobulosis occurring 3 years after perforated barium appendicitis: a case report.

BACKGROUND: Myxoglobulosis is considered a subtype of appendiceal mucinous neoplasm (AMN). Factors affecting the occurrence of myxoglobulosis include proximal appendiceal obstruction and mucosal secretion at the residual appendiceal mucosa. In addition, myxoglobulosis has also been reportedly associated with persistent chronic inflammation. We report a case of AMN with myxoglobulosis occurring 3 years after perforated barium appendicitis and the importance of caution during surgery for barium peritonitis and elucidate the pathology of myxoglobulosis. CASE PRESENTATION: A 45-year-old man with an AMN underwent laparoscopic ileocecal resection 3 years after peritonitis caused by perforated barium appendicitis. The patient had a medical history of perforated barium appendicitis after barium swallow imaging, which was treated conservatively 3 years ago. Computed tomography (CT) revealed cystic enlargement of the appendix and remnant barium around the appendix. He was then pathologically diagnosed with a low-grade AMN based on the resected specimen, and the appendix filled with white globules was diagnosed as myxoglobulosis. When barium is not absorbed, it causes chronic inflammation. As barium was observed around the appendix, prolonged inflammation, and appendicitis may have contributed to the myxoglobulosis. The circumference of the appendix firmly adhered to the surrounding tissue with barium; hence, it was difficult to perform appendectomy. Barium that enters the anastomotic site causes stenosis of this part; therefore, excision of the ileocecal region in the intestinal part where barium is not present was selected instead of appendectomy. Colonoscopy performed 1 year after surgery and showed no evidence of anastomotic stricture. CONCLUSION: This case suggested that barium peritonitis caused strong adhesions with the surrounding tissue; thus, careful manipulation was necessary to avoid perforating the appendix. Appendectomy and partial cecal resection were predicted to be difficult because of adhesion by barium. In addition, the ileocecal resection was selected because we had to choose an anastomotic site without barium. The perforated appendicitis caused stenosis of the appendix orifice, and barium surrounding the appendix caused persistent chronic inflammation. This was suggested to contribute to the myxoglobulosis.

Primary pulmonary mucosa-associated lymphoid tissue lymphoma with amyloid light chain-type amyloidosis.

BACKGROUND: A total of 75% of patients with Sjögren's syndrome are complicated with pulmonary lesions, of which 12% are lymphoma and 6% are amyloid nodules; the coexistence of both is considered to be rare. CASE PRESENTATION: A 67-year-old female with Sjögren's syndrome presented with multiple pulmonary nodules on chest computed tomography. Since a definitive diagnosis by transbronchial biopsy was not obtained, wedge resection of the nodules was performed. Pathologic diagnosis revealed eosinophilic deposition that stained positive with Congo red. In addition, lymphoepithelial lesions and lymphocytic infiltration were observed. Lymphocytes with monoclonal proliferation predominantly had κ chain. Based on these findings, the nodules were diagnosed as mucosa-associated lymphoid tissue (MALT) lymphoma with amyloid deposition. CONCLUSIONS: The combination of these diseases is very rare, and this is the sixth resected case to the best of our knowledge.

Life-threatening complications after pulmonary resection for lung cancer in patients on chronic hemodialysis.

PURPOSE: The morbidity and mortality associated with lung cancer surgery in patients on chronic hemodialysis (CHD) is high; however, the relationship between the severity of postoperative complications and clinicopathological features is unclear. METHODS: Among 1214 consecutive patients who underwent pulmonary resection for primary lung cancer in our institute between 2004 and 2015, we identified 21 patients on CHD, who were the subjects of this study. Life-threatening postoperative complications were defined as grade 4 and 5 per the Clavien-Dindo classification. RESULTS: Fourteen (67%) of these 21 patients suffered postoperative complications, which were life threatening in 5. There was a higher frequency of interstitial pneumonia (IP) in the patients with life-threatening postoperative complications than in those with complications that were not life threatening (p = 0.032). The rates of acute exacerbation and 90-day mortality in the patients with IP were 50% and 75%, respectively. The overall survival (OS) rate of the patients with life-threatening postoperative complications was significantly lower than that of those with complications that were not life threatening (1- and 3-year OS rates: 40% and 0% vs. 80% and 57%, respectively, p = 0.001). CONCLUSIONS: Postoperative mortality and morbidity were high in patients on CHD who underwent pulmonary resection, especially if they had coexisting IP. Although IP is not a contraindication to pulmonary resection, the surgical strategy for CHD patients with IP should be considered carefully.

Guidelines for Colonic Diverticular Bleeding and Colonic Diverticulitis: Japan Gastroenterological Association.

Colonic diverticular disease has been increasing in prevalence in Japan due to the rapidly aging population. Colonic diverticular bleeding can result in hemorrhagic shock requiring blood transfusion, and it carries a high risk of recurrence within 1 year. Colonic diverticulitis can cause abscess, fistula formation, and perforation of the colon that may require surgery, and it often recurs. As a result, patients with colonic diverticular disease are often bothered by required frequent examinations, re-hospitalization, and a consequent decrease in quality of life. However, the management of diverticular disease differs between Japan and Western countries. For example, computed tomography (CT) is readily accessible at Japanese hospitals, so urgent CT may be selected as the first diagnostic procedure for suspected diverticular disease. Endoscopic clipping or band ligation may be preferred as the first endoscopic procedure for diverticular bleeding. Administration of antibiotics and complete bowel rest may be considered as first-line therapy for colonic diverticulitis. In addition, diverticula occur mainly in the sigmoid colon in Western countries, whereas the right side or bilateral of the colon is more commonly involved in Japan. As such, diverticular disease in the right-side colon is more prevalent in Japan than in Western countries. Against this background, concern is growing about the management of colonic diverticular disease in Japan and there is currently no practice guideline available. To address this situation, the Japanese Gastroenterological Association decided to create a clinical guideline for colonic diverticular bleeding and colonic diverticulitis in collaboration with the Japanese Society of Gastroenterology, Japan Gastroenterological Endoscopy Society, and Japanese Society of Interventional Radiology. The steps taken to establish this guideline involved incorporating the concept of the GRADE system for rating clinical guidelines, developing clinical questions (CQs), accumulating evidence through a literature search and review, and developing the Statement and Explanation sections. This guideline includes 2CQs for colonic diverticulosis, 24 CQs for colonic diverticular bleeding, and 17 CQs for diverticulitis.

Effects of secondary EGFR mutations on resistance against upfront osimertinib in cells with EGFR-activating mutations in vitro.

OBJECTIVES: Non-small cell lung cancers (NSCLCs) that harbor activating mutations for epidermal growth factor receptor (EGFR) show remarkable initial response to EGFR-tyrosine kinase inhibitors (TKIs), but inevitably acquire resistance, half of which are due to a T790 M secondary mutation when first-generation (1 G) or 2 G EGFR-TKIs are used. Osimertinib, a 3 G EGFR-TKI, is a standard of care in this situation, but eventually also evokes resistance, reportedly due to some tertiary EGFR mutations. However, the FLAURA trial showed the superiority of osimertinib over 1 G EGFR-TKIs in treatment-naïve patients, thus providing an option of first-line osimertinib treatment. Resistance in this setting is also inevitable, but its mechanism is unclear. We investigated whether resistance mutations that emerged with T790 M were responsible for the osimertinib resistance in the first-line setting; i.e. without T790 M, and if so, what treatment option was available. MATERIALS AND METHODS: We used literature search to identify EGFR mutations at codons L718, G724, L792, G796, and C797 as mechanisms of osimertinib resistance in the presence of T790 M. These mutations were introduced into Ba/F3 cells in cis with activating EGFR mutations but not with T790 M; inhibitory effects of five EGFR-TKIs were evaluated. RESULTS: Only C797S conferred significant resistance against osimertinib when exon 19 deletion was the activating mutation. However, co-existence of L858R with C797S, C797 G, L718Q, or L718 V mutations all conferred resistance to osimertinib. Erlotinib showed the greatest activity for C797S-mediated resistance. However, 2 G EGFR-TKIs (afatinib or dacomitinib) were effective for other resistance mutations. CONCLUSION: After first-line osimertinib failure, 1 G or 2 G EGFR-TKIs are effective, depending on combinations of secondary and activating mutations.

Activity of a novel HER2 inhibitor, poziotinib, for HER2 exon 20 mutations in lung cancer and mechanism of acquired resistance: An in vitro study.

OBJECTIVES: Oncogenic HER2 mutations are present in 2-4% of lung adenocarcinomas, but the relevant clinical trials are unsatisfactory. The novel HER2 inhibitor poziotinib was recently developed and clinical trials are ongoing. We compared poziotinib with nine tyrosine kinase inhibitors (TKIs), and derived poziotinib-resistant clones to investigate the resistant mechanism. MATERIALS AND METHODS: We introduced three common HER2 mutations A775_G776insYVMA (YVMA), G776delinsVC (VC) and P780_Y781insGSP (GSP), which account for 94% of HER2 exon 20 insertions in the literature, into Ba/F3 cells. We then compared the activity of poziotinib with that of nine TKIs (erlotinib, afatinib, dacomitinib, neratinib, osimertinib, AZ5104, pyrotinib, lapatinib, and irbinitinib), determined the 90% inhibitory concentration (IC90) through a growth inhibition assay, and defined a sensitivity index (SI) as IC90 divided by the trough concentration at the recommended dose as a surrogate for drug activity in humans. We also generated resistant clones by exposure to poziotinib in the presence of N-ethyl-N-nitrosourea, and HER2 secondary mutations that might serve as a resistance mechanism were searched. RESULTS: YVMA showed resistance to all tested drugs except neratinib, poziotinib and pyrotinib. Poziotinib was the only drug with an SI less than 10 for YVMA, the most common HER2 exon 20 insertion. We established 62 poziotinib-resistant clones, and among these, only C805S of HER2, which is homologous to C797S of the EGFR, was identified as a secondary mutation in 19 clones. We also revealed that heat shock protein (HSP) 90 inhibitors show potent anti-growth activity to the C805S secondary mutant clone. CONCLUSIONS: Poziotinib showed the most potent activity against HER2 exon 20 mutations. We identified the secondary C805S at the covalent binding site of HER2 to poziotinib as a potential mechanism of acquired resistance. HSP90 inhibitors might be a therapeutic strategy for the C805S secondary mutation.

Laparoscopic treatment of rectal cancer and lateral pelvic lymph node dissection: are they obsolete?

Laparoscopic surgery for rectal cancer offers favorable short-term results without compromising long term oncological outcomes so far, according to the data from major trials. For this reason, it is currently considered as a standard option for rectal cancer surgery. The learning curve of laparoscopic rectal cancer surgery is generally longer compared to colon cancer. Appropriate standardization and training of laparoscopic rectal cancer surgery is required. Several RCTs suggested the potential negative effect on quality of resected specimen, which can increase local recurrence. The long-term outcomes - especially local recurrence rate - of these RCTs are awaited. Lateral pelvic lymph node dissection (LPLND) has a certain effect of reducing local recurrence of rectal cancer even after neoadjuvant radiotherapy. Since LPLND is associated with postoperative morbidity, we should carefully select the candidate to maximize the effect of LPLND and minimize the morbidity caused by LPLND. Recent advancements in imaging study such as CT and MRI enable us to find the suitable candidates for LPLND. The morbidity caused by LPLND could be reduced by minimally invasive surgeries such as laparoscopic surgery and robotic surgery. We have to improve oncological outcomes and reduce morbidity by the multidisciplinary strategy for rectal cancer including total mesorectal excision, neoadjuvant chemoradiotherapy and LPLND together with laparoscopic surgery.

[Multimodality Therapy against the Lateral Lymph Node Recurrence of Rectal Cancer].

BACKGROUND: The local recurrence of rectal cancer classifies 4 types, anterior, posterior, lateral compartment and anastomotic site. This study evaluates outcome of laparoscopic lateral lymph node dissection(LLND)against the lateral lymph node recurrence. METHOD: Five patients were diagnosed as the lateral lymph node recurrence and underwent laparoscopic LLND. We diagnosed the lateral lymph node recurrence by CT, MRI and PET-CT. All cases revealed abnormal uptake on PET-CT. RESULT: The median of age is 63. Three patients are male. About primary tumor, 4 patients had tumor below peritoneal reflection and one patient above it. Two patients received neoadjuvant(chemo)radiotherapy(RT group)and one of them underwent laparoscopic LLND at the first operation. The median period from operation to recurrence was 25 months. Before re-operation, 3 patients received chemotherapy. Pathological assessments confirmed pathological complete response(pCR) in all three cases. The median of operation time and bleeding were 257 min and 0 mL, respectively. No complications, more than Grade III(Clavien-Dindo classification)happened. The median follow-up period from re-operation was 34 months. Four patients have no recurrence and one presents lung metastasis. All 5 patients are alive. CONCLUSION: Laparoscope magnifies various pelvic structures. Therefore we perform operation more exactly and safety. In the case of local recurrence, especially lateral compartment, tumor is easy to invade adjacent structures. Then, it is often difficult to do R0 resection. If we find the recurrence lesions earlier and induce neoadjuvant chemotherapy, we can improve R0 resection rate.

EGFR T790M and C797S Mutations as Mechanisms of Acquired Resistance to Dacomitinib.

INTRODUCTION: Dacomitinib was superior to gefitinib in terms of progression-free survival in patients with EGFR-mutant lung cancer in a recent ARCHER 1050 trial. However, despite a marked initial response, lung cancers eventually acquire resistance to these inhibitors. This study aimed to elucidate the mechanisms of acquired resistance to dacomitinib in vitro. METHODS: Dacomitinib-resistant clones were established by exposure to fixed concentrations of dacomitinib by using N-ethyl-N-nitrosourea (ENU) mutagenesis or by chronic exposure to increasing concentrations of dacomitinib without ENU. EGFR secondary mutations were analyzed by Sanger sequencing. Time to resistance in each clone was compared according to the mutational status. EGFR Del19, L858R, and G719A mutations were introduced into Ba/F3 cells by using retroviral vectors. RESULTS: Chronic exposure to dacomitinib without ENU induced T790M in Ba/F3 cells expressing Del19. ENU mutagenesis resulted in 171 dacomitinib-resistant clones. Among these clones, 90% acquired T790M. However, C797S occurred in 11% of L858R-mutant clones (four of 35) and in 24% of G719A-mutant clones (12 of 38) established by using low-dose dacomitinib. Time to resistance was not significantly different between T790M- and C797S-mutant clones in both of L858R clones (p = 0.93) and G719A clones (p = 0.86). Cells expressing Del19 that acquired T790M were sensitive to osimertinib, whereas cells with L858R plus C797S mutations were sensitive to gefitinib or erlotinib. CONCLUSIONS: These in vitro data demonstrate that dacomitinib can directly induce T790M or C797S secondary mutations. Our data suggest the importance of analyzing these secondary mutations because appropriate selection of EGFR inhibitors could overcome acquired resistance to dacomitinib in a subset of lung cancers.

[A Case of Resected Superior Sulcus Tumor with Pathological Complete Response after Trimodality Therapy].

The current case was 73-year-oldwoman. She was referredto our hospital for an abnormal shadow of chest X-ray in the upper right lung field. Chest CT showed 3.5 cm of tumor located at the apex of right lobe with invasion of the chest wall. The tumor was diagnosed as squamous cell carcinoma using CT guided needle biopsy(superior sulcus tumor, clinical T3N0M0, Stage II B). The neoadjuvant therapy, 4 courses of chemotherapy(CBDCA plus PTX)andconcurrent radiotherapy(45 Gy/25 Fr)was performed. Chest CT revealed that tumor size was decreased to 2.3 cm in a diameter, and therapeutic effect was decided as partial response(34%). Upper right lobectomy combinedwith the chest wall(1th to 3th ribs)andmed iastinal lymph node dissection were performed. The pathological specimens showed no residual cancer cells(Ef3, pathological complete response[pCR]). She discharged without complications at 10 days after surgery. It is important to collect cases which obtainedpCR for development of more effective preoperative therapy.

A proposal for a comprehensive risk scoring system for predicting postoperative complications in octogenarian patients with medically operable lung cancer: JACS1303.

OBJECTIVES: Although some retrospective studies have reported clinicopathological scoring systems for predicting postoperative complications and survival outcomes for elderly lung cancer patients, optimized scoring systems remain controversial. METHODS: The Japanese Association for Chest Surgery (JACS) conducted a nationwide multicentre prospective cohort and enrolled a total of 1019 octogenarians with medically operable lung cancer. Details of the clinical factors, comorbidities and comprehensive geriatric assessment were recorded for 895 patients to develop a comprehensive risk scoring (RS) system capable of predicting severe complications. RESULTS: Operative (30 days) and hospital mortality rates were 1.0% and 1.6%, respectively. Complications were observed in 308 (34%) patients, of whom 81 (8.4%) had Grade 3-4 severe complications. Pneumonia was the most common severe complication, observed in 27 (3.0%) patients. Five predictive factors, gender, comprehensive geriatric assessment75: memory and Simplified Comorbidity Score (SCS): diabetes mellitus, albumin and percentage vital capacity, were identified as independent predictive factors for severe postoperative complications (odds ratio = 2.73, 1.86, 1.54, 1.66 and 1.61, respectively) through univariate and multivariate analyses. A 5-fold cross-validation was performed as an internal validation to reconfirm these 5 predictive factors (average area under the curve 0.70). We developed a simplified RS system as follows: RS = 3 (gender: male) + 2 (comprehensive geriatric assessment 75: memory: yes) + 2 (albumin: <3.8 ng/ml) + 1 (percentage vital capacity: ≤90) + 1 (SCS: diabetes mellitus: yes). CONCLUSIONS: The current series shows that octogenarians can be successfully treated for lung cancer with surgical resection with an acceptable rate of severe complications and mortality. We propose a simplified RS system to predict severe complications in octogenarian patients with medically operative lung cancer. Trial Registration Number: JACS1303 (UMIN000016756).

Can laparoscopic appendectomy be safely performed by surgical residents without prior experience of open appendectomy?

BACKGROUND: As laparoscopic surgery has become the mainstream technique for abdominal surgery, it has become difficult for surgical residents to have opportunities to perform open surgery. This study aimed to examine the appropriateness and feasibility of laparoscopic appendectomy performed by surgical trainees who had little experience with open appendectomy or laparoscopic training with animal models. METHODS: We retrospectively reviewed all the records of patients who underwent appendectomy for acute appendicitis from April 2008 to December 2014. Residents were assigned to two levels of seniority: junior residents who had undergone 1-3 years of residency and senior residents who had undergone 4-6 years of residency. Patient characteristics, histopathological results, operative time, blood loss, conversion to open procedure, complications, length of hospital stay, and mortality were compared between the two groups. RESULTS: During the study period, 174 patients with the clinical diagnosis of acute appendicitis underwent laparoscopic appendectomy by junior residents and 90 patients were operated on by senior residents. There were no statistical differences in the characteristics of the patients, conversion rates (0/174 vs. 1/90), median operative times (75 minutes vs. 75 minutes), complication rates (7% vs. 4%), and median lengths of hospital stay (4 days vs. 4 days). CONCLUSION: Laparoscopic appendectomy can be performed safely by surgical residents who had little experience or training with animal models or open appendectomy. In this era of laparoscopic surgery, laparoscopic appendectomy represents an important opportunity for training surgical residents with little experience of open surgery.