A case of nearly complete response in hepatocellular carcinoma with disseminated lung metastasis by combination therapy of nivolumab and ipilimumab after treatment failure of atezolizumab plus bevacizumab

Recently, the efficacy of immuno-oncologic agents for advanced hepatocellular carcinoma (HCC) has been proven in several trials. In particular, atezolizumab with bevacizumab (AteBeva), as a first-line therapy for advanced HCC, has shown tremendous advances in the IMBrave150 study. However, second or third-line therapy after treatment failure with AteBeva has not been firmly established. Moreover, clinicians have continued their attempts at multidisciplinary treatment that includes other systemic therapy and radiotherapy (RT). Here, we report a case that showed a near complete response (CR) of lung metastasis to nivolumab with ipilimumab therapy after achieving a near CR of intrahepatic tumor using sorafenib and RT in a patient with advanced HCC who had experienced treatment failure of AteBeva.

Predictive factors of drainage volume and drain duration after the inframammary approach to nipple-areolar-complex sparing mastectomy and implant-based breast reconstruction

Background@#The placement of a closed suction drain is indispensable for preventing serious infections; however, closed suction drains are inevitably accompanied by increases in local infections, pain, and length of hospital stay, and delays in breast cancer treatment including postoperative chemotherapy and radiotherapy. We analyzed predictive factors of total drainage volume and duration. @*Methods@#Among patients who were diagnosed with primary breast cancer between January 2016 and December 2017, we retrospectively analyzed those who underwent immediate implant-based breast reconstruction. Factors that could affect the total volume and duration of drainage, including lipo-prostaglandin E1 use, preoperative chemotherapy, resected breast issue weight, age, body mass index (BMI), serum white blood cell count, erythrocyte sedimentation rate, and C-reactive protein (CRP) level, were analyzed. @*Results@#The mean volume and duration of drainage were 1,213.6 mL and 14.8 days respectively. BMI and CRP on postoperative day (POD) 1 were correlated with the total drainage volume. Age, BMI, and resected breast tissue weight were correlated with the drainage duration. Multiple regression analysis showed that CRP level on POD 1, age, and resected breast tissue weight significantly affected the drainage duration. Multiple regression analysis also showed that the total drainage volume was significantly affected by BMI and CRP level on POD 1. @*Conclusions@#The factors found to affect the duration of drainage in patients undergoing implant-based breast reconstruction were CRP on POD 1, age, resected breast tissue weight, and BMI. The CRP level on POD 1 and BMI influenced the total volume of drainage.

Confirming Genetic Abnormalities of Hypokalemic Periodic Paralysis Using Next-Generation Sequencing: A Case Report and Literature Review

Hypokalemic periodic paralysis (hypoPP) is a disorder characterized by episodic, short-lived, and hypo-reflexive skeletal muscle weakness. HypoPP is a rare disease caused by genetic mutations related to expression of sodium or calcium ion channels. Most mutations are associated with autosomal dominant inheritance, but some are found in patients with no relevant family history. A 28-year-old man who visited the emergency room for paralytic attack was assessed in this study.He exhibited motor weakness in four limbs. There was no previous medical history or family history. The initial electrocardiogram showed a flat T wave and QT prolongation. His blood test was delayed, and sudden hypotension and bradycardia were observed. The blood test showed severe hypokalemia. After correcting hypokalemia, his muscle paralysis recovered without any neurological deficits. The patient’s thyroid function and long exercise test results were normal. However, because of the history of high carbohydrate diet and exercise, hypoPP was suspected. Hence, next-generation sequencing (NGS) was performed, and a mutation of Arg669His was noted in the SCN4A gene. Although hypoPP is a rare disease, it can be suspected in patients with hypokalemic paralysis, and iden tification of this condition is important for preventing further attacks and improving patient outcomes. Diagnosing hypoPP through targeted NGS is a cost-effective and useful method.

Acute Kidney Injury and Kidney Damage in COVID-19 Patients

Background@#Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This disease, which is quickly spreading worldwide, has high potential for infection and causes rapid progression of lung lesions, resulting in a high mortality rate. This study aimed to investigate the effects of SARS-CoV-2 infection on renal function in patients with COVID-19. @*Methods@#From February 21 to April 24, 2020, 66 patients diagnosed with COVID-19 at Chungnam National University Hospital were analyzed; all patients underwent routine urinalysis and were tested for serum creatinine, urine protein to creatinine ratio (PCR), and urine albumin to creatinine ratio (ACR). @*Results@#Acute kidney injury (AKI) occurred in 3 (4.5%) of the 66 patients, and 1 patient with AKI stage 3 underwent hemodialysis. Upon follow-up, all 3 patients recovered normal renal function. Compared with patients with mild COVID-19, AKI (n = 3) occurred in patients with severe COVID-19, of whom both urine PCR and ACR were markedly increased. @*Conclusion@#The incidence of AKI was not high in COVID-19 patients. The lower mortality rate in SARS-CoV-2 infection compared with previous Middle East respiratory syndrome and SARS-CoV infections is thought to be associated with a low incidence of dysfunction in organs other than the lungs.

Retrospective review of 108 breast reconstructions using the round block technique after breast-conserving surgery: Indications, complications, and outcomes

Background@#Several oncoplastic approaches have been implemented in recent years to enhance cosmetic results and to reduce complications. The round block technique is a volume displacement technique for breast reconstruction after breast-conserving surgery (BCS). However, its indications are currently limited according to tumor location, and its cosmetic results and complications have not been clearly established. We hypothesized that the round block technique could produce favorable cosmetic results without major complications regardless of tumor location or nipple-tumor distance, below a certain resected tumor volume and tumor-breast volume ratio. @*Methods@#All breast reconstructions using the round block technique after BCS were included in this analysis. Patients’ data were reviewed retrospectively to investigate complications during follow-up, and clinical photos were used to evaluate cosmetic results. The relationships of tumor location, nipple-tumor distance, tumor volume, and the tumor-breast volume ratio with cosmetic results were investigated. @*Results@#In total, 108 breasts were reconstructed. The mean resected tumor volume was 30.2±15.0 mL. The cosmetic score was 4.5±0.6 out of 5. Tumor location, nipple-tumor distance, tumor volume, tumor-breast volume ratio, radiotherapy, and chemotherapy had no significant effects on cosmetic results or complications. There were no major complications requiring reoperation. @*Conclusions@#Breast reconstruction using the round block technique after BCS can lead to good cosmetic results without major complications regardless of the tumor location, nipple-tumor distance, radiotherapy, or chemotherapy. Below the maximum tumor volume (79.2 mL) and the maximum tumor-breast volume ratio (14%), favorable results were consistently obtained.

A Case of Achieving Partial Remission with the Combination of Sorafenib and Nivolumab in a Patient with Hepatocellular Carcinoma Showing Disease Progression after Nivolumab Therapy

Sorafenib is a well-known approved systemic therapeutic agent used in patients with advanced hepatocellular carcinoma (HCC). Regorafenib and nivolumab are approved as second-line therapeutic drugs in patients showing disease progression after sorafenib therapy. However, there is no established third- or fourth-line therapy in patients with progression after regorafenib or nivolumab treatment. Recently, the combination of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICPIs) has been attempted as a first-line treatment strategy in advanced HCC patients based on the hypothesis that combination therapy may overcome resistance in ICPI monotherapy. On the basis of this suggestion, we herein describe the case of an HCC patient demonstrating macrovascular invasion, whereby partial remission was achieved via the combination of sorafenib and nivolumab following disease progression after nivolumab therapy. Further studies on the combination of TKIs and ICPIs are necessary to determine ways to manage HCC patients showing disease progression after ICPI therapy.

Factors affecting mastectomy specimen density in direct-to-implant breast reconstruction

BACKGROUND: Direct-to-implant breast reconstruction following nipple-sparing mastectomy is becoming increasingly common. The weight of the breast specimen informs implant selection. However, specimens of the same weight may have different volume. Therefore, identifying the factors affecting the density of breast specimens may facilitate the selection of implants with an appropriate volume. METHODS: From December 2015 to May 2018, 108 patients underwent direct-to-implant reconstruction following nipple-sparing mastectomy. The weight of the breast specimens was measured using an electronic scale in the operating room. Furthermore, the volume of specimens was measured using the water displacement technique. Multiple regression analysis was performed on factors that can affect breast density, such as menopause, neoadjuvant chemotherapy (CTx), age, body mass index, and diabetes mellitus. RESULTS: The average density of breast specimens in patients older than 50 years (n=36) was 0.96±0.04 g/mL, which was significantly lower than the 1.01±0.08 g/mL observed in patients younger than 50 years (n=72) (P=0.007). The mean density of breast specimens in patients who underwent neoadjuvant CTx (n=25) was 0.96±0.06 g/mL, which was significantly lower than the value of 1.00±0.08 g/mL in those who did not (n=83). CONCLUSIONS: It is advisable to select an implant slightly larger than the mastectomy specimen weight in patients older than 50 years or in those who have undergone neoadjuvant CTx.

Transient Blindness in a Patient with Severe Metformin-Associated Lactic Acidosis (MALA)

A 68-year-old man presented at the emergency room with sudden blindness. The day before, he had eaten sashimi and eel and drank alcohol for dinner. He experienced nausea, vomiting, and dizziness afterward. His medical history included hypertension and diabetes, and the latter was treated with metformin. Initial laboratory tests revealed severe metabolic acidosis (lactic acidosis). Massive hydration and intravenous sodium bicarbonate replacement therapies were initiated, but severe metabolic acidosis (lactic acidosis) did not resolve, in turn, leading to hemodialysis, which decreased metabolic acidosis. The patient's blindness improved, and his vision gradually recovered. As it is not easy to distinguish between blindness related to metformin-associated lactic acidosis (MALA) and blindness related to other causes, rapid correction of metabolic acidosis through hemodialysis might be helpful in differentiating this from of blindness from blindness related to other causes.

Clinicopathological Factors Associated with Remnant or Regrowth of Benign Breast Tumor after Previous Vacuum-Assisted Core Biopsy

PURPOSE: We sometimes encounter remnant or regrowth of benign breast tumors diagnosed as Breast Imaging-Reporting and Data System (BI-RADS) C4 in follow-up breast ultrasound after previous vacuum-assisted core biopsy (VACB). We aimed to evaluate the factors that influence remnant or regrowth tumors at post-VACB site or adjacent tissue. METHODS: From January 2010 to December 2015, we analyzed 647 cases on follow-up. Patients were divided into two groups; group A was defined as patients without recurrent masses on breast ultrasonography during the follow-up period, and group B was defined as those with recurrent masses diagnosed as more than BI-RADS C4 on ultrasonography. RESULTS: Fibrocystic changes, proliferative disease without atypia, intraductal papilloma, apocrine cell change, atypical ductal hyperplasia, sclerosing adenosis, and radial scars were observed in 89.5% (n=579), 15.9% (n=103), 15.3% (n=99), 5.3% (n=34), 5.7% (n=37), 7.6% (n=49), and 6.3% (n=41) of patients, respectively. During the follow-up period, 85 patients were diagnosed as group B. Group B was significantly associated with proliferative diseases without atypia, sclerosing adenosis, and microcalcifications compared to group A (p=0.008, p=0.007, and p=0.001, respectively). After adjustment for confounding variables, group B was more significantly associated with proliferative breast diseases than group A (hazard ratio [HR], 0.558; 95% confidence interval [CI], 0.343–0.907; p=0.018). Furthermore, group B was more significantly associated with intraductal papilloma (HR, 0.571; 95% CI, 0.342–0.953; p=0.032). CONCLUSION: Previously diagnosed proliferative diseases without atypia or microcalcification at first VACB were significantly associated with recurrent breast tumor. Intraductal papilloma was also significantly associated with tumor regrowth.

Prognostic Significance of Inner Quadrant Involvement in Breast Cancer Treated with Neoadjuvant Chemotherapy / 한국유방암학회지

PURPOSE: In the present study, we aimed to evaluate the initial tumor location as a prognostic factor in breast cancer patients treated with neoadjuvant chemotherapy (NAC). METHODS: Between March 2002 and January 2007, a total of 179 patients with stage II/III breast cancer underwent NAC followed by breast surgery. Using physical and radiologic findings, patients were grouped by their initial tumor location into inner/both quadrant (upper/lower inner quadrant involvement +/− multicentric tumor involving outer quadrant; n=97) and outer quadrant (n=82) tumor groups. All patients received neoadjuvant docetaxel/doxorubicin chemotherapy. One hundred two patients underwent modified radical mastectomy and 77 patients underwent breast-conserving surgery. Adjuvant radiotherapy (RT) and hormonal therapy were administered after surgery when indicated. While 156 patients underwent postoperative RT, 23 did not. The median follow-up duration was 61.1 (12–106) months. RESULTS: The 5-year disease-free survival (DFS) and overall survival rates of all patients were 74.8% and 89.9%, respectively. Patients with inner/both quadrant tumors had lower 5-year DFS than those with outer quadrant tumors (67.7% vs. 83.4%, respectively; hazard ratio [HR]=1.941, p=0.034). A nodal ratio >25% was also an independent adverse prognostic factor for DFS (HR=3.276; p<0.001). There was no significant difference in DFS (p=0.592) after RT on the internal mammary node (IMN). Treatment failed in 44 out of 179 patients (24.6%), of which 27 patients had inner/both quadrant tumors. Twenty-one out of 27 patients had distant failures. CONCLUSION: Among breast cancer patients treated with NAC, those with inner/both quadrant tumors had lower DFS than those with outer quadrant tumors. More aggressive neoadjuvant and/or adjuvant chemotherapy with IMN RT is required for improved disease control and long-term survival.

Bacteriology, Antibiotic Susceptibility and Empirical Antibiotics of Community-acquired Perforated Appendicitis / 감염과화학요법

BACKGROUND: The aim of this study was to study bacteriology and antibiotic susceptibility in patients with community-acquired perforated appendicitis over a five-year-period. MATERIALS AND METHODS: We conducted a retrospective review of the records of adult patients (age > or =18 years) who were diagnosed as having perforated appendicitis at Ulsan University Hospital between January 2007 and December 2011. Patients who had healthcare-associated or hospital-acquired appendicitis were excluded. Intraoperative specimens submitted to the microbiology laboratory were obtained either by aspiration of pus into a syringe or by use of a swab. Anaerobic bacterial cultures were not performed. RESULTS: Among 216 adult patients with perforated appendicitis, we analyzed 163 culture-positive cases. The overall mortality rate of patients was 0.6% (1/163). Escherichia coli was the most common pathogen (93/163, 57.0%), followed by Streptococcus spp. (45/163, 27.6%), Pseudomonas aeroginosa (13/163, 7.9%), and Enterococcus spp. (17/163, 10.4%). The susceptibility of E. coli to quinolones (ciprofloxacin or levofloxacin) was 74.1%. The susceptibility of E. coli to amoxicillin/clavulanate, cefoxitin, ceftriaxone, piperacillin/tazobactam, and carbapenem reached 75%, 86%, 90%, 98%, and 100%, respectively. Isolated E. coli, including ESBL producing organism and P. aeroginosa, were highly susceptible to piperacillin/tazobactam. Empirical antibiotics used most commonly were a combination of third generation cephalosporin and metronidazole. CONCLUSION: E. coli was the most common pathogen of community-acquired perforated appendicitis, and resistance to quinolone was greater than 25%. We cannot recommend quinolones for use as empirical therapy for treatment of perforated appendicitis.

Papillary Thyroid Carcinoma Manifesting as an Autonomously Functioning Thyroid Nodule

Hyperfunctioning thyroid carcinoma is very rare. Hence, radionuclide imaging of thyroid hot nodules usually suggests a benign tumor, and less than 4% of cases have been reported as malignant. We would like to present a case of a hyperfunctioning papillary thyroid carcinoma that was initially treated with radioactive iodine. A 58-year-old woman was referred to our hospital for palpable thyroid nodule and a 5-kg weight loss within 6 months. Thyroid function test revealed thyrotoxicosis, and thyroid autoantibodies were absent. 99mTc thyroid scintigraphy showed a 2 x 2 cm-sized hyperactive hot nodule at the left lobe. Despite radioactive iodine treatment with a dose of 10 mCi 131I, thyroid function did not improve. Fine needle aspiration revealed papillary thyroid cancer. The patient underwent total thyroidectomy. Although clinical features and thyroid scans suggest a benign nodule, the possibility of malignancy should not be ruled out. Malignant thyroid hot nodules are rare; however, its possibility should be taken into account. Therefore, we suggest that ruling out malignancy by existing diagnostic guidelines can misdiagnose even a typical case with benign features. As thyroid nodule detection is getting sensitive and accurate, we present this case to discuss whether additional diagnostic approaches would be necessary for thyroid nodules.

Adenocarcinoma of the Lung Progressing to Multiple Cystic Lesions in a 29-Year-Old Man / 결핵및호흡기질환

Cystic lesions or progressive cystic changes in adenocarcinoma of the lung have rarely been reported. We report a case of lung adenocarcinoma that progressed from ground-glass opacities (GGOs) and consolidations or nodules to extensive cystic lesions during 12 months in a young adult patient. A 29-year-old male was initially diagnosed with primary lung adenocarcinoma by transbronchial lung biopsy of the right lower lobe and lung to lung metastasis in both lungs according to imaging findings. The initial chest computed tomography (CT) scans showed multifocal GGOs, consolidations, and nodules in both lungs. Despite treatment with palliative chemotherapy, the patient's follow-up CT scans showed multiple, cystic changes in both lungs and that the lesions had progressed more extensively. He died of hypoxic respiratory failure one year after his diagnosis.

A Case of Painless Thyroiditis Followed by Graves' Disease

A 30-year-old man was admitted to our hospital because of fatigue, palpitation and severe weakness of both legs. The admission laboratory findings revealed thyrotoxicosis, and 131I thyroid scintigraphic imaging revealed a low radioactive iodine uptake. He was treated for painless thyroiditis for about 4 months. However, thyrotoxic state had continued and radioactive iodine uptake was markedly increased in the follow up scan. Painless thyroiditis often relapses, but rarely develops into Graves' disease. This is a rare case in which painless thyroiditis was followed by Graves' disease.

Salvage radiotherapy for lymph node recurrence after radical surgery in cervical cancer / 부인종양

OBJECTIVE: This study was to evaluate the treatment outcomes and prognostic factors of patients treated with salvage radiotherapy for the treatment of isolated lymph node recurrence of cervical cancer. METHODS: Between 1990 and 2009, 22 cervical cancer patients with lymph node recurrence who had previously undergone radical hysterectomy and pelvic lymph node dissection were treated with salvage radiotherapy with (n=18) or without (n=4) chemotherapy. Of the 22 patients, 10 had supraclavicular lymph node recurrence, 9 had para-aortic lymph node, and 3 had inguinal lymph node. The median total radiotherapy dose was 60 Gy (range, 40 to 70 Gy). Initial pathologic findings, latent period to lymph node recurrence and other clinical parameters such as squamous cell carcinoma antigen (SCC-Ag) level and concurrent chemotherapy were identified as prognostic factors for survival. RESULTS: The median follow-up period after salvage radiotherapy was 31.2 months (range, 12.1 to 148.9 months). The 5-year progression-free and overall survival rates of all patients were 32.7% and 30.7%, respectively. Concurrent chemoradiotherapy (p=0.009) and longer latent period to lymph node recurrence (>18 months vs. 8 ng/dL vs. < or =8 ng/dL, p=0.008) and longer latent period to lymph node recurrence (p=0.040) for overall survival. Treatment failure after salvage radiotherapy occurred in 14 (63.6%) for the 22 patients (in field, 2; out of field, 10; both in and out field, 2). Grade 3 acute skin (n=2) and hematologic toxicity (n=1) developed in 3 patients. CONCLUSION: For isolated lymph node recurrence of cervical cancer, salvage radiotherapy with concurrent chemotherapy should be considered, especially in patients with a long-term progression-free period.

Radial displacement of clinical target volume in node negative head and neck cancer

PURPOSE: To evaluate the radial displacement of clinical target volume in the patients with node negative head and neck (H&N) cancer and to quantify the relative positional changes compared to that of normal healthy volunteers. MATERIALS AND METHODS: Three node-negative H&N cancer patients and five healthy volunteers were enrolled in this study. For setup accuracy, neck thermoplastic masks and laser alignment were used in each of the acquired computed tomography (CT) images. Both groups had total three sequential CT images in every two weeks. The lymph node (LN) level of the neck was delineated based on the Radiation Therapy Oncology Group (RTOG) consensus guideline by one physician. We use the second cervical vertebra body as a reference point to match each CT image set. Each of the sequential CT images and delineated neck LN levels were fused with the primary image, then maximal radial displacement was measured at 1.5 cm intervals from skull base (SB) to caudal margin of LN level V, and the volume differences at each node level were quantified. RESULTS: The mean radial displacements were 2.26 (+/-1.03) mm in the control group and 3.05 (+/-1.97) in the H&N cancer patients. There was a statistically significant difference between the groups in terms of the mean radial displacement (p = 0.03). In addition, the mean radial displacement increased with the distance from SB. As for the mean volume differences, there was no statistical significance between the two groups. CONCLUSION: This study suggests that a more generous radial margin should be applied to the lower part of the neck LN for better clinical target coverage and dose delivery.

Molecular Targets for Treatment of Breast Cancer / 한국유방암학회지

Advances in molecular biology have made it possible to understand the tumor biology of breast cancer at the molecular level and have revealed molecular targets for the therapy of breast cancer. Nowadays, targeting agents are used as mono-therapy or as combined therapy with other anti-cancer drugs for the treatment of breast cancer. Much more efforts is also being made in the development of better therapeutic agents targeting molecules having an important role in tumor biology. In this article, promising molecules for targeted therapy are reviewed for their roles in the pathophysiology and the treatment of breast cancer. We also introduce and summarize new preclinical agents, developed or on developing, with preliminary results from clinical trials. Given the progress currently being made, targeted therapy could become a main strategy for the treatment of breast cancer in the near future.

Carcinoid Tumor Arising within a Tailgut Cyst: A Case Report

Tailgut cysts are rare congenital lesions. They are believed to develop from remnants of the embryonic hindgut. Malignancy in tailgut cyst is extremely unusual. We experienced a case of a carcinoid tumor arising within a tailgut cyst at the presacral space. A 40-year-old woman was admitted for acute anal pain. Digital rectal examination revealed a 2-cm-sized submucosal tumor in the posterior midline rectum 4 cm above the anal verge. On sigmoidoscopic examination, the overlying rectal mucosa seemed to be intact. We performed a transanal incisional biopsy. The pathological diagnosis of the tumor biopsy revealed a malignant neuroendocrine tumor. The patient underwent an abdominoperineal resection. The tumor proved to be mutilocular cysts with a solid component. The cysts were diagnosed as tailgut cysts that were lined by a variety of epithelial types, including inner columnar cells, outer cuboidal cells, and transitional cells. The solid component in the cysts was confirmed as a carcinoid tumor on microscopic examination. Six months after the operation, she was found to have liver and brain metastases.

Fine Needle Aspiration Cytology of Eccrine Acrospiroma of the Breast: Report of a Case Misdiagnosed as Ductal Carcinoma / 대한세포병리학회지

Eccrine acrospiroma is a rare adnexal tumor of the skin. When the clinical presentation is that of a breast lump, diagnosis can be difficult. Also, most of the cytopathologists are not familiar with the cytologic features of this tumor and this is responsible for diagnostic pitfalls. We experienced a case of eccrine acrospiroma of the right breast in a 41-year-old female, misdiagnosed by fine needle aspiration cytology(FNAC). FNAC was characterized by tight clusters or sheets of small round cells, polygonal cells, and spindle cells and tubule like structures within clusters. Myoepithelial cells were not noted in the clusters. The diagnosis of eccrine acrospiroma was confirmed by histology.

A Case of Intussusception of the Cecum and Appendix Due to Endometriosis Mistaken as a Cecal Tumor / 대한산부인과학회잡지

We report a case of intussusception of the cecum and appendix arising in pericecal endometriosis that are mistaken as a cecal tumor preoperatively. At the other OBGY clinic, the 1st lapalotomy was performed for management of leiomyoma but pelvic organs were adhesion severely and palpation mass in the cecum and appendix. The patient was transfer to our hospital for evaluation and treatment of mass. We investigated to intestine closely and diagnosis was cecal tumor colonoscopically. Total hystrectomy and iliocecectomy was performed successfully and discovered intussusception of the cecum and appendix due to endometriosis mistaken as a cecal tumor in operative field. Postoperatively, this case was diagnosed in pericecal endometriosis histologically.