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Biomedical subjects

J W Lim

Publications and source records attributed to J W Lim.

At least 19 recordsLinked to original sources
PubMed2006

Subcutaneous hyalohyphomycosis due to Cephalotheca foveolata in an immunocompetent host.

We report the first case of subcutaneous hyalohyphomycosis caused by the genus Cephalotheca, which has not been reported to cause human infection. A 67-year-old immunocompetent farmer presented with a 10-year history of verrucous erythematous plaques on the right foot dorsum, great toe, heel and sole. Histopathology of the lesions revealed chronic granulomatous inflammation with numerous nonpigmented fungal spores in the dermis. Cultures of biopsy specimens on Sabouraud's dextrose agar for 2 weeks developed into yellowish brown, velvety colonies that subsequently turned black after 8 weeks because of the production of black cleistothecia indicating the teleomorph. On the basis of mycological features, scanning electron microscopic morphology and molecular analysis data, a new species of Cephalotheca was identified and designated Cephalotheca foveolata. Because there was no response to the antifungal agents administered, the patient was successfully treated by surgical excision with skin graft.

Aged↗
PubMed2006

Prophylactic antibiotics in orthopaedic surgery: guidelines and practice.

The national clinical practice guideline has recommended that prophylactic antibiotic be given in orthopaedic surgery involving joint replacements and internal fixation of fractures. The aim of this study is to assess the current antibiotics prophylaxis practice in a state level hospital. One hundred and three patients (68 males, 35 females; mean age 41.6 +/- 22.2 years) undergoing internal fixation for closed fractures and joint replacement surgery were included in this prospective study. The choice of pre and post-operative antibiotics, their dosages and duration of administration were recorded. The pre-operative antibiotics were only deemed to have been given if it was documented in the case notes and in the case of post-operative antibiotics if it was signed on the drug chart. Eighty eight percent were given pre-operative prophylactic antibiotics and 92% were given post-operative antibiotics. For patients undergoing internal fixation of fractures, the most commonly used antibiotic for both pre and post-op is intravenous cefuroxime. For joint replacement surgery, the most commonly used antibiotic is intravenous cefoperazone. The duration or number of doses of post-operative antibiotics was highly variable. It was not stated in 56% of the post-operative instructions. Post-operative antibiotic was ordered for 48 hours or longer in 10%. In conclusion, prophylactic antibiotics appear to be widely practised. The first line antibiotics as recommended by the present guideline were not given in any of the patients. Second generation followed by third generation cephalosporins are the most popular antibiotics, with a trend towards using third generation cephalosporins in arthroplasty patients. Single dose prophylaxis was rarely practised.

Adolescent↗
PubMed2001

NF-kappaB, inducible nitric oxide synthase and apoptosis by Helicobacter pylori infection.

Oxygen radicals are considered as an important regulator in the pathogenesis of Helicobacter pylori (H. pylori)-induced gastric ulceration and carcinogenesis. Inflammatory genes including inducible nitric oxide synthase (iNOS) may be regulated by oxidant-sensitive transcription factor, nuclear factor-kappaB (NF-kappaB). iNOS induction has been related to gastric apoptosis. We studied the role of NF-kappaB on iNOS expression and apoptosis in H. pylori-stimulated gastric epithelial AGS cells. AGS cells were treated with antisense oligonucleotide (AS ODN) for NF-kappaB subunit p50, an antioxidant enzyme catalase, an inhibitor of NF-kappaB activation pyrrolidine dithiocarbamate (PDTC), iNOS inhibitors N(G)-nitro-L-arginine-methyl ester (L-NAME) and 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT), a peroxynitrite donor SIN-1, and a nitric oxide donor NOC-18 in the presence or absence of H. pylori. H. pylori induced cytotocixity time- and dose-dependently, which occurred with induction in iNOS expression and nitrite production. SIN-1 and NOC-18 induced dose-dependent cytotoxicity in AGS cells. Catalase, PDTC, L-NAME, and AMT prevented H. pylori-induced cytotoxicity and apoptosis. It was related to their inhibition on iNOS expression and nitrite production. The cells treated with AS ODN had low levels of p50 and NF-kappaB and inhibited H. pylori-induced cytotoxicity, apoptosis, iNOS expression, and nitrite production. In conclusion, NF-kappaB plays a novel role in iNOS expression and apoptosis in H. pylori-infected gastric epithelial cells.

Antioxidants↗
PubMed2001

Effect of alpha1-acid glycoprotein expressed in cancer cells on malignant characteristics.

The alpha1-acid glycoprotein (AAG) is a prototypical serum acute phase reactant in most mammalian species; it is synthesized mainly in liver parenchymal cells. Recently, we found that mRNAs of AAG were expressed in non-hepatic cancer cells, and the expression levels were regulated by the cytokines--IL-1, IL-6, and TNF-alpha. The functional role of AAG in non-hepatic cancer cells has not yet been established. In order to understand the functional role of the AAG expressed in HT-29 cells, the cancer cells were transfected with cloned cDNA for AAG, or exposed to antisense oligodeoxynucleotide (ODN) for AAG. The colony-forming capacity, invasion, and adhesion to laminin of these transformed cancer cells were measured. Overexpression of AAG by transfection, and inhibition of the AAG expression by antisense ODNs were identified by Western blot as well as nested reverse transcriptase-polymerase chain reaction (nested RT-PCR), respectively. Results showed that the overexpression of AAG by transfection reduced colony-forming capacities, invasion, and adhesion to laminin of the cancer cells; on the other hand, the antisense ODN for AAG elevated colony-forming capacities, invasion, and adhesion to laminin of the cancer cells. These results suggest that AAG, expressed in cancer cells inhibited proliferation, invasion, and metastasis of the cancer cells.

Acute-Phase Reaction↗
PubMed2001

Induction of alpha1-acid glycoprotein mRNA by cytokines and differentiation in human colon carcinoma cell.

The mRNA for the alpha1-acid glycoprotein (AAG) was expressed not only in hepatoma cells, but also in non-hepatic cancer cells. The expression of the AAG mRNA in HT-29 human colon carcinoma cells is induced by cytokines, IL-6, IL-1, and TNF-alpha, in a manner characteristic of the acute phase response, and the expression of AAG mRNA was up-regulated in differentiated HT-29 cells.

Cell Differentiation↗
PubMed2001

Prognostic significance of Bcl-2 and p53 expression in advanced laryngeal squamous cell carcinoma.

BACKGROUND: Proteins regulating the cell cycle and cell death are frequently abnormally expressed in cancer. Several of these, particularly p53 and Bcl-2, have been widely suggested as possible prognostic markers in diverse human malignancies. Their role in predicting outcome in squamous cell carcinomas of the head and neck is unclear and may depend on the location, stage, and treatment of the tumor. METHODS: To assess this question specifically for advanced squamous cell carcinoma of the larynx, we studied 69 patients with stage III or IV tumors, all but 6 of whom were treated with surgery plus postoperative irradiation by a single physician. We studied the patients retrospectively to test the association between expression of Bcl-2 and p53, as assessed by immunohistochemistry, with treatment outcome and survival. RESULTS: Twenty of the 69 patients died from their tumor (poor outcome); the rest were alive and tumor free at the last follow-up or died of unrelated causes without clinical tumor recurrence (good outcome). Fourteen tumors had detectable Bcl-2 expression, including 8 scored as overexpressors. Thirty-nine tumors overexpressed p53. Expression of neither Bcl-2 nor p53 was associated with outcome, overall survival, or disease-free survival. Only tumor stage was significantly associated with outcome and disease-free survival. CONCLUSION: These data indicate that assessing expression of p53 or Bcl-2 is unlikely to be prognostically useful for surgically treated advanced laryngeal carcinoma.

Adult↗
PubMed2001

Nuclear factor-kappaB regulates cyclooxygenase-2 expression and cell proliferation in human gastric cancer cells.

Nuclear factor-kappaB (NF-kappaB) is a transcriptional regulator of inducible expression of genes including cyclooxygenase-2 (COX-2), regulating cell proliferation. NF-kappaB is kept silent in the cytoplasm via interaction with the inhibitory protein IkappaBalpha and transmigrated into the nucleus upon activation. However, constitutive NF-kappaB has been found in the nucleus of some cancer cells. We investigated the role of NF-kappaB in COX-2 expression and cell proliferation in human gastric cancer AGS cells. AGS cells were treated with antisense oligodeoxynucleotide (AS ODN) or sense oligodeoxynucleotide (S ODN) for the NF-kappaB subunit p50, or they were transfected with a mutated IkappaBalpha gene (MAD-3 mutant) or a control vector, pcDNA-3. AGS cells were treated with COX-2 inhibitors such as indomethacine and NS-398 or prostaglandin E2. mRNA expression for COX-2, and protein levels for p50, IkappaBalpha, and COX-2 were determined by reverse transcription polymerase chain reaction and Western blot analysis. The NF-kappaB levels were examined by electrophoretic mobility shift assay. Thromboxane B2 (TXB2) and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) levels were determined by enzyme-linked immunosorbent assay. Cell proliferation was assessed by viable cell counting, [3H] thymidine incorporation, and colony formation. The nuclear level of p50 decreased in AGS cells treated with AS ODN. The IkappaBa mutant was observed in cells transfected with the mutated IkappaBa gene. NF-kappaB was inhibited in cells treated with AS ODN or transfected with the mutated IkappaBalpha gene, compared with the cells treated with S ODN or transfected with control vector. Cell proliferation, mRNA expression and protein level of COX-2, and production of TXB2 and 6-keto-PGF1alpha were inhibited in cells treated with AS ODN or transfected with the mutated IkappaBalpha gene, which had lower NF-kappaB levels than cells treated with S ODN or transfected with control vector. COX-2 inhibitors suppressed cell proliferation and production of TXB2 and 6-keto-PGF1alpha, in a dose-dependant manner. Prostaglandin E2 prevented the inhibition of proliferation in cells treated with AS ODN or transfected with the mutated IkappaBalpha gene. In conclusion, NF-kappaB mediates COX-2 expression, which may be related to cell proliferation, in human gastric cancer cells.

6-Ketoprostaglandin F1 alpha↗
PubMed2001

Helicobacter pylori-induced expression of interleukin-8 and cyclooxygenase-2 in AGS gastric epithelial cells: mediation by nuclear factor-kappaB.

BACKGROUND: Helicobacter pylori infection might activate nuclear factor-kappaB (NF-kappaB), a transcriptional regulator of inducible expression of inflammatory genes, interleukin-8 (IL-8) and cyclooxygenase-2 (COX-2). We studied the role of NF-kappaB on expression of IL-8 and COX-2 in H. pylori-stimulated AGS gastric epithelial cells by using antisense oligonucleotide (AS ODN) for NF-kappaB subunit p50 and an antioxidant, glutathione (GSH) as well as a NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC). METHODS: AGS cells were treated with p50 AS ODN, GSH or PDTC in the presence of H. pylori. mRNA expression and protein levels for IL-8 and COX-2 were determined by Northern blot analysis and Western blot analysis. Levels of IL-8, 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) and thromboxane B2 (TXB2) were measured in the medium by enzyme-linked immunosorbent assay. NF-kappaB activation was examined by electrophoretic mobility shift assay. RESULTS: H. pylori induced a time-dependent expression of mRNA and protein for IL-8 and COX-2 via activation of NF-kappaB and increased the levels of IL-8, 6-keto-PGF1alpha and TXB2, which were inhibited by GSH and PDTC. H. pylori-induced expression of IL-8 and COX-2 was blocked in AGS cells transfected with p50 AS ODN. CONCLUSION: NF-kappaB may play a novel role in expression of IL-8 and COX-2 in H. pylori-induced gastric inflammation.

Adenocarcinoma↗
PubMed2001

Diagnosis of nut-cracker phenomenon using renal Doppler ultrasound in orthostatic proteinuria.

BACKGROUND: We evaluated the efficacy of non-invasive renal Doppler ultrasound (US) to detect the nut-cracker phenomenon (NCP) and we studied the prevalence of NCP in children with orthostatic proteinuria. METHODS: Among a total 66 cases of orthostatic proteinuria, 39 cases of NCP were found, with 27 cases being detected in a normal control group. Using Doppler US, the anteroposterior (AP) diameter and peak velocity (PV) of the left renal vein (LRV) were measured at the hilar and aortomesenteric portion. We calculated the ratio of AP and PV diameters between the two portions. The parameters were analysed using Student's t-test. RESULTS: The AP diameters and the ratio in the hilar and narrow portions were all significantly different between the two groups (P<0.01). The PV in the narrow portion and the ratio of PV were significantly different (P<0.01), but the PV in the hilar portion was not statistically different between the two groups (P>0.05). If the diagnostic criteria for NCP was that the ratio of PV was more than 5, then 22 subjects (56.4%) in the orthostatic proteinuria group and none in the control group could be diagnosed as NCP. If, however, the cut-off values for the diagnosis of NCP were set at the mean+/-2 SD of the ratio (PV ratio 3.98 and size ratio 4.16), then the orthostatic proteinuria group showed abnormal AP diameter in 25 (64.1%), peak velocity in 28 (71.8%), and both in 21 patients (53.8%), and the control group showed an abnormal AP diameter in one subject (3.7%). CONCLUSIONS: NCP may be one of the leading causes of orthostatic proteinuria, and non-invasive renal Doppler US may be a useful diagnostic tool in the screening of NCP. In the future, the diagnostic criteria of NCP must be redefined in children.

Adolescent↗
PubMed2001

Sonographic findings of solid and papillary epithelial neoplasm of the pancreas.

OBJECTIVE: To evaluate the sonographic findings of solid and papillary epithelial neoplasm of the pancreas, a rare tumor occurring in young women. METHODS: The sonographic findings of 11 cases of pathologically proven solid and papillary epithelial neoplasm of the pancreas were retrospectively evaluated. RESULTS: In 6 cases (55%), combined cystic and solid portions of the masses were observed, whereas only solid-looking masses without anechoic cystic portions were seen in 4 cases (36%). One case (9%) had marginal calcification, consequently, the internal architecture was not evaluated by sonography. Internal echoes were seen in 3 of 6 cystic and solid masses. Septa were seen in 3 cases. Among 11 cases of solid and papillary epithelial neoplasm, tumor margins were well defined in 10, and tumor capsules were detected in 9 (echogenic in 7 and hypoechoic in 2). Calcifications were seen in 3 cases (27%). CONCLUSIONS: The characteristic sonographic findings of solid and papillary epithelial neoplasm were well-encapsulated, cystic, and solid masses, but sometimes the mass was seen as a pure solid-looking mass or had internal septations or calcifications.

Adult↗
PubMed2000

Suppression of NF-kappaB activation and cytokine production by N-acetylcysteine in pancreatic acinar cells.

Reactive oxygen species (ROS), generated by infiltrating neutrophils, are considered as an important regulator in the pathogenesis and development of pancreatitis. A hallmark of the inflammatory response is the induction of cytokine gene expression, which may be regulated by oxidant-sensitive transcription factor, nuclear factor-kappaB (NF-kappaB). Present study aims to investigate whether neutrophils primed by 4beta-phorbol 12beta-myristate 13alpha-acetate (PMA) affect the productions of H(2)O(2) and lipid peroxide (LPO), NF-kappaB activation and cytokine production in pancreatic acinar cells, and whether these alterations were inhibited by N-acetylcysteine (NAC) and superoxide dismutase (SOD). Neutrophils generated ROS by stimulation with PMA, which was inhibited by NAC and SOD. In acinar cells, PMA-primed neutrophils increased the productions of H(2)O(2), LPO, and cytokines both time and dose dependently. PMA-primed neutrophils resulted in the activation of two species of NF-kappaB dimers (a p50/p65 heterodimer and a p50 homodimer) in acinar cells. Both NAC and SOD inhibited neutrophil-induced, oxidant-mediated alterations in acinar cells. In conclusion, ROS, generated by neutrophils, activates NF-kappaB, resulting in upregulation of inflammatory cytokines in acinar cells. Antioxidants such as NAC might be useful antiinflammatory agents by inhibiting oxidant-mediated activation of NF-kappaB and decreasing cytokine production.

Acetylcysteine↗
PubMed2000

Effect of improved nasal breathing on obstructive sleep apnea.

OBJECTIVES: The goal was to compare the effect of an improved nasal airway on obstructive sleep apnea (OSA) by use of subjective and objective measures. METHODS: A prospective study of 50 consecutive patients with nasal airway obstruction and OSA was carried out. RESULTS: Subjectively, nasal breathing improved in 49 (98%) patients, whereas snoring decreased or disappeared in 17 (34%); the remaining 33 (66%) patients did not notice any significant change in their snoring. Daytime energy levels increased in 39 (78%) patients and remained unchanged or worsened in 11 (22%). In review of the polysomnographic data, the group overall did not have significant changes in respiratory disturbance index (RDI) or lowest oxygen saturation levels (LSaO(2)). Continuous positive airway pressure (CPAP) levels required to correct OSA decreased after nasal surgery (P < 0.01). Patients with mild OSA showed significant worsening in RDI (P < 0.05), whereas LSaO(2) levels were improved in the group with moderate OSA (P < 0.05). In patients with severe OSA neither the RDI levels nor the LSaO(2) changed, but CPAP levels required to alleviate the obstruction after surgery were reduced (P < 0.01). CONCLUSIONS: Most patients report improvement in nasal and sleep symptoms after correction of nasal airway obstruction. However, nasal surgery alone does not consistently improve OSA when measured objectively. Depending on the severity of OSA, nasal airway reconstruction may contribute to a decrease in CPAP level and improvement in oxygen saturation. Correction of the obstructed nasal airway should certainly be included in the overall treatment plan for OSA.

Adult↗
PubMed2000

Experience with percutaneous dilational tracheostomy.

Percutaneous dilational tracheostomy (PDT) has gained popularity among critical care specialists in the past 10 years. The initial studies in our specialty resulted in essentially banning the procedure as a dangerous substitute for standard operative tracheostomy. Despite this action, more than 1,100 cases of percutaneous tracheostomy have been reported with details on complications. We reviewed all published data and studied 311 patients of our own. A prospective study was performed in 3 groups of patients: 1) 50 patients scheduled for PDT performed in the operating room by a head and neck surgeon (group 1); 2) 50 patients who underwent standard operative tracheostomy performed by the same surgeon (group 2); and 3) 211 patients who underwent bedside PDT by critical care physicians (group 3). The intraoperative complication rates were 0% in group 1, 2% in group 2, and 4% in group 3; the postoperative complication rates were 13%, 4%, and 12%, respectively. There were 2 deaths in group 3, and none in groups 1 or 2. The statistically significant differences among the groups were the superiority of group I over group 3 in intraoperative complications, as well as the lower postoperative complication rate of the standard tracheostomy group. These results show that PDT can be performed with acceptable morbidity rates in relation to published complication rates of standard tracheostomy, but it has no advantage over standard tracheostomy with respect to postoperative morbidity. When they are performed by a head and neck surgeon, the morbidity associated with both standard and percutaneous tracheostomies can be reduced.

Adult↗
PubMed2000

Treatment of prostatic abscess: value of transrectal ultrasonographically guided needle aspiration.

The purpose of this study was to assess the effectiveness of transrectal ultrasonographically guided needle aspiration in the treatment of prostatic abscess. Fourteen patients with prostatic abscess were evaluated with this technique and treated with sonographically guided needle aspiration. Using this technique, all cases (100%) had one or more hypoechoic areas within the prostate that contained inhomogeneous materials; in 10 patients (71.0%), the lesion showed internal septa or solid portion. The margins of the hypoechoic area were well defined and thick in 11 patients (79.0%) and poorly defined in 3 patients (21.0%). The estimated volume of the prostatic abscess ranged between 2 and 28 ml (mean, 12.0 ml). The presence of a pus collection within the prostate was confirmed by transrectal ultrasonographically guided aspiration in all patients. However, successful treatment of prostatic abscess with transrectal needle aspiration was done in 12 (86.0%) of 14 patients; the treatment failed in 2 (14.0%) of 14 patients. One patient was treated with perineal incision and drainage and the other with transurethral resection. The amount of pus drained ranged between 1 and 39 ml (mean, 12.0 ml). On follow-up transrectal ultrasonographic examination, no remaining abscess pocket was found within the prostate in any of the cases. One year later, the prostatic abscess recurred in one case. In conclusion, transrectal ultrasonographic guidance is useful in the diagnosis of prostatic abscess as well as in the guidance for aspiration and the drainage of such abscesses. Transrectal ultrasonographically guided needle aspiration could be an effective method for treating prostatic abscess.

Abscess↗
PubMed1999

Laparoscopic versus open donor nephrectomy: comparing ureteral complications in the recipients and improving the laparoscopic technique.

BACKGROUND: Laparoscopic live donor nephrectomy (LDN) is a recently developed procedure, the performance of which needs to be studied. Given the reported advantages in the donors, this study looks at graft outcome and ureteral complications in recipients of kidneys procured by open donor nephrectomy (ODN) versus LDN. METHODS: The LDN recipients consisted of 193 patients since 3/27/96. A total of 168 ODN recipients from 1991 to 1998 served as controls. Immunosuppression protocols were similar for both groups. RESULTS: Two-year graft survival for LDN and ODN was 98% and 96%, respectively. Two-year patient survival for LDN and ODN was 98% and 97%, respectively. The incidence of delayed graft function and mean serum creatinine at 3 and 12 months was similar in both groups. However, the number of ureteral complications that required operative repair was significantly higher for LDN recipients compared to ODN recipients, 7.7% (n=15) vs. 0.6% (n=1) respectively (P=0.03). Ureteral stenting was required in an additional 3.1% (n=6) of LDN and 2.4% (n=4) of ODN (P=NS). There was, however, a learning curve with time. For the first 130 LDN patients, a total of 20 ureteral complications were recorded, whereas only one occurred in the more recent 63 patients (P=0.03). CONCLUSIONS: The higher ureteral complication rate in LDN recipients has improved over time as technical causes have been identified. We have noted significant improvement in ureteral viability by using the endogastrointestinal anastomosis instrument on the ureter and peri-ureteral tissue. LDN is therefore an excellent alternative to ODN. Identification of hazards unique to this technique is critical before its broader application.

Adult↗
PubMed1999

Early detection and treatment of postoperative pharyngocutaneous fistula.

Fever during the early postoperative period traditionally has not been considered an indication of a postoperative wound infection or breakdown. Atelectasis is considered the most likely source for these early fevers. We studied 200 consecutive patients who underwent major head and neck surgery that involved reconstruction with a pharyngeal suture line. Patients were divided into 2 groups: those who had preoperative irradiation and those who did not. All patients had prophylactic antibiotic coverage, and all patients had identical suture material for closure. We showed a high correlation between fever (>101.5 degrees F) that developed in the first 48 hours and eventual fistula formation and wound infection. We also studied length of hospitalization and number of days until decannulation and resumption of oral feedings. Our data indicate that in those patients in whom fistulas developed, early detection led to earlier healing and rehabilitation.

Antibiotic Prophylaxis↗
PubMed1999

Quantification of lymph nodes in selective neck dissection.

OBJECTIVES: Provide reference for surgeon and pathologist regarding expected yield from selective neck dissections. Quantify lymph nodes obtained from cadaver dissection based on current nodal classification and compare with clinical series. STUDY DESIGN: 1. Quantification of lymph nodes at levels I-V harvested from human cadavers and correlation with nodal grouping for supraomohyoid (I-III) and lateral (II-IV) neck dissections. 2. Retrospective review of operative specimens from clinical neck dissections for lymph node quantity. METHODS: 1. Twenty radical neck dissection specimens, harvested from 10 fresh human cadavers without evidence of head and neck cancer, were separated by nodal level for gross and microscopic examination by a pathologist. The quantity of nodes obtained per level for each specimen was tabulated. 2. Charts of patients treated with neck dissection for squamous cell carcinoma were reviewed and tabulated for type of dissection and number of lymph nodes reported. RESULTS: In the 20 cadaver neck dissections, the average number of lymph nodes removed for levels I-V was 24, with 13 for levels I-III and 19 for levels II-IV. In the clinical review, 98 total neck dissections were included. In the six supraomohyoid dissections, an average of 20 lymph nodes (range, 14-26) were found, with an average of 30 (range, 15-43) in the 11 lateral compartment specimens. In 81 radical or modified radical dissections, an average of 31 nodes (range, 19-63) was reported. CONCLUSIONS: The number of lymph nodes removed in selective neck dissection should be comparable to that of the corresponding levels in radical neck dissection, provided that strict adherence to surgical boundaries is maintained. Dissection of normal cadavers provides a reference for the surgeon and the pathologist but may under-represent lymph node quantity in the diseased state.

Carcinoma, Squamous Cell↗